Synthetic and structural studies of key intermediates toward forskolin and/or erigerol. Relative stereochemistry, conformational preferences and stereoselectivity control

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Abstract
An alternative stereoselective synthesis of compound 9c, an intermediate in the synthesis of the highly oxygenated diterpene erigerol 2, was accomplished through an organometallic addition to the α,β-unsaturated ketone 7, followed by osmylation and protection of the resultant diol. In spite of the fact that the addition of the Iithio derivative of N,S-dimethyl-S-phenylsulfoximide occurred exclusively from the β face of enone 7, this approach to the alcohol 8c, a key intermediate toward forskolin 1, is not suitable because of the low yield of the osmylation step. With the aid of one- and two-dimensional NMR techniques and a series of NOE experiments, the complete stereochemistry and conformational preferences of alcohols 8a, 8c, 9a and 9c were established. The lowest-energy conformations of alcohols 8a, 8c and 9c, based on molecular mechanics calculations, confirmed the results obtained by NMR spectroscopy.