Jie-Ping Wan

Recent advances in new multicomponent synthesis of structurally diversified 1,4-dihydropyridines

1,4-Dihydropyridines (DHPs) are one of the most important classes of heterocyclic compounds as privileged pharmacophores. They are therefore attractive synthetic targets of organic chemistry. Multicomponent reactions (MCRs) are the most efficient strategies for the synthesis of 1,4-DHPs in terms of providing both sufficient structural diversity and numbers for compound libraries. Following the classical multicomponent synthesis of 1,4-DHPs by the Hantzsch reaction, chemists have developed a large number of new MCRs to access 1,4-DHPs with significantly extended structural diversity, which is pivotal for the process of discovering new lead compounds and drugs of 1,4-DHPs. The advances on the synthesis of structurally diversified 1,4-DHPs through new MCRs beyond the classical Hantzsch reaction is reviewed.

Facile Synthesis of 2-(Phenylthio)phenols by Copper(I)-Catalyzed Tandem Transformation of C−S Coupling/C−H Functionalization

2-(Phenylthio)phenols were successfully synthesized from simple phenols and aromatic halides by using dimethyl sulfoxide as the oxidant. The transformation was accomplished via tandem copper(I)-catalyzed C-S coupling/C-H functionalization employing the CuI/L [L = (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one] catalyst system. The mechanism of the reaction was elucidated based on an isotope labeling strategy.

Water mediated chemoselective synthesis of 1,2-disubstituted benzimidazoles using o-phenylenediamine and the extended synthesis of quinoxalines

By applying water as the reaction medium, the one-pot synthesis of 1,2-disubstituted benzimidazoles has been achieved in excellent efficiency and selectivity at room temperature viatrimethylsilyl chloride promoted reaction of o-phenylenediamine with aldehyde. This green catalyst system has also been successfully extended to the synthesis of quinoxalines via the reaction of o-phenylenediamine with α-bromoketone. Water displayed a specific functionality in mediating the selectivity, and remarkable advantages over organic solvents in terms of yields as well as in the work up procedure of the reactions.

Advances in Copper-Catalyzed CC Coupling Reactions and Related Domino Reactions Based on Active Methylene Compounds

Active methylene compounds are a major class of reaction partners for C-C bond formation with sp(2) C-X (X = halide) fragments. As one of the most-classical versions of the Ullmann-type coupling reaction, activated-methylene-based C-C coupling reactions have been efficiently employed in a large number of syntheses. Although this type of reaction has long relied on noble-metal catalysis, the renaissance of copper catalysis at the end of last century has led to dramatic developments in Ullmann C-C coupling reactions. Owing to its low cost, abundance, as well as excellent catalytic activity, the exceptional atom economy of copper catalysis is gaining widespread attention in various organic synthesis. This review summarizes the advances in copper-catalyzed intermolecular and intramolecular C-C coupling reactions that use activated methylene species as well as in tandem reactions that are initiated by this transformation.

Novel regioselectivity: three-component cascade synthesis of unsymmetrical 1,4- and 1,2-dihydropyridines.

The three-component sequential reaction of alpha,beta-unsaturated aldehydes, amines, and enaminones proceeded smoothly to give 1,3,4-trisubstituted 1,4-dihydropyridines in aqueous DMF. Moreover, the unexpected regioselective formation of 1,2-dihydropyridines has been observed for the first time in such an approach. On the basis of a systematic study, the novel regioselectivity could be assigned both to steric and electronic effects originating from the amine partner.

KIO3-Catalyzed Aerobic Cross-Coupling Reactions of Enaminones and Thiophenols: Synthesis of Polyfunctionalized Alkenes by Metal-Free C–H Sulfenylation

The synthesis of polyfunctionalized aminothioalkenes has been realized via the direct C-H sulfenylation of enaminones and analogous enamines. These cross-coupling reactions have been achieved by simple KIO3 catalysis under aerobic conditions without employing any transition metal catalyst or additional oxidant. The employment of bio-based green solvent ethyl lactate as the reaction medium constitutes another sustainable feature of the present work.

Tunable Hydride Transfer in the Redox Amination of Indoline with Aldehyde: An Attractive Intramolecular Hydrogen‐Bond Effect

Analogous to atom economy and step economy, redox economy has received considerable attention in modern organic synthesis, especially in the total synthesis of natural products since it was proposed by Baran in 2008. Through using the inherent reducing power of hydrogen to reduce other functional groups, redox isomerizations can reduce the additional steps of oxidation or reduction. Moreover, selective C H bond functionalization has been accomplished via intramolecular hydride transfer in the process of redox isomerization. Recently, redox amination has become a very powerful tool in C N bond formation. Our group has been interested in this field. Herein, we report a Brønsted acid-catalyzed intermolecular redox amination of indoline 1 with aldehyde 2, which involves intramolecular hydride transfer and gives N-substituted product 3 [Eq. (1)]. N-Alkylindoles are prevalent in numerous biologically active natural products and pharmaceutical compounds and this firstly presented manipulation is unprecedented among those established protocols. Additionally, a novel type of amination involving intermolecular hydride transfer is also studied when salicylaldehyde is employed, which is switched by intramolecular hydrogen bond and leads to N-alkylindolines [Eq. (2)]. Our original hypothesis for the formation of N-benzylindole 3 a involves the condensation of indoline 1 with benzaldehyde 2 a in the presence of an acid (Scheme 1). The resulting iminium ion A is supposed to undergo intramolecular hydride transfer to furnish intermediate B. Ultimately, the final product 3 a is formed from B by deprotonation. The aromatization is considered to be the original motif of this redox process, which distinguishes indoline from some other cyclic secondary amine, such as tetrahydroquinoline and morpholine. To investigate the feasibility of this redox process, we initially tested the reaction of benzaldehyde (1 equiv) with indoline (2 equiv) in the presence of AcOH (0.2 equiv) at 110 8C using toluene as reaction medium. Just as expected, the reaction gave N-benzylindole with 40 % yield (Table 1, entry 1). Inspired by these results, we further investigated this transformation under different conditions. Various Brønsted and Lewis acids were evaluated as catalysts in this reaction (Table 1, entries 2–7). Generally, Brønsted acids catalyzed this reaction more efficiently than Lewis acids, and benzoic acid was found to be the best among those tested. Next, we began to study the solvent effect, and tolu[a] H. Mao, R. Xu, Dr. J. Wan, Z. Jiang, Prof. Dr. C. Sun, Prof. Dr. Y. Pan Department of Chemistry, Zhejiang University Hangzhou 310027 (P. R. China) Fax: (+86) 571-87951629 E-mail : cheyjpan@zju.edu.cn [b] Dr. J. Wan College of Chemistry and Chemical Engineering Jiangxi Normal University, Nanchang 330022 (P. R. China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201001896. Scheme 1. A proposed hypothesis for the formation of N-benzylindole 3a.

A Metal- and Azide-Free Multicomponent Assembly toward Regioselective Construction of 1,5-Disubstituted 1,2,3-Triazoles

The construction of 1,5-disubstituted 1,2,3-triazoles has been effected through the cascade dual C-N bond formation, N-N bond formation and an acyl migration-based C-C bond formation via the three-component reactions of enaminones, tosylhydrazine and primary amines. This metal- and azide-free, regioselective synthetic method proceeds in the presence of only molecular iodine.

Bio-based green solvent mediated disulfide synthesis via thiol couplings free of catalyst and additive

The bio-based green solvent ethyl lactate has been found to be a particularly efficient medium for oxidative coupling reactions of thiols yielding a broad array of disulfides. As a green solvent, ethyl lactate has shown an interesting promotion effect on the transformation by mediating corresponding reactions with high efficiency without using any catalyst or additive.

Synthesis of 3-sulfenylated indoles by a simple NaOH promoted sulfenylation reaction

The C-3 sulfenylation reaction of indoles has been achieved under mild reaction conditions by simply employing NaOH as promoter and thiols as thiolating reagents. This simple method allows for easy and rapid synthesis of various 3-sulfenylated indoles with generally good to excellent yields. Primary attempts in scale-up synthesis give satisfactory result.