Total synthesis of (+)-scyphostatin featuring an enantioselective and highly efficient route to the side-chain via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)

Abstract

(+)-Scyphostatin (1) was synthesized via (i) construction of a side-chain 3b of > or = 98% purity in 19% yield in eleven steps featuring ZACA reaction, Negishi coupling, and HWE olefination, (ii) an asymmetric synthesis of a fully protected core 4 from 10a, and (iii) a three-step assembly of 1 in 42% yield.