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1. Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone

   https://doi.org/10.3390/molecules25092128  

   Bellinger, Tania J.; Harvin, Teavian; Pickens-Flynn, Ti’Bran; Austin, Nataleigh; Whitaker, Samuel H.; Tang Yuk Tutein, Mai Ling; Hukins, Dabria T.; Deese, Nichele; Guo, Fenghai (May 2020, Molecules)

   Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4-adducts can be attained with CuCN∙2LiCl as the copper source. Excellent yields of 2-alkyl-substituted thiochroman-4-ones and thioflavanones (2-aryl substituted) are attained with a broad range of Grignard reagents. This approach works well with both alkyl and aromatic Grignard reagents, thus providing a unified synthetic approach to privileged 2-substituted thiochroman-4-ones and a potential valuable precursor for further synthetic applications towards many pharmaceutically active molecules. The use of commercially available and/or readily prepared Grignard reagents will expedite the synthesis of a large library of both 2-alkyl substituted thiochroman-4-ones and thioflavanones for additional synthetic applications. 

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2. Synthesis of oxaboranes via nickel-catalyzed dearylative cyclocondensation

   https://doi.org/10.1039/d2sc01840c  

   Koeritz, Mason T.; Banovetz, Haley K.; Prell, Sean A.; Stanley, Levi M. (July 2022, Chemical Science)

   We report Ni-catalyzed dearylative cyclocondensation of aldehydes, alkynes, and triphenylborane. The reaction is initiated by oxidative cyclization of the aldehyde and alkyne coupling partners to generate an oxanickelacyclopentene which reacts with triphenylborane to form oxaboranes. This formal dearylative cyclocondensation reaction generates oxaboranes in moderate-to-high yields (47–99%) with high regioselectivities under mild reaction conditions. This approach represents a direct and modular synthesis of oxaboranes which are difficult to access using current methods. These oxaboranes are readily transformed into valuable building blocks for organic synthesis and an additional class of boron heterocycles. Selective homocoupling forms oxaboroles, oxidation generates aldol products, and reduction and arylation form substituted allylic alcohols. 

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3. Improvements in Efficiency and Selectivity for C–F Bond Halogen-Exchange Reactions by Using Boron Reagents

   https://doi.org/10.1055/a-1941-2205  

   Ćorković, Andrej; Dorian, Andreas; Williams, Florence J. (January 2023, Synlett)

   Abstract The use of boron Lewis acids as instigators of bond cleavage offers a number of synthetic possibilities. A unique feature of this class of reagents is the ability to functionalize otherwise inert C–F bonds. We summarize notable developments in C–F bond halogen exchange using Lewis acidic boron reagents and we conclude by featuring our group’s advances in activating CF3 groups by using boron trihalides. 1 Introduction 2 Boron-Mediated Halogen Exchange 3 Mono-Selective C–F Activation 4 Conclusions 

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4. Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF ₂ CN

   https://doi.org/10.1021/jacs.4c03618  

   Nicolai, Jeremy; Fantoni, Tommaso; Butcher, Trevor W; Arlow, Sophie I; Ryabukhin, Serhiy V; Volochnyuk, Dmytro M; Hartwig, John F (June 2024, Journal of the American Chemical Society)

   Molecules bearing fluorine are increasingly prevalent in pharmaceuticals, agrochemicals, and functional materials. The cyanodifluoromethyl group is unique because its size is closer than that of any other substituted difluoromethyl group to the size of the trifluoromethyl group, but its electronic properties are distinct from those of the trifluoromethyl group. In addition, the presence of the cyano group provides synthetic entry to a wide range of substituted difluoromethyl groups. However, the synthesis of cyanodifluoromethyl compounds requires multiple steps, highly reactive reagents (such as DAST, NSFI, or IF5), or specialized starting materials (such as α,α-dichloroacetonitriles or α-mercaptoacetonitriles). Herein, we report a copper-mediated cyanodifluoromethylation of aryl and heteroaryl iodides and activated aryl and heteroaryl bromides with TMSCF2CN. This cyanodifluoromethylation tolerates an array of functional groups, is applicable to late-stage functionalization of complex molecules, yields analogues of FDA-approved pharmaceuticals and fine chemicals, and enables the synthesis of a range of complex molecules bearing a difluoromethylene unit by transformations of the electron-poor CN unit. Calculations of selected steps of the reaction mechanism by Density Functional Theory indicate that the barriers for both the oxidative addition of iodobenzene to [(DMF)CuCF2CN] and the reductive elimination of the fluoroalkyl product from the fluoroalkyl copper intermediate lie in between those of [(DMF)CuCF3] and [(DMF)CuCF2C(O)NMe2]. 

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5. Refining boron–iodane exchange to access versatile arylation reagents

   https://doi.org/10.1039/d1cc06341c  

   Karandikar, Shubhendu S.; Stuart, David R. (January 2022, Chemical Communications)

   Aryl(Mes)iodonium salts, which are multifaceted aryl transfer reagents, are synthesized via boron-iodane exchange. Modification to both the nucleophilic (aryl boron) and electrophilic (mesityl–λ 3 –iodane) reaction components results in improved yield and faster reaction time compared to previous conditions. Mechanistic studies reveal a pathway that is more like transmetallation than S E Ar. 

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