Article
Chemistry, Organic
Kentaro Sakai, Kounosuke Oisaki, Motomu Kanai
Summary: Selective C(sp(3))-H functionalization using photoredox catalysis and hydrogen atom transfer catalysis has attracted increasing attention. We report the use of a Ph2GeCl2 cocatalyst that greatly improves the yield of alpha-C(sp(3))-H alkylation of primary amines catalyzed by a PC-HAT hybrid system. The alpha-position of the amino group selectively reacts, even when weaker C-H bonds exist in the substrates. This finding may aid in the design of novel site-selective hybrid catalysis.
Article
Chemistry, Multidisciplinary
Youqing Yang, Constantin G. Daniliuc, Armido Studer
Summary: A radical 1,1,2-trifunctionalization of terminal alkynes is achieved using alkyl triflones as precursors and trapping reagents, with good yields of highly substituted cyclopentanes obtained at elevated temperatures using dibenzoyl peroxide or alpha,alpha '-azobisisobutyronitrile as initiators.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Jiayuan Wang, Youwan Ye, Tongzhi Sang, Chenxing Zhou, Xiazhen Bao, Yong Yuan, Congde Huo
Summary: A general C(sp3)-H/C(sp3)-H dehydrogenative coupling strategy for the preparation of various natural or unnatural amino acids from readily available glycine derivatives and hydrocarbons is reported, which involves a combination of SET and HAT process.
Article
Chemistry, Organic
Xiao-Ya Yuan, Ya-Feng Si, Xiang Li, Shao-Jie Wu, Fan-Lin Zeng, Qi-Yan Lv, Bing Yu
Summary: The direct coupling reaction between inert alkanes and quinoxalin-2(1H)-ones was successfully achieved under noble metal-free, acid-free, and oxidant-free conditions, leading to the synthesis of various 3-alkylated quinoxalin-2(1H)-ones with good to excellent yields.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Organic
Petros L. Gkizis
Summary: In the past decade, photochemical cross-coupling reactions have emerged as excellent tools for the formation of C-C bonds under mild reaction conditions. By functionalizing inert C(sp(3))-H substrates and utilizing modern transition metal catalysis, alkyl radicals can be easily generated and intersected with metals. This review summarizes the recent developments in this field and connects them with the seminal contributions that pioneered this research area.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Kedong Xu, Jiawen Yang, Haitao Qin, Feng Liu
Summary: We have reported an efficient photoredox-catalyzed reaction for site-selective C(sp(3))-H functionalization of carboxamides with silyl enol ethers as radical acceptors. The reaction proceeds through amidyl radical-directed 1,5-hydrogen atom transfer (1,5-HAT) and C(sp(3))-C(sp(3)) bond formation via radical addition of silyl enol ethers. The process exhibits mild conditions and high functional-group tolerance, enabling the preparation of a range of carboxamides with pendant carbonyl moieties.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Organic
Ziqi Ye, Yu-Mei Lin, Lei Gong
Summary: This article summarizes recent advances in dual photo-induced HAT and transition metal catalysis for C-H functionalization of alkanes and cycloalkanes. By combining the advantages of light and metal, this method solves the problem of chemical inertness in straight-chain alkanes and cycloalkanes, enabling a variety of selective synthetic reactions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
A. Young Ji, Annaram Thirupathi, Joon Young Hwang, Yuri Kim, Gyuri Han, Kwang-Hyun Ahn, Kyungtae Kang, Eun Joo Kang
Summary: The Fe-III(phen)(3) catalysis of the benzylic C(sp(3))-H azidation of indoles has been studied. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which are transformed into benzylic C(sp(3)) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were constructed, highlighting the utility of this mild first-row transition-metal catalyst system.
Article
Chemistry, Organic
A. Young Ji, Annaram Thirupathi, Joon Young Hwang, Yuri Kim, Gyuri Han, Kwang-Hyun Ahn, Kyungtae Kang, Eun Joo Kang
Summary: The FeIII(phen)3 catalysis of benzylic C(sp3)-H azidation of indoles was studied. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which further transform into benzylic C(sp3) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were synthesized, demonstrating the utility of this mild first-row transition-metal catalyst system.
Article
Chemistry, Organic
Huiwei Xu, Jia-Nan Mo, Wen -Deng Liu, Jiannan Zhao
Summary: A light-free approach using N-heterocyclic carbene catalysis and a radical-mediated 1,5-hydrogen atom transfer (HAT) mechanism is developed for the benzylic C-H acylation and cascade cyclization of o-alkyl benzamides. Different from photoredox catalysis, this method generates amidyl radicals through single-electron transfer (SET) with Breslow enolates. The mild process tolerates various functional groups and provides a variety of dihydroisoquinolinones in moderate to high yields. The electrochemical properties of the aryloxyamide support the hypothesis of ground-state SET, and a plausible mechanism for the organocatalytic transformation is proposed.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Organic
Zhu Cao, Huihui Zhang, Xinxin Wu, Yahong Li, Chen Zhu
Summary: The research achieved the heteroarylation of unactivated aliphatic C-H bonds through radical-mediated heteroaryl migration, leading to a variety of heteroaryl-substituted aliphatic ketones. The method is applicable to O-/S-/N-containing heteroaryls and features mild C-C bond cleavage and good selectivity for tertiary C-H bonds.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Xinyu Liu, Zhifan Wang, Qiwei Wang, Yuanhua Wang
Summary: The selective diamination of arylcyclobutanes was achieved by rhodium(II) catalysis using N-fluorobenzenesulfonimide as the oxidant and nitrogen source.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Fen Su, Juan Zou, Xiaokang Lv, Fengfei Lu, Yijie Long, Kun Tang, Benpeng Li, Huifang Chai, Xingxing Wu, Yonggui Robin Chi
Summary: The development of catalyst-controlled methods for direct functionalization of two distinct C-H bonds is an appealing approach for C-C formations in synthetic chemistry. This article describes an organocatalytic approach using readily available aldehyde as acyl source, which allows for the straightforward acylation of C(sp(3))-H bonds involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp(3))-H bonds. The developed method provides a wide range of ketones under mild conditions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Zeng-Hui Lin, Yu-Fei Yao, Cheng-Pan Zhang
Summary: Deuteration of arylthianthren-S-ium triflates with CD3OD or CD3OD/CD3COCD3 in the presence of Cs2CO3 by palladium catalysis or photoirradiation allows for the convenient synthesis of deuterated arenes in good yields. The Pd-catalyzed reaction generally gives better yields than the photoinduced deuteration, but exceptions exist. These reactions highlight eco-friendly conditions, simplicity, inexpensive deuterium sources, good functional group tolerance, and a range of substrates. This protocol provides a high selectively formal aromatic C-H deuteration for efficient deuterium labeling of multifunctionalized arenes and drug molecules.
Article
Multidisciplinary Sciences
Zhaoliang Yang, Yunhong Niu, Xiaoqian He, Suo Chen, Shanshan Liu, Zhengyu Li, Xiang Chen, Yunxiao Zhang, Yu Lan, Xiao Shen
Summary: The study introduces a strategy to inhibit 1,5-HAT by introducing a silyl group into the alpha-position of alkoxyl radicals, enabling the preparation of various alpha-functionalized products from alcohol substrates. In contrast to direct generation of alpha-carbon radicals, this strategy distinguishes itself by generating alkoxyl radicals and using silyl alcohols as limiting reagents to achieve selective transformations.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Soumik Biswas, Michael J. Blessent, Benjamin M. Gordon, Tian Zhou, Santanu Malakar, David Y. Wang, Karsten Krogh-Jespersen, Alan S. Goldman
Summary: The PCP-pincer iridium complexes exhibit high regioselectivity for the transfer dehydrogenation of n-alkanes, while the closely related PCOP and POCOP complexes do not. The difference in regioselectivity is a true kinetic phenomenon, not a result of isomerization subsequent to the formation of free alpha-olefin. The different regioselectivity of the POCOPIr vs PCPIr catalysts is attributable to the different rate-determining steps of their respective catalytic cycles, which can be explained in terms of different electronic effects of O versus CH2 linker exerted through the pincer aromatic ring.
Article
Chemistry, Inorganic & Nuclear
Quinton J. Bruch, Santanu Malakar, Alan S. Goldman, Alexander J. M. Miller
Summary: This study demonstrates the electrochemical N-2 binding and splitting capabilities of a molybdenum complex, and investigates the reaction pathways and intermediates involved. Electrochemical kinetic analysis, spectroelectrochemical monitoring, and computational studies reveal two concurrent reaction pathways.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Xiaoguang Zhou, Santanu Malakar, Thomas Dugan, Kun Wang, Aaron Sattler, David O. Marler, Thomas J. Emge, Karsten Krogh-Jespersen, Alan S. Goldman
Summary: A highly efficient catalyst for acceptorless dehydrogenation of alkanes was reported, featuring an iridium acetate complex with a fluorinated Phebox ligand. Computational studies shed light on possible mechanistic pathways, improving our understanding of this catalyst's behavior. The role of Na+ as a cocatalyst in promoting dechelation and lowering energy barriers was highlighted, along with the electrophilic nature of the reaction and the stability of the fluorinated catalyst.
Article
Chemistry, Multidisciplinary
[Anonymous]
Summary: Breslow intermediates are pivotal species in Umpolung catalysis. This study reveals that, under aprotic conditions, the Breslow intermediate itself promotes a critical hydrogen shift in an autocatalytic manner.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Alina Wessels, Martin Klussmann, Martin Breugst, Nils E. Schloerer, Albrecht Berkessel
Summary: In this study, the mechanism of the reaction between N-heterocyclic carbenes and aldehydes under aprotic conditions was investigated using kinetic studies and DFT calculations. Different mechanistic regimes were proposed depending on the NHC-to-aldehyde ratio, with the H-shift occurring either in the NHC-aldehyde adduct or in the equilibrium between the zwitterion and hemiacetal forms. Furthermore, an H-bonded complex of the reaction intermediate with excess NHC was detected.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Marco Galeotti, Chiara Trasatti, Sergio Sisti, Michela Salamone, Massimo Bietti
Summary: A kinetic study was conducted to investigate the hydrogen atom transfer (HAT) reactions from nitrogen-containing heterocycles to the cumyloxyl radical. The study revealed that HAT occurs through hyperconjugative overlap between the C-H bonds and the N-C???O π system. The size of the ring and the functional group have significant effects on the reaction rate.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Fengjiao Liu, Siqi Ma, Zeying Lu, Anjanay Nangia, Meng Duan, Yanmin Yu, Guochao Xu, Ye Mei, Massimo Bietti, K. N. Houk
Summary: Density functional theory calculations were employed to study the reactions of radicals with C-H bonds in different environments, and modified Evans-Polanyi treatments were used to analyze the variations in activation barriers, with a focus on polarity and unsaturation effects. The study revealed the quantitative importance of the thermodynamics of reactions and polar effects in determining barriers to reactions involving radicals and C-H bonds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Marco Galeotti, Laia Vicens, Michela Salamone, Miquel Costas, Massimo Bietti
Summary: The C(sp(3))-H bond oxygenation of cyclopropane-containing mechanistic probes has been studied using hydrogen peroxide catalyzed by manganese complexes. The study showed the presence of both unrearranged and rearranged oxygenation products, suggesting the involvement of cationic intermediates and different pathways. The selective formation of either unrearranged or rearranged product in high yield can be achieved by choosing appropriate catalyst structure and reaction conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Inorganic & Nuclear
Santanu Malakar, Benjamin M. Gordon, Souvik Mandal, Thomas J. Emge, Alan S. Goldman
Summary: The reaction between [(p-cymene)RuCl2]2 and the triphosphine ligand bis(2-di-tert-butylphosphinophenyl)phosphine (tBuPHPP) leads to an exchange reaction where a chloride ligand and a phosphorus-bound H atom are exchanged to form the (chlorophosphine)ruthenium hydride complex (tBuPClPP)RuHCl. The thermodynamics of Cl-P/Ru-H exchange depends on the nature of the ancillary ligand. This study has implications for five-coordinate d6 complexes.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Sergio Sisti, Fabio Ioele, Filippo Scarchilli, Marco Galeotti, Gino A. Dilabio, Michela Salamone, Massimo Bietti
Summary: Kinetic and product studies were conducted on the reactions of tert-alkoxyl radicals with secondary and tertiary alkanamides bearing benzylic alpha-C H bonds. The results revealed the exclusive HAT from the benzylic alpha-C H bonds, indicating a lack of benzylic activation and the presence of steric and stereoelectronic effects. In the isoindoline and tetrahydroisoquinoline derivatives, significant increases in kH were observed due to optimal overlap with both the phenyl p-system and the amide p-system or amine nitrogen lone pair, demonstrating the strong contribution of stereoelectronic activation.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Marco Galeotti, Woojin Lee, Sergio Sisti, Martina Casciotti, Michela Salamone, K. N. Houk, Massimo Bietti
Summary: A product and DFT computational study was conducted on the reactions of 3-ethyl-3-(trifluoromethyl)dioxirane (ETFDO) with bicyclic and spirocyclic hydrocarbons bearing cyclopropyl groups. The reactions exhibited good site-selectivities and diastereoselectivities, which were supported by calculated activation free energies. The computational results showed that hyperconjugative interactions between the cyclopropane C-C bonding orbitals and the sigma* orbitals of the C-H bonds activated these bonds towards hydrogen atom transfer to ETFDO.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Sergio Sisti, Marco Galeotti, Filippo Scarchilli, Michela Salamone, Miquel Costas, Massimo Bietti
Summary: A detailed study on C(sp(3))-H bond oxygenation reactions catalyzed by [Mn(OTf)(2)((TIPS)mcp)] complex was conducted, showing that the introduction of electron-withdrawing functional groups in different solvents significantly increased site-selectivity and product yield. The study also achieved selective control over multiple methylenic sites.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Andrea Palone, Guillem Casadevall, Sergi Ruiz-Barragan, Arnau Call, Siilvia Osuna, Massimo Bietti, Miquel Costas
Summary: This study describes a catalytic enantioselective hydroxylation method of tertiary C-H bonds in cyclohexane scaffolds using an evolved manganese catalyst and H2O2. The catalytic system provides structural complementarity to the substrate similarly to lock-and-key recognition in enzymatic active sites. Theoretical calculations reveal that enantioselectivity is determined by the precise fitting of the substrate scaffold into the catalytic site through a network of complementary weak non-covalent interactions. Stereoretentive C(sp(3))-H hydroxylation results in the generation of multiple stereogenic centers in a single step, which can be orthogonally manipulated to obtain a variety of chiral scaffolds from a single precursor molecule.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Marco Galeotti, Michela Salamone, Massimo Bietti
Summary: Direct functionalization of C(sp(3))-H bonds is a key focus in developing new synthetic methods. Among intermolecular C-H bond functionalization strategies, hydrogen atom transfer (HAT) methods using radical or radical-like reagents have gained increasing attention due to their ability to introduce a variety of atoms and groups in mild conditions. Selectivity control over aliphatic C-H bonds is crucial and factors influencing it have been discussed. This review article provides a detailed description of HAT reagents, associated mechanistic features, and selectivity patterns observed in the functionalization of increasingly complex substrates, based on an analysis of recent literature.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Organic
Sensheng Liu, Martin Klussmann
Summary: Transition metals are the main catalysts for redox reactions involving peroxides and organic substrates. However, triarylamines can also act as organic redox catalysts, facilitating oxidative difunctionalization reactions of alkenes and oxidative Ritter reactions. Mechanistic studies have shown that triarylamines act as catalysts, mediating the reactions through electron transfer processes.
ORGANIC CHEMISTRY FRONTIERS
(2021)
