Chaoqun Li

Metal−Brønsted Acid Cooperative Catalysis for Asymmetric Reductive Amination

Direct reductive amination of a wide range of ketones has been accomplished by the cooperative catalysis of an Ir(III)-diamine complex and a chiral phosphoric acid or its conjugate base.

pH-Regulated Asymmetric Transfer Hydrogenation of Quinolines in Water†

1,2,3,4-Tetrahydroquinolines exist as key structural elements in many natural products and have found broad commercial application. In particular, optically pure tetrahydroquinolines are commonly present in alkaloids and are required in pharmaceutical and agrochemical synthesis. Representative examples include the bioactive alkaloids (+)-galipinine and ( )-augustureine, 3] and the antibacterial drug (S)-flumequine.

Chiral Counteranion-Aided Asymmetric Hydrogenation of Acyclic Imines

When combined with a chiral phosphate counteranion, a chiral diamine-ligated Ir(III) catalyst displayed excellent enantioselectivities in the asymmetric hydrogenation of a wide range of acyclic imines, affording chiral amines in up to 99% ee.

Asymmetric hydrogenation of cyclic imines with an Ionic Cp*Rh(III) catalyst

When associated with a noncoordinating bulky counteranion, a cationic Cp*Rh(III)-diamine catalyst displayed excellent enantioselectivities in asymmetric hydrogenation of cyclic imines, affording bioactive tetrahydroisoquinolines and tetrahydro-beta-carbolines frequently with 99% ees.

Bifunctional catalysis: direct reductive amination of aliphatic ketones with an iridium-phosphate catalyst.

Chiral amines are one of the ubiquitous functional groups in fine chemical, pharmaceutical and agrochemical products, and the most convenient, economical, and eco-benign synthetic pathway to these amines is direct asymmetric reductive amination (DARA) of prochiral ketones. This paper shows that a wide range of aliphatic ketones can be directly aminated under hydrogenation conditions, affording chiral amines with good to excellent yields and with enantioselectivities up to 96% ee. The catalysis is effected by the cooperative action of a cationic Cp*Ir(III) complex and its phosphate counteranion.

Cooperative Catalysis: Combining an Achiral Metal Catalyst with a Chiral Brønsted Acid Enables Highly Enantioselective Hydrogenation of Imines

Asymmetric hydrogenation of imines leads directly to chiral amines, one of the most important structural units in chemical products, from pharmaceuticals to materials. However, highly effective catalysts are rare. This article reveals that combining an achiral pentamethylcyclopentadienyl (Cp*)-iridium complex with a chiral phosphoric acid affords a catalyst that allows for highly enantioselective hydrogenation of imines derived from aryl ketones, as well as those derived from aliphatic ones, with ee values varying from 81 to 98 %. A range of achiral iridium complexes containing diamine ligands were examined, for which the ligands were shown to have a profound effect on the reaction rate, enantioselectivity and catalyst deactivation. The chiral phosphoric acid is no less important, inducing enantioselection in the hydrogenation. The induction occurs, however, at the expense of the reaction rate.

Reactions Catalysed by a Binuclear Copper Complex: Aerobic Cross Dehydrogenative Coupling of N-Aryl Tetrahydroisoquinolines

Binuclear copper complex [{Cu(Sal)2 (NCMe)}2 ] (Sal=salicylate) was found to be an active catalyst for the aerobic oxidation of N-aryl tetrahydroisoquinolines to the corresponding iminium ions, which could be trapped by a wide range of nucleophiles to form coupled products. The reactions took place under 1 bar of O2 at room temperature with 1 mol % of the copper catalyst being sufficient in most cases, and are considerably accelerated by catalytic chloride anions. Mechanistic studies show that the CuII dimer oxidizes the amine to the iminium ion, and this two-electron process requires O2 , whereby the resulting CuI is concomitantly reoxidised back to CuII . Various lines of evidence suggest that the oxidative coupling reaction is turnover-limited by the step of iminium formation, and it is this step that is promoted by the chloride anion. Since it is more efficient than and mechanistically distinct from the well-studied simple copper salts such as CuBr and CuCl2 , the binuclear copper catalyst provides a new tool for oxidative coupling reactions.

Atmosphere-Controlled Chemoselectivity: Rhodium-Catalyzed Alkylation and Olefination of Alkylnitriles with Alcohols

The chemoselective alkylation and olefination of alkylnitriles with alcohols have been developed by simply controlling the reaction atmosphere. A binuclear rhodium complex catalyzes the alkylation reaction under argon through a hydrogen-borrowing pathway and the olefination reaction under oxygen through aerobic dehydrogenation. Broad substrate scope is demonstrated, permitting the synthesis of some important organic building blocks. Mechanistic studies suggest that the alkylation product may be formed through conjugate reduction of an alkene intermediate by a rhodium hydride, whereas the formation of olefin product may be due to the oxidation of the rhodium hydride complex with molecular oxygen.

Reactions Catalysed by a Binuclear Copper Complex: Relay Aerobic Oxidation of N-Aryl Tetrahydroisoquinolines to Dihydroisoquinolones with a Vitamin B1 Analogue

N-Aryl tetrahydroisoquinolines were oxidised to dihydroisoquinolones through the relay catalysis of a binuclear paddle-wheel copper complex and a vitamin B1 analogue with oxygen as oxidant. Mechanistic studies revealed that the copper catalyst oxidises amines to the corresponding iminium salts, which are then oxygenated to lactam products by catalysis of the vitamin B1 analogue.

Iron-Catalyzed Alkylation of Nitriles with Alcohols

A general, efficient iron-catalyzed α-alkylation of nitriles with primary alcohols through a hydrogen-borrowing pathway has been developed, allowing a wide variety of alkylated nitriles to be readily accessible. Detailed mechanistic studies suggest that the reaction proceeds via an olefin intermediate with the turnover rate limited by the hydrogenation of the olefin with an iron hydride. Apart from participating in the alkylation, the nitrile is found to play an important role in promoting the formation of and stabilizing the active catalytic species.