Chemoenzymatic synthesis of enantiopure geminally dimethylated cyclopropane-based C2- and pseudo-C2-symmetric diamines

Enantiopure (−)-(1S,3S)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxamide 2 and (+)-(1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylic acid 3 were easily obtained from a multigram scale biotransformation of racemic amide or nitrile in the presence of Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions. Coupled with efficient and convenient chemical manipulations, comprising mainly of the Curtius rearrangement, oxidation, and reduction reactions, chiral C2-symmetric (1S,2S)-3,3-dimethylcyclopropane-1,2-diamine 6 and ((1R,3R)-3-(aminomethyl)-2,2-dimethylcyclopropyl)methanamine 8 and pseudo-C2-symmetric (1S,3S)-3-(aminomethyl)-2,2-dimethylcyclopropanamine 11 were prepared. These were also transformed into the corresponding chiral salen derivatives 12, 13, and 14, respectively, in almost quantitative yields.

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C21H20N2O2Ee >99%[α]D25=-40 (c 1.0, CH2Cl2)Source of chirality: chemoenzymatic synthesisAbsolute configuration: (1R,2R)

C20H18N2O2Ee >99%[α]D25=+16 (c 1.5, CH2Cl2)Source of chirality: chemoenzymatic synthesisAbsolute configuration: (1S,3S)

(1S,2S)-3,3-Dimethylcyclopropane-1,2-diamine dihydrochlorideC5H14N2Cl2Ee >99%[α]D25=+5.5 (c 1.0, CH3OH)Source of chirality: chemoenzymatic synthesisAbsolute configuration: (1S,2S)

((1R,2R)-3,3-dimethylcyclopropane-1,2-diyl) dimethanamine dihydrochlorideC7H18N2Cl2Ee >99%[α]D25=-5 (c 1.0, CH3OH)Source of chirality: chemoenzymatic synthesisAbsolute configuration: (1R,2R)

(1S,3S)-3-(Aminomethyl)-2,2-dimethylcyclopropanamineC6H16N2Cl2Ee >99%[α]D25=-6 (c 1.0, CH3OH)Source of chirality: chemoenzymatic synthesisAbsolute configuration: (1S,3S)

C19H16N2O2Ee >99%[α]D25=+560 (c 1.0, CHCl3)Source of chirality: chemoenzymatic synthesisAbsolute configuration: (1S,2S)