Convenient preparation of optically active cibenzoline and analogues from 3,3-diaryl-2-propen-1-ols

(R)-(+)-Cibenzoline (95% ee) was synthesized in two steps from (+)-2,2-diphenylcyclopropylmethanol 3a (98% ee), which was oxidized with IBX in DMSO, followed by treatment with ethylenediamine in the presence of I-2 and K2CO3 in tBuOH. Compound (R)-(+)-3a (98% ee) was prepared by cyclopropanation of 3,3-diphenyl-2-propen-1-ol 1 with Et2Zn and CH2I2 in the presence of a catalytic amount of (S)-2-(methanesulfonyl)amino-1-(p-toluenesulfonyl)amino-3-phenylpropane 2, followed by esterification with 3,5-dinitorobenzoyl chloride, recrystallization, and hydrolysis. (C) 2009 Elsevier Ltd. All rights reserved.