Chun-Xiang Zhuo

Catalytic Asymmetric Dearomatization Reactions

This Review summarizes the development of catalytic asymmetric dearomatization (CADA) reactions. The CADA reactions discussed herein include oxidative dearomatization reactions, dearomatization by Diels-Alder and related reactions, the alkylative dearomatization of electron-rich arenes, transition-metal-catalyzed dearomatization reactions, cascade sequences involving asymmetric dearomatization as the key step, and nucleophilic dearomatization reactions of pyridinium derivatives. Asymmetric dearomatization reactions with chiral auxiliaries and catalytic asymmetric reactions of dearomatized substrates are also briefly introduced. This Review intends to provide a concept for catalytic asymmetric dearomatization.

Iridium-Catalyzed Allylic Alkylation Reaction with N-Aryl Phosphoramidite Ligands: Scope and Mechanistic Studies

A series of N-aryl phosphoramidite ligands has been synthesized and applied to iridium-catalyzed allylic alkylation reactions, offering high regio- and enantioselectivities for a wide variety of substrates. These ligands feature the synthetic convenience and good tolerance of the ortho-substituted cinnamyl carbonates. Mechanistic studies, including DFT calculations and X-ray crystallographic analyses of the (π-allyl)-Ir complexes, reveal that the active iridacycle is formed via C(sp(2))-H bond activation.

Enantioselective functionalization of indoles and pyrroles via an in situ-formed spiro intermediate.

Herein we report a highly enantioselective synthesis of polycyclic indoles and pyrroles with up to 99% ee by an iridium catalyst system consisting of a commercially available iridium precursor and a readily accessible ligand. Investigation of the reaction mechanism led to the discovery of an unprecedented dearomatized spiro intermediate and its in situ migration phenomenon. The new reaction mode features switching of the substituent from the indole C-3 position to the C-2 position (from the C-2 position to the C-3 position in the case of pyrrole) without loss of the enantiomeric purity, providing a novel concept in designing the asymmetric construction of enantiopure polycyclic indoles and pyrroles.

Asymmetric dearomatization of pyrrolesviaIr-catalyzed allylic substitution reaction: enantioselective synthesis of spiro-2H-pyrroles

Asymmetric dearomatization of pyrroles has been accomplished by using Ir-catalyzed intramolecular asymmetric allylic alkylation reactions. Reactions of allylic carbonate tethered pyrroles in the presence of [Ir(cod)Cl]2 and a BINOL-derived phosphoramidite ligand lead to efficient generation of spiro-2H-pyrrole derivatives with up to 96% ee.

Palladium‐Catalyzed Intermolecular Asymmetric Allylic Dearomatization Reaction of Naphthol Derivatives

Baring all: The title reaction provides β-naphthalenones bearing an all-carbon quaternary center in good to excellent yields, as well as excellent chemo- and enantioselectivity.

Asymmetric Dearomatization of β-Naphthols through an Amination Reaction Catalyzed by a Chiral Phosphoric Acid†

A highly efficient catalytic asymmetric dearomatization of naphthols by means of an electrophilic amination reaction catalyzed by chiral phosphoric acid is presented. This protocol provides a facile access to functionalized β-naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity (up to 99% yield, up to 96% ee).

Highly Regio- and Enantioselective Synthesis of Polysubstituted 2H-Pyrroles via Pd-Catalyzed Intermolecular Asymmetric Allylic Dearomatization of Pyrroles

A highly efficient synthesis of chiral polysubstituted 2H-pyrrole derivatives via a Pd-catalyzed intermolecular asymmetric allylic dearomatization reaction of pyrroles is presented. With the commercially available palladium precursor and chiral ligand, the polysubstituted 2H-pyrrole products containing a chiral quaternary carbon center were obtained with up to 97% ee and >95/5 regioselectivity.

Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

Enantioselective Construction of Spiroindolines with Three Contiguous Stereogenic Centers and Chiral Tryptamine Derivatives via Reactive Spiroindolenine Intermediates

The highly efficient synthesis of the enantioenriched spiroindolines by iridium-catalyzed asymmetric allylic dearomatization and reduction is presented. Spiroindolines containing three contiguous stereogenic centers were obtained with excellent diastereo- and enantioselectivity. In addition, a chiral tryptamine derivative could be easily accessed in good yield with excellent ee value through an unprecedented dearomatization/retro-Mannich/hydrolysis cascade reaction of an indole derivative.

Mechanistic insights into the Pd-catalyzed intermolecular asymmetric allylic dearomatization of multisubstituted pyrroles: understanding the remarkable regio- and enantioselectivity.

In this article we report a comprehensive density functional theory study on the Pd-catalyzed intermolecular asymmetric allylic dearomatization reactions of multisubstituted pyrroles. The calculated results are in line with the previous experimental observations (J. Am. Chem. Soc. 2014, 136, 6590), and the remarkable regio- and enantioselectivity are well explained. Of all the potential nucleophilic sites around the multisubstituted pyrrole ring, the reaction always occurs at the position where the HOMO of the molecule distributes most significantly. In contrast to the common view on the enantioselectivity of the Pd-catalyzed asymmetric allylic substitution reactions, we find that the steric interaction between the nucleophile and the chiral ligand does not have the dominating effect on the enantioselectivity of the reaction. Instead, the interaction between the allyl moiety and the incoming nucleophile plays an important role in the enantioselectivity-determining process.