Controlled diastereoselection in 2-lithio-1,3-dithiane additions onto α-substituted γ-lactols. Model studies toward bryostatins from (R)-pantolactone

Abstract

Homochiral α-substituted γ-lactols 3 and 4 derived from (R)-pantolactone 1 were used in 2-lithio-1,3-dithiane additions to afford very high controls in diastereoselectivities arising from 1,2-asymmetric inductions. Thus non-chelation controlled nucleophilic addition on 3 gave the anti diastereomer 5 as the major product (92% de), while the chelation controlled addition on 4 furnished the syn diastereomer 7 (96% de) as the almost exclusive product. The stereochemical outcomes of these reactions were proven unambiguously by locking the conformation of the syn- and anti-triol adducts 7 and 8 through their respective acetonides and by nuclear Overhauser enhancement measurements. The lack of 1,3-dioxolane formation in the case of the anti-triol 8 was taken as a further confirmation of the absolute configuration at the newly created stereocenter. Key words: byrostatin, pantolactone, α-hydroxylactol, dithiane.