Short Enantioselective Total Syntheses of trans-Clerodane Diterpenoids: Convergent Fragment Coupling Using a trans-Decalin Tertiary Radical Generated from a Tertiary Alcohol Precursor.

Abstract

The evolution of a convergent fragment-coupling strategy for the enantioselective total synthesis of trans-clerodane diterpenoids is described. The key bond construction is accomplished by 1,6-addition of a trans-decalin tertiary radical with 4-vinylfuran-2-one. The tertiary radical is optimally generated from the hemioxalate salt of the corresponding tertiary alcohol upon activation by visible light and an Ir(III) photoredox catalyst. The enantioselective total synthesis of trans-clerodane diterpenoid 1 reported here was accomplished in seven steps from 3-methyl-2-cyclohexenone. The synthetic strategy described in this report allows a number of trans-clerodane diterpenoids to be synthesized in enantioselective fashion by synthetic sequences of 10 steps or less. This study illustrates a powerful tactic in organic synthesis in which a structurally complex target structure is disconnected at a quaternary carbon stereocenter to fragments of comparable complexity, which are united in the synthetic pathway by conjugate addition of a nucleophilic tertiary radical to a fragment harboring an electron-deficient C-C double bond.