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A new group of ureylbenzamide-based receptors (1–4) has been synthesized; its binding affinity and capacity to form supramolecular complexes in solution with different anions have been investigated. For designing these receptors, it was considered a combination of the positions of the urea and amide groups (ortho and meta), and the chromophore groups naphthyl and nitrophenyl, yielding four receptors. The position and chromophore structure affected the acidity of the urea and amide hydrogens in the order 4>3>2>1. All the spectroscopic studies showed a significant change of 1 and 2 compared with 3 and 4 in the presence of different TBAX salts in acetonitrile. The 1H-NMR spectra show a preferential interaction of the anions with the urea group in receptors 1 and 2 due to the less steric hindrance, while there is a cooperative interaction of amide group in receptors 3 and 4 due to the closeness of both groups.

α-Amino-H-phosphinic acids and derivatives are an important group of compounds of synthetic and pharmacological interest, and particular attention has been dedicated toward their stereoselective synthesis in recent years. While some of these compounds show activity by themselves, they are also valuable starting materials in the synthesis of phosphinic bioisosteres of natural peptides, where the hydrolyzable bond is substituted by a phosphinic functionality that mimics the transition state of peptide hydrolysis, thus acting as efficient enzyme­ inhibitors in which the molecular stereochemistry is demonstrated to be critical. This review summarizes the latest developments on the asymmetric synthesis of acyclic and phosphacyclic α-amino-H-phosphinic acids and derivatives following an order according to the strategy used; in addition, some implications in medicinal chemistry are disclosed., The authors gratefully acknowledge CONACYT (grant 181816, 248868) and PRODEP (project UAEMOR-PTC-379) of Mexico, Ministerio de Economía y Competitividad (grant CTQ2013-40855-R) and Gobierno de Aragón – FSE (research group E40) for their financial support.

The synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a MIC of 14.2, 13.6 and 10.8μM, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4μM. The ex-vivo evaluation of hepatotoxicity on precision-cut rat liver slices was also tested for the α,β-unsaturated amides (S)-2b and (S)-2d,f and for the oxazolines (S)-3b and (S)-3d,f at different concentrations (5, 15 and 30μg/mL). The results indicate that these compounds possess promising antimycobacterial activity and at the same time are not hepatotoxic. These findings open the possibility for development of new drugs against tuberculosis.

This review outlines the most recent papers describing the stereoselective synthesis of γ-amino acids. In this update, the γ-amino acids have been classified according to the type of compounds, position and number of substituents, and depending on the type of substrate, acyclic, carbocyclic or azacyclic derivatives, following in the first case an order related to the strategy used, whereas in the second and third cases the classification is based on the ring size.

The authors thank Consejo Nacional de Ciencia y Tecnologia (CONACYT) for financial support through projects 181816 and 248868, the Ministerio de Ciencia e Innovacion – FEDER (grant CTQ2010-17436), and the Gobierno de Aragon-FSE (research group E40).

We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in the N-acyliminium ion intermediates, obtained from activation of the quinoline and isoquinoline heterocycles or from the appropriate δ-lactam with benzyl chloroformate. Finally, the hydrolysis of phosphonate moiety with simultaneous cleavage of the carbamate afforded the target compounds., Financial support to this work was provided by Consejo Nacional de Ciencia y Tecnología (CONACYT-Mexico, grants 181816 and 248868). Ministerio Economia y Competitividad (grant CTQ2013-40855-R), and Gobierno de Aragón-Fondo Social Europeo (research group E40). Consejo Superior de Investigaciones Científicas (grant 2008MX0044)., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

The alkylation reaction of diethyl N-(diphenylmethylene)aminomethylphosphonate (6) with alkyl dihalides under phase-transfer catalysis followed by hydrolysis of the benzophenone imine moiety and subsequent cyclization provides a simple and convenient method for the synthesis of known and new cyclic α-aminophosphonates 1–5 in moderate to good yields.

This review describes the synthesis, biological interest and importance of the α-aminophosphonic acids analogs of the 20 proteinogenic α-amino acids. Special attention is devoted to those stereoselective procedures that allow the synthesis of the required compounds in enantiomerically pure form. © 2012 Bentham Science Publishers.

We describe a protocol developed for the preparation of β-enaminoketones derived from 1,3-cyclohexanediones, and their subsequent reduction by sodium in THF-isopropyl alcohol to afford cis- and trans-3-aminocyclohexanols.

A microwave assisted method for the synthesis of some typical 4-substituted oxazolidinone chiral auxiliaries used in asymmetric synthesis is reported in this work. Under these conditions, treatment of (S)-phenylalaninol, (S)-phenylglycinol, (S)-valinol and (1S, 2R)-norephedrine with ethyl carbonate or carbon disulfide under the appropriate and specific microwave reaction conditions, led to an efficient synthesis of some oxazolidin-2-ones, oxazolidine-2-thiones and thiazolidine-2-thiones. The methodology reported in this paper provides these chiral auxiliaries with improved yields and a remarkable reduction on the reaction times, particularly in the case of thiazolidine-2-thiones, as compared with the conventional methods. All the auxiliaries prepared here show spectroscopic data in full agreement with those previously reported in the literature.

The synthesis of two phosphoproline analogues possessing an octahydroisoindole structure is described for the first time. The new α-aminophosphonic acids can be viewed as the result of fusing a cyclohexane ring to the [c] face of the five-membered pyrrolidine unit. The junction of the bicyclic system is cis in both compounds, but they differ in the relative stereochemistry of the cyclohexane and phosphonate moieties. Using phthalimide as a common precursor and following stereodivergent routes, the target α-aminophosphonic acids, (1R*,3aR*,7aS*)-and (1S*,3aR*,7aS*)-octahydroisoindole-1-phosphonic acids, have been prepared with completestereocontrol and in high overall yields. The structurally related isoindoline-1-phosphonic acid, containing a benzene ring [c]-fused to pyrrolidine, has also been obtained. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., The authors thank the Spanish Ministerio de Ciencia e Innovación (MICINN) (project CTQ2010-17436), Consejo Superior de Investigaciones Científicas (project 2008MX0044; JAE predoctoral fellowship to A. A.), Gobierno de Aragón (research group E40) and the Mexican Consejo Nacional de Ciencia y Tecnología (CONACYT) (projects 62271 and J000.400/2009) for financial support.

The first total synthesis of 5-hydroxy-3-methyl-4-propylsulfanyl-5H-furan-2-one, a newly discovered natural product with anticancer property is described by two different routes. A sequence involving an incorporation of a methyl group via a Gilman reagent and a chemoselective reduction of a cyclic anhydride functionality are the key steps. The methods proposed start from easily available starting materials and allow ready preparation of the final compound in good overall yield.

A convenient and efficient preparation of phosphonopropanoamides bearing (S)-1-(1′-naphthyl)ethylamine, (S)-3,3-dimethyl-2-butylamine, and (S)-2-amine-3-methylbutane in good yield has been achieved. The stereochemical outcome of the asymmetric benzylation reaction of their enolates changes dramatically with the LDA equivalents used. The enolization of the phosphopropanoamides with LDA (2 equiv.) followed by the reaction with benzyl bromide gives rise to the (R,S) quaternary phosphonoamides, whereas the (S,S) diastereoisomer can be obtained by enolization with LDA (≥2.5 equiv.) followed by the addition of benzyl bromide. This method provides access to both diastereoisomers changing only the base equivalents.

The diastereoisomers of α-aminophosphonates are key intermediates in the synthesis of enantiomerically pure α-aminophosphonic acids, which are analogs of α-amino acids. Although several methods have been reported for the diastereoselective synthesis of α-aminophosphonates, their mass spectrometry (MS) fragmentation patterns have not yet been fully investigated. The work described here involved a detailed study of the fragmentation of enriched α-aminophosphonate diastereoisomers by chemical ionization (CI-MS) and fast atom bombardment (FAB)-MS. The complete characterization of the different conventional MS fragmentation pathways is represented and this intriguing exercise required the use of tandem mass spectrometry (MS/MS) experiments and high-resolution accurate mass measurements. All α-aminophosphonates gave prominent pseudomolecular ions, protonated molecules [MH]+, and their fragmentations mainly showed a loss of dimethyl phosphite to give the corresponding iminium ions as base peaks for α-aminophosphonates bearing methylbenzyl and 2,2-dimethylbutyl fragments. The loss of the chiral fragment from the iminium ions bearing the (S)-1-(1-naphthyl)ethyl group gave rise to a base peak due to aryl cations. The nature of all fragment ions were confirmed by high-resolution mass spectrometry (HRMS). Copyright © 2011 John Wiley & Sons, Ltd.

The first diastereoselective total synthesis of 5-substituted morpholine-3-phosphonic acids is reported. The principal feature of the synthesis is the introduction of a dimethyl phosphonate group into 5-substituted morpholin-3-ones. The procedure is based on the preparation of N -Boc-( S )-5-phenyl- and N -Boc-( S )-5-benzylmorpholin-3-one from l -phenylglycine and l -phenylalanine methyl esters, followed by the formation of the 3-methoxylated compounds and subsequent reaction with trimethyl phosphite in the presence of BF 3 ·OEt 2 . Diastereoselectivity in the formation of cis -disubstituted products is in agreement with the nucleophilic addition to other methoxylated derivatives.

Uncatalyzed one-pot, three-component reactions of aldehydes, chiral α-methylamines, and dimethyl phosphite under solvent-free conditions were used for the diastereoselective synthesis of α-amino phosphonates. The reactions proceeded with extremely high efficiency under mild conditions and gave good yields and diastereoselectivities (70:30 to 93:7 dr). This approach could be useful for the large-scale synthesis of several α-amino phosphonates.

The synthesis and characterization of pure cis- and trans-1,4-diphenyl-1-methoxy-phosphorinanium tetrafluoroborate salts 11a and 11b, molecules designed to evaluate the effect of a phenyl substituent at C-4 on the stereochemical course of base-induced nucleophilic displacement of the methoxy group at phosphorus, was accomplished. The presence of a phenyl substituent at C-4 changes the stereochemical course of these reactions, from complete inversion with alkyl groups to products where retention of configuration at phosphorus predominates. We suggest a mechanism involving Berry pseudorotations and provide evidence that the hydroxide ion attacks the phosphorus atom through experiments with NaOH enriched with 17O.

γ-Amino acids such as GABA, GABOB, statine and carnitine have attracted considerable attention as biologically active compounds. Over the last few years, significant interest in the stereoselective synthesis of γ-aminophosphonic acids GABOB P , phosphocarnitine, phosphostatine and derivatives has been observed. An overview of synthetic approaches of γ-aminophosphonic acids and derivatives is presented. Data on the practical applications of the γ-aminophosphonic acids are also discussed.

Phosphonopropanoamides bearing ( S )-α-methylbenzylamine were easily obtained, and the benzylation of their enolates examined. Surprisingly, a reversal of the π-facial diastereoselectivity was observed by changing the number of equivalents of the lithium base. Reaction of the lithium enolate obtained using 2.0 equiv of LDA, LiHMDS or LTMP with benzyl bromide afforded the ( R , S )-diastereoisomer, whereas the use of ⩾2.5 equiv of lithium base gave the ( S , S )-diastereoisomer. In contrast, a reversal of diastereoselectivity was not observed with sodium or potassium bases. This reversal is attributed to the formation of aggregates of the enolates. The results presented here provide valuable guidelines to tune the selective preparation of enantiopure compounds from the same source of chirality.

Reduction of β-keto-diphenylphosphine oxide (S)-4 derived from (S)-mandelic acid with NaBH4 in methanol at −78 °C gave the anti-3-diphenylphosphinoyl-1,2-diol 6, whereas the reduction of (S)-4 with Zn(BH4)2 in THF at −78 °C afforded the syn-1,2-diol 5, both in high yield and excellent diastereoselectivity. This procedure represents a new approach to the diastereoselective synthesis of diphenylphosphinoyl diols and an example of highly diastereoselective 1,2-induction. A theoretical model to explain the direction and degree of asymmetric induction is proposed.

A series of novel naphthalimide–aminobenzamide (NAPIM-2ABZ) dyads 3 connected by different length polymethylene chains were synthesized and studied as fluorescent supramolecular receptors in metal ion binding. The photophysical properties were evaluated and compared with separated chromophores. The electronic absorption spectra of dyads 3 showed no interaction between chromophores in the ground state. The fluorescence quantum yields were lower in dyads 3 in comparison with N-propyl-2-aminobenzamide (8). The fluorescence quenching is attributed to a PET mechanism between fluorophores (from 2ABZ to NAPIM), which is dependent on the polymethylene chain length. In metal binding study was found a response towards transition metal ions such as Hg(II), Cu(II), Zn(II) and Ni(II). Dyad 3b presented selectivity towards Cu(II). The UV-vis, IR and 1H-NMR studies demonstrated the interaction with 2ABZ moiety in the ground state, and interestingly dyads with shorter polymethylene chains 3a (n = 0), 3b (n = 1) and 3c (n = 2) exhibited an OFF/ON fluorescence behaviour due to the PET inhibition and the quenching of 2ABZ fluorescence. Dyads 3d (n = 4) and 3e (n = 6) presented opposite response ON/OFF in the complex with metal ions evidencing the absence of PET in these dyads.

Chiral phosphonoacetamides bearing (S)-(α-methylbenzyl)benzylamine, (S,S)-bis(α-methylbenzyl)amine, l -phenylglycine methyl ester and l -phenylglycinol were easily prepared in good yield by means of the Michaelis–Arbuzov reaction of chiral bromoacetamides obtained in quantitative yield, with trimethyl phosphite, which under Horner–Wadsworth–Emmons conditions with several aryl and alkyl aldehydes under Masamune–Roush procedure using LiCl and DBU in THF or toluene gave the corresponding chiral α,β-unsaturated amides. The present procedure is a convenient and efficient methodology for the preparation of phosphonoacetamides and chiral α,β-unsaturated amides in high E-selectivity.

The efficient preparation of both enantiomers of dimethyl δ,β-dihydroxyethylphosphonate 2 has been achieved from salicylaldehyde as a starting material, through the resolution of dimethyl (±)-2-(2-O-benzylphenyl)-2-hydroxyethylphosphonate 4 using (S)-methoxyphenylacetic acid (MPA). The absolute configuration was assigned by the Dale and Mosher approach using extended Newman projections and ab initio calculations.

An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride.

Synthesis and structural characterization of 1,4,2-oxazaphosphepines is described. The 1,4,2-oxazaphosphepines were obtained from reaction of chiral 1,3-benzoxazines with dichlorophenylphosphine or triethyl phosphite. The configuration of some of these compounds was stablished by X-ray analysis.

The authors are thankful for financial support by the Mexican Consejo Nacional de Ciencia y Tecnologia (CONACYT) for financial support via project 181816, by the Spanish Ministerio de Ciencia e Innovacion (MICINN), FEDER (grant number CTQ2010- 17436) and by the Gobierno de Aragon-FSE (research group E40). J. L. V.-C. also thank CONACYT for graduate scholarships.

The amidation of unactivated ethyl esters with achiral and chiral 1,2-amino alcohols under microwave irradiation and base-free conditions is described. This procedure provides a convenient method for the synthesis of β-hydroxyacetamides bearing pyrazole, imidazole, and benzimidazole groups in high yields and without racemization. The protocol described herein is environmentally friendly and allows for the preparation of a wide variety of β-hydroxyacetamides, which are key intermediates in the synthesis of oxazolines and other derivatives of biological interest.

We gratefully acknowledge CONACyT of Mexico (grant 181816), Ministerio de Economia y Competitividad (grant CTQ2013-40855-R), and Gobierno de Aragon -FSE (research group E40).

The highly stereoselective synthesis of (E)-α,β-unsaturated amides bearing (S)-a-methylbenzylamine was achieved from 2-phosphonamides via Homer-Wadsworth-Emmons reaction. The starting phosphonamides are easily prepared in two steps with excellent yields via the standard Arbuzov reaction of trimethylphosphite and α-bromoamides.

The synthesis of some monocyclic analogues of mycophenolic acid in which the lactone ring has been eliminated, leaving the aromatic ring intact and the same oxygenated substituents flanking the hexenoic acid side chain with an (E)-geometry at the double bond, has been accomplished via the Johnson ortho ester Claisen rearrangement. The synthetic methodology reported here allows the preparation of mycophenolic acid analogues bearing alkyl substituents at the alpha- and beta-positions on the side chain.

The reduction of (3S)-N,N-dibenzylamino-2-ketophosphonate 5 derived from L-leucine with catecholborane at -20 o C afford the (3S)-N,N-dibenzylamino-(2R)-hydroxyphosphonate syn-6, whereas the reduction of (3S)-N-benzylamino-2-ketophosphonate 9 with Zn(BH4)2 at -78 o C gave the (3S)-N-benzylamino-(2S)-hydroxyphosphonate anti-10. The reduction in both cases was in good chemical yields and high diastereoselectivity. The hydrolysis and hydrogenolysis of syn-6 and anti-10 gave phosphostatine 12 and phosphoepistatine 13, respectively.

The reduction of dimethyl γ-[(N-p-toluenesulfonyl)amino]-β-ketophosphonates 7a–e with different hydrides gave dimethyl γ-[(N-p-toluenesulfonyl)amino]-β-hydroxyphosphonates 9a–e and 10a–e with good chemical yield and moderated diastereoselectivity. The configuration of all new stereogenic centers were assigned by X-ray analysis and chemical correlation.

The reduction of dimethyl 3-N,N-di(α-methylbenzyl)amino-2-ketophosphonates 9 with catecholborane at −78 °C in presence of LiClO4, gave γ-amino-β-hydroxyphosphonates 10 and 11 in good yield and with excellent diastereoselectivity. This procedure represents an example of highly diastereoselective 1,4-induction. The hydrolysis and hydrogenation of 10 and 11 afforded the (R)- and (S)-γ-amino-β-hydroxypropylphosphonic acid (GABOBP), respectively.

An efficient synthesis of both enantiomers of dimethyl δ-amino-β-hydroxyethylphosphonate 6 has been achieved starting from anthranilic acid, through the resolution of dimethyl (±)-2-(2-N,N-dibenzylaminophenyl)-2-hydroxyethylphosphonate 9 with (S)-O-methylmandelic acid. The absolute configuration of the enantiomers 9 was assigned by the Dale and Mosher approach using the extended Newman projections and molecular mechanics.

The Diels–Alder reaction of enantiomerically pure (E)-γ-keto-α,β-unsaturated p-tolylsulphoxides 3 with cyclopentadiene give four easily separable diastereomers. The effect of several Lewis acids on the reaction was studied, finding a high endo selectivity with respect to the carbonyl group and moderate π-diastereoselectivity using BF3·Et2O as catalyst. The reactivity of compounds 3 as well as their endo selectivity are both higher than those observed for the corresponding (E)-3-sulfinylacrylates.

An efficient synthesis of both enantiomers of γ-amino-β-hydroxypropylphosphonic acid, an analogue of GABOB, has been achieved for the first time starting from glycine, through the resolution of dimethyl (±)-3-( N , N -dibenzylamino)-2-hydroxypropylphosphonate 7 with ( S )- O -methylmandelic acid.

Practical and high stereoselective synthesis of 3-(arylmethylene)isoindolin-1-ones is reported. The synthetic method involves the preparation of dimethyl isoindolin-1-one-3-yl-phosphonates by a ‘one-pot’ three-component reaction of 2-formylbenzoic acid with 4-methoxybenzylamine or aminoacetaldehyde dimethyl acetal and dimethyl phosphite under solvent and catalyst free-conditions, followed by a Horner reaction with several aryl aldehydes.

The reduction of γ-N,N-dibenzylamino-β-ketophosphonates 4 derived from readily available (S)-tribenzylated amino acids was achieved with catecholborane at –20°C affording γ-amino-β-hydroxyphosphonates 5 in high diastereoselectivity and good chemical yield. These reactions provide a new entry to enantiomerically pure γ-amino-β-hydroxyphosphonates.

Phenylphosphonic acid is an efficient, friendly and reusable heterogeneous catalyst for the synthesis of α-aminophosphonates through a ‘one-pot’ three-component reaction of amines, carbonyl compounds and dialkyl phosphites under solvent-free conditions. This methodology illustrates a very simple procedure, with wide applicability, extending the scope to aliphatic and aromatic amines, aliphatic and aromatic aldehydes and aliphatic ketones. It also enabled the synthesis of α-aminophosphonates in large scale, clean conversion, easy workup and purification. Excellent results were obtained in each case obtaining the desire compounds in moderate to good yields.

A series of 3-alkylideneisoindolinones (III)/(IV) are synthesized by a simple HWE reaction.

Diastereoselective nucleophilic addition of trimethyl phosphite to an N-acyliminium intermediate derived from substrate (I) gives cyclic α-aminophosphonates.

Herein we report a practical and efficient method for the synthesis of optically active 2,4-disubstituted oxazolines (S)-1a–h in good to excellent yields. The target compounds were prepared in good yield through the Horner–Wadsworth–Emmons reaction of β-phosphonoamide 3 bearing l -phenylalaninol with commercially available aryl aldehydes followed by the cyclodehydration of the corresponding N-(cinnamoyl)-(S)-phenylalaninol derivatives (S)-2a–h. Additionally, the cyclodehydration of β-phosphonoamide (S)-3 followed by the Horner–Wadsworth–Emmons reaction of β-phosphono-oxazoline (S)-4 with aryl aldehydes also gave the 2,4-disubstituted oxazolines (S)-1a–h.

The preparation of both isomers at sulphur of N -(benzyloxycarbonyl)- S -methyl (-propyl)- S -oxo- l -cysteine methyl ester has been carried out using l -cysteine and diacetone- d -glucose (DAG) as starting material and inductor of the chirality at sulphur, respectively.

Regio- and diastereoselective nucleophilic allylic substitutions of optically pure (E)-γ-acetoxy-α,β-unsaturated p-tolylsulfoxides 2 and 3 with sodium dimethyl malonate have been carried out. The reactivity of these substrates is controlled by both the chiral sulfinyl group and the size of the alkyl group attached at the γ-terminus of the allylic system. This process constitutes an example of palladium-mediated resolution of a 1:1 mixture of acetates 2 and 3.

( E )-γ-Hydroxy-α,β-unsaturated p -tolylsulfoxides 1 have been efficiently resolved via irreversible enzymatic acylation with lipase PS ( Pseudonomas cepacia ) and vinyl acetate.

The conformational preference of the diphenylphosphinoyl group at the alpha position in the thiane ring was estimated by low temperature NMR, ΔG o 173K = + 0.46 ± 0.11 kcal/mol, and at 50°C, via chemical equilibration of anancomeric models, ΔG o 323K = − 0.26 ± 0.10 kcal/mol. These thermodynamic data allowed the estimation of the enthalpic and entropic contributions to the axial equatorial conformational equilibrium of 2-(diphenyl-phosphinoyl)thiane, ΔH o = + 1.29 ± 0.12 kcal/mol, and ΔS o = + 4.8 ± 0.7 cal/K·mol. Comparison of the enthalpic S-C-P(O) anomeric effect in the thiane and 1,3-dithiane systems, 2.68 versus 3.39 kcal/mol, respectively, leads to the conclusion that no additivity of the S-C-P(O) anomeric effect takes place.

Enantioselective Diels-Alder reactions were conducted successfully using chiral magnesium complexes prepared from magnesium iodide and chiral hydroxysulfoxides derived from ( R )- and ( S )-methyl 1-naphthyl sulfoxide. Convenient methods for the preparation of these chiral sulfoxides have also been developed. Hydroxysulfoxide 6 (and its enantiomer 10 ) showed the highest enantioselectivity.