Catalytic asymmetric Claisen rearrangement of Gosteli-type allyl vinyl ethers: total synthesis of (-)-9,10-dihydroecklonialactone B

J Org Chem. 2014 Apr 4;79(7):3040-51. doi: 10.1021/jo5001466. Epub 2014 Mar 12.

Abstract

The enantioselective synthesis of (-)-9,10-dihydroecklonialactone B is described. The catalytic asymmetric Claisen rearrangement of a Gosteli-type allyl vinyl ether was utilized to afford an acyclic α-keto ester building block endowed with functionality amenable to the preparation of the carbocyclic target molecule by suitable postrearrangement transformations: A highly diastereoselective Corey-Bakshi-Shibata reduction of a β-chiral α-keto ester and a reductive homologation of an α-hydroxy ester. A transprotection tactic by a chemoselective intramolecular 6-exo-trig iodoetherification enabled regioselective ring-closing alkene metatheses to afford the 5- as well as the 14-membered ring, however, with mixed success in terms of E/Z selectivity.