STEREOSELECTIVE SYNTHESIS OF HETEROCYCLIC ZINC REAGENTS VIA A NICKEL-CATALYZED RADICAL CYCLIZATION

Unsaturated iodo or bromo acetals of type 2 undergo a smooth cyclizati on mediated by diethylzinc (2 equiv) and Ni(acac)(2) as catalyst (2-5 mol %). These cyclizations proceed via a radical mechanism affording a (tetrahydrofuranylmethyl)zinc halide of type 1, which can be reacted with various electrophiles after a transmetalation with CuCN . 2LiCl. High stereoselectivities are usually observed in the ring closures, es pecially if monocyclic cyclization precursors are used. In these cases , bicyclic products of the endo-configuration are obtained with over 9 4% diastereoselectivity. The synthetic method has been extended to the preparation of a nitrogen heterocycle and over 98% pure trans-4,5-dis ubstituted gamma-butyrolactones. A short enantioselective synthesis of (-)-methylenolactocine (3) using the radical cyclization and a novel oxidation of alpha-silyl zinc peroxide as a key step is also described .