Stereoselective Synthesis of the Four Stereoisomers of 4-(N,N-Dibenzylamino)-2,2-dimethyl-3-hydroxypentanenitrile

Abstract

The title compounds 1(a,b) and 1(c,d) were synthesized by (i) non-chelation controlled sodium borohydride reduction of their corresponding α-N,N-dibenzylaminoketones and (ii) the Aldol-type condensation of optically pure N,N-dibenzylaminoaldehydes with the lithium derivative of isobutyronitrile, respectively. Attempted inversion of configurations of these secondary alcohols using the Moriarty method yielded 4-chloro-3-N,N-dibenzylaminonitrile via an aziridinium ion intermediate instead of the expected inverted alcohols.

Notes

The e.e-values were determined by ¹H NMR spectroscopy using (R)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetic acid (Mosher's acid) as a chiral solvating agent.