Preparation of 8-Alkyl-14-hydroxydihydrocodeinones

Article abstract of DOI:10.1021/jo00333a015

Reaction of 14-<(trimethylsilyl)oxy>codeinone (1b) with lithium dimethylcuprate gave a 2:1 isomeric mixture of the corresponding 8α-methyl (2) and 8β-methyl (3) 14-(trimethylsilyl)oxydihydro derivatives.Selective removal of the silyl group from α isomer 2 to give 4, by use of silica gel, allowed resolution of the mixture. 8β-Methyl-14-hydroxydihydrocodeinone (5) was prepared from 3 by cleavage of the silyl ether with n-Bu4NF.Treatment of 14-hydroxycodeinone with Me2CuLi gave a 4:1 mixture of alkylated products 4 and 5.The (tert-butyldimethylsilyl)oxy ether 1c under similar conditions gave exclusively the stable 8α isomer 6.Reaction of trimethylsilyl compound 1b with Et2CuLi or n-Bu2CuLi gave approximately equal amounts of the corresponding 8-alkyl 14-O-silylated isomers.These results are in contrast to previous work with codeinone which demonstrated that lithium organocopper reagents add almost exclusively to the β face of "T-shaped" morphinone derivatives.