From C-glycosides to pyranopyrans: An approach to thyrsiferol using titanium(III)-promoted redox couplings

Article abstract of DOI:10.1021/jo050465d

An approach to the pyranopyran ring system that is found in many natural products, including thyrsiferol, is described. The route entails the assembly of an α,β-unsaturated ketone (11) from geraniol and dihydropyran (23) from acetyl acetaldehyde dimethyl acetal (19) and their titanium-(III)-promoted coupling to afford a respectable 60% yield of keto alcohol 26. The σ-bond formed in this process corresponds to the pro-C₉-C₁₀ bond of thyrsiferol (4). Attempts to invert the stereochemistry at the pro-C ₁₁ center were thwarted by the congestion imparted by the presence of the vicinal TBS-ether. Consequently, cyclization of the coupling adduct under conditions developed by Olah and Prakash and co-workers led to the cis-fused pyranopyran 27. X-ray analysis of this crystalline material confirmed each of the stereochemical assignments. After much effort, it was determined that the hydroxyl group at C₁₂ could be removed by treating the derived methyl xanthate with a tri-n-butylphosphine-borane complex under radical-forming conditions. The reaction sequence worked well, despite the hindered working environment and the presence of a potentially labile C-Br bond.