Total Synthesis of Thromboxane B 2 via a Key Bicyclic Enal Intermediate.

A 12-step asymmetric synthesis of thromboxane B-2(TxB(2)) from 2,5-dimethoxytetrahydrofuran is described. The synthesis employs our organocatalytic aldol reaction of succinalde-hyde to give a key bicyclic enal intermediate. From here, the synthetic strategy involves a conjugate addition of an alkenyl side chain to the bicyclic enal, Baeyer-Villiger oxidation, and a highly Z-selective Wittig olefination of a hemiacetal. Key to success was minimizing redox operations and the manipulation of functional groups in the correct order.