Controlling Reaction Selectivity Via Molecular Dynamics

The traditional way to produce only one out of several possible products of a reaction is to stabilize the transition state that leads to that desired compound. But in some reactions a single transition state leads to multiple products, requiring a different approach to selectivity. Such is the case with [1,2]- versus [2,3]-sigmatropic rearrangements. Working with an ammonium ylide containing an enolate group (Y, shown), Bibaswan Biswas and Daniel A. Singleton of Texas A&M University have demonstrated that they can select for either the [1,2] or [2,3] rearrangement product by choosing reaction conditions geared toward promoting particular molecular dynamics paths (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b08635). Alkali-metal bases that do not hydrogen bond to the ylide allow for early formation of the transition state with dynamic motion that favors fragmentation and [1,2] rearrangement. In contrast, methanol or protonated 1,8-diazabicycloundec-7-ene does form a hydrogen bond to the enolate oxygen, increasing the reaction barrier and promoting later formation of the transition state with dynamic motion that favors [2,3] rearrangement.