On the regio- and stereoselectivity of pyridinyl radical dimerization

Abstract

The present work was carried out in order to elucidate the combined effects of the electron spin density on the ring carbons and the steric hindrance of the ring substituents upon the regio- and stereoselectivity of the dimerization of 3-carbamoyl- and 3-cyanopyridinyl radicals. To this purpose the composition of mixtures of diastereoisomeric dimers arising from the one-electron electrochemical reduction of several 3-carbamoyl and 3-cyano substituted pyridinium salts has been studied by ¹H NMR spectroscopy. In some cases, single diastereoisomers have been isolated from mixtures by preparative HPLC.

The results show that: (a) hindering steric effect of substituents at coupling sites prevails over electron spin density on coupling carbons in governing regioselectivity of 3-carbamoylpyridinyl radical dimerization; (b) large bulky N-ring substituents produce a significant shielding effect on the adjacent dimerization site; (c) the relative amounts of diastereoisomers in the mixtures of 4,4′- and 6,6′-linked dimers indicate that the dimerization process is largely stereoselective; (d) otherwise, nearly equal amounts of 4,4′- and 4,6′-linked dimers, and relative diastereoisomers as well, arise from the reduction of 3-cyano substituted pyridinium salts. This finding indicates that the presence of the carbamoyl substituent at the 3 position is a primary factor in inducing the regio- and stereoselectivity of pyridinyl radical dimerization.