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1. Palladium‐Catalyzed Aryldifluoromethylation of Aryl Halides with Aryldifluoromethyl Trimethylsilanes

   https://doi.org/10.1002/anie.202208204  

   Choi, Kyoungmin; Mormino, Michael G.; Kalkman, Eric D.; Park, John; Hartwig, John F. (September 2022, Angewandte Chemie International Edition)

   Abstract Diaryl difluoromethanes are valuable targets for medicinal chemistry because they are bioisosteres of diaryl ethers and can function as replacements for diaryl methane, ketone, and sulfone groups. However, methods to prepare diaryl difluoromethanes are scarce, especially methods starting from abundant aryl halides. We report the Pd‐catalyzed aryldifluoromethylation of aryl halides with aryldifluoromethyl trimethylsilanes (TMSCF₂Ar). The reaction occurs when the catalyst contains a simple, but unusual, dialkylaryl phosphine ligand that promotes transmetallation of the silane. Computational studies show that reductive elimination following transmetallation occurs with a low barrier, despite the fluorine atoms on the α‐carbon, due to coordination of the difluorobenzyl π‐system to palladium. The co‐development of a cobalt‐catalyzed synthesis of the silanes broadened the scope of the process including several applications to the synthesis biologically relevant diaryl difluoromethanes. 

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2. Fe-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and Grignard reagents

   https://doi.org/10.1039/D0SC02127J  

   Liu, Lei; Lee, Wes; Youshaw, Cassandra R.; Yuan, Mingbin; Geherty, Michael B.; Zavalij, Peter Y.; Gutierrez, Osvaldo (August 2020, Chemical Science)

   null (Ed.)

   A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp 2 -hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp 2 -hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C–C bonds. 

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3. Fe-Catalyzed dicarbofunctionalization of electron-rich alkenes with Grignard reagents and (fluoro)alkyl halides

   https://doi.org/10.1039/D1CC04619E  

   Rotella, Madeline E.; Sar, Dinabandhu; Liu, Lei; Gutierrez, Osvaldo (November 2021, Chemical Communications)

   An iron-catalyzed regioselective dicarbofunctionalization of electron-rich alkenes is described. In particular, aryl- and alkyl vinyl ethers are used as effective linchpins to couple alkyl or (fluoro)alkyl halides and sp 2 -hybridized Grignard nucleophiles. Preliminary results demonstrate the ability to engage thioethers as linchpins and control enantioselectivity in these transformations, an area which is largely unexplored in iron-catalyzed three-component cross-coupling reactions. 

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4. Forging C−S Bonds Through Decarbonylation: New Perspectives for the Synthesis of Privileged Aryl Sulfides

   https://doi.org/10.1002/cctc.202101206  

   Liu, Chengwei; Szostak, Michal (October 2021, ChemCatChem)

   Abstract Aryl thioethers are tremendously important motifs in various facets of chemical science. Traditional technologies for the precise assembly of aryl thioethers rely on transition‐metal‐catalyzed cross‐coupling of aryl halides; however, despite the continuous advances, the scope of these methods remains limited. Recently a series of reports has advanced an alternative manifold in which thio(esters) are subject to transition‐metal‐catalyzed decarbonylation, which (1) permits to exploit ubiquitous carboxylic acids as highly desirable and orthogonal precursors to aryl halides; (2) overcomes the issues of high concentration of thiolate anion leading to catalyst poisoning; (3) enables for novel disconnections not easily available from aryl halides; and (4) introduces new concepts in catalysis. 

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5. Palladium-catalyzed cross-couplings by C–O bond activation

   https://doi.org/10.1039/d0cy01159b  

   Zhou, Tongliang; Szostak, Michal (September 2020, Catalysis Science & Technology)

   null (Ed.)

   Although palladium-catalyzed cross-coupling of aryl halides and reactive pseudohalides has revolutionized the way organic molecules are constructed today across various fields of chemistry, comparatively less progress has been made in the palladium-catalyzed cross-coupling of less reactive C–O electrophiles. This is despite the fact that the use of phenols and phenol derivatives as bench-stable cross-coupling partners has been well-recognized to bring about major advantages over aryl halides, such as natural abundance of phenols, (2) avoidance of toxic halides, (3) orthogonal cross-coupling conditions, (4) prefunctionalization of phenolic substrates by electrophilic substitution or C–H functionalization, (5) ready availability of phenols from a different pool of precursors than aryl halides. In this review, we present an overview of recent advances made in the field of palladium-catalyzed cross-coupling of C–O electrophiles with a focus on catalytic systems, (2) reaction type, and (3) class of C–O coupling partners. Although the field has been historically dominated by nickel catalysis, it is now evident that the use of more versatile, more functional group tolerant and highly active palladium catalysts supported by appropriately designed ancillary ligands enables the cross-coupling with improved substrate scope and generality, and likely represents a practical solution to the broadly applicable cross-coupling of various C–O bonds across diverse chemical disciplines. The review covers the period through June 2020. 

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