Probing Regio- and Enantioselectivity in the Formal [2+2] Cycloaddition of C(1)-Alkyl Ammonium Enolates with beta- and alpha,beta-Substituted Trifluoromethylenones

The isothiourea-catalyzed regio- and enantioselectiveformal [2+ 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolateswith beta- and alpha,beta-substituted trifluoromethylenoneshas been developed. In all cases, preferential [2 + 2]-cycloadditionover the alternative [4 + 2]-cycloaddition is observed, giving beta-lactoneswith excellent diastereo- and enantioselectivity (34 examples, upto >95:5 dr, >99:1 er). The regioselectivity of the processwas dictatedby the nature of the substituents on both reaction components. Solely[2 + 2] cycloaddition products are observed when using alpha,beta-substitutedtrifluoromethylenones or alpha-trialkylsilyl acetic acid derivatives;both [2 + 2] and [4 + 2] cycloaddition products are observed whenusing beta-substituted trifluoromethylenones and alpha-alkyl-alpha-trialkylsilylacetic acids as reactants, with the [2 + 2] cycloaddition as the majorreaction product. The beneficial role of the alpha-silyl substituentwithin the acid component in this protocol has been demonstrated bycontrol experiments.