The isothiourea-catalyzed regio- and enantioselective
formal [2
+ 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates
with β- and α,β-substituted trifluoromethylenones
has been developed. In all cases, preferential [2 + 2]-cycloaddition
over the alternative [4 + 2]-cycloaddition is observed, giving β-lactones
with excellent diastereo- and enantioselectivity (34 examples, up
to >95:5 dr, >99:1 er). The regioselectivity of the process
was dictated
by the nature of the substituents on both reaction components. Solely
[2 + 2] cycloaddition products are observed when using α,β-substituted
trifluoromethylenones or α-trialkylsilyl acetic acid derivatives;
both [2 + 2] and [4 + 2] cycloaddition products are observed when
using β-substituted trifluoromethylenones and α-alkyl-α-trialkylsilyl
acetic acids as reactants, with the [2 + 2] cycloaddition as the major
reaction product. The beneficial role of the α-silyl substituent
within the acid component in this protocol has been demonstrated by
control experiments.