Efficient and stereoselective access to the polyol fragment C9-C16 of ansamycin antibiotics.

Efficient synthesis of the fragment C9-C16 bearing the anti,syn stereotriad of ansamycin antibiotics is described. Key steps for controlling the configuration of the three stereogenic centers involve a stereoselective Reformatsky-type reaction followed by a diastereoselective reduction of a beta-ketosulfoxide.

Polysubstituted oxygen heterocycles by a Reformatsky-type reaction/reductive cyclization approach from enantiopure beta-ketosulfoxides.

The stereoselective synthesis of tetrasubstituted tetrahydrofurans and trisubstituted tetrahydropyrans bearing a sulfoxide was achieved by reductive cyclization (Et3SiH/TMSOTf) from the corresponding enantiopure hydroxy ketones protected as a dioxolane. These derivatives are easily accessible from a Reformatsky-type reaction between alpha-bromo-alpha'-sulfinyl ketones and protected alpha- or beta-ketoaldehydes, followed by diastereoselective reduction of the resulting beta-ketosulfoxide.

Reformatsky-type reaction of chiral nonracemic alpha-bromo-alpha'-sulfinyl ketones with aldehydes. Synthesis of enantiomerically pure 2-methyl-1,3-diol moieties.

Chiral nonracemic alpha-bromo-alpha'-sulfinyl ketones were shown to react with aldehydes in the presence of SmI(2) in a Reformatsky-type reaction to give the corresponding adduct with excellent syn diastereoselectivity. Further reduction of the Reformatsky adducts furnished anti- and syn-2-methyl-1,3-diol moieties in excellent yields and diastereoselectivities.