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1. A base-catalyzed approach for the anti-Markovnikov hydration of styrene derivatives

   https://doi.org/10.1039/D2SC02827A  

   Pajk, Spencer P.; Qi, Zisong; Sujansky, Stephen J.; Bandar, Jeffrey S. (October 2022, Chemical Science)

   The base-catalyzed addition of 1-cyclopropylethanol to styrene derivatives with an acidic reaction workup enables anti-Markovnikov hydration. The use of either catalytic organic superbase or crown ether-ligated inorganic base permits hydration of a wide variety of styrene derivatives, including electron-deficient, ortho -substituted and heteroaryl variants. This protocol complements alternative routes to terminal alcohols that rely on stoichiometric reduction and oxidation processes. The utility of this method is demonstrated through multigram scale reactions and its use in a two-step hydration/cyclization process of ortho -halogenated styrenes to prepare 2,3-dihydrobenzofuran derivatives. 

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2. Stereospecific and Regioselective Synthesis of E -Allylic Alcohols through Reductive Cross Coupling of Terminal Alkynes

   https://doi.org/10.1021/jacs.3c06963  

   Shaff, Austin B; Yang, Langxuan; Lee, Mitchell T; Lalic, Gojko (November 2023, Journal of the American Chemical Society)

   We have developed a convergent method for the synthesis of allylic alcohols that involves a reductive coupling of terminal alkynes with α-chloro boronic esters. The new method affords allylic alcohols with excellent regioselectivity (anti-Markovnikov) and an E/Z ratio greater than 200:1. The reaction can be performed in the presence of a wide range of functional groups and has a substrate scope that complements the stoichiometric alkenylation of α-chloro boronic esters performed using alkenyl lithium and Grignard reagents. The transformation is stereospecific and allows for the robust and highly selective synthesis of chiral allylic alcohols. Our studies support a mechanism that involves hydrocupration of the alkyne and cross-coupling of the alkenyl copper intermediate with α-chloro boronic esters. Experimental evidence excludes a radical mechanism of the cross-coupling step and is consistent with the formation of a boron-ate intermediate and a 1,2-metalate shift. 

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3. Regioreversed Carbosulfenylation of Fluoroalkenes via Nickel‐Mediated Radical Sorting

   https://doi.org/10.1002/anie.202509664  

   Zhu, Chuan; Liu, Qian; Wang, Nannan; Ma, Rui; Chen, Kai; Walsh, Patrick_J; Guo, Kai; Feng, Chao (June 2025, Angewandte Chemie International Edition)

   Abstract Carbosulfenylation of olefins represents an important class of reactions for the synthesis of structurally diverse organosulfur compounds. Previous studies typically yield 1,2‐regioselectivity. In the context of diversity‐oriented synthesis, accessing the regioreversed products is desirable, significantly broadening the scope of these reactions. In this study, we report a nickel‐catalyzed 2,1‐carbosulfenylation of trifluoromethyl‐ andgem‐difluoroalkenes, using free thiols and benzyl bromides as sulfur and carbon sources, respectively. The unusual regioselectivity observed is enabled by a “radical sorting” mechanism. The Ni catalyst activates benzyl bromide to generate a benzylic radical that undergoes hydrogen atom transfer (HAT) with the thiol to form a sulfur‐centered radical. The sulfur radical subsequently adds to the fluoroalkenes, resulting in an α‐fluoroalkyl C‐radical. This radical undergoes S_H2 with a Ni–CH₂Ar to form a C(sp³)─C(sp³) bond and quaternary center, ultimately producing valuable fluoroalkyl thioethers. Isotopic labeling experiments corroborate a hydrogen atom transfer (HAT) event within the working mechanism. 

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4. Ligand‐Controlled Regiodivergence in Nickel‐Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids**

   https://doi.org/10.1002/anie.202010840  

   Li, Zi‐Qi; Fu, Yue; Deng, Ruohan; Tran, Van T.; Gao, Yang; Liu, Peng; Engle, Keary M. (October 2020, Angewandte Chemie International Edition)

   Abstract A nickel‐catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand‐free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti‐Markovnikov products can be accessed with a novel 4,4‐disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover‐limiting and selectivity‐determining step induced by the optimal ligand. DFT calculations reveal that in the anti‐Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate‐ and regioselectivity‐determining transmetalation transition state. 

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5. Photoredox-mediated hydroalkylation and hydroarylation of functionalized olefins for DNA-encoded library synthesis

   https://doi.org/10.1039/d1sc03191k  

   Badir, Shorouk O.; Lipp, Alexander; Krumb, Matthias; Cabrera-Afonso, María Jesús; Kammer, Lisa Marie; Wu, Victoria E.; Huang, Minxue; Csakai, Adam; Marcaurelle, Lisa A.; Molander, Gary A. (September 2021, Chemical Science)

   null (Ed.)

   DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctional building blocks (BBs) with high C(sp 3 ) carbon counts is integral for success. In this report, a decarboxylative-based hydro alkylation of DNA-conjugated trifluoromethyl-substituted alkenes enabled by single-electron transfer (SET) and subsequent hydrogen atom termination through electron donor–acceptor (EDA) complex activation is detailed. In a further photoredox-catalyzed hydro arylation protocol, the coupling of functionalized, electronically unbiased olefins is achieved under air and within minutes of blue light irradiation through the intermediacy of reactive (hetero)aryl radical species with full retention of the DNA tag integrity. Notably, these processes operate under mild reaction conditions, furnishing complex structural scaffolds with a high density of pendant functional groups. 

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