Copper-catalysed asymmetric radical cyanation

In this Perspective, we discuss catalytic asymmetric cyanation reactions and the key carbon radicals involved, such as benzylic, allylic and propargylic radicals. In particular, we outline the control of selectivity by considering the mechanism of formation for the carbon radicals as well as the subsequent copper-catalysed radical cyanation step. The carbon radicals can be generated from a diverse range of precursors, which include C–H substrates, alkenes, esters, cyclopropanol and so on. As a consequence, copper-catalysed asymmetric radical cyanation has the potential to expand the scope of catalytic asymmetric cyanation and is expected to find broad utility in organic synthesis and the late-stage functionalization of complex molecules. This Perspective is published in Nature Synthesis. Congratulations Fei Wang Read More

Catalytic remote hydrohalogenation of internal alkenes

Primary alkyl halides have broad utility as fine chemicals in organic synthesis. The direct halogenation of alkenes is one of the most efficient approaches for the synthesis of these halides. We report the remote oxidative halogenation of alkenes under palladium catalysis via which both terminal and internal alkenes yield primary alkyl halides efficiently. Engineering pyridine-oxazoline ligands by introducing a hydroxyl group is essential for achieving excellent chemo- and regioselectivity. The catalytic system is also good for the mixture of alkene isomers generated from dehydrogenation of alkanes, providing a window to investigate the high-value utilization of inexpensive alkanes. This result is published in Nature Chemistry. Congratulations Xiang Li and Jianbo Jin. Read More

Congratulations to Ronghua Lu (陆荣华) to obtain his doctorate degree.

Enantioselective Copper-Catalyzed Radical Cyanation of Propargylic C–H Bonds: Easy Access to Chiral Allenyl Nitriles

The first enantioselective copper-catalyzed cyanation of propargylic C–H bonds via radical relay was established using novel BoxOTMS ligands, providing an efficient and straightforward tool for the construction of structurally diverse chiral allenyl nitriles in good yields with excellent enantioselectivities. This reaction features high functional group tolerance and mild conditions. In addition, the chiral allene products can be readily converted to other chiral compounds via axis-to-center chirality transfer. This result is published in JACS. Congratulations Ronghua Lu. Read More

Asymmetric Palladium-Catalyzed Oxycarbonylation of Terminal Alkenes: Efficient Access to β-Hydroxy Alkylcarboxylic Acids

A novel Pd-catalyzed enantioselective oxycarbonylation of alkenes has been established. The ligand with an ethyl group at the C-6 position of Pyox plays a significant role in the intermolecular oxypalladation process, leading to high reactivity and excellent enantioselective control. this method allows for broad alkene substrate scope, excellent regio- and enantioselectivities, scalabilities and a wide array of applications, and provides a useful route for the convenient and straightforward synthesis of chiral β-hydroxy alkylcarboxylic acids/esters. This result is published in ACIE. Congratulations Bing Tian. Read More

Palladium-catalysed enantioselective diacetoxylation of terminal alkenes

A Pd(II)-catalysed enantioselective diacetoxylation of terminal alkenes, including challenging substrates such as 1-propene and 1-butene was reported. Notably, ligand engineering of the simple pyridinyl oxazoline ligand is essential for substantially increasing the catalytic reactivity of Pd(OAc)2. The method allowed precise asymmetric diacetoxylation reactions from feedstock alkenes to complex molecules bearing multiple alkenic moieties, which provides rapid and efficient access to various synthetically useful chiral 1,2-diols. This result is published in Nat. Catal. Congratulations Bing Tian. Read More

Anionic Bisoxazoline Ligands Enable Copper-Catalyzed Asymmetric Radical Azidation of Acrylamides

Asymmetric radical azidation for the synthesis of chiral alkylazides remains a tremendous challenge in organic synthesis. We report here an unprecedented highly enantioselective radical azidation of acrylamides catalyzed by 1 mol % of a copper catalyst. The substrates were converted to the corresponding alkylazides in high yield with good‐to‐excellent enantioselectivity. This result is published in ACIE. Congratulations Lianqian Wu and Dunqi Wu. Read More

Enantioselective Copper-Catalyzed Trifluoromethylation of Benzylic Radicals via Ring Opening of Cyclopropanols

The asymmetric trifluoromethylation of aryl-substituted cyclopropanols via a radical ring-opening pathway is reported herein, which provides an easy and straightforward access to structurally diverse β-CF3 ketones in good yields and excellent enantioselectivities under very mild conditions. This result is published in Chem. Congratulations Chao Jiang. Read More

Asymmetric Coupling of Carbon-Centered Radical Adjacent to Nitrogen: Copper-Catalyzed Cyanation and Etherification of Enamides

The first copper-catalyzed asymmetric cyanation and etherification of enamides have been established, where a carbon-centered radical adjacent to a nitrogen atom (CRAN) is enantioselectively trapped by a chiral copper (II) species. This result is published in ACIE. Congratulations Guoyu Zhang and Song Zhou. Read More

Enantioselective Copper-Catalyzed Alkynylation of Benzylic C-H Bonds via Radical Relay

The first enantioselective alkynylation of benzylic C-H bonds via copper-catalyzed radical relay has been established, which provides an easy access to structurally diverse benzylic alkynes in good yields with excellent enantioselectivities. This result is published in JACS. Congratulations Liang Fu. Read More

Palladium(II)-Catalyzed Enantioselective Azidation of Unactivated Alkenes

The first Pd-catalyzed enantioselective azidation of unactivated alkenes using readily accessible 1‐azido‐1,2‐benziodoxol‐3(1H)‐one (ABX) as an azidating source has been established, which affords a wide variety of structurally diverse 3‐N3‐substituted piperidines in good yields with excellent enantioselectivities. Notably, the employment of both an electrophilic azidating reagent and the sterically bulky chiral pyridinyl‐oxazoline (Pyox) ligand is crucial to the successful reaction. This result is published in ACIE. Congratulations Xiaonan. Read More

Enantioselective Pd(II)-Catalyzed Oxidative Aminofluorination of Unactivated Alkenes Using Et4NF·3HF as a Fluoride Source

The first asymmetric Pd(II)-catalyzed aminofluorination of unactivated alkenes using chiral quinolone-oxazolines (Quox) as ligand has been developed, which provides an easy access to a wide array of enantiomerically enriched β‐fluoropiperidines in good yields with excellent enantioselectivities. Notably, Et4NF·3HF as a readily accessible nucleophilic fluoride source was found to play an essential role in the enantioselective control, and CsOCF3 also acts a key additive to improve the excellent ee value of products. This result is published in ACIE. Congratulations Chuanqi. Read More

Congratulations to Lianqian Wu(吴联谦) and Xiang Li(李响) on obtaining their PhD degree.

Welcome Dr. Weigang Fan from Université de Lyon, INSA Lyon (France) to join our group as a Postdoc.

Proton-Coupled Electron Transfer Enables Tandem Radical Relay for Asymmetric Copper-Catalyzed Phosphinoylcyanation of Styrenes

A tandem radical relay strategy was realized for the first Cu(I)-catalyzed enantioselective phosphinocyanation of styrenes. In this reaction, tBuOOSiMe3 generated in situ from tBuOOH serves as a radical initiator to trigger t-butoxy radical production upon oxidization of L*Cu(I) species via proton-coupled-electron transfer (PCET) pathway, which leads to sequential phosphinoyl radical and benzyl radical formations. This result is published in Org Lett. Congratulations Guoyu Zhang. Read More

Enantioselective Arylation of Benzylic C-H bonds via CopperCatalyzed Radical Relay

A novel enantioselective Cu-catalyzed arylation of benzylic C-H bonds using alkylarenes as a limiting reagent has been developed, where a chiral bisoxazoline ligand bearing an acetate ester moiety plays a key role in both reactivity and enantioselectivity. The reaction provides an efficient access to various chiral 1,1- diarylalkanes in good yields with good to excellent enantioselectivities, and displays excellent functional group tolerance. This result is published in ACIE. Congratulations Wen Zhang. Read More

Enantioselective Construction of Quaternary All-Carbon Centers via Copper-Catalyzed Arylation of Tertiary Carbon-Centered Radicals

An enantioselective copper-catalyzed arylation of tertiary carbon-centered radicals, leading to quaternary all-carbon stereocenters, has been developed. The tertiary carbon-centered radicals, including both benzylic and nonbenzylic radicals, were produced by the addition of trifluoromethyl radical to α-substituted acrylamides, and subsequently captured by chiral aryl copper(II) species to give C−Ar bonds with excellent enantioselectivity. This result is published in JACS. Congratulations Lianqian Wu. Read More

Palladium(II)-Catalyzed Enantioselective Aminotrifluoromethoxylation of Unactivated Alkenes using CsOCF3 as a Trifluoromethoxide Source

Asymmetric Pd(II)-catalyzed intramolecular aminotrifluoromethoxylation of unactivated alkenes using readily accessible and stable CsOCF3 as a trifluoromethoxide source has been developed, which affords a wide variety of enantiomerically enriched β-substituted OCF3-containing piperidines in good yields. This result is published in ACIE . Congratulations Chaohuang Chen. Read More

Pd-Catalyzed Intermolecular Arylcarbonylation of Unactivated Alkenes: Incorporation of Bulky Aryl at Room Temperature

A Pd-catalyzed intermolecular arylcarbonylation of unactivated alkenes has been established herein. Unsymmetric diaryliodonium salts (DAIS) are used as arylation reagents, in which the bulky aryls (ArL) are exclusively incorporated into the arylcarbonylated products bearing the ArL group and a carboxylic ester group at the α- andβ-carbon position on the terminal C-C double bond, respectively. This result is published in ACIE. Congratulations Xiang Li. Read More

Enantioselective Trifluoromethylalkynylation of Alkenes via Copper-Catalyzed Radical Relay

A novel enantioselective copper-catalyzed trifluoromethylalkynylation of styrenes, proceeding through a radical relay process, is described herein, which affords structurally diverse CF3-containing propargylic compounds in good yield with excellent enantioselectivities under very mild conditions. In addition, the reaction features wide substrate scope and good functional group tolerance. Moreover, the trifluoromethylalkynylated products can be easily converted into synthetically useful chiral terminal alkynes, allenes, Z-alkenes, as well as CF3-modified nonsteroidal anti-inflammatory drugs. This result is published in JACS. Congratulations Liang Fu. Read More

Copper-Catalyzed Radical Relay for Asymmetric Radical Transformations

We present our recent studies on the enantioselective induction of prochiral benzylic radicals using a chiral bisoxazoline (Box)/Cu catalytic system as part of the Accounts of Chemical Research special issue “Hydrogen Atom Transfer”. Congratulations Fei Wang. Read More

Welcome Xintuo Yang to our group as a PhD candidate, who got his MS degree at Chengdu Institute of Organic Chemistry, CAS.

Enantioselective Pd(II)-Catalyzed Intramolecular Oxidative 6-endo Aminoacetoxylation of Unactivated Alkenes

A novel asymmetric 6-endo aminoacetoxylation of unactivated alkenes by palladium catalysis, which yields chiral β-acetoxylated piperidines with excellent chemo-, regio- and enantioselectivities under very mild reaction conditions, has been established herein by employing a new designed pyridine-oxazoline (Pyox) ligand. Importantly, introducing a sterically bulky group into the C-6 position of Pyox is crucial to enhance the reactivity of the amino-acetoxylation of alkenes. This result is published in JACS. Congratulations XIaoxu. Read More

Divergent Synthesis of CF3-Substituted Allenyl Nitriles by Ligand-Controlled Radical 1,2- and 1,4-Addition of 1,3-Enynes

A ligand-controlled radical 1,2- and 1,4-addition of 1,3-enynes has been developed, which provides an access to a variety of CF3-containing tri- and tetra-substituted allenyl nitriles. The reaction features broad substrate scope and excellent functional group compatibility. Moreover, this protocol represents a novel regioselectivity-tunable functionalization of 1,3-enynes via radicals. This result is published in ACIE. Congratulations Fei & Dinghai. Read More

Regioselective Palladium-Catalyzed C-H Bond Trifluoroethylation of Indoles: Exploration and Mechanistic Insight

A selective palladium-catalyzed trifluoroethylation reaction of indoles has been developed. The C-H bond activation process, using CF3CH2I as the fluoroalkyl source, can be employed to prepare a variety of 2-CF3CH2 substituted indoles. The results of a preliminary mechanistic study and DFT calculations show that a β-diketone, acting as an ionic palladium ligand, plays an important role in governing the efficiency of the palladium-catalyzed trifluoroethylation reaction by accelerating the oxidative addition step. In contrast, transfer of the indole N-H proton in the palladium center is involved in the rate-determining step. This result is published in ACS Catal. Congratulations Hao. Read More

Welcome Philipp.Pflüger from University of Münster(Germany) to our group for research internship.

Welcome Dr. TianBing(田兵) to our group as a Postdoc, who got his PhD at Heidelberg University(Germany).

Palladium-Catalyzed Intermolecular Ditrifluoromethoxylation of Unactivated Alkenes: CF3O‑Palladation Initiated by Pd(IV)

A novel palladium-catalyzed intermolecular ditrifluoromethoxylation of unactivated alkenes has been developed, using a new electrophilic reagent, SelectfluorCN, as a strong oxidant, and AgOCF3 as a trifluoromethoxide source. Preliminary mechanistic studies revealed that the reaction was possibly initiated by Pd(IV) species, and an unusual cis-addition of CF3O−Pd(IV) into the double bond leads to the formation of the first C−OCF3 bond; in addition, the second C−OCF3 bond was produced through reductive elimination at high-valent palladium center. Congratulations to Chaohuang Chen. Read More

[From 2007 to 2017]
Celebrating the 10th Anniversary of founding of Liu's Group.

Awards Notification

Congratulations to Wen Zhang(张文) to win the "Special Prize of the Presidential Scholarship of Chinese Academy of Sciences(中国科学院院长特别奖)".

Enantioselective Decarboxylative Cyanation Employing Cooperative Photoredox Catalysis and Copper Catalysis

The merger of photoredox catalysis with asymmetric copper catalysis have been realized to convert achiral carboxylic acids into enantiomerically enriched alkyl nitriles. Under mild reaction condition, the reaction exhibits broad substrate scope, high yields and high enantioselectivities. Furthermore, the reaction can be scaled up to synthesize key chiral intermediates to bioactive compounds. Congratulations to Dinghai Wang. Read More

Palladium-Catalyzed Intermolecular Azidocarbonylation of Alkenes via a Cooperative Strategy

We have developed a novel intermolecular β-azidocarbonylation reaction of alkenes, in which a combination of iodine(III)-mediated alkene activation and palladium-catalyzed carbonylation was demonstrated as an efficient strategy for the difunctionalization of alkenes. A variety of -azido carboxylic esters were obtained from mono- and 1,1-disubstituted terminal alkenes with excellent regioselectivities. In addition, the introduced azido group can be reduced to amine group, providing a facile access to β-amino acid derivatives from simple olefins. This result is published in JOC. Congratulations to Ming Li and Feng Yu. Read More

Palladium-Catalyzed Intermolecular Oxidative Fluorocarbonylation of Unactivated Alkenes: Efficient Access of β-Fluorocarboxylic esters

We have developed a novel palladium-catalyzed and iodine (III)-mediated intermolecular fluorocarbonylation of alkenes with a cooperative strategy. The employment of iodoarene difluorides as the oxidant and fluoride source is crucial for the successful catalytic transformation. The current transformation presents the first convenient method to generate β-fluorinated carboxylic acid derivatives under mild reaction conditions from simple alkenes with excellent regioselectivity. .This result is published in ACIE. Congratulations Xiaoxu. Read More

Awards Notification

Due to the excellent work, Dr. Fei Wang has won the "2017 Reaxys PhD Prize", Congratulate him.

Congratulations to Zhaoli Liang(梁兆利), Chaohuang Chen(陈朝煌) and Dinghai Wang(王定海) to obtain their doctorate degrees.

Catalytic Oxidative Trifluoromethoxylation of Allylic C-H Bonds using a Palladium Catalyst

We have developed a novel catalytic intermolecular allylic C-H trifluoromethoxylation of alkenes using a palladium catalyst, in which CsOCF3 was employed as the trifluoromethoxide source and BQ as the oxidant. This reaction provides an efficient route for directly accessing allylic trifluoromethoxy ether derivatives with excellent regioselectivities from terminal alkenes via an allylic C-H bond activation process.This result is published in ACIE. Congratulations Xiaoxu. Read More

Copper-Catalyzed Arylation of Benzylic C–H bonds with Alkylarenes as the Limiting Reagents

Based on the concept of our Science paper, we have developed a novel copper-catalyzed arylation of benzylic C–H bonds with nucleophilic arylboronic acids that provides an efficient way to synthesize various 1,1-diarylalkanes with a broad substrate scope and excellent functional group compatibility. The reactions occur at room temperature using alkylarenes as the limiting reagents, which allows access to the arylation of the more valuable and complex bioactive compounds. This result is published in JACS. Congratulations Wen Zhang. Read More

Asymmetric Copper-Catalyzed Intermolecular Aminoarylation of Styrenes: Efficient Access to Optical 2,2-diarylethylamines

We have developed a copper-catalyzed enantioselective intermolecular aminoarylation of alkenes using a novel N-fluoro-N-alkylsulfonamide as the amine reagent, which could react with the Cu(I) catalyst to release a related amino radical. Varieties of optical 2,2-diaryl-ethylamines were efficient synthesized from simple styrenes with high enantioselectivity, and these products can serve as valuable synthons toward bioactive molecules synthesis. This result is published in JACS. Congratulations Dinghai. Read More

Welcome Dr. Liang Fu to our group as a Postdoc, who got his PhD at RWTH Aachen University (Germany).

Awards Notification

Due to their excellent works, Dinghai Wang has won the honor of “Shanghai Outstanding Graduates”(上海市优秀毕业生);Wen Zhang has won the honor of “Good Student Model”(三好学生标兵);Lianqian Wu has won the honor of “Outstanding Student” (优秀学生). Congratulations them.

Enantioselective Palladium(II)-Catalyzed Intramolecular Aminoarylation of Alkenes by Dual N-H and Aryl C-H Bond Cleavage

We have developed an asymmetric palladium-catalyzed intramolecular oxidative aminoarylation of alkenes with quinoline–oxazoline chiral ligands and Ag2CO3 as the oxidant. Various indolines containing a quaternary stereogenic center were synthesized in high yield with excellent enantioselectivity. This result is published in ACIE. Congratulations Wen. Read More

Asymmetric Cu-Catalyzed Intermolecular Trifluoromethylarylation of Styrenes: Enantioselective Arylation of Benzylic Radicals

Based on the radical relay strategy, we have developed a novel asymmetric radical trifluoromethyl-arylation of alkenes, in which which provides an efficient approach to access chiral CF3-containing 1,1-diarylmethane derivatives with good to excellent enantioselectivity. Various vinyl arenes and aryl boronic acids are compatible with these conditions. The utility of the method is demonstrated by accessing modified bioactive molecules. This result is published in JACS. Congratulations Lianqian. Read More

Enantioselective Copper-Catalyzed Intermolecular Amino- and Azido-cyanation of Alkenes via radical relay process

Based on the radical relay strategy, we have developed a novel enantioselective copper-catalyzed intermolecular amino- and azido-cyanation of alkenes, in which a variety of enantiomerically enriched β-amino/azido alkylnitriles were efficiently synthesized. And β-azido alkylnitriles could be converted to a series of highly valuable optical nitrogen-containing building blocks and bioactive compounds. This result is published in ACIE. Congratulations Dinghai. Read More

Enantioselective Copper-Catalyzed Intermolecular Cyanotrifluoromethylation of Alkenes via Radical Process

Based on the concept of our Science paper, we have developed a novel enantioselective copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes, in which a variety of CF3-containing alkylnitriles are furnished with excellent enantiomeric excess. This result is published in JACS. Congratulations Fei Wang. Read More

Author Profile of Guosheng Liu in Angewandte Chemie

Prof Liu has published 10 articles in Angewandte Chemie in the last 10 years, and an author profile is presented. Congratulations Prof. Liu. Read More

Palladium(II)-Catalyzed Oxidative Difunctionalization of Alkenes: Bond Forming at a High-Valent Palladium Center

Difunctionalization of alkenes has emerged as a powerful transformation to greatly increase molecular complexity in organic synthesis with improved efficiency, which is a major research topic in our group. To summarize our work in the past nine years, we published a review in Acc. Chem. Res. In this account, we discuss our exploration and application of a “high-valent palladium strategy” for the synthesis of fluorine-containing organic molecules that are typically inaccessible from other methods, besides, hydrogen peroxide, which is an environmentally friendly oxidant, is also mentioned to oxidize alkyl C–Pd(II) species to form high-valent alkyl C–Pd intermediates. Congratulations Guoyin Yin, Xin Mu and Prof. Liu. Read More

Our lab, in collaboration with the Stahl's lab@ University of Wisconsin–Madison has developed a method for stereoselective functionalization of sp3-hybridized carbon–hydrogen [C(sp3)–H] bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals which is published in Science. Congratulations Wen and Fei.Read More

Cooperative Strategy for the Highly Selective Intermolecular Oxycarbonylation Reaction of Alkenes using palladium catalyst

Our group has developed a novel method for intermolecular functionalization of terminal and internal alkenes in which hypervalent iodine, plays a key role by activating the alkene C=C bond for nuleophilic addition of the palladium catalyst. Utilizing the new approach, intermolecular oxycarbonylaton reactions of alkenes have been achieved and carried out under mild conditions to produce the corresponding β-oxycarbonylic acids with excellent efficiencies and levels of regio- and diastereo-selectivity. Congratulations Ming. [Angew. Chem. Int. Ed. 2016, 55, 10.1002/anie.201607248R1]

Efficient Pathway for the Preparation of Aryl(isoquinoline)iodonium(III) Salts and Synthesis of Radiofluorinated Isoquinolines

Our lab, in collaboration with the Liang lab@ Massachusetts General Hospital and Harvard Medical School has developed a novel “one-pot” process to assemble aryl(isoquinoline)iodonium salts in 40–94%yields from mesoionic carbene silver complex and Aryl-IPy2(OTf)2. The method is general, practical, and compatible with well-functionalized molecules as well as useful for the preparation of a wide range of 18F-labeled isoquinolines resulting in up to 92% radiochemical conversion. Congratulations Zheliang. Read More