Article
Chemistry, Multidisciplinary
Giuseppe Zuccarello, Suzanne M. Batiste, Hyungdo Cho, Gregory C. Fu
Summary: Due to increasing interest in the pharmaceutical industry, the synthesis of chiral alpha-aminoboronic derivatives has become an important challenge. In this study, we demonstrate the enantioselective synthesis of these derivatives using a chiral copper catalyst generated from commercially available components. Mechanistic studies were also conducted to optimize the process and provide insights into the reaction mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jialin Qi, Fang Wei, Shuai Huang, Chen-Ho Tung, Zhenghu Xu
Summary: A new method has been developed for the synthesis of sulfur-containing chiral beta-lactams with two consecutive stereogenic centers using copper(I)-catalyzed asymmetric, three-component interrupted Kinugasa reaction. The key lies in the interception of in situ formed chiral four membered copper(I) enolate intermediate with sulfur electrophiles, resulting in good yields and excellent diastereo- and enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Jian Chen, Gao Deng, You Wang, Shaolin Zhu
Summary: In this study, we have achieved a highly chemo-, regio- and enantioselective reductive hydrocarbonylation of alkenes using a chloroformate ester as a source of CO. This method allows for the rapid increase in molecular complexity and the selective generation of a wide range of structurally diverse alpha-hydroxy ketones, which are important structural elements in bioactive molecules and useful building blocks.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Pierre Plouard, Ulysse Elmerich, Mina Hariri, Severine Loiseau, Ludovic Clarion, Jean Luc Pirat, Pierre-Georges Echeverria, Tahar Ayad, David Virieux
Summary: Asymmetric transfer hydrogenation (ATH) is a powerful method for synthesizing chiral compounds, but the reduction of alpha-ketophosphonates has been less explored. This study reports an efficient Ru-catalyzed ATH method for a broad range of alpha-ketophosphonates, offering mild conditions, operational simplicity, limited waste generation, broad substrate scope, good to excellent yields, and excellent levels of stereoinduction.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ming Hu, Boon Beng Tan, Shaozhong Ge
Summary: Selective defluoroborylation and asymmetric hydro-boration reactions have been developed for fluoroalkyl-substituted terminal alkenes, resulting in the synthesis of chiral alkylboronates with fluoroalkyl-substituted stereogenic carbon centers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Applied
Alemayehu Gashaw Woldegiorgis, Zhao Han, Xufeng Lin
Summary: An enantioselective synthesis of unnatural pyrazole-based alpha-chiral amino acid derivatives was developed using a chiral spirocyclic phosphoric acid catalyst, with yields ranging from 67-98% and enantioselectivities of 73-99%. The NH2 functionality in the products enables further transformations to a chiral thiourea and a lactam, providing a versatile synthetic route for obtaining tetrasubstituted carbon stereocenters in pyrazole-based alpha-amino acid derivatives.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Xiaohui Zhang, Wei Ma, Jinyu Zhang, Weijun Tang, Dong Xue, Jianliang Xiao, Huaming Sun, Chao Wang
Summary: The asymmetric hydroalkylation of racemic allylic alcohols has been developed for the synthesis of chiral amino acid derivatives with two remote chiral centers by borrowing hydrogen catalysis. The stereoselectivities are controlled by a single chiral Ru catalyst via a dynamic kinetic asymmetric transformation process and an interesting diastereoselectivity amplification process of the product.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Jin-Tao Xia, Ling Li, Xiang-Ping Hu
Summary: A copper-catalyzed asymmetric decarboxylative propargylic alkylation has been successfully achieved, allowing for the highly stereoselective formation of acyclic vicinal tri- and tetrasubstituted stereocenters. This strategy has demonstrated high potential in resolving challenges present in traditional catalytic propargylic alkylation by preparing optically active quaternary alpha-amino acid esters with chiral tertiary propargylic moieties in high yields and good to excellent diastereo- and enantioselectivities.
Article
Chemistry, Multidisciplinary
Lingpu Meng, Jingjie Yang, Mei Duan, You Wang, Shaolin Zhu
Summary: Regio- and enantioselective hydroarylamination, hydroalkylamination and hydroamidation of styrenes have been developed using NiH catalysis with a simple bioxazoline ligand under mild conditions. A variety of enantioenriched benzylic arylamines, alkylamines and amides can be easily accessed by employing nitroarenes, hydroxylamines and dioxazolones as amination reagents. Chiral induction in these reactions is proposed to proceed through an enantiodifferentiating syn-hydronickellation step.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Jiali Wang, Jun Yao, Chunqi Jia, Dandan Hu, Yun-Hua Chen, Jinyu Song, Jun-Qi Zhang, Hongjun Ren
Summary: This article describes a robust metal-free catalytic strategy for the rapid synthesis of valuable compounds using cheap and easily available starting materials. The protocol exhibits excellent functional group tolerance and can be easily scaled up. Compared to transition metal-catalyzed methods, this strategy is more environmentally friendly due to the use of a catalytic amount of H3PO4.
Article
Chemistry, Multidisciplinary
Aibo Li, Xinjian Song, Qiao Ren, Peiwang Bao, Xinyu Long, Fuli Huang, Lvjiang Yuan, Jianrong Steve Zhou, Xurong Qin
Summary: A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol resulted in the synthesis of highly enantioselective α,β-dideuterio-α-amino esters with almost complete deuteration (99%). This new protocol was successfully employed for the preparation of dideuterio-α-amino acid fragments in certain drugs, and also applied in the concise synthesis of dideuterio L-DOPA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Cheng Sheng, Zheng Ling, Junzhe Xiao, Kai Yang, Xie Fang, Shengming Ma, Wanbin Zhang
Summary: In this study, enantio- and diastereoselective α-additions of 1-alkynyl ketimines with dual-copper-catalysis were successfully achieved under mild conditions, leading to the synthesis of chiral tetrasubstituted α-amino allenoates bearing a vicinal all-carbon quaternary stereocenter in high yields (up to 99% yield) with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to >20:1 dr). The stereodivergent synthesis of the products was realized by the asymmetric α-addition reaction and the Grignard reagent promoted epimerization. Importantly, the reaction could be smoothly scaled up and applied to introduce chiral tetrasubstituted allenyl moieties into bioactive molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ming-Yao Huang, Yu-Tao Zhao, Cheng-Da Zhang, Shou-Fei Zhu
Summary: This study reports a highly selective method for the B-H bond insertion reactions of alpha-silylcarbenes generated from 1-silylcyclopropenes using a chiral copper(I)/bisoxazoline catalyst. The method allows for the construction of chiral gamma,gamma-disubstituted allylic gem-silylboranes, which cannot be prepared using any other known methods. The newly developed products are versatile allylic bimetallic reagents with high stability and great synthetic potential for the construction of complex molecules with continuous chiral centers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Hui-Min Wu, Zongpeng Zhang, Liang Wei, Xiu-Qin Dong, Chun-Jiang Wang
Summary: An efficient synthetic methodology was developed to access biologically important and synthetically useful alpha-quaternary cysteine derivatives via asymmetric catalytic alpha-allylation. A wide array of alpha-quaternary cysteine derivatives were obtained with good to excellent enantioselectivities, and gram-scale asymmetric allylation was performed to maintain high yields. Additionally, synthetic transformations to access chiral spirocyclic compounds proceeded smoothly, demonstrating the utility of this methodology.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Yuqi Zhu, Ting Zhou, Hong Zhang, Jieyin He, Hongguang Li, Ming Lang, Jian Wang, Shiyong Peng
Summary: This study reports a Rh(II)-catalyzed reaction method for the synthesis of α-aryl-β-aminocyclopropane carboxylic acid derivatives with stereo-isomeric centers using donor-acceptor carbenes derived from a-aryldiazoesters and vinylsulfonamides.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Han-Zhe Miao, Yang Liu, Ye-Wei Chen, Han-Yu Lu, Jian Li, Guo-Qiang Lin, Zhi-Tao He
Summary: A novel palladium-catalyzed remote hydroamination reaction has been discovered, which enables a series of azoles and skipped dienes to undergo migratory allylic C-H amination with good yields and selectivities. A desymmetric migratory azolation process has also been developed to demonstrate the reliability of the transformation. Preliminary mechanistic experiments confirm the designed metal walking and allylic substitution cascade strategy via Pd-H catalysis, which is different from the ligand-to-ligand hydrogen transfer pathway used for conjugated dienes.
Article
Chemistry, Applied
Jia-Ying Zhao, Qi Liao, Jian-Wei Zhang, Guo-Qiang Lin, Zhengtao Wang, Dingding Gao, Qing-Hua Li, Ping Tian
Summary: In this study, a metal-free cascade dihalogenation-cyclization reaction was reported for the convenient preparation of dibrominated cis-tetrahydrobenzofuran-5(4H)-ones and cis-dihydrobenzopyran-6(5H)-ones. These products bear 1,4-dibromobut-1-enyl subunit in trans-trans and trans-cis form. The anticancer activity against MDA-MB-468 cells was also observed for the corresponding products.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Medicinal
Dingding Gao, Shuai Tang, Yixin Cen, Liang Yuan, Xiaojing Lan, Qing-Hua Li, Guo-Qiang Lin, Min Huang, Ping Tian
Summary: PHGDH is an important enzyme in serine biosynthesis pathway, and its overexpression in malignant tumor cells makes it a potential target for cancer treatment. In this study, a series of novel PHGDH inhibitors were discovered using compound screening and structural optimization. The lead compound D8 showed strong enzymatic inhibitory activity, high binding affinity, and sensitivity to PHGDH gene amplification or overexpression. Further experiments revealed the binding site of D8 on PHGDH and its potential antitumor efficacy in a xenograft mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Ya-Jie Wang, Yi-Fan Wang, Wen-Yu Kang, Wen-Ya Lu, Yu-Hui Wang, Ping Tian
Summary: Here, a highly enantioselective homoenolate Michael addition/esterification sequence of cyclo-hexadienone-tethered enals via N-heterocyclic carbene (NHC) catalysis is reported, leading to the formation of enantiopure cis-hydrobenzofurans, cis-hydroindoles, and cis-hydroindenes. The introduction of a nitro group in the NHC catalyst greatly enhances the stereocontrol, while a bulky N-aryl substituent in the triazolium salt is beneficial for preventing further aldol condensation. The utility of this method is demonstrated through a gram-scale experiment and versatile downstream transformations.
Article
Chemistry, Multidisciplinary
Xin Wang, Han-Zhe Miao, Guo-Qiang Lin, Zhi-Tao He
Summary: This study describes feasible protocols to achieve regiodivergent allylic C-H functionalizations via palladium-catalyzed remote substitution, which provides a novel strategy for the seldomly studied migratory Tsuji-Trost reaction. Dictated by a suitable ligand, a process involving 4,3-hydrofunctionalization of the generated conjugated diene intermediate via metal walking is observed with generally >20 : 1 regioselectivity. A major route is also found for 1,4-hydrofunctionalization with a newly synthesized electron-rich bisphosphine ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Qi-Ying Liao, Chao Ma, Yu-Chao Wang, Shao-Qian Yang, Jiang-Shan Ma, Zhi-Tao He
Summary: Because of the widespread applications of optically active alkyl fluorides in medicinal and agrochemicals, the study of enantioselective and stereodivergent construction of alkyl fluorides remains highly desirable. In this study, a palladium-catalyzed enantioselective hydromonofluoroalkylation reaction was developed to achieve this goal.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Shao-Qian Yang, Ai-Jun Han, Yang Liu, Xin-Yuan Tang, Guo-Qiang Lin, Zhi-Tao He
Summary: In this study, a comprehensive investigation was conducted towards the stereoselective formal hydration and hydroaminoxylation of conjugated dienes by synthesizing new P,N-ligands and identifying an aryl-derived oxime as a surrogate for water and hydroxylamine. Additionally, the asymmetric hydroalkoxylation with new P,N-ligands was elucidated. Furthermore, versatile derivatizations following hydration provided indirect but concise routes to formal hydrophenoxylation, hydrofluoroalkoxylation, and hydrocarboxylation of conjugated dienes that have not been reported before. Finally, a ligand-to-ligand hydrogen transfer process was proposed based on preliminary mechanistic experiments.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Qing-Hua Li, Gui-Shan Zhang, Feng Wang, Yixin Cen, Xi-Liang Liu, Jian-Wei Zhang, Yu-Hui Wang, Albert W. M. Lee, Dingding Gao, Guo-Qiang Lin, Ping Tian
Summary: Researchers report an asymmetric rearrangement of cyclopropylcarbinyl cations using artificial organic catalysts, resulting in chiral homoallylic sulfide products with high yields and enantioselectivities (up to 99% enantiomeric excess). The reaction involves the dehydration of prochiral cyclopropylcarbinols catalyzed by a chiral SPINOL-derived N-triflyl phosphoramide catalyst, followed by trapping of the resulting cyclopropylcarbinyl cations by thione-containing nucleophiles. The synthetic utility of the process is demonstrated through subgram-scale experiments and downstream transformations.
Article
Chemistry, Multidisciplinary
Xian-Xiao Chen, Hao Luo, Ye-Wei Chen, Yang Liu, Zhi-Tao He
Summary: Chain walking has been an efficient method for the functionalization of inert C(sp(3))-H bonds, but it has limitations on mono-olefin migration and functionalization. In this study, we demonstrate the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation. The use of palladium hydride catalysis and secondary amine morpholine as a solvent is crucial for achieving high substrate compatibility and stereochemical control.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yu-Ze Sun, Zi-Yang Ren, Yuan-Xiang Yang, Yang Liu, Guo-Qiang Lin, Zhi-Tao He
Summary: This study presents a novel method for dearomatization reactions, utilizing the involvement of a d-orbital electron of the transition metal as a driving force. By using a modified PyBox ligand, valuable skeletons were constructed with high enantioselectivities. An unexpected tandem reaction process was discovered, leading to the formation of an enantioenriched C-N axis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Xian-Xiao Chen, Zhi-Tao He
Summary: The migratory Tsuji-Trost reaction is a new concept beyond the scope of classical Tsuji-Trost reaction, which focuses on the transformation of alkene substrates bearing a remote leaving group. By olefin migration or leaving group migration, typical allyl intermediates are formed for subsequent substitution reactions.
Article
Chemistry, Organic
Tao Wang, Ji-Xun Guan, Yun-Xuan Tan, Ping Tian
Summary: This paper reports the first cobalt-catalyzed highly selective arylation carbocyclization reaction of 1,6-allenynes with arylboronic acids. The reaction demonstrates moderate to high yields, broad substrate scope, and good compatibility with functional groups.
Article
Multidisciplinary Sciences
Ming-Qiao Tang, Zi-Jiang Yang, Zhi-Tao He
Summary: Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via pi-n(3) substitution are reliable methods to construct stereogenic centers. In this study, asymmetric formal sp(2) hydrocarbonations were achieved via hydroalkylation and Wittig reaction cascade. The protocol can facilely construct various unachievable motifs with high selectivity. The interesting mechanistic feature is that alkynes undergo hydrocarbonation via the formation of a conjugated diene intermediate.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Pei-Ying Peng, Gui-Shan Zhang, Mei-Ling Gong, Jian-Wei Zhang, Xi-Liang Liu, Dingding Gao, Guo-Qiang Lin, Qing-Hua Li, Ping Tian
Summary: An efficient strategy for the preparation of bicyclic boronates through metal-free heteroatom-directed alkenyl sp2-C-H borylation is reported. The synthetic approach exhibits good functional group compatibility, and various boronates with halides, aryls, acyclic and cyclic frameworks are obtained in high yields (43 examples, up to 95% yield). Downstream transformations of the bicyclic boronates are also pursued to afford natural products, drug scaffolds, and chiral hemiboronic acid catalysts.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Organic
Si-Yuan Luo, Guo-Qiang Lin, Zhi-Tao He
Summary: A feasible protocol for Cu-catalyzed asymmetric alkynylallylic dimethylamination has been developed using tetramethyldiaminomethane as a new, stable and convenient substitute for dimethylamine. The method allows the construction of a series of enantioenriched 1,4-enynes with reasonable yields, high regioselectivities and moderate to good enantioselectivities. Mechanistic experiments and DFT calculations provide insights into the reaction mechanism and the origin of regio- and enantioselectivity.
ORGANIC CHEMISTRY FRONTIERS
(2023)
