Hélène Pellissier
email: h.pellissier@univ-amu.fr

Asymmetric Zinc Catalysis in Green One-Pot Processes

Keywords: Asymmetric one-pot reactions, asymmetric domino reactions, asymmetric tandem reactions, asymmetric zinc catalysis, metal catalysis, chirality

This review collects for the first time enantioselective one-pot processes promoted by green chiral zinc catalysts. It illustrates how much these cheap, non-toxic and environmentally benign catalysts allow unprecedented asymmetric domino and tandem reactions of many types to be achieved, allowing direct access to a wide variety of very complex chiral molecules.

INTRODUCTION

With the aim of conciliating efficient sustainable chemical production with safeguarding human health as well as environment, organic chemists have taken a decisive step in the last decades towards green catalytic synthesis. In this context, the development of novel, nontoxic and effective catalytic systems capable of driving value-added chemical transformations in environmentally benign conditions has become an urgent challenge [START_REF] Ye | A high-efficiency corrosion inhibitor of N-doped citric acid-based carbon dots for mild steel in hydrochloric acid environment[END_REF][START_REF] Ye | Study on self-healing and corrosion resistance behaviors of functionalized carbon dot-intercalated graphenebased waterborne epoxy coating[END_REF][START_REF] Ye | Evaluation of the inhibition behavior of carbon dots on carbon steel in HCl and NaCl solutions[END_REF]. As a cheap, abundant [START_REF] Rudnick | Nature and composition of the continental crust: a lower crustal perspective[END_REF] and less toxic metal in comparison with many transition metals employed in catalysis [START_REF] Noyori | Asymmetric Catalysts in Organic Synthesis[END_REF], zinc has gained significant importance in green catalysis. While underdeveloped for a long time, zinc catalysts are more and more applied as Lewis acid complexes to promote all types of more economical and ecological transformations spanning from simple reactions [6] to more sophisticated domino and tandem processes, allowing very complex molecules to be synthesized in a single vessel without costly isolation and purification of intermediates [7]. Among these one-pot reactions are powerful domino processes occurring under strictly the same reaction conditions [8] and combining these simple methodologies with asymmetric zinc catalysis perfectly suit the growing demand for more efficient and environmentally benign synthesis. This interest has resulted in a spectacular development of highly enantioselective zinc-catalyzed one-pot processes in the last decade that this review intends to collect for the first time. Zinc is an essential element for life with high biological importance [START_REF] Prasad | Zinc deficiency[END_REF][START_REF] Prakash | Zinc: indications in brain disorders[END_REF], since it is present as a co-catalyst in more than 300 enzymes and 1000 transcription factors [START_REF] Cherasse | Dietary zinc acts as a sleep modulator[END_REF], which has inspired chemists to design artificial zinc chiral catalysts. Actually, zinc is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes [START_REF] Broadley | Zinc in plants[END_REF]. In proteins, zinc is coordinated to the amino acid side chains of aspartic acid, glutamic acid, cysteine and histidine [START_REF] Brandt | Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site[END_REF]. Zinc becomes toxic above an overdose of around 50 mg in-gested. The consequence of excessive absorption of zinc is the suppression of copper and iron absorption. The free zinc ion in solution is highly toxic to bacteria, plants, invertebrates and vertebrate fishes [START_REF] Rout | Effect of metal toxicity on plant growth and metabolism: I[END_REF][START_REF] Smith | Zinc toxicity in rats; antagonistic effects of copper and liver[END_REF][START_REF] Muyssen | Mechanisms of chronic waterborne Zn toxicity in Daphnia magna[END_REF].

On the other hand, zinc constitutes an essential trace metal with very low toxicity in humans with a daily dose of 12-15 mg [START_REF] Fosmire | Zinc toxicity[END_REF][START_REF] Ciubotariu | Zinc involvement in opioid addiction and analgesia--should zinc supplementation be recommended for opioid-treated persons?[END_REF]. In the area of asymmetric catalytic applications of zinc, a wide diversity of chiral zinc complexes have been developed and employed to promote many reactions, reflecting that of the processes disclosed. A range of chiral ligands, including semi-aza-crown ligands, bis(oxazoline)s, bis(imidazoline)s, N,N'-dioxides, 1,1'-bi-2naphthol (BINOL) derivatives, diamines, amino alcohols, cinchona alkaloids, among others, have been already chelated to zinc. It must be noted that the field of asymmetric zinc-catalyzed reactions of all types was most recently updated by Mlynarski in 2015 including only three references concerning asymmetric domino processes [START_REF] Lowicki | Chiral zinc catalysts for asymmetric synthesis[END_REF]. Moreover, the more general field of zinc catalysis (not especially asymmetric) was reviewed by Enthaler and Wu the same year [20]. Also in 2015 Lee and Bouffard reported the field of tandem reactions based on the use of organozinc reagents, albeit with no reference dealing with asymmetric zinc-catalyzed tandem reactions [START_REF] Kim | Advances in tandem reactions with organozinc reagents[END_REF]. In 2019, a review on the synthesis of heterocycles via zinc catalysis was published by Beller and Anilkumar, including no reference concerning asymmetric work [START_REF] Krishnan | Recent advances and perspectives in the synthesis of heterocycles via zinc catalysis[END_REF]. In 2020, Anilkumar reviewed zinc-catalyzed multicomponent reactions but with only one asymmetric work [START_REF] Neetha | Zinc-catalysed multicomponent reactions: an overview[END_REF]. Even if the general field of asymmetric metal-catalyzed domino reactions has been the subject of precedent reviews covering the literature up to 2018 [5p,w-x], it must be noted that the largest share of activity in enantioselective zinccatalyzed one-pot reactions dated after 2018. This demonstrates that this special and original field has blossomed in very recent years to become an area in its own right, deserving a special review. The present review is divided into six parts according to the type of chiral ligands employed to promote the reactions, highlighting successively semi-aza-crown ligands, bis(oxazoline)s and bis(imidazoline)s, N,N'-dioxides, BINOL derivatives, 1,2-diamines, and other ligands. The low price of zinc makes zinc catalysis suiting the growing demand for greener processes and offers the real opportunity to replace other toxic and expensive metals in the near future. This review demonstrates that zinc brings a novel potential for green catalysis when combined with complex asymmetric one-pot processes and that this original area is growing very rapidly.

REACTIONS USING SEMI-AZA-CROWN LIGANDS 2.1. ProPhenol Ligand and Derivatives

ProPhenol is a semi-aza-crown ligand [24], which was firstly developed in 2000 by Trost and Ito and applied to promote asymmetric zinc-catalyzed aldol reactions [START_REF] Trost | A direct catalytic enantioselective Aldol reaction via a novel catalyst design[END_REF]. The authors showed that this ligand generated, in the presence of diethyl zinc, a dinuclear bifunctional zinc catalyst Zn 2 Et(ProPhenol) 1 (Scheme 1), possessing both a Brønsted base site and a Lewis acid site embedded within a chiral pocket formed by the ProPhenol ligand. In the aldol reaction, one zinc atom bound to the enolate form of the ketone substrate while the second zinc atom chelated the aldehyde/ketone substrate. The aldol condensation in the chiral pocket formed by the semi-crown ligand was achieved with enantioselectivities of up to 99% ee and high yields. Later, Trost's ligand was successfully applied to many types of other enantioselective zinc-catalyzed reactions [START_REF] Trost | ProPhenol-catalyzed asymmetric additions by spontaneously assembled dinuclear main group metal complexes[END_REF], including Henry reaction [START_REF] Trost | A dinuclear Zn catalyst for the asymmetric nitroaldol (Henry) reaction[END_REF], Mannich reactions [28], Michael additions [29], alkynylations of carbonyl compounds [30], Friedel-Crafts reactions [START_REF] Trost | Asymmetric Friedel-Crafts alkylation of pyrroles with nitroalkenes using a dinuclear zinc catalyst[END_REF], among others. In 2012, Trost and Hirano also demonstrated the use of this ligand to catalyze more complex asymmetric reactions, such as enantioselective domino Michael/lactonization reaction between 3-hydroxyoxindoles 2 and α,β-unsaturated esters 3 [START_REF] Trost | Dinuclear zinc catalyzed asymmetric spirannulation reaction: an umpolung strategy for formation of α-alkylated-αhydroxyoxindoles[END_REF]. This process, performed in the presence of 5 mol% of (R,R)-ProPhenol as ligand and 10 mol% of ZnEt 2 in a mixture of toluene and acetonitrile as solvent, afforded at 40 °C the corresponding chiral spirocyclic oxindoles 4 in moderate to excellent yields (38-98%), diastereoselectivities (40-86% de) and enantioselectivities (47-99% ee), as illustrated in Scheme 1. A range of variously substituted phenyl groups (R 2 ) were tolerated on the α,β-unsaturated esters, providing spirocyclic δ-lactones 4 in uniformly excellent enantioselectivities (92-99% ee), good to high yields (65-89%) albeit combined with variable diastereoselectivities (52-86% de) dependent on the electronic properties of the substituents on the phenyl ring. Excellent results (72-98% yield, 58-72% de, 95-98% ee) were also obtained in the reaction of esters bearing heteroaromatic substituents. On the other hand, alkyl-substituted esters (R 2 = Me, c-Pr) provided lower enantioselectivities (54-75% ee) and yields (38-67%) combined with moderate diastereoselectivities (40-62% de). A ferrocenyl-substituted ester (R 2 = 1-ferrocenyl) also underwent the domino process with 55% yield, 84% de and 96% ee while the reaction of an ynenoate (R 2 = TIPS-C≡C) was performed with 84% yield, 84% de and 76% ee. It was found that β,γ,δ-unsaturated esters (R 2 = (E)-PhCH=CH, (E)-MeCH=CH) also yielded the conjugated products exclusively in excellent enantioselectivities (97-98% ee), high yields (82-83%) and moderate to good diastereoselectivities (42-74% de). The lowest enantioselectivity (47% ee) was obtained in the reaction of phenyl acrylate (R 2 = H), which gave the corresponding product with 67% yield. Moreover, different nitrogen protecting groups (R 1 ) on the 3-hydroxyoxindoles were tolerated, including methyl, allyl, methoxymethyl, benzyl and p-methoxybenzyl.

To explain these results, the authors proposed the catalytic cycle depicted in Scheme 2. In a first time, 3-hydroxyoxindole 2 was deprotonated by an ethylzinc species to give intermediate A. In 2013, Marek et al. reported asymmetric alkynylation of acyl silanes 5 with alkyne 6 promoted by 2.4 equivalents of ZnEt 2 and 5 mol% of (S,S)-ProPhenol in toluene at 5 to 15 °C, leading in a onepot operation to propargylic alcohols 7 after subsequent addition of an electrophile (EX) followed by oxidation [START_REF] Smirnov | One-pot zinc-promoted asymmetric alkynylation/brook-type rearrangement/ene-allene cyclization: highly selective formation of three new bonds and two stereocenters in acyclic systems[END_REF]. Actually, the first step of the sequence consisted of a tandem alkynylation/Brook rearrangement/ene-allene cyclization of acyl silanes 5 with alkyne 6, providing intermediate G. As depicted in Scheme 3, the zincpromoted asymmetric alkynylation led to chiral zinc intermediate E, which then underwent a Brook rearrangement to give allenyl zinc intermediate F. Then, the latter was submitted to zincpromoted ene-allene cyclization, leading to cyclic zinc intermediate G. The addition of an electrophile (EX) trapped G into functionalized product 8 which was subsequently oxidized in the presence of aqueous hydrogen peroxide H 2 O 2 with concomitant desilylation into final acyclic product 7. This tandem alkynylation/Brook rearrangement/ene-allene cyclization/electrophile addition/oxida-tion sequence performed in one-single vessel allowed a range of chiral propargylic alcohols 7 to be synthesized as single diastereomers (>96% de) in good yields (56-83%) and high enantioselectivities (76-90% ee).

2 4 N R 1 OH O 3 N R 1 O O R 2 O N R 1 O OH R 2 O OPh lactonization R 1 = Me, allyl, MOM, Bn, PMB R 2 = Ph, p-MeOC 6 H 4 , p-ClC 6 H 4 , p-NCC 6 H 4 , 3,5-(MeO) 2 C 6 H 3 , 3,5-Br 2 C 6 H 3 , o-ClC 6 H 4 , 1-Naph, 1-furyl, 2-furyl, 1-thienyl, 1-ferrocenyl, (E)-PhCH=CH, (
O R 2 OPh 2 4 N R 1 OH O 3 N R 1 O O R 2 O N Ph O Ph O N O Ph Ph Zn Zn Et 1 N Ph O Ph O N O Ph Ph Zn Zn A N O R 1 O H N Ph O Ph O N O Ph Ph Zn Zn B N O R 1 O O OPh H R 2 N Ph O Ph O N O Ph Ph Zn Zn C N O R 1 O O OPh R 2 N Ph O Ph O N O Ph Ph Zn Zn D OPh 2 N R 1 OH O ethane Scheme 2.
Catalytic cycle for domino Michael/lactonization reaction of 3hydroxyoxindoles with α,β-unsaturated esters.

In 2014, Chang et al. reported the use of (S,S)-ProPhenol in an enantioselective zinc-catalyzed domino Michael/hemiketalization reaction of cyclic 1,3-diketones 9 with aryl-substituted β,γunsaturated α-ketoesters 10 [34]. The sequence was performed at 10 °C in tetrahydrofuran (THF) as a solvent in the presence of 10 mol% of ZnEt 2 and 5 mol% of (S,S)-ProPhenol. It yielded the corresponding chiral chromenes 11 in both uniformly high yields (85-96%) and enantioselectivities (76-94% ee), as shown in Scheme 4. The yields were found lower when the steric hindrance of the ester group (R 1 ) increased. Different substituents on the phenyl ring of the aryl-substituted β,γ-unsaturated α-ketoester were tolerated in both meta and para positions, providing high yields and enantioselectivities, whereas ortho-substituted aryl substrates afforded very low yields (≤7%) because of steric reasons. To explain the stereoselectivity of the reaction, a transition state is proposed in Scheme 4, in which the cyclic 1,3-diketone activated by the Brønsted basic zinc nucleus formed the corresponding zinc enolate. Meanwhile, the β,γ-unsaturated α-ketoester was activated by the other Lewis acidic zinc nucleus through bidentate coordination of the 1,2dicarbonyl moiety. In these conditions, the zinc enolate attacked from the Re face of the coordinated Michael acceptor.

In 2018, Trost et al. described an enantioselective tandem Mannich/aldol reaction of branched aldehydes 12 with Nbenzyloxycarbonyl (Cbz)-protected aromatic aldimines 13 and ketones 14 catalyzed by a combination of 10 mol% of (R,R)-ProPhenol ligand and 20 mol% of ZnEt 2 in toluene at -10 °C [START_REF] Trost | Branched aldehydes as linchpins for the enantioselective and stereodivergent synthesis of 1,3aminoalcohols featuring a quaternary stereocentre[END_REF].

This one-pot reaction required the separated addition of ketones 14 into the reaction vessel upon completion of the asymmetric Mannich process (Scheme 5). It delivered the corresponding chiral 1,3aminoalcohols 15 exhibiting three contiguous stereocenters in good yields (71-82%), combined with both high diastereo-(82->90% de) and enantioselectivities (98-99% ee). The same catalyst system could be applied to related enantioselective tandem Mannich/Henry reaction of N-Cbz protected aromatic aldimines 13, branched aldehydes 12 and nitromethane 16 as added nucleophilic third partner, affording the corresponding chiral 1,3-aminoalcohols 17 as single diastereomers (>90% de) in excellent enantioselectivities (96-99% ee) and high yields (72-88%), as presented in Scheme 5. Later in 2019, the same authors developed an enantioselective zinc-catalyzed tandem Mannich/cycloisomerization reaction of Nprotected aldimines 13,18 with alkynones 19 performed in the presence of 10 mol% of (S,S)-ProPhenol and 20 mol% of ZnEt 2 in THF at room temperature [START_REF] Trost | Synthesis of chiral, densely substituted pyrrolidones via phosphine-catalyzed cycloisomerization[END_REF]. The Mannich reaction led to intermediate β-amino ynone 20, which was subsequently cycloisomerized at 75 °C in toluene as a solvent to afford pyrrolidones 21 after the addition of 10 mol% of PPh 3 and 40 mol% of acetic acid (AcOH). The chiral products were obtained with a good E/Z selectivity (up to 9:1) with good to high yields (66-87%) and enantioselectivities (70-99% ee), as shown in Scheme 6. N-Cbz-protected aldimines provided comparable results as N-tert-butoxycarbonyl (Boc) derivatives in terms of yields and enantioselectivities. A range of aromatic aldimines exhibiting neutral or electron-rich substituents on the phenyl ring gave uniformly excellent enantioselectivities (83-99% ee) while the lowest enantioselectivity (70% ee) was obtained in the reaction of a heteroaromatic aldimine (R 1 = 1-furyl). Moreover, a vinyl aldimine (R 1 = (E)-PhCH=CH) was cyclized with 68% yield and 87% ee. In contrast, the reaction of c-propyl aldimine (R 1 = c-Pr) required the use of a more nucleophilic catalyst, such as methyldiphenylphosphine (MePPh 2 ) instead of triphenylphosphine (PPh 3 ), to promote the cycloisomerization, leading to the corresponding pyrrolidone in 79% yield and 92% ee. Interestingly, heterocyclic chiral spirocycles, such as a tetrahydropyran (R 2 ,R 3 = (CH 2 ) 2 O(CH 2 ) 2 ) and an N-Boc piperidine (R 2 ,R 3 = (CH 2 ) 2 NBoc(CH 2 ) 2 ), could be synthesized with good yields (86 and 66%, respectively) and high enantioselectivities (92 and 82% ee, respectively).

Ar CO 2 R 1 O O O R 2 R 2 O OH CO 2 R 1 Ar O R 2 R 2 transition state: N Ph O Ph O N O Ph Ph Zn Zn Ar O O R 1 O O O R 2 R 2
Re face attack Scheme 4. Domino Michael/hemiketalization reaction of cyclic 1,3diketones with aryl-substituted β,γ-unsaturated α-ketoesters.

In 2020, a combination of 5 mol% of (S,S)-ProPhenol with 10 mol% of ZnEt 2 was used at room temperature in THF as a solvent to promote an asymmetric pseudo-three-component process between two equivalents of N-protected aldimines 13,18 and ynones 22 [START_REF] Trost | Enantio-and diastereoselective double Mannich reaction between ketones and imines catalyzed by Zn-prophenol[END_REF]. This remarkable reaction evolved through a domino double Mannich reaction, yielding enantiopure 1,3-diamines 23 (>99% ee) in good to excellent yields (61-92%). Moreover, in all cases of substrates, the domino products were obtained as almost single diastereomers (>90% de), as shown in Scheme 7. In addition to a range of (hetero)aromatic aldimines which all delivered the enantiopure domino products, nonaromatic aldimines, such as cyclopropyl imine (R = c-Pr), underwent the double Mannich reaction with 78% yield and remarkable enantio-and diastereoselectivities (>90% de, >99% ee). Various (hetero)aromatic ynones were compatible to the catalyst system. ZnEt 2 (20 mol%) ZnEt 2 (20 mol%) Earlier in 2019, ProPhenol derivative ligand 24 (10 mol%) was combined to ZnEt 2 (20 mol%) to promote in toluene at 25 °C an enantioselective domino phospha-Michael/Michael reaction between o-dienones 25 and dialkyl phosphates 26 [START_REF] Tao | Dinuclear zinc synergistic catalytic asymmetric phospha-Michael/Michael cascade reaction: synthesis of 1,2,3-trisubstituted indanes bearing phosphoryl groups[END_REF]. The reaction afforded the corresponding chiral biologically interesting 1,2,3trisubstituted indane derivatives 27, bearing phosphoryl groups and three contiguous stereocenters, as single diastereomers (>98% de) in good to high yields (65-92%) and uniformly excellent enantioselectivities (94->99% ee), as illustrated in Scheme 8. Various dialkyl phosphates were compatible with the catalytic system, providing homogeneously excellent results (96-99% ee). Furthermore, comparable excellent yields and enantioselectivities were achieved in the reaction of a series of aryl substituted o-dienones, regardless of the electronic nature of the substituents present in the aryl group (Ar 2 ). This work constituted a rare example of enantioselective double Michael domino reactions catalyzed by metals. ZnEt 2 (20 mol%) Another ProPhenol-type ligand, such as 28, was employed in 2019 by Wang et al. to catalyze at only 2 mol% of catalyst loading combined with 4 mol% of ZnEt 2 an enantioselective threecomponent domino reaction of isatins 29, malononitrile 30 and α-hydroxy acetophenones 31 [START_REF] Miao | Dinuclear zinc cooperative catalytic three-component reactions for highly enantioselective synthesis of 3,3′dihydrofuran spirooxindoles[END_REF]. This process, performed at 25 °C in dichloromethane as a solvent, evolved through a domino Knoevenagel/Michael/cyclization reaction to yield the corresponding chiral 3,3'-dihydrofuran spirooxindoles 32 in both uniformly high yields (86-99%) and enantioselectivities (82->99% ee) combined with variable diastereoselectivities (4-98% de). Generally, the reaction of isatins bearing electron-rich substituents provided slightly higher enantioselectivities than those exhibiting electrondeficient groups. As depicted in Scheme 9, the sequence began with the Knoevenagel condensation of malononitrile 30 to isatin 29 to give product 33. In the presence of the chiral dinuclear zinc catalyst in situ generated from ZnEt 2 and ligand 28, α-hydroxy acetophenone 31 was deprotonated into a zinc enolate which underwent asymmetric Michael addition to intermediate 33, leading to intermediate 34. The latter was then submitted to cyclization followed by isomerization to afford the final 3,3'-dihydrofuran spirooxindole.

3Å MS Ar NCbz CHO R 1 R 2 O Ar CbzHN R 2 O OH R 1 then mechanism: + 13 12 Ar NCbz CHO R 1 Mannich Ar CbzHN CHO R 1 R 2 O aldol 15 Ar CbzHN R 2 O OH R 1 Ar = p-FC 6 H 4 , m-Tol, o-BrC 6 H 4 , o-Tol R 1 = Me, Ph R 2 = TMS-C C, Ph-C C, Ph, TBS(CH 2 ) 3 C C, (1-cyclohexenyl)-C C toluene, 4 °C (R,R)-ProPhenol (10 mol%) + 72-88%, >90% de, 96-99% ee
1. R 1 NPG R 2 R 3 O Ph 2. PPh 3 or MePPh 2 (10 mol%) AcOH (40 mol%) toluene, 75 °C N R 1 PG Ph O R 2 R 3 R 1 = p-FC 6 H 4 , Ph, p-MeOC 6 H 4 , o-BrC 6 H 4 , 1-furyl, o-Tol, o-(MeO 2 CCH=CH)C 6 H 4 , c-Pr, (E)-PhCH=CH R 2 = Me, HC C-CH 2 R 3 = Me, Bn, i-Bu, Ph, CH 2 =C(Me)-CH 2 R 2 ,R 3 = (CH 2 ) 5 , (CH 2 ) 3 , (CH 2 ) 2 O(CH 2 ) 2 , (CH 2 ) 2 NBoc(CH 2 ) 2 PG = Boc, Cbz 20 NH R 1 PG O R 2 R 3
Ar 2 = Ph, m-FC 6 H 4 , m-ClC 6 H 4 , m-BrC 6 H 4 , m-MeOC 6 H 4 , p-FC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , p-Tol, p-MeOC 6 H 4 , p-PhC 6 H 4 , 2-thienyl R = Et, Me, i-Pr, i-Bu

(2 mol%)

N Ar 1 OH

Ar 1 OH N HO Ar 1
Ar 1

86-99%, 4-98% de, 82->99% ee 31 32 30 ZnEt 2 (4 mol%) Among spirooxindoles, chiral tetrahydrofuran spirooxindoles are especially attractive related to their potent biological activities [40]. In this context, a novel route to these products was developed in 2020 by Hua and Wang on the basis of an enantioselective zinccatalyzed domino Michael/hemiketalization reaction followed by Friedel-Crafts reaction [START_REF] Guo | Catalytic asymmetric synthesis of tetrahydrofuran spirooxindoles via a dinuclear zinc catalyst[END_REF]. This sequence involved α-hydroxy aryl ketones 31 and β,γ-unsaturated α-ketoamides 35 as substrates. The domino reaction, performed at 20 °C in dichloromethane as solvent, was promoted by a chiral dinuclear zinc catalyst in situ generated from 20 mol% of ZnEt 2 and 10 mol% of chiral ProPhenol-derived ligand 36. The domino products were not isolated but directly submitted to Friedel-Crafts reaction performed at room temperature by adding trifluoroacetic acid (TFA). The one-pot sequence afforded a wide range of chiral tetrahydrofuran spirooxindoles 37 in high yields (71-90%), moderate to high diastereoselectivities (50-86% de) and high to excellent enantioselectivities (75->99% ee), as illustrated in Scheme 10. Actually, the enantioselectivities were uniformly excellent (90->99% ee) for differently substituted substrates excepted for ortho-methoxy-substituted αhydroxy aryl ketone (Ar 2 = o-MeOC 6 H 4 ), which provided the corresponding product with the lowest ee value (75% ee).

Ar 2 = Ph, p-FC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , p-MeOC 6 H 4 , p-Tol, m-ClC 6 H 4 , m-BrC 6 H 4 , o-MeOC 6 H 4 , m-Tol, 2-Naph, 2-thienyl, 2,5-(MeO) 2 C 6 H 3 R = H, 5-Me, 5-MeO, 5-F, 5-Cl, 5-Br, 6-Br Ar 1 = 2-Naph CH 2 Cl 2 , 25 °C 4Å MS CN CN Ar 2 O OH N H O O R 29 + + N H O R O NC H 2 N O Ar 2 mechanism: 30 CN CN N H O O R 29 + 32 N H O R O NC H 2 N O Ar 2
3 = 2-thienyl 4Å MS OH Ar 1 O N O R 1 R 2 O N O Ar 1 Ar 2 O R 2 R 1 1. 2. TFA, r.t. O N O Ar 1 Ar 2 O R 2 R 1

OH domino Michael/ hemiketalization

Friedel-Crafts reaction TFA Zn 2 Et [START_REF] Trost | Synthesis of chiral, densely substituted pyrrolidones via phosphine-catalyzed cycloisomerization[END_REF] Scheme 10. Domino Michael/hemiketalization reaction of α-hydroxy aryl ketones with β,γ-unsaturated α-ketoamides followed by Friedel-Crafts reaction.

AzePhenol Ligand and Derivatives

In 2014, Chang and Wang reported the synthesis of a novel chiral semi-aza-crown ligand, namely AzePhenol, exhibiting a more rigid azetidine ring compared with that of pyrrolidine present in ProPhenol ligand [START_REF] Hua | Photostable p-type dye-sensitized photoelectrochemical cells for water reduction[END_REF]. The corresponding chiral dinuclear zinc catalyst Zn 2 Et((S,S)-AzePhenol), in situ generated from 2 mol% of this ligand and 4 mol% of ZnEt 2 , was employed in 2015 by the same authors to promote an enantioselective domino Michael/hemiketalization reaction (Scheme 11) [START_REF] Hua | A new strategy for enantioselective construction of multisubstituted five-membered oxygen heterocycles via a Domino Michael/Hemiketalization reaction[END_REF]. It involved arylsubstituted β,γ-unsaturated α-ketoesters 10 and α-hydroxyacetophenone 31 as substrates in dichloromethane as a solvent, leading at 0 °C to the corresponding chiral 2,2,4,5-tetrasubstituted tetrahydrofurans 38 in good yields (64-90%), uniformly excellent enantioselectivities (90-98% ee) and low to good diastereoselectivities (26-82% de). The lowest diastereoselectivities (26-40% de) were obtained in the reaction of β,γ-unsaturated α-ketoesters with substituents on the phenyl ring at the meta-position. Interestingly, products 38 could be converted under acidic conditions into the corresponding chiral 2,3,5-trisubstituted 2,3-dihydrofurans 39 without loss of enantiopurity. In 2019, the same authors developed a novel route to chiral bispirotetrahydrofuran oxindoles based on an enantioselective cascade Michael/hemiketalization/Friedel-Crafts reaction of β,γunsaturated α-ketoamides 35 with 2-hydroxy-1-indanones 40 (Scheme 12) [START_REF] Liu | Synthesis of chiral bispirotetrahydrofuran oxindoles by cooperative bimetallic-catalyzed asymmetric Cascade Reaction[END_REF]. The sequence began with an asymmetric domino Michael/hemiketalization catalyzed by a chiral dinuclear zinc complex Zn 2 Et(41) derived from 4 mol% of ZnEt 2 and 2 mol% of chiral AzePhenol-type ligand 41. The reaction, performed in THF at 0 °C, afforded the unstable hemiketal domino product 42 which was not isolated but directly submitted to TFA which promoted the final Friedel-Crafts reaction, leading to expected chiral bispiro[3,2′tetrahydrofuran-5′,2′′indanone] oxindoles 43 exhibiting three stereocenters in moderate to high yields (32-79%), combined with uniformly high diastereo-(82->90% de) and enantioselectivities (87-99% ee). The scope of the process was wide since a range of either electron-donating or electron-withdrawing substituents (R 2 , R 3 ) were tolerated on the phenyl ring of each substrate. However, the reaction of a ketoamide bearing a strong electron-withdrawing group (R 2 = NO 2 ) led to the corresponding product with a low yield (32%) albeit combined with 97% ee. Moreover, variously Nsubstituted ketoamides all proceeded smoothly. In the same year, these authors employed the dinuclear zinc complex Zn 2 Et((S,S)-AzePhenol), in situ generated from 5 mol% of (S,S)-AzePhenol and 10 mol% of ZnEt 2 , to catalyze an enantioselective domino Michael/lactonization reaction between 2-hydroxy-1-indanones 40 and phenyl α,β-unsaturated esters 3 [START_REF] Liu | Dinuclear zinc-catalyzed asymmetric tandem reaction of α-hydroxy-1-indanone: access to spiro[1-indanone-5,2′-γ-butyrolactones[END_REF]. Performed at 55 °C in THF as a solvent, the process afforded a range of variously substituted chiral spiro[1-indanone-5,2′-γ-butyrolactones] 44 as almost single diastereomers (>90% de) in uniformly high yields (76-92%) and remarkable enantioselectivities (95->99% ee), as presented in Scheme 13.

N O R 1 R 2 O OH R 3 N O O R 3 R 2 R 1 O Ar N O O R 3 R 2
In the same area, comparable excellent results were reported by the same group in 2020 in a related enantioselective zinc-catalyzed domino Michael/lactonization reaction between α-hydroxy indanones 40 and ortho-ester chalcones 45 [START_REF] Yang | Enantioselective synthesis of indanone spiro-isochromanone derivatives via a dinuclear zinc-catalyzed Michael/transesterification tandem reaction[END_REF]. In this case, a related chiral AzePhenol derivative 46 was used at 5 mol% of catalyst loading as an optimal ligand in combination with 10 mol% of ZnEt 2 . The corresponding in situ generated chiral dinuclear zinc complex Zn 2 Et( 46) promoted the domino reaction in THF at 10 °C, leading to a range of enantio-and diastereomerically pure spiro[indanone-2,3'-isochromane-1-one] derivatives 47 in good to high yields (59-92%) and remarkable diastereo-and enantioselectivities (>90% de, and 96->99% ee, respectively). As shown in Scheme 14, the electronic nature and position of substituents on the phenyl ring of either α-hydroxy indanones or ortho-ester chalcones had little impact on the stereoselectivities of the reaction. This novel methodology allowed simple and direct access to chiral isochromanones, which are potent biologically active products. THF, 55 °C (S,S)-AzePhenol (5 mol%)

R 1 = H, 5-F, 5-Cl, 5-Br, 5-OMe, 4-Br, 6-Br R 2 = Ph, p-FC 6 H 4 , p-ClC 6 H 4 , p-Tol, p-MeOC 6 H 4 , m-ClC 6 H 4 , m-BrC 6 H 4 , m-Tol, m-MeOC 6 H 4 , o-BrC 6 H 4 , o-MeOC 6 H 4 , 3-Br-4-ClC 6 H 3 , 2-F-4-BrC 6 H 3 , 2,4-Cl 2 C 6 H 3 , 3,4-OCH 2 O-C 6 H 3 , 1-Naph, 2-Naph, 2-thienyl, H, Me
O OH R 1 O R 1 R 2 OPh O O O R 2 O R 1 PhO O R 2
OH Scheme 13. Domino Michael/lactonization reaction of α-hydroxy-1indanones with phenyl α,β-unsaturated esters.

C 1 -Symmetric Aza-Crown Ligands

In 2019, Wang and Hua developed new access to chiral pyrrolidinyl dispirooxindoles 48 which constitute potent biologically active products [START_REF] Yang | Access to chiral 2,5-pyrrolidinyl dispirooxindoles via dinuclear zinccatalyzed asymmetric Cascade reactions[END_REF]. The methodology was based on a novel asymmetric domino Michael/cyclic ketoimine formation reaction followed by a Friedel-Crafts reaction performed in a single vessel. The sequential reaction occurred at -45 °C between 3-amino oxindole hydrochlorides 49 and aryl-substituted β,γ-unsaturated αketoamides 35 in a mixture of acetonitrile and dichloromethane as solvent. Among chiral ligands investigated in this process, C 2symmetric (S,S)-ProPhenol and AzePhenol derivatives all provided low enantioselectivities (≤33% ee). In this context, the authors developed nonsymmetrical ligands, such as C 1 -symmetric ligand 50, with electronically and sterically divergent units. The use of a combination of 10 mol% of this ligand with 20 mol% of ZnEt 2 allowed a range of pyrrolidinyl dispirooxindoles 48 exhibiting two quaternary stereocenters as single diastereomers (>90-96% de) to be synthesized in high yields (66-85%) and moderate to high enantioselectivities (43-95% ee), as illustrated in Scheme 15. The presence of various substituents at the phenyl ring of aryl-substituted β,γunsaturated α-ketoamides 35 was tolerated. Generally, substrates with electron-donating groups at the para position of the phenyl ring (Ar 1 ) provided higher enantioselectivities than those with electron-withdrawing groups. The catalytic system was also compatible with heteroaromatic-substituted β,γ-unsaturated α-ketoamides and γ-naphthyl-substituted substrates.

MeCN/CH 2 Cl 2 , -45 °C 50 (10 mol%)

R 1 = Me, Bn R 2 = H, Me, F R 3 = Me, Et, Bn R 4 = Me, H R 5 = H, Me, OMe, F, Cl, Br Ar 1 = Ph, p-MeOC 6 H 4 , p-Tol, p-BrC 6 H 4 , p-ClC 6 H 4 , p-FC 6 H 4 , p-O 2 NC 6 H 4 , m-BrC 6 H 4 , 2-furyl, 2-thienyl, 2-Naph, 3,4-(Me
O R 2 R 1 O TFA Friedel-Crafts domino Michael/cyclic ketoimine formation R 4 R 1 R 2 Ar 1 R 3 R 4 R 5 Zn 2 Et(50) N N N O R 2 R 1 O Ar 1 R 3 R 4 R 5
Scheme 15. Domino Michael/ cyclic ketoimine formation reaction of 3amino oxindole hydrochlorides with β,γ-unsaturated α-keto amides followed by Friedel-Crafts reaction.

REACTIONS USING BIS(OXAZOLINE) AND BIS(IMIDA-ZOLINE) LIGANDS

Chiral bis(oxazoline)s [START_REF] Stanley | Privileged Chiral Ligands and Catalysts[END_REF] have been successfully employed as zinc ligands in various types of asymmetric reactions, including Michael additions [3e], and hydrosilylations of ketones [START_REF] Junge | Enantioselective zinc-catalyzed hydrosilylation of ketones using pybox or pybim ligands[END_REF], among others. In 2006, this type of ligands was investigated by Takemoto et al. in an enantioselective zinc-catalyzed domino radical addition/cyclization reaction between hydroxamate esters 51 and alkyl iodides 52 [START_REF] Miyabe | Enantioselective cascade radical addition-cyclization-trapping reactions[END_REF]. The reaction evolved through the addition of a radical generated from the alkyl iodide followed by cyclization of the thus formed radical intermediate 53 into five-membered intermediate 54. Then, the latter led to final lactam 55 through iodide atom-transfer (Scheme 16). Several chiral lactams 55 were synthesized by this methodology as almost single diastereomers (>96% de) with good yields (71-78%) and good enantioselectivities (75-88% ee). It must be noted that this novel domino reaction presented the disadvantage to require a stoichiometric quantity of catalyst derived from zinc trifluoromethanesulfonate (Zn(OTf) 2 ) and bis(oxazoline) 56. [START_REF] Guan | Cooperative catalysis in multicomponent reactions: highly enantioselective synthesis of γ-hydroxyketones with a quaternary carbon stereocenter[END_REF]. As shown in Scheme 17, the process was multicatalyzed by a combination of a chiral zinc complex, in situ generated from 30 mol% of Zn(OTf) 2 and the same quantity of chiral bis(oxazoline) ligand 59, and 2 mol% of dirhodium tetraacetate ([Rh 2 (OAc) 4 ]) in dichloromethane as solvent. This cooperative catalysis allowed at -8 °C to synthesize a range of chiral γhydroxyketones 60 bearing two contiguous stereogenic centers, including one quaternary. These products were obtained in good yields (60-81%) and diastereoselectivities (72-98% de) combined with high enantioselectivities (85-99% ee). The rhodium catalyst was supposed to promote the formation of an oxonium ylide from the diazoacetate reagent and water, which was further trapped by the α,β-unsaturated 2-acyl imidazole activated by the zinc catalyst through a Michael reaction to give the final domino product. It was found that electronic variations on the aromatic substituents of both the imidazoles and the diazoacetates were tolerated.

CH 2 Cl 2 , -78°C + Zn(OTf) 2 (1 equiv) BEt 3 (2.5 equiv) 56 (1 equiv) Me N O OR 1 N O OR 1 I N O OR 1 R 2 R 2 Me N O OR 1 R 2 BEt 3 O 2 R 2 EtI + + 53 54
R 2 I R 2 I Et R 1 = Me, t-Bu R 2 = i-Pr, t-Bu
In 2011, Shibata et al. developed an enantioselective threecomponent Kabachnik-Fields reaction of aldehydes 61, paminophenol 62 and diarylphosphite 26a catalyzed by a chiral zinc complex derived from 10 mol% of bis(imidazoline) ligand 63 and the same quantity of zinc di[bis(trifluoromethylsulfonyl)imide] (Zn(NTf 2 ) 2 ) [START_REF] Ohara | Direct enantioselective threecomponent Kabachnik-fields reaction catalyzed by chiral bis(imidazoline)zinc(II) catalysts[END_REF]. Performed at -50 °C in dichloromethane as solvent, the one-pot process afforded a range of chiral αaminophosphonates 64 in excellent yields (86-99%) and good to high enantioselectivities (61-93% ee), as presented in Scheme 18. Actually, the reaction of (hetero)aromatic aldehydes all provided high enantioselectivities (82-93% ee), while the lowest enantioselectivity (61% ee) was obtained in the reaction of an aliphatic aldehyde (R = Cy). In a possible transition state depicted in Scheme 18, the imine in situ generated from aldehyde 61 and p-aminophenol 62 coordinated to the chiral zinc catalyst in equatorial position by avoiding the steric repulsion from the bis(imidazoline) ligand. The coordination of the oxygen atom in phosphite to zinc and deprotonation of phosphite afforded the corresponding phosphonate, which attacked the imine avoiding steric repulsion with phenyl groups to give the final product. Using chiral bis(oxazoline) ligand (S,S)-65 bearing a free NH group, a novel enantioselective zinc-catalyzed domino Michael/cyclization reaction of 3-nitro-2H-chromenes 66 (X = O) with 3-isothiocyanatooxindoles 67 was developed by Chen and Xiao in 2014 [START_REF] Tan | Enantioselective cascade Michael addition/cyclization reactions of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles: efficient synthesis of functionalized polycyclic spirooxindoles[END_REF]. Indeed, a combination of 11 mol% of ligand (S,S)-65 with 10 mol% of Zn(OTf) 2 promoted this domino process at room temperature in toluene as solvent, which led to complex and densely functionalized chiral spirooxindoles 68 as single diastereomers (>90% de) in good to quantitative yields (72-99%) and uniformly excellent enantioselectivities (91->99% ee), as shown in Scheme 19. The catalyst system was compatible with the presence of both electron-withdrawing and electron-donating substituents (R 1 ) at different positions on the aromatic ring of 3-nitro-2Hchromenes, providing comparable excellent results. Moreover, variously (N)-substituted 3-isothiocyanatooxindoles all provided comparable high levels of stereoselectivities. Furthermore, when the oxygen atom of 3-nitro-2H-chromene was replaced by a methylene group (X = CH 2 ), the reaction also proceeded, affording the corresponding product in 95% yield, >90% de and >99% ee. In 2015, Xu and Yuan reported a related enantioselective domino Michael/cyclization reaction by using the (R,R)-enantiomer of the same ligand 65 [START_REF] Zhao | Zn-Catalyzed diastereo-and enantioselective Cascade reaction of 3isothiocyanato oxindoles and 3-nitroindoles: stereocontrolled syntheses of polycyclic spirooxindoles[END_REF]. As shown in Scheme 20, the reaction occurred between 3-isothiocyanatooxindoles 67 and 3-nitroindoles 69 in the presence of 11 mol% of ligand (R,R)-65 and 10 mol% of Zn(OTf) 2 in toluene at 50°C, affording the corresponding chiral polycyclic spirooxindoles 70 in quantitative yields (95-99%), uniformly impressive enantioselectivities (91->99% ee) and generally excellent diastereoselectivities (70->98% de). In most cases of substrates, they were obtained as single diastereomers especially for Nmethyl protected 3-isothiocyanatooxindoles. Indeed, the lowest diastereo-(70% de) and enantoselectivities (91% ee) were observed in the reaction of N-phenyl protected 3-isothiocyanatooxindole (R 2 = Ph). Furthermore, the catalytic system was compatible with a range of 3-nitroindoles with no influence of both the electronic nature and the substitution pattern of the substituents (R 3 ) on the phenyl ring. Moreover, substrates bearing different N-substituents (R 4 ) provided comparable excellent results. toluene, 50 °C + (R,R)-65 (11 mol%) Zn(OTf) 2 (10 mol% In 2018, the same authors developed enantioselective domino Michael/cyclization reaction of 3-isothiocyanatooxindoles 67 with 3-nitrobenzothiophenes 71 [START_REF] Yue | Zinc-Catalyzed enantioselective dearomative [3+2] cycloaddition reaction of 3-nitrobenzothiophenes and 3-nitrothieno[2,3-b]yridine with 3-isothiocyanato oxindoles[END_REF]. The reaction was promoted at 50 °C in toluene by a chiral zinc catalyst in situ generated from 5 mol% of Zn(OTf) 2 and 6 mol% of chiral bis(oxazoline) ligand 72. It afforded the corresponding chiral polycyclic spirooxindoles 73 containing a 2,3-dihydrobenzothiophene motif with excellent yields (90-99%), diastereoselectivities (96->98% de) and enantioselectivities (90->99% ee), as presented in Scheme 21. Different electrondonating and electron-withdrawing substituents on the phenyl ring of either the 3-isothiocyanatooxindole substrate or the 3nitrobenzothiophene were tolerated, providing similar exceptional results whatever their position. Moreover, different alkyl groups on the N1-position of the 3-isothiocyanatooxindole were compatible. The same catalyst system was also applied by these authors to the related enantioselective domino Michael/cyclization reaction of 2-nitrobenzothiophenes 74 with 3-isothiocyanatooxindoles 67 [START_REF] Zhou | Zn-Catalyzed diastereo-and enantioselective dearomative [3+2] cycloaddition reaction of 2-nitroindoles and 2-nitrobenzothiophenes[END_REF]. Again, the results were impressive since the reaction performed in xylene at 50 °C resulted in the formation of the corresponding complex polycyclic spirooxindoles 75 as almost single diastereo-(96->98% de) and enantiomers (>99% ee) in uniformly excellent yields (93-99%), as illustrated in Scheme 22. The presence of various groups on the aromatic rings was tolerated as well as that of different alkyl N-substituents. It must be noted that this work represented the first asymmetric formal dearomative [3+2] cycloaddition of 2-nitroindoles with 3-isothiocyanatooxindoles.

Zn(OTf) 2 (10 mol%) N R 2 O R 3 R 2 NCS X NO 2 R 1 N HN R 3 O S NO 2 X R 1 H N H O N N O Ph Ph Ph Ph 72-99%,
) N O R 2 NCS R 3 N HN R 2 O S NO 2 H N H O N N O Ph Ph Ph Ph N NO 2 R 4 R 1 R 1 N R 4
, K 2 CO 3 R 3 R 2 R 4 R 5 R 3 R 2 R 4 R 5 N N R 1 O O 2 N S R 3 R 2 R 4
, K 2 CO 3 R 4 R 1 R 1 5Å MS NO 2 R 2 R 5 N N R 4 R 5 R 3 O SMe NO 2 R 2
Scheme 22. Domino Michael/cyclization reaction of 2-nitrobenzothiophenes with 3-isothiocyanatooxindoles.

Despite the prevalence of piperidine moieties in drugs, the azaversion of the all-carbon [4+2] cycloaddition is less developed [58]. In this context, Rovis reported in 2015 a rare example of asymmetric synthesis of piperidines which was based on an enantioselective tandem aza-Diels-Alder/reduction reaction of 1-azadienes 76 with nitroalkenes 77 (Scheme 23) [59]. The chiral catalyst was in situ generated from 20 mol% of Zn(OTf) 2 and the same quantity of chiral bis(oxazoline) 78 in toluene at -38 °C, affording a range of chiral piperidines 79 in variable yields (31-87%) and enantioselectivities (46-92% ee) as single regio-and diastereomers (>90% de). Actually, due to the instability of the tetrahydropyridine 80 arisen from the cycloaddition, its enamine functionality was further reduced by treatment with ZnCl 2 and sodium cyanoborohydride (NaBH 3 CN) in methanol to give a more stable 3-nitropiperidine 79. The lowest enantioselectivity (46% ee) was obtained in the reaction of an alkyl-substituted azadiene (R 1 = i-Pr). Furthermore, the reaction of a more conjugated azatriene (R 1 = (E)-PhCH=CH) required 30 mol% of catalyst to provide the corresponding product in 65% yield and 63% ee. For all the other differently substituted substrates, enantioselectivities ≥ 69% ee were obtained.

In 2020, Zhang et al. disclosed an enantioselective domino inverse-electron-demand Diels-Alder/oxidation reaction between indoles 81 and 2-(2-nitrovinyl)-1,4-benzoquinone 82 [START_REF] Zhao | Synthesis of chiral [2,3]-fused indolines through enantioselective dearomatization inverse-electron-demand Diels-Alder reaction/oxidation of indoles with 2-(2-nitrovinyl)-1,4-benzoquinone[END_REF]. It was promoted by a combination of 17 mol% of chiral bis(oxazoline) 78 combined with 10 mol% of Zn(OTf) 2 at 70 °C in toluene as solvent, providing the formation of chiral six-membered [START_REF] Ye | Study on self-healing and corrosion resistance behaviors of functionalized carbon dot-intercalated graphenebased waterborne epoxy coating[END_REF][START_REF] Ye | Evaluation of the inhibition behavior of carbon dots on carbon steel in HCl and NaCl solutions[END_REF]-fused indolines 83 as single diastereomers in moderate to quantitative yields (34-99%) and enantioselectivities (37-88% ee), as presented in Scheme 24. The cycloaddition underwent through the Re face of the 2-(2-nitrovinyl)-1,4-benzoquinone activated by the chiral zinc catalyst which was also N-chelated to the indole substrate through NH-p interaction to give Diels-Alder cycloadduct 84. The latter was unstable and subsequently underwent oxidation to give the final product 83.

Zn(OTf) 2 (20 or 30 mol%) + 77 76

Ar = p-PhOC 6 H 4 , p-MeOC 6 H 4 , Ph R 1 = Ph, p-O 2 NC 6 H 4 , p-BrC 6 H 4 , p-MeOC 6 H 4 , 2-furyl, i-Pr, (E)-PhCH=CH R 2 = Bu, BnCH 2 , i-Bu, i-Pr, TBSOCH 2
31-87%, >90% de, 46-92% ee 78 (20 or 30 mol%)

79 toluene, -38 °C N H O N N O Bn Bn F F 4Å MS 2. ZnCl 2 , NaCNBH 3 Ar N R 1 R 2 NO 2 Ar N R 1 R 2 NO 2 1. Ar N R 1

REACTIONS USING N,N'-DIOXIDE LIGANDS

Chiral N,N'-dioxide ligands developed by Feng et al. have been widely employed as ligands in asymmetric catalysis so far [61]. In 2011, these authors employed a combination of 20 mol% of N,N'dioxide ligand 85 with 10 mol% of precatalyst zinc perchlorate hexahydrate (Zn(ClO 4 ) 2 (H 2 O) 6 ) to promote in dichloromethane as solvent an enantioselective three-component reaction between salicylaldehydes 86, malononitrile 30 and indoles 87 [START_REF] Chen | Enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes[END_REF]. As presented in Scheme 25, the reaction performed at 35 °C led to a range of chiral 2-amino-4H-chromenes 88 in good to high yields (37-89%) and high enantioselectivities (80-90% ee). The one-pot process evolved through a domino Knoevenagel/Pinner/Friedel-Crafts reaction. First, a Knoevenagel/Pinner sequence between salicylaldehyde 86 and malononitrile 30 provided an iminochromene intermediate 89 which subsequently underwent in the presence of indole 87 and the chiral zinc catalyst a Friedel-Crafts reaction to afford the final product. It was found that indoles containing electronwithdrawing groups on the aromatic ring gave higher enantioselectivities than those exhibiting electron-donating groups. The lowest yield (37%) was observed in the reaction of 4-methoxy-substituted salicylaldehyde. Related to the biologic importance of many natural chromenes, this novel simple route to this type of products is attractive.

In 2019, the first catalytic enantioselective domino α-alkenyl addition/proton shift reactions of silyl enol ethers with cyclic ketimines, such as isatin-and pyrazolinone-derived ketimines, was developed by the same authors in the presence of other N,N'dioxide ligands [START_REF] Kang | Chiral Zinc(II)-catalyzed enantioselective Tandem α-alkenyl addition/proton shift reaction of silyl enol ethers with ketimines[END_REF]. As depicted in Scheme 26, silyl enol ethers 90 and 91 reacted with isatin-derived ketimine 92 in the presence of 2.5-5 mol% of a chiral zinc catalyst in situ generated from Zn(OTf) 2 and chiral N,N'-dioxide ligand 93 at 40 °C to give the corresponding β-amino silyl enol ethers 94 and 95, respectively, in excellent enantioselectivities (87-93% ee) and variable yields (21-90%). With the aim of extending the scope of this novel process, the authors investigated the reaction of pyrazolinone-derived ketimines 96 with silyl enol ethers 90. In this case, the best results were achieved by using a closely related N,N'-dioxide ligand 97 in combination with Zn(NTf 2 ) 2 . Under these conditions, a series of other chiral β-amino silyl enol ethers 98 were synthesized with both high yields (84-98%) and enantioselectivities (84-97% ee).

Zn(OTf) 2 (10 mol%) + 82 81 In the same year, these authors also reported an enantioselective domino reaction of β,γ-unsaturated α-ketoesters 10 with diazoimides 99 promoted at 30 °C in 1,2-dichloroethane (DCE) as solvent through bimetallic relay catalysis using an achiral rhodium complex, such as dirhodium tetrapivalate (Rh 2 Piv 4 ) (0.5 mol%), and a chiral zinc catalyst in situ generated from 10 mol% of Zn(OTf) 2 and 10 mol% of chiral N,N'-dioxide ligand 100 [START_REF] Xu | Asymmetric synthesis of oxabridged oxazocines through a catalytic Rh II /Zn II relay [4+3] cycloaddition reaction[END_REF]. The rhodium catalyst allowed to generate a carbonyl ylide intermediate from the diazoimide which subsequently reacted through asymmetric [4+3] cycloaddition with the β,γ-unsaturated α-ketoester catalyzed by the chiral zinc complex. As illustrated in Scheme 27, this domino carbonyl imide formation/[4+3] cycloaddition reaction resulted in the formation of a range of chiral oxa-bridged oxazocines 101 as almost single exo-diastereomers (>90% de) in good to high yields (51-90%) and uniformly high enantioselectivities (85-99% ee). The catalyst system was compatible with various (hetero)arylsubstituted β,γ-unsaturated α-ketoesters 10, bearing either electronwithdrawing or electron-donating substituents at different positions of the phenyl group. Heteroaromatic-substituted substrates were also compatible, as well as various alkyl ester groups (R 1

R 1 = Me, allyl, n-Pr, 2-propynyl, Bn, p-BrC 6 H 4 CH 2 R 2 = Me, MeO(CH 2 ) 2 R 3 = H, F, Cl, Br, OMe, OBn, m-Tol, p-MeOC 6 H 4 , p-FC 6 H 4 , p-F 3 CC 6 H 4 , Me R 4 = H, F, Cl, Br, OMe, OBn, m-Tol, p-MeOC 6 H 4 , p-FC 6 H 4 , p-F 3 CC 6 H 4 , Me 34-99%, 37-88% ee 78 (17 mol%) 83 toluene, 70 °C N H O N N O Bn Bn N R 3 R 4 R 1 R 2 O O NO 2 N R 3 R 4 R 1
R 3 N O O N 2 O R 4 Rh 2 Piv 4 R 3 N O O Rh O R 4 H R 3 N R 4 O O O I O R 2 OR 1 O 10 Zn(OTf) 2 100 R 2 R 1 O 2 C O *[Zn] N O O OR 1 R 2 O O R 4

REACTIONS USING BINOL-DERIVED LIGANDS

In 2009, Xu et al. reported an asymmetric zinc-promoted threecomponent reaction occurring between N-tosylaldimines 102 and two different terminal alkynes 103 and 104 [START_REF] Yin | Alkylzinc-mediated addition of alkynes to N-tosylaldimines: enantioselective synthesis of (E)-(2-En-3-ynyl)amines[END_REF]. The process was mediated by two equivalents of dimethyl zinc combined with 20 mol% of BINOL-derived ligand 105 in toluene at room temperature to reflux. It resulted in the formation of chiral propargylic amines 106 in moderate to high yields (51-92%) and uniformly high enantioselectivities (84-99% ee), as shown in Scheme 28. The mechanism involved the formation of alkynylzinc J which added to Ntosylaldimine 102 to give π-complex intermediate K. Then, the latter underwent an attack by another alkynylzinc to form cyclic intermediate L. The carbon-zinc bond in L could be subsequently cleaved by an excess of alkyne to give intermediate M. Then, the acidic hydrolysis of M led to the final product. In 2015, Ishihara et al. reported the first asymmetric domino Diels-Alder/lactonization reaction of 2,4-dienols 107 with acrylates 108 performed in the presence of a catalyst system composed of 20 mol% of (R)-H 8 -BINOL, 20 mol% of ZnMe 2 and 20 mol% of methyl magnesium bromide [START_REF] Ishihara | Lewis acid template-catalyzed asymmetric diels-alder reaction[END_REF]. This bimetallic catalyst allowed at room temperature in dichloromethane as a solvent the formation of chiral bicyclic γ-lactones 109 as single diastereomers in low to quantitative yields (16->99%) and moderate to excellent enantioselectivities (41-97% ee), as shown in Scheme 29.

REACTIONS USING 1,2-DIAMINE LIGANDS

In 2015, Song et al. demonstrated that chiral 1,2-amino phosphoramide ligand 110 was efficient in both the asymmetric β-H transfer reduction of aryl α-trifluoromethylketones 111,112 and enantioselective addition of ZnEt 2 of aromatic aldehydes performed in one-pot under the same reaction conditions [START_REF] Huang | Chemo-and enantioselective addition and β-hydrogen transfer reduction of carbonyl compounds with diethylzinc reagent in one pot catalyzed by a single chiral organometallic catalyst[END_REF]. As shown in Scheme 30, the corresponding chiral fluorinated diols 113,114 were obtained from the domino transfer reduction/ethylation reaction performed in toluene at -20 °C in the presence of 30 mol% of ligand 110 in high yields (86-90%) with excellent enantioselectivities (92-97% ee) albeit combined with moderate diastereoselectivities (40-42% de).

ZnMe 2 (20 mol%) + 108 107 In 2020, a novel asymmetric synthesis of β-hydroxy esters was disclosed by Mlynarski et al. through the first enantioselective three-component domino reductive Michael/aldol reaction of acrylates 108, (hetero)aromatic ketones 115 and triethoxysilane ((EtO) 3 SiH) using zinc acetate as cheap precatalyst [START_REF] Węglarz | Zinc acetate catalyzed enantioselective reductive aldol reaction of ketones[END_REF]. Among chiral ligands based on (R,R)-diphenylethylenediamine, diamine 116 was selected as optimal ligand to promote this reaction at 15 mol% of catalyst loading in m-xylene as a solvent. As illustrated in Scheme 31, a series of chiral β-hydroxy esters 117 were generated at -30 °C with moderate to high yields (50-90%) and enantioselectivities (51-91% ee). However, the diastereoselectivity of the reaction was found low (4-36% de) and substrate-dependent.

R 1 = H, Me R 2 = Me, H, BnO(CH 2 ) 2 R 3 = Me, H R 4 = Me, Et, i-Bu, 1-Naph, 2-Naph 16->99%, 41-97% ee (R)-H 8 -BINOL (20 mol%) 109 CH 2 Cl 2 , r.t. MeMgBr (20 mol%) 4Å MS CO 2 R 4 R 1 R 2 R 3 OH O R 2 R 3 R 1 H H O OH OH OH R 2 R 3 R 1

REACTIONS USING OTHER LIGANDS

In 2007, Bolm et al. disclosed an asymmetric synthesis of Naryl propargylic amines based on an enantioselective threecomponent reaction of aldehydes 61, terminal alkynes 103 and omethoxyaniline 118 (Scheme 32) [START_REF] Zani | Dimethylzinc-mediated, enantioselective synthesis of propargylic amines[END_REF]. This reaction was mediated at room temperature in dichloromethane as solvent by four equivalents of ZnMe 2 in the presence of 4 mol% of chiral β-amino alcohol ligand 119 derived from norephedrine. It evolved by forming an imine from aldehyde 61 and o-methoxyaniline 118, which was then submitted to alkynylation to give the corresponding domino imine formation/alkynylation product 120 in both variable yields (24-85%) and enantioselectivities (13-97% ee). Homogeneously good to high enantioselectivities (68-97% ee) were obtained in the reaction of phenylacetylene, whereas much lower enantioselectivities (13-53% ee) were observed with other alkynes. Moreover, a range of aromatic, heteroaromatic and also aliphatic aldehydes provided, by reaction with o-anisidine and phenylacetylene, moderate to high enantioselectivities (68-97% ee). In 2017, Nakamura et al. investigated for the first time the ringopening reaction of protected aziridines 121 with malononitrile 30 using 12-24 mol% of a cinchona alkaloid zinc catalyst derived from ligand 122 and ZnEt 2 (10-20 mol%) [START_REF] Shiomi | Desymmetrization of aziridine with malononitrile using cinchona alkaloid amide/zinc(II) catalysts[END_REF]. As illustrated in Scheme 33, acyclic aziridines 121 reacted with malononitrile 30 to give the corresponding ring-opened products 123 which subsequently underwent an intramolecular nucleophilic addition of the amide nitrogen to the cyano group to provide chiral 2,3-dihydro-1H-pyrrole products 124 in excellent enantioselectivities (90-94% ee) and good yields (64-75%).

ZnEt 2 (10-20 mol%) 122 [START_REF] Broadley | Zinc in plants[END_REF][START_REF] Brandt | Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site[END_REF][START_REF] Rout | Effect of metal toxicity on plant growth and metabolism: I[END_REF][START_REF] Smith | Zinc toxicity in rats; antagonistic effects of copper and liver[END_REF][START_REF] Muyssen | Mechanisms of chronic waterborne Zn toxicity in Daphnia magna[END_REF][START_REF] Fosmire | Zinc toxicity[END_REF][START_REF] Ciubotariu | Zinc involvement in opioid addiction and analgesia--should zinc supplementation be recommended for opioid-treated persons?[END_REF][START_REF] Lowicki | Chiral zinc catalysts for asymmetric synthesis[END_REF](20)[START_REF] Kim | Advances in tandem reactions with organozinc reagents[END_REF][START_REF] Krishnan | Recent advances and perspectives in the synthesis of heterocycles via zinc catalysis[END_REF][START_REF] Neetha | Zinc-catalysed multicomponent reactions: an overview[END_REF](24) In 2019, a bimetallic rhodium/zinc catalysis was employed by Shao et al. to promote the first enantioselective domino ringopening/cyclopropanation reaction of oxabenzonorbornadienes 125 with phosphorus ylides 126 [START_REF] Chen | Rhodium(I)/Zn(OTf)2 -catalyzed asymmetric ring opening/cyclopropanation of oxabenzonorbornadienes with phosphorus ylides[END_REF]. The dual catalysis involved a combination of 5 mol% of bis (1,5-cyclooctadiene)rhodium(I) tetrafluoroborate (Rh(cod) 2 BF 4 ), 50 mol% of Zn(OTf) 2 and 5.5 mol % of chiral biphosphine ligand 127. The reaction allowed a range of chiral benzonorcaradienes 128 to be synthesized as single diastereomers (>99% de) in good to quantitative yields (56-99%) and high enantioselectivities (86-99% ee), as illustrated in Scheme 34.

O R 4 R 3 R 3 O R 2 R 1 R 1 R 2 R 3 R 2 R 1 R 1 R 2 H O R 4
Scheme 34. Domino ring-opening/cyclopropanation reaction of oxabenzonorbornadienes with phosphorus ylides.

In 2020, Fang and Ding developed an enantioselective domino alkynylation/cyclization reaction of alkynyl 1,2-diketones 129 with alkynes 104 catalyzed by a combination of 20 mol% of Zn(OTf) 2 and 20 mol% of chiral amino alcohol ligand 130 at room tempera-ture (Scheme 35) [START_REF] Liu | Lewis-acidcatalyzed asymmetric alkynylation of alkynyl 1,2-diketones: controllable formation of 3(2H)-furanones and α-hydroxy ketones[END_REF]. The reaction was performed at 40 °C in the presence of triethylamine (TEA) as the base, resulting in the formation of biologically important chiral 3(2H)-furanones 131 in moderate to good yields (41-81%) and uniformly high enantioselectivities (81-99% ee). It evolved through the mechanism depicted in Scheme 35, involving the nucleophilic addition of TEA to the alkyne unit of the alkynylation product 132 to give allenic intermediate 133. Then, the latter underwent a proton transfer to provide intermediate 134, which cyclized into the final domino product 131.

CONCLUSION

As an abundant, inexpensive and less toxic metal, zinc has gained significant importance in green catalysis. While underdeveloped for a long time, zinc catalysts are more and more applied to promote economic and ecologic transformations. Especially, a spectacular development of highly enantioselective zinc-catalyzed onepot reactions has emerged. This review highlights for the first time the developments in enantioselective domino and tandem reactions promoted by chiral zinc catalysts derived from various types of ligands, such as semi-aza-crown ligands, bis(oxazoline)s, bis(imidazoline)s, N,N'-dioxides, BINOL derivatives, 1,2-diamines, amino alcohols, among others. It shows that zinc catalysis suits the growing demand for greener processes and offers the real opportunity to replace other toxic and expensive metals in the near future. It demonstrates that zinc brings a novel potential for green catalysis, especially when combined with efficient sophisticated asymmetric one-pot processes and that this original area is growing very rapidly. Indeed, this field is in full bloom, allowing one-pot access to many types of complex functionalized chiral molecules from simple starting materials by using environmentally benign catalysts, and will undoubtedly continue to be expanded in the future with the discovery of novel catalysts. Even if remarkable results have been described, challenges remain, such as the application of these processes in the total synthesis of important biologically active and natural products, as well as the involvement of zinc in even more complicated multicatalyzed processes.

LIST OF ABBREVIATIONS

Ar

= Aryl BArF = Tetrakis [3,5-bis(trifluoromethyl)

1 Scheme 1 .

 11 Scheme 1. Domino Michael/lactonization reaction of 3-hydroxyoxindoles with α,β-unsaturated esters.

4 Scheme 5 .

 45 Scheme 5. Tandem Mannich/aldol reaction of branched aldehydes, aromatic aldimines and ketones and tandem Mannich/Henry reaction of branched aldehydes, aromatic aldimines and nitromethane.

  Scheme 6. Tandem Mannich/cycloisomerization reaction of aldimines with alkynones.

  Scheme 8. Domino phospha-Michael/Michael reaction of o-dienones with dialkyl phosphates.

Scheme 9 .

 9 Scheme 9. Three-component domino Knoevenagel/Michael/cyclization reaction of isatins, malononitrile and α-hydroxy acetophenones.

  Me, Et, Bn, p-BrC 6 H 4 CH 2 R 2 = H, F, Cl, Br, Me, OMe R 3 = H, 5-F, 5-Cl, 5-Br, 5-OMe, 4-Br, 6-Br Ar = Ph, p-FC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , p-O 2 NC 6 H 4 , p-Tol, p-MeOC 6 H 4 , m-BrC 6 H 4 , m-Tol, o-BrC 6 H 4 , 2-Naph, 2-thienyl, 2

Scheme 12 .

 12 Scheme 12. Domino Michael/hemiketalization reaction of aryl-substituted β,γ-unsaturated α-ketoamides and 2-hydroxy-1-indanones followed by Friedel-Crafts reaction.

Scheme 14 .

 14 Scheme 14. Domino Michael/lactonization reaction of α-hydroxy-1indanones with ortho-ester chalcones.

Scheme 16 .

 16 Scheme 16. Domino radical addition/cyclization reaction of hydroxamate esters with alkyl iodides.Multicatalysis attracts more attention from chemists[51]. As an example, Hu et al. developed in 2010 an enantioselective threecomponent domino oxonium ylide formation/Michael reaction of α,β-unsaturated 2-acyl imidazoles 57, diazo compounds 58 and water[START_REF] Guan | Cooperative catalysis in multicomponent reactions: highly enantioselective synthesis of γ-hydroxyketones with a quaternary carbon stereocenter[END_REF]. As shown in Scheme 17, the process was multicatalyzed by a combination of a chiral zinc complex, in situ generated from 30 mol% of Zn(OTf) 2 and the same quantity of chiral bis(oxazoline) ligand 59, and 2 mol% of dirhodium tetraacetate ([Rh 2 (OAc) 4 ]) in dichloromethane as solvent. This cooperative catalysis allowed at -8 °C to synthesize a range of chiral γhydroxyketones 60 bearing two contiguous stereogenic centers, including one quaternary. These products were obtained in good yields (60-81%) and diastereoselectivities (72-98% de) combined with high enantioselectivities (85-99% ee). The rhodium catalyst was supposed to promote the formation of an oxonium ylide from the diazoacetate reagent and water, which was further trapped by the α,β-unsaturated 2-acyl imidazole activated by the zinc catalyst through a Michael reaction to give the final domino product. It was found that electronic variations on the aromatic substituents of both the imidazoles and the diazoacetates were tolerated.

R 1 =

 1 H, 6,8-Br 2 , 6-NO 2 , 6-Me, 6-OMe, 7-OMe, 8-OMe R 2 = H, 5-F, 5-Me, 5

Scheme 19 .

 19 Scheme 19. Domino Michael/cyclization reaction of 3-nitro-2H-chromenes (X = O) with 3-isothiocyanatooxindoles.

  Scheme 20. Domino Michael/cyclization reaction of 3-nitroindoles with 3isothiocyanatooxindoles.

21 .

 21 Scheme 21. Domino Michael/cyclization reaction of 3-nitrobenzothiophenes with 3-isothiocyanatooxindoles.

23 .

 23 Scheme 23. Tandem aza-Diels-Alder/reduction reaction of 1-azadienes with nitroalkenes.

  Scheme 24. Domino inverse-electron-demand Diels-Alder/oxidation reaction of indoles with 2-(2-nitrovinyl)-1,4-benzoquinone.

25 .Scheme 26 .

 2526 Scheme 25. Three-component domino Knoevenagel/Pinner/Friedel-Crafts reaction of salicylaldehydes, malononitrile and indoles.

27 .

 27 Scheme 27. Domino carbonylimide formation/[4+3] cycloaddition reaction of β,γ-unsaturated α-ketoesters with diazoimides.

R 1 =

 1 Scheme 28. Three-component reaction of N-tosylaldimines with two different terminal alkynes.

32 .

 32 Scheme 32. Three-component domino imine formation/alkynylation reaction of aldehydes, terminal alkynes and o-methoxyaniline.

33 .

 33 Scheme 33. Domino ring-opening/cyclization reaction of aziridines with malononitrile.

Scheme 35 .

 35 Scheme 35. Domino alkynylation/cyclization reaction of alkynyl 1,2diketones with alkynes.

  Then, α,β-unsaturated ester 3 coordinated to the less hindered zinc atom to form intermediate B, which tautomerized into intermediate C. The latter subsequently underwent intramolecular transesterification to release the final spirocyclic oxindole 4 and regenerate the zinc phenoxide species D that could deprotonate another equivalent of 3hydroxyoxindole.

	Ph	OH		HO	Ph
	Ph				Ph
		N	OH	N
	OPh	(R,R)-ProPhenol (5 mol%)
	O
	+	toluene/MeCN, 40 °C
	R 2
		38-98%, 40-86% de, 47-99% ee
	Michael

  Ph, p-O 2 NC 6 H 4 , p-FC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , p-Tol, p-MeOC 6 H 4 , m-BrC 6 H 4 , o-BrC 6 H 4 , 1-Naph, 2-Naph, 2-furyl R 2 = H, F, Cl, Br, Me, OMe Ar 2 = Ph, p-Tol, p-FC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , p-MeOC 6 H 4 , m-BrC 6 H 4 , m-MeOC 6 H 4 , o-MeOC 6 H 4

	Ar 2	31 35 O	71-90%, 50-86% de, 75->99% ee ZnEt 2 (20 mol%) Ar 1 = Ar R 1 = Me, Et, Bn	37

  Ph, p-FC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , p-O 2 NC 6 H 4 , p-Tol, p-MeOC 6 H 4 , m-ClC 6 H 4 , m-BrC 6 H 4 , m-MeOC 6 H 4 , m-Tol, 3-Br-4-ClC 6 H 3

				Ph	OH	HO	Ph
				Ph		Ph
					N	OH	N
	Ph	O 31	CH 2 Cl 2 , 0 °C (S,S)-AzePhenol (2 mol%) OH CO 2 Me Ph O O Ar = ZnEt 2 (4 mol%) OH + MeO O O Ar Ar Michael 64-90%, 26-82% de, 90-98% ee 10	Ph MeO 2 C Ar hemiketalization O O OH 38
			Ph	O		Ph	O
			Ar		H 2 SO 4	Ar
				O	CH 2 Cl 2 , 0 °C	O
			MeO 2 C	OH		CO 2 Me
			38	without loss of enantiopurity	39
		structure of the in situ generated dinuclear active catalyst:
				Ph	O	Et	O	Ph
				Ph	Zn	Zn	Ph
					N	O	N
				EtZn 2 ((S,S)-AzePhenol)
	Scheme 11. Domino Michael/hemiketalization reaction of aryl-substituted
	β,γ-unsaturated α-ketoesters with α-hydroxyacetophenone.

  Bn R 2 = Ph, p-Tol, o-MeOC 6 H 4 , m-MeOC 6 H 4 , p-MeOC 6 H 4 , p-PhC 6 H 4 , p-HOC 6 H 4 , p-FC 6 H 4 , m-ClC 6 H 4 , p-ClC 6 H 4 , p-BrC 6 H 4 , 2-Naph, 2-thienyl, 3-furyl, (E)-PhCH=CH R 3 = Ph, i-Pr, p-ClC 6 H 4 , p-MeOC 6 H 4 , Me R 4 = Me, Bn

												). Fur-
	thermore, variously (N)-substituted diazoimides reacted smoothly.
	The mechanism proposed in Scheme 27 shows the formation of
	rhodium carbene species H from diazoimide 99 and Rh 2 Piv 4 . Then,
	an intramolecular carbonyl attack on the rhodium carbene occurred
	to form intermediate I. The latter reacted with the β,γ-unsaturated
	α-ketoester 10 activated by the chiral zinc catalyst through a [4+3]-
	cycloaddition to provide the final product.
							N	N
						O	O	O	O
	R 2		O		OR 1	100 (10 mol%) NHAr ArHN Ar = 2,6-Et 2 -4-(1-adamantyl)C 6 H 2		O	O
	+	O	O 10	O	O		Zn(OTf) 2 (10 mol%) Rh 2 Piv 4 (0.5 mol%)	R 3 R 4	N	O	O	R 2
	R 3	N					DCE, 30 °C					O	OR 1
		R 4		N 2			51-90%, >90% de, 85-99% ee				101
			99
	R 1 = Me, i-Pr, c-Pent, mechanism:
		99

  Ar = Ph, m-Tol, p-Tol, m-EtC 6 H 4 , m-MeOC 6 H 4 , p-MeOC 6 H 4 , m-BrC 6 H 4 , m-ClC 6 H 4 , p-ClC 6 H 4 , 2-furyl, 2-thienyl R = Me, t-Bu, Et

				t-Bu
				t-Bu
			Ph	NH
			Ph	NH
				t-Bu
	CO 2 R	O	t-Bu
		+	Ar	116 (15 mol%) Zn(OAc) 2 (15 mol%)	HO	O
					Ar	OR
	108		115	m-xylene, -30 °C
	+	(EtO) 3 SiH		then K 2 CO 3 /MeOH	117
			50-90%, 4-36% de, 51-91% ee
	Scheme 31. Three-component domino reductive Michael/aldol reaction of
	acrylates, aromatic ketones and (EtO)3SiH.
		+		119 (4 mol%)
	61		118	ZnMe 2 (4 equiv)
				CH 2 Cl 2 , r.t.
					120
					24-85%, 13-95% ee
		R 1 = Ph, p-Tol, p-ClC 6 H 4 , o-Tol, p-MeOC 6 H 4 , m-MeOC 6 H 4 , o-MeOC 6 H 4 ,
		o-BrC 6 H 4

  OMe, OBn, OEt, Me, Et, c-Pr, Ph, o-MeOC 6 H 4 , m-MeOC 6 H 4 , p-MeOC 6 H 4 , p-(NMe 2 )C 6 H 4 , o-Tol, t-Bu, 1-adamantyl, o-F 3 CC 6 H 4 , p-FC 6 H 4 , o-FC 6 H 4 , 2-Naph, 3,4-(MeO) 2 C 6 H 3 , 3,4-(O(CH 2 ) 3 O)C 6 H 3 , NPh 2

		Pt-Bu 2
		PPh 2
		Fe
		127 (5.5 mol%)
		Rh(cod) 2 BF 4 (5 mol%)
		Zn(OTf) 2 (50 mol%)
	+	PPh 3
		DCE, 50 or 70 °C
		126
	125 R 1 = H, Me, Br, F R 2 = H, Me, OMe R 3 = H, Me R 4 = 56-99%, >99% de, 86-99% ee	128

  Ar = Ph, p-ClC 6 H 4 , p-EtC 6 H 4 , 3-thienyl R 1 = Ph, p-ClC 6 H 4 , 1-Naph, 2-thienyl, (E)-PhCH=CH, p-MeOC 6 H 4 , p-Tol R 2 = p-Tol,Ph, p-FC 6 H 4 , (E)-PhCH=CH, p-EtOC 6 H 4 , 3-thienyl, p-MeOC 6 H 4 , p-EtC 6 H 4 , m-ClC 6 H 4 , o-FC 6 H 4

					130 (22 mol%)
	O				Zn(OTf) 2 (20 mol%)
		R 1	+	R 2	TEA (1 equiv)
	Ar	O			40 °C
	129			104
					41-81%, 81-99% ee

ACKNOWLEDGEMENTS

This work was supported by the National Centre for Scientific Research: CNRS.

FUNDING

None.

CONFLICT OF INTEREST

The author declares no conflict of interest, financial or otherwise.


H Courjon

Cory

S Ducourtieux

S G R Ésillon

J C Rivoal

D Courjon

Imaging subwavelength

Keywords: Microscopy of surfaces, interfaces and thin films, Near-field scanning optical microscopes, Atomic force microscopes

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Scanning near-field optical microscopy has undergone a remarkable growth over the last decade [START_REF]Proceedings of NFO-7: 7th International Conference on Near Field Optics and Related Techniques[END_REF]. The various techniques which have been used in the design of near field optical microscope involve either an apertureless diffusion tip or a sharpened optical fibre as a local probe to map the optical near field over the sample surface. Advances in instrumentation correlated with theory and modelling have led to a better understanding of the signals which are detected in the near zone. A recent review of both theoretical formalism used and experimental potentialities can be found in reference [START_REF]Le champ proche optique, Théorie et applications,e d i t e d[END_REF]. However, well defined test samples investigated with various types of Scanning Near-Field Microscope (SNOM) or Scanning Tunnelling Optical Microscope (STOM) working in several illumination modes are sparse. The investigations on such test samples have stimulated much efforts in the CNRS framework of the French Research Group "Optique du Champ Proche". A comparison of the test images recorded by means of a set of five different microscopes has been made recently [START_REF] Bainier | [END_REF]. The samples investigated are truncated circular holes created in a chromium layer deposited on a cover glass slide. Such test objects are well suited to understand the nature of the optical signal recorded by different apparatus. The a Groupement de Recherche "Optique du Champ Proche", CNRS 1860.

b e-mail: rivoal@optique.espci.fr nominal diameter of the test sample is close to half the wavelength of the excitation source as it was for the subwavelength aperture studied by Lezec et al. [4]. Metal is chromium instead of silver avoiding the possibility of surface plasmon excitation when studied in the visible optical domain.

It is well known that sharpened optical fibres can detect the intensity of the evanescent field [START_REF] Barchiesi | STOM: Theoretical study of polarisation effects with two models of tip[END_REF]6]. Moreover the known field enhancement at the metallic tip apex [7][8][9][10] could allow the detection of the axial component of the electromagnetic field [11]. This assumption was made in recent studies [12].

The main purpose of the present study is to correlate the near-field optical signal experimentally obtained with a crude theoretical approach. It appears in reference [START_REF] Bainier | [END_REF] that in similar illumination geometries, signals differ significantly depending on fibre or tip detection. We address the question: could the same theoretical model be used to interpret the images obtained with two different devices one using a fibre and the other a metallic tip? In Section 2 we describe the investigated samples. Two set-ups working in transmission mode are chosen, their characteristics are depicted in Section 3. The near-field optical images are presented in Section 4 and the formalism used to model the near-field optical signals is explained in Section 5. A comparison between experiment and computed results is made in Section 6 and in the last section conclusions are given.

Samples preparation 2.1 Sample preparation

Test samples are prepared from deposition of polystyrene latex beads (diameter ∼ 300 nm) onto a thin microscope plate (thickness 400 nm) using a method close to that described in reference [13]. The substrate is cleaned with distilled water and ethanol, and dried in clean ambient conditions. Latex spheres in water dilution are deposited onto the surface. After drying one obtains isolated spheres or small groups of spheres or even mono-layers depending on suitable concentration of beads versus the area of deposition. A chromium layer of a few nanometers of thickness is then evaporated on the surface and finally the latex spheres are chemically lifted off. A random distribution of perfectly circular holes is obtained reproducing faithfully the original positions of the spheres before removal.

Sample characterization by SEM or AFM imaging

A typical SEM image is presented in Figure 1. It shows the imprint of the latex spheres in the metal surface. A group of undissolved latex spheres remaining on the surface can also be observed. Scanning the surface with an AFM tip enables to determine the radius of the isolated holes and the approximate depth of the chromium layer. This measurement does not take into account the convolution by the conical tip.

The measured average diameter of the holes is less than 200 nm at the bottom and about 350 nm at the top of the chromium surface. Their depth is about 25 nm as shown in reference [START_REF] Bainier | [END_REF] see Figures 3b,e,f. It is also clear that there remains some roughness at the bottom of the hole (typically 2 or 3 nm) due probably to some pollutant.

3 Experimental set-ups

Apertureless configuration

In this SNOM/AFM configuration the probe is an apertureless metallic tip made from a tungsten wire etched by electrochemical erosion. The typical radius of curvature of the conical tip end is smaller than 50 nm, sometimes less than 10 nm (measured by scanning electron microscopy SEM) as shown in Figure 2.

The tip is 90-deg. bent at 1 or 2 mm from its extremity. The "L" shaped tip is then stuck onto a piezoelectric transducer and thus it oscillates periodically above the sample, and perpendicularly to the sample surface, as in AFM tapping-mode technique. The frequency of vibration is close to the resonance frequency (about 5 kHz depending on the length of the "L" shaped tip). The vibration amplitude is chosen to be close to 50 nm, and it is optically monitored.

A feedback system keeps the amplitude of vibration constant while the sample is scanned by the tip, giving The optical part is composed of a conventional microscope (Olympus BH). Various illumination modes are possible we briefly describe the transmission mode used in the experiment (Fig. 3).

A laser diode source beam (or a Ti/sapphire laser beam) is directed towards a first microscope objective (20X, f =1 0 ,NA=0 .4), which focuses the light on the sample surface. The polarisation of the incident light is controlled externally using a polariser. The light collection ensured by a second microscope objective (for instance 50X, f =6 .9,NA =0 .6) placed just above the sample and the tip, is axially symmetrical. The tip periodically scatters the near-field at the sample surface and radiates it in the far-field. This near-field contribution is recorded via a photomultiplier and a lock-in amplifier. The optical image resolution is relevant to the tip apex dimension [14].

Isotropic STOM configuration

The Isotropic Incoherent Scanning Tunneling Microscope (I2STOM) is a new microscope based on a particular illumination system. A quasi-polychromatic, incoherent and depolarised source generated by stimulated Raman scattering within an optical fibre is used [15]. The refraction through an axicon prism ensures an isotropic lighting of the sample in total internal reflection mode. The evanescent field is detected by the use of a stand-alone microscope head whose local probe is a nanometric tapered optical fibre working in collection mode. The tip sample distance is kept constant by means of an electronic shearforce feedback loop. The tip glued onto a tuning fork scans the sample and the near-field signal is amplified through a photomultiplier and a lock-in system. Topography and optical images simultaneously recorded are strongly correlated and optical artefacts are very low.

Comparison of both set-ups

Both set-ups appear quite different but they share some common properties. In both cases the sample illumination comes through the substrate and the beam shape is globally conical and axially symmetric. The near-field optical signal is collected above the hole by a feedback controlled probe. These experimental similarities will be useful for choosing the theoretical formalism used to fit the experimental results.

SNOM experimental results

Typical results obtained with the two described set-ups are shown. In each case topography and SNOM signals are recorded simultaneously for each sample.

Apertureless configuration

In the optical image (SNOM) of Figure 4 two lobes with opposite contrast are observed on each hole and an amplitude change occurs along the polarisation direction (y).

To clarify the polarisation behaviour of the SNOM signal we have introduced in the detection channel an analyser oriented at right angle to the incident polarisation. With the tip far from the surface the detected signal is greatly reduced and we realise a detection almost in a dark field configuration. In such a configuration only the SNOM signal due to the diffusion by the tip is detected with a decrease of the signal-to-noise ratio compared to

Isotropic SNOM results

The test sample is isotropically illuminated in total internal reflection mode with an incoherent unpolarised polychromatic Raman source as explained above. Topography and optical images simultaneously recorded in near-field are shown in Figures 6 and7.

Various hole distributions are observed. For example, the doublet allows us to give an estimation of the optical resolution using a separation criterion (Fig. 6 see arrow), whereas isolated apertures will quantify the optical confinement (Fig. 7).

In Figure 7 [AB] and [CD] cuts show that the evanescent field is confined inside the nano-hole and centred on it. The skin thickness of chrome is about 10 nm at middle Raman spectrum wavelength (λ = 590 nm). Thus a widening of confinement is expected versus the inside hole diameter. The estimated diameter at half-height of the topography image is 230 nm (see [AB] cut in Fig. 7) and the same cutting on the optical image with the confinement effect gives an estimated diameter of 270 nm (see [CD] cut in Fig. 7).

The formalism of Grober's group

A theoretical formalism giving the optical near-field generated by an aperture is given in reference [17]. The aperture is assumed to lie in the plane z =0a n dd i ff r a c t s an incident plane wave normal to the aperture from the half-plane z<0 see Figure 8. The electric field of the incident plane wave, E =x exp[i(k 0 z -ωt)], is linearly polarized with the electric field oriented along the x axis and of unit amplitude while k 2 0 =( ω/c) 2 . The expression of the diffracted fields in the plane of the aperture is based on the analytical expressions proposed by Bethe [18] and corrected by Bouwkamp [19] for the electromagnetic field diffracted by a small aperture in a metallic plane. The techniques of Fourier optics (i.e. modal analysis) are used to describe the electromagnetic field detected by a nearfield optical probe.

Attempts to use Fourier optics to provide a quantitative understanding of this problem were initiated by D. Van Labeke et al. [20], who used plane-wave solutions to the wave equation (in Cartesian coordinates) as the basis for a modal analysis. Also the behaviour of the Poynting vector near a small aperture was investigated numerically by Y. Leviatan [21] and T. Nakano and S. Kawata [22]. The strength of the Grober et al. analysis [17] is that: (a) the vector nature of the electromagnetic field is preserved, (b) an analytical expression for the Fourier transform of the field is provided, (c) the electromagnetic field can be determined by evaluating one-dimensional integrals, and (d) both the divergent behaviour of the nearfield and the dipolar nature of the far-field are recovered. Their judicious use of cylindrical coordinate system adapted to the geometry of the aperture enables to reduce the modal expansion from a two-dimensional integral to a one-dimensional integral.

If the complex time factor, exp(-iωt), is omitted since it plays no role in the derivation the transverse magnetic (TM) and transverse electric (TE) expansion coefficients, f TM (k)a n df TE (k), respectively, are defined as

E(ρ, θ, z)= ∞ 0 dk f TM (k) E TM (k, ρ, θ, z) + f TE (k) E TE (k, ρ, θ, z) , (1)
B(ρ, θ, z)= ∞ 0 dk f TM (k) B TM (k, ρ, θ, z) + f TE (k) B TE (k, ρ, θ, z) , ( 2
)
where k is the lateral spatial frequency, i.e. k ρ . By an inverse transformation of these equations, Grober et al. [17] are able to determine f TM (k)a n d f TE (k) from the fields in the plane of the aperture, E(z = 0) and B(z = 0). The azimuthal symmetry of Bouwkamp's solution enables a dramatic simplification of the modal expansion by requiring only the n = ±1 terms. Let us denote by κ the longitudinal spatial frequency i.e. k z .W h e n k>k 0 κ → iκ and the modes become evanescent. The components of the electric field are given as follows:

E ρ = k0 0 iκ cos θ ∂J 1 (kρ) ∂(kρ) f 1 TM exp(iκz) dk + ∞ k0 iκ cos θ ∂J 1 (kρ) ∂(kρ) f 2 TM exp(iκz) dk + ∞ 0 -k 0 cos θ J 1 (kρ) kρ f TE exp(iκz) dk (3)
E θ = k0 0 -iκ sin θ J 1 (kρ) kρ f 1 TM exp(iκz) dk + ∞ k0 -iκ sin θ J 1 (kρ) kρ f 2 TM exp(iκz) dk + ∞ 0 k 0 sin θ ∂J 1 (kρ) ∂(kρ) f TE exp(iκz) dk (4)
E z = k0 0 k cos θJ 1 (kρ)f 1 TM exp(iκz) dk + ∞ k0 k cos θJ 1 (kρ)f 2 TM exp(iκz) dk. (5)
Similarly the components of the magnetic field are given, thus:

B ρ = k0 0 ik 0 sin θ J 1 (kρ) kρ f 1 TM exp(iκz) dk + ∞ k0 ik 0 sin θ J 1 (kρ) kρ f 2 TM exp(iκz) dk + ∞ 0 -κ sin θ ∂J 1 (kρ) ∂(kρ) f TE exp(iκz) dk (6)
B θ = k0 0 ik 0 cos θ ∂J 1 (kρ) ∂(kρ) f 1 TM exp(iκz) dk + ∞ k0 ik 0 cos θ ∂J 1 (kρ) ∂(kρ) f 2 TM exp(iκz) dk + ∞ 0 -κ cos θ J 1 (kρ) kρ f TE exp(iκz) dk (7) B z = ∞ 0 [ik sin θJ 1 (kρ)f TE ]e x p ( iκz) dk (8)
where J 1 (kρ) is a Bessel function of the first kind. The relevant optical modes for the region z>0h a ving been determined, the remaining analysis of Grober et al. [17] is to determine analytical forms for f TM (k)and f TE (k) while maintaining a physically meaningful result. The expressions obtained are given below

f 1 TM (k<k 0 )=- 4k 0 a 3 3π exp(-ik 0 a) k (k 2 0 -k 2 ) 1/2 (9)
Fig. 8. Scheme of the coordinate system used in the calculation.

f 2 TM (k ≥ k 0 )= 4ik 0 a 3 3π exp(-ik 0 a) -1+ k (k 2 -k 2 0 ) 1/2 + sin(ka) ka ( 10
)
f TE (k)= 4ia 2 π exp(-ik 0 a)  1 (ka) ( 11
)
where  1 (ka) is a spherical Bessel function.

Putting back these expressions in equations (1, 2), Grober et al. [17] were able to calculate the diffracted field at any point in the half-plane z>0 .T h et i m ea v e raged electric field intensity follows Bouwkamp's solution in the near-field and it smoothly evolves far from the aperture to the field intensity of a radiating magnetic dipole oriented along the y axis. We have used the analytical expressions above to calculate the near-field components of the electromagnetic fields and the Poynting vector in the transmission mode configuration. We first calculated numerically the values of E ρ , E θ and E z using the one dimensional equations for any value of z>0a n dt h e n obtained the numerical values of the E x , E y and E z components.

In Figure 9 we illustrate the results obtained for the electric field components E x , E y and E z for z>0 for an incident wavelength λ = 780 nm. The amplitude of the fields in the xy plane at an altitude z = 6 nm are shown in Figure 9 (top) and their corresponding phase is shown in Figure 9 (bottom).

In Figure 10 we show the intensity of the Poynting vector defined as

Poynt = P 2 x + P 2 y + P 2 z ( 12
)
where P x , P y and P z are the Cartesian coordinates of the vector calculated at λ = 590 nm.

6 Comparison between experiments and calculations

Apertureless tip

The calculated amplitude and phase signals shown in Figure 9 for the wavelength λ = 780 nm depend on the inci-

I tot ∼|E tot | 2 = |E dif + E ref | 2 = |E dif | 2 + |E ref | 2 +2|E dif ||E ref | cos ϕ ( 13
)
where ϕ is the relative phase of the two interfering fields. This signal enters the lock-in detector whose reference is the signal driving the modulation of the tip at the frequency ω.As|E ref | 2 is not modulated and |E dif | 2 is modulated at twice the frequency (2ω), the lock-in output at the frequency ω delivers the term 2|E dif ||E ref | cos ϕ, which contains the information on the phase ϕ of the nearfield signal [23,24]. The experimental SNOM signal detected by the lockin at the frequency of the tip can be seen in a first approximation as the difference between the signals collected very close to the plane and well above it. To simulate the detected signal we have calculated the complex amplitudes E x , E y and E z for z =6n m( z ≃ λ/130) and for z =5 1n m( z ≃ λ/15). The results are very similar to those of Figure 9 except that the fields are less localized and their amplitude is reduced. The E x component is almost flat all over the surface of the hole. The E y component presents a quadrangular distribution in both the amplitude and the phase, its amplitude maxima occurring inside the hole. The E z component is dominant with a clear phase variation. The behaviour of the amplitude of the field's components is illustrated in Figure 11 as a function of the altitude z. The profiles are taken along the incident polarisation direction for the E x and E z components. Because the E y component is zero along this direction the E y profile is shown along a line y = x which corresponds to a rotation by a 45 deg. angle to the direction of polarisation. It is clear, whatever the component, that the field is highly localised in the vicinity of the hole.

Obviously the E z component presents the two lobes experimentally observed in Figure 5. Moreover, the calculated opposite phase change is revealed by an opposite contrast in the experimental SNOM images. This is in agreement with recent experiments [25] done using an optical phase control. The calculated and the observed signals present a mirror symmetry along the x-z plane and the agreement between the calculations and the transmission experiments is satisfactory.

Isotropic SNOM

It has been shown [26] that a small aperture tip detects both the electric and the magnetic fields. Whether it detects the Poynting vector or the sum of the squares of the E x and E y components is not clear. Within the limitations y x Fig. 12. Calculated E 2

x + E 2 y at z =6nmandλ = 590 nm.

of our crude model we have calculated both quantities in order to compare them with the experimental results. The Poynting vector shown in Figure 10 is calculated at λ = 590 nm which is the central wavelength of the Raman spectra. The E 2

x +E 2 y = E 2 xy quantity is depicted at the same wavelength in Figure 12. In both figures the polarization of the incident electric field is directed along x.

In the experiment done with the isotropic source the incident polarization of the electric field is also isotropic. The averaged resultant Poynting vector and E 2 xy can be approximated by a weighted linear combination of the vectors or of the intensity calculated for two orthogonal polarizations. Because the source is also polychromatic, comparison with experiment requires a calculation at different wavelengths and the weighting by the incident intensity of the source components. The Raman source used in the experiment is composed of many emission lines, which span the range 532 nm to 680 nm and have quite different integrated intensities. We have made the same calculation of the Poynting vector and E 2 xy as the ones shown in Figures 10 and 12 using three different wavelengths and keeping constant the z =6n mv a l u e .T h e weighted calculated profiles along the diameter of the hole are shown in Figure 13. Comparison with the experiment a lp r o fi l e( s e eF i g .7 )l e a d sto a better agreement with the calculated Poynting vector.

Remark

Several experimental factors can affect the measurements and lead to different results. Also we note that the crude theoretical formalism of Grober et al. uses an incident plane wave normal to the sample. At off-normal angles of incidence, which is the case of the two experimental results presented here the theory appears to become numerically intractable for the moment. Better adjustment could probably be gained using the conical geometry imposed by the focusing microscope objective and recently explored by Drezet et al. [27].

Discussion

In most of the experiments done on the test object [START_REF] Bainier | [END_REF], the SNOM signal observed (in transmission mode) when scanning an isolated hole shows two lobes aligned with the direction of polarisation of the incident beam. Only in the case of the isotropic illumination is the SNOM signal homogeneous. In the two experiments done in transmission mode and described above, the SNOM signal resembles either the E z component of the near field calculated at a few nanometers above the plane z = 0 in the apertureless configuration (see Fig. 9) or the intensity of the weighted Poynting vector which is similar to the E 2 xy intensity of the electric field (see Fig. 13) in the I2STOM configuration.

Although the results shown in Figures 9 and11 give the local field calculated without taking into account the interaction with the tip, the agreement with the experimentally detected signal is quite satisfactory. This is not surprising given the theoretical analysis of [28], which shows in particular why the SNOM transmission signals from Figure 5 follow the expected polarisation behaviour.

The existence of extremely strong field gradients at the tip apex have been demonstrated in several tip geometries [29][30][31]. Consideration of higher Hermite-Gaussian modes for the illumination of the tip leads also to strong field enhancements at the tip apex [9]. Whatever the shape of the probe, the calculations have been performed numerically. The total electric field generated by a plane electromagnetic wave incident on a perfectly conducting conical probe situated above a dielectric surface has been investigated [8]. The results, which are analytical, partly agree with those found in [9,30]. The field at a short distance r from the tip apex (kr ≪ 1) can be written [8,32]:

E = k(kr) ν-1 sin β u r + u θ ν ∂ ∂θ a(θ 0 ,θ,α) (14)
where a is a function of the angle of incidence θ 0 , the angle of observation θ, and the semi-angle of aperture α of the cone tip. u r and u θ are the unit vectors in spherical coordinates. ν is positive and smaller than 1, and depends on α. The other parameters are the wave vector k = ω/c and the angle of polarisation β of the incident wave. While this expression of the field is asymptotic, it is not an electrostatic approximation and therefore it includes retardation effects. It is worth noticing that the field given by equation ( 14) is highly enhanced near the tip apex and that its spatial distribution does not depend on the illumination conditions.

In the theoretical approach of reference [28] the derivation of the signal detected in apertureless SNOM is based on the reciprocity theorem of electromagnetism. The detected field is an overlapping integral between the experimental field and a term proportional to the response function of the instrument [33], which is proportional to the derivative of the reciprocal field. To determine an approximate and practical description of this reciprocal field the authors use the expression of E given in equation (14). With this model their approach provides a versatile and useful tool to analyze the experimental results.

The calculations outlined above show that in apertureless SNOM configuration the tip enhances mostly the E z component along the axis of the cone tip. With this last assumption it is possible to compute the signal |E z | cos ϕ corresponding to the interference term between the field diffused by the tip, which is sensitive to the field components oriented along z, and a reference wave whose modulus is 1 and its phase is zero relative to E z . This reference wave could be the one partially transmitted by the hole. We have computed the expected SNOM signal within the model developed above and the result is shown in Figure 14.

It is clear that the calculated and experimental results are in good agreement. It would be interesting to compare these results either theoretically or experimentally with the images which could be obtained with the use of heterodyne detection [25,34] or with a SNOM coupled with a Mach-Zehnder interferometer [35].

8Conclusion

The study of these test objects was undertaken to compare the potentialities of the different devices currently in use in the French community of Near Field Optics. We have demonstrated with two transmission configurations that the topography and SNOM signals can be detected simultaneously. The vertical resolution in AFM is of the order of 1 nm and is limited transversely by the shape of the conical tip. Modelling SNOM observations with the Grober's formalism [17] has lead to a better understanding of the detected signals. The SNOM signals obtained with two different configurations are strikingly different but they can be described with the same model. In the I2STOM configuration the quality of the image is excellent. The recorded signals agree with the calculated intensities whereas in apertureless configuration two lobes are observed with a polarisation behaviour of the observed SNOM signal in agreement with the amplitude of the electric field.

Fig. 1 .

 1 Fig. 1. SEM image of a chromium layer with random distribution of holes and a group of remaining spheres at right hand.

Fig. 2 .

 2 Fig. 2. SEM image of a tungsten tip.

Fig. 3 .

 3 Fig. 3. Experimental apertureless SNOM set-up.

Fig. 4 .

 4 Fig. 4. AFM (top) and SNOM (bottom) images of the holes, at λ = 780 nm, in the apertureless configuration. The direction of polarisation is along the vertical direction (y direction).

Fig. 5 .

 5 Fig. 5. AFM (top) and SNOM (bottom) images of the holes, at λ = 780 nm, in the apertureless configuration. (a) Incident polarisation vertical and output polarisation horizontal (left) (b) both polarisations rotated by 90-deg. angle (right).

Fig. 6 .

 6 Fig. 6. Shear-force image (top) and optical image (bottom) of a distribution of holes in a chromium layer from of a typical area observed in near-field with an isotropic STOM, (scanned area 4.02 × 4.02 µm 2 ).

Fig. 7 .

 7 Fig. 7. Near-field confinement inside the holes. Shear-force and optical images (top and middle), corresponding profiles (below) respectively. Scanned area 4.02 × 4.02 µm 2 .

Fig. 9 .

 9 Fig. 9. Calculated electric field components at z =6n m : amplitude (top), phase (bottom).

Fig. 10 .

 10 Fig. 10. Calculated Poynting vector at z =6n ma n dλ = 590 nm.

Fig. 11 .

 11 Fig. 11. Profiles of the amplitude of the electric field as a function of z for λ = 780 nm: (a) Ex (top), (b) Ey (middle) rotated by 45 deg. with respect to the polarisation direction, (c) Ez (bottom).

Fig. 13 .

 13 Fig. 13. Profile of the weighted calculated Poynting vector (continuous line) and E 2 xy (dashed line).

Fig. 14 .

 14 Fig. 14. Calculated SNOM image of a single hole assuming that the tip detects the Ez component of the local field. (The vertical scale is the same as the one in Fig.9). Incident polarization horizontal.

The authors would like to thank L. Aigouy for his help in the experimental work and for providing the image of the metallic tip. They are indebted to Y. de Wilde and C. Boccara for fruitful discussions.