The origin of Felkin–Anh control from an electropositive substituent adjacent to the carbonyl group

Abstract

Ab initio calculations on the gas phase reaction of lithium hydride with 2-silylacetaldehyde, 2-silylpropionaldehyde, 2-trimethylsilylacetaldehyde, 2-trimethylsilylpropionaldehyde and 3-trimethylsilylbutan-2-one have been performed. For each of the substrates containing an SiH₃ group, the hydride approaches syn to the silyl substituent in the lowest-energy transition structure. In contrast, for each of the substrates containing the larger SiMe₃ group, the more conventional Felkin–Anh transition structure, in which the hydride attacks anti to this substituent, is lowest in energy. These results suggest that the diastereoselectivity of nucleophilic attack on a carbonyl group, adjacent to a stereogenic centre to which a trimethylsilyl group is attached, is largely controlled by the size of this substituent, rather than by the electronic effect of the electropositive silicon it contains. Other influences on the preferred conformations of the reactants and transition structures are discussed.