Structure analysis of substrate catalyst complexes in mixtures with ultrafast two-dimensional infrared spectroscopy

The understanding of reaction mechanisms requires structure elucidation of short-lived intermediates, even in the presence of other, similar structures. Here we show that polarization dependent two-dimensional infrared spectroscopy is a powerful method to determine the structure of molecules that participate in fast equilibria, in a regime where standard techniques such as nuclear magnetic resonance spectroscopy are beyond their limits. Using catalyst-substrate complexes in a Lewis acid catalyzed enantioselective Diels-Alder reaction as an example we present two methods that allow the resolution of molecular structure in mixtures even when the spectroscopic signals partially overlap. The structures of N-crotonyloxazolidin-2-one, a reactant carrying the Evans auxiliary, and its complex with the Lewis acid SnCl(4) were determined in a mixture as used under the typical reaction conditions. In addition to the chelate that mainly forms, three additional substrate-catalyst complexes were detected and could be tentatively assigned. Observation of minor complex conformers suggests a rationale for the observed diastereoselectivity of the reaction using SnCl(4) as compared to other Lewis acids. Knowledge about additional species may lead to a better understanding of the different selectivities for various Lewis acids and allow reaction optimization.