Yuanjiang Pan

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.

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.

Dissociative Protonation and Proton Transfers : Fragmentation of α, β-Unsaturated Aromatic Ketones in Mass Spectrometry

In mass spectrometry of the alpha,beta-unsaturated aromatic ketones, Ph-CO-CH=CH-Ph, losses of a benzene from the two ends and elimination of a styrene are the three major fragmentation reactions of the protonated molecules. When the ketones are substituted on the right phenyl ring, the electron-donating groups are in favor of losing a styrene to form the benzoyl cation, PhCO(+), whereas the electron-withdrawing groups strongly favor loss of benzene of the left side to form a cinnamoyl cation, PhCH=CHCO(+). When the ketones are substituted on the left phenyl ring, the substituent effects on the reactions are reversed. In both cases, the ratios of the two competitive product ions are well-correlated with the sigma p(+) substituent constants. Theoretical calculations indicate that the carbonyl oxygen is the most favorable site for protonation, and the olefinic carbon adjacent to the carbonyl is also favorable especially when a strong electron-releasing group is present on the right phenyl ring. The energy barrier to the interconversion between the ions formed from protonation at these two sites regulates the overall reactions. Transfer of a proton from the carbonyl oxygen to the ipso position on either phenyl ring, which is dissociative, triggers loss of benzene.

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.

Hydride transfer reactions via ion–neutral complex: fragmentation of protonated N‐benzylpiperidines and protonated N‐benzylpiperazines in mass spectrometry

An ion-neutral complex (INC)-mediated hydride transfer reaction was observed in the fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in electrospray ionization mass spectrometry. Upon protonation at the nitrogen atom, these compounds initially dissociated to an INC consisting of [RC(6)H(4)CH(2)](+) (R = substituent) and piperidine or piperazine. Although this INC was unstable, it did exist and was supported by both experiments and density functional theory (DFT) calculations. In the subsequent fragmentation, hydride transfer from the neutral partner to the cation species competed with the direct separation. The distribution of the two corresponding product ions was found to depend on the stabilization energy of this INC, and it was also approved by the study of substituent effects. For monosubstituted N-benzylpiperidines, strong electron-donating substituents favored the formation of [RC(6)H(4)CH(2)](+), whereas strong electron-withdrawing substituents favored the competing hydride transfer reaction leading to a loss of toluene. The logarithmic values of the abundance ratios of the two ions were well correlated with the nature of the substituents, or rather, the stabilization energy of this INC.

Gas‐Phase Nucleophilic Aromatic Substitution between Piperazine and Halobenzyl Cations: Reactivity of the Methylene Arenium Form of Benzyl Cations

Nucleophilic aromatic substitution (SNAr) [1] is one of the most fundamental reactions in organic chemistry. The most popular mechanism for SNAr reactions is an addition–elimination process involving a s complex (Meisenheimer complex) intermediate. Although SNAr reactions in solution have been well documented, there are only a few reports on their gas-phase chemistry. Studying chemical reactions in the gas phase allows to determine the intrinsic features of reactions and to characterize the short-lived intermediates in isolation from solvent, counterion, catalyst interference and aggregation effects. The key stage in a SNAr reaction is the formation of the s complex, which has become a subject of special concern. The typical anionic s complexes formed between anionic nucleophiles and aromatic substrates bearing strong electron-withdrawing groups are found to be relatively stable. In recent years there has been a breakthrough in studies on the gas-phase anionic SNAr reactions [2] and anionic s complexes alone. Although several s complextype structures in the cationic state, such as HC6H6, H + C6H5F and C6H6NH3 + , had been observed in the gas phase by spectroscopy, they showed no aromatic substitution reactivity due to their poor leaving group. Cationic s-complex-mediated SNAr reactions in the gas phase are still rare. Among the few studies performed, the substrate is merely ionized halobenzenes and the nucleophile is ammonia or methyl isocyanide. In this study, we report the gas-phase SNAr reactions between piperazine (nucleophile) and halogen-substituted benzyl cations (substrate) using electrospray ionization mass spectrometry (ESI-MS). Benzyl cations are highly reactive intermediates in various chemical and biochemical reactions. It has been demonstrated that two major resonance forms (A and B), as shown in Scheme 1, contribute significantly to the total structure of the benzyl cation. However the “methylene arenium” form (B) has little contribution in reactions, because the reaction of benzyl cation with electron-rich reagents nearly always occurs at the benzylic methylene group both in solution and in the gas phase due to its maintenance of the aromaticity of the product. One exception in the gas phase was observed in the fragmentation reaction of Fr chet dendrons. In that example, steric constraints force the intramolecular reaction to occur at the phenyl ring of the benzyl cation but not at the benzylic position. To our knowledge, the reaction of halobenzyl cations with piperazine reported here is the first non-restricted case in which the methylene arenium exhibits nucleophilic substitution reactivity at the phenyl ring. Because of the advantages of being solventand counterion-free, mass spectrometry can be exploited to synthesize ions and study gas-phase organic reactions. In the present study, the reactants of piperazine and halobenzyl cations were simultaneously in-situ-generated by collision-induced dissociation (CID) of protonated N-(halobenzyl)piperazines using an ESI ion trap mass spectrometer (Scheme 2). The two nascent reactants with a suitable amount of internal energy are consequently trapped in an ion/neutral complex through electrostatic interactions. The two components of the ion/neutral complex are able to rotate with respect to one another, and therefore they show reactivities similar to those expected for the isolated species. Under CID conditions, the inverse process, in which piperazine attacks the benzylic position of the halobenzyl cation, is prevented; hence, other reactions between the reactants are quite likely to take place. It should be added that the rear-

Brønsted Acid-Catalyzed Decarboxylative Redox Amination: Formation of N-Alkylindoles from Azomethine Ylides by Isomerization

A Brønsted acid-catalyzed decarboxylative redox amination involving aldehydes with 2-carboxyindoline for the synthesis of N-alkylindoles is described. The decarboxylative condensations of aldehydes with 2-carboxyindoline produce azomethine ylides in situ, which then transform into N-alkylindoles by isomerization.

Identification of isomers of resveratrol dimer and their analogues from wine grapes by HPLC/MSn and HPLC/DAD-UV

A facile method based on HPLC/(-)ESI-MS(n) is established for the analysis of seven isomers of resveratrol dimers and three of their analogues in Xinjiang wine grapes. The structures of these compounds are positively or tentatively determined. Among them, three are tentatively identified as new compounds. MS(n) experiments on the [M-H](-) ions provide abundant structural information, especially regarding the relative abundance of the key product ions, m/z 333 and 369 (385 in compound 3), which can be utilised to distinguish whether or not the compound identified contains the scaffold of the isomer of a resveratrol dimer. The relative abundance of key product ions remains unchanged as collision energy varies from 0.60 to 0.95V. All the trans-, and cis-isomers could be identified by HPLC/DAD-UV spectra. The UV spectra of compounds 2 and 9 tentatively show cis and trans- configurations, respectively.

pH-switched HRP-catalyzed dimerization of resveratrol: a selective biomimetic synthesis

A selective, concise and green biomimetic synthesis strategy of seven resveratrol dimers from natural resveratrol monomer as starting material is described. By succinct adjustment of environmental pH, the enzyme used, horseradish peroxidase (HRP), can perform in three distinctly different patterns and five dimers form with considerable selectivity. Two other derivative dimers are subsequently synthesized.