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1. Transition-Metal-Catalyzed Alkyl Heck-Type Reactions

   https://doi.org/10.1055/s-0037-1611659  

   Kurandina, Daria; Chuentragool, Padon; Gevorgyan, Vladimir (February 2019, Synthesis)

   The Heck reaction is one of the most reliable and useful strategies for the construction of C–C bonds in organic synthesis. However, in contrast to the well-established aryl Heck reaction, the analogous reaction employing alkyl electrophiles is much less developed. Significant progress in this area was recently achieved by merging radical-mediated and transition-metal-catalyzed approaches. This review summarizes the advances in alkyl Heck-type reactions from its discovery early in the 1970s up until the end of 2018. 1 Introduction 2 Pd-Catalyzed Heck-Type Reactions 2.1 Benzylic Electrophiles 2.2 α-Carbonyl Alkyl Halides 2.3 Fluoroalkyl Halides 2.4 α-Functionalized Alkyl Halides 2.5 Unactivated Alkyl Electrophiles 3 Ni-Catalyzed Heck-Type Reactions 3.1 Benzylic Electrophiles 3.2 α-Carbonyl Alkyl Halides 3.3 Unactivated Alkyl Halides 4 Co-Catalyzed Heck-Type Reactions 5 Cu-Catalyzed Heck-Type Reactions 6 Other Metals in Heck-Type Reactions 7 Conclusion 

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2. Cooperative Photometallobiocatalysis: Nonheme Fe Enzyme‐Catalyzed Enantioconvergent Radical Decarboxylative Azidation, Thiocyanation, and Isocyanation of Redox‐Active Esters

   https://doi.org/10.1002/anie.202506361  

   Zhao, Liu‐Peng; Lin, Ken; Xie, Pei‐Pei; Liu, Huichong; Xiang, Hengye; Liu, Xin; Zhao, Yunlong; Liu, Peng; Yang, Yang (July 2025, Angewandte Chemie International Edition)

   Abstract Cooperative catalysis with an enzyme and a small‐molecule photocatalyst has recently emerged as a potentially general activation mode to advance novel biocatalytic reactions with synthetic utility. Herein, we report cooperative photobiocatalysis involving an engineered nonheme Fe enzyme and a tailored photoredox catalyst to achieve enantioconvergent decarboxylative azidation, thiocyanation, and isocyanation of redox‐active esters via a radical mechanism. We repurposed and further evolved metapyrocatechase (MPC), a nonheme Fe extradiol dioxygenase not previously studied in new‐to‐nature biocatalysis, for the enantioselective C─N₃, C─SCN, and C─NCO bond formation via an enzymatic Fe─X intermediate (X═N₃, NCS, and NCO). A range of primary, secondary, and tertiary alkyl radical precursors were effectively converted by our engineered MPC, allowing the syntheses of organic azides, thiocyanates, and isocyanates with good to excellent enantiocontrol. Further derivatization of these products furnished valuable compounds including enantioenriched amines, triazoles, ureas, and SCF₃‐containing products. DFT and MD simulations shed light on the mechanism as well as the binding poses of the alkyl radical intermediate in the enzyme active site and the π‐facial selectivity in the enantiodetermining radical rebound. Overall, cooperative photometallobiocatalysis with nonheme Fe enzymes provides a means to develop challenging asymmetric radical transformations eluding small‐molecule catalysis. 

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3. Migratory functionalization of unactivated alkyl bromides for construction of all-carbon quaternary centers via transposed tert-C-radicals

   https://doi.org/10.1038/s41467-020-18658-4  

   Zhu, Chuan; Liu, Ze-Yao; Tang, Luning; Zhang, Heng; Zhang, Yu-Feng; Walsh, Patrick J.; Feng, Chao (December 2020, Nature Communications)

   null (Ed.)

   Abstract Despite remarkable recent advances in transition-metal-catalyzed C(sp 3 )−C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary -C(sp 3 )−C bonds, presumably due to unfavorable steric interactions and competing isomerizations of tertiary alkyl metal intermediates. Reported herein is a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary centers. This approach enables the facile construction of otherwise difficult to prepare all-carbon quaternary centers. Key to the success of this transformation is an unusual remote functionalization via chain walking to the most sterically hindered tertiary C(sp 3 ) center of the substrate. Preliminary mechanistic and radical trapping studies with primary alkyl bromides suggest a unique mode of tertiary C-radical generation through chain-walking followed by Ni–C bond homolysis. This strategy is complementary to the existing coupling protocols with tert -alkyl organometallic or -alkyl halide reagents, and it enables the expedient formation of quaternary centers from easily available starting materials. 

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4. Modifying the internal substituents of self-assembled cages controls their molecular recognition and optical properties

   https://doi.org/10.1039/D2DT01451C  

   Woods, Connor Z.; Wu, Hoi-Ting; Ngai, Courtney; da Camara, Bryce; Julian, Ryan R.; Hooley, Richard J. (July 2022, Dalton Transactions)

   Self-assembled Fe4 L 6 cage complexes with variable internal functions can be synthesized from a 2,7-dibromocarbazole ligand scaffold, which orients six functional groups to the cage interior. Both ethylthiomethylether and ethyldimethylamino groups can be incorporated. The cages show strong ligand-centered fluorescence emission and a broad range of guest binding properties. Coencapsulation of neutral organic guests is favored in the larger, unfunctionalized cage cavity, whereas the thioether cage has a more sterically hindered cavity that favors 1 : 1 guest binding. Binding affinities up to 10 6 M −1 in CH3 CN are seen. The dimethylamino cage is more complex, as the internal amines display partial protonation and can be deprotonated by amine bases. This amine cage displays affinity for a broad range of neutral organic substrates, with affinities and stoichiometries comparable to that of the similarly sized thioether cage. These species show that simple variations in ligand backbone allow variations in the number and type of functions that can be displayed towards the cavity of self-assembled hosts, which will have applications in biomimetic sensing, catalysis and molecular recognition. 

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5. General method for iron-catalyzed multicomponent radical cascades–cross-couplings

   https://doi.org/10.1126/science.abj6005  

   Liu, Lei; Aguilera, Maria Camila; Lee, Wes; Youshaw, Cassandra R.; Neidig, Michael L.; Gutierrez, Osvaldo (October 2021, Science)

   Transition metal–catalyzed cross-coupling reactions are some of the most widely used methods in chemical synthesis. However, despite notable advantages of iron (Fe) as a potentially cheaper, more abundant, and less toxic transition metal catalyst, its practical application in multicomponent cross-couplings remains largely unsuccessful. We demonstrate 1,2-bis(dicyclohexylphosphino)ethane Fe–catalyzed coupling of α-boryl radicals (generated from selective radical addition to vinyl boronates) with Grignard reagents. Then, we extended the scope of these radical cascades by developing a general and broadly applicable Fe-catalyzed multicomponent annulation–cross-coupling protocol that engages a wide range of π-systems and permits the practical synthesis of cyclic fluorous compounds. Mechanistic studies are consistent with a bisarylated Fe(II) species being responsible for alkyl radical generation to initiate catalysis, while carbon-carbon bond formation proceeds between a monoarylated Fe(II) center and a transient alkyl radical. 

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