A novel enantioselective synthesis of (S)-(-)- and (R)-(+)-nornicotine viaalkylation of a chiral 2-hydroxy-3-pinanone ketimine template

An asymmetric synthesis of the optically pure isomers of the minor tobacco alkaloid and CNS nicotine metabolite, nornicotine, has been achieved with m oderately high optical purity. The synthetic pathway involves alkylation of a chiral ketimine, prepared from either 1R,2R,5R-(+)- or 1S,2S,5S-(-)-2-hy droxy-3-pinanone and 3-(aminomethyl) pyridine with 3-bromopropan-1-ol. Afte r cleavage of the respective C-alkylated ketimines with NH2OH . HCl, and tr eatment of the resulting amino alcohols with HBr, followed by base-catalyze d intramolecular ring closure, (S)-(-)-nornicotine and (R)-(+)-nornicotine were obtained with ee values of 91% and 81%, respectively. Chirality 11:316 -318, 1999. (C) 1999 Wiley-Liss, Inc.