.alpha.-Amino acids as chiral educts for asymmetric products. The synthesis of .alpha.'-amino-.alpha.,.beta.-ynones

Abstract

ct-Amino acid isoxazolidides have been developed as educís for the preparation of optically pure a'-amino-,ß-ynones. The -amino acids were first N-protected as their ethoxycarbonyl, tert-butoxycarbonyl, or phenylsulfonyl derivatives. The isoxazolidides then were formed by the simple, high yield acylation of isoxazolidine by in situ generated -amino acid isobutyl carbonic anhydrides. Individual isoxazolidides of L-a-N-substituted alanine, phenylalanine, and methionine, when treated with lithium acetylide, lithium (trimethylsilyl)acetylide, or 1-hexynyllithium, gave high yields of the corresponding optically pure a,(¡-acetylenic ketones.

Alkylation of α-tert-butoxycarbonylamino ketone enolate anions. A useful synthesis of α-alkyl-α-amino ketones, 2-acylpyrrolidines, and 2-acylpiperidines

“…A particular advantage of this process is that one substrate can serve as the progenitor of many new a-alkyl-a-amino ketones. This desirable characteristic is also found in the generation of such compounds based on the reaction of alkyl Grignard or alkyllithium reagents with N-protected a-amino acids (1 1-14) or with N-protected 0,N-dialkyl-a-amino acid hydroxamates (15,16) but is absent in many previously reported syntheses (e.g., see ref. 1 pp.…”

Recent advances in the synthesis of polysubstituted 3-pyrazolidinones

“…Under these optimized conditions, the conversion of 41a was complete after 12 hours and the cycloadduct 66a was isolated in 98% yield upon chromatographic workup. Cycloadditions of racemic azomethine imines 41a-c,f,g to tert-butyl (S)-(3-oxopent-4-yn-2-yl)carbamate (67) [78][79][80] under the above conditions afforded mixtures of diastereomeric cycloadducts 68a-c,f/68′a-c,f and 69g/69′g in 68-95% yields. Subsequently, diastereomers 68a-c,f/68′a-c,f and 69g/69′g were separated by medium-performance liquid chromatography (MPLC) to furnish diastereomerically pure non-racemic compounds 68a-c,f, 68′a-c,f, 69g, and 69′g in 3-45% yields.…”

Amino acid chlorides: a journey from instability and racemization toward broader utility in organic synthesis including peptides and their mimetics

“…producing largely the corresponding tertiary alcohol 209. 93,249,259 Scheme 51. Synthesis of α-amino acid isoxazolidides and α'-amino-α,β-ynones.…”