The Horner–Wadsworth–Emmons reaction of mixed phosphonoacetates and aromatic aldehydes: geometrical selectivity and computational investigation

The substituent effect on the geometrical selectivity in the Horner–Wadsworth–Emmons (HWE) reaction was studied employing several mixed phosphonoacetates. Their reactions with aromatic aldehydes showed a gradual change in Z-selectivity according to the electron-withdrawing ability of the phosphonate substituents, and there was a good correlation between the observed selectivities and 31P chemical shifts of the phosphonoacetates. Some variables such as the metal cation and crown ether also affected the selectivity. A computational study using ab initio and semi-empirical calculations suggests that the electron-withdrawing substituents stabilize the intermediates as well as the transition states, which reduces the reversibility to increase Z-products. This is in agreement with the experimentally observed selectivity.