Changwei Zhai

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.

Copper(II)-catalyzed highly diastereoselective three-component reactions of aryl diazoacetates with alcohols and chalcones: an easy access to furan derivatives

Copper(II) complexes are efficient catalysts in three-component reactions of aryl diazoacetates with alcohols and chalcones to give gamma-hydroxyketone derivatives in high yield with excellent diastereoselectivity. The resulting coupling adducts can be easily converted into furan-containing oligoaryls, tetrahydrofuran and 2,3-dihydrofuran derivatives.

Asymmetric C-H functionalization of indoles via enantioselective protonation

Asymmetric C—H functionalization of indoles from Rh2(OAc)4 and chiral phosphoric acid co-catalyzed reactions of aryl diazoacetates with indoles has been investigated. Through mechanistic study regarding to the proton transfer pathway of the C—H functionalization of indoles, a new strategy to achieve the asymmetric C—H functionalization of indoles from metal carbenoids via enantioselective protonation has been proposed. We initially carried out a deuterium isotope experiments in order to obtain more insight into the proton transfer process of the C—H functionalization of indoles, and the experiments indicated an “indirect proton transfer” in the reaction. A proton-transfer shuttle such as H2O was needed to complete the reaction. The observation provides us an opportunity to design a chiral proton-transfer shuttle to achieve the asymmetric C—H functionalization. In this paper, Rh2(OAc)4 catalyzed diazo decomposition of a aryl diazoacetate generates a metal carbenoid. Reaction of the metal carbenoid with an indole at C-3 position generates a zwitterionic intermediate. A bifunctional chiral phosphoric acid serves as a chiral proton shuttle and helps the proton transfer process via an enantioselective protonation to finish the reaction in high yield and enantioselectivity. A number of indoles including N-alkyl, aryl , silyl and a number of α-aryl-α-diazoesters are well tolerated under the established catalytic conditions, providing good to high enantioselectivity (up to 94% ee) in excellent yield (up to 99% yield). A representative procedure for the enantioselective C—H functionalization of indoles is as following: A mixture of 6-chloro-N-methyl indole (1e) (41 mg, 0.25 mmol), transition metal catalyst Rh2(OAc)4 (1 mg, 0.0025 mmol, 1 mol%), chiral phosphoric acid co-catalyst (R)-4j (3.8 mg, 0.005 mmol, 2 mol%) and 4A MS (100 mg) in 1 mL of toluene was stirred at the 0 °C. Methyl phenyldiazo acetate (2a) (53 mg, 0.3 mmol) in 1 mL of toluene was added over 1 h period of time via a syringe pump. After completion of the addition, the reaction was stirred for additional 5 min at the same temperature. Solvent was evaporated under reduced pressure to give corresponding crude product. The crude product was purified by flask chromatography on silica gel (eluent: EtOAc/light petroleum ether, V∶V=1∶ 40~1∶10) to give the pure product 3q in 92% yield with 94% ee.

Iron porphyrin-catalyzed three-component reaction of ethyl diazoacetate with aliphatic amines and β,γ-unsaturated α-keto esters.

An iron porphyrin-catalyzed three-component reaction of ethyl diazoacetate with aliphatic amines and β,γ-unsaturated α-keto esters is reported. The use of iron porphyrin catalyst allows aliphatic amines to be used as the substrate without encountering catalyst poisoning issue and a series of β-hydroxy-α-amino esters are produced in high yields with excellent regioselectivities.

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.