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1. Substrate‐Mediator Duality of 1,4‐Dicyanobenzene in Electrochemical C(sp ² )−C(sp ³ ) Bond Formation with Alkyl Bromides

   https://doi.org/10.1002/anie.202312128  

   Johnston, Brandon; Loh, Daniel M.; Nocera, Daniel G. (November 2023, Angewandte Chemie International Edition)

   Abstract Electrochemical approaches to form C(sp²)−C(sp³) bonds have focused on coupling C(sp³) electrophiles that form stabilized carbon‐centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp³) coupling partners owing to their availability and cost‐effectiveness, their tendency to undergo radical‐radical homocoupling makes them challenging substrates for electroreductive cross‐coupling. Herein, we disclose a metal‐free regioselective cross‐coupling of 1,4‐dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4‐dicyanobenzene radical anions, leading to negligible homocoupling and high cross‐selectivity to form 1,4‐alkyl cyanobenzenes. The cross‐coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp³) precursors. 

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2. Copper Catalyzed Benzylic sp ³ C-H Alkenylation

   https://doi.org/10.1039/D4SC03430A  

   Chen, Ting-An; Staples, Richard J; Warren, Timothy H (September 2024, Chemical Science)

   The prenyl group is present in numerous biologically active small molecule drugs and natural products. We introduce benzylic C-H alkenylation of substrates Ar-CH3 with alkenylboronic esters (CH2)3O2B-CH=CMe2 as a pathway to form prenyl functionalized arenes Ar-CH2CH=CMe2. Mechanistic studies of this radical relay catalytic protocol reveal diverse reactivity pathways exhibited by the copper(II) vinyl intermediate [CuII]-CH=CMe2 that involve radical capture, bimolecular C-C bond formation, and hydrogen atom transfer (HAT). 

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3. α-Branched amines through radical coupling with 2-azaallyl anions, redox active esters and alkenes

   https://doi.org/10.1039/D2SC00500J  

   Duan, Shengzu; Zi, Yujin; Wang, Lingling; Cong, Jielun; Chen, Wen; Li, Minyan; Zhang, Hongbin; Yang, Xiaodong; Walsh, Patrick J. (March 2022, Chemical Science)

   α-Branched amines are fundamental building blocks in a variety of natural products and pharmaceuticals. Herein is reported a unique cascade reaction that enables the preparation of α-branched amines bearing aryl or alkyl groups at the β- or γ-positions. The cascade is initiated by reduction of redox active esters to alkyl radicals. The resulting alkyl radicals are trapped by styrene derivatives, leading to benzylic radicals. The persistent 2-azaallyl radicals and benzylic radicals are proposed to undergo a radical–radical coupling leading to functionalized amine products. Evidence is provided that the role of the nickel catalyst is to promote formation of the alkyl radical from the redox active ester and not promote the C–C bond formation. The synthetic method introduced herein tolerates a variety of imines and redox active esters, allowing for efficient construction of amine building blocks. 

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4. Copper( ii ) ketimides in sp ³ C–H amination

   https://doi.org/10.1039/D1SC01990B  

   Jayasooriya, Isuri U.; Bakhoda, Abolghasem; Palmer, Rachel; Ng, Kristi; Khachemoune, Nour L.; Bertke, Jeffery A.; Warren, Timothy H. (December 2021, Chemical Science)

   Commercially available benzophenone imine (HNCPh 2 ) reacts with β-diketiminato copper( ii ) tert -butoxide complexes [Cu II ]–O t Bu to form isolable copper( ii ) ketimides [Cu II ]–NCPh 2 . Structural characterization of the three coordinate copper( ii ) ketimide [Me 3 NN]Cu–NCPh 2 reveals a short Cu-N ketimide distance (1.700(2) Å) with a nearly linear Cu–N–C linkage (178.9(2)°). Copper( ii ) ketimides [Cu II ]–NCPh 2 readily capture alkyl radicals R˙ (PhCH(˙)Me and Cy˙) to form the corresponding R–NCPh 2 products in a process that competes with N–N coupling of copper( ii ) ketimides [Cu II ]–NCPh 2 to form the azine Ph 2 CN–NCPh 2 . Copper( ii ) ketimides [Cu II ]–NCAr 2 serve as intermediates in catalytic sp 3 C–H amination of substrates R–H with ketimines HNCAr 2 and t BuOO t Bu as oxidant to form N -alkyl ketimines R–NCAr 2 . This protocol enables the use of unactivated sp 3 C–H bonds to give R–NCAr 2 products easily converted to primary amines R–NH 2 via simple acidic deprotection. 

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5. Aliphatic Radical Relay Heck Reaction at Unactivated C(sp ³ )−H Sites of Alcohols

   https://doi.org/10.1002/anie.201812398  

   Chuentragool, Padon; Yadagiri, Dongari; Morita, Taiki; Sarkar, Sumon; Parasram, Marvin; Wang, Yang; Gevorgyan, Vladimir (January 2019, Angewandte Chemie International Edition)

   Abstract The Mizoroki–Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp³)−H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β‐, γ‐, and δ‐C(sp³)−H sites. The use of an easily installed/removed Si‐based auxiliary enables selective I‐atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible‐light‐mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks. 

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