Enantiospecific Total Synthesis of the Highly Strained (-)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization

Pengfei Hu; Scott A Snyder

doi:10.1021/jacs.7b01454

Enantiospecific Total Synthesis of the Highly Strained (-)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization

J Am Chem Soc. 2017 Apr 12;139(14):5007-5010. doi: 10.1021/jacs.7b01454. Epub 2017 Mar 29.

Authors

Pengfei Hu^{1

2}, Scott A Snyder^{1

2}

Affiliations

¹ Department of Chemistry, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
² Department of Chemistry, University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.

PMID: 28355073
DOI: 10.1021/jacs.7b01454

Abstract

A rare element of high strain in molecules of natural origin is a 1,2-trans fusion of 5-membered rings within a [3.3.0]-bicycle, a motif present in (-)-presilphiperfolan-8-ol. This molecule also possesses a 1,3-trans stereochemical arrangement of substituents on one of its 5-membered rings, a pattern shared by a number of other terpenes. Herein, we disclose the first total synthesis of this highly strained target in 13 steps. The key operation is a Pd-catalyzed tandem cyclization that directly establishes the requisite 1,3-trans stereochemical arrangement on one ring while concurrently setting the stage for the controlled generation of the highly strained 1,2-trans ring fusion of the final architecture.