Light on Catalytic Reaction Mechanisms: Uncovering the Conformation of Thiourea-Based Organocatalysts and Their Interaction with Nitroolefins Using Mid-infrared Spectroscopy

Abstract

Thiourea-based organocatalysts offer a wide variety of benefits over conventional metal-based catalysts; among other things, they are cheap, harmless, and highly enantioselective. At the core of their catalytic activity is the ability to simultaneously coordinate reactants through hydrogen bonds and lower energy barriers. Detailed insight into the structure and conformational heterogeneity of the catalyst together with the coordination of the reactants is thus key to understanding the mechanisms by which organocatalysts perform their function. Here, using the Takemoto organocatalyst and 1-(2-nitroethyl)naphthalene as a prototypical catalyst-reactant system involved in Michael addition reactions, we show that mid-infrared spectroscopy covering the wide spectral range from 650 to 3500 cm-1 combined with molecular beam experiments and density functional theory calculations is a powerful approach to meet these challenges. We determine the precise geometry adopted by the catalyst-nitroolefin complex, thereby providing direct information about the hydrogen bonds involved. Moreover, we solve a long-standing problem of the preferred conformation of the bare catalyst by providing an unambiguous determination of its structure. The general applicability of our approach holds great promise for extending it to elucidate other relevant complex reactions involving (organo)catalysts.