Unveiling the Delicate Balance of Steric and Dispersion Interactions in Organocatalysis Using High-Level Computational Methods.

Diana Yepes,Frank Neese,Benjamin List,Giovanni Bistoni

doi:10.1021/jacs.9b13725

Diana Yepes, Frank Neese + Show 2 more

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https://doi.org/10.1021/jacs.9b13725

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Abstract

High-level quantum electronic structure calculations are used to provide a deep insight into the mechanism and stereocontrolling factors of two recently developed catalytic asymmetric Diels–Alder (DA) reactions of cinnamate esters with cyclopentadiene. The reactions employ two structurally and electronically very different in situ silylated enantiopure Lewis acid organocatalysts: i.e., binaphthyl-allyl-tetrasulfone (BALT) and imidodiphosphorimidate (IDPi). Each of these catalysts activates only specific substrates in an enantioselective fashion. Emphasis is placed on identifying and quantifying the key noncovalent interactions responsible for the selectivity of these transformations, with the final aim of aiding in the development of designing principles for catalysts with a broader scope. Our results shed light into the mechanism through which the catalyst architecture determines the selectivity of these transformations via a delicate balance of dispersion and steric interactions.

Highlights

Over the last two decades, numerous chiral organocatalysts that efficiently facilitate highly stereo- and regioselective transformations by activating the reactants through either covalent[1−3] or noncovalent interactions[4−7] have been reported.[8−10]In the vast majority of cases, the design of new organocatalysts relies on a trial and error procedure where different prototypes are synthesized and tested under variable experimental conditions
In our preliminary computational investigation of these systems,[16] we suggested that a chiral ion pair held together by highly directional electrostatic interactions is formed between the chiral anion and the activated substrate
Our discussion starts by analyzing their energy profiles (Figure 2), which were obtained using the computational protocol outlined in the previous section

Summary

■ INTRODUCTION

Over the last two decades, numerous chiral organocatalysts that efficiently facilitate highly stereo- and regioselective transformations by activating the reactants through either covalent[1−3] or noncovalent interactions[4−7] have been reported.[8−10]. To achieve this goal in the case of ACDC, the first challenge is to identify the thermally accessible conformations for intermediates and TSs from among the thousands of potential structures.[56] extremely accurate free energy calculations are needed to get reliable selectivities.[57] the identification and quantification of the most important attractive/repulsive interactions that take place at the TSs is fundamental to develop designing principles for better catalysts.[56] To tackle these challenges, a computational protocol was developed that relies on four key components. Optimized geometries were plotted using the CYLview[95] program using the following atom color code: H, white; C, gray; N, blue; O, red; F, green; Si, beige; P, orange; S, yellow

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ REFERENCES