Diastereoselective synthesis of pentasubstituted gamma-butyrolactones from silyl glyoxylates and ketones through a double Reformatsky reaction.

Three contiguous stereocenters can be established with remarkable diastereoselectivity in a double Reformatsky sequence. Densely functionalized gamma-butyrolactones were assembled rapidly by this approach, in which a ketone is used as the terminal electrophile (see scheme). Secondary transformations of the lactone products enhance their synthetic utility. R(1) = Me, H; R(2) = alkyl, aryl, CF(3); Bn = benzyl, TBS = tert-butyldimethylsilyl.