Article
Chemistry, Multidisciplinary
Amelia Messara, Armen Panossian, Koichi Mikami, Gilles Hanquet, Frederic R. Leroux
Summary: The deprotonative functionalization of alpha,alpha-difluoromethyl ketones is achieved by using a catalytic organosuperbase and a silane additive, leading to the generation of difluoroenolates that can be trapped with aldehydes to produce alpha,alpha-difluoro-beta-hydroxy ketones. This strategy allows for the direct deprotonation of the difluoromethyl unit and is tolerant of various functional groups. The diastereoselective version of the reaction was also explored, with high diastereomeric ratios. Several transformations demonstrate the synthetic potential of these alpha,alpha-difluoro-beta-hydroxy ketones. Additionally, the method can be extended for the use of other electrophiles and nucleophiles, resulting in a diversity of difluoromethylene compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Xiaorui Jiao, Zhonghou Huang, Weidong Meng, Shengqing Zhu, Lingling Chu
Summary: A catalyst-free and mild visible-light-induced reductive defluoroallylation of difluoromethyl ketones with allylic chlorides is presented, providing efficient access to α-fluoro alkenylketones. The alkyl amines play a dual role in this reaction as both electron donors for selective C-F bond cleavage of CF2H-ketones and halogen-atom transfer agents for activation of the C-Cl bond in allylic chlorides. The protocol shows a broad substrate scope and synthetic derivatizations of the resulting α-fluoro alkenylketones as well as preliminary mechanistic studies are discussed.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Review
Chemistry, Organic
Fengyun Gao, Boyu Li, Yalan Wang, Qushuo Chen, Yongzhen Li, Kairong Wang, Wenjin Yan
Summary: This review summarizes routine asymmetric synthetic methods for the effective and selective introduction of difluoromethyl groups into desired compounds, which is valuable for the synthesis of fluorine-containing compounds and for modulating the properties of organic compounds in drug design.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Dong Xia, Xin-Fang Duan
Summary: The cleavage of an unactivated aryl nitro group triggered by alkyl radicals enables a dearomative cyclization, providing diversified alkylated spiro[5.5]trienones in good yields. Various alkyls have been implanted into the spirocycles via C(sp(3))-H and Ar-NO2 bond activation using readily available compounds as alkylating reagents, demonstrating high functional group tolerance. This protocol presents a distinctive method for activating the aryl nitro group.
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
Hongyu Wang, Chen-Fei Liu, Robert T. Martin, Osvaldo Gutierrez, Ming Joo Koh
Summary: This study presents a new directing-group-free, nickel-catalysed strategy for the catalytic addition of carbogenic groups to unactivated and activated olefins with control of regioselectivity, achieving up to 93% yield and >98% site selectivity. The method can be extended to other types of reactions by switching reagents, and mechanistic and computational investigations provide insights into the regiochemical outcome of the reaction. The utility of the method is demonstrated through the concise syntheses of biologically active molecules, and the reported catalyst control principles are expected to advance efforts towards developing general site-selective alkene functionalizations.
Article
Chemistry, Applied
Nuo Xu, Jianeng Xu, Qing Zhu, Chao Liu
Summary: A method for the synthesis of allylboronates via Zweifel-type deprotonative olefination was demonstrated using tetrasubstituted vinylboronates as substrates and NCS as a bifunctional additive, electrophile, and base. This method showed a different elimination strategy in Zweifel type transformation to produce allylboronates, which could be further stereoselectively converted to homo-alcohols and alkenes, demonstrating the synthetic value of this methodology.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Fengyun Gao, Yifei Guo, Mengmeng Sun, Yalan Wang, Changyan Yang, Yuqiang Wang, Kairong Wang, Wenjin Yan
Summary: A novel difluoromethylated ketimine building block was synthesized for the first time by condensation of thioisatin and difluoroethylamine, providing efficient access to enantioenriched products with difluoroethylamine units. Further transformation of the intermediate led to the generation of versatile functional blocks while retaining the enantiomeric excess at the difluoromethyl-bound carbon.
Article
Chemistry, Inorganic & Nuclear
Ita Hajdin, Romana Pajkert, Haibo Mei, Jianlin Han, Gerd-Volker Roeschenthaler
Summary: A catalyst- and solvent-free 1,3-dipolar cycloaddition reaction using a bench-stable diazo reagent has been developed to obtain a series of novel 3H-pyrazoles bearing difluoromethyl phosphonate unit in moderate-to-excellent yields. This method provides an efficient and easy route to synthesize valuable compounds.
JOURNAL OF FLUORINE CHEMISTRY
(2024)
Article
Chemistry, Organic
Erika L. Lucas, Tristan M. McGinnis, Anthony J. Castro, Elizabeth R. Jarvo
Summary: This study presents a novel strategy for synthesizing fluorinated cyclopropanes, achieving the first example of an XEC reaction using a difluoromethyl group as an electrophile. Through a combination of photocatalytic and nickel-catalyzed reactions, the desired product was successfully synthesized, with a plausible mechanism discussed along with DFT calculations supporting the observed stereochemical outcome.
Article
Chemistry, Organic
Ashfaq Ahmad, Himangsu Sekhar Dutta, Mohit Kumar, Raziullah, Manoj Kumar Gangwar, Dipankar Koley
Summary: A palladium catalyzed directing group assisted cross-coupling reaction has been developed for the synthesis of β-arylethylamine derivatives. The method is applicable to a wide range of substrates and can tolerate the presence of various external additives.
Article
Chemistry, Multidisciplinary
Masanori Shigeno, Akihisa Kajima, Eito Toyama, Toshinobu Korenaga, Hiroyuki Yamakoshi, Kanako Nozawa-Kumada, Yoshinori Kondo
Summary: We demonstrate that lithium hexamethyldisilazide (LiHMDS) is an effective base for deprotonative coupling reactions of toluenes with ketones to produce stilbenes. Various functionalities are allowed on the toluenes. Notably, this system works with low-reactive toluenes with large pKa values compared to that of the conjugate acid of LiHMDS.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Cheng Wu, Xiao Shen, Jianjun Dai, Jun Xu, Huajian Xu
Summary: By utilizing a direct nucleophilic substitution reaction under transition metal free conditions, easily available aryl and alkyl thiocyanates were converted into the desired products, enabling the synthesis of (benzenesulfonyl)difluoromethyl thioethers.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Amandine Pons, Laetitia Delion, Thomas Poisson, Andre B. Charette, Philippe Jubault
Summary: Fluorine-containing cyclopropanes are a subclass of cyclopropane derivatives with significant medicinal chemistry interest. Replacing a cyclopropane C-H or C-CH3 bond with fluorine can enhance biological activity and metabolic profile. This account discusses the development of new synthetic routes for fluoro-, difluoromethyl-, or trifluoromethyl-cyclopropanes, focusing on optimizing reaction efficiency and substrate selection.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Xin Xu, Lin Zhang, Haoqiang Zhao, Yixiao Pan, Jiajie Li, Zhenli Luo, Jiahong Han, Lijin Xu, Ming Lei
Summary: A highly regio- and stereoselective direct C6 olefination of 2-pyridones with alkynes using Co(III) catalysis and chelation assistance has been developed. Varying reaction conditions allows for different pathways to achieve tetrasubstituted 6-vinyl-2-pyridones or C6-olefinated 2-pyridones. The protocol features 100% atom economy, excellent site selectivity, high stereoselectivity, and good compatibility of functional groups, with experimental and theoretical studies providing mechanistic insight.
Article
Chemistry, Multidisciplinary
Marta G. Avello, Stephane Golling, Lai Truong-Phuoc, Loic Vidal, Thierry Romero, Vasiliki Papaefthimiou, Nathalie Gruber, Michael J. Chetcuti, Frederic R. Leroux, Morgan Donnard, Vincent Ritleng, Cuong Pham-Huu, Christophe Michon
Summary: This study demonstrates the successful synthesis of nickel(0) nanoparticles coordinated to NHC ligands bearing N-coordinated cinnamyl moieties. The unique ligand structure prevents aggregation of the nanoparticles into larger inactive species and enables effective and (Z)-selective semi-hydrogenation of alkynes and ynamides.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Florian Audet, Morgan Donnard, Armen Panossian, David Bernier, Sergii Pazenok, Frederic R. Leroux
Summary: Sulfuryl fluoride is a gas used as a fumigant, but it has also gained interest in organic synthesis due to its unique properties. It has been used for sulfur-fluoride exchange chemistry and as an efficient activator in classic organic synthesis, forming fluorosulfonates. Recent research has focused on metal-catalyzed transformations from aryl fluorosulfonates and nucleophilic substitution reactions on polyfluoroalkyl alcohols, highlighting the advantages of polyfluoroalkyl fluorosulfonates compared to alternative reagents.
Article
Chemistry, Multidisciplinary
Clemence Bonnefoy, Armen Panossian, Gilles Hanquet, Frederic R. Leroux, Fabien Toulgoat, Thierry Billard
Summary: In this study, 2,4-dinitro-trifluoromethoxybenzene (DNTFB) was used as a trifluoromethoxylating reagent to perform nucleophilic substitution reactions under mild metal-free conditions. The reactions involved substrates with different leaving groups, including direct dehydroxytrifluoromethoxylation. A mechanistic study rationalized the reactions and proposed only three reaction conditions based on the reactivity of the starting substrates.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Laura Santos, Florian Audet, Morgan Donnard, Armen Panossian, Jean-Pierre Vors, David Bernier, Sergii Pazenok, Frederic R. Leroux
Summary: An efficient method for the synthesis of high-value N-polyfluoroalkyl anilines, primary polyfluoroalkylamines, and N,N-bis(polyfluoroalkyl) amines via N-polyfluoroalkylation of sulfonamides and phthalimide derivatives using sulfuryl fluoride (SO2F2) is reported. The in situ formation of polyfluoroalkyl fluorosulfonates from commercially available fluorinated alcohols and economical sulfuryl fluoride is advantageous in terms of environmental impact and cost. This general method allows for the polyfluoroalkylation of a variety of substrates, providing valuable building blocks for life science applications.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Clotilde Placais, Sherif J. Kaldas, Morgan Donnard, Armen Panossian, David Bernier, Sergii Pazenok, Frederic R. Leroux
Summary: This work presents the synthesis of aryl and alkenyl halides from fluorosulfonates using commercially available ruthenium catalysts. It is the first study to efficiently convert phenols to aryl halides with chloride, bromide, and iodide. Fluorosulfonates can be easily prepared using sulfuryl fluoride (SO2F2) and cost-effective substitutes for triflates. Additionally, this work also reports an efficient coupling of alkenyl fluorosulfonates for the first time. Representative examples demonstrate that the reaction can be carried out in a one-pot process, starting directly from phenol or aldehyde.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Inorganic & Nuclear
Marie-Charlotte Belhomme, Thomas Guerin, Armen Panossian, Frederic R. Leroux
Summary: The reaction of diphenylphosphine oxide with two aryne precursors was studied to obtain functionalizable nonsymmetrical dibenzophospholes. The reactions were found to be influenced by substituents on the aryne precursors that can coordinate with the incoming lithiated nucleophile.
PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
(2023)
Article
Chemistry, Organic
Anais Loison, Gilles Hanquet, Fabien Toulgoat, Thierry Billard, Armen Panossian, Frederic R. Leroux
Summary: This paper reports an unprecedented synthesis of difluoromethoxylated nitrogen-containing heterocycles from α-(difluoromethoxy)ketones as versatile building blocks. Pyrazoles, isoxazoles, and pyrimidines were obtained via an enaminone intermediate, and a Fischer indole synthesis was achieved in the direct reaction of α-(difluoromethoxy)ketones with arylhydrazines. These uncommon or even novel scaffolds, with the directly attached emerging fluorinated group (OCF2H), have high potential in life sciences and provide an interesting alternative to classical fluorinated groups.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Anthony J. Fernandes, Bastien Michelet, Armen Panossian, Agnes Martin-Mingot, Frederic R. Leroux, Sebastien Thibaudeau
Summary: Understanding the impact of emerging fluorinated motifs is crucial due to the increasing use of fluorine in various fields. This study demonstrates the significant effect of a local partial charge inversion through the replacement of a CHCH3 group with a CFCF3 group. This strategy enables the diastereoselective reduction of 5-membered ring oxocarbenium ions, leading to the formation of highly substituted tetrahydrofurans.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Pierre Hansjacob, Celia Schwoerer, Frederic R. Leroux, Morgan Donnard
Summary: Here we report the efficient and selective two-step synthesis of various 3-silyl-2-amidoindenones from easily accessible ynamides. This synthesis involves a regio- and stereo-selective silylcyanation followed by a Houben-Hoesch type cyclization. By utilizing post-transformations, a range of 3-substituted 2-amidoindenones could be obtained. This method offers a simple and selective approach to synthesize polyfunctionalized 2-amidoindenones, with the notable achievement of true structural diversity at position 3.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
