Organocuprate-Mediated Methods for the Stereospecific Introduction of Steroid Side Chains at C-20

Article abstract of DOI:10.1021/jo00157a002

The reactions of organocuprates with various Δ¹⁷⁽²⁰⁾-unsaturated steroid substrates leads to the stereocontrolled introduction of the side chain onto the steroid nucleus to give either desired C-20 epimer.The reaction of an E-Δ¹⁷⁽²⁰⁾-16-keto steroid with lithium diisohexylcuprate leads to α-face attack, giving exclusively a product having the "natural" 20R chirality.This product was then converted to cholesterol.The reactions of either the E-Δ¹⁷⁽²⁰⁾-16α-pivaloyloxy or the corresponding 16β-pivaloyloxy steroid with lithium isohexylcyanocuprate each proceeded in a regio- and stereocontrolled manner.The former (16α) compound gave exclusively the "unnatural" 20S chirality while the latter (16β) compound gave exclusively the "natural" 20R chirality.The 20S compound was converted to 20-epicholesterol, and similarly, the 20R compound was converted to cholesterol.A result complementary to that of the pivalates ensued from the E-Δ¹⁷⁽²⁰⁾-16α-N-phenylcarbamoyl steroid, which was converted by the action of a presumed internal mixed cuprate to a compound having 20R chirality.