A 4+3 cycloaddition/quasi-Favorskii rearrangement approach to the total synthesis of sterpurene.

摘要

The area of 4+3 cycloaddition reactions has provided a direct and convenient route to seven-membered and polycyclic fused rings. Using this methodology along with the quasi-Favorskii rearrangement fused polycycles can be rapidly created. It was found that only one equivalent of a rigid diene is needed in the 4+3 cycloaddition with 2,5-dibromocyclopentanone. Subsequent quasi-Favorskii rearrangement of the cycloadduct led to the compound containing a 4/6/5 fused ring system. Expanding on this methodology led to an efficient synthesis of the unnatural product, isosterpurene. Isosterpurene differs from the natural product, sterpurene, by a single stereocenter. The sterpurene precursor has an inherent facial selectivity that was overcome by the reduction of an α-β unsaturated tosylhydrazone which formed the desired stereocenter through the intramolecular delivery of a hydride. The total synthesis of sterpurene was achieve in a 6% overall yield for 13 steps.; In the study of heteroatom stabilized 4+3 cycloaddition reactions, two alcohols cyclized with unprecedented high simple diastereoselection, affording 4+3 cycloadducts in good yield.