Asymmetric synthesis of cycloalkenyl and alkenyloxiranes from allylic sulfoximines and aldehydes and application to solid-phase synthesis

An asymmetric synthesis of cycloalkenyl and alkenyloxiranes from allylic sulfoximines and aldehydes is described. Lithiation and titanation of cyclic and acyclic allylic sulfoximines with chlorotris(diethylamino)titanium and subsequent treatment with aldehydes gave, as described previously, enantio- and diastereomerically pure, syn-configured, sulfoximine-substituted homoallylic alcohols. Treatment of the sulfoximine-substituted homoallylic alcohols with chloroethyl chloroformate resulted in a facile substitution of the sulfoximine group by a Cl atom, with formation of the corresponding alkenyl chlorohydrins. In the case of the cycloalkenyl derivatives the substitution proceeded with high diastereoselectivities with retention of configuration, while in the case of the alkenyl derivatives, medium diastereoselectivities with inversion of configuration were observed. While elimination reactions of the cycloalkenyl chlorohydrins gave the corresponding enantio- and diastereomerically pure cis-configured cycloalkenyloxiranes in good overall yields, the alkenyl chlorohydrins afforded mixtures of enantiomerically pure trans and cis isomers in which the trans isomers dominated. The solution-phase synthesis was extended to the solid phase by the synthesis of an enantiomerically pure, polymer-bound allylic sulfoximine and its conversion into an alkenyloxirane. The initial results proved that the concept of the utilization of the sulfoximine group as a traceless chiral linker is feasible and suggest that the solid-phase asymmetric synthesis of cycloalkenyloxiranes by this route should be possible. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.