Asymmetric syntheses via heterocyclic intermediates, XL. Studies on the acylation of lithiated bislactim ethers of cyclo(‐L‐Val‐Ala‐) and cyclo(‐L‐Val‐Gly‐) Asymmetric synthesis of (R)‐α‐alkenyl and (R)‐α‐ethinyl alanine methyl esters by the bislactim ether method

Abstract

AbstractThe lithiated bislactim ether 2a of cyclo(‐L‐Val‐Ala‐) reacts with acyl chlorides 3 highly diastereoselectively to yield the compounds 4. with (2S,5S)‐configuration. With acetyl chloride (3a) the N‐acetyl compound 7 is formed as a sideproduct. Alternatively, the compounds 4 can be obtained by oxidation of the carbinols 8. From 4a and b, the olefins 11a and b are obtained by Wittig reaction. These are precursors of methyl (R)‐α‐alkenyl alanine methyl esters of type 13. (R)‐α‐ethinyl alanine methyl ester 17 is obtainable from 4a and 4c via the intermediates 14 or 15 and 16a. The lithiated bislactim ether 2c of cyclo(‐L‐Val‐Gly‐) reacts with benzoyl chloride (3b) to give the „bis adduct”︁ 18. However, 6b is obtained from 2c and the benzamide 19, though as a 1:1 diastereomeric mixture. Presumably, 6b epimerizes via the enol 21a subsequently to its diastereoselective formation.