Lewis Acid-Assisted C(sp3)–C(sp3) Reductive Elimination at Gold published in the J. Am. Chem. Soc.

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The phosphine-borane iPr2P(o-C6H4)BFxyl2 (Fxyl = 3,5-(F3C)2C6H3) 1-Fxyl was found to promote the reductive elimination of ethane from [AuMe2(μ-Cl)]2. Nuclear magnetic resonance monitoring revealed the intermediate formation of the (1-Fxyl)AuMe2Cl complex. DFT calculations identified a zwitterionic path as the lowest energy profile, with an overall activation barrier more than 10 kcal/mol lower than without borane assistance. The Lewis acid moiety first abstracts the chloride to generate a zwitterionic Au(III) complex, which then readily undergoes C(sp3)–C(sp3) coupling. The chloride is finally transferred back from boron to gold. The electronic features of this Lewis-assisted reductive elimination at gold have been deciphered by intrinsic bond orbital analyses. Sufficient Lewis acidity of boron is required for the ambiphilic ligand to trigger the C(sp3)–C(sp3) coupling, as shown by complementary studies with two other phosphine-boranes, and the addition of chlorides slows down the reductive elimination of ethane.
This paper by Yago García-Rodeja and collaborators can be found in:

https://pubs.acs.org/doi/10.1021/jacs.3c01974

Aromaticity rules. A comment article in Nature Chemistry

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Since the formulation of the Hückel’s rule, a variety of rules have been proposed to determine if a molecule is aromatic. These allow chemists to better understand molecules and their behavior, as well as identify the formation or elimination of (anti)aromatic species in a reaction, which helps understand and predict possible outcomes. In this comment article, Prof. Miquel Solà first briefly discusses the most widespread rules associated with different types of aromaticity, then draws attention to their limitations, and finally propose future directions for the development of this fascinating topic.

The paper can be read in Nature Chemistry journal through the following link:

https://www.nature.com/articles/s41557-022-00961-w

Directed evolution for abiological radical-relay C(sp3)−H azidation. First Science publication of our group!

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In this work, we show that it is possible to perform directed evolution guided by computational results (performed in our group) to reprogram nonheme iron enzymes to catalyze an abiological C(sp3)‒H azidation reaction through iron-catalyzed radical relay. This biocatalytic transformation uses amidyl radicals as hydrogen atom abstractors and Fe(III)‒N3 intermediates as radical trapping agents. We established a high-throughput screening platform based on click chemistry for rapid evolution of the catalytic performance of identified enzymes. The final optimized variants deliver a range of azidation products with up to 10,600 total turnovers and 93% enantiomeric excess. Given the prevalence of radical relay reactions in organic synthesis and the diversity of nonheme iron enzymes, we envision that this discovery will stimulate future development of metalloenzyme catalysts for synthetically useful transformations unexplored by natural evolution.

This work was carried out by J. Rui, Q. Zhao, A. J. Huls, Z. Chen, V. Reshetnikov and Prof. X. Huang from the Department of Chemistry of the Johns Hopkins University, J. C. Paris and Prof. Y. Guo from the Department of Chemistry of Carnegie University and J. Soler and Dr. M. Garcia-Borràs from the DiMoCat group of the Institute of Computational Chemistry and Catalysis of the University of Girona.

We are very proud of the work by Marc Garcia-Borràs and Jordi Soler! Congratulations!!!

 

Jinyan Rui, Qun Zhao, Anthony J. Huls, Jordi Soler, Jared C. Paris, Zhenhong Chen, Viktor Reshetnikov, Yunfang Yang, Yisong Guo*, Marc Garcia-Borràs* and Xiongyi Huang*. Directed evolution of nonheme iron enzymes to access abiological radical-relay C(sp3)-H azidation. Science, 2022, 376, 6595. DOI: 10.1126/science.abj2830.