Steric and Conformational Effects in Nicotine Chemistry

Article abstract of DOI:10.1021/jo00328a010

The stereoselectivity of iodomethylation of nicotine and seven nicotine analogues having pyridine alkyl groups was determined by using 13C NMR.Alkylation at the pyridine (N) and at the pyrrolidine (N') nitrogens was observed.Two modes of N'-iodomethylation occur, cis and trans to the pyridine ring.N'-Iodomethylation occurs regioselectively cis to the pyridine ring for all compounds examined.The N/N' and N'_cis/N'_trans ratios for the nicotinoids were evaluated with regard to (1) the orientation of the N'-methyl group in the free base, (2) conformational properties of the pyridine ring with respect to the pyrrolidine ring, and (3) steric hindrance and buttressing effects on the pyridine nitrogen.The Curtin-Hammett principle and the Winstein-Holness equation are used to analyse reactions.