Due to the chiral nature of enzymes in the body, the biological activity of any given molecule is often highly dependent on its stereochemical configuration. (1-hydroxy-2-methylbutyl) fragments are commonly present in a number of natural (<i>S</i>)-2-methylbutanal would be an attractive building block for such natural products because of its ready availability; however, stereoselectivity of nucleophilic additions to this aldehyde is notoriously poor. An aldehyde bearing a 1,3-dithiane has thus been explored as an alternative to the readily available but poorly stereoselective (<i>S</i>)-2-methylbutanal. For a wide variety of organometallic nucleophiles, the 1,3-dithiane group provides excellent Felkin selectivity for the nucleophilic addition, regardless of nucleophile steric demand or metal counterion. Desulfurization of the adduct affords the (1-hydroxy-2-methylbutyl) moiety found in a number of natural products with very high selectivity, with minimal concession steps.

Stereochemical control via a 1,3-dithiane moiety: Access to well-defined (1-hydroxy-2-methylbutyl) fragments

2019 Spring National Meeting

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