Asymmetric synthesis of β-amino acid derivatives by Michael addition to chiral 2-aminomethylacrylates

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

“…The 1,4-addition of a lithium enolate to chiral aminomethylacrylates has also been demonstrated to proceed with excellent diastereoselectivities (up to 99% ds), providing an expeditious synthesis of ␤ 2 -homoglutarate derivatives for the construction of neutral endopeptidase inhibitors in multi gram scale (up to 500 g) 223 (Scheme 39). Thus, condensation of 2-bromomethylacrylic esters with commercially available C 2 -symmetrical (S,S)-bis-phenethylamine in the presence of potassium carbonate gives the chiral acrylates, which are subsequently treated with the enolates of cyclopentanecarboxylic acid or methyl ester to afford the corresponding ␤ 2 -amino acids with almost complete diastereoselectivity.…”

The Role of an Amphiphilic Capping Group in Covalent and Non-Covalent Dipeptide Inhibitors of HCV NS3 Serine Protease

“…Compounds (2), (3), (5-7) (10) and (11) presented in Table 1 were synthesized similarly from (16) and the appropriate anhydride. Compounds (4), (12) and (9) were prepared by coupling (16) respectively with valeric acid, [1-(2-methoxy-2-oxoethyl)cyclopentyl]acetic acid and 1-(3-ethoxy-3-oxopropyl) cyclopentanecarboxylic acid [17] using EDC and HOBt as coupling reagents.…”

Asymmetric synthesis of 2-alkyl- and 2-aryl-3-aminopropionic acids (β2-amino acids) from (S)-N-acryloyl-5,5-dimethyloxazolidin-2-one SuperQuat derivatives

“…2 A variety of asymmetric syntheses have been developed for the preparation of these desirable compounds in enantiomerically enriched form, 3 with the most popular involving the stereoselective alkylation of chiral b-alanine enolate equivalents, 4 asymmetric Mannich reactions, 5 the conjugate addition of nitrogen nucleophiles 6 or the addition of carbon nucleophiles to a-methylene b-alanine derivatives. 7 We report herein our preliminary findings concerning the conjugate addition of lithium amides to N-acryloyloxazolidinones, and the utility of this methodology for the asymmetric synthesis of a range of a-substituted-b-amino acid derivatives.…”