TsOH-catalyzed dehydroxylative cross-coupling of alcohols with phenols: rapid access to propofol derivatives

Modification of the parent structure of molecules often alters their physicochemical properties and biological activities. Herein, a practical, efficient, and highly regioselective C-H alkylation of phenols with alcohols via dehydroxylative cross-coupling was developed to produce para-alkylated phenols with excellent regioselectivities and yields, using which propofol derivatives were rapidly synthesized. This process is performed under mild and simple conditions and is well-compatible with a variety of alcohols (secondary and tertiary benzylic alcohols as well as allyl alcohols) as alkylated agents. In addition, high aryl ether derivatives were also obtained using this catalytic system.