Lei Liu

Name:

Organization: Shandong University

Department: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences

Title:

Chemicals
References

Regio- and Diastereoselective Cross-Dehydrogenative Coupling of Tetrahydropyridines with 1,3-Dicarbonyl Compounds

Co-reporter:Huan Long, Gang Wang, Ran Lu, Mengmeng Xu, Kelian Zhang, Shutao Qi, Yiheng He, Yuxiang Bu, and Lei Liu

Organic Letters April 21, 2017 Volume 19(Issue 8) pp:

Publication Date(Web):April 12, 2017

DOI:10.1021/acs.orglett.7b00787

A regio- and diastereoselective cross-dehydrogenative coupling of N-carbamoyl tetrahydropyridines with a variety of 1,3-dicarbonyl compounds is described. The method exhibits good functional group tolerance, diastereoselectively generating cis-2,6- or cis-2,4-substituted tetrahydropyridines by using different types of 1,3-dicarbonyls. Moreover, a two-step sequence involving diastereoselective cross-dehydrogenative coupling followed by epimerization was also developed, allowing facile access to trans-2,6-substituted tetrahydropyridines as single isomers. Applications in natural product synthesis and divergent analogue preparation were further demonstrated.

Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy

Co-reporter:Miao Wan;Shutao Sun;Yangshan Li; Dr. Lei Liu

Angewandte Chemie 2017 Volume 129(Issue 18) pp:5198-5202

Publication Date(Web):2017/04/24

DOI:10.1002/ange.201701439

AbstractThe first redox deracemization of a series of cyclic benzylic ethers, including 6H-benzo[c]chromenes, isochromans, and 1H-isochromenes, is described. An “acetal pool” strategy was adopted to harmonize the complete oxidation of secondary ethers with imidodiphosphoric acid catalyzed asymmetric transfer hydrogenation. The synthetic utility of the process was demonstrated by the effective deracemization of biologically active molecules of interest that are difficult to prepare by other methods.

Organocatalytic Enantioselective Cross-Dehydrogenative Coupling of N-Carbamoyl Cyclic Amines with Aldehydes

Co-reporter:Zhiyu Xie, Xin Zan, Shutao Sun, Xinhui Pan, and Lei Liu

Organic Letters 2016 Volume 18(Issue 16) pp:3944-3947

Publication Date(Web):August 2, 2016

DOI:10.1021/acs.orglett.6b01625

The existing catalytic enantioselective cross-dehydrogenative coupling of cyclic amines predominantly focused on reactive N-aryl tetrahydroisoquinolines, which typically suffered from limited substrate generality and synthetic utility, and required the use of metal catalyst. Herein, a metal-free catalytic enantioselective cross-dehydrogenative coupling of N-carbamoyl cyclic amines and aldehydes has been reported for the first time. Employing an easily installed and functionalized acyl protecting group rather than the widely adopted aryl moiety endows the enantioselective process with better substrate generality and broader synthetic utility.

Diastereoselectively Complementary C–H Functionalization Enables Access to Structurally and Stereochemically Diverse 2,6-Substituted Piperidines

Co-reporter:Gang Wang, Ying Mao, and Lei Liu

Organic Letters 2016 Volume 18(Issue 24) pp:6476-6479

Publication Date(Web):December 8, 2016

DOI:10.1021/acs.orglett.6b03372

The preparation of 2,6-substituted piperidine derivatives through diastereoselective C–H functionalization of corresponding nitrogen heterocycles represents an appealing protocol and yet remains a formidable challenge. Here, we describe a stereochemically complementary oxidative C–H functionalization of N-carbamoyl tetrahydropyridines with a wide variety of building blocks, providing either the cis- or trans-2,6-substituted piperidines with diverse patterns of functionalities. The mild metal-free process exhibits excellent regio- and diastereoselectivities as well as functional group tolerance. The synthetic utilities in natural product and analogue syntheses are also described.

Copper-Catalyzed Aerobic Enantioselective Cross-Dehydrogenative Coupling of N-Aryl Glycine Esters with Terminal Alkynes

Co-reporter:Zhiyu Xie, Xigong Liu, and Lei Liu

Organic Letters 2016 Volume 18(Issue 12) pp:2982-2985

Publication Date(Web):June 7, 2016

DOI:10.1021/acs.orglett.6b01328

A copper-catalyzed enantioselective cross-coupling of a Csp3–H moiety (N-aryl glycine ester) with a Csp–H component (terminal alkyne) using molecular oxygen as the terminal oxidant is described for the first time. The sustainable method provides an efficient and environmentally friendly approach to rapidly prepare a diverse array of optically active non-natural α-amino acids.

Copper(II) Triflate-Catalyzed Aerobic Oxidative CH Functionalization of Glycine Derivatives with Olefins and Organoboranes

Co-reporter:Zhiyu Xie;Jiong Jia;Xigong Liu

Advanced Synthesis & Catalysis 2016 Volume 358( Issue 6) pp:919-925

Publication Date(Web):

DOI:10.1002/adsc.201501015

An economical synthesis of substituted quinoline-2-carboxylates through the potassium persulfate-mediated cross-dehydrogenative coupling of N-aryl glycine derivatives with olefins

Co-reporter:Guoliang Liu, Jiarui Qian, Jing Hua, Feng Cai, Xia Li and Lei Liu

Organic & Biomolecular Chemistry 2016 vol. 14(Issue 3) pp:1147-1152

Publication Date(Web):01 Dec 2015

DOI:10.1039/C5OB02216A

A practical and economical K2S2O8-mediated oxidative cross-dehydrogenative coupling of N-aryl glycine derivatives with olefins has been established, affording structurally diverse quinoline-2-carboxylates in good to high efficiency. The low cost, negligible toxicity, and ease of handling of K2S2O8 combined with the absence of hazardous byproducts and the easy workup consisting of simple filtration are attractive based on economic and environmental factors.

C1-Benzyl and benzoyl isoquinoline synthesis through direct oxidative cross-dehydrogenative coupling with methyl arenes

Co-reporter:Miao Wan, Hongxiang Lou and Lei Liu

Chemical Communications 2015 vol. 51(Issue 73) pp:13953-13956

Publication Date(Web):23 Jul 2015

DOI:10.1039/C5CC04791A

An oxidative cross-dehydrogenative coupling (CDC) of isoquinolines with methyl arenes has been developed, allowing for the facile synthesis of a broad range of structurally diverse C1-benzyl and -benzoyl isoquinolines. The direct use of readily available methyl arenes as coupling partners avoids unproductive steps for preactivating the functional group installation, and is therefore attractive. The method exhibits excellent chemoselectivity, affording exclusive benzylated products in the presence of DTBP and a catalytic amount of Y(OTf)3, and yielding benzoylated ones with TBHP and a catalytic amount of MnO2.

Organocatalytic Asymmetric C–H Vinylation and Arylation of N-Acyl Tetrahydroisoquinolines

Co-reporter:Xigong Liu, Shutao Sun, Zhilin Meng, Hongxiang Lou, and Lei Liu

Organic Letters 2015 Volume 17(Issue 10) pp:2396-2399

Publication Date(Web):May 5, 2015

DOI:10.1021/acs.orglett.5b00909

The first organocatalytic enantioselective oxidative C–H functionalization of N-acyl tetrahydroisoquinolines with vinyl and aryl boronates promoted by a chiral Brønsted acid is described. This metal-free process tolerates a wide range of electronically varied N-acyl tetrahydroisoquinolines and structurally diverse boronates with good to excellent enantioselectivities.

Highly Enantioselective Catalytic Cross-Dehydrogenative Coupling of N-Carbamoyl Tetrahydroisoquinolines and Terminal Alkynes

Co-reporter:Shutao Sun, Chengkun Li, Paul E. Floreancig, Hongxiang Lou, and Lei Liu

Organic Letters 2015 Volume 17(Issue 7) pp:1684-1687

Publication Date(Web):March 17, 2015

DOI:10.1021/acs.orglett.5b00447

The first catalytic asymmetric cross-dehydrogenative coupling of cyclic carbamates and terminal alkynes has been established. The reaction features high enantiocontrol and excellent functional group tolerance and displays a wide range of structurally and electronically diverse carbamates as well as terminal alkynes. N-Acyl hemiaminals were identified as the reactive intermediates through preliminary control experiments. Employing readily removable carbamates as substrates rather than traditionally adopted N-aryl amines allows applications in complex molecule synthesis and therefore advances the C–H functionalization strategy to a synthetically useful level.

Copper(II)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes

Co-reporter:Shutao Sun, Ying Mao, Hongxiang Lou and Lei Liu

Chemical Communications 2015 vol. 51(Issue 53) pp:10691-10694

Publication Date(Web):21 May 2015

DOI:10.1039/C5CC03314D

The first catalytic asymmetric alkylation of N-acyl quinoliniums with aldehydes has been described. A copper/amine synergistic catalytic system has been developed, allowing the addition of functionalized aldehydes to a wide range of electronically varied N-acyl quinoliniums in good yields with excellent enantiocontrol. The synergistic catalytic system was also effective for N-acyl dihydroisoquinoliniums and β-caboliniums, demonstrating the general applicability of the protocol in the enantioselective alkylation of diverse cyclic N-acyl hemiaminals.

Indium-catalyzed oxidative cross-dehydrogenative coupling of chromenes with 1,3-dicarbonyls and aryl rings

Co-reporter:Fanmei Li, Zhilin Meng, Jing Hua, Wei Li, Hongxiang Lou and Lei Liu

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 20) pp:5710-5715

Publication Date(Web):14 Apr 2015

DOI:10.1039/C5OB00277J

An effective indium-catalyzed oxidative cross-dehydrogenative coupling of electronically varied chromenes with 1,3-dicarbonyl compounds and aryl rings has been established. Both the C–H alkylation and arylation proceed smoothly at room temperature to afford diverse α-substituted chromene compounds in up to 91% yields. Besides these two types of C–H components, simple ketones like cyclohexanones also prove to be well tolerated.

TBHP/TFA mediated oxidative cross-dehydrogenative coupling of N-heterocycles with aldehydes

Co-reporter:Jiayu Chen, Miao Wan, Jing Hua, Yi Sun, Zheng Lv, Wei Li and Lei Liu

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 47) pp:11561-11566

Publication Date(Web):01 Oct 2015

DOI:10.1039/C5OB01763G

An effective and metal-free oxidative cross-dehydrogenative coupling (CDC) of N-heterocycles with diverse aldehydes has been established in the presence of TBHP/TFA. The scope with respect to aldehyde and N-heterocycle components is broad, allowing facile synthesis of a broad range of structurally diverse C1-acyl substituted heterocycles in good efficiency.

Organocatalytic Enantioselective Oxidative CH Alkenylation and Arylation of N-Carbamoyl Tetrahydropyridines and Tetrahydro--carbolines

Co-reporter:Xigong Liu;Zhilin Meng;Chengkun Li; Hongxiang Lou ; Lei Liu

Angewandte Chemie 2015 Volume 127( Issue 20) pp:6110-6113

Publication Date(Web):

DOI:10.1002/ange.201500703

Abstract

The first organocatalytic enantioselective CH alkenylation and arylation reactions of N-carbamoyl tetrahydropyridines and tetrahydro-β-carbolines (THCs) are described. The metal-free processes represent an efficient and straightforward approach to a variety of structurally and electronically diverse α-substituted tetrahydropyridines and THCs in good yields with excellent regio- and enantioselectivities. Preliminary control experiments provide important insights into the reaction mechanism.

Organocatalytic Enantioselective Oxidative CH Alkenylation and Arylation of N-Carbamoyl Tetrahydropyridines and Tetrahydro--carbolines

Co-reporter:Xigong Liu;Zhilin Meng;Chengkun Li; Hongxiang Lou ; Lei Liu

Angewandte Chemie International Edition 2015 Volume 54( Issue 20) pp:6012-6015

Publication Date(Web):

DOI:10.1002/anie.201500703

Abstract

Structurally Diverse α-Substituted Benzopyran Synthesis through a Practical Metal-Free C(sp3)–H Functionalization

Co-reporter:Wenfang Chen, Zhiyu Xie, Hongbo Zheng, Hongxiang Lou, and Lei Liu

Organic Letters 2014 Volume 16(Issue 22) pp:5988-5991

Publication Date(Web):November 11, 2014

DOI:10.1021/ol503004a

A trityl ion-mediated practical C–H functionalization of a variety of benzopyrans with a wide range of nucleophiles (organoboranes and C–H molecules) at ambient temperature has been disclosed. The metal-free reaction has an excellent functional group tolerance and high chemoselectivity and displays a broad scope with respect to both benzopyran and nucleophile partners, efficiently affording a collection of benzopyrans bearing diverse skeletons and α-functionalities in one step.

An economical and environmentally friendly oxidative biaryl coupling promoted by activated MnO2

Co-reporter:Jingjing Yang, Shutao Sun, Ziyu Zeng, Hongbo Zheng, Wei Li, Hongxiang Lou and Lei Liu

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 39) pp:7774-7779

Publication Date(Web):07 Aug 2014

DOI:10.1039/C4OB01409J

An activated manganese dioxide (MnO2)–BF3·OEt2 oxidation system was developed to efficiently mediate the intramolecular as well as intermolecular biaryl coupling. The oxidative coupling proceeds smoothly at ambient temperature to deliver the corresponding five- to eight-membered tricyclic products in good to excellent yields. The employment of the combination of MnO2 and BF3·OEt2 is attractive on the basis of economical and environmental issues.

Seven- and eight-membered heterocyclic biaryl synthesis through a metal-free oxidative coupling reaction

Co-reporter:Shutao Sun, Jingjing Yang, Fanmei Li, Zheng Lv, Wei Li, Hongxiang Lou, Lei Liu

Tetrahedron Letters 2014 Volume 55(Issue 50) pp:6899-6902

Publication Date(Web):10 December 2014

DOI:10.1016/j.tetlet.2014.10.103

A metal-free intramolecular biaryl coupling mediated by DDQ and BF3·OEt2 was developed. The reaction proceeds smoothly at room temperature to give seven- and eight-membered heterocyclic biaryl compounds in up to 95% yields. Only 1 equiv of DDQ sufficed for the reaction, obviating the use of a large excess of oxidants and undesired chlorination pathway in metal-mediated process.

A metal-free cross-dehydrogenative coupling of N-carbamoyl tetrahydroisoquinoline by sodium persulfate

Co-reporter:Wenfang Chen, Hongbo Zheng, Xinhui Pan, Zhiyu Xie, Xin Zan, Bin Sun, Lei Liu, Hongxiang Lou

Tetrahedron Letters 2014 Volume 55(Issue 17) pp:2879-2882

Publication Date(Web):23 April 2014

DOI:10.1016/j.tetlet.2014.03.094

A metal-free cross-dehydrogenative coupling of N-carbamoyl tetrahydroisoquinoline with a variety of CH nucleophiles mediated by Na2S2O8 is developed. The reaction proceeds smoothly to give the coupled product in up to 83% yields. The nucleophile scope is broad, including simple ketones, aldehydes, and aryl rings. The carbamoyl protecting group can be readily removed under mild condition. The use of Na2S2O8 as the sole reagent for the CDC reaction is attractive based on economical and environmental factors.

Copper(II) catalyzed cross-dehydrogenative coupling of cyclic benzylic ethers with simple carbonyl compounds by Na2S2O8

Co-reporter:Xinhui Pan, Qingwen Hu, Wenfang Chen, Xigong Liu, Bin Sun, Zhouli Huang, Ziyu Zeng, Liguo Wang, Dan Zhao, Mei Ji, Lei Liu, Hongxiang Lou

Tetrahedron 2014 70(21) pp: 3447-3451

Publication Date(Web):

DOI:10.1016/j.tet.2014.03.074

Practical Metal-Free C(sp3)H Functionalization: Construction of Structurally Diverse -Substituted N-Benzyl and N-Allyl Carbamates

Co-reporter:Zhiyu Xie; Lei Liu;Wenfang Chen;Hongbo Zheng;Qingqing Xu; Huiqing Yuan; Hongxiang Lou

Angewandte Chemie International Edition 2014 Volume 53( Issue 15) pp:3904-3908

Publication Date(Web):

DOI:10.1002/anie.201310193

Abstract

Described is a practical and universal CH functionalization of readily removable N-benzyl and N-allyl carbamates, with a wide range of nucleophiles at ambient temperature promoted by Ph₃CClO₄. The metal-free reaction has an excellent functional-group tolerance, and displays a broad scope with respect to both N-carbamates and nucleophile partners (a variety of organoboranes and CH compounds). The synthetic utility in target- as well as diversity-oriented syntheses is demonstrated.

Practical and Highly Selective CH Functionalization of Structurally Diverse Ethers

Co-reporter:Miao Wan;Zhilin Meng; Hongxiang Lou ; Lei Liu

Angewandte Chemie International Edition 2014 Volume 53( Issue 50) pp:13845-13849

Publication Date(Web):

DOI:10.1002/anie.201407083

Abstract

A trityl ion mediated CH functionalization of ethers with a wide range of nucleophiles at ambient temperature has been developed. The reaction displays high chemoselectivity and good functional group tolerance. The protocol also exhibits excellent regio- and diastereoselectivities for the unsymmetric ethers, thus stereoselectively generating highly functionalized disubstituted 2,5-trans tetrahydrofurans (THF), 2,6-trans tetrahydropyrans (THP), 2,6-trans dihydropyrans (DHP), and 1,3-trans isochromans, and highlighting the capacity of the protocol in complex molecule synthesis.

Catalytic Enantioselective Oxidative Cross-Coupling of Benzylic Ethers with Aldehydes

Co-reporter:Zhilin Meng;Shutao Sun;Dr. Huiqing Yuan;Dr. Hongxiang Lou;Dr. Lei Liu

Angewandte Chemie International Edition 2014 Volume 53( Issue 2) pp:543-547

Publication Date(Web):

DOI:10.1002/anie.201308701

Abstract

The first one-pot enantioselective oxidative coupling of cyclic benzylic ethers with aldehydes has been developed. A variety of benzylic ethers were transformed into the corresponding oxygen heterocycles with high enantioselectivity. Mechanistic experiments were conducted to determine the nature of the reaction intermediates. The application of this strategy to coupling reactions with other nucleophiles besides aldehydes was also explored.

Practical and Highly Selective CH Functionalization of Structurally Diverse Ethers

Co-reporter:Miao Wan;Zhilin Meng; Hongxiang Lou ; Lei Liu

Angewandte Chemie 2014 Volume 126( Issue 50) pp:14065-14069

Publication Date(Web):

DOI:10.1002/ange.201407083

Abstract

Practical Metal-Free C(sp3)H Functionalization: Construction of Structurally Diverse -Substituted N-Benzyl and N-Allyl Carbamates

Co-reporter:Zhiyu Xie; Lei Liu;Wenfang Chen;Hongbo Zheng;Qingqing Xu; Huiqing Yuan; Hongxiang Lou

Angewandte Chemie 2014 Volume 126( Issue 15) pp:3985-3989

Publication Date(Web):

DOI:10.1002/ange.201310193

Abstract

Manganese Dioxide–Methanesulfonic Acid Promoted Direct Dehydrogenative Alkylation of sp3 C–H Bonds Adjacent to a Heteroatom

Co-reporter:Xigong Liu, Bin Sun, Zhiyu Xie, Xiaojun Qin, Lei Liu, and Hongxiang Lou

The Journal of Organic Chemistry 2013 Volume 78(Issue 7) pp:3104-3112

Publication Date(Web):March 18, 2013

DOI:10.1021/jo4000674

A manganese dioxide (MnO2)–methanesulfonic acid (CH3SO3H) oxidation system has been developed to efficiently promote direct coupling of benzylic ethers and carbamates with simple ketones via oxidative C–H bond activation. The alkylation proceeds smoothly under air atmosphere to afford the corresponding products in good to excellent yields (53–87%). The employment of the combination of MnO2 and CH3SO3H is attractive on the basis of economical and environmental issues.

TBHP/TFA mediated oxidative cross-dehydrogenative coupling of N-heterocycles with aldehydes

Co-reporter:Jiayu Chen, Miao Wan, Jing Hua, Yi Sun, Zheng Lv, Wei Li and Lei Liu

Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 47) pp:NaN11566-11566

Publication Date(Web):2015/10/01

DOI:10.1039/C5OB01763G

Indium-catalyzed oxidative cross-dehydrogenative coupling of chromenes with 1,3-dicarbonyls and aryl rings

Co-reporter:Fanmei Li, Zhilin Meng, Jing Hua, Wei Li, Hongxiang Lou and Lei Liu

Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 20) pp:NaN5715-5715

Publication Date(Web):2015/04/14

DOI:10.1039/C5OB00277J

Copper(II)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes

Co-reporter:Shutao Sun, Ying Mao, Hongxiang Lou and Lei Liu