Catalytic asymmetric allylation of ketones and cyclic enones: Tandem diastereoselective epoxidation with TBHP or sequential oxy-Cope rearrangement

ORGN 97

Jeung Gon Kim, Karen M. Waltz, Iliana Garcia, and Patrick J. Walsh. Department of Chemistry, University of Pennsylvania, 231 South 34th St., Philadelphia, PA 19104
A simple procedure is reported for the catalytic asymmetric allylation of ketones, utilizing titanium tetraisopropoxide, BINOL, isopropanol additive, and tetraallylstannane as allylating agent. A variety of ketone substrates, including acetophenone derivatives and a, b-unsaturated cyclic enones, reacted to form tertiary alcohols in good yields (67-99%) and with high levels of enantioselectivity (generally >80%). A novel one-pot enantioselective allylation/diastereoselective epoxidation has also been introduced. Thus, upon completion of the allylation addition to conjugated cyclic enones, 1 equiv TBHP (tert-butyl hydroperoxide) is added and the directed epoxidation of the allylic double bond ensues. The epoxidation is proposed to be catalyzed by the titanium employed to promote the allylation reaction. In this tandem process, only a single diastereomer of the epoxy alcohol was observed. The products of allylation of cyclic enones are 1,5-dien-3-ols and can be further transformed via a diastereoselective oxy-Cope rearrangement to give trans-2,3-disubstituted ketones. The net result of this two-step allylation/oxy-Cope rearrangement process is equivalent to the asymmetric conjugate addition of an allyl to a cyclic enone, a challenging class of compounds to prepare.