Chemoenzymatic preparation of enantiopure homoadamantyl β-amino acid and β-lactam derivatives

Racemic cis-10-azatetracyclo[7.2.0.12,6.14,8]tridecan-11-one was prepared from homoadamant-4-ene by chlorosulfonyl isocyanate addition. The transformation of the β-lactam to the corresponding β-amino ester followed by Candida antarctica lipase A-catalyzed enantioselective (E>>200) N-acylation with 2,2,2-trifluoroethyl butanoate afforded methyl (1R,4R,5S,8S)-5-aminotricyclo[4.3.1.13,8]undecane-4-carboxylate and the (1S,4S,5R,8R)-butanamide with>99% ee at 50% conversion. Alternatively, transformation of the β-lactam to the corresponding N-hydroxymethyl-β-lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase-catalyzed enantioseletive O-acylation provided the (1S,4S,6R,9R)-alcohol (ee=87%) and the corresponding (1R,4R,6S,9S)-butanoate (ee>99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)-butanoate, 2,2,2-trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)-alcohol with time.