Enantioselective synthesis of 2-substituted 5-, 6- and 7-membered lactams via α-alkylation of their chiral N-dialkylamino derivatives

Article abstract of DOI:10.1055/s-1996-4443

2-Alkyl-substituted lactams 4 were synthesized in good overall yields and high enantiomeric purities (ee = 71-99%) by α-alkylation of chiral N-(dialkylamino)lactams 2 and subsequent reductive N-N bond cleavage of the resulting lactams 3 with lithium in liquid ammonia. The lactams 2, in turn, were prepared in good yields by cyclization of ω-chloroalkanohydrazides 1 with sodium hydride. Acidic hydrolysis of lactams 4 leads to γ-aminobutanoic acid (GABA) derivatives 5 (ee ≤ 99%). The absolute configuration was determined by polarimetry and an X-ray structure analysis of (S,S)-3e'.