Copper-catalysed amination of alkyl iodides enabled by halogen-atom transfer

Górski, Bartosz; Barthelemy, Anne‐Laure; Douglas, James J.; Juliá, Fabio; Leonori, Daniele

doi:10.1038/s41929-021-00652-8

Cited by 101 publications

(50 citation statements)

References 44 publications

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“…As demonstrated herein by the broad scope of applications in late-stage functionalization, this method represents an attractive tool for synthetic and medicinal chemists to rapidly build molecular complexity and contributes to a rapidly developing field of XAT dual first-row transition metal catalysis. [11,12,22,23] Future challenges include expanding the scope of organic halide partners to aryl/alkyl chlorides without bulky silane XAT agents.…”

Section: Discussionmentioning

confidence: 99%

α‐Amino Radical Halogen Atom Transfer Agents for Metallaphotoredox‐Catalyzed Cross‐Electrophile Couplings of Distinct Organic Halides

et al. 2022

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α‐Amino radicals from simple tertiary amines were employed as halogen atom transfer (XAT) agents in metallaphotoredox catalysis for cross‐electrophile couplings of organic bromides with organic iodides. This XAT strategy proved to be efficient for the generation of carbon radicals from a range of partners (alkyl, aryl, alkenyl, and alkynyl iodides). The reactivities of these radical intermediates were captured by nickel catalysis with organobromides including aryl, heteroaryl, alkenyl, and alkyl bromides, enabling six diverse C−C bond formations. Classic named reactions including Negishi, Suzuki, Heck, and Sonogashira reactions were readily achieved in a net‐reductive fashion under mild conditions. More importantly, the cross coupling was viable with either organic bromide or iodide as limiting reactant based on the availability of substrates, which is beneficial to the late‐stage functionalization of complex molecules. The scalability of this method in batch and flow was investigated, further demonstrating its applicability.

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Section: Discussionmentioning

confidence: 99%

α‐Amino Radical Halogen Atom Transfer Agents for Metallaphotoredox‐Catalyzed Cross‐Electrophile Couplings of Distinct Organic Halides

et al. 2022

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“…In our protocols, a variety of easily available 2-aryl- N -acryloyl indoles can easily react with alkyl radicals, which are generated from alkyl halides through either the XAT or the HAT process, to furnish valuable benzindolo-fused polycyclic compounds in moderate to good yields (Scheme 1d). Compared with the reported works for the preparation of alkyl-substituted indolo[2,1-α]isoquinolines, 15,21,22 our method shows a wide substrate scope of organohalides with highly negative reduction potentials, and should be attractive to the organic chemistry community as there is no need for transition metal catalysts and high temperature.…”

Section: Introductionmentioning

confidence: 95%

Cascade cyclization for the synthesis of indolo[2,1-α]isoquinoline derivatives via visible-light-induced halogen-atom-transfer (XAT) and hydrogen-atom-transfer (HAT)

Guo

Shen

et al. 2022

Org. Biomol. Chem.

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“…To trigger the homolytic activation of organic halides through XAT process, various abstractors such as -aminoalkyl radicals, catalytic Mn specie, organosiliane, and Tin have been developed recently due to the weak C-halogen energy (50 to 70 kcal/mol for C-I bond) 1,16,17 . Leonori 16,[18][19][20][21] and Doyle groups 22,23 independently disclosed -aminoalkyl radicals could abstract the iodide atom under very mild reaction conditions to generate the active alkyl radical which would couple efficiently with broad nucleophiles to construct C-C, C-N and C-S bonds. Zhang reported that catalytic Mn2(CO)10 exhibited powerful reactivity in converting alkyl iodides to alkyl radicals under green LEDs, producing a series of valuable 4-alkyl-1,4-dihydropyridines in high yields 24 .…”

Section: Introductionmentioning

confidence: 99%

Transition-metal Free C-N Bond Formation from Alkyl Iodide via Halogen-atom Transfer (XAT): Dual Roles of Diazonium Salts

Zhang

Jiang

Wang

et al. 2022

Preprint

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The precise and effective construction of challenging C-N bond continues to be one part of the most significant goals in organic chemistry because of the universal applications of amines containing C-N bonds in pharmaceuticals, materials as well as agrochemicals. However, E2 elimination through classic SN2 substitution of alkyl halides with nitrogen nucleophiles often occurs and alkenes are generated as the major side-products especially when secondary or tertiary substrates are employed. Thus, formation of a challenging C(sp3)-N bond especially on tertiary carbon center remains highly desirable. Herein, we present a practically alternative approach to prepare primary, secondary and tertiary alkyl amines with high efficiency between alkyl iodides and electrophilic diazonium salts which are easily accessible and widely utilized in synthetic chemistry. This robust transformation only employs Cs2CO3 as the base promoting the halogen-atom transfer (XAT) process under transition-metal-free reaction conditions, thus providing a rapid and green method to assemble diverse C(sp3)-N bonds. And also, the reaction can be achieved by continuous-flow technology in large scare with Et3N was employed as organic base. Moreover, diazonium salts are found to serve as two important roles (alkyl radical initiator and amination reagent) in this process which was rarely explored in the previous radical reactions. Initial mechanism studies suggest this reaction undergoes through a halogen-atom transfer (XAT) between alkyl iodides and diazonium salts, resulting in the generation of the active alkyl radical which can couple well with diazonium cations to furnish the final products.

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Copper-catalysed amination of alkyl iodides enabled by halogen-atom transfer

Cited by 101 publications

References 44 publications

α‐Amino Radical Halogen Atom Transfer Agents for Metallaphotoredox‐Catalyzed Cross‐Electrophile Couplings of Distinct Organic Halides

α‐Amino Radical Halogen Atom Transfer Agents for Metallaphotoredox‐Catalyzed Cross‐Electrophile Couplings of Distinct Organic Halides

Cascade cyclization for the synthesis of indolo[2,1-α]isoquinoline derivatives via visible-light-induced halogen-atom-transfer (XAT) and hydrogen-atom-transfer (HAT)

Transition-metal Free C-N Bond Formation from Alkyl Iodide via Halogen-atom Transfer (XAT): Dual Roles of Diazonium Salts

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