DFT study of pyridine catalyzed reactions

The Story

When the pandemic hit and kept us away from the lab, I had just joined the Jiao Group and hadn’t yet started independent wet-lab experiments. Instead of waiting it out, I decided to dive into computational chemistry to solve real-world problems from my laptop.

Our group has a long-standing interest in pyridine catalysis, which sparked my own curiosity. I eventually focused on the mechanism of 4,4′-Bipyridine-Catalyzed Nitrobenzene Reduction by Diboron(4) Compounds.

This period was also when I first discovered the power of programming in research. To handle the volume of data, I taught myself Python and Matlab and wrote several automation scripts to streamline my workflow.

Ultimately, I managed to resolve the reaction mechanism. With the guidance of Prof. Jiao, this work was published in The Journal of Organic Chemistry (JOC). Looking back, I feel fortunate that this challenging time turned into such a foundational experience for my career in mechanistic chemistry.

Academic Summary

This study provides a detailed mechanistic auditing of the 4,4′-bipyridine-catalyzed reduction of nitrobenzene by $\text{B}_2\text{nep}_2$ using Density Functional Theory calculations.1 The research establishes that the activation of diboron(4) compounds begins with the generation of a crucial N-boryl 4,4’-bipyridyl radical intermediate (18) through a sequence involving a [3,3]-sigmatropic rearrangement and subsequent homolytic cleavage.

[Image of a [3,3] -sigmatropic rearrangement mechanism]

This radical species then drives the formation of the boryl bipyridinylidene intermediate (3) via a radical chain mechanism. In this catalytic cycle, intermediate 3 functions as a stable reservoir that releases radical 18 to react with nitrobenzene, ultimately yielding intermediate 30.

The subsequent elimination of $(\text{Bnep})_2\text{O}$ to afford nitrosobenzene is identified as a complex, single-step reaction that proceeds through three distinct stages of dissociation and migration. A similar single-step pathway governs the interaction between nitrosobenzene and $\text{B}_2\text{nep}_2$ to form intermediate 7.

A key discovery in this work concerns the formation of arylnitrene, which is found to occur on a triplet potential energy surface. The transition from the singlet manifold to the triplet intermediate (35) via intermediate 34 requires an intersystem crossing (ISC).

[Image of an intersystem crossing Jablonski diagram]

This crossing is essential to achieving a kinetically feasible activation energy barrier for the nitrene generation process. These insights into radical chain processes and spin-multiplicity changes provide a theoretical framework for the rational design of pyridine- and bipyridine-based catalysts in reductive transformations.

Diboron(4) compounds serve as useful reagents for borylation, diboration, and reduction in organic synthesis. A variety of pyridine derivatives have been found capable of activating diboron(4) compounds, and different reaction mechanisms have been identified. 4,4′-Bipyridine was found to activate diboron(4) to form N,N′-diboryl-4,4′-bipyridinylidene in 2015, and very recently, it has been found that this transformation is crucial in the 4,4′-bipyridine-catalyzed reduction of nitroarenes by bis(neopentylglycolato)diboron (B2nep2), which features the formation of arylnitrene intermediates. However, the mechanism of N,N′-diboryl-4,4′-bipyridinylidene formation, as well as its role in the transformation of nitroarene to arylnitrene, remains unknown. In this work, we investigated the possible pathways of this intriguing transformation and discovered several important intermediates through density functional theory (DFT) calculations. An N-boryl 4,4′-bipyridyl radical was found to be a crucial intermediate in both the formation of N,N′-diboryl-4,4′-bipyridinylidene and the reduction of nitroarene. A type of single-step reaction with three stages, including a dissociation and two migration steps, was identified in the generation of nitrosobenzene and its reduction. Arylnitrene formation was found to occur on a triplet potential energy surface, and an intersystem crossing was found to be important for achieving a reasonable activation energy barrier for nitrene formation. We anticipate our work to provide deeper insights into the nature of this reaction that could facilitate further rational design of pyridine- and bipyridine-based catalysts.

DFT study of pyridine catalyzed reactions

The Story

Academic Summary

References

2020