Mechanism-Guided Development of a Highly Active Bis-thiourea Catalyst for Anion-Abstraction Catalysis

We describe the rational design of a linked, bis-thiourea catalyst with enhanced activity relative to monomeric analogues in a representative enantio­selective anion-abstraction reaction. Mechanistic insights guide development of this linking strategy to favor substrate activation though the intra­molecular cooperation of two thiourea subunits while avoiding nonproductive aggregation. The resulting catalyst platform overcomes many of the practical limitations that have plagued hydrogen-bond-donor catalysis and enables use of catalyst loadings as low as 0.05 mol %. Computational analyses of possible anion-binding modes provide detailed insight into the precise mechanism of anion-abstraction catalysis with this pseudo-dimeric thiourea.