Adrien Quintard
email: adrien.quintard-inv@univ-amu.fr

Jean Rodriguez
email: jean.rodriguez@univ-amu.fr

Catalytic enantioselective OFF 2 ON activation processes initiated by hydrogen transfer: concepts and challenges

Hydrogen transfer initiated processes are eco-compatible transformations allowing the reversible OFF 2 ON activation of otherwise unreactive substrates. The minimization of stoichiometric waste as well as the unique activation modes provided by these transformations make them key players for a greener future for organic synthesis. Long limited to catalytic reactions that form racemic products, considerable progress on the development of strategies for controlling diastereo-and enantioselectivity has been made in the last decade. The aim of this review is to present the different strategies that enable enantioselective transformations of this type and to highlight how they can be used to construct key synthetic building blocks in fewer operations with less waste generation.

Introduction (a) OFF 2 ON activation by hydrogen transfer

From fundamental to applied research, most efforts from synthetic organic chemists are focused on the same goal: how can we obtain valuable molecular objects (materials, bioactive molecules. . .) in the most practical, straightforward and economically reliable approach? To conceptualize the efforts towards more eco-compatible transformations, several principles such as atom-, 1 step-2 or redox-3 economies have been formulated. Consequently, and in agreement with the concept of green chemistry, the chemical synthetic route should be the shortest with minimum waste production and energy consumption. 4 This is a daunting challenge when relatively inert and simple substrates need to be selectively functionalized to construct complex enantioenriched products. Such a situation often results in the use of tedious and non-user friendly multiple operations such as separate stoichiometric oxidation and reduction steps.

In the quest for new eco-compatible reactions, hydrogen transfer based reactions have recently changed the way people conceive chemical transformations. They provide genuine solutions for the transient activation of otherwise unreactive species triggering carbon-carbon or carbon-heteroatom bondformation. As a result, by using the smallest possible atom (hydrogen) as an activating agent, considerable step, waste and atom economies have been achieved in reactions of fundamental importance.

The general principle behind these hydrogen based transformations lies in the ability of a metal complex to catalytically promote reversible hydrogen transfer reactions through OFF 2 ON activation processes (Scheme 1). 5 For example, dehydrogenation of an unreactive saturated OFF compound can form a reactive unsaturated ON transient derivative ready for subsequent in situ bond-forming events (Scheme 1a). 6 On the contrary, an unreactive unsaturated OFF compound can be hydrogenated to form a reactive saturated ON substrate involved in the formation of the product of the reaction (Scheme 1b). Overall this allows the combination of catalytic dehydrogenation and hydrogenation that simultaneously activates and merges together several unsaturated and saturated compounds allowing for unique reactivities. The main advantage of this strategy is to associate distinct redox operations that minimize the utilization of stoichiometric activating agents such as oxygen, quinones or TEMPO. The aim of this paper is to present an overview of the development of enantioselective transformations based on this OFF 2 ON activation approach initiated by hydrogen transfer. [START_REF]Reactions involving a single hydride transfer such as hydroacylation or using stoichiometric reductants such as Hantzch esters to initiate subsequent bond formation do not enter the field of the chemistry detailed herein[END_REF] The concepts behind this general reactivity, the advantages, the challenges and future research directions will be discussed in detail. Notably, while the racemic version of this approach has witnessed an impressive number of publications, the development of enantioselective counterparts is still in its infancy. This is mainly due to the difficulty in discovering efficient enantioselective catalytic systems compatible with hydrogen transfer conditions. [START_REF] Hollmann | [END_REF] Indeed, the crucial question in all the presented systems is how to insert a point of stereocontrol? As will be discussed later, each fundamental step of these processes (dehydrogenation, hydrogenation and subsequent carbon-carbon or carbon-heteroatom bond-formation) can become a strategy to control the stereochemistry of the final product. This challenge has pushed chemists to find innovative solutions to introduce chirality control notably using multiple catalysis as discussed here in detail. 9

(b) Different approaches for hydrogen activation

The general concept highlighted in Scheme 1 shows several ways to initiate a process by hydrogen transfer. The first one concerns the rapid racemization of a stereogenic center, which has found numerous applications in the resolution of racemic alcohols (vide infra). The other famous approach is the so-called borrowing hydrogen or hydrogen auto-transfer resulting in an overall redox-free sequence (Scheme 2). [START_REF] Guerbet | For the pioneering report on borrowing hydrogen[END_REF] From an initial saturated unreactive OFF substrate (alcohol for example), and in the presence of a nucleophilic species (primary amine for example), a metal complex [Met] abstracts H 2 forming a [Met]-H 2 complex and an unsaturated reactive ON intermediate prone to react with the nucleophile. After dehydration, the resulting new unsaturated ON derivative (imine for example) suffers hydrogen back-transfer delivering the final OFF product. Without the hydrogen transfer, the direct reaction from the unreactive OFF starting material to the OFF product would be impossible. The metal makes this transformation possible by an efficient transient catalytic activation avoiding the use of any stoichiometric redox reagents.

The main challenge in performing this type of process in an enantioselective manner is to find a way to displace the overall hydrogen transfer equilibrium towards product formation at temperatures where good enantiodiscrimination can be achieved. Moreover, as discussed in the following examples, the chirality of the product can be created at each fundamental step of the process and there is no general solution to determine the catalytic enantiodetermining event.

In some specific cases, the borrowing hydrogen process can be truncated and oxidation of the starting material occurs by hydrogen removal from the mixture either as a gas or using a hydrogen acceptor (Scheme 3). As compared to borrowing 10458 | Chem. Commun., 2016, 52, 10456--10473 This journal is © The Royal Society of Chemistry 2016 hydrogen, the result of the process is a saturated reactive ON final product that might be ready for additional cascade transformations. Interestingly, since the metal catalyst is still present in the mixture at the end of the process, it can also be used in one-pot for further transformations (like hydrogenation) by simply modulating the reaction conditions.

The last general approach for the hydrogen transfer activation involves metal hydride species and has found numerous applications in enantioselective carbon-carbon bond formation (Scheme 4). In these types of transformations, two distinct unreactive OFF substrates can be activated synergistically by two concomitant catalytic cycles using the same metallic center. The sequence is initiated by dehydrogenation of the first OFF substrate (alcohol for example) leading to the corresponding reactive ON oxidized intermediate (carbonyl compound) and a crucial reactive metal hydride able to activate the second OFF substrate (unsaturated double bond) to an ON metal alkyl or alkenyl complex. A final addition liberates the OFF product and turns back the metal complex. The chirality can arise from two distinct steps, either from the metal hydride insertion on the unsaturated substrate or during the last organometallic addition to the in situ generated ON electrophile. Alternative pathways to this general scheme also exist such as insertion into alkyl halide or metal promoted cyclometallation and will be discussed in more detail in part 6.

Alcohols and amines as ON substrates (a) Dynamic kinetic resolution of alcohols

As stated in the introduction, alcohols can be used either as OFF or ON reactants depending on the reaction. The dynamic kinetic resolution (DKR) of alcohols by enantioselective acylation is an example of hydrogen transfer process where an alcohol is the actual ON reactant in equilibrium with its corresponding OFF carbonyl derivative (Scheme 5). This property was advantageously used at the end of the 90s in pioneering studies by the group of Ba ¨ckvall in Sweden and Williams from United Kingdom on the DKR of racemic alcohols. 11 Notably, to efficiently develop this concept, Ba ¨ckvall took advantage of dual catalysis based on a ruthenium complex [START_REF] Blum | For the first preparation of Shvo complex[END_REF] for the rapid isomerization of alcohols, and enzymes such as Novozym-435 for enantioselective acylation. 13 Only one enantiomer of the chiral alcohol is acylated by the chiral enzyme while in the presence of the Shvo ruthenium complex Ru-cat1, the other less reactive one is rapidly inter-converted by reversible hydrogen transfer through the prochiral ketone. 14 As a result, both enantiomers of the starting racemic alcohol converge to the final acetylated product demonstrating the potential of this method for the preparation of enantioenriched alcohols in 91 to 499% ee. 15 The challenge in the development of these types of dynamic processes is to find a metal complex able to promote racemization at a rate considerably higher than the rate of acylation of the undesired enantiomer. In order to obtain systems able to promote the fastest isomerization rates at low temperatures and potentially improve the reaction efficiency and its scope, a great deal of work has been done on the design of the best possible isomerization catalysts. Most notably, in addition to the classical Shvo complex Ru-cat1, complexes based on either Ruthenium or Iridium presented in Scheme 6 perform efficiently in the DKR of alcohols. Complexes Ru-cat2 and Ru-cat3 are easily synthesized alternatives to the Shvo complex, efficient for a wide range of alcohols even at room temperature. 16 However, a base is needed to convert these pre-complexes to active catalysts possessing a vacant site on the ruthenium. [START_REF] Do | For an alternative photo-activated ruthenium complex avoiding the use of base see[END_REF] On the contrary, iridium complexes Ir-cat1 and Ir-cat2 are efficient for a broad range of alcohols in the absence of any basic additive. 18 Since the original developments of this efficient approach, a large number of papers on the topic have appeared and this chemistry has been applied to the resolution of a broad range of racemic alcohols (Scheme 7). [START_REF] Martin-Matute | For reviews on this approach see[END_REF] For example, beside classical aromatic or aliphatic substituted alcohols 1a, optically active 1,2-to 1,5-diols can be prepared with perfect stereocontrol in some cases. It is interesting to note that starting from a mixture of 4 stereoisomers of racemic diol 1b, the system converges to a single major diastereomer with high enantioselectivity. 20 Functionalized alcohols such as 1c or 1d are also tolerated in the ruthenium-enzyme catalytic system providing synthetic entries to amino-alcohols or epoxides for example. 21 In addition, structurally diversified allylic alcohols 1e can also be resolved by this method introducing a versatile adjacent double-bond to the alcohols. 22 Finally, primary alcohols 1f with a vicinal stereogenic center can also be prepared with enantioselectivities up to 99%. 23 The broad scope and the high efficiency to create enantiopure building blocks have largely been exploited for the synthesis of various natural products, highlighting the robustness of the processes. [START_REF] Leijondahl | For examples of synthetic applications of this methodology[END_REF] In an interesting alternative study, the groups of Janssen, Feringua and de Vries from Netherlands reported that racemic b-haloalcohols could be resolved in the presence of enzymes in a buffered solution to provide directly enantioenriched epoxides (Scheme 8). 25 They found that iridacycle Ir-cat3 in the presence of a catalytic amount of base was the catalyst of choice to promote the fast alcohol racemization at room temperature, providing an efficient DKR route for these types of alcohols.

Beside enzymes, there is a unique example of DKR of alcohols employing an organocatalyst proposed by the group of Fu with a chiral aminopyridine DMAP* (Scheme 9). 26 This is of particular interest because of the potential complementary scope achievable using this catalytic system. For example, a wider variety of R 2 groups (longer alkyl chain for example) can be used in the present transformation forming enantioenriched products in 82 to 93% ee. In addition to alcohols, enantiopure amines can also be efficiently prepared through the isomerization mechanism by the combination between metals and enzymes. In these cases, amines act as the reactive ON reagents while the corresponding imines represent the unreactive OFF substrates. The first report on hydrogen initiated preparation of enantiopure amines came in 2001 from the group of Kim in Korea. Starting from a ketoxime, under a positive hydrogen pressure, Pd on charcoal promoted both the reduction of the ketoxime to the racemic amine as well as its racemization through imine formation. In combination with an appropriate enzyme and an acyl transfer agent, the DKR is efficiently promoted allowing the formation of chiral amines with excellent stereocontrol (94 to 99% ee, Scheme 10). 27 Subsequently, several groups showed that amines could efficiently be resolved through in situ imine formation, by various heterogeneous catalysts or by the Shvo-type complex Ru-cat4 (Scheme 11). In combination with enzymes notably Novozym-435, clean convergence to the formation of one single acetylated enantioenriched amine (93 to 98% ee) could be observed.

Using Pd/BaSO 4 , RANEY s -Ni or RANEY s -Co, low hydrogen pressure is also necessary to form the active heterogeneous catalyst. Even-though it has been less studied, this process interestingly complements the chemistry of alcohol DKR providing access to various substituted amines.

(c) Enantioselective lactone formation

Pioneered by early work in 1990 from the group of Noyori in Japan, alcohols were also used as ON reactants in lactone synthesis. Using a chiral ruthenium complex based on BINAP, under a high hydrogen pressure (100 atm), several keto-esters could be efficiently hydrogenated providing directly or after subsequent acidic treatment six-membered ring lactones in excellent 96 to 99% ee (Scheme 12). 28 This approach constitutes an attractive enantioselective eco-compatible access to this heterocyclic framework that prevails in many important natural products and fragrances.

The process was subsequently extended to transfer hydrogen using isopropanol as a hydrogen source notably by the group of Carpentier in France. 29 By employing a chiral diamine ruthenium complex, Ru-cat5, they could avoid the use of high hydrogen pressure from the original Noyori's report (Scheme 13). Unfortunately, the transformation was less general providing enantiocontrol on the final lactone from low 10 to excellent 97% ee.

A related lactonization process was proposed in 2003 by the group of Hiroi in Japan showing that meso-diols could be oxidatively desymmetrized by the use of different amino-alcohols as chiral ligands of [Cp*IrCl 2 ] 2 (Scheme 14). 30 The key enantiodiscriminating step of the reaction is the dehydrogenation of one of the two prochiral alcohols to form an ON hydroxyaldehyde that evolves by hemiacetalization. The resulting lactol suffers a final dehydrogenation giving the corresponding optically active lactone. The results in terms of enantiocontrol remained moderate (42 to 81% ee) and the reaction required a stoichiometric amount of acetone to perform the net-oxidation of the substrate. Given the recent progress in acceptorless dehydrogenation, a greener and more efficient version of this transformation might be envisaged.

The group of Johnson in the United States reported the dynamic kinetic asymmetric reduction of racemic a-keto-esters by hydrogenation using a HCOOH/Et 3 N mixture as the hydrogen source (Scheme 15). 31 Thanks to the appropriate ruthenium complex in the presence of a chiral 1,2-aminosulfonamide ligand, one single enantiomer of the starting material is selectively reduced, providing two contiguous stereocenters with excellent diastereocontrol (420 : 1 dr) and 78 to 92% ee. The other nonreactive enantiomer is racemized through reversible enolization, providing a pathway for the dynamic resolution. Finally, the generated secondary ON hydroxyester spontaneously evolved by diastereoselective lactonization leading to synthetically attractive g-butyrolactones bearing three contiguous stereocenters.

Finally, the group of Dong in the United States showed in 2013 that starting from 1,5-hydroxyketones, the chiral Noyori's ruthenium complex Ru-cat6 was able to catalyze successive hydrogen transfers resulting in the formation of optically active d-valerolactones (Scheme 16). 32 Initially, the enantioselective reduction of the ketone to 1,5-diol is followed by dehydrogenation of the primary alcohol providing an enantioenriched ON secondary hydroxyaldehyde able to form a lactol intermediate by hemiacetalization from which final dehydrogenation gave the enantioenriched d-valerolactones in 86 to 96% ee. The transformation is significantly accelerated by using a mixture of acetone and isopropanol to facilitate both successive reduction and oxidation reactions, and the stability of the final lactone drives the thermodynamic equilibrium. As a result of this strong thermodynamic gain, only 1.2 equivalent of acetone is required for the net oxidation of the product and 3 equivalents of isopropanol are used as an autocatalyst to increase the transfer hydrogenation rate. This reaction highlights the power of hydrogen transfer initiated-transformations where both reduction and oxidation occur under the same conditions and use one single catalyst to act simultaneously in apparently opposite reactions (oxidation and reduction).

From all these transformations using alcohols and amines as ON or OFF substrates, it appears that the DKR of alcohols and amines by acylation is already a mature field allowing excellent results on a wide array of substrates. On the contrary, other transformations such as the formation of lactones, eventhough they seem attractive in terms of eco-compatibility have only remained limited examples for now. Given the value of these processes it would not be surprising that these studies should inspire other research on the topic.

Carbonyl alkylation with alcohols as OFF substrates (a) Hydrogenation as the enantioselective step

The use of alcohols as initial OFF reagents for the catalytic dehydrogenative alkylation of ketones is a modern eco-compatible approach to rapidly combine products without the need to prefunctionalize the substrates or the requirement of any stoichiometric redox agents. 33 Notably, when used in a borrowing hydrogen process, alcohols act both as an alkyl source and also as a hydrogen source increasing the eco-compatibility of the transformations.

Despite the interest in borrowing hydrogen for ketone alkylation and an intensive research in the discovery of more and more efficient catalysts for the racemic version, the enantioselective variant is particularly over-looked. This is rather surprising given the possibility of inserting a point of stereocontrol during the hydrogenation event for which a huge number of metal catalysts should potentially be highly efficient.

As highlighted in the precedent chapters, enzymes have been known for a long time to promote enantioselective redox-neutral transformations. Therefore, the first successful examples of efficient borrowing hydrogen with alcohols as alkylating reagents were disclosed using different enzymes as catalysts. 34 In this area, Baker's yeast or C.lunata notably allowed the dehydrative condensation of a-cyano-ketones with different alcohols without the requirement of any extra stoichiometric reagent (Scheme 17). Interestingly, the alcohol used as a solvent not only acts as an alkyl donor by in situ forming the required ON aldehyde but also as an extra hydrogen source triggering the successive reduction of the transient Knoevenagel-type unsaturated adduct. The resulting ON cyanoketone is directly reduced to the expected b-cyanoalcohol with good to high diastereoselectivity and 86 to 99% ee. It must be pointed out that the enzymes used in these studies are able to promote both reversible hydrogen transfers but also the C-C bond-forming event highlighting the versatility of this bioconversion.

The difficulty in finding an appropriate catalytic system able to promote enantioselectively the several distinct reactions explains why besides enzymes, other hydrogen transfer initiated reactions were scarcely disclosed in the literature. The first report on a metal catalyst variant of the above mentioned transformation only appeared in 2006 by a work from the group of Nishibayashi in Japan devoted to the enantioselective reductive alkylation of acetophenones with primary alcohols. 35 They proposed a sequential one-pot operation with two complementary metal catalysts involved successively in each reductive step of the transformation (Scheme 18). The first achiral iridium complex in combination with KOH promoted the borrowing hydrogen ketone alkylation via a Claisen-Schmidt condensation, while the second chiral ferrocenyl ruthenium catalyst added subsequently induced the enantioselective full reduction of the transient unsaturated ketone by hydrogen transfer from the added isopropanol. By sequentially combining those two distinct catalysts, elongated chiral alcohols were obtained in 88 to 98% ee. The important aspect for the reaction to work with good levels of enantiocontrol is the ability of the ruthenium complex to act independently from the iridium complex in the enantioselective ketone transfer hydrogenation. It must be pointed out that the use of inorganic base (KOH or others) in this process as well as in the following ketone alkylation is crucial to promote the C-C bond-forming event by aldolization.

The challenge associated with the discovery of a single metal catalytic system for the direct use of alcohols in alkylation was tackled in 2007 by the group of Williams in the United Kingdom by combining a Wittig reagent with chiral BINAPiridium complexes in a borrowing hydrogen alcohol alkylation (Scheme 19). 36 In this process, the phosphorus ylide adds to the in situ generated reactive ON aldehyde providing an a-,b-unsaturated ester enantioselectively hydrogenated by the iridium-hydrogen complex. This represented the first success in this strategy even thought the final chiral product was obtained in a moderate 58% yield and 87% ee. It must be pointed out here that as in many cases of borrowing hydrogen, the reaction is performed at 110 1C, a temperature at which a lot of enantioselective processes provide lower enantiocontrol. This crucial point implies that the development of more efficient processes goes through the discovery of catalysts either being able to significantly decrease the reaction temperature or being highly enantioselective regardless of the conditions.

In this context, the group of Adolfsson in Sweden proposed in 2014 a ruthenium based methodology performed between 40 and 65 1C for the reductive alkylation of acetophenones with primary alcohols (Scheme 20). 37 Contrary to the work of Williams 36 and more related to the Nishibayashi report, 35 they did not attempt to perform final alkene enantioselective hydrogenation but focused more on ketone reduction as the stereoselective step. Using an excess of alcohol, in the presence of a chiral amino alcohol ligand, acetophenones are alkylated through the auto-transfer mechanism. Thanks to the chiral ruthenium complex, the excess starting alcohol subsequently promoted the enantioselective transfer hydrogenation of the ketone providing chiral alcohols in 57 to 89% ee. It is important to note that the same ruthenium complex is able to promote both the borrowing hydrogen as well as the enantioselective ketone transfer hydrogenation even though the yields remain moderate and the ee remains below 90%.

From all these examples, it clearly appears that promoting direct enantioselective borrowing hydrogen C-C bond formation through hydrogenation remains a challenging task. Notably, finding a single catalytic system able to promote high reactivity in the reversible hydrogen transfer for efficient C-C bond formation and enantioselective hydrogenation remain difficult. Given the number of known hydrogenation catalysts, and given the amount of research on the racemic version of this highly eco-compatible reaction, rapid progresses can be expected in the near future.

(b) Dehydrogenation as the enantioselective step

The challenging direct enantioselective alkylation of ketones involving the final stereodetermining hydrogenation has been circumvented in 2013 by the group of Suzuki in Japan developing instead an enantioselective dehydrogenative desymmetrization of meso-1,3-diols in the presence of an excess of aldehyde. 38a They first proposed an auto-transfer approach with a chiral diamino iridium complex in the presence of KOH for the generation of the optically active ON hydroxy ketone. Subsequent crotonization, followed by a final hydrogen transfer provided the chiral a-alkylated ketone in an excellent 92% ee and 499 : 1 dr albeit in moderate 33% yield (Scheme 21a). Indeed, some unsaturated ketone (14%) is also isolated as a side product probably due to the loss of hydrogen by competitive addition to the excess aldehyde. To solve this problem, a sequential alternative involving the addition of an extra hydrogen source (alcohols) after borrowing hydrogen allows to cleanly form the enantioenriched hydroxy ketones in good yields, perfect diastereocontrol and 88 to 94% ee (Scheme 21b).

Building on these results, the same group reported in 2015 that this type of reactivity could be applied to meso-1,4-diols in a purely dehydrogenative process (Scheme 22). 38b Hydrogen was transferred enantioselectively from the 1,4-diol to the excess aldehyde in-situ forming the key optically ON hydroxy ketone involved in the final aldolization/dehydration one-pot sequence promoted by CsOHÁH 2 O delivering the enantioenriched hydroxy enones in 92 to 99% ee.

From these two examples, it appears that dehydrogenation is a valuable approach in terms of enantiocontrol for alkylation processes even though an excess of aldehyde as a hydrogen acceptor is required for better reactivity. Therefore future developments should be devoted to the design of more efficient acceptorless dehydrogenation systems to get rid of the required excess aldehyde.

Allylic alcohol functionalization by borrowing hydrogen

The precedent examples highlight the challenges facing the development of enantioselective borrowing hydrogen transformations notably in terms of efficient enantiocontrol. A breakthrough in the use of alcohols for an enantioselective borrowing hydrogen C-C bond-forming process came in 2013 from the group of Quintard and Rodriguez in France. To overcome the difficulty in performing both the reversible hydrogen transfer and the enantioselective hydrogenation with a chiral organometallic complex, they proposed a dual catalytic system involving a metal catalyzed borrowing hydrogen and an organocatalytic enantioselective reaction (Scheme 23). Starting from an OFF allylic alcohol, an easily available achiral iron complex [Fe] 39 promoted dehydrogenation to the crucial ON a,b-unsaturated aldehyde. A chiral secondary amine organocatalyst subsequently promoted the iminium-type enantioselective Michael addition forming an enantioenriched aliphatic aldehyde able to be reduced by the iron hydride to form directly the enantioenriched alcohol. The interest in introducing an organocatalytic step in the borrowing hydrogen mechanism lies in the possible easy insertion of an enantiocontrol point as well as displacing the overall hydrogen transfer equilibrium towards product formation. As a result, the process using the iron complex occurs at relatively low temperatures (10-25 1C).

In an initial study, the addition of variously substituted ketoesters to allylic alcohols was performed. The Kno ¨lker complex Fe-cat1 (activated by CO decoordination with Me 3 NO) 40 in combination with diarylprolinol silyl ether O-cat1 was efficiently combined to give rise to the products with good enantiocontrol (79 to 90% ee) (Scheme 24).

It is interesting to note that the chiral linear alcohols obtained from this transformation are in equilibrium with the closed lactol form. This led to a following study from the same group to attempt a subsequent cascade fragmentation from the lactol to directly form linear protected 3-alkylpentanol scaffolds 2 (Scheme 25). These structures are present in numerous pheromones 41 and used in various natural product synthesis. Unfortunately, their preparation highlights the challenge associated with the synthesis of products containing relatively inert functions (protected alcohols, unreactive ketones) from raw materials. As a result, the reported literature procedures are poorly eco-compatible and require multiple redox as well as protecting group manipulations.

With simple diketones instead of keto-esters, the designed cascade proceeds smoothly providing directly the optically active protected alcohols 2 from inexpensive starting materials. Using the combination between the iron complex and diarylprolinol silyl ethers, the expected protected 3-alkylpentanols were obtained in 40 to 92% ee depending on the substitution pattern (Scheme 25). 42 This cascade strategy allows the rapid preparation of crucial synthetic intermediates that would otherwise require lengthy synthesis. For example, Doremox (an odorant rose scent) and key fragments of lyconadin A or apratoxin A were prepared in 2-3 steps vs. 5 to 11 steps by the known literature approaches. 43 In a more recent study, the mechanism of the iron-organocatalyzed transformation was studied in more detail leading to the development of an innovative triple catalyzed process involving iron-, copper-and organo-catalysis (Scheme 26). 42b In this transformation, the additional copper catalyst [5 mol% Cu(acac) 2 ] is used to activate the diketone, modulating the transition state of the Michael addition. The cooperative role of this added catalyst allows for a systematic improvement of the enantiomeric excess in the allylic alcohol functionalization.

Amine alkylation by alcohols using borrowing hydrogen

The direct amine alkylation by alcohols is another key borrowing hydrogen reaction. 44 A wide variety of metal complexes notably based on iridium or rhodium have been used for this attractive reaction avoiding stoichiometric leaving group utilization and forming only water as the side product. Even though the enantioselective preparation of chiral amines is a crucial industrial reaction, the first report on the enantioselective version of this eco-compatible transformation only appeared in 2013 by a work from the group of Oe in Japan (Scheme 27). 45 In the presence of a secondary amine, racemic 1,2-diols are fully oxidized by abstraction of two hydrogen molecules with a ruthenium complex providing crucial reactive ON glyoxaldehyde imines 3. A final enantioselective back hydrogen transfer controlled by a chiral ferrocenyl diphosphine ligand forms the corresponding enantioenriched b-amino alcohols with moderate enantioselectivities (o78% ee). Even though acyclic amines showed low reactivity and no enantiocontrol, a broad range of chiral amino alcohols could be synthesized with five-and six-membered ring amines in 25 to 99% yield.

Soon after, the group of Zhao in Singapore discovered an innovative solution for the successful enantioselective amine alkylation (Scheme 28). 46 Based on the recent discoveries on enantioselective counterion catalysis, 47 they hypothesized that a combination between a chiral metal hydrogenation complex and a chiral phosphoric acid might provide a synergistic transition state for the key enantioselective reduction improving the stereocontrol of these transformations.

Extensive screening of metal-complex/phosphoric acid systems revealed that the best results were obtained by using a combination between Ir-cat4 and O-cat3. Under optimized conditions, the dual catalysis allows the formation of diversely functionalized amines in 64 to 98% yield and up to 97% ee. The use of molecular sieves is necessary to remove the formed water molecule from the reaction mixture. The remarkable enantioselectivity obtained by the synergistic catalysis at rather high temperature (100 1C) accounts for a well-defined transition state opening new opportunities for other borrowing hydrogen strategies.

Building on this initial report, the same team reported a dynamic kinetic resolution for the construction of a-branched amines possessing two contiguous stereocenters (Scheme 29). 48 Using a combination of the same iridium complex with a spirocyclic chiral phosphoric acid, the final amines are constructed in excellent diastereo-and enantiocontrol (9 : 1 to 449 : 1 dr and 96 to 98% ee). Starting from a mixture of four stereoisomers of the alcohol, the efficient system converges to the formation of one single major diasteroisomer with high enantioselectivity. This enantioselective DKR is made possible by the fast equilibrium between the intermediate iminium ion through enamine formation prior to enantioselective hydrogenation.

Very recently, the group of Beller in Germany showed that racemic 1,2-diols could be condensed with urea to generate valuable oxazolidinones and only ammonia and water as by-products (Scheme 30). 49 Interestingly, the use of a chiral biphosphine ligand (R)-(+)-MeOBIPHEP in combination with Ru 3 (CO) 12 provided the final oxazolidones in good 82 to 92% ee. This is notable given the relatively high temperature required for the borrowing hydrogen (150 1C), highlighting the robustness of the catalytic system used.

Scheme 27 Amino alcohols synthesis by ruthenium catalysis.

Scheme 28 Dual iridium phosphoric acid catalysis in amine alkylation by alcohols.

Scheme 29 Amino-alcohols synthesis by DKR through borrowing hydrogen.

This journal is © The Royal Society of Chemistry 2016

Finally, it must be added that the diastereoselective variants of amine alkylation by alcohols notably using Ellman's sulfinamide or -1-phenylethylamine as chiral auxiliaries were reported by several groups in the United States. 50 The diastereoselective reactions using achiral iridium or ruthenium complexes provided chiral amines with 70 : 30 to 495 : 5 dr.

From this part, it is clear that enantioselective borrowing hydrogen transformations are still in their infancy but recent results notably based on multicatalysis clearly show that these highly eco-compatible reactions can be run with high stereocontrol, opening avenues for the development of other related processes.

Hydrogen-promoted catalytic metal hydride insertion forming reactive organometallics

Reactive organometallic intermediates such as Grignard, organozinc, or boron reagents are highly useful to introduce elongated carbon chains on various functional groups (aldehydes, imines, epoxides. . .). Unfortunately, their preparation requires the generation of a large amount of waste and these products are often associated with pyrophoric behavior. On the contrary, use of hydrogen, a simple non-heavy molecule, to promote a metal hydride insertion into an unsaturated substrate is an eco-compatible alternative to these classical organometallic reactions and recent powerful developments on this topic will be outlined in the following sections. [START_REF] Quintard | Hydroacylation is a reaction with a metal hydride not involving H 2 transfer and as a result is not discussed in this review. Another approach to this enantioselective metal hydride insertion creating subsequent C-C bond is to combine allylic alcohol isomerization and C-C bond formation by enamine catalysis[END_REF]

(a) Hydroformylation

Enantioselective metal catalyzed hydroformylation is a typical example of activation by metal hydrides formed upon hydrogen transfer. It received a full coverage in recent reviews and as a result is not presented in detail herein. 52 The metal of choice for this transformation is rhodium in combination with chiral phosphorus donor ligands and the general concept relies on the insertion of a metal hydride into an alkene (Scheme 31).

Under a positive pressure of carbon-monoxide, the resulting reactive organometallic transient species evolves by CO insertion to form a crucial acyl-metal intermediate. Finally, under the hydrogen pressure, the chiral aldehyde is released after H 2 oxidative insertion and reductive elimination giving back the catalytically active metal hydride complex.

One of the biggest challenges in hydroformylation reactions concerns the regioselectivity of metal insertion at a less or more hindered position delivering either linear or branched aldehydes. Huge efforts have been devoted in the past twenty years to solve this challenge and a wide array of chiral ligands, notably chiral phosphines, phosphites or phosphoramidites have been developed to promote selectively the formation of either products. In addition, thanks to the design of these ligands, excellent stereocontrol can be obtained in these enantioselective processes.

Besides this highly useful general method to access branched saturated aldehydes recent extensions to the insertion of other classes of functional groups will be presented in more detail in the following sections. Indeed, by distracting the process from the final CO insertion to the addition to other chemical functions, a variety of structurally diverse scaffolds can be created in an eco-compatible manner.

(b) Metal hydride insertion into unsaturated systems and subsequent functionalization

The group of Krische in the United States has considerably increased the scope of metal hydride insertions resulting in an incredible improvement of the potential of hydrogen mediated coupling reactions for the synthesis of complex molecules. 53 This has led to the development of a broad range of original and eco-compatible reactions combining different donor-acceptor systems.

The first enantioselective developments in these transformations were performed by inserting the metal hydride onto alkynes and trapping the resulting organometallic complex with unsaturated acceptors such as alkenes, aldehydes or imines (Scheme 32). Subtle differences exist between the catalytic systems used and the donor-acceptor combination but the general principles highlighted in this scheme prevail. Insertion of the metalhydride into the alkyne forms a nucleophilic organometallic ON intermediate able to react with an acceptor (Scheme 32a). Under H 2 pressure, oxidative addition occurs forming a metal hydrogen complex ready for a reductive elimination providing a functionalized alkene with concomitant release of the catalytically active initial metal-hydride. Alternatively, the reaction might in some cases occur through initial cycloaddition between the alkyne and the acceptor from a cationic rhodium Following these lines, a wide range of alkynes can be activated simply by rhodium(I) complexes in combination with chiral bisphosphine ligands while an acid co-catalyst is sometimes required to modulate the counterion around the rhodium catalyst (Scheme 33). Only 1 atmosphere of hydrogen is sufficient to promote reductive coupling and the metal hydride formed can be added to aldehydes or imines in typically 490% enantiocontrol (products 4a-4d). 54 The intramolecular version allows the use of aldehydes or even alkenes as potential acceptors in 98-99% ee (products 4e-4f). 55 Moreover, highly reactive keto-esters are also good substrates for this transformation forming dienes such as 4g in 93% ee. 56 Finally, if widely available acetylene is used as the starting alkyne, dimerization occurs before condensation to the acceptor (aldehydes or imines) forming valuable dienes such as 4h or 4i. 57 Beside alkynes, enones also perform efficiently in these transformations (Scheme 34). 58 In this case, hydrogenation of the double bond generates a chiral rhodium enolate involved in a stereoselective aldolization with the aldehyde leading to the expected syn aldol product. Compared to other aldolizations neither an excess of reagents nor the participation of stoichiometric additives is required except 1 atmosphere of hydrogen. In addition, a total regioselectivity for a-branched aldol products is observed.

Another major breakthrough came with the discovery of the specific reactivity of functionalized allylic (propargylic) derivatives or simple allenes. With these OFF substrates, reactive allylic nucleophiles can be easily generated by oxidative addition to a metal opening new avenues for the synthesis of eco-compatible complex molecules. As compared to classical allylation methodologies employing allylic silane, stannane or Scheme 32 General mechanism for hydrometallation of alkynes. borane reagents, this chemistry considerably decreases the waste generated to form metal allyl complexes. Most notably, the group of Krische has discovered that these metal hydride insertions could be promoted either as shown before using an aldehyde in combination with a H 2 source (gaz or isopropanol) or directly in an eco-compatible auto-transfer from an alcohol (Scheme 35). 59 In this case, the alcohol acts both as the hydrogen source for metal hydride insertion but also in situ generates a reactive aldehyde avoiding the use of positive hydrogen pressure.

Mechanistically, this allylation catalyzed by iridium(III) complexes in the presence of chiral phosphine ligands follows the general pathway shown in Scheme 36. An initial active iridacyclic p-allyl catalyst arising from insertion into an aromatic carboxylic acid co-catalyst, coordinates to the alcohol leading to a key metal alkoxide. Hydride insertion liberates the reactive ON aldehyde and the iridium(III) hydride in equilibrium with the anionic iridium(I). This Ir(I) complex adds to the allylic partner liberating the leaving group and forming the nucleophilic p-allyl metal. Nucleophilic addition to the electrophilic aldehyde enantioselectively creates a new carbon-carbon bond and final ligand exchange by another alcohol molecule closes the catalytic cycle.

In most cases the iridium complexes derived from [Ir(COD)Cl] 2 , biphosphine ligand such as BIPHEP or SEGPHOS, and activated benzoic acids (e.g.: m-NO 2 -BzOH) are the most efficient in this type of chemistry (Scheme 37). In the presence of allyl acetate, the active iridium complex Ir-cat5 is formed. This bisphosphine iridium(III) complex features an iridacycle from CH insertion into the aromatic carboxylic acid and an allyl moiety coming from insertion in allyl acetate with concomitant acetic acid release. This stable complex can be isolated and is now commercially available.

Following this general catalytic activation, a wide range of substrates are amenable to hydrogen initiated coupling (Scheme 35). Starting from either the aldehyde level in combination with a hydrogen source or starting directly from the alcohol, numerous functional groups can be incorporated increasing the toolbox available in such types of transformations. Different substituted allylic esters such as 5a-5f allow the creation of one or two contiguous stereocenters in 83 to 99% ee. 59 The high level of enantiocontrol is another interesting aspect of this chemistry and a crucial point for its implementation in total synthesis.

Using allylic diester 5e, anti-1,2-diols are prepared in 410 : 1 dr and 490% ee. 60 Starting from cyclic carbonate 5f, 1,3-diols are also prepared in typically excellent enantiocontrol. 61 Allylic aziridine 5g is also amenable to the reductive coupling creating enantioenriched amino-alcohols. 62 Cyclopropane 5h can also be opened by metal hydrides introducing an ester containing a carbon chain with excellent dia-and enantiocontrol (6 : 1 to 420 : 1 dr and 491% ee). 63 Substitution on the internal position of the alkene of the allylic partner is also possible as in 5i providing useful entries to g-butyrolactones for example. 64 Alternatively, propargyl chlorides can also be used as in 5j, inserting a propargyl chain into chiral alcohols. 65 Finally, vinyl epoxide 5k proved excellent to introduce 1,3-diols possessing a stereogenic quaternary center in 491% ee. 66 Interestingly, ketones also performed well in these types of transformations 67 and for example variously substituted isatins react with allylic acetates or allenes in the presence of isopropanol as the hydrogen source forming tertiary chiral allylic alcohols in 80 to 96% ee (Scheme 38). It must be pointed out that opposite absolute stereochemistry at the newly formed chiral carbon is observed starting from allyl acetate (R 2 = H) and 1,1-dimethylallene (R 2 , R 3 = Me) suggesting two different transition states for nucleophilic addition.

At this stage, we must highlight a particular example of this efficient hydrogen coupling chemistry: the use of 1,3-propanediols as OFF substrates in bi-directional condensations. The corresponding oxidized 1,3-dialdehydes are poorly stable and cannot be applied in stereoselective synthesis. However, thanks to their in situ generation from 1,3-diols, a nucleophile-electrophile pair is efficiently combined allowing the direct access to chiral 1,3-diols (Scheme 39a). 68 More impressively, using substituted allylic acetates, the four acyclic stereogenic centers created in one single operation are obtained in 5 : 1 to 6 : 1 dr and perfect enantiocontrol (499% ee) and ready for subsequent synthetic transformations (Scheme 39b). Chiral 1,3-diols (polyketides and polypropionates) are pivotal to an almost infinite number of complex natural molecules possessing a broad range of different bioactivities. Unfortunately, until then, their enantioselective preparation usually required iterative step-wise processes often requiring several redox group inter-conversion and protecting group manipulation. 69 The discovery of the hydrogen initiated coupling of 1,3-diols constitutes a new scientific paradigm in the construction of these polyols and have been successfully applied in the synthesis of different complex natural products. 70 For example, thanks to this approach, the synthesis of key fragments of Bryostatin 7, Roxaticin or Zincophorin methyl ester has been considerably shortened. 71 Finally, the last breakthrough in this type of chemistry came from the discovery that reactive p-allyl complexes can also be generated from non-prefunctionalized conjugated alkenes or alkynes allowing access to an all new range of chiral alcohols by enantioselective addition to simple aldehydes. Interestingly, in this chemistry, depending on the substrate used, alternatives to iridium such as less expensive ruthenium complexes can also be applied successfully. Dienes 6a or 6c as well as enyne 6b are efficient starting materials providing chiral alcohols possessing an adjacent stereogenic center with 43.8 : 1 dr and 86 to 99% ee (Scheme 40). 72 Interestingly, allenes can also be used in this chemistry either directly like in the case of 6e or generated from easily available alkynes 6d through hydrogen transfer. 73 In the case of 1,1-disubstituted allene 6e the reactive p-allyl metal reacted regioselectively generating chiral alcohols with challenging contiguous quaternary stereocenters. Finally, propargylic alcohols 6f or 6g are also able to promote metal p-allyl formation through internal hydride transfer. This results in the formation of silyl enol ethers or 1,4 diols after subsequent reduction. 74 From all these substrates, the use of butadiene, a feedstock reagent produced industrially is particularly interesting for the synthesis of complex molecules starting from raw materials and features a valuable diastereodivergent process depending on the nature of the acidic co-catalyst used. Indeed, the group of Krische showed that by using an achiral bisphosphine ligand (dppf) in combination with a chiral counterion (binol derived phosphoric acid), the anti-allylation product was formed predominantly (Scheme 41a). 72c On the contrary, using a combination of chiral SEGPHOS and TADDOL derived phosphoric acid as a counterion, the opposite syn-allylation adduct was formed highlighting the potential of this chemistry in the synthesis of all possible steroisomers of a given molecule at hand (Scheme 41b). 72d In conclusion to this part, by applying the principle of hydrogen transfer metal hydride insertion to unsaturated carbon bonds and trapping the in situ generated organometallics with a wide variety of acceptors, an extraordinary rich chemistry has been developed allowing rapid and eco-compatible access to key enantioenriched building blocks. This strategy has already found applications in the efficient synthesis of numerous natural products considerably short-cutting existing routes. 70 Given the generated economies and the excellent stereocontrol observed, a broad range of other transformations should be available based on this concept. Alternatively, because of the strong economic pressure related to the use of noble metals (Ir, Rh, Ru), future research studies should be devoted to the development of cheap metals as shown notably by recent progresses in hydrogen transfer reactions catalyzed by iron complexes. 75 In addition, nickel [START_REF]For a review on Nickel coupling: (a) J. Montgomery[END_REF] or copper complexes also seem to be viable alternatives and through research studies innovative ways need to be found to avoid the use of stoichiometric reducing additives such as boranes or dialkylzinc. [START_REF] Deschamp | For examples of copper catalyzed enantioselective variant using stoichiometric reductant[END_REF]

Conclusion

The current worldwide preoccupation on waste decrease and energy economy pushes the chemistry community at a point in its history requiring a dramatic change in the current approaches to construct complex chiral molecules by introducing greener processes in the synthetic routes. The initiation of eco-compatible transformations by hydrogen transfer appears to be an attractive method to this end. By applying simple hydrogen transfers, a wide range of molecules can be activated efficiently without the generation of any side products through a reversible OFF 2 ON activation pathway providing genuine solutions for enantioselective catalysis.

Long limited to alcohol or amine dynamic resolution as well as chiral lactone formation, recent developments in multi-catalysis and metal hydride insertion-addition have considerably increased the potential of this approach providing a broad range of eco-compatible tools for the synthesis of complex building blocks.

Considering the many advantages of these methods, the future should see an explosion in the development of related transformations notably through the discovery of innovative activation modes. In particular, the field should benefit from the huge amount of research done on the development of new complexes for transfer hydrogenations. 78 In this field, an explosion in the alternative use of non-noble metals such as iron should additionally increase the interest in this approach in the context of eco-compatibility.

  This journal is © The Royal Society of Chemistry 2016 Chem. Commun., 2016, 52, 10456--10473 | 10457

Scheme 3

 3 Scheme 3 General concept of dehydrogenative activation.

Scheme 6 Scheme 8

 68 Scheme 6 Efficient metal catalysts for the DKR of alcohols.

Scheme 9

 9 Scheme 9 Dual organocatalytic/ruthenium catalysis for DKR of alcohols.

Scheme 14

 14 Scheme 14 Enantioselective lactone formation from meso-diols.

Scheme 17

 17 Scheme 17 Enzyme catatalyzed a-cyano-ketone alkylation-reduction sequence.

Scheme 20

 20 Scheme 20 Hydrogen auto-transfer ketone alkylation and enantioselective transfer hydrogenation.

Scheme 23

 23 Scheme 23 Concept of the dual allylic alcohols functionalization.

Scheme 30

 30 Scheme 30 Synthesis of oxazolidinones from racemic diols through borrowing hydrogen.Scheme 31 General pathway for enantioselective hydroformylation.

Scheme 33

 33 Scheme 33 Alkyne activation by chiral rhodium complexes in the presence of 1 atmosphere of H 2 .

Scheme 35

 35 Scheme 35 Scope of the hydrogen mediated allyaltion.

Scheme 37

 37 Scheme 37 Example of active iridium complex formation.

Scheme 40

 40 Scheme 40 Scope of alkene and allene hydrogen mediated addition to aldehydes.

This journal is © The Royal Society of Chemistry 2016

Acknowledgements

The Agence Nationale pour la Recherche (ANR-13-PDOC-0007-01), the Centre National de la Recherche Scientifique (CNRS) and the Aix-Marseille Universite ´are gratefully acknowledged for financial support of our work on OFF 2 ON systems.

Notes and references

Adrien Quintard

Adrien Quintard studied chemistry at the University of Toulouse and then at the CPE/University of Lyon. He completed his PhD in 2011 under the supervision of Prof. A. Alexakis at the University of Geneva. He subsequently moved to the University of Stanford for a one year post-doctoral stay working with Prof. B. M. Trost. He was appointed as an associate researcher at Aix-Marseille University in 2012 and has been a CNRS French researcher since 2014. His research interests include the development of organometallic/ organocatalytic enantioselective methodologies and their application to natural product synthesis.

Jean Rodriguez

Jean Rodriguez was born in Cieza (Spain) in 1958 and in 1959 his family immigrated to France. After studying chemistry at the University of Aix-Marseille (France), he completed his PhD as a CNRS researcher with Prof. B. Waegell and Prof. P. Brun in 1987. He completed his Habilitation in 1992, also at Marseille, where he is currently Professor and Director of the UMR-CNRS-7313-iSm2. His research interests include the development of domino and multicomponent reactions, and their application in stereoselective organocatalyzed synthesis. In 1998 he was awarded the ACROS prize in Organic Chemistry, in 2009 he was awarded the prize of the Division of Organic Chemistry from the French Chemical Society and in 2013 he became a ''Distinguished member'' of the French Chemical Society.


Abstract-In this paper, a novel fully inkjet-printed via fabrication technology and various inkjet-printed substrate integrated waveguide (SIW) structures on thick polymer substrates are presented. The electrical properties of PMMA are thoroughly studied up to 8 GHz utilizing the T-resonator method, and inkjet-printable silver nanoparticle ink on PMMA are characterized. A "long via" fabrication process up to 1 mm utilizing inkjet printing technology is demonstrated and its characteristics are presented for the first time. The inkjet-printed vias on 0.8 mm thick substrate have a resistance of about 0.2 Ω. An equivalent circuit model of the inkjet-printed stepped vias is also discussed. An inkjet-printed microstrip-to-SIW interconnect and a SIW cavity resonator utilizing the proposed inkjet-printed via fabrication process are also presented. The design of the components and the fabrication steps are discussed, and the measured performances over the microwave frequency range of the prototypes are presented.

Index Terms-Additive fabrication, inkjet-printed Substrate Integrated Waveguide (SIW), inkjet-printed via, low-cost via fabrication, Polymethyl methacrylate (PMMA).

I. INTRODUCTION

NKJET printing technology is investigated and widely utilized as an alternative fabrication method to the conventional subtractive fabrication methods, such as milling and etching. The importance of "green", scalable and cost-efficient technology is ever increasing for numerous applications like the Internet of Things (IoT), the radio frequency identification tags (RFIDs), and the wireless sensor networks (WSNs) [START_REF] Atzori | The Internet of Things: A survey[END_REF][START_REF] Lakafosis | Progress Towards the First Wireless Sensor Networks Consisting of Inkjet-Printed, Paper-Based RFID-Enabled Sensor Tags[END_REF][START_REF] Singh | Inkjet Printing-Process and Its Applications[END_REF]. The inkjet printing technology does not produce any byproducts because it only deposits the controlled amount of functionalized inks such as silver nanoparticles on desired position. In addition, it is a completely dry process which is compatible with most modern fabrication processes [START_REF] Calvert | Inkjet Printing for Materials and Devices[END_REF]. Arbitrary geometries with small feature sizes (less than 50 µm) can be printed on numerous substrates without any special masking [START_REF] Yang | RFID Tag and RF Structures on a Paper Substrate Using Inkjet-Printing Technology[END_REF][START_REF] Mantysalo | Evaluation of Inkjet Technology for Electronic Packaging and System Integration[END_REF][START_REF] Park | High-resolution electrohydrodynamic jet printing[END_REF]. Recently, the development of various types of nanoparticle-based inks such as polymers, carbon nanotubes (CNTs), piezoelectric materials, and high dielectric constant materials has attracted significant interest from many researchers [START_REF] Mabrook | Inkjet-Printed Polymer Films for the Detection of Organic Vapors[END_REF][START_REF] Kordás | Inkjet Printing of Electrically Conductive Patterns of Carbon Nanotubes[END_REF][START_REF] Hossain | Development of a Bioactive Paper Sensor for Detection of Neurotoxins Using Piezoelectric Inkjet Printing of Sol-Gel-Derived Bioinks[END_REF][START_REF] Kaydanova | Direct-write inkjet printing for fabrication of barium strontium titanate-based tunable circuits[END_REF]. Numerous studies and applications utilizing inkjet printing technology in microwave area have been reported including inkjet-printed wireless power transfer topologies, RFID-based sensors and microwave components for high-speed communication systems [START_REF] Kim | An Inkjet-Printed Solar-Powered Wireless Beacon on Paper for Identification and Wireless Power Transmission Applications[END_REF][START_REF] Kim | Inkjet-printed Antennas, Sensors, and Circuits on Paper Substrate[END_REF]. However, most of these works are single-layered structures because it is challenging to realize inkjet-printed vias, which are one of the most critical factors for the realization of highly integrated systems, packages and multi-layered structures.

In this work, the implementation of inkjet-printed stepped vias on thick substrates (thickness > 100 µm) is presented for the first time. Only a small number of technologies for implementing vias utilizing inkjet printing technology have been reported, all of which have been implemented on thin substrates with thickness below 100 µm [START_REF] Reinhold | Inkjet printing of electrical vias[END_REF][START_REF] Kawase | Inkjet Printed Via-Hole Interconnections and Resistors for All-Polymer Transistor Circuits[END_REF][START_REF] Falat | Nano-silver inkjet printed interconnections through the microvias for flexible electronics[END_REF][START_REF] Mckerricher | All Inkjet Printed 3D Microwave Capacitors and Inductors with Vias[END_REF][START_REF] Terani | Fully inkjet-printed multilayer microstrip and T-resonator structures for the RF characterization of printable materials and interconnects[END_REF]. Such thin substrates are unsuitable for applications in relatively lower frequency bands, such as mobile, WiFi, ISM, etc. The feature size of microwave components, such as the width of microstrip line, is narrow on thin substrate, which results in high design sensitivities to fabrication tolerances. On the other side, the radiation efficiency of antennas, like patches, resonators and waveguide structures (such as substrate-integrated waveguides (SIW)) is significantly affected by the substrate thickness [START_REF] Bozzi | Review of substrate-integrated waveguide circuits and antennas[END_REF]. Therefore, it is necessary to develop via fabrication concepts or techniques which can be applied to various substrates of different thicknesses. The major issue in the metallization of via holes utilizing inkjet printing technology is to maintain a continuous and uniform metal layer since the printed traces shrink after the sintering process, which is challenging because the inkjet-printed silver nanoparticles shrink during sintering process. Cylindrical copper pillars were inserted in laser drilled via holes to metalize the thick via holes [START_REF] Moro | Inkjet-Printed Paper-Based Substrate Integrated Waveguide (SIW) Components and Antennas[END_REF]. High conductivity and thick metal thickness compared with those of the printed nanoparticle-based metallic layers can be achieved by using this technology since thick copper pillars are utilized. However, it has limited design degrees of freedom because the size of copper pillar (i.e. length, radius, etc.) is fixed and additional soldering process is required to ensure the contact between planar metallic layers and the copper vias.

In this work, a novel via hole topology with an exponentially tapered profile is introduced in order to facilitate the formation of continuous metal layers using conductive inks. As a proof-of-concept demonstration of the proposed inkjet-printed stepped via configuration, an equivalent circuit model and a SIW structure, such as a microstrip-to-SIW transition, are presented on the polymethyl methacrylate (PMMA) substrate. A via array and a SIW cavity resonator are also presented on RT/Duroid 5880 to verify the repeatability of via fabrication process and its performance. SIW structures require a large number of vias, which makes them good benchmarking structures to test the repeatability and performance of the proposed stepped vias. PMMA, which is also known as Plexiglas or acrylic, is a widely used commercial polymer

I

material for numerous applications such as display devices and medical instruments due to its high transparency and good compatibility with human tissues [START_REF] Srivastava | Polymethylmethacrylate membrane for fluid encapsulation and release in microfluidic systems[END_REF]. However, the electrical properties of PMMA at microwave frequency range as well as the characteristics of inkjet-printed silver nanoparticles on PMMA are not well known. Therefore, PMMA is chosen as a substrate, and its electrical properties are characterized for the first time in this work. In addition, the demonstration of the first fully inkjet-printed SIW structures suggests the importance of inkjet-printing technology toward implementing the system-on-substrate (SoS) concept in communication, sensing and Internet of Things (IoT) applications [START_REF] Kim | Inkjet-printed Antennas, Sensors, and Circuits on Paper Substrate[END_REF][START_REF] Bozzi | Review of substrate-integrated waveguide circuits and antennas[END_REF].

In Section II, the characterization of PMMA and inkjet-printed silver nanoparticles on PMMA is presented, while in Section III, the fabrication process of inkjet-printed stepped via is introduced. Section IV introduces the first fully inkjet-printed SIW structures including a SIW cavity resonator and a microstrip-to-SIW transition.

II. INKJET PRINTING PROCESS ON PMMA SUBSTRATE

PMMA was chosen as the substrate for the realization of the via-enabled structures in this work because its electrical properties at microwave frequency range were not clearly reported although it is widely utilized for microwave applications, such as in microfluidic sensors. A thorough characterization of inkjet-printed silver nanoparticles on PMMA is necessary in order to extend the capabilities of inkjet-printed technologies to include via metallization and fabrication of SIW topologies.

In this section, the properties (conductivity, thickness) of inkjet-printed conductive traces using silver nanoparticles on PMMA substrate are investigated, while the electrical properties of PMMA are characterized within microwave frequency range (1 ~ 8 GHz) utilizing the T-resonator method [START_REF] Latti | A review of microstrip t-resonator method in determining the dielectric properties of printed circuit board materials[END_REF].

A. Inkjet-printed Silver Nanoparticles on PMMA

The properties of inkjet-printed silver nanoparticles have different values depending on the substrate properties. It is because different substrates have different physical surface properties such as roughness, surface energy, and contact angle with the ink, that result in different inkjet-printability and printing challenges [START_REF] Son | Spreading of Inkjet Droplet on a Solid Surface with a Controlled Contact Angle at Low Weber and Reynolds Numbers[END_REF].

Simple rectangular traces (0.5 mm  5 mm) were printed on PMMA substrate (Goodfellow, London, UK [24]) in order to investigate the properties of inkjet-printed silver nanoparticles on PMMA. The DMP2800 inkjet printer was utilized to print silver nanoparticles in this work. For printing, the Dimatix 10 pL cartridge (DMC-11610) was used, and it was kept at a distance of 250 μm from the surface of the substrate. The printer head angle was 4.5˚ which achieves a printing resolution of 1270 dpi (dots per inch). Cabot conductive ink CCI-300 was jetted at a nozzle temperature of 36 °C, while the substrate was maintained at room temperature (25 °C). Fig. 1(a) shows the thickness of the printed silver nanoparticle-based lines depending on the number of printed layers. The printed patterns were sintered at 120 ˚C for 2 hours, and the thickness was measured using a Veeco Dektak 150 surface profilometer. Each printed layer added about 500 nm of thickness to the printed traces. A reported minimum feature size of the silver nanoparticle ink using a commercially available printer is about 50 μm up to 5 layers of printing. After printing the third layer, the coffee ring effect has been observed because of the high surface energy of PMMA. The high surface energy of PMMA results in different drying speeds of ink at the edge and middle of the printed patterns [START_REF] Soltman | Inkjet-Printed Line Morphologies and Temperature Control of the Coffee Ring Effect[END_REF][START_REF] Van Osch | Inkjet Printing of Narrow Conductive Tracks on Untreated Polymeric Substrates[END_REF]. The width of the printed trace is additionally increased by about 80 µm for each additional printed layer when the thickness (height) of the printed traces has exceeded 1.5 µm. The inkjet printing technology is a thin metal process that thickness of printed traces, such as metals and polymers, is about one skin depth or less at the microwave frequency range. However, it takes advantage of flexibility, ease of fabrication, and cost efficiency of the printing technology which are critical properties for implementing novel applications, such as IoT. The conductivity (ζ) of the inkjet-printed silver nanoparticles was also extracted using the measured profiles of the printed traces using Eqs. (1),

𝜎 = 𝑙 𝑅•𝐴 (S/m) ( 1
)
where l is the length of the trace, R is the resistance across the trace, and A is the cross-section area of trace. The cross-section areas of the printed traces were numerically integrated over the line width (Fig. 1 conductivities for different sintering temperatures as a function of the number of printed layers. The conductivity value converges after printing 3 layers because the particle density is saturated. Higher sintering temperatures resulted in higher conductivity values as reported in previous studies [START_REF] Kim | Inkjet-printed Antennas, Sensors, and Circuits on Paper Substrate[END_REF][START_REF] Perelaer | Ink-jet Printing and Microwave Sintering of Conductive Silver Tracks[END_REF]. The converged conductivity values of the silver nanoparticle ink were around 4.4 10 6 S/m at 120 ˚C, 5.7 10 6 S/m at 150 ˚C, and 6.9 10 6 S/m at 180 ˚C. It corresponds to 6.98 %, 9.05 %, and 10.95 % of bulk silver's conductivity (ζ Ag = 6.3 10 7 S/m), respectively.

B. RF Characterization of PMMA

A commercially available PMMA sample has been characterized up to 8 GHz through the microstrip T-resonator method in this work. The relative permittivity (ε r ) and loss tangent (tan δ) have been extracted from the measurements. where n is the odd resonance mode order (n = 1, 3, 5 ... ), c is the speed of light in free space, L phy is the physical length of the open stub, L O is the correction factor for the open-end effect of the open stub, L T is the correction factor for the T-junction effect, and ε eff is the relative effective permittivity [START_REF] Latti | A review of microstrip t-resonator method in determining the dielectric properties of printed circuit board materials[END_REF].

The loss tangent (tan δ) of the PMMA substrate was extracted from the quality factor (Q) of each resonance as reported in [START_REF] Latti | A review of microstrip t-resonator method in determining the dielectric properties of printed circuit board materials[END_REF]. The conductor losses were theoretically estimated using equations reported in [START_REF] Pucel | Losses in Microstrip[END_REF], and radiation losses were also theoretically calculated utilizing 3D full wave simulator, ANSYS HFSS v11.1.1. A thin copper sheet (thickness = 100 µm, σ = 5.8 10 7 S/m) was utilized as the metal layer.

The coaxial SMA connectors were mounted using a conductive silver epoxy and TRL calibration was applied to de-embed the effects of feeding lines and the SMA connectors. The extracted effective permittivity (ε eff ) was converted to relative permittivity (ε r ). The resulting relative permittivity (ε r ) was 2.38  0.12 and the extracted tan δ was 0.011  0.002 over the frequency of 1 ~ 8 GHz band as shown in Fig. 4. The error intervals were estimated for a 99 % confidence interval. Characterization results using the two-line-method are included in Fig. 4 for validation purpose [START_REF] Ko | Rapid Self-assembly of Monodisperse Colloidal Spheres in an Ink-jet Printed Droplet[END_REF]. Two transmission lines with the same characteristic impedance and two different lengths (20 mm and 70 mm) were prepared on the same substrate and their scattering parameters (S 21 ) were measured. The lengths of the transmission lines were corresponding to effective electrical length of 30° and 100° at 1 GHz, respectively. These transmission lines were utilized as the delay lines for TRL calibration. The relative dielectric constants (ε r ) over the frequency range of operation were extracted from the phase difference of the test transmission lines and the tan δ over the frequency were calculated from the attenuation constant (α) of the transmission lines. The calculated radiation loss using 3D EM simulator of the transmission line was subtracted from the measurement. These results are in good agreement and support the extracted values from the T-resonator method. The extracted dielectric constant values from the T-resonators vary compared to the values from the transmission line method. It is because of fabrication error of each resonator since the T-resonators were cut out from a copper tape. However, the extracted values from each resonators, such as a T-resonator for 1 GHz (resonant frequencies: 1 GHz, 3 GHz, 5 GHz, and 7 GHz), are robust over the frequency band.

III. INKJET-PRINTED VIA

In this section, a novel via fabrication process on thick substrates utilizing inkjet printing technology is presented. In previously reported research efforts, inkjet-printed via holes have been successfully implemented on thin substrates [START_REF] Reinhold | Inkjet printing of electrical vias[END_REF][START_REF] Kawase | Inkjet Printed Via-Hole Interconnections and Resistors for All-Polymer Transistor Circuits[END_REF][START_REF] Falat | Nano-silver inkjet printed interconnections through the microvias for flexible electronics[END_REF][START_REF] Mckerricher | All Inkjet Printed 3D Microwave Capacitors and Inductors with Vias[END_REF][START_REF] Terani | Fully inkjet-printed multilayer microstrip and T-resonator structures for the RF characterization of printable materials and interconnects[END_REF], as shown in Table I. In [START_REF] Reinhold | Inkjet printing of electrical vias[END_REF], 3 layers of silver nanoparticles have been printed over a thin vertical wall utilizing 50 pL cartridge. In [START_REF] Kawase | Inkjet Printed Via-Hole Interconnections and Resistors for All-Polymer Transistor Circuits[END_REF], a crater-like via hole is made by inkjet printing an ethanol drop to dissolve a polyvinyl phenol (PVP) layer. In [START_REF] Falat | Nano-silver inkjet printed interconnections through the microvias for flexible electronics[END_REF], a micro-via array, which consists of small laser-drilled micro-vias, is presented on polyimide substrate. In [START_REF] Mckerricher | All Inkjet Printed 3D Microwave Capacitors and Inductors with Vias[END_REF] and [START_REF] Terani | Fully inkjet-printed multilayer microstrip and T-resonator structures for the RF characterization of printable materials and interconnects[END_REF], printed microwave structures, such as microstrip lines, are presented, and the reported loss of printed microstrip lines are about 0.3 ~ 0.5 dB/mm up to 10 GHz. The reported printed vias shown in [START_REF] Reinhold | Inkjet printing of electrical vias[END_REF] ~ [START_REF] Terani | Fully inkjet-printed multilayer microstrip and T-resonator structures for the RF characterization of printable materials and interconnects[END_REF] are built on a thin substrate which thickness is less than 100 µm. The proposed stepped via approach (with a 2 mm diameter) achieved the via thickness of 800 ~ 1000 µm with a good via resistance of 0.2 Ω compared to the reported works.

It is challenging to metalize via holes on relatively thick substrates. If the via holes are metalized with a similar approach to other inkjet-printed structures, i.e. printing multiple layers on drilled via holes, it results in discontinuities, as shown in Fig. 5. For demonstration purposes, a straight via hole was drilled on 1 mm thick PMMA using CO 2 laser, and silver nanoparticles were printed over the via hole 5 times. The printed via hole was sintered at 120 ˚C for an 1 hour. The printed silver nanoparticles failed to form a continuous metal layer on the via hole because of the shrinkage of the silver ink during the sintering process due to the evaporation of the solvents, the polymers (a dispersant on the silver nanoparticles) and the impurities of the ink. The gravity force further enhances the downward shrinkage of the ink, which results in cracks on the metalized via wall. The shrinkage of the inkjet-printed silver nanoparticles on the vertical via wall is briefly depicted in Fig. 5(a). The inkjet-printed silver nanoparticles on the vertical wall are shrinking in different directions, and these results in cracks as shown in Fig. 5

(b).

A novel stepped via hole topology is introduced in order to create a gradual transition between the top and the bottom planar substrate surfaces and reduce the stress on printed silver nanoparticles on the via hole during the sintering process. The fabrication process is described in Fig. 6. A thin concentric circular cylinder is engraved on the substrate to form a stepped via profile (Fig. 6(a)-(i), (ii)). Then, the substrate is flipped to drill another stepped via on the bottom side (Fig. 6(a)-(iii), (iv)). It is necessary to form a smooth transition from the via top to the bottom of the substrate. The final step is the inkjet printing process (Fig. 6(a)-(v), (vi)). The This fabrication process is suitable for the inkjet printing because the drilling process and inkjet printing process are completely separate, while the via metallization is easily achieved during the inkjet printing (totally dry) process without any additional steps. The fabrication concept shown here on PMMA substrate is for proof of concept only, and is equally applicable to any other inkjet printable substrates. The fabricated inkjet-printed vias are shown in Fig. 7 and Fig. 8. The geometries of the stepped via (top and side views) are shown in Fig. 7(a) and Fig. 8(a). Five concentric disks were drilled to form a stepped via profile on the top and two concentric disks were drilled on the bottom. A symmetric via profile (the same number of disks on the top and the bottom) requires precise control of the laser power level and alignment to match each end of the drilled stepped via topology which is more significantly challenging than the asymmetric stepped via topology. The ratio of the drilled disks is kept to the same value. The two concentric disks on the bottom with gradually increasing radii make sure that the penetration of the via hole runs through the entire substrate, because the upper five concentric disks with gradually decreasing radii sometime fail to form a through hole due to misalignment of the laser focus or uneven substrate surface. The bottom disks also improve the metal continuity, because they enable a smoother transition from the via to the bottom by chamfering the transition from the via to the bottom layer. The disk radii of R 1 and R 2 are chosen for the bottom disks to facilitate the alignment and fabrication, since misalignment and fabrication errors can be compensated within the larger radii R 1 and R 2 . The equal via radii at the top and bottom via disks assist in the easier continuation of the layout at the top layer to the layout at the bottom layer. The radius of each circular disk is tabulated in Fig. 7(a), featuring exponentially tapered values (r n+1 = e -1 •r n ). A Universal laser system's PLS6.75 CO 2 laser was utilized. The laser was raster-scanned over the concentric circles at 1.4 W in a speed of 71 cm/s and a resolution of 1000 pulses per inch (PPI). Five layers of silver nanoparticle ink were printed over the engraved stepped via hole using the same inkjet printing machine and settings discussed in Section II-A. The printed via sample was sintered at 120 ˚C for 2 hours. Scanning

IV. VIA MODELING

A typical cylindrical via can be modeled as an inductor and a resistor in series. Circuit models for a straight cylindrical and for a generalized stepped via are in Fig. 10. The proposed stepped via can be considered as a series of cylindrical vias (Fig. 10(a)) as modeled in Fig. 10(b). The transition between the adjacent cylinders, such as D 2 , D 1 and D n-k+1 , can be easily achieved when the both top and bottom sides are printed one by one as discussed in section III. The equivalent shunt capacitance of the stepped via is negligible when the length of the stepped via is much smaller than a wavelength at the operation frequency. For simplicity and without loss of generality, the cylinder on the bottom is chosen to have the same dimensions with the cylinders on the top as shown in Fig. 10(b) An inductance value (L eq ) and a resistance value (R eq ) of a straight cylindrical via can be expressed as shown in Eqs. ( 3) and ( 4), where the radius of the cylindrical via hole is r eq , the metal thickness is t and the height of the via is H.

L eq = 𝜇 0 H 4𝜋 𝑓(𝑟 𝑒𝑞 , 𝑡) R eq = H 𝜎𝜋 𝑔(𝑟 𝑒𝑞 , 𝑡) (3)
where

𝑓 𝑟 𝑒𝑞 , 𝑡 = 𝑟 𝑒𝑞 2 -𝑟 𝑒𝑞 -𝑡 2 -2 𝑟 𝑒𝑞 -𝑡 2 ln 𝑟 𝑒𝑞 𝑟 𝑒𝑞 -𝑡 𝑟 𝑒𝑞 2 -𝑟 𝑒𝑞 -𝑡 2 𝑔 𝑟 𝑒𝑞 , 𝑡 = 1 𝑡 2𝑟 𝑒𝑞 -𝑡 (4)
Similarly, the circuit model (L s & R s ) of the proposed stepped via hole can be derived based on Eqs. ( 3) and (4) as shown in Eqs. ( 5) and [START_REF] Mantysalo | Evaluation of Inkjet Technology for Electronic Packaging and System Integration[END_REF].

L s = 𝜇 0 h 4π 2 𝑓 𝑟 𝑖 , 𝑡 𝑛 𝑖=1 + 𝑓 𝑟 𝑖 , 𝑡 𝑛 𝑖=𝑛-𝑘+1 R s = 1 σπ [h 𝑔 𝑟 𝑖 , 𝑡 𝑛 𝑖=1 + 𝑔 𝑟 𝑖 , 𝑡 𝑛 𝑖=𝑛-𝑘+1 + 𝑟 𝑖+1 , 𝑟 𝑖 , 𝑡 𝑛-1 𝑖=1 + 𝑟 𝑖+1 , 𝑟 𝑖 , 𝑡 𝑛-1 𝑖=𝑛-𝑘+1 ] (N = n + k, k ≥ 1) (5) 𝑓 𝑟 𝑖 , 𝑡 = 𝑟 𝑖 2 -𝑟 𝑖 -𝑡 2 -2 𝑟 𝑖 -𝑡 2 ln 𝑟 𝑖 𝑟 𝑖 -𝑡 𝑟 𝑖 2 -𝑟 𝑖 -𝑡 2 𝑔 𝑟 𝑖 , 𝑡 = 1 𝑡 2𝑟 𝑖 -𝑡 𝑟 𝑖+1 , 𝑟 𝑖 , 𝑡 = 𝑡 𝑟 𝑖+1 -𝑡 2 -𝑟 𝑖 -𝑡 2 (6)
The performance of the inkjet-printed via, such as the cut-off frequency, the inductance, and the resistance of the printed via, is a strong function of the via radius based on Eqs. ( 5) and [START_REF] Mantysalo | Evaluation of Inkjet Technology for Electronic Packaging and System Integration[END_REF]. A via segment with a smallest radius is the most important segment of the proposed stepped-via topology since the inductance increases exponentially as the radius decreases while the resistance is inversely proportional to the via radius.

The proposed stepped via topology is easy to fabricate utilizing inkjet printing technology but it is impractical to model every different stepped via topology in full wave 3D simulators, such as HFSS and CST. It is convenient to derive an effectively "equivalent straight cylindrical via" circuit model where the composite inductance and resistance values are the same with the proposed stepped via. The 5-layered stepped via was assumed on 0.8 mm thick RT/Duroid 5880 as presented in Fig. 10 as a design example. The height of each cylinder (h) was 200 µm, the radius of the largest cylinder (r 4 ) was 1 mm, and the metal thickness (t) was set to 210 nm with a conductivity value of 9 10 6 S/m. The radii were exponentially increased (r n+1 = e•r n ). The equivalent circuit model (L eq & R eq ) of a cylindrical via was designed based on Eqs. (3) ~ ( 6). The equivalent radius (r eq ) of a cylindrical via was 360 µm with a metal thickness of 180 nm and a conductivity value of 1.0  10 7 S/m. Each value was calculated from the proposed equations, Eqs. (3) ~ [START_REF] Mantysalo | Evaluation of Inkjet Technology for Electronic Packaging and System Integration[END_REF]. The designed equivalent circuit model of the cylindrical via has the same inductance and resistance with those values of the stepped via (L eq =L s =45.28 pH & R eq =R s =0.2 Ω). The resistance value agrees with the measurement shown in Fig. 9. The simulated equivalent via and stepped via models at microwave frequency band are shown in Fig. 11 and the results agree very well.

V. INKJET-PRINTED SIW COMPONENTS

A SIW technology is one of the most promising technologies for high frequency applications, and numerous researches have been reported at the microwave frequency band [START_REF] Bozzi | Review of substrate-integrated waveguide circuits and antennas[END_REF]. However, there are not many reported works on printed SIW components including via metallization methods using a printing technology. The results of the inkjet-printed stepped vias and the substrate characterization at microwave frequency range suggest that relatively high conductivity values of inkjetprinted silver nanoparticles (4.6  10 6 ~ 8.0  10 6 S/m) and fabrication of numerous vias can be easily achieved. As a proof of the via fabrication concept and its application, various SIW components with large number of vias were designed, and the prototypes were experimentally investigated. Therefore, in this work, SIW structures are chosen as a design example utilizing the proposed stepped via topology to implement fully printed SIW components. In this section, a microstrip-to-SIW transition and a SIW cavity resonator are presented.

A. SIW cavity Resonator

An inkjet-printed SIW cavity resonator has been designed to verify the performance of the inkjet-printed vias. The cavity was designed to resonate at 5.8 GHz on 0.8 mm thick Rogers RT/Duroid 5880 (ε r = 2.2, tan δ = 0.0009 at 10 GHz) in order to minimize the effect of substrate loss. The geometry of the designed SIW cavity is shown in Fig. 12. The top and bottom side of substrate were drilled utilizing a laser to form a stepped via profile as discussed in Section III. The designed pattern was printed 5 layers on top side, and a 45 mm  40 mm patch was printed on the bottom side as a ground plane.

The measured and simulated reflection coefficients (S 11 ) are shown in Fig. 13. The results match reasonably well and their small discrepancy is due to fabrication errors stemming from the dispersion of ink on substrate after printing. The quality factor (Q-factor) of the fabricated SIW cavity is calculated using Eqs. [START_REF] Park | High-resolution electrohydrodynamic jet printing[END_REF] 𝑄 = 𝑓 𝑟 ∆𝑓 3𝑑𝐵 [START_REF] Park | High-resolution electrohydrodynamic jet printing[END_REF] where f r is the resonant frequency and Δf 3dB is the 3-dB bandwidth (half power bandwidth). The measured resonant frequency was 5.79 GHz and the 3-dB bandwidth was 0.23 GHz which results in a Q-factor of 25.13 while the simulated Q-factor was 20.05 at 5.73 GHz. The achieved Q-factor of the inkjet-printed SIW cavity was relatively low compared to the conventional cavity resonators [START_REF] Collado | Mechanically Tunable Substrate Integrated Waveguide (SIW) Cavity Based Oscillator[END_REF][START_REF] Martinez | Compact CPW-Fed Combline Filter in Substrate Integrated Waveguide Technology[END_REF] since the inkjet-printed metallic layer has thin metal thickness (< 5 μm) and a relatively low conductivity value compared to a bulk copper (σ printed = 9 × 10 6 S/m, σ cu = 5.96 × 10 7 S/m) resulting in a high loss from metal layers.

B. Inkjet-printed Microstrip-to-SIW Transition

A simple microstrip-to-SIW transition on PMMA has been designed, and it was fully inkjet-printed by utilizing the stepped via structure for the first time. Its fundamental mode cutoff frequency (f 0 ) has been set to 4 GHz in order to enable an operating frequency of 5 GHz. The geometry of the proposed microstrip-to-SIW transition is shown in Fig. 14(a). Each corner of PMMA was bent due to the thermal expansion of the substrate but the middle of the SIW was flat. The SIW and the tapered transition were designed and optimized by following the reported design guide described in [START_REF] Deslandes | Accurate modeling, wave mechanisms, and design considerations of a substrate integrated waveguide[END_REF][START_REF] Deslandes | Design equations for tapered microstrip-to-Substrate Integrated Waveguide transitions[END_REF]. The width (W SIW ) and the length (L SIW ) of the SIW were 24 mm and 23 mm, respectively. The diameter (D via ) and the pitch (P via ) of the stepped vias were both equal to 2 mm. The length (L taper ) of the tapered microstrip-to-SIW transition was 12 mm and the width (W taper ) of it was 6 mm. The thickness of the substrate is 1 mm. Fig. 14(b) shows the fully inkjet-printed microstrip-to-SIW transition on PMMA. Vias were drilled as introduced in the Section III, and then the SIW pattern and the ground plane were printed. The printer settings and sintering temperature were the same as presented in Section II-A.

The

VI. CONCLUSION & FUTURE WORK

In this work, the inkjet printing process of silver nanoparticles on thick substrates, such as a PMMA and RT/Duroid 5880, for microwave applications as well as the fabrication process of fully inkjet-printed low-cost vias and SIW components are demonstrated. The inkjet-printed silver nanoparticle inks on PMMA feature good conductivity values (4.5 10 6 ~ 8.0 10 6 S/m) to implement practical microwave topologies. The fully inkjet-printed vias on the PMMA substrate were implemented by introducing a novel stepped via hole configuration with an exponentially tapered radial profile. As a proof-of-concept, fully inkjet-printed SIW structures such as a SIW cavity resonator and a microstrip-to-SIW transition were designed and experimentally demonstrated, verifying the feasibility of inkjet-printed stepped vias on various substrates.

The work presented in this paper is a fundamental study toward the future fully inkjet-printed low-cost via-enabled devices and systems including packaging. The next step of this study is to increase the thickness of the inkjet-printed silver nanoparticle films in order to reduce the skin depth effect. A proper surface treatment such as the modification of the surface energy (surface functionalization or ozone treatment), and applying mechanical constraints (increase surface roughness or implement channel for the inks) [START_REF] Hendriks | Invisible" Silver Tracks Produced by Combining Hot-Embossing and Inkjet Printing[END_REF] could improve the printable thickness, adhesion, and uniformity of silver nanoparticles. He is currently a Professor with School of Electrical and Computer Engineering, Georgia Institute of Technology (Georgia Tech), Atlanta, GA, USA. He has published more than 600 papers in refereed journals and conference proceedings, five books, and 24 book chapters. He has helped develop academic programs in highly integrated/multilayer packaging for radio frequency (RF) and wireless applications using ceramic and organic flexible materials, paper-based RFIDs and sensors, biosensors, wearable electronics, 3-D/4-D/inkjet-printed electronics, "green" electronics, energy harvesting and wireless power transfer systems, NFC systems, nanotechnology applications in

Fig. 1 .

 1 Fig. 1. Thickness and conductivity of inkjet-printed traces: (a) thickness (b) conductivity.

  Fig. 2 shows the fabricated T-resonator structures and the thrureflection-line (TRL) calibration structures on 1 mm thick PMMA. The T-resonators consist of 50 Ω feeding lines and an open stub. The length of the open stub is quarter-wavelength (λ g /4) at the desired resonant frequency. The width of the microstrip feeding lines was 2.8 mm and the length of the T-resonator for 1 GHz is 51.92 mm and for 2 GHz is 25.56 mm. Fig. 3 shows the measured S 21 of the fabricated T-resonator for 1 GHz. The measurement and simulation results are in good agreement. The resonant frequencies (f n ) of the T-resonator can be determined by Eqs. (2) 𝑓 𝑛 = 𝑛 •𝑐 4(𝐿 𝑝 𝑦 +𝐿 𝑂 -𝐿 𝑇 ) 𝜀 𝑒𝑓𝑓 (2)

Fig. 3 .

 3 Fig. 3. S21 of the 1 GHz T-resonator.

Fig. 2 .

 2 Fig. 2. Fabricated T-resonators and TRL calibration lines on PMMA substrate

Fig. 5 .Fig. 4 .

 54 Fig. 5. (a) Crack formation of inkjet-printed silver nanoparticle on a straight vertical via hole and (b) SEM image of the crack on the metalized via hole.

Fig. 7 .Fig. 6 .

 76 Fig. 7. (a) Geometry of stepped via hole and (b) SEM images of metalized stepped via hole: top view

Fig. 9 .Fig. 8 .

 98 Fig. 9. Inkjet-printed stepped via array (inset) and measured DC resistance of the via chain.

Fig. 10 .

 10 Fig. 10. (a) Equivalent circuit model of a stepped via and (b) equivalent via model of a cylindrical via and a stepped via.

  measured and simulated values of the magnitude of the scattering parameters (|S 11 | & |S 21 |) are shown in Fig. 15, demonstrating a good agreement. The measured insertion loss (IL) of the proposed microstrip-to-SIW at 5 GHz is 2.4 dB. It is notable that inkjet-printed vias have been successfully implemented.

Fig. 13 .

 13 Fig. 13. Simulated and measured reflection coefficient (S11) of the inkjet-printed SIW cavity resonator.

Fig. 12 .

 12 Fig. 12. Geometry of the SIW cavity resonator: Wfeed = 2.5 mm, Lfeed = 10 mm, Wcav = 32 mm, Lcav = 22.4 mm, Dvia = 1.6 mm, Pvia = 3.2 mm, Lmat = 17 mm, Wmat = 0.6 mm and Win = 1.25 mm.

Fig. 11 .

 11 Fig. 11. Simulated S-parameters of the SIW structure with a stepped via topology and an equivalent cylindrical via topology.

Fig. 14 .

 14 Fig. 14. MicroStrip-to-SIW transition: (a) geometry: Wfeed = 2.8 mm, Wtaper = 6 mm, LSIW = 23 mm, WSIW = 24 mm, Dvia = 2 mm, Pvia = 2 mm, Lfeed = 5 mm, Ltaper = 12 mm (b) fabricated component on PMMA.

Fig. 15 .

 15 Fig. 15. Measured scattering parameters of microstrip-to-SIW transition.

  Fabrication of Fully Inkjet-Printed Vias and SIW Structures on Thick Polymer Substrates

Sangkil Kim, Member, IEEE, Atif Shamim, Senior Member, IEEE, Apostolos Georgiadis, Senior Member, IEEE, Hervé Aubert, Senior Member, IEEE, and Manos M. Tentzeris, Fellow, IEEE

Scientific Research (CNRS), Toulouse, in February 2006. Since January 2015 he is the Head of the Micro-and Nano-systems for Wireless Communications Research Group at LAAS-CNRS.

ACKNOWLEDGEMENT

The work of S. Kim and M. Tentzeris was supported by NSF and NEDO. The work of A. Georgiadis has been supported by the EU COST Action IC1301 WiPE Wireless Power Transmission for Sustainable Electronics, the Generalitat de Catalunya under grant 2014 SGR 1551 and by EU H2020 Marie Sklodowska-Curie grant agreement No 661621. RF, origami-folded electromagnetics, microwave MEMs, SOP-integrated (UWB, multiband, mmWave, conformal) antennas and heads the ATHENA research group (20 researchers). He has served as the Head of the GT-ECE Electromagnetics Technical Interest Group, as the Georgia Electronic Design Center Associate Director for RFID/Sensors research from 2006-2010 and as the Georgia Tech NSF-Packaging Research Center Associate Director for RF Research and the RF Alliance Leader from 2003-2006. He was a Visiting Professor with the Technical University of Munich, Germany for the summer of 2002, a Visiting Professor with GTRI-Ireland in Athlone, Ireland for the summer of 2009, and a Visiting Professor with LAAS-CNRS in Toulouse, France for the summer of 2010. He has given more than 100 invited talks to various universities and companies all over the world. Dr. Tentzeris was the recipient/co-recipient of the 2015 IET Microwaves, Antennas and Propagation Premium Award, the 2014 Georgia Tech ECE Distinguished Faculty Achievement Award, the 2014 IEEE RFID-TA Best Student Paper Award, the 2013 IET Microwaves, Antennas and Propagation Premium Award, the 2012 FiDiPro Award in Finland, the iCMG Architecture Award of Excellence, the 2010 IEEE Antennas and Propagation Society Piergiorgio L. E. Uslenghi Letters Prize Paper Award, the 2011 International Workshop on Structural Health Monitoring Best Student Paper Award, the 2010 Georgia Tech Senior Faculty Outstanding Undergraduate Research Mentor Award, the 2009 IEEE Transactions on Components and Packaging Technologies Best Paper Award, the 2009 E.T.S.Walton Award from the Irish Science Foundation, the 2007 IEEE APS Symposium Best Student Paper Award, the 2007 IEEE IMS Third Best Student Paper Award, the 2007 ISAP 2007 Poster Presentation Award, the 2006 IEEE MTT Outstanding Young Engineer Award, the 2006 Asian-Pacific Microwave Conference Award, the 2004 IEEE Transactions on Advanced Packaging Commendable Paper Award, the 2003 NASA Godfrey "Art" Anzic Collaborative Distinguished Publication Award, the 2003 IBC International Educator of the Year Award, the 2003 IEEE CPMT Outstanding Young Engineer Award, the 2002 International Conference on Microwave and Millimeter-Wave Technology Best Paper Award (Beijing, CHINA), the 2002 Georgia Tech-ECE Outstanding Junior Faculty Award, the 2001 ACES Conference Best Paper Award and the 2000 NSF CAREER Award and the 1997 Best Paper Award of the International Hybrid Microelectronics and Packaging Society. He was the TPC Chair for IEEE IMS 2008 Symposium and the Chair of the 2005 IEEE CEM-TD Workshop and he is the Vice-Chair of the RF Technical Committee (TC16) of the IEEE CPMT Society. He is the founder and chair of the RFID Technical Committee (TC24) of the IEEE MTT Society and the Secretary/Treasurer of the IEEE C-RFID. He is an Associate Editor of IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, IEEE TRANSACTIONS ON ADVANCED PACKAGING, and the International Journal on Antennas and Propagation. He is a member of URSI-Commission D, a member of MTT-15 committee, an Associate Member of the European Microwave Association, a Fellow of the Electromagnetic Academy, and a member of the Technical Chamber of Greece. He served as one of the IEEE Microwave Theory and Techniques Society Distinguished Microwave Lecturers from 2010-2012, and he is currently serving as one the IEEE C-RFID Distinguished Lecturers.