Article
Chemistry, Multidisciplinary
Ming Dong, Linjun Qi, Jinlong Qian, Shuling Yu, Xiaofeng Tong
Summary: In this study, a Pd(0)-catalyzed hydroacyloxylative cyclization of 1,6-enyne was developed, which proceeds in either a 7-endo-trig or 6-exo-trig fashion when paired with an appropriate dihaloacetic acid reactant. The reaction can produce highly enantiopure seven-membered heterocycles or six-membered rings with moderate enantioselectivity, depending on the substituents on the alkene moiety. Preliminary experimental studies suggest an unusual reaction mechanism involving E-to-Z isomerization of a vinyl-Pd(II) species and alkene trans-oxypalladation, which is governed by the carboxylate selected.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Elaine C. Reichert, Kaibo Feng, Aaron C. Sather, Stephen L. Buchwald
Summary: We report a versatile method for the Pd-catalyzed C-N cross-coupling of heteroaryl halides with primary and secondary amines, achieving good-to-excellent yields. The use of a specific base and a supported Pd catalyst enables the coupling of challenging heteroarenes and sterically demanding amines. This method has broad applicability and allows the synthesis of densely functionalized medicinal chemistry building blocks.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Fu-Peng Wu, Yang Yuan, Xiao-Feng Wu
Summary: A novel copper-catalyzed carbonylative trifluoromethylation of unactivated alkenes has been developed, allowing the preparation of a broad range of beta-trifluoromethylated carboxylic acid derivatives in moderate to excellent yields with excellent regioselectivity. It is worth noting that even the simplest olefin, ethylene gas, can be directly applied to obtain beta-trifluoromethylated amides and esters. This transformation represents the first example of carbonylative trifluoromethylation of alkenes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Melisa Alkan, Haley K. K. Banovetz, Mark S. S. Gordon, Levi M. M. Stanley
Summary: A combination of density functional theory (DFT), second order perturbation theory (MP2) calculations, and experimental methods were used to investigate the computational and mechanistic studies of Pd-catalyzed alkene carboacylation via ester bond activation. The key elementary steps of the catalytic cycle were examined, revealing a novel mechanism for the carboacylation reaction. The calculations showed that the Pd(II) intermediate preceding migratory insertion is a cationic intermediate, and a new organoboron species was identified as a nucleophile in this transition metal-catalyzed reaction. Experimental control studies confirmed the computational findings.
Article
Chemistry, Multidisciplinary
Ping Zhao, Yun Guo, Xinjun Luan
Summary: This study presents a concise total synthesis of Dalesconol A through a polycyclization/oxidation approach, involving key steps of polycyclization and oxidation state adjustments.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Chemistry, Organic
Hong-Chao Chen, Yichen Wu, Yang Yu, Peng Wang
Summary: This article summarizes the methods of alkene isomerization, which can efficiently construct multi-substituted alkenes via the stereoselective or positional-selective modulation of carbon-carbon double bonds. These methods have important applications in the synthesis of drug molecules and natural products.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Applied
Antonio Mourino
Summary: 1α,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D3, plays a crucial role in regulating mineral homeostasis, cell growth, and immune responses. However, its clinical applications are limited due to hypercalcemic effects. Therefore, there has been a focus on synthesizing highly active and non-calcemic analogs of 1,25D3 for the treatment of hyperproliferative diseases.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Jiaoyu Wu, Lu Bai, Lingbo Han, Jingjing Liu, Xinjun Luan
Summary: A chemo- and regioselective Pd(0)-catalyzed spiroannulation method was successfully developed, utilizing readily available 1,2-dihaloarenes, alkynes, and 2-naphthols for rapid assembly of spirocarbocyclic molecules. The mechanistic studies revealed that the reaction proceeded through a cascade of oxidative addition, alkyne migratory insertion, and 2-naphthol-facilitated dearomatizing [4+1] spiroannulation.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Yifan Wang, Yuanyuan Ping, Wangqing Kong
Summary: A cooperative Pd/Cu-catalyzed three-component cross-coupling reaction of alkynes, B 2 Pin 2 and alkenetethered aryl halides is reported. This reaction proceeds under mild conditions and shows broad substrate scope, providing a variety of heterocycles containing tetrasubstituted alkenylboronate moieties in synthetically useful yields with excellent chemoselectivity and regioselectivity. An enantioselective cascade cyclization/cross-coupling process has also been developed for the synthesis of enantiomerically enriched oxindole bearing a tetrasubstituted alkenylboronate moiety.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Organic
Grace L. Trammel, Abby C. Kerlin, Christian Zachau, M. Kevin Brown
Summary: The synthesis of (+/-)-phyltetralin is described, featuring a diastereoselective Cu/Pd-catalyzed arylboration reaction and a Matteson homologation.
Article
Chemistry, Physical
Jayabrata Das, Tanay Pal, Wajid Ali, Sumeet Ranjan Sahoo, Debabrata Maiti
Summary: Allyl alcohols are used as unique coupling partners in C-H functionalization reactions. This study presents a simple strategy for the synthesis of gamma-lactones through dual-1,1-C(sp(3))-H activation of free aliphatic acids. Various allyl alcohols and aliphatic acids, including long-chain ones, have been used to generate a diverse range of gamma-lactones. The rate-determining step is identified as C-H activation, followed by allylic C-H activation in the reaction. The synthesized lactones with alpha,beta-unsaturated fragments can be useful in the synthesis of complex molecules through further synthetic manipulation.
Article
Chemistry, Physical
Jayabrata Das, Tanay Pal, Wajid Ali, Sumeet Ranjan Sahoo, Debabrata Maiti
Summary: In this study, a simple strategy for the direct synthesis of gamma-lactones containing alpha,beta-unsaturated groups at the gamma-position through dual-1,1-C(sp3)-H activation of free aliphatic acids is reported. Various allyl alcohols, including primary, secondary, and tertiary ones, have been used as suitable coupling partners to generate a diverse range of gamma-lactones. The obtained lactones with alpha,beta-unsaturated fragments are expected to be useful in the synthesis of complex molecules through further synthetic manipulation.
Article
Chemistry, Organic
Zi-Yu Dong, Jia-Hui Zhao, Peng Wang, Jin-Quan Yu
Summary: In this study, a class of bifunctional monoprotected amino-imidazoline (MPAI) ligands were developed and applied in Pd-catalyzed C(sp(3))-H arylation of free aliphatic acids. The newly developed MPAI ligand enables the use of 1.0 equiv of aliphatic acids containing an alpha hydrogen for the first time.
Article
Chemistry, Organic
Lin Huang, Li-Ping Chen, Yu Du, Mao-Ying Fang, Bi-Qin Wang, Chun Feng, Shi-Kai Xiang
Summary: The annulative pi-extension of o-iodobiphenyls with aliphatic anhydrides in the bay-region leads to efficient synthesis of phenanthrol derivatives. Control experiments suggest dibenzopalladacyclopentadienes as reaction intermediates.
Article
Chemistry, Multidisciplinary
Liang Hu, Guangrong Meng, Jin-Quan Yu
Summary: This study reports the first Pd(II)-catalyzed intermolecular fi-methylene C(sp3)-H arylation of free aliphatic acids using bidentate pyridine-pyridone ligands. The bite angle of the ligand plays a key role in promoting fi-methylene C-H activation of free carboxylic acid. This transformation provides a disconnection for alkylation of arenes with simple aliphatic acids.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Raphael Simonet-Davin, Jerome Waser
Summary: In this short review, applications of hypervalent iodine reagents for the azidation of organic compounds were described, with a focus on stable cyclic reagents. Important advances in the azidation of C-H bonds, alkenes, and other transformations were highlighted through selected key reports.
SYNTHESIS-STUTTGART
(2023)
Review
Chemistry, Multidisciplinary
Eliott Le Du, Jerome Waser
Summary: Although small, alkynes are highly versatile building blocks in organic chemistry, with applications ranging from biochemistry to material sciences. Traditional alkynylation reactions rely on the use of acetylenes as nucleophiles. However, the discovery and development of ethynyl hypervalent iodine reagents have greatly expanded the transfer of alkynes as electrophilic synthons. This feature article presents the progress in the field since 2018, including synthesis of alkynyl hypervalent iodine reagents, their use in base-mediated and transition-metal catalyzed alkynylations, and progress in radical-based alkynylations and atom-economical transformations.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Stephanie G. E. Amos, Franck Le Vaillant, Jerome Waser
Summary: Alkynes and nitriles are important building blocks in organic synthesis, chemical biology, and materials science. This study investigates the conversion of alcohols into alkynes and nitriles using cesium oxalates and Ethynyl BenziodoXolones (EBXs), and explores the effects of backbone modification of EBXs on the deoxyalkynylation of cesium oxalates. Preliminary data on the development of new deoxycyanation and dethioalkynylation processes are also presented, along with the serendipitous discovery of C-H alkynylation of 1,2-dichloroethane.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Emma G. L. Robert, Vincent Pirenne, Matthew D. Wodrich, Jerome Waser
Summary: A convenient method for the one-step synthesis of beta-aminocyclobutane monoesters using commercially available reagents is reported. The obtained strained rings undergo dearomative annulation with indole partners using silylium catalysis, providing tricyclic indolines with four new stereocenters. The reaction can proceed both intra- and intermolecularly and the outcome can be selectively controlled based on reaction temperature, resulting in the formation of either akuamma or malagasy alkaloid-like tetracyclic structures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xing-Yu Liu, Xinjian Ji, Christian Heinis, Jerome Waser
Summary: We present a new method for modifying peptides using highly reactive hypervalent iodine reagents called ethynylbenziodoxolones (EBXs). These peptide-EBXs can be easily synthesized through solution- and solid-phase peptide synthesis (SPPS). They can be used to couple peptides to other peptides or proteins via reaction with Cys, resulting in thioalkynes in organic solvents or hypervalent iodine adducts in water buffer. Additionally, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed, leading to macrocyclic peptides with unprecedented crosslinking.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Nieves P. P. Ramirez, Jerome Waser
Summary: An asymmetric 3-component reaction catalyzed by a Cu-I-BOX catalyst was developed for the synthesis of chiral trifluoromethylated propargyl ethers and anilines. The reaction showed high enantioselectivity and yield with various nucleophiles and different electrophiles. The method also exhibited good diastereoselectivity with chiral substrates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Eliott Le Du, Nieves P. Ramirez, Stefano Nicolai, Rosario Scopelliti, Farzaneh Fadaei-Tirani, Matthew D. Wodrich, Durga Prasad Hari, Jerome Waser
Summary: First synthesized in 1991, EthynylBenziodoXolones (EBXs) are now among the most versatile electrophilic alkynylation reagents. Due to their cyclic structure, these reagents exhibit enhanced stability compared to previously used alkynyl iodonium salts. The collected structural data of EBXs and their analogues, along with the calculated molecular electrostatic potentials (MEP), is expected to be highly useful for further developments in the field, considering the tight relationship between structure and reactivity in hypervalent iodine reagents.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Tobias Michael Milzarek, Jerome Waser
Summary: The first trifluoromethylation of vinylbenziodoxolones (VBX) using bench-stable, high-valent copper(III) species is reported. The reaction can be initiated under thermal conditions and/or irradiation (365 nm) and leads to stereoselective formation of trifluoromethylated alkenes. Various VBX reagents derived from tyrosine, cysteine, small peptides, thiols, and amides can be used as precursors. The obtained alkenes can be further functionalized through reduction or epoxidation of the trifluoromethylated double bond. The method is suitable for large-scale batch/flow synthesis and can be conducted under visible light irradiation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ilias Koutsopetras, Abhaya Kumar Mishra, Rania Benazza, Oscar Hernandez-Alba, Sarah Cianferani, Guilhem Chaubet, Stefano Nicolai, Jerome Waser
Summary: Peptide and protein bioconjugation is increasingly important in the pharmaceutical industry. This study introduces the crosslinking ethynylbenziodazolone (EBZ) reagent JW-AM-005 for selective conjugation of peptides and proteins using cysteine residues. The reagent allows for the formation of peptide dimers or stapled peptides under mild and tuneable conditions. Additionally, it demonstrates high regioselectivity in the rebridging of antibody fragments, surpassing commonly used reagents for this transformation.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Vladyslav Smyrnov, Jerome Waser
Summary: An electrophile-induced semipinacol rearrangement of cyclopropenylcarbinols is described, enabling the synthesis of polyfunctionalized cyclopropanes under mild metal-free conditions. The reaction demonstrates broad scope, accommodating various electrophiles, migrating groups, and substitution patterns on the cyclopropene. It is particularly useful for the synthesis of small ring-containing spirocycles, which are important building blocks in medicinal chemistry.
Article
Chemistry, Organic
Pierre Palamini, Julien Borrel, Mael Djaid, Morgane Delattre, Jerome Waser
Summary: We report the synthesis of ketene dithioarylacetals in 40-97% yield using thiophenols and acyl-EBXs generated in situ from a common hypervalent iodine precursor and alkynyl trifluoroborate salts. The products could be further modified to afford functionalized ketene dithioacetals and various S-substituted heterocycles.
Article
Chemistry, Multidisciplinary
Julien Borrel, Jerome Waser
Summary: We present a method for azidoalkynylation of alkenes, which provides a straightforward route to homopropargylic azides by using hypervalent iodine reagents and alkynyltrifluoroborate salts. The development of a photocatalytic redox-neutral radical polar crossover process was crucial for this transformation. A range of homopropargylic azides with electron-rich and -poor aryls, heterocycles, or ether substituents could be obtained in yields of 34-84%. These products serve as valuable building blocks that can be easily converted into pyrroles or bioactive amines.
Article
Chemistry, Multidisciplinary
Mikus Purins, Lucas Eichenberger, Jerome Waser
Summary: We present a mild approach for the synthesis of propargyl silanes from terminal alkynes. A bromonaphthyl-substituted silane was used as a silylmethyl electrophile surrogate, which underwent an aryl-to-alkyl Pd-migration followed by a Sonogashira reaction. A total of 27 propargyl silanes were obtained with yields up to 88%. The resulting products serve as versatile building blocks for addition reactions with electrophiles, triple bond hydrogenation, or silyl group cleavage with acid or fluoride sources.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Tobias M. Milzarek, Nieves P. Ramirez, Xing-Yu Liu, Jerome Waser
Summary: Bis(trifluoromethylated)benziodoxoles are widely used cyclic hypervalent iodine reagents with stability and unique chemical properties. However, current methods for accessing them are tedious. This study reports a direct one-pot synthesis of bis(trifluoromethylated) Bx reagents, enabling the synthesis of functionalized reagents.
CHEMICAL COMMUNICATIONS
(2023)
