Phorboxazole Synthetic Studies. 2. Construction of a C(20−28) Subtarget, a Further Extension of the Petasis−Ferrier Rearrangement

Abstract
In this, the second of two Letters, we describe the efficient assembly of (+)-4, a C(20−28) subtarget for the total synthesis of phorboxazoles A (1) and B (2). The synthesis was achieved in 12 linear steps (20% overall yield) via Petasis−Ferrier rearrangement of an E/Z mixture of trisubstituted enol ethers (15) to assemble the C(22−26) cis-tetrahydropyran. A mechanism for the observed diastereoconvergence of 15 is proposed. In addition, a new tactic for the synthesis of enol ethers (e.g., 15) based on the elegant work of Julia is described.