Synthetic Studies on Aphidicolane and Stemodane Diterpenes. IV.A Stereoselective Formal Total Synthesis of (±)-Aphidicolin

Abstract

A formal total synthesis of (±)-aphidicolin (1) was accomplished starting from the tricyclic ketone (2)corresponding to the B/C/D ring system. The quaternary carbon center adjacent to the spirocarbon was constructed stereoselectively by conjugate addition of a methyl group to the enone (7) obtained from 2 in a four-step sequence.The tetracyclic enone (3) was obtained via acid-catalyzed intramolecular aldol condensation of the tricarbonyl compound (10) followed by 1, 3-carbonyl transposition, in which Pd(0)-catalyzed reductive deacetoxylation of γ-acetoxy-α, β-enone (15) was a crucial step. The A-ring manipulation was performed by a similar procedure to the Ireland method to give the keto-acetonide (4), a degradation product of 1, which has already been efficiently reconverted to 1.