Review
Chemistry, Multidisciplinary
Clement Jacob, Bert U. W. Maes, Gwilherm Evano
Summary: Direct functionalization of C-H bonds is a fundamental transformation in organic synthesis, often relying on directing groups for activation. The development of transient directing groups strategy has revolutionized C-H bond functionalization, allowing for direct and selective introduction of functional groups onto various substrates.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Yi-Hao Li, Yuxin Ouyang, Nikita Chekshin, Jin-Quan Yu
Summary: Pd(II)-catalyzed site-selective beta- and gamma-C(sp3)-H arylation of primary aldehydes is achieved by rational design of L,X-type transient directing groups (TDG). External 2-pyridone ligands are crucial for the observed reactivity. By minimizing the loading of acid additives, the ligand effect is enhanced to achieve high reactivities of the challenging primary aldehyde substrates. Site selectivity can be switched by changing the bite angle of TDG to match the desired palladacycle size, as supported by experimental and computational investigations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Yangyang Wang, Gaorong Wu, Xiaobo Xu, Binghan Pang, Shaowen Liao, Yafei Ji
Summary: This study develops a method for the direct arylation of aliphatic ketones via Pd-catalyzed beta-C(sp(3))-H bond functionalization using 2-(aminooxy)-N,N-dimethylacetamide as a novel transient directing group (TDG), resulting in moderate to good yields. The reaction is tolerant to abundant substrate of ketones and aryl iodides, expanding the applications of TDGs.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ming-Shun Mei, Yanghui Zhang
Summary: A new approach for the synthesis of naphthalimides via a tandem reaction of o-methylbenzaldehydes and maleimides is developed in this work. The reaction involves Pd(II)-catalyzed benzylic C(sp(3))-H oxidation using an amino acid as the transient directing group and Diels-Alder reaction. The subsequent dehydration forms naphthalimides, allowing for easy access to a range of naphthalimides with a variety of substituents.
Article
Chemistry, Multidisciplinary
Changseok Lee, Hyung-Joon Kang, Huiyeong Seo, Sungwoo Hong
Summary: This study reports a highly enantio- and regioselective Ni-catalyzed hydroamination of unactivated alkenes. It is applicable to common but unreactive alkenes and has a broad range of amine coupling partners, showing great potential for late-stage functionalization of complex molecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Yi-Hao Li, Yuxin Ouyang, Nikita Chekshin, Jin-Quan Yu
Summary: Pd(II)-catalyzed gamma-C(sp3)-H (hetero)arylation of aliphatic ketones using alpha-amino acids as transient directing groups (TDG) has been developed. By reducing the loading of acid additives, the crucial ligand effect of 2-pyridone is enhanced, leading to improved reactivity and the possibility of cyclic gamma-methylene C(sp3)-H arylation of ketones. Mechanistic investigation and comparison to the gamma-C-H arylation of aldehydes provide structural insights for designing site-selective TDGs.
Editorial Material
Chemistry, Multidisciplinary
Sara Kopf, Fei Ye, Helfried Neumann, Matthias Beller
Summary: A novel ruthenium-catalyzed C-H activation method for hydrogen isotope exchange of aromatic carbonyl compounds is presented, achieving high levels of deuterium incorporation and showing good functional group tolerance. The methodology offers cost-efficient alternatives to state-of-the-art iridium-catalyzed procedures and can be applied in pharmaceutical drug labeling.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Sara Kopf, Fei Ye, Helfried Neumann, Matthias Beller
Summary: A novel ruthenium-catalyzed method for hydrogen isotope exchange of aromatic carbonyl compounds is presented, achieving high degrees of deuteration and selective labeling of the alpha-carbonyl position. The methodology demonstrates good functional group tolerance and potential for labeling and modification of pharmaceutical drugs.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Sadegh Shabani, Yuezhou Wu, Hannah G. Ryan, Craig A. Hutton
Summary: The importance of peptide modifications and the use of C-H activation/functionalization as an effective pathway for peptide modification are discussed. Bidentate directing group strategies are recognized as one of the most efficient methods for site-selective C-H activation and functionalization.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Organic
Saqib A. Iqbal, Clement R. P. Millet, Juergen Pahl, Kang Yuan, Michael J. Ingleson
Summary: Two templates used in meta-directed C-H functionalization under metal catalysis cannot direct meta-C-H borylation under electrophilic borylation conditions. One template forms Lewis adducts with Lewis basic sites in the presence of BCl3, while the other template, containing an amide linker, only leads to amide directed ortho C-H borylation with no pyridyl directed meta borylation. The selective ortho borylation of the aniline derived unit in the template suggests a higher barrier to pyridyl directed meta borylation and the need for customized templates for enabling meta-directed electrophilic borylation.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jin-Tang Cheng, Li-Jun Xiao, Shao-Qun Qian, Zhe Zhuang, An Liu, Jin-Quan Yu
Summary: In this study, we report the first example of selective Pd(II)-catalyzed tertiary C-H activation of cyclobutylmethyl ketones using a transient directing group. An electron-deficient 2-pyridone ligand was identified as the optimal external ligand to achieve tertiary C-H activation. Various cyclobutylmethyl ketones with quaternary carbon centers were obtained in high yields without the need for preinstalling internal directing groups, and showed high regioselectivity for tertiary C-H arylation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Multidisciplinary
Jayabrata Das, Wajid Ali, Debabrata Maiti
Summary: In this review, the development of C(sp3)-H activation is highlighted, including its origins, progression, and overcoming of limitations, to identify future research directions. The three main strategies for C(sp3)-H activation in aliphatic molecules are static directing group (DG) or template-assisted approach, transient DG (TDG) approach, and native functional group (NFG)-assisted approach. Each section provides a brief discussion on the evolution, functionalization type, advantages, and shortcomings of C(sp3)-H activation.
TRENDS IN CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Sara Kopf, Helfried Neumann, Matthias Beller
Summary: The novel manganese-catalyzed method enables selective hydrogen isotope exchange of benzaldehydes using D2O as a cheap and convenient source of deuterium. The reaction shows excellent functional group tolerance and high ortho-selectivity can be achieved in the presence of catalytic amounts of specific amines that form a transient directing group in situ.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Isaac Maksso, Ramesh C. Samanta, Yifei Zhan, Kai Zhang, Svenja Warratz, Lutz Ackermann
Summary: The chemical up-cycling of polymers into value-added materials provides an opportunity for a circular economy. This study demonstrates the selective up-cycling of polystyrenes and polyolefins to C(sp(3))-H azidated materials through chemo-selective mangana-electrocatalysis. The functionalized polymers obtained showed high mass retention and functionalization. The electrocatalysis approach proved to be scalable and has implications for a green hydrogen economy.
Article
Chemistry, Organic
Subhashree. S. S. Panda, Nagendra. K. K. Sharma
Summary: This report describes a new synthetic methodology for the ortho-arylation of arylamines and alpha-aromatic amino acids using a Pd-catalyzed C(sp(2))-H activation. The use of diethoxyethyl-l-proline as a transient directing group allows for the formation of mono-arylated arylamines as the major products using aryliodides. This method shows promise for the synthesis of various biphenyl amines and novel peptidomimetics.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Juan J. Rojas, Rosemary A. Croft, Alistair J. Sterling, Edward L. Briggs, Daniele Antermite, Daniel C. Schmitt, Luka Blagojevic, Peter Haycock, Andrew J. P. White, Fernanda Duarte, Chulho Choi, James J. Mousseau, James A. Bull
Summary: Bioisosteres offer valuable design elements for adjusting the structural and pharmacokinetic characteristics of bioactive compounds. This study explores the potential of aryl oxetane amines as bioisosteres for benzamides, and presents a novel reaction pathway for the synthesis of amino-oxetanes using sulfonyl fluorides. The reaction is compatible with various polar functionalities and can be applied to existing amine libraries. Computational and kinetic studies support the formation of an oxetane carbocation as the rate-determining step in the reaction.
Article
Chemistry, Applied
Amalia-Sofia Piticari, Daniele Antermite, Joe Higham, J. Harry Moore, Matthew P. Webster, James A. Bull
Summary: This study achieved the selective Pd-catalyzed C-H cis-functionalization of piperidine and tetrahydropyran carboxylic acids using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity was obtained by adding mesityl carboxylic acid. The reaction conditions developed in this study had significantly lower temperatures compared to other reported heterocycle C(sp(3))-H functionalization reactions, and a one-pot C-H functionalization-epimerization procedure was established to directly obtain the trans-3,4-disubstituted isomers. Diverse aminoquinoline removals were achieved by installing carboxylic acid, alcohol, amide, and nitrile functional groups. Overall, fragment compounds suitable for screening were synthesized in 3-4 steps from readily-available heterocyclic carboxylic acids.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Joe Higham, James A. Bull
Summary: Transient directing groups (TDGs) combined with copper have been used for efficient C-H functionalization without additional steps for directing group introduction and removal. This method demonstrates high regioselectivity in the beta-C(sp(2))-H sulfonylation and gamma-(peri)-sulfonylation reactions of benzaldehydes and achieves through the use of catalytic beta-alanine and sulfinate salts, with copper fluoride serving as both the copper source and oxidant.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Juan J. Rojas, Elena Torrisi, Maryne A. J. Dubois, Riashat Hossain, Andrew J. P. White, Giovanni Zappia, James J. Mousseau, Chulho Choi, James A. Bull
Summary: This paper reports a method for synthesizing 1,4-dioxanes and explores the catalytic mechanism of the reaction. The reaction exhibits high regio- and diastereoselectivity, and the resulting products serve as interesting motifs for drug discovery.
Article
Chemistry, Organic
Zhenhao Zhong, Julian Chesti, Alan Armstrong, James A. Bull
Summary: Sulfoximines offer a new approach for improving medicinal chemistry with the addition of other functional groups in sulfonyl compounds. By optimizing conditions, successful synthesis of carbamates with previously low yields, especially those containing pi-functionality, was achieved, including the preparation of propargyl sulfoximine carbamates as potential click handles. Notably, using Rh-2 (esp)(2) as catalyst and a DOE optimization approach led to significantly increased yields.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Renzo Luisi, James A. A. Bull
Summary: The development of NH transfer reactions using hypervalent iodine and simple ammonia sources has facilitated the synthesis of sulfoximines and sulfonimidamides. These methods have been widely used in medicinal chemistry and the preparation of biologically active compounds, including large-scale preparation of an API intermediate. This review provides an overview of the development of these synthetic methods, including the mechanism of the reactions, identification of key intermediates, and improvements in reagents and reaction conditions.
Article
Chemistry, Multidisciplinary
Juan J. Rojas, James A. Bull
Summary: 4-Membered heterocycles have potential for drug discovery, but methods to access them are limited. This study presents a general strategy using oxetane and azetidine-benzylic carbocations to obtain valuable 3,3-disubstituted derivatives.
Article
Chemistry, Organic
Maryne A. J. Dubois, Juan J. Rojas, Alistair J. Sterling, Hannah C. Broderick, Milo A. Smith, Andrew J. P. White, Philip W. Miller, Chulho Choi, James J. Mousseau, Fernanda Duarte, James A. Bull
Summary: This study develops a method for the radical functionalization of benzylic oxetanes and azetidines using visible light photoredox catalysis, resulting in the synthesis of 3-aryl-3-alkyl substituted derivatives. The influence of ring strain and heterosubstitution on the reactivity of small-ring radicals is evaluated. The results demonstrate high product yields for oxetanes due to ring strain and Bent's rule.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
James A. Bull
Summary: This article describes the synthesis of sulfoximines and sulfonimidamides using metal-free NH-transfer to sulfoxides and NH/O transfer to sulfides, employing convenient sources of ammonia and hypervalent iodine reagents. Additionally, it discusses the preparation of enantioenriched sulfonimidoyl fluorides and their stereospecific reactions with amines and Grignard reagents.
PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
(2023)
Article
Chemistry, Organic
Joe I. Higham, Tsz-Kan Ma, James A. Bull
Summary: This study presents the first example of using a dual catalytic system (copper(II) acetate and 2-hydroxynicotinaldehyde) to achieve transient C(sp(2))-H sulfonylation of benzylamines with sulfinate salts via a dynamically formed imine directing group. Manganese(IV) oxide was found to be an effective oxidant and base. Computational density functional theory investigations indicate that the transient directing group lowers the energy barrier for an acetate-mediated, turnover-limiting C-H activation step and subsequent combination of the cupracycle with a RSO2 radical.
Article
Chemistry, Physical
Daniele Antermite, Andrew J. P. White, Luis Casarrubios, James A. Bull
Summary: This study presents a combined experimental and computational investigation on the regio- and stereoselective C4 arylation of pyrrolidines and piperidines using C3 aminoquinoline amide directing groups. The mechanistic experiments reveal a cis-selective pathway and the discovery of an improved directing group. This study contributes to the understanding and improvement of C-H functionalization of N-heterocycles.
Article
Chemistry, Organic
Peerawat Saejong, Juan J. Rojas, Camille Denis, Andrew J. P. White, Anne Sophie Voisin-Chiret, Chulho Choi, James A. Bull
Summary: Oxetanes and azetidines are of great interest in medicinal chemistry due to their small, polar and non-planar characteristics. They can serve as interesting substitutes for carbonyl-containing functional groups. In this study, a synthesis method for 3,3-disubstituted oxetane- and azetidine-ethers is reported, with a comparison to ester functional group. The tertiary benzylic alcohols of the 4-membered rings are selectively activated using Bronsted acid catalysis, allowing the formation of ethers while maintaining the integrity of the oxetane ring. This approach avoids the use of strong bases and halide alkylating agents and enables the utilization of alcohol libraries. Oxetane ethers demonstrate excellent chemical stability and improved stability compared to analogous esters under basic and reducing conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Arianna Tota, Mauro Spennacchio, Edward L. Briggs, Tsz-Kan Ma, Zhenhao Zhong, Leonardo Degennaro, James A. Bull, Renzo Luisi
Article
Chemistry, Organic
Edward L. Briggs, Tsz-Kan Ma, Zhenhao Zhong, Arianna Tota, Leonardo Degennaro, Renzo Luisi, James A. Bull
Article
Chemistry, Multidisciplinary
Stephanie Greed, Oliver Symes, James A. Bull
Summary: Enantioenriched alkyl sulfonimidoyl fluorides were prepared for the first time and their stereospecific reaction with Grignard reagents at sulfur was investigated. The nature of the N-group was found to be crucial for the success of the reaction.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
