Stereoselective cyclopropanation and ring-opening: Application to the synthesis of pure (S)-2-methyl-3-arylpropylamines

Article abstract of DOI:10.1016/S0040-4020(98)00549-3

Stereoselective catalytic and stoichiometric cyclopropanation of styrenes 3a,3b was studied; the stoichiometric method turned out superior in the terms of enantioselectivity. The intermediate carboxymethyl cyclopropane 11a,11b, obtained on reduction of carbethoxy derivatives 4a,4b, were hydrogenolyzed to (S)-1,3-substituted-2-methylpropanes 15a,15b. The highest conversion and regioselectivity was obtained with 3% Pd/C as the catalyst. The final steps, chlorination of alcohol 15a into 19a, and alkylation of cyclic sec amines were already demonstrated by us (ref. 2c) to afford (S)-(- )-2-(4-tert-butylphenyl)-1-cis-2,6-dimethylmorpholyl)propane (S-1a) and (S)- (-)-2-(4-tert-butylphenyl)-1-piperidylpropane (S-2a), the (S)-enantiomers of two systemic fungicides presently commercialized as racemates, without any lost of enantiomeric purity.