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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).

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.

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).

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.

This work was carried out with the financial support of CONACYT of Mexico (project 62271), FOSISS-10-ST-564, Ministerio de Educacion y Ciencia-FEDER (project CTQ2010-17436), Gobierno de Aragon (group E40) and bilateral proyect CONACYT-CSIC (project J000.400/2009 and 2008MX0044).

Aliphatic and aromatic aldehydes react with benzylamine and dimethyl phosphite within a short time to give the title compounds in good to excellent yields.

A three-component reaction of o-formylbenzoic acid, primary amines and dimethyl phosphite constitutes an efficient synthesis of isoindolinone phosphonates, which readily undergo dephosphorylation with LiAlH4.

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.

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.

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.

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 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 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 addition of Et 2 AlCN in the presence of ZnBr 2 or Et 2 AlCl to 1,3-dicarbonyl compounds derived from ( S )-4-isopropyl-2-oxazolidinone, proceeds with high diastereoselectivity (94–98% de) and good chemical yields. This type of addition to chiral β-dicarbonyl substrates represents a new synthetic methodology leading to the formation of enantiomerically pure cyanohydrins.

( 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.