Racemic synthesis of 2′-substituted nicotine analogs

The chemical and pharmacological properties of 2′-substituted nicotines are poorly understood relative to other substituted nicotines. We developed a practical synthesis of the key intermediate (±)-2′-cyanonicotine using the Polonovski reaction. Alkylation of (±)-2′-cyanonicotine with Grignard reagents led to several 2′-alkylnicotines; (±)-2′-aminomethylnicotine, (±)-2′-hydroxymethylnicotine, and (±)-2′-carbamoylnicotine were also synthesized. J. Heterocyclic Chem., (2012).