Article
Chemistry, Physical
Xavier Abel-Snape, Gina Wycich, Mark Lautens
Summary: A palladium-catalyzed three-component domino reaction for accessing indene derivatives is described. The reaction involves the sequential formation of three bonds, with the first two resulting from inter- and intramolecular carbopalladation, and the final bond arising from an attack by a terminating nucleophilic reagent. The starting tether on the iodoarene can be modified to yield either indenes or benzofulvenes. Additionally, the use of an oxabicycle as an acetylene surrogate is demonstrated, and the enantioselective synthesis of indenes is preliminarily explored.
Article
Chemistry, Applied
Yuxin Ding, Ruiqin Zhang, Renchao Ma, Yongmin Ma
Summary: An iodine-catalyzed double [4+2] oxidative annulation of ketones and diamines is reported, leading to the synthesis of substituted dimeric pyrazines under metal-free conditions through a multi-pathway coupled domino strategy. During this process, one C-C and four C-N bonds are formed from two ketones and two diamines.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Applied
Nicholas D. C. Tappin, Philippe Renaud
Summary: An improved procedure for halogen atom and chalcogen group transfer radical additions is reported, utilizing the thermal decomposition of DTBHN to produce reactive methyl radicals. This initiation method generates gaseous or volatile byproducts for easy purification, with simple reaction conditions and broad scope of application demonstrated. Additionally, an alternative source of radicals, DTBPO, is also shown to be effective under identical conditions.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Zhigang Huang, Longji Dai, Zhiyuan Chen
Summary: A palladium-catalyzed tandem cyclization reaction was developed to synthesize aminated tetracyclic 1,2-benzothiazepine 1-oxides with a highly fused cyclic unit. The use of an acetyl group as the protecting group for sulfoximines effectively suppressed the formation of intramolecular cyclization side products, resulting in excellent chemoselectivity and regioselectivity.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Fang Xie, Jie Zhao, Deyue Ren, Jianming Xue, Jingyi Wang, Qin Zhao, Lu Liu, Xiaodan Liu
Summary: A Cu-catalyzed coupling reaction between cyclic imino esters and 2H-azirines has been developed, allowing for the synthesis of novel optically active aziridines in high yields and with excellent levels of diastereo- and enantioselectivities under mild conditions. This method features a broad substrate scope, good functional group compatibility, and enriches the existing reaction type for the rapid synthesis of optically active aziridines bearing vicinal tetrasubstituted stereogenic carbon centers.
Article
Chemistry, Organic
Futao Peng, Liliang Huang, Junhai Huang, Huangdi Feng
Summary: The Aza-Morita-Baylis-Hillman cascade strategy mediated by 1,4-diazabicyclo-[2.2.2]octane (DABCO) was utilized to efficiently produce amino derived 1,6-dienes using a variety of primary amines. Surprisingly, using an aqueous medium promoted reaction efficiency and increased product yield. The protocol demonstrated significant advances in synthetic chemistry and pharmaceutical chemistry with its one-pot operation, high chemoselectivity, and broad substrate scope.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shaomin Chen, Rongxian Bai, Minghao Li, Ping Liu, Yanlong Gu
Summary: Adding an additive-like component to induce acid-acid-catalyzed tandem reactions can enrich method diversity, simplify operation, and enhance synthetic efficiency.
Article
Chemistry, Organic
Ji-Gang Gao, Xu-Kai Guan, Dong-Yang Sun, Heng Zhang, Wen-Hua Mi, Xiang-Shuo Qin, Guang-Liang Zhang, Suoqin Zhang
Summary: This study presents an enantioselective domino reaction between 3-vinylindole and p-quinone methide for the preparation of 3-indolyl cyclopenta[b]indoles containing multiple chiral centers. The cascade asymmetric process enabled by chiral imidodiphosphoric acids delivers products with excellent yields, enantioselectivities, and diastereoselectivities.
Article
Chemistry, Organic
Ke Li, Zhenjie Gan, Er-Qing Li, Zheng Duan
Summary: A novel phosphine-catalyzed (4 + 2) cyclization reaction has been reported for the generation of functionalized dihydropyran skeletons from electron-deficient conjugated dienes and enones. Mechanistic investigation reveals the formation of a new phosphonium zwitterion, which undergoes consecutive reactions. An asymmetric variant has also been developed through efficient and economical chiral phosphine catalysis.
Article
Chemistry, Multidisciplinary
Mehran Ghasemi, Banafshe Rahimi, Maryam Dehghan, Mohammad Hossein Bernoosha, Farnaz Jafarpour
Summary: A palladium (ii)-catalyzed borono-ortho-CH activation/amination cascade for the construction of C-N and C-C bonds in a single synthetic sequence is reported. This method involves a formal syn-carbopalladation of alkynes with organoboron compounds, followed by trapping of the resulting alkenyl palladium species with simple amines to form highly substituted indoles. In the case of electron-rich arylboronic acid, an unexpected anti-carbopalladation terminated by ortho-CH activation of diarylalkyne/amination reaction leads to the formation of unsymmetrically substituted 2,3-diaryl indole. The participation of urea in this cascade reaction is also demonstrated, providing a variety of free NH-indoles.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Nerea Conde, Maria Teresa Herrero, Garazi Urgoitia, Raul SanMartin
Summary: Metal-catalyzed cascade processes based on hydrofunctionalization of alkynes have the potential to provide advantageous approaches to otherwise synthetically challenging compounds. A CNN pincer palladium(II) complex, acting as a homogeneous catalyst, provides the corresponding polyheterocycles with a higher substrate/catalyst ratio.
Article
Chemistry, Organic
Ya-Qiong Li, Guo-Dong Xu, Zhi-Zhen Huang
Summary: An efficient organophosphorus-mediated cross-Rauhut-Currier/Wittig domino reaction has been developed for the synthesis of trisubstituted cyclopentenes, showing advantages of mild reaction conditions, high efficiency, environmental friendliness, and satisfactory yields.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Dakoju Ravi Kishore, Komal Goel, Chander Shekhar, Gedu Satyanarayana
Summary: This report presents the intramolecular cascade cycloaromatization of 1,7-ynones promoted by BF3·OEt2 to synthesize structurally diverse benzofluorene scaffolds. The method features simplicity, scalability, and a wide range of applicability.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Cang Cheng, Yanghui Zhang
Summary: A Pd-catalyzed trans-selective carbosilylation reaction of alkynes has been developed, leading to the formation of multisubstituted vinylsilanes. This method offers a useful strategy for the stereoselective synthesis of exocyclic tetrasubstituted vinylsilanes containing isoquinolinone.
Article
Chemistry, Physical
Jian-Shu Wang, Jiangjie Zhang, Siqi Wang, Jun Ying, Chuan-Ying Li, Xiao-Feng Wu
Summary: A novel palladium-catalyzed domino carbonylative cyclization has been developed for the rapid construction of functionalized heterocycles. The reaction proceeds smoothly with the consecutive formation of C-C and C-X bonds using benzene-1,3,5-triyl triformate as the CO source, yielding a variety of biologically relevant derivatives.
JOURNAL OF CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Ramon Arora, Jose F. Rodriguez, Andrew Whyte, Mark Lautens
Summary: A palladium-catalyzed strategy has been proposed for synthesizing unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins, with high yields and excellent stereoselectivities achieved using low catalyst loadings. Mechanistic studies suggest a syn-carbopalladation of the carbamoyl chloride followed by Pd-II-catalyzed cyclization of alkyne-tethered nucleophiles.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Rachel J. Baker, Justin Ching, Teh Ren Hou, Ivan Franzoni, Mark Lautens
Summary: The dearomatization of 2-naphthols is a simple method for constructing complex 3D structures from simple planar starting materials using rhodium and acid catalysis under mild conditions. The vinyl cyclopropane molecules formed in this reaction exhibit high chemoselectivity and scalability, and can be further functionalized at different sites. Both computational and experimental evidence were used to understand the reaction mechanism.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Austin D. Marchese, Andrew G. Durant, Mark Lautens
Summary: A simple and modular approach using palladium catalysis to synthesize bis-heterocyclic spirocycles is reported. The method leverages a Mizoroki-Heck-type reaction to generate neopentylpalladium species, allowing for intramolecular C-H activation on a wide array of C-H bonds to produce a variety of spirocycles. The reaction is scalable, allowing for easy incorporation of biologically relevant heterocycles without the need for flash column chromatography.
Editorial Material
Chemistry, Organic
Mark Lautens
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Austin D. Marchese, Bijan Mirabi, Colton E. Johnson, Mark Lautens
Summary: This paper reports a comprehensive study of reversible C-C bond formation using palladium catalysis. It was found that different diastereomers can be converted to the same product under identical catalytic conditions. Experimental and computational studies also investigated key concepts such as the effect of electronic and steric parameters on the C-C bond cleavage step.
Article
Chemistry, Organic
Jonathan Bajohr, Matthias D. Boehme, Jiacheng Gao, F. Ekkehardt Hahn, Mark Lautens
Summary: The diastereoselective synthesis of sulfonylated indolines has been reported. Reactive benzylic sulfinates are generated through a palladium-catalyzed dearomative sulfination of (aza)indole-tethered aryl iodides. These intermediates react with electrophiles in a one-pot, two-step process to give sulfonylated products with good yields and excellent diastereoselectivity. This scalable three-component sequence can also be used for the synthesis of sulfonamides. Furthermore, further derivatizations of aryl iodide containing products lead to the formation of spiro- and alkynylated indoline products.
Article
Chemistry, Physical
Xavier Abel-Snape, Gina Wycich, Mark Lautens
Summary: A palladium-catalyzed three-component domino reaction for accessing indene derivatives is described. The reaction involves the sequential formation of three bonds, with the first two resulting from inter- and intramolecular carbopalladation, and the final bond arising from an attack by a terminating nucleophilic reagent. The starting tether on the iodoarene can be modified to yield either indenes or benzofulvenes. Additionally, the use of an oxabicycle as an acetylene surrogate is demonstrated, and the enantioselective synthesis of indenes is preliminarily explored.
Article
Chemistry, Physical
Mark Lautens, Egor M. Larin, Jeanne Masson-Makdissi, Jin Jang
Summary: In this study, a rhodium-catalyzed domino strategy was developed for the synthesis of oxindole-containing products from simple ortho-bromoaniline-derived acrylamides. Mechanistic and computational studies elucidated that the reaction proceeds through a Heck-type process to generate benzylidene intermediate and subsequent beta-hydride elimination, followed by the formation of RhI-hydride species and a 1,4-conjugate addition to yield the final oxindole products. Importantly, the use of sodium formate was found to be crucial for generating the rhodium hydride species and enabling the catalyst turnover.
Article
Chemistry, Multidisciplinary
E. Ali McKnight, Ramon Arora, Ekadashi Pradhan, Yuriko H. Fujisato, Ayonitemi J. Ajayi, Mark Lautens, Tao Zeng, Christine M. M. Le
Summary: A BF3-catalyzed atom-economical fluorocarbamoylation reaction was reported, which enables the insertion of alkynes into strong C-F bonds through a halide recycling mechanism. The developed method provides stereoselective access to 3-(fluoromethylene) oxindoles and gamma-lactams, including fluorinated derivatives of known protein kinase inhibitors. Experimental and computational studies support a stepwise mechanism for the fluorocarbamoylation reaction involving a cyclization step followed by internal fluoride transfer.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Sean Harrington, Jacob Pyche, Andrew R. Burns, Tina Spalholz, Kaetlyn T. Ryan, Rachel J. Baker, Justin Ching, Lucien Rufener, Mark Lautens, Daniel Kulke, Alexandre Vernudachi, Mostafa Zamanian, Winnie Deuther-Conrad, Peter Brust, Peter J. Roy
Summary: Nematode parasites of humans and livestock are a significant burden to human health, economic development, and food security. The discovery of Nemacol, a novel anthelmintic drug, provides a potential solution to the problem of drug resistance and lack of effective treatments for nematode parasites. Nemacol inhibits the vesicular acetylcholine transporter (VAChT) and enhances the efficacy of existing anthelmintic drugs.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Ramon Arora, Regina M. Oechsner, Clara Jans, Bijan Mirabi, Austin D. Marchese, Mark Lautens
Summary: A palladium-catalyzed epimerization reaction of stereogenic alkyl iodides is reported using an air-stable precatalyst. Mechanistic experiments revealed the stereoinversion of the C-I bond via reversible bond formation, supported by density functional theory studies. Stoichiometric experiments showed that irradiation of isolable alkyl-Pd(II) complexes promoted C-I reductive elimination, with potential application in C-Br bond formation.
Article
Chemistry, Multidisciplinary
Eric N. Donders, Kai V. Slaughter, Christian Dank, Ahil N. Ganesh, Brian K. Shoichet, Mark Lautens, Molly S. Shoichet
Summary: The pK(a) of colloid-forming drugs can be manipulated to achieve endosomal disruption while avoiding phospholipidosis and minimizing toxicity, leading to the design of drug-rich nanoparticles. By synthesizing ionizable derivatives of fulvestrant analogs, which are lipid-stabilized drug colloids, the pK(a) of these ionizable colloids influenced the mechanism of endosomal and lysosomal disruption. This study establishes a tunable and generalizable strategy for endosomal disruption by manipulating the pK(a) of colloid-forming drugs.
Article
Chemistry, Organic
Jonathan Bajohr, Aureilien Dupeux, Daniel Schenk, Clara Jans, Mark Lautens
Summary: The synthesis of bis-heterocyclic spirocycles containing pyrroline and indoline motifs through palladium-catalyzed reactions is reported. In situ generation of palladacycles via Narasaka-Heck/C-H activation reactions using di-tert-butyldiaziridinone as a functionalizing reagent. The scalability of the reaction and the synthetic utility of the spirocyclic products are demonstrated through their deprotection, reduction, and (3 + 2) cycloaddition reactions. Kinetic isotope effect experiments provide evidence for a turnover-limiting C-H functionalization step in the catalytic cycle.
Article
Chemistry, Multidisciplinary
Xavier Abel-Snape, Colton E. Johnson, Bianca Imbriaco, Mark Lautens
Summary: A palladium-catalyzed spirocyclization reaction was reported, which involved the insertion of an oxabicycle into a palladacycle. The reaction proceeded via carbocyclization and a C-H functionalization sequence, and the diastereoselective nature of the insertion was observed. The spirooxindoles produced in the reaction allowed for further transformations and were previously unaccessible.
Article
Chemistry, Organic
Colton E. Johnson, Shangyu Li, Ramon Arora, Bijan Mirabi, Mark Lautens
Summary: This article focuses on the mechanism, recent applications, challenges, and outlook of Ni-catalyzed C-H activation of sp(3)-hybridized carbon atoms. The study highlights the differences between Ni and Pd in C-H activation and discusses the choice of directing groups as well as primary, secondary, and tertiary C-H activation.