ENANTIOSELECTIVE SYNTHESIS OF 2-SUBSTITUTED 5-MEMBERED, 6-MEMBERED AND 7-MEMBERED LACTAMS VIA ALPHA-ALKYLATION OF THEIR CHIRAL N-DIALKYLAMINO DERIVATIVES

2-Alkyl-substituted lactams 4 were synthesized in good overall yields and high enantiomeric purities (ee = 71-99%) by alpha-alkylation of ch iral N-(dialkylamino)lactams 2 and subsequent reductive N-N bond cleav age of the resulting lactams 3 with lithium in liquid ammonia. The lac tams 2, in turn, were prepared in good yields by cyclization of omega- chloroalkanohydrazides 1 with sodium hydride. Acidic hydrolysis of lac tams 4 leads to gamma-aminobutanoic acid (GABA) derivatives 5 (ee grea ter than or equal to 99%). The absolute configuration was determined b y polarimetry and an X-ray structure analysis of (S,S)-3e'.