Total Synthesis of (+)‐Machaeriol D with a Key Regio‐ and Stereoselective SN2′ Reaction

A general strategy for the synthesis of hexahydrodibenzopyrans (HHDBPs) is illustrated in the enantioselective total synthesis of (+)-machaeriol D. In the key step, an SN2′ reaction of an aryl cyanocuprate with a silyl enol ether of an optically active α,β-epoxycyclohexanone enabled the construction of the four stereocenters of the natural product with high regio- and stereoselectivity (see scheme; R=methoxymethyl). TMS=trimethylsilyl, TBS=tert-butyldimethylsilyl.