Enantioselective Cross-Dehydrogenative Coupling Research Articles

Electricity-driven enantioselective cross-dehydrogenative coupling of two C(sp3)-H bonds enabled by organocatalysis

An efficient and scalable electrochemical asymmetric protocol with metal-free catalysts and even without additional oxidants for the cross-dehydrogenative coupling reaction (CDC) of two C(sp3)-H bonds is reported. A series of aldehydes including natural products and various substrates containing C(sp3)-H bonds including xanthenes, acridines, cycloheptatrienes and even diarylmethane have been shown to undergo asymmetric CDC to afford a series of carbon-carbon bond coupling products with up to 94% yield and 98% ee. Mechanistic studies such as radical clock experiment suggest that the reaction proceeds via nucleophilic attack by enamine under electrochemical conditions.

Enantioselective cross-dehydrogenative coupling enabled by organocatalysis

Organocatalytic enantioselective cross-dehydrogenative coupling reaction provides a great opportunity for the synthesis of highly enantioenriched molecules. In this review, recent progress in this field is summarized.

Iodine-enabled organoelectrocatalysis: enantioselective cross dehydrogenative coupling of sulfides and aldehydes

A method for the direct asymmetric α-sulfenylation of aldehydes with sulfides was developed.

Cooperative photocatalysis and l-/d-proline catalysis enables enantioselective oxidative cross-dehydrogenative coupling of acyclic benzylic secondary amines with ketones

We developed an enantioselective cross-dehydrogenative coupling of acyclic benzylic secondary amines with ketones by combining photocatalysis and l-/d-proline catalysis.

An atom economical approach for enantioselective cross dehydrogenative coupling

Asymmetric C−H/C−H cross coupling offers an efficient strategy for direct synthesis of enantioriched molecules. In this issue of Chem Catalysis, You and coworkers disclosed a Pd catalyzed approach for enantioselective cross coupling between indolizines and dialkylaminomethylferrocenes. Using this protocol, a range of chiral planar ferrocenes have been accessed under mild condition.

New Trends in Enantioselective Cross-Dehydrogenative Coupling

The development of cross-dehydrogenative coupling in recent years has simplified the synthesis of many materials, as a result of facile C–H activation, which, together with its greater atom economy and environmental friendliness, has made an impact on modern organic chemistry. Indeed, many C–C and C–X (X = N, O, P, S, B, or Si) coupling reactions can now be performed directly between two C–H bonds or a C–H and an X–H bond, simply by adding catalytic amounts of a metal salt to a mixture of the two and an oxidant to accept the two hydrogen atoms released. Chiral organocatalysts or chiral ligands have been joined to promote enantioselective processes, resulting in the development of efficient reaction cascades that provide products in high yields and high levels of asymmetric induction through cooperative catalysis. In recent years, photochemical oxidation and electrochemistry have widened even more the scope of cross-dehydrogenative coupling (CDC). In this review, we summarized the recent literature in this subject, hoping that it will inspire many new synthetic strategies.

Catalytic enantioselective oxidative coupling of saturated ethers with carboxylic acid derivatives

Catalytic enantioselective C–C bond forming process through cross-dehydrogenative coupling represents a promising synthetic strategy, but it remains a long-standing challenge in chemistry. Here, we report a formal catalytic enantioselective cross-dehydrogenative coupling of saturated ethers with diverse carboxylic acid derivatives involving an initial oxidative acetal formation, followed by nickel(II)-catalyzed asymmetric alkylation. The one-pot, general, and modular method exhibits wide compatibility of a broad range of saturated ethers not only including prevalent tetrahydrofuran and tetrahydropyran, but also including medium- and large-sized cyclic moieties and acyclic ones with excellent enantioselectivity and functional group tolerance. The application in the rapid preparation of biologically active molecules that are difficult to access with existing methods is also demonstrated.

Catalytic enantioselective cross dehydrogenative coupling of sp3 C-H of heterocycles.

C-C bond formation in heterocycles via the direct coupling of C-H bonds, under oxidative conditions, classified as cross dehydrogenative coupling (CDC), is without doubt one of the most atom efficient methods for the functionalization of these molecules. The most common is the coupling at the position alpha to the heteroatom, owing to the stabilization of forming carbocation by the heteroatom. The corresponding asymmetric versions, except for a few isolated reports, have been rather evasive for several years. Optically active heterocycles with the chiral center alpha to the heteroatom are widely present in natural products and pharmaceuticals, thus making them an attractive synthetic target. Persistent efforts towards the asymmetric CDC of heterocycles since the beginning of this decade have led to several developments in this challenging area. Particularly, in the last few years, considerable progress has been witnessed in this field. This review summarizes the progress made in the area of asymmetric cross dehydrogenative coupling of heterocycles in recent years. The review covers the catalytic asymmetric CDC of sp3 C-H bonds of the heterocycles with various coupling partners and illustrates the different catalytic systems employed.

Catalytic enantioselective cross-dehydrogenative coupling of 3,6-dihydro-2H-pyrans with aldehydes

The first catalytic asymmetric cross-dehydrogenative coupling of 3,6-dihydro-2H-pyrans and aldehydes with excellent enantioselectivity is described.

Tetrahydropyrans by an Enantioselective Cross-Dehydrogenative Coupling

Tetrahydropyrans by an Enantioselective Cross-Dehydrogenative Coupling

An Enantioselective Cross-Dehydrogenative Coupling Catalysis Approach to Substituted Tetrahydropyrans.

An enantioselective cross-dehydrogenative coupling (CDC) reaction to access tetrahydropyrans has been developed. This process combines in situ Lewis acid activation of a nucleophile in concert with the oxidative formation of a transient oxocarbenium electrophile, leading to a productive and highly enantioselective CDC. These advances represent one of the first successful applications of CDC for the enantioselective couplings of unfunctionalized ethers. This system provides efficient access to valuable tetrahydropyran motifs found in many natural products and bioactive small molecules.

Enantioselective cross dehydrogenative coupling reaction catalyzed by Rose Bengal incorporated-Cu(I)-dimeric chiral complexes

A novel dimeric chiral Cu(I) amino alcohol based in-situ generated catalyst in combination with Rose Bengal as a photo-redox catalyst were used for the first time for asymmetric cross dehydrogenative coupling of N-aryl tetrahydroisoquinoline with terminal alkynes enroute for propargylic amines synthesis using molecular oxygen as a terminal oxidant. This methodology provides an atom economical and green way to access diversified optically active alkynylation product selectively at C1-position of N-aryl tetrahydroisoquinoline under moderate conditions with high enantioselectivity (up to 99%) and excellent yield (up to 90%).

Organocatalytic Enantioselective Cross-Dehydrogenative Coupling of N-Carbamoyl Cyclic Amines with Aldehydes.

The existing catalytic enantioselective cross-dehydrogenative coupling of cyclic amines predominantly focused on reactive N-aryl tetrahydroisoquinolines, which typically suffered from limited substrate generality and synthetic utility, and required the use of metal catalyst. Herein, a metal-free catalytic enantioselective cross-dehydrogenative coupling of N-carbamoyl cyclic amines and aldehydes has been reported for the first time. Employing an easily installed and functionalized acyl protecting group rather than the widely adopted aryl moiety endows the enantioselective process with better substrate generality and broader synthetic utility.

Copper-Catalyzed Aerobic Enantioselective Cross-Dehydrogenative Coupling of N-Aryl Glycine Esters with Terminal Alkynes.

A copper-catalyzed enantioselective cross-coupling of a Csp3-H moiety (N-aryl glycine ester) with a Csp-H component (terminal alkyne) using molecular oxygen as the terminal oxidant is described for the first time. The sustainable method provides an efficient and environmentally friendly approach to rapidly prepare a diverse array of optically active non-natural α-amino acids.

ChemInform Abstract: Enantioselective Synthesis of Planar‐Chiral Benzosiloloferrocenes by Rh‐Catalyzed Intramolecular C—H Silylation.

The first synthesis of planar-chiral benzosiloloferrocenes was achieved by the intramolecular reaction of 2-(dimethylhydrosilyl)arylferrocenes. The enantioselective cross dehydrogenative coupling of an sp2 C–H bond of ferrocene with a Si–H bond proceeded efficiently with the use of a Rh-chiral diene catalyst.

Asymmetric Catalytic Carbon-Carbon Coupling Reactions via Cross-Dehydrogenative Coupling Reactions

Asymmetric catalytic C—C coupling reactions via cross-dehydrogenative coupling are currently among the most attractive and powerful tools in synthetic organic chemistry. In the past few decades, a variety of catalytic asymmetric C—C coupling reactions via cross-dehydrogenative coupling have been reported. Compared with traditional asymmetric C—C bond formation reactions, cross-dehydrogenative coupling strategies have more advantages in terms of power and cost- effective- ness. In this review, the recent studies on enantioselective cross dehydrogenative-coupling are reviewed. Keywords asymmetric catalysis; cross-dehydrogenative coupling; C—H activation

Brønsted Acid Catalyzed Enantioselective Cross-Dehydrogenative Coupling

Brønsted Acid Catalyzed Enantioselective Cross-Dehydrogenative Coupling