Stereoselective reactions play an important role in chemistry, especially in the synthesis of pharmaceutical compounds. For this purpose, there are presently insufficient methods for asymmetric catalysis without the use of toxic and costly transition-metal based compounds. Here we report a computational study of the enantioselective addition of 4,7-dihydroindoles to trans-nitroalkenes catalyzed by a novel dual hydrogen-bonding helical catalyst recently developed by Takenaka and co-workers [J. Am. Chem. Soc. 2010,  132, 4536]. Through the use of density functional theory (DFT) methods at the B97-D/TZV(2d,2p) level, the mechanistic pathways for this reaction were explored to identify the key features of the transition state (TS). It is shown that the helical structure of the catalyst induces a stepwise mechanism through non-covalent interactions resulting in kinetic discrimination and high enantioselectivity. Ongoing studies involve application of the distortion-interaction model to quantify the role of these non-covalent interactions in the enantioselectivity. Understanding the salient features of this reaction is essential for the rational design of improved organocatalysts that utilize similar hydrogen-bonding interactions.

Origin of enantioselectivity in helical dual hydrogen-bonding catalysts

245th National Meeting (2013)

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