Preparation of (1 R,8 S)- and (1 S,8 R)-9-azabicyclo[6.2.0]dec-4-en-10-one: potential starting compounds for the synthesis of anatoxin -a

Abstract

9-Azabicyclo[6.2.0]dec-4-en-10-one (±)- 2, obtained from cyclooctadiene by addition of chlorosulfonyl isocyanate, was N-hydroxymethylated to (±)- 3 and then resolved by lipase-catalysed asymmetric acylation of the primary OH group at the ( S)-stereogenic centre. High enantioselectivity ( E=94) was observed when lipase PS and vinyl butyrate were used in di- iso-propyl ether at −15°C, resulting in the enantiomerically enriched ester 3a and alcohol 3b (e.e. ≥92%). Treatment of 3a and 3b with NH 4OH/MeOH afforded the corresponding β-lactams (1 R,8 S)- 2a and (1 S,8 R)- 2b (e.e. ≥93%), potential starting compounds in anatoxin- a synthesis. The ring opening of lactams (±)- 2, (±)- 7, 3a and 3b, followed by reduction, resulted in racemic 4– 6 and 8 and enantiomeric 4a, 4b, 5a and 5b eight-membered cyclic β-amino acid derivatives.