Radical Borylation of Alkyl Bromides by Photoinduced Halogen‐Atom Transfer

Schull, Cullen R.; McGill, Matthew J.; Renteria‐Gómez, Ángel; Mukherjee, Poulami; Tyndall, Samuel B.; Shoemaker, Aaron H.; Wasielewski, Michael R.; Gutierrez, Osvaldo; Scheidt, Karl A.

doi:10.1002/anie.202510162

Radical Borylation of Alkyl Bromides by Photoinduced Halogen‐Atom Transfer

Journal Article · Mon Aug 04 00:00:00 EDT 2025 · Angewandte Chemie (International Edition)

DOI:https://doi.org/10.1002/anie.202510162· OSTI ID:3014147

Schull, Cullen R. ^[1]; McGill, Matthew J. ^[1]; Renteria‐Gómez, Ángel ^[2]; Mukherjee, Poulami ^[2]; Tyndall, Samuel B. ^[1]; Shoemaker, Aaron H. ^[1]; Wasielewski, Michael R. ^[1]; Gutierrez, Osvaldo ^[2]; ^[1]

Northwestern University, Evanston, IL (United States)
University of California, Los Angeles, CA (United States)

Alkyl organoboron compounds are versatile synthons in organic synthesis, enabling rapid access to a variety of carbon─carbon and carbon-heteroatom bonds. As such, strategies to efficiently access carbon-boron bonds from simple chemical feedstocks are highly desirable. The radical borylation of alkyl bromides presents an attractive approach. However, the activation of alkyl bromides typically requires strong reductants or transition-metal catalysts. Herein, we report a metal-free radical borylation strategy of various alkyl bromides utilizing a photoinduced silyl radical to mediate a halogen-atom transfer process. This method demonstrates broad utility and functional group tolerance among various primary, secondary, and tertiary unactivated alkyl bromides and can facilitate the functionalization of pharmaceutically relevant motifs. Mechanistic and computational studies support a radical-chain pathway involving a silyl radical-mediated halogen-atom transfer.

View Accepted Manuscript (DOE)

Research Organization:: Northwestern University, Evanston, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: FG02-99ER14999

OSTI ID:: 3014147

Journal Information:: Angewandte Chemie (International Edition), Journal Name: Angewandte Chemie (International Edition) Journal Issue: 38 Vol. 64; ISSN 1521-3773; ISSN 1433-7851

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

Alkylboronic Esters from Copper‐Catalyzed Borylation of Primary and Secondary Alkyl Halides and Pseudohalides Yang, Chu‐Ting; Zhang, Zhen‐Qi; Tajuddin, Hazmi Angewandte Chemie International Edition, Vol. 51, Issue 2 https://doi.org/10.1002/anie.201106299	journal	December 2011
Zinc‐Catalyzed Borylation of Primary, Secondary and Tertiary Alkyl Halides with Alkoxy Diboron Reagents at Room Temperature Bose, Shubhankar Kumar; Fucke, Katharina; Liu, Lei Angewandte Chemie International Edition, Vol. 53, Issue 7 https://doi.org/10.1002/anie.201308855	journal	January 2014
Selective C−N Borylation of Alkyl Amines Promoted by Lewis Base Hu, Jiefeng; Wang, Guoqiang; Li, Shuhua Angewandte Chemie International Edition, Vol. 57, Issue 46 https://doi.org/10.1002/anie.201809608	journal	November 2018
Metal‐Free Radical Borylation of Alkyl and Aryl Iodides Cheng, Ying; Mück‐Lichtenfeld, Christian; Studer, Armido Angewandte Chemie International Edition, Vol. 57, Issue 51 https://doi.org/10.1002/anie.201810782	journal	November 2018
Deoxygenative Borylation of Secondary and Tertiary Alcohols Friese, Florian W.; Studer, Armido Angewandte Chemie International Edition, Vol. 58, Issue 28 https://doi.org/10.1002/anie.201904028	journal	June 2019
Photoinduced Deoxygenative Borylations of Aliphatic Alcohols Wu, Jingjing; Bär, Robin M.; Guo, Lin Angewandte Chemie International Edition, Vol. 58, Issue 52 https://doi.org/10.1002/anie.201910051	journal	November 2019
Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4‐Phenylpyridine Zhang, Li; Wu, Zhong‐Qian; Jiao, Lei Angewandte Chemie International Edition, Vol. 59, Issue 5 https://doi.org/10.1002/anie.201912564	journal	December 2019
Radical Brook Rearrangements: Concept and Recent Developments Zhang, Ying; Chen, Jun‐Jie; Huang, Huan‐Ming Angewandte Chemie International Edition, Vol. 61, Issue 37 https://doi.org/10.1002/anie.202205671	journal	July 2022
Deaminative Borylation of Aliphatic Amines Enabled by Visible Light Excitation of an Electron Donor–Acceptor Complex Sandfort, Frederik; Strieth‐Kalthoff, Felix; Klauck, Felix J. R. Chemistry – A European Journal, Vol. 24, Issue 65 https://doi.org/10.1002/chem.201804246	journal	October 2018
Photoinduced NaI‐Promoted Radical Borylation of Alkyl Halides and Pseudohalides Wang, Chenglan; Zhou, Lu; Yang, Kai Chinese Journal of Chemistry, Vol. 39, Issue 7 https://doi.org/10.1002/cjoc.202100115	journal	May 2021
Photoinduced Radical Borylation of Alkyl Chlorides Bai, Lutao; Jiao, Lei European Journal of Organic Chemistry, Vol. 27, Issue 14 https://doi.org/10.1002/ejoc.202400043	journal	March 2024
Recent Developments in Organoboron Chemistry: Old Dogs, New Tricks Fyfe, James W. B.; Watson, Allan J. B. Chem, Vol. 3, Issue 1 https://doi.org/10.1016/j.chempr.2017.05.008	journal	July 2017
Design and discovery of boronic acid drugs Plescia, Jessica; Moitessier, Nicolas European Journal of Medicinal Chemistry, Vol. 195 https://doi.org/10.1016/j.ejmech.2020.112270	journal	June 2020
Boronic acid-functionalized nanoparticles: synthesis by microemulsion polymerization and application as a re-usable optical nanosensor for carbohydrates Cannizzo, Caroline; Amigoni-Gerbier, Sonia; Larpent, Chantal Polymer, Vol. 46, Issue 4 https://doi.org/10.1016/j.polymer.2004.11.052	journal	February 2005
Flow photochemical Giese reaction via silane-mediated activation of alkyl bromides Fanini, Fabiola; Luridiana, Alberto; Mazzarella, Daniele Tetrahedron Letters, Vol. 117 https://doi.org/10.1016/j.tetlet.2023.154380	journal	March 2023
The Chemistry of Boronic Acids in Nanomaterials for Drug Delivery Stubelius, Alexandra; Lee, Sangeun; Almutairi, Adah Accounts of Chemical Research, Vol. 52, Issue 11 https://doi.org/10.1021/acs.accounts.9b00292	journal	October 2019
Photoinduced Borylation for the Synthesis of Organoboron Compounds Tian, Ya-Ming; Guo, Xiao-Ning; Braunschweig, Holger Chemical Reviews, Vol. 121, Issue 7 https://doi.org/10.1021/acs.chemrev.0c01236	journal	February 2021
Applications of Halogen-Atom Transfer (XAT) for the Generation of Carbon Radicals in Synthetic Photochemistry and Photocatalysis Juliá, Fabio; Constantin, Timothée; Leonori, Daniele Chemical Reviews, Vol. 122, Issue 2 https://doi.org/10.1021/acs.chemrev.1c00558	journal	December 2021
Photoinduced Fragmentation Borylation of Cyclic Alcohols and Hemiacetals Shu, Chao; Madhavachary, Rudrakshula; Noble, Adam Organic Letters, Vol. 22, Issue 18 https://doi.org/10.1021/acs.orglett.0c02513	journal	September 2020
Aryl Boronic Esters Are Stable on Silica Gel and Reactive under Suzuki–Miyaura Coupling Conditions Oka, Naoki; Yamada, Tsuyoshi; Sajiki, Hironao Organic Letters, Vol. 24, Issue 19 https://doi.org/10.1021/acs.orglett.2c01174	journal	May 2022
Decarboxylative Borylation of Aliphatic Esters under Visible-Light Photoredox Conditions Hu, Dawei; Wang, Linghua; Li, Pengfei Organic Letters, Vol. 19, Issue 10 https://doi.org/10.1021/acs.orglett.7b01181	journal	May 2017
Transition-Metal-Free Borylation of Alkyl Iodides via a Radical Mechanism Liu, Qianyi; Hong, Junting; Sun, Beiqi Organic Letters, Vol. 21, Issue 17 https://doi.org/10.1021/acs.orglett.9b01951	journal	June 2019
Highly Efficient Synthesis of Alkylboronate Esters via Cu(II)-Catalyzed Borylation of Unactivated Alkyl Bromides and Chlorides in Air Bose, Shubhankar Kumar; Brand, Simon; Omoregie, Helen Oluwatola ACS Catalysis, Vol. 6, Issue 12 https://doi.org/10.1021/acscatal.6b02918	journal	November 2016
Photochemical Organocatalytic Borylation of Alkyl Chlorides, Bromides, and Sulfonates Mazzarella, Daniele; Magagnano, Giandomenico; Schweitzer-Chaput, Bertrand ACS Catalysis, Vol. 9, Issue 7 https://doi.org/10.1021/acscatal.9b01482	journal	May 2019
Molecular Tectonics. Use of the Hydrogen Bonding of Boronic Acids To Direct Supramolecular Construction Fournier, Jean-Hugues; Maris, Thierry; Wuest, James D. Journal of the American Chemical Society, Vol. 125, Issue 4 https://doi.org/10.1021/ja0276772	journal	December 2002
Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, To Generate Carbon–Boron Bonds Dudnik, Alexander S.; Fu, Gregory C. Journal of the American Chemical Society, Vol. 134, Issue 25 https://doi.org/10.1021/ja304068t	journal	June 2012
Iron-Catalyzed Borylation of Alkyl Electrophiles Atack, Thomas C.; Lecker, Rachel M.; Cook, Silas P. Journal of the American Chemical Society, Vol. 136, Issue 27 https://doi.org/10.1021/ja505199u	journal	June 2014
Cross-Electrophile Coupling of Unactivated Alkyl Chlorides Sakai, Holt A.; Liu, Wei; Le, Chi “Chip” Journal of the American Chemical Society, Vol. 142, Issue 27 https://doi.org/10.1021/jacs.0c04812	journal	June 2020
Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution Gould, Colin A.; Pace, Andria L.; MacMillan, David. W. C. Journal of the American Chemical Society, Vol. 145, Issue 30 https://doi.org/10.1021/jacs.3c05405	journal	July 2023
Persistent Boryl Radicals as Highly Reducing Photoredox Catalysts for Debrominative Borylations Wu, Jingjing; Wang, Hui; Fang, Huaquan Journal of the American Chemical Society, Vol. 147, Issue 23 https://doi.org/10.1021/jacs.5c03864	journal	May 2025
Manganese-Catalyzed Borylation of Unactivated Alkyl Chlorides Atack, Thomas C.; Cook, Silas P. Journal of the American Chemical Society, Vol. 138, Issue 19 https://doi.org/10.1021/jacs.6b03157	journal	May 2016
Transition Metal-Free 1,2-Carboboration of Unactivated Alkenes Cheng, Ying; Mück-Lichtenfeld, Christian; Studer, Armido Journal of the American Chemical Society, Vol. 140, Issue 20 https://doi.org/10.1021/jacs.8b03333	journal	May 2018
Photoinduced Deaminative Borylation of Alkylamines Wu, Jingjing; He, Lin; Noble, Adam Journal of the American Chemical Society, Vol. 140, Issue 34 https://doi.org/10.1021/jacs.8b07103	journal	July 2018
Palladium-Catalyzed Borylation of Primary Alkyl Bromides Joshi-Pangu, Amruta; Ma, Xinghua; Diane, Mohamed The Journal of Organic Chemistry, Vol. 77, Issue 15 https://doi.org/10.1021/jo301156e	journal	July 2012
Copper(I)-Catalyzed Boryl Substitution of Unactivated Alkyl Halides Ito, Hajime; Kubota, Koji Organic Letters, Vol. 14, Issue 3 https://doi.org/10.1021/ol203413w	journal	January 2012
Organoboranes. 31. A simple preparation of boronic esters from organolithium reagents and selected trialkoxyboranes Brown, Herbert C.; Cole, Thomas E. Organometallics, Vol. 2, Issue 10 https://doi.org/10.1021/om50004a009	journal	October 1983
Metal-free photoinduced C(sp3)–H borylation of alkanes Shu, Chao; Noble, Adam; Aggarwal, Varinder K. Nature, Vol. 586, Issue 7831 https://doi.org/10.1038/s41586-020-2831-6	journal	October 2020
Selection of boron reagents for Suzuki–Miyaura coupling Lennox, Alastair J. J.; Lloyd-Jones, Guy C. Chem. Soc. Rev., Vol. 43, Issue 1 https://doi.org/10.1039/C3CS60197H	journal	January 2014
Stereospecific functionalizations and transformations of secondary and tertiary boronic esters Sandford, Christopher; Aggarwal, Varinder K. Chemical Communications, Vol. 53, Issue 40 https://doi.org/10.1039/C7CC01254C	journal	January 2017
Boronic acids as building blocks for the construction of therapeutically useful bioconjugates António, João P. M.; Russo, Roberto; Carvalho, Cátia Parente Chemical Society Reviews, Vol. 48, Issue 13 https://doi.org/10.1039/C9CS00184K	journal	January 2019
New avenues for C–B bond formationviaradical intermediates Friese, Florian W.; Studer, Armido Chemical Science, Vol. 10, Issue 37 https://doi.org/10.1039/C9SC03765A	journal	January 2019
Transition metal-free synthesis of alkyl pinacol boronates Das, Kanak Kanti; Paul, Swagata; Panda, Santanu Organic & Biomolecular Chemistry, Vol. 18, Issue 44 https://doi.org/10.1039/D0OB01721C	journal	January 2020
Transition metal- and light-free radical borylation of alkyl bromides and iodides using silane Sun, Beiqi; Zheng, Sihan; Mo, Fanyang Chemical Communications, Vol. 57, Issue 46 https://doi.org/10.1039/D1CC02134F	journal	January 2021
C(sp³)–C(sp³) coupling of non-activated alkyl-iodides with electron-deficient alkenes via visible-light/silane-mediated alkyl-radical formation Mistry, Sanesh; Kumar, Roopender; Lister, Andrew Chemical Science, Vol. 13, Issue 44 https://doi.org/10.1039/D2SC03516B	journal	January 2022
Fluorescent saccharide receptors: a sweet solution to the design, assembly and evaluation of boronic acid derived PET sensors James, Tony D.; Linnane, Patrick; Shinkai, Seiji Chemical Communications, Issue 3 https://doi.org/10.1039/cc9960000281	journal	January 1996
A Protocol for Direct Stereospecific Amination of Primary, Secondary, and Tertiary Alkylboronic Esters Morken, James; Edelstein, Emma; Grote, Andrea Synlett, Vol. 29, Issue 13 https://doi.org/10.1055/s-0037-1610172	journal	June 2018
Photoinduced decarboxylative borylation of carboxylic acids Fawcett, Alexander; Pradeilles, Johan; Wang, Yahui Science, Vol. 357, Issue 6348 https://doi.org/10.1126/science.aan3679	journal	July 2017
A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes Le, Chip; Chen, Tiffany Q.; Liang, Tao Science, Vol. 360, Issue 6392 https://doi.org/10.1126/science.aat4133	journal	May 2018
Suzuki–Miyaura cross-couplings for alkyl boron reagent: recent developments—a review Ahmed, Adnan; Mushtaq, Irfan; Chinnam, Sampath Future Journal of Pharmaceutical Sciences, Vol. 9, Issue 1 https://doi.org/10.1186/s43094-023-00520-1	journal	August 2023
Recent Applications of the (TMS)3SiH Radical-Based Reagent Chatgilialoglu, Chryssostomos; Lalevée, Jacques Molecules, Vol. 17, Issue 1 https://doi.org/10.3390/molecules17010527	journal	January 2012

Similar Records

Carbon-halogen bond dissociation at copper surfaces: Alkyl radicals versus metal alkyls

Thesis/Dissertation · Thu Dec 31 23:00:00 EST 1992 · OSTI ID:7283831

Cobalt‐Catalyzed Electroreductive Alkylation of Unactivated Alkyl Chlorides with Conjugated Olefins

Journal Article · Tue Nov 28 19:00:00 EST 2023 · Angewandte Chemie · OSTI ID:2223003

Cobalt‐Catalyzed Electroreductive Alkylation of Unactivated Alkyl Chlorides with Conjugated Olefins

Journal Article · Tue Nov 28 19:00:00 EST 2023 · Angewandte Chemie (International Edition) · OSTI ID:2222841

Related Subjects

Alkyls
Borylation
Halogens
Photochemistry
Radicals

Radical Borylation of Alkyl Bromides by Photoinduced Halogen‐Atom Transfer

Citation Formats

References (50)

Similar Records

Related Subjects