Regioselective Synthesis Using the Deuterium Isotope Effect

Article abstract of DOI:10.1021/jo00322a022

Dehydration of 1a by various procedures invariably produced more exo olefin 2a than endo olefin 3a.This could be reversed by introduction of deuterium in the Me-21 group of the starting material.Thus, dehydration of 1b could afford more endo olefin 3b than exo olefin 2b due to the deuterium isotope effect.A regioselective synthesis of 18-oxoprogesterone (15a) from 3β-hydroxypregn-5-en-20-one (5a) was carried out taking advantage of the deuterium isotope effect as depicted in Scheme I.The key steps were dehydration of 7b to predominantly endo olefin 9b and removalof the deuteriums from 18-oxoprogesterone-17α,21,21,21-d4 (15b) to give 15a.