Yinjun Xie

Copper-Catalyzed Oxidative Amination of Benzoxazoles via C−H and C−N Bond Activation: A New Strategy for Using Tertiary Amines as Nitrogen Group Sources

An efficient and conceptually new method for oxidative amination of azoles with tertiary amines via copper-catalyzed C-H and C-N bond activation has been developed. This protocol can be performed in the absence of external base and only requires atmospheric oxygen as oxidant. The catalyst system is very simple and efficient, which opens a new way for using tertiary amines as nitrogen group sources for C-N bond formation reactions.

Palladium-Catalyzed Oxidative Carbonylation of Benzylic C–H Bonds via Nondirected C(sp3)–H Activation

A new strategy for generating benzylpalladium reactive species from toluenes via nondirected C(sp(3))-H activation has been developed. This led to construction of an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives from inexpensive, commercially available starting materials.

An Efficient Rh/O2 Catalytic System for Oxidative C–H Activation/Annulation: Evidence for Rh(I) to Rh(III) Oxidation by Molecular Oxygen

A novel and efficient Rh/O2 catalytic system has been developed and shown to catalyze highly efficient oxidative C-H activation/annulation reactions, producing a broad range of isoquinolinium salts with high turnover numbers (up to 740). Mechanistic studies provided strong evidence of facile oxidation of Rh(I) to Rh(III) by molecular oxygen facilitated by acid.

Iron-catalyzed direct alkenylation of 2-substituted azaarenes with N-sulfonyl aldimines via C-H bond activation.

A novel iron-catalyzed alkenylation of 2-substituted azaarenes through sp(3) C-H bond activation has been developed. A favorable E2-elimination is proposed as a key step to cleavage of C-H and C-N bonds for the construction of a C═C bond in high stereoselectivity. This transformation represents an efficient way to synthesize 2-alkenylated azaarenes from simple starting materials.

Palladium-Catalyzed Vinylation of Aminals with Simple Alkenes: A New Strategy To Construct Allylamines

A novel, highly selective palladium-catalyzed vinylation reaction for the direct synthesis of allylic amines from styrenes and aminals has been established. The utility of this method was also demonstrated by the rapid synthesis of cinnarizine from aldehydes, amines, and simple alkenes in one-pot manner. Mechanistic studies suggested that the reaction proceeds through a valuable cyclometalated Pd(II) complex generated by the oxidative addition of aminal to a Pd(0) species.

Diastereo‐ and Enantioselective Catalytic Tandem Michael Addition/Mannich Reaction: Access to Chiral Isoindolinones and Azetidines with Multiple Stereocenters

Construction of multiple contiguous stereogenic centers in acyclic compounds by asymmetric catalysis represents a particularly difficult challenge. For the success of such a catalytic process, carbon–carbon bond-forming tandem reactions using well-known reactions as key transformation steps that give high diastereoand enantiocontrol are a prerequisite. The asymmetric Mannich-type reaction is a popular method for preparing optically active b-aminocarbonyl frameworks, which are interesting structures found in many useful biologically active compounds. This type of reaction has been frequently used as a fundamental step for establishing tandem protocols, and in those processes, the catalytic generation of chiral enolates is crucial for achieving high activity and selectivity. It is widely appreciated that copper-catalyzed conjugate addition of R2Zn to a,b-unsaturated carbonyl compounds is one of the most attractive way for constructing a carbon– carbon bond, in which the chiral zinc enolate is generated in situ. In the case when an appropriate electrophile is added to the reaction system, the tandem conjugate addition/ electrophilic trapping reaction might be realized. Based on this concept, various electrophiles such as aldehydes, ketones, esters, nitriles, oxocarbenium ions, carboxylates, alkyl halides, nitrosos, and tosylates have been used in the intermolecular or intramolecular conjugate addition/electrophilic trapping reactions for the construction of complex molecular frameworks through tandem processes. As with the carbon electrophile, imines might be another attractive substrate for the conjugate addition/electrophilic trapping reaction. However, to the best of our knowledge, the use of this type of synthetically versatile aldimine as the terminal electrophile for this kind of reaction remains unexplored—presumably owing to their relatively lower electrophilicity in comparison with aldehydes and other carbonyl-containing electrophiles. Moreover, most of the stereoselective tandem reactions of this kind install the stereogenic centers on cyclic compounds. This limitation is probably due to difficulty in the stereoselective construction of contiguous stereogenic centers in acyclic compounds as compared to cyclic systems. Herein we report a highly diastereoand enantioselective construction of three contiguous acyclic stereogenic centers through a copper-catalyzed tandem conjugate addition/Mannich reaction of organozinc reagents and acyclic a,b-unsaturated ketones in the presence of imines to afford b-aminocarbonyl derivatives (Scheme 1). Thus, allowing the asymmetric synthesis of chiral azetidines in high enantioselectivity. Notably, in a one-pot manipulation, chiral isoindolinones can also be obtained with high levels of relative and absolute stereochemical control by using this method. First, we investigated the reactivity of several types of imines as electrophiles toward the chalcone 1 and Et2Zn in the presence of Cu(CH3CN)4BF4 (1 mol%) and with (S,S)-L1 (1.2 mol%) as a chiral ligand in toluene at 10 8C for 12 hours—these are the same reaction conditions that previously led to good results for the copper-catalyzed conjugate Michael addition protocol. The desired tandem reactions did not proceed with either N-arylimine or N-alkylimine, and only the 1,4-conjugate addition products were obtained. However, the use of N-tosyl aldimine 2a as an electrophile under the same reaction conditions gave the desired tandem adduct in 72% yield with good enantioselectivity (76% ee) for the major diastereomer (Table 1, entry 1). Also, only two of the four possible diastereomers were detected. This exceptionally high reactivity may be attributed to the higher electrophilicity of the N-tosyl aldimine or the strong coordination of the copper ion to the N-tosyl aldimine through a 1,3binding mode of the nitrogen atom of the imine moiety and the oxygen atom of the sulfonyl group. We then focused our attention on this type of imine as the electrophilic tapping reagent and examined several catalytic systems. We used chalcone 1a, N-tosyl aldimine 2a, and Et2Zn as the reactants, and the reaction was performed at 10 8C in toluene for 12 hours. With L1 as a ligand, we screened a variety of copper sources including copper(I) and copper(II) species, and found the stereoselectivity was significantly affected by the nature of the counterion of the copper salts (Table 1, entries 1–8). The more coordinating counterions proved to be more suitable, and among those tested, CuBr led to the best results with respect to reactivity and stereoselectivity (Table 1, entry 3). Among the solvents [*] S. Guo, Y. Xie, Prof. Dr. X. Hu, Prof. Dr. C. Xia, Prof. Dr. H. Huang State Key Laboratory for Oxo Synthesis and Selective Oxidation Lanzhou Institute of Chemical Physics Chinese Academy of Sciences, Lanzhou, 730000 (China) Fax: (+ 86)931-496-8129 E-mail: hmhuang@licp.cas.cn

Palladium-Catalyzed Difunctionalization of Enol Ethers to Amino Acetals with Aminals and Alcohols

A new strategy was developed for intercepting the palladium-alkyl species generated in Heck reaction via nucleophilic addition prior to the step of migratory insertion, which leads to a new palladium-catalyzed difunctionalization of enol ethers with aminals and alcohols to afford amino acetals. Mechanistic studies suggested that the cationic cyclometalated Pd(II) complex generated by the oxidative addition of aminal to a Pd(0) species was crucial for this unusual transformation.

Palladium-Catalyzed Insertion of an Allene into an Aminal: Aminomethylamination of Allenes by CN Bond Activation†

A new and atom-economic palladium-catalyzed aminomethylamination of allenes with aminals by CN bond activation is described. This direct and operationally simple method provides a fundamentally novel approach for the synthesis of 1,3-diamines. Mechanistic studies suggest that a unique cationic π-allylpalladium complex containing an aminomethyl moiety is generated as a key intermediate through the carbopalladation of the allene with a cyclometalated palladium-alkyl species.

Enantioselective Aminomethylamination of Conjugated Dienes with Aminals Enabled by Chiral Palladium Complex-Catalyzed C–N Bond Activation

A novel highly enantioselective aminomethylamination of conjugated dienes with aminals catalyzed by a chiral palladium complex ligated with BINOL-derived chiral diphosphinite has been successfully developed. This reaction proceeds via a Pd-catalyzed cascade C-N bond activation, aminomethylation, and asymmetric allylic amination reaction under mild reaction conditions, providing a unique and efficient strategy for the synthesis of enantiomerically pure allylic 1,3-diamines.

A Highly Diastereo‐ and Enantioselective Reaction for Constructing Functionalized Cyclohexanes: Six Contiguous Stereocenters in One Step

the Chinese Academy of Sciences and the National Natural Science Foundation of China (21172226 and 21133011)