From C-Glycosides to Pyranopyrans: An Approach to Thyrsiferol Using Titanium(III)-Promoted Redox Couplings

J. Org. Chem., 70 (13), 5249 -5256, 2005. 10.1021/jo050465d S0022-3263(05)00465-2
Web Release Date: June 1, 2005

From C-Glycosides to Pyranopyrans: An Approach to Thyrsiferol Using Titanium(III)-Promoted Redox Couplings

Gisele A. Nishiguchi and R. Daniel Little*

Department of Chemistry & Biochemistry, University of California, Santa Barbara, California 93106

little@chem.ucsb.edu

Received March 9, 2005

Abstract:

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

-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

-bond formed in this process corresponds to the pro-C₉-C₁₀ bond of thyrsiferol (4). Attempts to invert the stereochemistry at the pro-C₁₁ 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.

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