Halocarbocyclization Entry into the Oxabicyclo[4.3.1]decyl Exomethylene-δ-Lactone Cores of Linearifolin and Zaluzanin A - Exploiting Combinatorial Catalysis

Authors

Sandeep K. Ginotra, University of Nebraska - Lincoln
Jacob A. Friest, University of Nebraska - Lincoln
David B. Berkowitz, University of Nebraska - LincolnFollow

Date of this Version

2-17-2012

Citation

Org Lett. 2012 February 17; 14(4): 968–971. doi:10.1021/ol203088g.

Comments

Copyright 2012. Used by permission.

Abstract

A streamlined entry into the sesquiterpene lactones (SQL) cores of linearifolin and zaluzanin A is described. Stereochemistry is controlled through transformations uncovered by ISES (In-Situ- Enzymatic-Screening). Absolute stereochemistry derives from kinetic resolution of 5- benzyloxypentene-1,2-oxide, utilizing a β-pinene-derived-Co(III)-salen. Relative stereochemistry (1,3-cis-fusion)is set via formal halometalation/carbocyclization, mediated by [Rh(O₂CC₃F₇)₂]₂/ LiBr. Subsequent ring-closing metathesis (RCM-Grubbs II) yields the title exomethylene-δ- lactone SQL-cores. In complementary fashion, RCM with Grubbs-I catalyst provides the oxabicyclo[3.3.1]nonyl-core of xerophilusin R and zinagrandinolide.