Changcheng Jing

Facile Synthesis of 3-Aryloxindoles via Brønsted Acid Catalyzed Friedel–Crafts Alkylation of Electron-Rich Arenes with 3-Diazooxindoles

A simple metal-free method for the synthesis of 3-aryloxindoles via Brønsted acid catalyzed aromatic C-H functionalization of electron-rich arenes with 3-diazooxindoles is developed. In the presence of a catalytic amount of TfOH, a series of 3-aryloxindoles are synthesized as single regioisomers in good to excellent yields. This transformation is proposed to proceed through acid-catalyzed protonation of 3-diazooxindoles into diazonium ions followed by Friedel-Crafts-type alkylation of arenes.

Dual Catalysis in Highly Enantioselective Multicomponent Reaction with Water: An Efficient Approach to Chiral β-Amino-α-Hydroxy Acid Derivatives

Water, as one of the most abundant, safe, and environmentally benign liquid materials, has been widely used in chemical synthesis and production, serving in most cases as a solvent or a OH /H source. As a reactant, water has also been used in asymmetric catalysis. However, it is very challenging to control enantioselectivity in asymmetric catalysis by employing water as a substrate, likely due to the small size of the water molecule. Recently, Zhou et al. reported highly enantioselective O H insertions with water from transition metal-catalyzed diazo decomposition, in which all atoms of water were efficiently incorporated into the insertion products. Multicomponent reactions (MCRs) are considered as a powerful and atom-efficient strategy to form multiple chemical bonds from three or more starting materials in one step. In the case of MCRs in which two or more stereogenic centers are produced, control of both diastereoand enantioselectivity is of the utmost importance. We report herein an enantioselective three-component reaction cocatalyzed by a transition metal and a chiral Brønsted acid with water. In this reaction system, cooperatively catalyzed by dual catalysts, both diastereoand enantioselectivity are well controlled to afford freehydroxy polyfunctional molecules bearing two newly formed stereogenic centers in good yield with high d.r. and ee. As an important structural building block, b-amino-a-hydroxy acid derivatives have gained much attention as they are frequently used in natural product synthesis, chiral ligands, and pharmaceutically relevant compounds. In addition, great efforts have been devoted to developing efficient approaches for the derivatives. Recently, we demonstrated an efficient three-component reaction of diazo compounds with alcohols and imines, catalyzed by [Rh2(OAc)4] and chiral Brønsted acid, to produce b-amino-a-hydroxy acid derivatives in high yield with excellent diastereoselectivity and enantioselectivity (Scheme 1). However, the great selectivity was only achieved with bulky alcohols, and removal of the O-protecting group in the product required an additional tedious reaction step. This limitation, at least in part, limits the application of this reaction as an efficient synthetic method in organic synthesis. With this background in mind, as part of our continuing efforts in this area, we present herein recent progress to overcome this limitation by employing water as a substrate. The reaction with water would generate unprotected hydroxy compounds. The proposed reaction pathway, which is similar to that reported previously, is shown in Scheme 2.

Divergent Synthesis of Multisubstituted Tetrahydrofurans and Pyrrolidines via Intramolecular Aldol-type Trapping of Onium Ylide Intermediates.

This paper reports a divergent strategy for the synthesis of multisubstituted tetrahydrofurans and pyrrolidines, starting from easily accessible β-hydroxyketones or β-aminoketones to react with diazo compounds. Under Rh(II) catalysis, this transformation is proposed to proceed through a metal-carbene-induced oxonium ylide or ammonium ylide formation followed by an intramolecular aldol-type trapping of these active intermediates. A series of highly substituted tetrahydrofurans and pyrrolidines are synthesized in high yields with good to excellent diastereoselectivities. Preliminary biological evaluations revealed that both types of heterocycles show good PTP1B inhibitory activities.

A highly enantioselective four-component reaction for the efficient construction of chiral β-hydroxy-α-amino acid derivatives

An enantioselective four-component reaction of a diazoketone, water, an aniline and ethyl glyoxylate in the presence of catalytic Rh2(OAc)4 and a chiral Brønsted acid was developed to efficiently produce β-hydroxy-α-amino acid derivatives in good yields with high diastereoselectivity and enantioselectivity.

Highly Regio- and Enantioselective Formal [3 + 2]-Annulation of Indoles with Electrophilic Enol Carbene Intermediates

Chiral cyclopentane-fused indolines are synthesized with high regio- and enantiocontrol by formal [3 + 2]-annulation reactions of indoles and electrophilic enol carbenes. High enantioselectivity and exclusive regiocontrol occurred with enoldiazoacetamides using a less sterically encumbered prolinate-ligated dirhodium(II) catalyst in reactions with N-substituted indoles without substituents at the 2- or 3-positions via a selective vinylogous addition process. In this transformation, donor-acceptor cyclopropenes generated from enoldiazoacetamides serve as the carbene precursors to form metal carbene intermediates.

CuSO4-catalyzed three-component reaction of α-diazo ester, water and isatin: an efficient approach to oxindole derivatives

A highly efficient three-component reaction of α-diazo ester, water and isatin was developed by using CuSO4 as the catalyst. In this reaction, water was used as both a reactant and the solvent. With this highly environmentally benign and economical protocol, a series of 3-hydroxyindolin-2-one derivatives were efficiently produced in good yields with moderate to high diastereoselectivities.

Enantioselective oxidative functionalization of the Csp3–H bond adjacent to a nitrogen atom for rapid access to β-hydroxyl-α-amino acid derivatives

Highly chemoselective and enantioselective one-pot reactions involved in the oxidative functionalization of Csp3-H bonds adjacent to nitrogen atoms in N-aryl glycine esters were developed. The method provided rapid access to a variety of highly functionalized β-hydroxyl-α-amino acid derivatives from simple starting materials under mild conditions.

Hg(OTf)2 Catalyzed Intramolecular 1,4-Addition of Donor-Acceptor Cyclopropenes to Arenes

A Hg(OTf)2 catalyzed intramolecular arene 1,4-addition reaction of N-benzyl donor-acceptor cyclopropenecarboxamides was developed to synthesize a series of [3.2.2]nonatriene derivatives. This novel reaction is also observed with silver(I) catalysts known to form metal carbene intermediates in competition with the Buchner reaction.

Discovery of Bisindole as a Novel Scaffold for Protein Tyrosine Phosphatase 1B Inhibitors

Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an effective target for the treatment of both type II diabetes and obesity. However, no PTP1B inhibitor has come into clinic application. Herein, we report mixed 3,3′‐bisindoles as novel PTP1B inhibitors with low micromole‐ranged inhibitory activity. The best active compound 9f inhibited PTP1B activity with an IC50 of 2.79 µM. Meanwhile, it had low cytotoxicity and enhanced glucose uptake in vitro. Further studies demonstrated that some of these active compounds had a specific selectivity over other PTPs. Computational analysis further showed the binding mode of compound 9f with the active pocket of PTP1B. Our studies provide a novel scaffold for further development of more promising PTP1B inhibitors and potential drugs for type II diabetes and obesity.