Recently, we reported the cyclization reaction of 2-alkynylphenyl alkyl sulfoxides catalyzed by mercury chloride that turn out to be a more efficient way to construct 3-benzoyl benzo[b]thiophenes.[1] Herein, we wish to report our application of this methodology to synthesize raloxifene (1) and compound 2 through the key intermediate, 4-methoxybenzyl 2-bromo-4-methoxyphenyl sulfoxide (3), respectively.[2] It was found that the sulfinyl group at ortho position could accelerate the Sonogashira coupling reaction of aryl bromides. Thus, compound 6 was coupled with 3,4,5-trimethoxyphenyl acetylene, followed by mercury-catalyzed cyclization reaction afford compound 2 in 79% overall yield. Raloxifene (1) was also prepared starting from compound 3 in four steps and 33% overall yield via coupling reaction with 1-trimethylsily-2-(4-tert-butyldimethylsiloxy)phenylethyne, mercury-catalyzed cyclization reaction, alkylation and demethylation.

Efficient synthesis of 3-benzoyl benzo[b]thiophenes and raloxifene via mercury(II)-catalyzed cyclization of 2-alkylphenyl alkyl sulfoxides

2019 Fall National Meeting

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