Stereocontrolled Synthesis of a Cn-Cn+6 Building Block for the Unnatural Enantiomers of Important Polyol,Polyene Antibiotics from an Epoxy Alcohol by a Reduction/Conjugate Addition/Hydroxylation Sequence

Epoxy alcohol anti‐10, derived from a desymmetrizing Sharpless epoxidation (up to 97 % ee) of divinylcarbinol 9, provided the unsaturated 1,3‐diol syn‐11 upon treatment with RedAl®; syn‐11 was converted into the α,β‐unsaturated esters (E)‐ or (Z)‐7b in three steps. Cu‐promoted 1,4‐addition of vinylmagnesium halides to the (E)‐ester proceeded with diastereoselectivities of up to 91 % and Cu‐catalyzed 1,4‐additions with diastereoselectivities of up to 82 %. The potassium enolate of the major vinylation product syn‐22b was hydroxylated by the Davis oxaziridine with perfect but unprecedented diastereoselectivity. The resulting hydroxy ester, α,βsyn,β,γsyn‐32, furnished the “eastern moiety” building block 6 of the title compounds in three steps. A CuBr·SMe2/LiBr/LiSPh‐promoted 1,4‐addition of vinylmagnesium chloride to a γ‐chiral α,β‐unsaturated ester, obtained from a Sharpless epoxide, and an ensuing hydroxylation of the C‐α position with the Davis oxaziridine has established the stereocenter of the epoxide ring.