Florian Gallier
email: florian.gallier@u-cergy.fr

Metal Promoted Diels-Alder Reactions

Keywords: Diels-Alder reaction, Catalysis, Selectivity, Asymmetric synthesis. 1

The Diels-Alder cycloaddition between a (hetero)diene and a (hetero)dienophile can be performed with metal Lewis Acids. Such activation often increases the rate of the reaction and has an influence on the observed selectivity. The most recent advances on metal promoted Diels-Alder reactions are reviewed.

In 1928, German chemists Otto Diels and Kurt Alder reported the reaction of p-quinone with cyclopentadiene to afford a bicyclic product [START_REF] Diels | Synthesen in der hydroaromatischen Reihe[END_REF]. Although this reaction proved to be highly versatile (as demonstrated by the Nobel Prize awarded to the authors), reaction between other 2 electrons systems (dienophiles) with 4 electrons systems (dienes) still suffers from limitations. For instance, the geometry of the cycloadduct, depends on the configuration of the dienophile (Z olefins would give the cis-substituted product, whereas E olefins would give the trans one). The conformation of the diene is also important as the s-trans conformation (the most thermodynamically stable) is unreactive. Assuming the reaction pathway is synchronous and concerted the major product obtained is rather easily predicted. However, synchronicity can be biased or worse the reaction can occur in a stepwise manner, thus furnishing diastereroisomeric products.

The reaction is in reality governed by frontier molecular orbitals (FMO). The lowest energy difference between the HOMO and the LUMO of the reactants is usually preferred (Fig. 1). The normal electron demand is the case where the HOMO of the diene is closer in energy to the LUMO of the dienophile. The opposite (interaction between the LUMO of the diene and the HOMO of the dienophile) is called inverse electron demand (IED). When there is (almost) no energy difference, the electron demand is neutral (NED). In addition, regioselectivity can be explained by matching the orbital coefficients of the frontier orbitals at each reactive atom. The largest lobe of the atom at the HOMO level (the most electron-rich) would preferentially react with the largest lobe of the atom at the LUMO level (the less electron-rich).

The transition state of such pericyclic reaction is usually very high in energy and often requires elevated temperature to proceed. Other modes of activation such as microwave irradiation [START_REF] Kappe | Microwaves in Organic and Medicinal Chemistry[END_REF][START_REF] Saber | Microwave-assisted Cycloaddition Reactions in Carbo-and Heterocyclic Chemistry[END_REF][START_REF] Appukkuttan | Microwave-assisted cycloaddition reactions[END_REF]

Florian Gallier

high-pressure (1-20 kbar) [START_REF] Fringuelli | The Diels-Alder Reaction: Selected Parctical Methods[END_REF][START_REF] Hugelshofer | High-pressure transformations in natural product synthesis[END_REF] have been developed over the years to overcome such difficulties. The most reliable method is probably to reduce the energy gap between the HOMO and the LUMO. Introduction of an electron-withdrawing group on either diene or dienophile tends to deepen the orbitals energy (both the HOMO and the LUMO) whereas an electron-donating group tends to raise the energy levels of the frontier orbitals. However, introduction of such functional group is not an easy task, especially on complex molecules. Therefore, two other strategies have been pointed out. The first one (HOMO-raising) relies on the formation of an enamine. The other one (LUMO-lowering) consists on the formation of either an iminium ion or on the complexation of a Lewis acid. The decrease in energy of the LUMO is related to the strength of the Lewis acid. From a general point of view, the Lewis acidity will increase along with the oxidation state of an element. In addition, the more dissociated the ligands are (increased cationic character), the more Lewis Acid it would be. For this reason, anions such as BF 4 -, SbF 6 -, PF 6are often used. Many Lewis acids are known and most of them are based on a central metal atom.

The aim of this review is to highlight the most recent advances (from 2009 to the end of 2014) in (Hetero-)Diels-Alder reactions promoted (or catalysed) by a metallic Lewis acid.

s-BLOCK METALS

Elements of the first two columns of the Periodic Table belong to the s-block. Alkali metals ions (group 1) are easily produced (due to the low ionization potential of their atoms) but have not been found useful recently as cycloaddition promoter, contrary to the alkaline earth metals.

Group 2 (Alkaline Earth Metals)

Magnesium (Mg)

Magnesium salts have been widely used in organic synthesis because of their Lewis acidity as well as their chelating properties. However, these highly reactive species can form oligomeric structures thus decreasing their reactivity. Hatano et al. have shown that careful addition of an external Lewis base (benzyl alcohol) to the Mg II /BINOL oligomer yields a defined trinuclear complex 3 which is able to promote the cycloaddition of benzaldehyde [START_REF] Diels | Synthesen in der hydroaromatischen Reihe[END_REF] with the Danishefsky's diene 2a (Scheme 1) [START_REF] Hatano | Chiral supramolecular magnesium(II) binaphtholate catalysts for the enantioselective direct mannich-type reaction and hetero-diels-alder reaction[END_REF]. High enantiodiscrimination is observed and explained by preferential shielding of the BINOL aromatic rings.

N,N'-dioxide ligands have been efficiently employed for the cycloaddition of isatins 5 with either Danishefsky-(2a) or Brassardtype dienes (6) (Scheme 2) [START_REF] Zheng | Magnesium(II)catalyzed asymmetric hetero-Diels-Alder reaction of Brassard's dienes with isatins[END_REF][START_REF] Zheng | Asymmetric Hetero-Diels-Alder reaction of danishefsky's diene with -ketoesters and isatins catalyzed by a chiral N ,N -dioxide/magnesium(II) complex[END_REF]. In this reaction Mg showed superior activity or selectivity over other metals such as Sc, In or Cu.

Chiral magnesium phosphates derived from BINOL [START_REF] Liang | Chiral metal phosphate catalysis: Highly asymmetric hetero-Diels-Alder reactions[END_REF] are mild Lewis, chemically neutral and rather non-toxic [START_REF] Li | An asymmetric diels-alder reaction catalyzed by chiral phosphate magnesium complexes: Highly enantioselective synthesis of chiral spirooxindoles[END_REF]. They were used as catalysts for the synthesis of spirooxindoles 12 with very good diastero-and enantio-selectivities and in higher yield if molecular sieves are added (Scheme 3). Magnesium hydrates are less Lewis acidic due to an increase of donating ligands hence changing the coordination geometry of the metal from tetrahedral to octahedral and therefore reducing their activity.

Calcium (Ca)

Similarly, calcium analogues (14 and 19) have demonstrated high activity not only with isatins 16 but also with pyruvates (13) (Scheme 4) [START_REF] Liang | Chiral metal phosphate catalysis: Highly asymmetric hetero-Diels-Alder reactions[END_REF]. These are challenging substrates due to the particular electronic and steric properties of ketones. Such catalysts are also effective to promote inverse electron demand Hetero-Diels-Alder reactions [START_REF] Mao | Enantioselective construction of dihydropyran-fused indoles through chiral calcium phosphate catalyzed oxo-hetero-diels-alder reactions by using 2oxoindolin-3-ylidenes as heterodienes[END_REF].

Barium (Ba)

During the course of the synthesis of Tamiflu, the Shibasaki group devised the use of chiral barium complexes (Scheme 5) [START_REF] Yamatsugu | A synthesis of tamiflu by using a barium-catalyzed asymmetric diels-alder-type reaction[END_REF]. This reaction is supposed to occur through a HOMO-raising mechanism: the fluoride additive is believed to activate the silyl diene, facilitating transmetallation. Then, a dual activation of both diene 21 and dienophile 22 allows the formation of the desired cycloadduct 24 in high yield and enantiomeric excess, and can be performed on a 50 g scale.

P-BLOCK METALS

Located on the left-hand side of the periodic table, the p-block elements are the most encountered in organic chemistry. Some of them have a metallic character and are sometimes coined as posttransition metals.

Group 13

Aluminium (Al)

Aluminium salts are widely used as Lewis acids and AlCl 3 was the first Lewis Acid to be reported as remarkably accelerating the Diels-Alder reaction [START_REF] Yates | Acceleration of the Diels-Alder reaction by aluminum chloride[END_REF]. It is still heavily used in total synthesis and has been shown to be compatible with a wide range of substrates. Recently, siloles have been efficiently employed furnishing 1,4-diols after Tamao-Fleming oxidation of the corresponding cycloadducts [START_REF] Stevens | Diels-Alder chemistry of siloles and cyclohex-2-ene-1,4-cis-diols[END_REF]. The highly electron-rich Danishefsky or Brassardtype dienes were efficient partners for the heterocycloaddition of acyl phosphonates [START_REF] Polat-Cakir | Hetero Diels-Alder reactions of acyl phosphonates: Synthesis of glycosyl type phosphonates[END_REF]. The group of Danishefsky has also expanded the scope of dienophiles by introducing 2-halocycloalk-2enones [START_REF] Lee | Diels-Alder routes to angularly halogenated cis-fused bicyclic ketones: Readily accessible cyclynone intermediates[END_REF] or N-formyl amides [START_REF] Townsend | Enhancing the scope of the Diels-Alder reaction through isonitrile chemistry: Emergence of a new class of acyl-activated dienophiles[END_REF] which is as reactive as the classical oxazolidinone dienophiles.

An interesting feature of the aluminium complexes is the ease of tuning their electronic properties providing more or less reactive Lewis acids (AlBr 3 > AlCl 3 > MeAlCl 2 > Me 2 AlCl > Me 3 Al). Mixing Me 3 Al with an equimolar amount of Tf 2 NH yields Me 2 AlNTf 2 which is a very highly reactive Lewis acid, and has been especially efficient for the cycloaddition of hindered substrates (Scheme 6) [START_REF] Jung | Trimethylaluminum-triflimide complexes for the catalysis of highly hindered diels-alder reactions[END_REF]. MeAl(NTf 2 ) 2 is even more reactive. Interestingly, the endo isomer is preferentially obtained in this case. However it is known that the substitution of the terminal diene and/or dienophile yields mainly the exo isomer [START_REF] Henderson | A concise Diels-Alder strategy for the asymmetric synthesis of (+)-albicanol, (+)-albicanyl acetate, (+)dihydrodrimenin, and (-)-dihydroisodrimeninol[END_REF]. Computational investigations have put forward a twist-asynchronicity model to account for the observed selectivity [START_REF] Lam | Diels-alder exo selectivity in terminal-substituted dienes and dienophiles: Experimental discoveries and computational explanations[END_REF]. Care must be taken however since these results were obtained involving the chelation of the aluminium atom with both carbonyls of the dienophile (Evans' model [START_REF] Evans | Asymmetric Diels-Alder cycloaddition reactions with chiral , -unsaturated N-acyloxazolidinones[END_REF]). For low concentration of Lewis Acid (catalysis) this chelation seems unlikely and alternative mechanism should occur [START_REF] Bakalova | An alternative mechanism for Diels-Alder reactions of Evans auxiliary derivatives[END_REF].

Sterics tuning at the aluminium atom can have interesting results on the stereochemistry of the adduct. The intramolecular cyclization of 28 usualy gives the cis isomer predominantly with AlCl 3 or under thermal conditions. Remarkably, the use of APTH [START_REF] Lin | Indium (III)-catalyzed asymmetric hetero-Diels-Alder reaction of brassard-type diene with aliphatic aldehydes[END_REF] reverses the observed selectivity, due to destabilizing steric interactions in the cis transitions state (Scheme 7) [START_REF] Pearson | Experimental and computational studies into an ATPH-Promoted exoselective IMDA reaction: A short total synthesis of 9-THC[END_REF].

The use of the tridentate ligands 2,2'-thiobis(4,6-dimethylphenolate) (Smdiol 33b) or 2,2'-thiobis(4,6-di-tert-butylphenolate) (Stdiol 33a) with AlCl 3 yields defined complexes (Scheme 8) [START_REF] Tiempos-Flores | Aluminium complexes derived from tridentate thioetherbis(phenolate) ligands and their activity in Diels-Alder catalysis[END_REF]. They have been found to catalyse the reaction between cyclopentadiene 31 and methacrolein 32 with moderate conversion but with good exo selectivity.

Gallium (Ga)

Gallium becomes increasingly used in organic synthesis. Its triflate salt Ga(OTf) 3 has been used for the inverse electron demand hetero-Diels-Alder of alkyl arylidene pyruvates 37 with a cyclic enamine (36, generated by 5-exo-dig gold-cyclization of aminoalkyne 35) (Scheme 9) [START_REF] Wang | Synthesis of fused bicyclic aminals through sequential gold/Lewis acid catalysis[END_REF]. The bicycloaminal adducts 38 are usually obtained in high yield in favour of the endo isomer.

The Lewis acids from this group 13 have a vacant p orbital at the metal center, which can be involved in the coordination with an external ligand. As a result, the Lewis acidity is decreased. Therefore, Nakajima et al. have designed a caged tridentate ligand backshielding the vacant p orbital from external ligands and enhancing the Lewis acidity (Scheme 10) [START_REF] Nakajima | Synthesis and theoretical studies of gallium complexes back-shielded by a cage-shaped framework of tris(m-oxybenzyl)arene[END_REF]. The adduct 4 is obtained in 61% yield with such caged-shaped gallium complex instead of 34% yield with the related open-shape gallium phenoxide.

Indium (In)

Prior to the use of magnesium salts, the Feng's group employed their N,N'-dioxide ligands with indium(III) triflate (Scheme 11). The mechanism of the hetero-Diels-Alder reaction with butadiene with benzaldehyde has been investigated by DFT calculations [START_REF] Cao | Theoretical study on Hetero-Diels-Alder reaction of butadiene with benzaldehyde catalyzed by chiral In(III) complexes[END_REF].

The reaction seems to proceed via a concerted asynchronous mechanism through a zwitterionic transistion state favouring the endo isomer due to less steric hinderance. Brassard-type dienes have later been found rather efficient for this kind of cycloaddition [START_REF] Lin | Indium (III)-catalyzed asymmetric hetero-Diels-Alder reaction of brassard-type diene with aliphatic aldehydes[END_REF].

The group of Loh has explored the asymmetric hetero-Diels-Alder reaction of the Danishefsky's diene 44 with -ketoesters [START_REF] Bull | An air stable moisture resistant titanium triflate complex as a lewis acid catalyst for C-C bond forming reactions[END_REF] using In(III)-PyBox complexes 45 (Scheme 12) [START_REF] Zhao | Asymmetric Hetero-Diels-Alder reaction of danishefsky 's dienes with -carbonyl esters catalyzed by an indium (III)-PyBox complex[END_REF]. The adducts 46 are obtained after TFA desilylation in moderate to high yields with usually high enantioselectivity (up to 95% ee).

Finally, the dual activation of , -unsaturated--ketoesters 47 with InBr 3 and a chiral phosphoric acid [START_REF] Hirama | An efficient synthesis of chiral isoquinuclidines by Diels-Alder reaction using Lewis acid catalyst[END_REF] can lead to either a Diels-Alder or an Hetero-Diels-Alder reaction with cyclopentadienes; the latter being favoured with cyclopentadiene itself [START_REF] Lv | Asymmetric binary-acid catalysis with InBr3 in the inverse-electron-demanding hetero-Diels-Alder reaction of mono-and bis-substituted cyclopentadienes: Remote fluoro-effect on stereocontrol[END_REF] or disubstituted cyclo-pentadienes (Scheme 13) [START_REF] Lv | Asymmetric binary-acid catalysis with InBr3 in the inverse-electron-demanding hetero-Diels-Alder reaction of mono-and bis-substituted cyclopentadienes: Remote fluoro-effect on stereocontrol[END_REF]. All adducts (49 and 50) are obtained with very high enantioselectivites. 51 are not thermodynamically stable (they tend to equilibrate to the corresponding cyclic 1-amidodiene) therefore their reaction must be performed at low temperature [START_REF] Fang | A highly stereoselective Diels-Alder cycloaddition of enones with chiral cyclic 2-amidodienes derived from allenamides[END_REF]. SnCl 4 proved to be the most efficient promoter for the cycloaddition with various enones 52 and the reaction can be run as low as -78°C yielding the bicyclic adduct 53 with moderate (aromatic enones) to high (aliphatic enones) diastereoisomeric ratios (Scheme 14).

Group 14

Tin (Sn)

Chiral oxazaborolidines are highly potent Lewis acids. Their protonation or metallation (AlBr 3 ) affords efficient catalysts for the Diels-Alder reactions [START_REF] Mukherjee | Enantioselective synthesis based on catalysis by chiral oxazaborolidinium cations[END_REF][START_REF] Schubert | Enantioselective total synthesis of the diterpenes kempene-2, kempene-1, and 3-epi-kempene-1 from the defense secretion of higher termites[END_REF]. Shibatomi et al. have demonstrated that tin(IV) chloride could also activate Corey's oxazaborolidines [START_REF] Zulauf | Original use of the same heterogeneous chiral catalyst batch to promote different asymmetric reactions[END_REF] and they have studied the cycloaddition of -halo enones 59 or -(poly)-fluoroacrylates (55a-c) with various dienes in order to attain easily and selectively valuable pharmaceuticals compounds (Scheme 15) [START_REF] Shibatomi | A Diels-Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers[END_REF][START_REF] Shibatomi | Stereoselective construction of halogenated quaternary stereogenic centers via catalytic asymmetric diels-alder reaction[END_REF].

d-BLOCK METALS (TRANSITION METALS)

The middle of the periodic table is filled with elements which have all partially or totally filled d-orbitals, conferring them particular reactivity.

Group 3

Scandium (Sc)

Such particular reactivity has been observed by the group of Luo [START_REF] Lv | Switchable diastereoselectivity in enantioselective [4+2]cycloadditions with simple olefins by asymmetric binary acid catalysis[END_REF]. The cycloaddition of , -unsaturated--ketoesters 37 with disubstituted alkenes catalysed by indium complex yields the exo isomer in good yield and commonly with diastereo-and enantioselectivity. Whereas the use of a scandium complex 62 and styrene 61 yields the endo adduct [START_REF] Terada | Diastereoselective construction of trans-fused octalone framework via ruthenium-porphyrin-catalyzed cycloaddition[END_REF] in very high diastereo-and enantioselectivity (Scheme 16). The rationale for this lies in a stepwise mechanism (and formation of a zwitterionic intermediate) in the case of indium while the reaction is concerted with scandium.

Zeolites are solid Brønstedt acids but some of the protic site can be easily exchanged for a metal cation, thus conferring additional Lewis acidity to the zeolites [START_REF] Chassaing | Copper(I)-zeolites as new heterogeneous and green catalysts for organic synthesis[END_REF]. Sc-zeolites 65 have been efficiently used for the Povarov reaction as well as for the imino-Diels-Alder reaction [START_REF] Olmos | Scandium(III)-zeolites as new heterogeneous catalysts for imino-Diels-Alder reactions[END_REF]. In this reaction the yields are often slightly higher if the imine 64 is formed prior to the cycloaddition (Scheme 17). Although the Danishefsky's diene 2a is an efficient partner, other dienes only yields the 1,4-addition product, presumably due to the zeolite acidity. More interestingly, the heterogeneous zeolite catalyst is easily recovered and can be reused at least 10 times without any loss of reactivity.

Yttrium (Y)

The [4+2] cycloaddition of , -unsaturated--ketoesters 47 with cyclic ketones is a challenging task mainly due to the low reactivity of the cyclic ketone. However, the group of Wang showed that the use of a chiral chelating ligand bearing a primary amine (68) was beneficial (Scheme 18) [START_REF] Xu | Asymmetric inverse-electron-demand hetero-Diels-Alder reaction of six-membered cyclic ketones: An enamine/metal lewis acid bifunctional approach[END_REF]. The amino group allows the formation of the more reactive enamine tethered to the ligand, while the chelating moiety brings the diene in close proximity to the dienophile. Several metals were screened and Y(OTf) 3 was the most efficient even if for some substrates the aldol product (69') is unavoidable. Heteroadducts 69 are obtained in very high enantioselectivity (> 90%).

They next turned their attention to the related aza-Diels-Alder reaction by introducing an aryl amine (70) in the system (Scheme 19) [START_REF] Deng | Arylamine-catalyzed enamine formation: Cooperative catalysis with arylamines and acids[END_REF]. This seems even more challenging since either the enamine or the 1-azadiene is not thermodynamically favored. In order to obtain the desired product 72 in good enantioselectivity, the presence of a catalytic amount of chiral silver phosphate is required.

Group 4

Titanium (Ti)

Titanium is widely used as Lewis acid in organic reactions. Its halide salts are highly reactive and considered slightly less acid than the aluminium counterparts [START_REF] Hilt | A lewis acidity scale in relation to rate constants of lewis acid catalyzed organic reactions[END_REF]. Titanium can also easily form stable complexes with alkoxides, lowering the overall acidity (TiCl 4 >TiCl 2 (O i-Pr) 2 >Ti(O i-Pr) 4 ). Although cheap and commercially available, these catalysts suffer from air and moisture sensitivity, as well as caustic and corrosive hazards. The group of Bull and Davidson devised the use of a propeller-type tridentate ligand that binds the titanium center (Scheme 20) [START_REF] Bull | An air stable moisture resistant titanium triflate complex as a lewis acid catalyst for C-C bond forming reactions[END_REF]. The triflate salt 74 is mandatory for the activity, nevertheless the crystalline solid is bench stable for several months. This catalyst has been efficiently used for imino-Diels-Alder with the Danishefsky's diene 2a or for homo-Diels-Alder of dienes with electron-poor dienophiles. More interestingly the ligand scaffold allows a higher endo selectivity than with the classical TiCl(O i-Pr) [START_REF] Saber | Microwave-assisted Cycloaddition Reactions in Carbo-and Heterocyclic Chemistry[END_REF] .

Ligand exchange with chiral alcohols allows the formation of chiral catalysts. (S)-BINOL has been described for the cycloaddition of aza-chalcone with cyclopentadiene [START_REF] Wang | Asymmetric catalysis of Diels-Alder cycloaddition of 2-alkenoyl pyridine with cyclopentadiene by binaphthol-titanium complex[END_REF]. One of the best chiral ligands for titanium is TADDOL. Recently, such catalyst [START_REF] Watanabe | Enantio-and diastereoselective hetero-Diels-Alder reactions between 4-methyl-substituted Rawal's diene and aldehydes catalyzed by chiral dirhodium(II) carboxamidates: Catalytic asymmetric synthesis of (-)-cis-aerangis lactone[END_REF] has been found useful for the asymmetric synthesis of isoquinucli-dines (79) by cycloaddition of 1-(phenoxycarbonyl)-1,2-dihydropyridine 76 with acryloyl oxazolidinone 77 (Scheme 21) [START_REF] Seki | Asymmetric synthesis of isoquinuclidines by Diels-Alder reaction of 1,2-dihydropyridine utilizing a chiral Lewis acid catalyst[END_REF].

In addition, theoretical studies have been carried out to identify the mechanism involved in the titanium-mediated hetero-Diels-Alder [START_REF] Sogani | Hetero-Diels-Alder reaction of aromatic aldehydes catalyzed by titanium tetrachloride: Computational and experimental results[END_REF][START_REF] Su | Theoretical investigations on the mechanism of hetero-diels-alder reactions of brassard's diene and 1,3-butadiene catalyzed by a tridentate schiff base titanium(IV) complex[END_REF]. Both studies highlights the formation of a zwitterionic intermediate arising from a stepwise mechanism.

Hafnium (Hf)

In 2010, the group of Matsuyama devised a Diels-Alder route to isoquinuclidine frameworks (81) from 1,2-dihydropyridine (76) and chiral acryloyl camphorsultam 80 (Scheme 22) [START_REF] Hirama | An efficient synthesis of chiral isoquinuclidines by Diels-Alder reaction using Lewis acid catalyst[END_REF]. Interestingly, such reaction has been found effective with Ti(IV), Zr(IV) or Hf(IV) chlorides. Although less reactive (the reaction has to be performed at room temperature instead of -78°C) hafnium chloride is at least as stereoselective as titanium chloride, and excellent endo/exo ratios as well as endo diastereomeric excess are obtained. Such selectivity is accounted by interamolecular chelation of the metal between the acryloyl carbonyl and one oxygen atom of the sultam moiety.

Group 5

Niobium (Nb)

Niobium(V) chloride is highly oxophilic and highly Lewis acidic and has been used for several chemical transformations including the Diels-Alder reaction [START_REF] Lacerda | The growing impact of niobium in organic synthesis and catalysis[END_REF]. Furan 82 can be used as a diene, however it is fairly unreactive and highly reactive dienophiles or harsh activation conditions (strong Lewis acids, elevated temperatures or high pressure) are required. In addition, its aromatic stability enables the easy retro-cycloaddition pathway. Lacerda's group found that a catalytic amount of Nb(V) chloride is highly efficient for the cycloaddition of furan with methyl acrylate 83, yielding quantitatively the adduct (84) with slight endo selectivity (Scheme 23) [START_REF] Santos | Niobium(V) chloride as catalyst in Diels-Alder reaction of furan ring[END_REF].

Group 6

Chromium (Cr)

The Salen ligand is one of the privileged structure (i.e. efficient for a wide array of reactions) [START_REF] Yoon | Privileged chiral catalysts[END_REF][START_REF] Zhang | Privileged Chiral Ligands and Catalysts[END_REF] and can accommodate several metals such as Al, Co, Mn (Jacobsen's catalyst) or Cr. The group of Nishida intensively studied the cycloaddition of the Rawal's diene 86 with cyclic dienophiles [START_REF] Carmona | Chiral octahedral phosphano oxazoline iridium(III) complexes as catalysts in asymmetric cycloaddition reactions[END_REF] catalysed by the Cr-Salen-F 87 (Scheme 24) [START_REF] Mihara | Asymmetric synthesis of hydroisoquinoline derivatives, a key intermediate for manzamine synthesis, by Diels-Alder reaction using 4-amino-2siloxybutadiene[END_REF][START_REF] Ohfusa | Reactivity and stereoselectivity of the Diels-Alder reaction using cyclic dienophiles and siloxyaminobutadienes[END_REF]. They have rationalized the observed selectivity of the adduct depending on the structure of the starting dienophile. The general trend in reactivity is interesting since such bicyclic adducts would be key-intermediates in the synthesis of several natural products. However, the use of trifluorotoluene and molecular sieves is required.

Trentin et al. have showed that the Cr-Salen-Cl 90 could efficiently be used for the cycloaddition of cyclopentadiene 31 and trans-, -unsaturated aldehydes 89 under micellar catalysis (Scheme 25) [START_REF] Trentin | Micellar-driven substrate selectivity in Cr(salen)Cl catalytic Diels-Alder reaction in water[END_REF].

By introducing thiophene groups on the Salen scaffold anionic polymerization can be performed leading to an insoluble polymeric chiral catalyst 93' [START_REF] Zulauf | Original use of the same heterogeneous chiral catalyst batch to promote different asymmetric reactions[END_REF]. Either the monomeric unit 93 or the polymer has been found useful for several transformations including the hetero-Diels-Alder reaction of heptanal 92 and the Danishefsky's diene 2a (Scheme 26). After protic workup adduct is obtained in 53 % and 63 % respectively with an enantiomeric excess of 72 % and 63 % respectively.

The chirality in the classical Salen ligand is ensured by the trans-1,2-diaminocyclohexyl moiety. The use of cis-2,5diaminobicyclo[2.2.2]octane where the two nitrogen atoms are further separated would induce a larger chiral volume and could thus accommodate even more metals [START_REF] White | cis-2,5-diaminobicyclo[2.2.2octane, a new scaffold for asymmetric catalysis via salen-metal complexes[END_REF]. The cycloaddition of the Danishefsky's diene 2a with various aromatic aldehydes 40 with this Cr(III)-Salen-Cl 95 uniformly yields the adduct in excellent yields and enantioselectivity (Scheme 27). Finally, other Schiff base has been used as chiral ligand for the chromium(III) [START_REF] Mi Sowicz | Oxo-Diels-Alder reaction of Danishefsky's diene with aldehydes, catalyzed by chiral tridentate chromium(III)-Schiff base complexes[END_REF]. Jurczak's group demonstrated that a tridentate ligand bearing an adamantyl group (97) was highly efficient for the cycloaddition of the Danishefsky's diene 2a with various aldehydes (40) (Scheme 28). The authors have noticed that the enantioselectivity was slightly dependent on the temperature. In fact, a tetrameric form may be involved in the mechanism as seen by a double curved nonlinear effect.

PhCF 3 MS 4Å COR 3 Allyl R 1 R 2 n (R) (R) N N O O t-Bu t-Bu t-Bu t-Bu Cr F R 1 R 2 n N Allyl COR 3 OTBS CHO R = H, OPMB R CO 2 Me O X CHO X = CH 2 ,

Group 7

Manganese (Mn)

Complexation of a metal tricarbonyl to an arene ring dramatically modifies its properties. It has been shown that ( 5arene)Mn(CO) 3 is able to stabilize both negative and positive charges at the benzylic position [START_REF] Eloi | Ferrocenyl-substituted ( 5hydroxyalkylcyclohexadienyl)tricarbonylmanganese complexes: Synthesis, structural determinations, and formation of carbenium ions[END_REF]. The benzylic carbocation can be further stabilized by introduction of a ferrocenyl group to afford a cationic complex which can be isolated. Three of these catalysts were used for the cycloaddition of cyclopentadiene 31 with methacrolein 32. The best one (98) allows the complete conversion to the adducts 34 in 2 hours with 10 mol% with high exo selectivity (Scheme 29).

90 (2 mol%) H 2 O rt, 20 h (R) (R) N N O O t-Bu t-Bu t-Bu t-Bu Cr Cl OSO 3 Na H O R + CHO R + CHO R 91b (

Group 8

Iron (Fe)

Among the most used Lewis acids is iron(III) chloride. Moreover, it is widely available and is considered as eco-compatible. Donatoni et al. have showed that FeCl 3 can be easily adsorbed onto Aerosil ® silica (101) [START_REF] Donatoni | Solvent-free Diels-Alder reactions catalyzed by FeCl3 on Aerosil® silica[END_REF]. Aerosil ® silica is obtained by flamepyrolysis of SiCl 4 or quartz sand (thus also called fumed silica), and results 100-300 m /g of surface area. Quinones (100) can efficiently react with non-activated dienes [START_REF] Barroso | Highly enantio-and diastereoselective inverse electron demand hetero-Diels-Alder reaction using 2-alkenoylpyridine N-oxides as oxo-heterodienes[END_REF] without the need of a solvent (Scheme 30). When appropriate, the regioselectivity is governed by the substrates. The exact nature of the catalyst cannot be determined accurately, however a change in the Raman spectrum of the adsorbed catalyst compared to FeCl 3 is observed, some of the characteristic bands may be attributed to FeCl 4 and FeCl 2 4 . The porphyrin macrocycle is naturally occurring as metal complexes such as chlorophyll (coordinated to magnesium(II)) or heme (coordinated to iron(II)). The group of Kurahashi and Matsubara prepared the cationic complex [Fe III (TPP)] + 104 and its application in the Diels-Alder reaction (Scheme 31) [START_REF] Fujiwara | Cationic iron(III) porphyrincatalyzed [4 + 2]cycloaddition of unactivated aldehydes with simple dienes[END_REF]. This catalyst is very efficient since it promotes efficiently the hetero-cycloaddition of unactivated dienes 103 and dienophiles: the corresponding adducts [START_REF] Xie | The catalytic asymmetric Diels-Alder reactions and post-cycloaddition reductive transpositions of 1-hydrazinodienes[END_REF] are obtained usually in very high yields. It also shows a large functional group tolerance and the presence of water is tolerated. Subsenquently, the authors have prepared the iron(IV) corrole analogue [Fe IV (tpc)]BF 4 (107) (the corrole ring being 1 carbon atom shorter than the porphyrin ring) [ is more Lewis acidic than [Fe III (TPP)]BF 4 yielding the desired adducts 108 in better yield albeit with a decrease in selectivity.

R 3 R 1 + benzene 80°C, 12 h H O O Ph Ph N N N N Ph Ph Ph Ph Fe SbF 6 R 2 R 3 R 2

Ruthenium (Ru)

The above-mentioned catalysts were inefficient for the formation of octalones through cycloaddition of cyclohexenones 109 with butadienes 110. However, the [Ru III (TBPP)(CO)]SbF 6 complex ( 111) is able to perform such reaction in good yields (Scheme 32) [START_REF] Terada | Diastereoselective construction of trans-fused octalone framework via ruthenium-porphyrin-catalyzed cycloaddition[END_REF]. Interestingly, the cis-configured octalone is formed first but gradually epimerize to the trans isomer 112.

The use of ruthenium as Lewis acid is motivated by its moderate oxygen stability and its high water tolerance. In addition, compared to other strong Lewis acids, ruthenium complexes offer an increased rate of substrate-product exchange (i.e. better catalytic performance) and a decreased side-product formation [START_REF] Faller | Lewis acid catalysis by ruthenium complexes[END_REF]. The "three-legged piano stool" Ru complex 114 bearing adiketiminate ligand synthesized by Schreiber et al. was active for the cycloaddition of cyclopentadiene 31 with acrolein (113) yielding mainly the endo isomer 115a, while the methacrolein (32) furnishes predominantly the exo isomer 34b (>70 % yield) (Scheme 33) [START_REF] Schreiber | Application of electron-withdrawing coordinatively unsaturated 6 -arene -diketiminatoruthenium complexes in lewis acid catalyzed Diels-Alder reactions[END_REF]. The cationic character of the metal is crucial for its activity: the empty coordination site can interact with a carbonyl group and activate the substrate through a decrease of the LUMO energy.

Bis(phosphoroamidite) ligands 116 can equally be used for this cycloaddition [START_REF] Arena | Chiral cyclopentadienyl ruthenium(II) complexes with P,P-ligands derived from (1R,2R)-1,2-diaminocyclohexane: Synthesis, crystal structures and catalytic activity in Diels-Alder reactions[END_REF]. With higher catalyst loading, the exo adduct 34b is formed in a better yield and with better diastereoselectivity (Scheme 34). Despite the use of a chiral ligand, asymmetric induction is seldom observed in this case. Similar monocationic chiral Ru complexes 118 have been found uselful by the group of Kündig for the intramolecular Diels-Alder (IMDA) [START_REF] Thamapipol | Chiral ruthenium Lewis acid catalyzed intramolecular Diels-Alder reactions[END_REF][START_REF] Thamapipol | Intramolecular Diels-Alder reactions using chiral ruthenium Lewis acids and application in the total synthesis of entledol[END_REF]. These complexes are very mild Lewis acids, comparable to ZnCl 2 , but their electronic and steric properties can easily be tuned. For example, changing from cyclopentadienyl (118a) to indenyl (118b) ligand improves both yield and selectivity due to a looser coordination of the carbonyl to the metal (thus increasing the turnover) and to a more restricted space at the reactive site (Scheme 35).

t-Bu t-Bu t-Bu t-Bu CO R 4 R 3 O R 4 R 3 R 2
Carmona et al. have prepared dicationic Ru complexes which are fairly active for the cycloaddition of methacrolein 32 and cyclopentadiene 31 (up to 86 % yield and exo ratio > 92 %) albeit the enantioselectivity remains low (10-52 %) probably due to a rapid interconversion of the ligands in solution (Scheme 36) [START_REF] Carmona | Enantioselective Diels-Alder reactions catalyzed by well-defined Arene-Ruthenium complexes. Relationship between catalyst structure and enantioselectivity[END_REF].

Salen-type ligands (PNNP) 123 can also be useful for the cycloaddition of unsaturated -ketoesters [START_REF] Liu | Asymmetric Hetero-Diels Alder reaction of diazenes catalyzed by chiral silver phosphate: Water participates in the catalysis and stereocontrol[END_REF] [START_REF] Schotes | Asymmetric Diels-Alder reactions of unsaturated -ketoesters catalyzed by chiral ruthenium PNNP complexes[END_REF][START_REF] Schotes | Asymmetric Diels-Alder and Ficini reactions with alkylidene -ketoesters catalyzed by chiral ruthenium PNNP complexes: Mechanistic insight[END_REF]. Various dienes 122 were screened furnishing the cis-fused adducts 124 in 80-99 % yield with high enantioselectivity (Scheme 37).

Finally, [Ru(bpz) 3 ] 2+ 127 has been described to promote a radical cation Diels-Alder reaction photocatalysis [START_REF] Lin | Radical cation Diels-Alder cycloadditions by visible light[END_REF]. Under visible light, the Ru complex is excited and able to oxidize the dienophile 125 to a radical cation which can subsequently react with a moderately electron-rich diene [START_REF] Zhu | Formal syntheses of (±)-platensimycin and (±)-platencin via a dual-mode lewis acid induced cascade cyclization approach[END_REF] affording the desired product 128 within a good yield (Scheme 38).

Group 9

Cobalt (Co)

The group of Hilt is actively involved in the cobalt(I) 1,4hydrovinylation. They have shown that the ligand around the cobalt has a dramatic influence on the outcome of the reaction leading either to 1,3-or 1,4-substituted cyclohexa-1,4-diene (m-131 or p-131) through [4+2] cycloaddition or even cyclooctatrienes from a [4+2+2] reaction (Scheme 39) [START_REF] Erver | Cobalt(I) catalysis in the diastereoselective two-step synthesis of tricyclic systems[END_REF][START_REF] Fiebig | Cobalt catalysis in the gas phase: Experimental characterization of cobalt(I) complexes as intermediates in regioselective Diels-Alder reactions[END_REF][START_REF] Hilt | Studies of electronic effects of modified pyridine-imine ligands utilized in cobaltcatalyzed meta-selective Diels-Alder reactions[END_REF].

Kurahashi and Matsubara's group devised the use of [Co III (TPP)]SbF 6 133 for the imino-Diels-Alder reaction of unactivated imines [START_REF] Tan | Enantioselective [4+2]cycloadditions of 2-vinyl-1H-indoles with 3-nitro-2Hchromenes catalyzed by a Zn(OTf)2/bis(oxazoline) complex: An efficient approach to fused heterocycles with a quaternary stereocenter[END_REF] and simple dienes 106 [START_REF] Wakabayashi | Cobalt(III) porphyrin catalyzed aza-Diels-Alder reaction[END_REF]. While other metallo-porphyrins (Fe or Mn) or usual cobalt Lewis acids ([Co(salen)]SbF 6 or CoCl 2 ) remained inactive, the Co(III) complex is highly efficient and totally chemoselective (Scheme 40). Indeed, in the presence of other carbonyl heterodienophiles the sole imine reacts.

Ru

O P P OHC R 2 R 1 Z Z 117 R 1 , R 2 = H, Me Z = H, CO 2 Me Z Z H H CHO R 1 R 2 O O Ph Ph (F 5 C 6 ) 2 (C 6 F 5 ) 2

Rhodium (Rh)

Chiral rhodium(II) carboxylates are widely used in organic chemistry for their facile formation of carbenoids which can in turn react with a nucleophile to yield a X H insertion product (X = C, O, N,…). They can also be used as traditional Lewis acids for the complexation a carbonyl group in hetero-Diels-Alder reactions. Although the Rawal's diene is more reactive than the Danishefsky's one, it is also more sensitive towards moisture or (Lewis) acidity (coordination of the Lewis basic amino group would deactivate the diene). The rhodium carboxamidate Rh 2 (S-BPTPI) 4 136 proved to be highly efficient for the cycloaddition of Rawal type dienes with different unactivated aldehydes yielding the adducts in very high enantioselectivities [START_REF] Watanabe | Highly enantioselective hetero-Diels-Alder reactions between Rawal's diene and aldehydes catalyzed by chiral dirhodium(II) carboxamidates[END_REF][START_REF] Watanabe | Enantio-and diastereoselective hetero-Diels-Alder reactions between 4-methyl-substituted Rawal's diene and aldehydes catalyzed by chiral dirhodium(II) carboxamidates: Catalytic asymmetric synthesis of (-)-cis-aerangis lactone[END_REF]. Using this complex, 1,3-oxazinan-4ones 137 can be obtained from the cycloaddition of aldehydes [START_REF] Xu | Asymmetric inverse-electron-demand hetero-Diels-Alder reaction of six-membered cyclic ketones: An enamine/metal lewis acid bifunctional approach[END_REF] with 2-aza-3-siloxy-1,3-butadienes 135 (Scheme 41) [START_REF] Watanabe | Enantio-and diastereoselective hetero-Diels-Alder reactions between 2-aza-3-silyloxy-1,3-butadienes and aldehydes catalyzed by chiral dirhodium(ii) carboxamidates[END_REF].

A rhodium(I) complex bearing a chiral phosphine-phosphite ligand [START_REF] Harada | Chiral holmium complex-catalyzed Diels-Alder reaction of silyloxyvinylindoles: Stereoselective synthesis of hydrocarbazoles[END_REF] has been used for the intramolecular Diels-Alder reac-tion (Scheme 42) [START_REF] Falk | Rhodiumcatalyzed enantioselective intramolecular [4+2]cycloaddition using a chiral phosphine-phosphite ligand: Importance of microwave-assisted catalyst conditioning[END_REF]. Although the active species has not been isolated (but supposed to be Rh[(L* 2 ) 2 ] + ), the catalyst preparation is crucial for the both yield and enantioselectivity and microwaveconditioning gave the best results. The mechanism for similar neutral electron demand cycloadditions has been investigated through DFT calculations [START_REF] Liao | DFT Study of the mechanism and stereochemistry of the Rh(I)-catalyzed Diels Alder reactions between electronically neutral dienes and dienophiles[END_REF]. The initial rhodium coordination to the diene is followed by a cis-coordination with the alkene. Then a cis oxidative cyclization and a reductive elimination yields the cisconfigured adduct.

Iridium (Ir)

Following their studies concerning the Diels-Alder reaction catalysed by [( 6 -arene)Ru II tivity was diminished by -substitution) [START_REF] Carmona | Enantioselective catalysts based on the chiral fragment ( 5-C5Me5)Ir(Prophos) for Diels-Alder reactions[END_REF]. They even found that methyl (or ethyl) vinyl ketone 142 were suitable partners in this cycloaddition though with reversed facial selectivity (endo) (Scheme 43) [START_REF] Carmona | Enantioselective catalytic Diels-Alder reactions with enones as dienophiles[END_REF]. By varying the chiral phosphine ligand they managed to obtain the 5-methyl-5-formyl-2-norbornene with almost perfect exo ratio and very high enantioselectivity (> 80 %) [START_REF] Carmona | Enantioselective catalysts for the Diels-Alder reaction between methacrolein and cyclopentadiene based on the chiral fragment ( 5-C5Me5)M(chiral diphosphane) (M = Rh, Ir)[END_REF]. They eventually showed that chiral iridium(III) hydrides 146 were active for both 1,3-dipolar cycloaddition of nitrones or for the [4+2] cycloaddition of cyclopentadiene 31 with nitrostyrene 145 [START_REF] Carmona | Chiral octahedral phosphano oxazoline iridium(III) complexes as catalysts in asymmetric cycloaddition reactions[END_REF]. The adducts 147 are usually obtained with almost perfect endo selectivity and with high enantiomeric excess (Scheme 44).

Me

Group 10

Nickel (Ni)

The use of 1-aza-1,3-dienes in hetero-Diels-Alder allows the formation of piperidine derivatives, however these dienes have low reactivity and tend to decompose under Lewis acidic conditions. The use of a heteroarylsulfonyl protecting group on the nitrogen gives the opportunity of another coordination site thus improving the reactivity and/or the selectivity [START_REF] Esquivias | Inverseelectron-demand Diels-Alder reactions of N-(heteroarylsulfonyl)-1-aza-1,3dienes catalyzed by chiral lewis acids[END_REF]. In particular the imine 148 allows the formation of the corresponding adducts 151 in good yields and enantioselectivity (although a drop of the enantiomeric excess is observed when -substituted enol ethers are used) (Scheme 45). The nickel(II) bearing a chiral bis(oxazolidine) ligand 150 has been found superior to copper(II) since a larger scope of dienophiles can be used (and in a smaller excess: 5 eq. instead of 20 eq.) and the enantiocontrol is better.

Palladium (Pd)

Palladium is generally used for the creation of C C bonds through a coupling reaction yet it has also been used as catalyst for the Diels-Alder cycloaddition [START_REF] Nishiuchi | Reactivity and efficient recycling of a chiral Pd-BINAP catalyst for catalytic asymmetric Diels-Alder reaction in ionic liquid[END_REF]. Nishiuchi et al. has demonstrated that ionic liquid as solvent was important for the recycling of the Pd II -BINAP catalyst 153 (Scheme 46). Although the yield is moderate it remained constant for 7 consecutive runs while the facial selectivity and the enantiomeric excess stayed very high throughout the recycling experiment.

Group 11 (Coinage Metals)

Copper (Cu)

The chiral bis(oxazoline) (BOX) ligand is a C2-symmetric and widely used scaffold for organic transformations [START_REF] Stanley | Privileged Chiral Ligands and Catalysts[END_REF]. Since the seminal report of Cu II (BOX) as catalyst for the Diels-Alder reaction by Evans [START_REF] Evans | Bis (oxazoline)copper(II) complexes as chiral catalysts for the enantioselective Diels-Alder reaction[END_REF], numerous reports of such complexes are found in the literature for carbo-or hetero-Diels-Alder both normal or inverse electron demand.

For example, the group of Desimoni used a chiral aminodiol to prepare pentacoordinated copper(II) complex 155 having a square pyramidal geometry (Scheme 47) [START_REF] Desimoni | A new copperII/isopropylidene-2,2-bis(oxazoline) catalyst and its stable reactive complex with acryloyloxazolidinone in enantioselective reactions[END_REF]. This catalyst is very active, yielding quantitatively the adduct 154a with a loading of 1 mol %, however the facial selectivity and the enantiomeric excess remains slightly lower than the original catalyst. A similar ligand design (156) was introduced by the group of Ishihara however the sulphonamide group provides a weak secondary interaction that increases the Lewis acidity of the copper atom (n-cation interaction) and induces a more rigid scaffold [START_REF] Sakakura | Rational design of highly effective asymmetric Diels-Alder catalysts bearing 4,4sulfonamidomethyl groups[END_REF]. In turn, this catalyst provides excellent selectivity as well as activity at 1 mol % loading.

Unless the two oxazoline rings are tethered by a quaternary carbon atom, double bond isomerisation (conjugation) may occur. Therefore, O'Leary's group developed chiral oxazoline ligands derived from renewable sources, in particular arabitol (158) possessing the stereogenic centers on the backbone (Scheme 48) [START_REF] Frain | Preparation, structure and catalytic activity of copper(II) complexes of novel 4,4 -BOX ligands[END_REF][START_REF] Kellehan | AraBOX and XyliBOX based catalysts for cyclopropanations, Diels Alder cycloadditions and allylic additions[END_REF]. Despite good activity, these ligands lack selectivity with a moderate endo ratio (64-82%) and up to 57 % ee.

The stereochemistry of both the scaffold and the chiral oxazolines can have an influence on the selectivity of the cycloaddition. The study by Le Maux et al. shows that maximum enantiomeric excess is obtained with the (11S,12S)-Bis[(4'R)phenyloxazoline]-9,10-dihydro-9,10-ethanoanthracene 160 (or its enantiomer) (Scheme 49) [START_REF] Maux | Asymmetric copper-catalyzed Diels-Alder reaction revisited: Control of the structure of bis(oxazoline) ligands[END_REF]. The other diastereoisomer only leads to reduced selectivity.

By analogy with the well-known Pyridine bis(oxazoline) (Py-BOX) ligands, the group of Lassaletta and Fernández synthesised chiral pyridine bis(hydrazone) frameworks (161) which would act as tridentate ligands [START_REF] Monge | Design and synthesis of new bis-hydrazones and pyridine bis-hydrazones: Application in the asymmetric Diels-Alder reaction[END_REF]. In non-dried toluene up to 95% yield can be obtained with a good 92% endo ratio and 74 % ee (Scheme 50).

Camphor-based oxazoline ligands were used for the exoselective cycloaddition of ethyl vinyl ether and (E)-ethyl 2-oxo-4phenylbut-3-enoate in good yield, but with a moderate enantioselectivity [START_REF] Barba | Exoselective asymmetric inverse-electron demand hetero-Diels-Alder reaction catalyzed by Cu(II)-hydroxy oxazoline ligands[END_REF]. The , -unsaturated--ketoesters 162 can react with the electron-rich Danishefsky's diene 2a under the catalysis of a chiral copper-prolinol complex 163 [START_REF] Hu | Copper-catalyzed enantioselective hetero-Diels Alder reaction of Danishefsky's diene with , -unsaturated -ketoesters[END_REF]. Dihydroyrones 164 are obtained in high yields (> 80 %) with high optical purity (> 93% ee) (Scheme 51). With 2-vinylindoles (166), , -unsaturated--ketoesters 165 affords tetrahydrocarbazoles 168, thus reacting as a carbadienophile [START_REF] Ouyang | The asymmetric Cu(II)indolinylmethanol complex catalyzed Diels-Alder reaction of 2-vinylindoles with , -unsaturated -ketoesters: An efficient route to functionalized tetrahydrocarbazoles[END_REF]. High diastereoselection and moderate to good enantiomeric excesses are obtained using a chiral indolinylmethanol ligand 167 (Scheme 52).

Having a large selection of ligands in hand, attention has also been drawn to expand the substrate scope of the Diels-Alder reaction (Scheme 53). For example 2-alkenoylpyridine-N-oxides (169, 172) have been found useful both as heterodiene (with ethyl vinyl ether 17 at -40°C) [START_REF] Barroso | Highly enantio-and diastereoselective inverse electron demand hetero-Diels-Alder reaction using 2-alkenoylpyridine N-oxides as oxo-heterodienes[END_REF] or as dienophile (for the cycloaddition with cyclopentadiene 31 at -20°C) [START_REF] Livieri | Enantioselective cycloadditions of 2-alkenoylpyridine-N-oxides catalysed by a bis(oxazoline)/CuII complex: Structure of the reactive intermediate[END_REF] yielding the corresponding adducts in very high yield and selectivities. Similar behaviour has been observed with , -unsaturated--ketoesters 47 and cyclopentadiene by Feng's group [START_REF] Zhu | Asymmetric Diels-Alder and inverse-electron-demand hetero-Diels-Alder reactions of , -unsaturated -ketoesters with cyclopentadiene catalyzed by N,N -dioxide copper(II) complex[END_REF]. Keeping the same chiral catalyst 175, the Diels-Alder pathway is favoured at room temperature while the hetero-Diels-Alder product 49 is obtained at lower temperature (-20°C).

Allylsilanes (177) are less nucleophilic than enol ethers therefore less reactive. The n-cation catalyst 156 developed by Ishihara's group allows the hetero-cycloaddition of allysilanes with ,unsaturated--ketoesters 176 with endo/exo ratio depending mainly on the steric hindrance of the ester moiety (Scheme 54) [START_REF] Matsumura | Catalytic enantioselective inverse electron demand hetero-Diels-Alder reaction with allylsilanes[END_REF].

Various nitrogen heterodienes can be used in the Cu(BOX) (181) catalysed cycloaddition such as 1,2-diaza-1,3-dienes 180 (with ethyl vinyl ether 17) [START_REF] Gao | Coppercatalyzed enantioselective inverse electron-demand hetero-Diels-Alder reactions of diazadienes with enol ethers: Efficient synthesis of chiral pyridazines[END_REF], 1,2-dihydropyridine 76 with a pyrazolidinone derivative 183 [START_REF] Hutabarat | Highly enantioselective synthesis of isoquinuclidine by diels-alder reaction of 1,2dihydropyridine utilizing chiral bisoxazoline-Cu(II) complex[END_REF] or 1-hydrazinodiene 185 (with N-acryl-oyloxazolidinone 186) to afford selectively the exo adduct 187 (Scheme 55) [START_REF] Xie | The catalytic asymmetric Diels-Alder reactions and post-cycloaddition reductive transpositions of 1-hydrazinodienes[END_REF].

Dithioesters (188) have also been used for the enantioselective or asymmetric diastereoselective thia-Diels-Alder cycloaddition (Scheme 56) [START_REF] Dentel | First catalytic enantioselective version of a thia hetero-Diels-Alder reaction with dithioesters[END_REF][START_REF] Dentel | Asymmetric diastereoselective thia-hetero-Diels-Alder reactions of dithioesters[END_REF].

Methodological improvements have also concerned the recyclability of the chiral catalyst. To this end, two imidazolium tags can be incorporated in the ligand core of the catalyst 192 [START_REF] Zhou | Recyclable copper catalysts based on imidazolium-tagged C2-symmetric bis(oxazoline) and their application in D-A reactions in ionic liquids[END_REF]. Interestingly, the cycloaddition between cyclohexadiene 191 and N- acryloyloxazolidinone 152 proceeds only in hydrophobic ionic liquids ([Bmim]NTf 2 being the best) and gives better results than the classical CuBOX catalyst (Scheme 57). In addition, it can be reused for at least 20 times without a significant loss of yield or endo and enantioselectivity. Ionic liquids can also serve to immobilize Cu(BOX) in a noncovalent fashion. The catalyst can be adsorbed on an ionic liquid film which can be used in solution (Supported Ionic Liquid Phase catalysis) or further immobilized on a solid support such as an ionic polymer (Polymer Immobilized Ionic Liquid Phase system) [START_REF] Goodrich | Asymmetric carbon-carbon bond forming reactions catalysed by metal(II) bis(oxazoline) complexes immobilized using supported ionic liquids[END_REF][START_REF] Doherty | An efficient Cu(II)-bis(oxazoline)-based polymer immobilised ionic liquid phase catalyst for asymmetric carbon-carbon bond formation[END_REF]. This latter system offers better enantiomeric excess and diastereoselectivity over SILP catalysis, in the detriment of the recyclability (copper leaching being the main drawback).

Another immobilization strategy is to form charge-transfer complexes (CTC) which are noncovalent interactions between an electron-rich arene (donor) and an electron-poor (receiver) arene. The group of Schulz successively investigated the incorporation of a donor and a receiver on the Cu(BOX) scaffold [START_REF] Chollet | Reusable chiral bis(oxazoline)-copper complexes immobilized by donor-acceptor interactions on insoluble organic supports[END_REF][START_REF] Didier | A reusable TNF-tagged chiral bis(oxazoline)-copper catalyst for Diels-Alder transformations[END_REF]. While the anthracenyl ligand (donor) gave moderate results in terms of recyclability, the electron-poor ligand bearing a TNF group 194 was still affording quantitative conversion (about 90% yield) and good ee's of the endo adduct 159a' after 20 different runs (Scheme 58). The catalyst can be recovered by a mere filtration after addition of anthracene and precipitation with pentane.

One important characteristic of copper(II) species is their azaphilic character. Peptides are therefore good candidates as chiral ligands. The cyclo[-His(Tr)-His(Tr)-] diketopiperazine 195 shows moderate induction (35% ee) but good facial selectivity (92 % in favour of the endo isomer 154a') (Scheme 59) [START_REF] Furutani | Cyclo[-His-His-]derived C2symmetric diketopiperazine as chiral ligand for asymmetric diels-alder reactions[END_REF].

Cyclic peptides containing a disulphide bridge (197) have been designed and prepared by the group of Herrmann for the asymmetric copper-catalysed Diels-Alder cycloaddition (Scheme 60) [START_REF] Zheng | Conformationally constrained cyclic peptides: Powerful scaffolds for asymmetric catalysis[END_REF]. They further optimised the sequence in order to obtain efficient catalysts. High endo selectivity (> 93%) as well as enantiomeric excess (> 88%) was obtained with acryloylimidazole dienophile 196. A 30-mer peptide derived from the bovine pancreatic polypeptide (bPP) in the presence of Cu 2+ is able to catalyse the same reaction however the substrate scope is more dependent on the peptide sequence [START_REF] Coquière | Enantioselective artificial metalloenzymes based on a bovine pancreatic polypeptide scaffold[END_REF]. Though a maximum of 83 % ee has been obtained.

Artificial copper enzymes can also be used for the Diels-Alder reaction. Deuss et al. have prepared such enzymes by conjugation of sterol carrier protein type 2 like domain (SCP-2L) mutants with a tridentate copper ligand through thiol-maleimide ligation [START_REF] Deuss | Artificial copper enzymes for asymmetric Diels-Alder reactions[END_REF]. The best enantiomeric excess obtained is still limited (25 %). Feringa and Roelfes have shown that copper catalysed asymmetric Diels-Alder reaction can be performed with salmon testes DNA (st-DNA) and a poly-pyridine ligand 200 [START_REF] Boersma | Ligand denticity controls enantiomeric preference in DNA-based asymmetric catalysis[END_REF]. Interestingly, the denticity of the ligand has a strong influence on the asymmetric induction (Scheme 61). The copper bound to the terpyridine ligand adopts an octahedral geometry while its geometry is a trigonal bipyramid when bound to the bipyridine ligand. The opposite enantiomer is obtained in this latter case, often with higher enantiomeric excess.

As already evoked (vide supra) the geometry of the copper ion in its chiral environment is important for the stereoselectivity of the reaction. EPR studies were conducted to decipher the intermediates involved in the cycloaddition of ethyl glyoxylate 202 and cyclohexadiene 191. Complexation of Cu(OTf) 2 with the ( t-Bu)BOX ligand generates a tetrahedral intermediate (181a) which evolves to a penta-coordinated 18-electron complex after chelation with both carbonyls of the glyoxylate (Scheme 62) [START_REF] Umamaheswari | Ligand spheres in asymmetric hetero Diels-Alder reactions catalyzed by Cu(II) box complexes: Experiment and modeling[END_REF]. With the ( i- Pr)PyBOX ligand, the copper atom adopts a penta-coordinated distorted square pyramidal geometry (204) throughout the reaction stages [START_REF] Umamaheswari | Catalytically active Cu(II)-pybox complexes: Insights by EPR Spectroscopy and DFT Computations[END_REF].

Silver (Ag)

Silver(0) nanoparticles supported on silica (207) were found active in promoting the cycloaddition of hydroxychalocones 205 [START_REF] Cong | Silver nanoparticle-catalyzed Diels -Alder cycloadditions of 2 -hydroxychalcones[END_REF]. Although the endo/exo ratio is moderate, turnover numbers up to 8700 are achieved (Scheme 63). The mechanism is believed to proceed through single electron transfer and generation of phenoxyl radical stabilized by the nanoparticle.

Chiral silver phosphates derived from BINOL (211) are able to catalyse the hetero-Diels-Alder reaction of diazenes 210 with unactivated dienes 209 with high enantiocontrol (Scheme 64) [START_REF] Liu | Asymmetric Hetero-Diels Alder reaction of diazenes catalyzed by chiral silver phosphate: Water participates in the catalysis and stereocontrol[END_REF]. Interestingly, the authors have noted a reversed regioselection if a hydrogen-bond donor was present in the diene. Indeed, a hydrogenbond with the phosphate function and additional interaction with the silver atom (already involved in the -coordination of the urea nitrogen) has been computed.

N O O t-Bu t-Bu Cu OTf TfO N N O O t-Bu t-Bu Cu(OTf) 2 CH 2 Cl 2 N N O O t-Bu t-Bu Cu O O EtO H OTf O CO 2 Et N N O i-Pr N O i-Pr N N O i-Pr N O i-Pr Cu OTf TfO N N O i-Pr N O i-

Gold (Au)

Other metal phosphates such as magnesium, calcium or gold also allow the formation of the desired adduct, albeit in the racemic form. However gold(I) phosphoramidite ligands were found even more reactive (better yields and a reduced reaction time) and more selective [START_REF] Liu | Chiral gold complex-catalyzed hetero-diels-alder reaction of diazenes: Highly enantioselective and general for dienes[END_REF].

Gold has recently been employed in organic transformations because of its rather unique properties of carbophilic Lewis acidity and -complexation, both resulting from relativistic effects. The cycloaddition of allenyl ethers 214 is catalysed by the cationic complex [(Ph 3 P)Au]SbF 6 (215) which coordinates first to the terminal allenic double bond ensued by the formation of an allylic cation intermediate (Scheme 65) [START_REF] Wang | Cationic gold(I)-catalyzed intermolecular [4+2]cycloaddition between dienes and allenyl ethers[END_REF]. Computation shows that the transition state leading to the Z isomer was lower in energy, and thus confirms the experimental observations.

Similarly, the group of López and Mascareñas has shown that allenamides 217 can play the role of dienophile in the Diels-Alder reaction [START_REF] Faustino | Gold(I)-catalyzed intermolecular (4+2) cycloaddition of allenamides and acyclic dienes[END_REF]. They have pointed out that both cationic gold complexes and neutral AuCl can catalyse this transformation, even though the neutral complex is less reactive (but more selective towards the [4+2] cyclisation). The use of atropisomeric NHC ligands allows the formation of enantioenriched adducts 220 (> 87 % ee) with cationic gold complexes 219 (Scheme 66) [START_REF] Francos | Axially chiral triazoloisoquinolin-3-ylidene ligands in gold(I)-catalyzed asymmetric intermolecular (4+2) cycloadditions of allenamides and dienes[END_REF].

Group 12

Zinc (Zn)

With their filled valence-shell ((n-1)d 10 ns 2 configuration), group 12 elements does not belong to the transition metals according to the IUPAC definition (which is an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell). However, for the sake of convenience and since they share similar features than transition elements (as defined by the IUPAC) they will be discussed in this section.

Recently, Zhu et al. have shown by DFT computation thatbinding to propene or -binding to acetaldehyde requires similar enthalpies in the case of zinc(II) salts [START_REF] Zhu | Formal syntheses of (±)-platensimycin and (±)-platencin via a dual-mode lewis acid induced cascade cyclization approach[END_REF]. Therefore, they are able to act as bifunctional catalysts allowing for a cascade cyclisation yielding cis-hydrindane cores (222) [START_REF] Han | A highly convergent cascade cyclization to cis-hydrindanes with all-carbon quaternary centers and its application in the synthesis of the aglycon of dendronobiloside A[END_REF] or 6,6,5-tricyclicfused systems (225) [START_REF] Zhu | A bifunctional lewis acid induced cascade cyclization to the tricyclic core of ent-kaurenoids and its application to the formal synthesis of (±)-platensimycin[END_REF] (Scheme 67). In this last example, a dimeric zinc complex is involved in a first -Lewis acid catalysed Diels-Alder reaction followed by a -Lewis acid catalysed carbocyclisation. The simultaneous use of microwave and ZnCl 2 as Lewis acid has been defined as optimum conditions for the cycloadditions of the Danishefsky's diene 2a with aldehydes (226a) or imines (226b) derived from carbohydrates (Scheme 68) [START_REF] Burland | Rapid synthesis of carbohydrate derivatives, including mimetics of C-linked disaccharides and C-linked aza disaccharides, using the hetero-Diels-Alder reaction[END_REF]. The nature of the starting sugar has an influence on the reactivity due to both steric and electronic interactions: galacto-and mannopyranoside derivatives are less reactive than glucose. In addition, electronwithdrawing protecting groups (acetates) allow better yields than electron-donating ones (benzyl).

+ N • O O R 1 R 5 R 3 R 4 R 2 N N N Ad Au R X CH 2 Cl 2 -50°C, 1 h R 5 R 3 R 4 R 2
Zinc(II) chloride has also been found valuable in the cycloaddition of unusual dienophiles such as 2-phosphono-2-alkenoates [START_REF] Liao | Investigation on Lewis acid mediated Diels-Alder reactions of 2-phosphono-2-alkenoates. Application to total synthesis of (±)--Alasken-8-one via reductive alkylation of resulting adduct[END_REF] or highly reactive cyclobutenones [START_REF] Li | Cyclobutenone as a highly reactive dienophile: Expanding upon diels-alder paradigms[END_REF].

Among other metals, zinc(II) has been found the best to perform the enantioselective cycloaddition of 3-nitro-2H-chromenes 228 with N-benzyl-2-vinyl-1H-indoles 229 [START_REF] Tan | Enantioselective [4+2]cycloadditions of 2-vinyl-1H-indoles with 3-nitro-2Hchromenes catalyzed by a Zn(OTf)2/bis(oxazoline) complex: An efficient approach to fused heterocycles with a quaternary stereocenter[END_REF]. The fused heterocyclic 231 were obtained with excellent diastereoisomeric ratios (> 95%) and 70-96% ee (Scheme 69).

Although imino-Diels-Alder involving an electron-poor azadienophile and an electron-rich diene are well-known, inverse elec-tron demand imino-Diels-Alder between an electron-poor diene (232) and an electron-rich imine (233) is seldom. Chiral indoloquinolizines 235 can be prepared in this manner by Zn II -BINOL catalysis (Scheme 70) [START_REF] Eschenbrenner-Lux | An enantioselective inverse-electron-demand imino Diels-Alder reaction[END_REF]. Good yields are obtained (51-96 %) along with high optical purity (usually > 88 %).

f-BLOCK METALS

Although sometimes referred to as "inner transition metals" elements of the f-block possess peculiar properties (such as increased coordination number) which lead them to be treated apart.

Lanthanides

The first sub-group concerns the elements from Z=57 (La) to Z=71 (Lu). They mainly adopt the +3 oxidation state and basicity decreases as the atomic number increases.

Lanthanum (La)

As already stated gold is a -Lewis acid (vide supra) often used for hetero-or carbocyclisation whose resulting intermediate can further be involved in a cycloaddition step. Xu's group has investigated the synthesis of spiroketals and spiroaminals from ,unsaturated--ketoesters 37 [START_REF] Wang | Synthesis of spiroaminals and spiroketals with bimetallic relay catalysis[END_REF]. The dienophile 237 is prepared by Au(I)-catalysed 5-exo-dig cyclisation of either benzylic alcohols or amines (236) (Scheme 71). Spiroketals are best prepared by Y(OTf) 3 cycloaddition while La(OTf) 3 is necessary for efficient synthesis of spiroaminals 238 (71-90 % yield).

Europium (Eu)

Eu(fod) 3 is a potent oxophilic Lewis acid which has been extensively used for inverse electron demand hetero-Diels-Alder reaction, especially by the group of Dujardin. Although very mild Lewis acid, they have shown that this catalyst can be used under hyperbaric conditions when the intrinsic reactivity of the partners is too low [START_REF] Maingot | High-pressure Hetero-Diels-Alder route to (±)-6,6,6-trifluoro--C-naphthyl glycosides[END_REF]. The reaction between , -unsaturated--ketoester 239 and chiral N-alkenyloxazolidinones 240 is highly endo selective (Scheme 72) when catalysed by Eu(fod) 3 (assuming a concerted mechanism occurs) whereas a complete reversed facial selectivity is observed when SnCl 4 is used (explained by the formation of a zwitterionic intermediate) [START_REF] Vu | A convergent hetero-Diels-Alder strategy for asymmetric access to a lactone containing two lipidic chains[END_REF]. In addition, the yields are lower due to the high acidic character of SnCl 4 (partial decomposition of the heterodiene). With an appropriate dienophile, analogues of steganacin can be obtained [START_REF] Laurent | New two-step sequence involving a hetero-Diels-Alder and a nonphenolic oxidative coupling reaction: A convergent access to analogs of steganacin[END_REF].

The use of dienophiles derived from ketones (cyclic in particular) is limited due to their low reactivity. Gallier et al. have shown that chiral cyclic enamides 243 were able to yield the bicyclic adducts 244 with high facial and endo selectivity (Scheme 73) [START_REF] Gallier | Hetero-Diels-Alder reactions of cyclic ketone derived enamide. A new and efficient concept for the asymmetric Robinson annulation[END_REF]. This reaction has been developed as an alternative Robinson annulation.

Gadolinium (Gd)

Chiral Gd(hfc) 3 has been used in the cycloaddition of benzaldhyde with the Danishefsky's diene with moderate induction (35-40 % ee) slightly higher than Eu(hfc) 3 [START_REF] Stockinger | Comparison of a Molecular and an immobilized gadolinium(III)-tris[(1R,4S)-3-heptafluorobutanoyl-camphor]as catalyst in the asymmetric danishefsky-hetero-Diels-Alder-reaction[END_REF]. However, when immobilized on a polysiloxane and used as a catalytically active stationary phase in on-column reaction gas chromatography the optical purity dropped to only 12 % ee.

Holmium (Ho)

The asymmetric synthesis of highly substituted hydrocarbazoles 247 has been described by the group of Nishida using a chiral holmium(III) thiourea complex 246 [START_REF] Harada | Chiral holmium complex-catalyzed Diels-Alder reaction of silyloxyvinylindoles: Stereoselective synthesis of hydrocarbazoles[END_REF]. Silyloxyvinylindoles 245 undergoes a complete exo selective cycloaddition with Nacyloxazolidinones 186 (Scheme 74). Ho(NTf 2 ) 3 has been found superior than Yb(OTf) 3 .

Erbium (Er)

The asymmetric inverse electron demand cycloaddition of ,unsaturated--ketoesters 242 with electron-rich dienophiles has been performed with a chiral N,N'-dioxide/Er III complex 249 (Scheme 75) [START_REF] Zhu | Asymmetric cycloaddition of , -unsaturated -ketoesters with electron-rich alkenes catalyzed by a chiral Er(OTf)3/N,N'-dioxide complex: Highly enantioselective synthesis of 3,4-dihydro-2H-pyrans[END_REF]. Erbium is superior to the other metals salts tested especially lanthanides yielding the bicyclic adduct 250 with better yields, endo selectivity and optical purity. Amounts of catalyst as low as 0.05 mol% can be used still giving quantitative formation of the adduct.

Natural abundance of lanthanides is rather low, so efficient way of recycling is strongly recommended. Bortolini et al. have demon-strated the use of ionic liquid to perform Er(OTf) 3 -catalysed Diels-Alder reactions (Scheme 76) [START_REF] Bortolini | Erbium triflate in ionic liquids: A recyclable system of improving selectivity in Diels-Alder reactions[END_REF]. The ionic phase containing the catalyst can be reused for at least 6 times without loss of the activity (which remains higher than using CH 2 Cl 2 as solvent). Additionally, the endo/exo ratio has been found slightly dependent upon the ionic liquid used.

Ytterbium (Yb)

The inverse electron demand cycloaddition of vinyl ethers and , -unsaturated aldehydes or ketones can be performed on a wide range of substrates with Yb(fod) 3 upon conventional or microwave heating [START_REF] Armstrong | Oxidative rearrangement of 2-alkoxy-3,4-dihydro-2H-pyrans: Stereocontrolled synthesis of 4,5-cisdisubstituted tetrahydrofuranones including whisky and cognac lactones and crobarbatic acid[END_REF].

The cycloaddition of cyclopentadiene with chiral dienophiles bearing a remote p-tolylsulfinyl group (252 and 254) catalysed by Yb(OTf) 3 has been investigated [START_REF] Maestro | Remote stereocontrol by the sulfinyl group. Diels-Alder reaction of cyclopentadiene with substituted (S)-[2-(ptolylsulfinyl)styrenes and (S)-[2-(p-tolylsulfinyl)phenyl]vinyl ketones[END_REF]. Unless a highly reactive dienophile is used, hyperbaric conditions are required (8.2 kbar). Moderate to good diastereoselectivity was obtained albeit depending on the type of substrate used (Scheme 77).

The use of the chiral BINUREA ligand with Yb(OTf) 3 (256) allows the enantioselective cycloaddition of the Danishefsky's diene 2b with acryloyloxazolidinones 186 [START_REF] Harada | Highly enantioselective Diels-Alder reaction of Danishefsky-type diene and electron-deficient olefins catalyzed by an Yb(III)/chiral bis-urea complex[END_REF]. The desired cyclohexenones 257 were obtained usually with very high yields and with excellent optical purity (Scheme 78).

Cyclic imines 259 derived from chiral tartaric or malic acid can be transformed to indolizidinone 260 by cycloaddition with Danishefsky-type dienes 258 catalysed by Yb(OTf) 3 (Scheme 79) [START_REF] Shao | A diastereoselective cyclic imine cycloaddition strategy to access polyhydroxylated indolizidine skeleton: Concise syntheses of (+)-/(-)-lentiginosines and (-)-2-epi-steviamine[END_REF] Diastereoselectivity of this reaction is governed by the configuration of the stereogenic center at C3 position of the imine as well as by the steric requirements of its protecting groups. Imino-Diels-Alder reactions can also be achieved using polyoxometalates (POM) incorporating a metallic Lewis Acid [START_REF] Dupré | Chemoselective catalysis with organosoluble lewis acidic polyoxotungstates[END_REF]. The authors used a Dawson-type polyoxotungstate ([P 2 W 17 O 61 ] 10 ) and Yb III (262) showed a better catalytic activity than Hf IV , Zr IV or Y III (Scheme 80). Noteworthy, these metal POMs are organosoluble but can easily be precipitated thus allowing for recovery. This has been demonstrated in a Mannich reaction for at least ten times with Yb/POM.

Actinides

Actinides are a special group of elements since most of them are non-natural and radioactive. Therefore, their use in organic chemistry is extremely limited.

Uranium (U)

Increasing the oxidation state is expected to increase the Lewis acidity at the metal centre. Therefore, Robinson et al. have prepared uranium(IV) chiral heterobimetallic complexes derived from BI-NOL [START_REF] Robinson | Uranium(IV) BINOLate heterobimetallics: Synthesis and reactivity in an asymmetric Diels-Alder reaction[END_REF]. They show interesting reactivity and selectivity, only slightly lower than the Yb(III) analogue (Scheme 81). The radioactivity in such a reaction may be a concern, however the authors have measured its intensity after filtration on a silica plug, and none of the aqueous or organic phase is contaminated with uranium.

CONCLUSION

In the past few years, numerous metal salts or catalysts have been developed for the homo-or hetero-Diels-Alder cycloadditions (either normal or inverse electron demand). These latest advances can address specific needs towards the synthesis of a desired target or belongs to a methodological development. To this end, several compounds have been used as benchmark reagents in order to probe the reactivity/selectivity of any cycloaddition. Among the most used dienes is the Danishefsky's diene 2a, which is very reactive (due to the two electron-donating groups) and selective (by chelation of its methoxy group with the Lewis acid) yielding (hetero)cyclic ketones. Cyclopentadiene 31 is also often used to quantify the asymmetric induction of a catalyst through the formation of known bicyclic adducts. However, its tendency to dimerize may hamper its use. Inverse electron demand hetero-Diels-Alder is performed using , -unsaturated--ketoesters 37 as highly regioselective diene. Since 2009, major improvements have been described regarding the reactivity of the substrates, in particular highly congested reactants (especially those yielding adducts with a quaternary chiral center) or ketones which traditionally react sluggishly as heterodienophiles. An increasing number of catalysts is now able to promote these transformations more efficiently, but room is still available for improvement. The same remark can be formulated for diastereo-and/or enantio-selectivity. Yet, obtaining only either the endo or the exo adduct for a specific cycloaddition is not always possible. Neutral-electron-demanding Diels-Alder reactions may undergo the most significant progress in the near future as the activation of either the diene or dienophile seems more easily feasible.

Sustainability of the whole process has become increasingly significant. Alternative solvents have emerged recently and have to be further investigated. These reactions are totally atom-economic but recyclability of the promoters (which are sometimes rather expensive) is crucial for improving their viability. Although interesting examples are already described, the selectivity or reactivity may be diminished to some extent.

Therefore, the quest for the ideal promoter is not achieved yet, and efforts are still ongoing to further improve the reactivity and selectivity issues. Finally a more in-depth understanding of the reactivity (secondary interactions, solvent effect…) would be desirable in order to design even more efficient promoters.

LIST OF ABBREVIATIONS

Fig. ( 1 )

 1 Fig. (1). FMO interactions diagram.

  Scheme 1.

  Scheme 3.

  Scheme 19.

  Scheme 24.

  Scheme 31.

  Scheme 32.

  Scheme 38.

  Scheme 41.

  Scheme 45.

  Scheme 56.

  Scheme 59.

  Scheme 63.

  Scheme 66.

+ ZnCl 2

 2 Scheme 68.

  Scheme 77.

  Scheme 80.

Scheme 10.

												Ar
														Ar
				AuCl•DMS							37		H
		TsHN		(5 mol%)				RO 2 C		O
			35	3	Toluene		N Ts 36		Ga(OTf) 3 (10 mol%) 40°C, 90 min	RO 2 C	O 38	N Ts
													14 examples
													50-90 % yield
													d.r. = 2:1 -16:1
	Scheme 9.
					OMe					N			O
				O
				+			CH 2 Cl 2		O	Ga	O
			Ph	H	OSiMe 3	rt, 16 h			O			O	Ph
				1	2a								4
													61 % yield
									39 (10 mol%)
				OSiMe 3									O
	O		MeO		Toluene/ THF (2:1)	O		N		N	O		O
	R	H	+	Me	OMe	0°C, anh. Na 2 SO 4	Ph	NH Ph	O In(OTf) 3 O	HN Ph	Ph	R	OMe
				6					41 (5 mol%)			42
														6 examples
														up to 86 % yield
														cis/trans: 65:35 -97:3
														ee = 72-94 %
										Tin halides are generally considered less Lewis acid than alu-
									minium halides, still they are highly reactive. Cyclic 2-amidodienes

40 Scheme 11.

							OMe
			Me	O 43	CO 2 i-Pr +	44	OSiMe 3 Me	CH 2 Cl 2 rt, 24 h MS 4Å	H	O	N H		N In I I I	N H	O	H	then TFA	Me	O (R) O	CO 2 i-Pr Me
												45 (10 mol%)	46 77 % yield
																		95 % ee
	Scheme 12.
			Ph			CH 2 Cl 2		C 6 F 5							Ph	H
							MS 4Å		O	O		InBr 3
	MeO 2 C	47	O	+	31 (5 eq.)	-70°C 12 h		O C 6 F 5 P OH 2						MeO 2 C	O 49	H	+ 99 % yield	50	Ph COCO 2 Me
									48 (2.5 mol%)							HDA (49)/DA (50) = 81:19
																		99% ee	98% ee
	Scheme 13.
					O				O									O
					O	N		+	R			SnCl 4 (1 eq.)	O	N
												CH 2 Cl 2 , MS 4Å
						i-Pr 51		52				-78°C, 1 h		i-Pr	53	COR
																		48-76 % yield
																		d.r. 66:34
	Scheme 14.
											i-Pr	Ph	Ph
	R		CO 2 Et	+		CH 2 Cl 2 -78°C	Cl 4 Sn	N	B Ph	O			R	CO 2 Et
	55a R = CF 3 55b R = CHF 2 55c R = CH 2 F					56 (10-50 mol%)				57a R = CF 3 : 81 % yield endo/exo = 22:78 ee = 99 % (exo & endo)
																		57b R = CHF 2 : 90 % yield
																		endo/exo = 43:57
																		ee = 99 % (exo & endo)
																		57c R = CH 2 F : 99 % yield
																		endo/exo = 67:33 ee = 99 %(exo & endo)	Br	O
	MeO					+	Br	O	CH 2 Cl 2 -40°C				N i-Pr Cl 4 Sn	Ph B Ph O	Ph	MeO	H	H
																		60
												56 (5-20 mol%)	Yield = 73 % 94 % ee

31 58 59 Scheme 15.

  [START_REF] Kuwano | Iron corrole-catalyzed [4+2]cycloaddition of dienes and aldehydes[END_REF]]. It appears that [Fe IV (tpc)]BF 4

			O
	+	Me	H		-20°C, 2 h CH 2 Cl 2	MeO		Ph	Fe	CHO Me	+	Me	CHO
	31	32					Mn OC OC	H CO		34a (endo)		34b (exo)
							98 (10 mol%)		100 % conv. endo/exo: 10:90
	Scheme 29.
		+	Me	O	R 2 R 1	neat	FeCl 3 @	O Si OH O O		Me	O	R 2 R 1
		99		O 100			101 (4-10 mol % FeCl 3 )	H 102 80-89 % yield O
	Scheme 30.

  Pr

	181a
	O
	H	CO 2 Et
	202
	CH 2 Cl 2	191	203
	Cu(OTf) 2
	CH 2 Cl 2		Cu OTf O
		H	CO 2 Et
	204
	Scheme 62.

  .

	TIPSO			O	O							S		Me				TIPSO
	N PMPO 2 S 245	+	R	N 186	O	CH 2 Cl 2 DBU (10 mol%) 0°C, < 2 h				N H H N	S	N H H N	Me	Ph Ph	Ho(NTf) 3	N PMPO 2 S	H	O	R N	O	O
											246 (5 mol%)					247 11 examples
																			> 86 % yield
																			75-94 % ee
	Scheme 74.
				R														R	H
							CH 2 Cl 2	N	O	O	N
		R'O 2 C	O	+	O	0°C 2-36 h	ArHN	O Er(OTf) 3 O	NHAr			R'O 2 C	O	H	O
			242		248		Ar = 2,6-i-Pr 2 C 6 H 3			250 16 examples
										249						> 50 % yield
									(0.5 mol%)				89-98 % ee
	Scheme 75.
						O
				+		H	Er(OTf) 3 (10 mol%) [bmim]OTf						+			CHO
								rt, 2h								CHO
			31		113									251a (endo)	251b (exo)
																endo/exo = 80:20
																95-98 % conversion
																over 6 consecutive runs
	Scheme 76.

ACKNOWLEDGEMENTS

Declared none.

CONFLICT OF INTEREST

The author(s) confirm that this article content has no conflict of interest.