Atroposelective Total Synthesis of (+)‐Isokotanin A via Combined Metal and Enzyme Catalysis

Abstract

AbstractIn this report a new atroposelective total synthesis of (+)‐isokotanin A is described. The combination of metal‐ and enzyme catalysis facilitates a scalable route towards the key axially chiral 2,2′‐biphenol building block. We established a one‐pot Miyaura‐Suzuki homocoupling towards the tetra‐ortho‐substituted biphenol on a decagram scale, applying Buchwald's precatalyst PdG4SPhos and SPhos in low loadings. Next, an enzymatic kinetic resolution method was achieved by utilizing commercially available Candida rugosa lipase for catalyzing the enantioselective hydrolysis of biphenyl dipropionate. The enantiomerically pure tetra‐ortho‐substituted biphenol was converted in 8 steps to the natural product.