Article
Chemistry, Multidisciplinary
Guangzhu Wang, Chaoren Shen, Xinyi Ren, Kaiwu Dong
Summary: An intramolecular Heck cyclization catalyzed by Ni/(S,S)-BDPP was developed for the synthesis of oxindoles with good enantioselectivities. The use of an electrophilic cyanation reagent was found to address the deleterious effect of the coordinative cyanide ion in asymmetric alkene arylcyanation.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Ting Yu, Zhong-Qiu Li, Jing Li, Sidi Cheng, Jiali Xu, Jun Huang, Yu-Wu Zhong, Shuang Luo, Qiang Zhu
Summary: Enantioenriched pyrido[6]helicenes and furan-containing pyrido[7]helicenes have been synthesized through a palladium-catalyzed double imidoylative cyclization. This method allows for the construction of two pyridyl rings in one pot, leading to structurally diverse optically pure pyridohelicenes. This research provides potential for optical studies and applications of this important class of azahelicenes.
Article
Chemistry, Organic
Travis Menard, Aragorn Laverny, Scott E. Denmark
Summary: This method describes the catalytic, enantioselective carbosulfenylation of alkenes to construct difficult-to-generate, enantioenriched, 3,4-disubstituted chromans with moderate to high yields and excellent enantioselectivities. The resulting thioether moiety is amenable to various functional group manipulations and transformations, providing access to sulfur-containing functional groups present in natural products and pharmaceuticals.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Applied
Yoshikazu Horino, Mayo Ishibashi, Juri Sakamoto, Miki Murakami, Toshinobu Korenaga
Summary: The diastereoselective synthesis of anti-homoallylic alcohols bearing conjugated (Z)-enynes through a palladium-catalyzed three-component reaction is described, featuring a broad substrate scope, good functional group compatibility, and high levels of (Z)-alkene stereocontrol. The reaction involves Pd(0) functioning as a catalyst in two fundamental steps: the generation of a borylated pi-allylpalladium species inducing umpolung allylation of aldehydes, and C(sp(2))-C(sp) cross-coupling. Further transformations of the obtained products highlight their synthetic utility.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Biao Zhang, Junhao Ruan, Daniel Seidel, Weijie Chen
Summary: Unprotected cis-2,3-diarylpiperidines are synthesized through a palladium-catalyzed cross-coupling reaction between aryl halides and endocyclic 1-azaallyl anions. These intermediates are generated in situ by the deprotonation of 2-aryl-1-piperideines, precursors that are readily prepared from simple piperidines. An asymmetric version of this reaction provides products with moderate to good yields and enantioselectivities when using (2R, 3R)-iPr-BI-DIME as the ligand. This study expands the synthetic utility of endocyclic 1-azaallyl anions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Bao-Cheng Wang, Yi Wei, Feng-Ya Xiong, Bao-Le Qu, Wen-Jing Xiao, Liang-Qiu Lu
Summary: The concise synthesis of eight-membered lactones, which are widely found in many bioactive natural products, has been a challenging task. In this study, an enantioselective synthesis of eight-membered lactones through a Pd-catalyzed asymmetric (6+2) dipolar annulation was successfully achieved. The reaction exhibits simple operation, mild conditions, and good enantioselectivity.
SCIENCE CHINA-CHEMISTRY
(2022)
Article
Chemistry, Organic
Zhen-Sheng Jia, Yong-Jie Wu, Qi-Jun Yao, Xue-Tao Xu, Kun Zhang, Bing-Feng Shi
Summary: A Pd-catalyzed atroposelective C-H allylation with 1,1-disubstituted alkenes was carried out using the chiral ligand L-pGlu-OH, resulting in the synthesis of enantioenriched N-aryl peptoid atropisomers. High yields and excellent enantioselectivities were achieved, with up to 90% yield and 97% ee.
Article
Chemistry, Organic
Zhenbang Chen, Zengming Shen
Summary: An efficient method for Ni-catalyzed asymmetric reductive arylcyanation of alkenes is developed, producing chiral 3-cyanomethyl oxindoles with all-carbon quaternary stereocenters in high yields and enantioselectivities. The use of acetonitrile as a cyano source through beta-carbon elimination assisted by Zn(OTf)(2) avoids the release of free cyanide anions, preventing competitive coordination with the metal center and maintaining enantioselectivity. This method also finds valuable applications in the synthesis of natural alkaloids (-)-physostigmine and (-)-esermethole.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Shao-Bo Duan, Hong-Yu Zhang, Bo-Ya Hao, Jiquan Zhao, Ya-Ping Han, Yuecheng Zhang, Yong-Min Liang
Summary: This study has successfully developed a novel dearomative reaction method for the synthesis of structurally diverse tetracyclic indolines through a series of reaction steps. The reaction exhibits high yields, excellent diastereoselectivities, and good compatibility with functional groups.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Siyuan Guo, Baode Ma, Gen-Qiang Chen, Xumu Zhang
Summary: Optically enriched racetam analogues were synthesized through highly remote diastereocontrolled and enantiocontrolled Pd/C-catalyzed hydrogenation of alpha,beta-unsaturated gamma-lactams. Various mono- and disubstituted 2-pyrrolidones were obtained with excellent yields and stereoselectivities, and a concise and large-scale synthesis of brivaracetam was developed from inexpensive L-2-aminobutyric acid. Surprisingly, stereodivergent hydrogenation was observed by modifying remote functionalized stereocenters and additives, which would provide alternative stereochemical options for chiral racetams synthesis.
Article
Chemistry, Physical
Palagulla Maheswar Reddy, Kuppan Ramachandran, Pazhamalai Anbarasan
Summary: An efficient palladium-catalyzed diastereoselective synthesis of 2,2,3-trisubstituted dihydrobenzofurans has been achieved in good yield as a single diastereomer. The transformation involves in-situ generation of oxonium ylide from 2-hydroxyphenyl substituted enone and diazo compound followed by intramolecular trapping via Michael addition, leading to potent dibenzofuran derivatives in good yield.
JOURNAL OF CATALYSIS
(2021)
Article
Chemistry, Organic
Jun-An Xiao, Huan Zhang, Xue-Ling Luo, Ru-Fang Meng, Wei Wang, Wei-dong Lu, Wei Su, Chenxiang Lin, Peng-Ju Xia, Hua Yang
Summary: A palladium-catalyzed ring-opening [3 + 2]-annulation reaction was developed for the synthesis of seven-membered benzosultams from spirovinylcyclopropanyloxindoles and cyclic N-sulfonylimines. The reaction yielded a wide range of compounds with both a quaternary center and axially chiral biaryl scaffolds, with an average yield of 87% and moderate to excellent diastereoselectivities. Enantioenriched benzosultams were also successfully synthesized in good yields with excellent atropoenantioselectivities using the Pd-2(dba)(3)/(S,S,S)-SKP ligand. The practical utility of this method was demonstrated through gram-scale reactions and diversified synthetic transformations.
Article
Chemistry, Multidisciplinary
Wang Yao, Chuan-Jun Lu, Li-Wen Zhan, Yi Wu, Jia Feng, Ren-Rong Liu
Summary: In this study, a palladium-catalyzed enantioselective C-H activation method for pyrroles was reported, which successfully synthesized structurally diverse indole-pyrrole atropisomers with a chiral N-N axis, showing high yields and enantioselectivities. Furthermore, the kinetic resolution of trisubstituted N-N heterobiaryls with more sterically demanding substituents was also achieved. This versatile method enables the rapid and selective functionalization of pyrroles, facilitating the synthesis of valuable and complex N-N atropisomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Xiaosa Lu, Jie Zhu, Yinhua Huang
Summary: A rhodium-catalyzed highly enantio- and diaster-eoselective alkenylation reaction of Ay-unsaturated butenolides is reported. The use of a chiral diene ligand enables the synthesis of chiral butyrolactones in high yields with extremely high enantioselectivities and high diastereoselectivities. The key process involves the isomerization of butenolides and subsequent dynamic kinetic resolution.
Article
Chemistry, Multidisciplinary
Tian-Yu Jiang, Yi-Ting Ke, Yong-Jie Wu, Qi-Jun Yao, Bing-Feng Shi
Summary: In this study, enantioenriched N-aryl peptoid atropisomers were synthesized via Pd(ii)-catalyzed atroposelective C-H olefination using easily accessible l-pyroglutamic acid as the chiral ligand. The obtained optically active N-aryl peptoid atropisomers exhibited high enantioselectivities and useful yields.
CHEMICAL COMMUNICATIONS
(2023)
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, Multidisciplinary
Austin D. Marchese, Andrew G. Durant, Cian M. Reid, Clara Jans, Ramon Arora, Mark Lautens
Summary: A Pd(0)/blue light catalyzed carboiodination reaction has been reported, which generates a variety of iodinated hetero- and carbocycles. The reaction system is simple and stable, and shows good tolerance towards sensitive functional groups, delivering products in high yields. Experimental evidence supports the reversible C-I bond formation via a single electron mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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.