SYNTHESIS OF Α-Hydroxytamoxifen AND ITS 4-Hydroxy ANALOG

Photoredox-Catalyzed C–H Arylation of Internal Alkenes to Tetrasubstituted Alkenes: Synthesis of Tamoxifen

“…First, α-acetyl ketene di­(methylthio)­acetal ( 1n ) was transformed to 1,1- S,S -functionalized tetrasubstituted alkene 4a (Scheme ), which was then successively arylated by PhB­(OH) 2 and 4-(2-dimethylaminoethoxy)­phenylboronic acid through Liebeskind–Srogl cross-coupling, affording 6b and 11 in 87% and 63% yields, respectively (Scheme ). Luche reduction of 11 gave tamoxifen analogue 12 in 58% yield (( Z )- 12 , 29%; ( E )- 12 , 29%), and subsequent dehydration/hydrogenation yielded tamoxifen ( 13 ) in 75% yield ( Z / E = 1.4/1). An alternative route was also developed for the transformation of alkenes 1 to all-carbon tetrasubstituted alkenes.…”