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

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 O H group at the (S)-stereogenic centre. High enantioselectivity (E=94) was o bserved when lipase PS and vinyl butyrate were used in di-iso-propyl ether at -15 degreesC, resulting in the enantiomerically enriched ester 3a and al cohol 3b (e.e. greater than or equal to 92%). Treatment of 3a and 3b with N H4OH/MeOH afforded the corresponding beta -lactams (1R,8S)-2a and (1S,8R)-2 b (e.e. greater than or equal to 93%), potential starting compounds in anat oxin-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, 3 b, 5a and 5b eight-membered cyclic beta -amino acid derivatives. (C) 2001 P ublished by Elsevier Science Ltd.