Total Synthesis of (+/-)-Tremulenolide A and (+/-)-Tremulenediol A via a Stereoselective Cyclopropanation/Cope Rearrangement Annulation Strategy

Abstract

Short total syntheses of (+/-)-tremulenolide A (1) and (+/-)-tremulenediol A (2) are described. The critical step is a dirhodium tetracarboxylate-catalyzed tandem cyclopropanation/Cope rearrangement between the vinyldiazoacetate 4 and the 2(Z),4(E)-hexadiene 5. This step results in full control of the relative stereochemistry at the three stereogenic centers that exist in the natural products. Due to problems with alkene face selectivity, the approach was not amenable to an efficient asymmetric synthesis of 1 and 2.