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1. The tension-activated carbon–carbon bond

   https://doi.org/10.1016/j.chempr.2024.05.012  

   Sun, Yunyan; Kevlishvili, Ilia; Kouznetsova, Tatiana B; Burke, Zach P; Craig, Stephen L; Kulik, Heather J; Moore, Jeffrey S (June 2024, Chem)

   Mechanical force drives distinct chemical reactions; yet, its vectoral nature results in complicated coupling with reaction trajectories. Here, we utilize a physical organic model inspired by the classical Morse potential and its differential forms to identify effective force constant (keff) and reaction energy (ΔE) as key molecular features that govern mechanochemical kinetics. Through a comprehensive experimental and computational investigation with four norborn-2-en-7-one (NEO) mechanophores, we establish the relationship between these features and the force-dependent energetic changes along the reaction pathways. We show that the complex kinetic behavior of the tensioned bonds is generally and quantitatively predicted by a simple multivariate linear regression based on the two easily computed features with a straightforward workflow. These results demonstrate a general mechanistic framework for mechanochemical reactions under tensile force and provide a highly accessible tool for the large-scale computational screening in the design of mechanophores. 

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2. Reversible Homolysis of a Carbon–Carbon σ-Bond Enabled by Complexation-Induced Bond-Weakening

   https://doi.org/10.1021/jacs.2c01229  

   Kim, Suhong; Chen, Pan-Pan; Houk, K. N.; Knowles, Robert R. (August 2022, Journal of the American Chemical Society)
3. Mechanistic analysis of carbon–carbon bond formation by deoxypodophyllotoxin synthase

   https://doi.org/10.1073/pnas.2113770119  

   Tang, Haoyu; Wu, Min-Hao; Lin, Hsiao-Yu; Han, Meng-Ru; Tu, Yueh-Hua; Yang, Zhi-Jie; Chien, Tun-Cheng; Chan, Nei-Li; Chang, Wei-chen (January 2022, Proceedings of the National Academy of Sciences)

   Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate–dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS’s catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel–Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs. 

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4. Recent advances in enzymatic carbon–carbon bond formation

   https://doi.org/10.1039/D4RA03885A  

   Zhao, Hua (August 2024, RSC Advances)

   Enzymatic carbon‒carbon (C–C) bond formation reactions have become an effective and invaluable tool for designing new biological and medicinal molecules, often with asymmetric features. This review provides a systematic overview of key C–C bond formation reactions and enzymes, with the focus of reaction mechanisms and recent advances. These reactions include aldol reaction, Henry reaction, Knoevenagel condensation, Michael addition, Friedel-Crafts alkylation and acylation, Mannich reaction, Morita–Baylis–Hillman (MBH) reaction, Diels-Alder reaction, acyloin condensations via Thiamine Diphosphate (ThDP)-dependent enzymes, oxidative and reductive C–C bond formation, C–C bond formation through C1 resource utilization, radical enzymes for C–C bond formation, and other C–C bond formation reactions. 

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5. Plasma Electrochemistry for Carbon–Carbon Bond Formation via Pinacol Coupling

   https://doi.org/10.1021/jacs.3c01779  

   Wang, Jian; Üner, Necip B; Dubowsky, Scott Edwin; Confer, Matthew P; Bhargava, Rohit; Sun, Yunyan; Zhou, Yuting; Sankaran, R Mohan; Moore, Jeffrey S (May 2023, Journal of the American Chemical Society)

   The formation of carbon-carbon bonds by pinacol coupling of aldehydes and ketones requires a large negative reduction potential, often realized with a stoichiometric reducing reagent. Here, we use solvated electrons generated via a plasma-liquid process. Parametric studies with methyl-4-formylbenzoate reveal that selectivity over the competing reduction to the alcohol requires careful control over mass transport. The generality is demonstrated with benzaldehydes, benzyl ketones, and furfural. A reaction-diffusion model explains the observed kinetics, and ab initio calculations provide insight into the mechanism. This study opens the possibility of a metal-free, electrically-powered, sustainable method for reductive organic reactions. 

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