Synthesis of the non-adjacent bis(tetrahydrofuran) core of squamostanin C by silicon-tethered, size-selective triple ring-closing metathesis

Abstract

Synthesis of the C2-symmetric, non-adjacent bis(tetrahydrofuran) core of squamostanin C in seven steps and 24% overall yield from (R,R)-1,5-hexadiene-3,4-diol is reported. Silicon-tethered, size-selective triple ring-closing metathesis of an acyclic hexaene is employed for assembly of the central 1,4-diol unit and concurrent chain extension via lactone formation. Stereoselective construction of both tetrahydrofuran rings is achieved in one step through the use of two-directional Mukaiyama aerobic alkenol cyclization.