Chemoenzymatic enantioselective synthesis of 7-azabicyclo[2.2.1]heptane derivatives

The enantioselective acylation (desymmetrization) of meso-7-azabicyclo[2.2.1]heptanediol 2 by vinyl acetate in the presence of Candida antarctica lipase B gave the corresponding (1R,2R,3S,4S)-monoester 4 in high enantiomeric purity (ee ⩾ 98%).

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(1R,2R,3S,4S)-2-(Acetoxymethyl)-3-(hydroxymethyl)-7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptaneC15H25NO5Ee ⩾ 98% (NMR)Source of chirality: enzymatic desymmetrization[α]D20=-8.4 (c 0.5, CHCl3)Absolute configuration: (1R,2R,3S,4S)

(1R,2R,3S,4S)-2-(Acetoxymethyl)-3-(tosyloxymethyl)-7-azabicyclo[2.2.1]heptane hydrochlorideC17H23NO5S·HClEe ⩾ 98% (NMR)Source of chirality: enzymatic desymmetrization[α]D20=-1.3 (c 2.34, MeOH)Absolute configuration: (1R,2R,3S,4S)