Article
Chemistry, Multidisciplinary
Matthieu Hedouin, Anne-Laure Barthelemy, Nicolas Vanthuyne, Hend Besrour, Jacques Maddaluno, Emmanuel Magnier, Hassan Oulyadi
Summary: This work explains the importance of using an excess of butyllithium in the directed ortho-lithiation of a trifluoromethyl sulfoximine. The study shows that the presence of excess n-BuLi leads to deprotonation on the ortho-position of the aromatic, resulting in the formation of six different aggregates. DFT calculations provide optimized solvated structures for these aggregates that are consistent with the experimental NMR data.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Matthew J. Fleming, David M. Hodgson
Summary: The reaction involves the cross-coupling of alpha-lithiated terminal epoxides and N-(tert-butylsulfonyl)aziridines with alpha-lithio ethers to yield allylic alcohols and allylic amines. The mechanism proceeds through selective strain-relieving attack and beta-elimination of the lithium alkoxide.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Andreas Hess, Jan P. Prohaska, Sabrina B. Doerrich, Florian Trauner, Ferdinand H. Lutter, Sebastien Lemaire, Simon Wagschal, Konstantin Karaghiosoff, Paul Knochel
Summary: A new toluene-soluble reagent, sBu(2)Mg, has been developed for regioselective ortho-magnesiations of various N-arylated pyrazoles and 1,2,3-triazoles, as well as arenes with specific directing groups. The resulting diarylmagnesium reagents can be further functionalized and double ortho,ortho'-magnesiations can be achieved by repeating the magnesiation/electrophile trapping sequence, allowing for the preparation of valuable functionalized arenes.
Article
Chemistry, Multidisciplinary
Kristian J. Chambers, Patthadon Sanghong, Daniel Carter Martos, Giorgia Casoni, Rory C. Mykura, Durga Prasad Hari, Adam Noble, Varinder K. Aggarwal
Summary: Enones are important functional groups in chemical synthesis and molecular biology. This study developed a one-pot strategy for the stereospecific conversion of boronic esters into enones using methoxyallene as a three-carbon building block. The methodology is versatile and has been successfully applied to the total synthesis of polyketide 10-deoxymethynolide.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Xuan-Di Song, Meng-Meng Guo, Shuang Xu, Chuanji Shen, Xiaocong Zhou, Xue-Qiang Chu, Mengtao Ma, Zhi-Liang Shen
Summary: A nickel-catalyzed direct reductive cross-coupling of disubstituted cycloalkyl iodides with aryl iodides was developed, allowing for efficient stereocontrolled synthesis of a variety of cross-coupled products with high diastereoselectivity and wide functional group tolerance. The one-pot reaction is simple to operate, providing a convenient method for the synthesis of complex molecules.
Article
Chemistry, Multidisciplinary
Nathan W. Dow, P. Scott Pedersen, Tiffany Q. Chen, David C. Blakemore, Anne-Marie Dechert-Schmitt, Thomas Knauber, David W. C. MacMillan
Summary: We have developed a photoinduced strategy that converts (hetero)aryl acids into aryl radicals for ambient-temperature borylation. This method operates under mild conditions and does not require prefunctionalization. Additionally, we have combined catalytic borylation with palladium-catalyzed Suzuki-Miyaura reactions to access a range of valuable products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Inorganic & Nuclear
Sailajah Gukathasan, Sean Parkin, Esther P. Black, Samuel G. Awuah
Summary: Transition-metal-based methods show promise in selectively modifying proteins, with potential applications in chemical biology. By tuning ancillary ligands of cyclometalated gold(III), rapid modification of a desired cysteine residue on target proteins can be achieved, opening up possibilities for the rational design of cysteine-targeted covalent inhibitors and metal-mediated ligand affinity chemistry (MLAC) on native proteins.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Hanbin Lee, Tiancheng He, Silas P. Cook
Summary: Here, we report an iron-catalyzed benzylic C-H borylation reaction that achieves high-value boronic esters under mild conditions with short reaction times (7-8 min). The reaction is tolerant of various functional groups and exhibits complete site selectivity in the presence of multiple benzylic C-H bonds.
Article
Chemistry, Organic
Fangdong Hu, Ying Xia, Zihao Zhang, Jie Jia
Summary: A rhodium-catalyzed olefination reaction of aliphatic aldehydes with arylboroxines is reported. The use of a simple rhodium(I) complex [Rh(cod)OH]2 without any external ligands or additives enables the reaction to proceed in air and under neutral conditions, resulting in efficient synthesis of aryl olefins with good functional group tolerance. Mechanistic investigation reveals that the binary rhodium catalysis, involving Rh(I)-catalyzed 1,2-addition and Rh(III)-catalyzed elimination, is crucial for this transformation.
Article
Chemistry, Organic
Sarah G. Scrivener, Yidong Wang, Yi-Ming Wang
Summary: The iron-catalyzed coupling of alkenes and enones through allylic C(sp3)-H functionalization is achieved using a cyclopentadienyliron(II) dicarbonyl catalyst and simple alkene substrates. The reaction generates catalytic allyliron intermediates for 1,4-addition to chalcones and other conjugated enones. Mild, functional group-tolerant conditions are facilitated by the use of 2,4,6-collidine as the base and a combination of triisopropylsilyl triflate and LiNTf2 as Lewis acids. Both electronically unactivated alkenes and allylbenzene derivatives, as well as enones with various substituents, can be employed as pronucleophilic coupling partners.
Article
Chemistry, Multidisciplinary
Michael W. Milbauer, Jeff W. Kampf, Melanie S. Sanford
Summary: In this study, we successfully isolated a cyclometalated nickel(IV) complex that is similar to a key intermediate proposed in aminoquinoline-directed C-H functionalization catalysis. The complex undergoes bond-forming reaction under mild conditions and demonstrates the importance of LX-type ligands in stabilizing these nickel(IV) species.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Hao Liang, James P. Morken
Summary: Enantioenriched tertiary alkylboronic esters can be activated by in situ generated adamantyllithium, leading to stereoretentive boron-to-copper transmetalation. The resulting alkylcopper species can react with various electrophiles through cross-coupling reactions, providing synthetically useful compounds with quaternary stereocenters. DFT calculations of the transmetalation process offer insights into reactivity and selectivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Boriss Strumfs, Jekaterina Hermane, Sergey Belyakov, Artjoms Sobolevs, Kirils Velikijs, Romans Uljanovs, Peteris Trapencieris, Ilze Strumfa
Summary: The reaction of N,N-Dimethylaziridine-2-carboxamides with organolithium reagents yields 2-aziridinylketones, which can further react to form symmetrical and unsymmetrical aziridinyl carbinols. The use of excess phenyllithium can serve as a unique N-Boc protecting group cleavage method for acid-sensitive substrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Hao Chen, Juntian Fan, Yuqing Fu, Chi-Linh Do-Thanh, Xian Suo, Tao Wang, Ilja Popovs, De-en Jiang, Yating Yuan, Zhenzhen Yang, Sheng Dai
Summary: A novel method using mechanochemical Ullmann-type reactions to promote direct aromatic ring knitting has been demonstrated to afford CPNs with high surface areas and mesoporous architecture under neat and ambient conditions. The versatility of this approach has been confirmed by successful construction of various CPNs and even highly crystalline graphite product, showing good electrochemical performance in lithium-ion batteries. This strategy expands the frontiers of CPN synthesis and provides new opportunities for their scalable applications.
ADVANCED MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Christoph Helling, Cameron Jones
Summary: The influence of aryl substituents on the Schlenk-type equilibria of arylberyllium bromides was systematically studied, and the structures of the complexes were characterized using spectroscopic methods and X-ray diffraction. The study provides insights into the steric effects of aryl groups on the reactivity and selectivity of the complexes.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Pantaleo Musci, Timo von Keutz, Ferdinand Belaj, Leonardo Degennaro, David Cantillo, C. Oliver Kappe, Renzo Luisi
Summary: A telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1-azabicyclo[1.1.0]butanes has been reported, showcasing its efficiency with over 20 examples. The flow method allows for exquisite control of reaction parameters and operates at higher temperatures and safer conditions compared to batch mode.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Michael Andresini, Leonardo Degennaro, Renzo Luisi
Summary: The reported flow-batch approach allows for the easy preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines using environmentally friendly cyclopentyl methyl ether (CPME) as a solvent. This method provides a sustainable, safe, and potentially automatable way to synthesize interesting strained compounds.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Gregory B. Craven, Edward L. Briggs, Charlotte M. Zammit, Alexander McDermott, Stephanie Greed, Dominic P. Affron, Charlotte Leinfellner, Hannah R. Cudmore, Ruth R. Tweedy, Renzo Luisi, James A. Bull, Alan Armstrong
Summary: Vinyl sulfoximines and sulfonimidamides, as S(VI) aza-isosteres of vinyl sulfones and sulfonamides, have been less studied and not yet applied to protein bioconjugation. This study reports various synthetic methodologies for constructing these structures, demonstrating their application in generating fully functionalized probes. Furthermore, a workflow for determining the absolute configuration of enantioenriched vinyl sulfoximines and sulfonimidamides is established.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Michael Andresini, Arianna Tota, Leonardo Degennaro, James A. Bull, Renzo Luisi
Summary: In recent years, there has been a significant increase in the use of sulfoximines in the field of chemistry, as they are considered valuable motifs in medicinal chemistry, due to pioneering works in clinical trials and the development of synthetic methods. Recent developments in sulfoximine synthesis, focusing on S-N and S-C bond formations since 2015, as well as the use of flow chemistry processes and subsequent transformations, particularly in N-functionalization, have been covered in this review.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Michael Andresini, Sebastien Carret, Leonardo Degennaro, Fulvio Ciriaco, Jean-Francois Poisson, Renzo Luisi
Summary: This study reports a multistep continuous flow synthesis method for the preparation of poorly explored NH2-sulfinamidines by nucleophilic attack of organometallic reagents. The method allows for the synthesis of the target compounds under mild conditions via a highly chemoselective halogen-lithium exchange reaction, and the synthetic potential of the methodology was evaluated.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Arminas Urbonavicius, Graziana Fortunato, Emilija Ambrazaityte, Elena Plytninkiene, Aurimas Bieliauskas, Vaida Milisiunaite, Renzo Luisi, Egle Arbaciauskiene, Sonata Krikstolaityte, Algirdas Sackus
Summary: An efficient synthetic route to diverse pyrazole-based chalcones from 1-phenyl-1H-pyrazol-3-ols with a formyl or acetyl group at the C4 position is described. Isomeric chalcones were further reacted to form 3,5-disubstituted 1,2-oxazoles via regioselective reaction with N-hydroxy-4-toluenesulfonamide. The novel compounds were characterized by in-depth NMR spectroscopy analysis.
Article
Chemistry, Multidisciplinary
Mauro Spennacchio, Marco Colella, Michael Andresini, Roberta Savina Dibenedetto, Elena Graziano, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Summary: A direct nucleophilic monofluoroalkylation strategy using lithium fluorocarbenoids has been developed. By employing flow microreactor technology, the synthetic potential of short-lived intermediates generated through lithium/iodine exchange reaction, such as 1-fluoro-2-phenylethyllithium, 1-fluoro-3-phenylpropyllithium, and 1-fluorononyllithium, can be fully capitalized. This robust protocol allows for the preparation of new fluorinated products using various electrophiles, making it a valuable tool for direct fluoroalkylation chemistry.
CHEMICAL COMMUNICATIONS
(2023)
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, Organic
Arianna Tota, Michael Andresini, Marco Colella, Roberta Savina Dibenedetto, Leonardo Degennaro, Renzo Luisi
Summary: In this study, (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (R)-4-methylbenzenesulfonimidate was synthesized via stereoselective NH-transfer from (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (S)-4-methylbenzenesulfinate. The reaction took place in acetonitrile at room temperature, with diacetoxyiodobenzene and ammonium carbamate as the reactants. The sulfur imidation reaction proceeded with complete stereocontrol, giving a single diastereoisomer product with high enantiocontrol.
Article
Chemistry, Organic
Marco Colella, Yuri Gelato, Michael Andresini, Elena Graziano, Gianvito Vile, Leonardo Degennaro, Renzo Luisi
Summary: A strategy for anti-Markovnikov hydroalkyl/aryl thiolation and disulfidation of 2-azetines under continuous flow conditions has been developed. Thiyl radicals are generated from thiols or disulfides and subsequently propagate into the azetine unsaturation to forge the C-S bond and shape a secondary radical intermediate. The use of flow technology ensures efficient irradiation of the reaction mixture leading to extremely fast, robust, and scalable protocols. Furthermore, ethyl acetate was adopted as an environmentally responsible solvent.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Marco Colella, Yuri Gelato, Michael Andresini, Elena Graziano, Gianvito Vile, Leonardo Degennaro, Renzo Luisi
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Organic
Michael Andresini, Marco Colella, Leonardo Degennaro, Renzo Luisi
Summary: Significant progress has been made in the synthesis of underappreciated aza-S(iv) motifs, thanks to efficient and complementary synthetic strategies. The reactivity of these compounds has also been studied, revealing the electrophilic nature of sulfinimidate esters and the nucleophilic character of sulfinamidines. Additionally, sulfinamidines have been found to undergo oxidation, leading to the formation of important aza-S(vi) derivatives. This review aims to provide a comprehensive overview of the preparation and structural characterization of these overlooked compounds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Alessandra Sivo, Tae Keun Kim, Vincenzo Ruta, Renzo Luisi, Jose Osorio-Tejada, Marc Escriba-Gelonch, Volker Hessel, Mattia Sponchioni, Gianvito Vile
Summary: We report an improved approach that integrates flow synthesis and continuous chromatography for the end-to-end preparation of pharmaceutically-relevant small molecules. Compared to traditional methods, our approach offers higher yields, productivity, and reduced solvent consumption.
REACTION CHEMISTRY & ENGINEERING
(2022)
Review
Chemistry, Organic
Marco Colella, Pantaleo Musci, Michael Andresini, Mauro Spennacchio, Leonardo Degennaro, Renzo Luisi
Summary: Fluoroiodomethane (CH2FI) has emerged as a convenient and readily available platform for monofluoromethylation strategies. Recent applications demonstrate its potential in the preparation of organofluorine compounds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Pantaleo Musci, Marco Colella, Michael Andresini, Andrea Aramini, Leonardo Degennaro, Renzo Luisi
Summary: The use of flow technology as a tool for accessing compounds with strained heterocycles is reported. Reactivity and chemoselectivity were also evaluated, and new chemical space and structural motifs were explored.
CHEMICAL COMMUNICATIONS
(2022)
