A Bifunctional β-Isocupreidine Derivative as Catalyst for the Enantioselective Morita–Baylis–Hillman Reaction and a Mechanistic Rationale for Enantioselectivity†

Starting from β-isocupreidine (β-ICD), a series of difunctional catalysts were synthesized to ascertain their usefulness in the asymmetric Morita–Baylis–Hillman (MBH) reaction. The trichloroacetylcarbamate derivative was found to give the (R)-MBH adducts in excellent optical purities (90–99 % ee) and moderate to good yields (43–83 %), in some cases, better than β-ICD. A number of acrylates were also tested and 2,6-dimethyl-4-nitrophenyl acrylate was identified as a suitable alternative to the popular hexafluoroisopropyl acrylate, with both the β-ICD and trichloroacetylcarbamate derivatives. The mechanism of the rate- and selectivity-determining step was ascertained by means of experimental observations and a computational investigation aimed at clarifying the transition state structures is reported. These studies have clarified the reasons for the effectiveness of these structurally related catalysts in the asymmetric MBH reaction between acrylates and aldehydes.