An improved chemoenzymatic synthesis of both enantiomers of trans-cyclopentane-1,2-diamine

An improved chemoenzymatic protocol for the synthesis of both enantiomers of trans-cyclopentane-1,2-diamine is described. The key part of the strategy relies on the synthesis and subsequent enzymatic resolution of its racemic precursor trans-N,N-diallylcyclopentane-1,2-diamine in which the primary amino group is masked as a tertiary diallylamine. Lipase B from Candida antarctica (CAL-B) catalyzes the N-acylation of this diamine with excellent enantioselectivity (E >200). Further deallylation and derivatization of the enantioenriched compounds (ee ⩾ 97%) obtained in the biotransformation gave access to diversely substituted derivatives.

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(1S,2S)-N,N-Diallylcyclopentane-1,2-diamineC11H20N2Ee >99%[α]D20=+72.8 (c 0.5, CHCl3)Absolute configuration: (1S,2S)

tert-Butyl (1S,2S)-N-[2-(N′,N′-diallylamino)cyclopentyl]carbamateC16H28N2O2Ee >99%[α]D20=+23.6 (c 0.5, CHCl3)Absolute configuration: (1S,2S)

(1R,2R)-N-[2-(N′,N′-Diallylamino)cyclopentyl]acetamideC13H22N2OEe = 97%[α]D20=-21.6 (c 0.6, CHCl3)Absolute configuration: (1R,2R)