Xi-Sha Zhang

Pyridinyl Directed Alkenylation with Olefins via Rh(III)-Catalyzed C–C Bond Cleavage of Secondary Arylmethanols

Novel C-C bond cleavage of secondary alcohols through Rh(III)-catalyzed β-carbon elimination directed by a pyridinyl group is reported. A five-membered rhodacycle is proposed as a key intermediate, which undergoes further alkenylation with various olefins. This novel transformation shows high efficiency along with excellent selectivity in mild conditions. A wide range of functionalities are compatible. This study offers a new strategy to carry out C-C bond activation.

Transition metal-catalyzed direct nucleophilic addition of C–H bonds to carbon–heteroatom double bonds

Transition metal-catalyzed direct C–H functionalization has drawn great attention in the past several decades owing to its advantages compared to conventional organic transformations, including higher atom-, step- and cost-economy and the avoidance of tedious prefunctionalization and waste emission. At the current stage, to make the C–H functionalization more applicable, chemists have devoted themselves to expanding the substrate and reaction scope. In the past decade, we exerted ourselves to develop new transformations based on direct C–H functionalization. In this minireview we report on our recent achievements on the addition of C–H bonds to carbonyls and imines. The addition of organometallic reagents, such as Grignard reagents, toward carbon–heteroatom double bonds is one of the most powerful reactions in organic synthesis to produce secondary and tertiary alcohols and amines. This chemistry is broadly used in both laboratory and industry. However, this powerful transformation suffers from some drawbacks: (1) the preparation of initial organohalides from easily available fossil feedstocks is tedious and sluggish; (2) substantial amounts of metal halide salts are emitted as waste; (3) last but not least, the manipulation of organometallic reagents is complicated due to their sensitivity to air and moisture. In contrast, direct insertion of polar double bonds to C–H bonds via transition-metal catalysis is ideal from the viewpoint of atom-, step- and cost-economy and the avoidance of the waste emission, as well as of the complex manipulation of sensitive reagents. Starting from this point, we made a commitment to this project years ago and have made credible achievements in this field. We first carried out Ir-catalyzed addition of pyridinyl C–H bonds to aldehydes promoted by silane, showing an unusual C-3 selectivity. Later on, we developed Rh-catalyzed addition of aryl C–H bonds with aldimines in the absence of any additives with directing strategy with highest atom- and step-economy. The mechanism was investigated in depth by the isolation of key intermediates and systematic thermodynamic and kinetic studies. Such a concept was expanded to the coupling of aryl/alkenyl C–H bonds with aldehydes and imines. Notably, a tandem process of relayed C–H activation/alkyne insertion/cyclization between benzoates/benzimide and alkynes was developed, indicating the potential of the direct coupling of esters and amides with C–H bonds. Ideally, this strategy opens a new window to approach the ideal reactions to produce amines and alcohols from hydrocarbons.

N-Directing group assisted rhodium-catalyzed aryl C-H addition to aryl aldehydes.

Direct aryl C-H addition to aryl aldehydes to produce biaryl methanols was reported via Rh catalysis with an N-containing directing group. The method is highly atom-, step-, and redox-economic. The procedure is robust, reliable, and compatible with water and air.

Mechanistic understanding of Rh-catalyzed N-sulfonylaldimine insertion into aryl C–H bonds

A detailed investigation is presented to understand the catalytic pathway of our recently reported Rh(III)-catalyzed N-tosylaldimine insertion into aryl C–H bonds. Herein, the key intermediates were isolated and determined by X-ray crystallography of their single crystals. The kinetic characterization of each factor in this catalytic reaction was conducted. The studies indicate that N-tosyl aldimine insertion into the C–Rh bonds rather than C–H bond activation or protonolysis is the rate-determining step. These mechanistic insights have significant implications for the development of a more efficient catalytic reaction system to realize the addition of C–H bonds to normal aldehydes and ketones, to achieve sp3 C–H bond activation, and to implement asymmetric catalysis in the near future.

Olefinic C–H Bond Addition to Aryl Aldehyde and Its N-Sulfonylimine via Rh Catalysis

The first example of olefinic C-H addition to N-sulfonylaldimines and aryl aldehydes is reported. This strategy offered a concise and high atom-economic approach to vinyl amines and vinyl alcohols.

Controllable Mono‐/Dialkenylation of Benzyl Thioethers through Rh‐Catalyzed Aryl CH Activation

Under solvent control: Benzyl thioethers were alkenylated in excellent yields with broad substrate scope and the selectivity (mono- vs. disubstituted product) was controlled by the solvent and ratio of reactants. Sequential alkenylation with two different alkenes was also carried out in a one-pot process. In addition, the thioether directing group was removed in a one-pot process with simultaneous hydrogenation of the double bond to give the toluene derivatives.

Direct oxidative arylation via rhodium-catalyzed C–C bond cleavage of secondary alcohols with arylsilanes

An unprecedented example of sequential pyridinyl directed C–C cleavage of secondary alcohols/oxidative arylation with arylsilanes via Rh(III) catalysis is reported. Preliminary studies indicated that the arylation initiated from Rh(III)-catalyzed C–C cleavage, and a 5-membered rhodacycle was involved as a key intermediate.

Palladium-catalyzed base-accelerated direct C–H bond alkenylation of phenols to synthesize coumarin derivatives

A palladium-catalyzed base-accelerated ortho-selective C–H alkenylation of phenols to synthesize bioactive coumarin derivatives was developed. The reaction condition was mild and the substrate scope was broad with both electron-neutral and electron-deficient phenols, which is complementary to the previous methods to synthesize electron-rich coumarins. Several bioactive molecules were functionalized and several coumarins with bioactive properties were synthesized. Mechanistic studies showed that this reaction underwent C–H bond activation via direct metallation rather than the Friedel–Crafts pathway.

Rh‐Catalyzed CC Cleavage of Benzyl/Allylic Alcohols to Produce Benzyl/Allylic Amines or other Alcohols by Nucleophilic Addition of Intermediate Rhodacycles to Aldehydes and Imines

We report three transformations: 1)u2005direct transformation from biarylmethanols into biarylmethylamines; 2)u2005direct transformation from one biarylmethanol into another biarylmethanol; 3)u2005direct transformation from allylic alcohols into allylic amines. These transformations are based on pyridyl-directed Rh-catalyzed C-C bond cleavage of secondary alcohols and subsequent addition to C=X (X = N or O) double bonds. The reaction conditions are simple and no additive is required. The driving force of C-C bond cleavage is the formation of the stable rhodacycle intermediate. Other directing groups, such as the pyrazolyl group, can also be used although it is not as efficient as the pyridyl group. We carried out in-depth investigations for transformation 1 and found that: 1)u2005the substrate scope was broad and electron-rich alcohols and electron-deficient imines are more efficient; 2)u2005as the leaving group, aldehyde had no significant impact on either the C-C bond cleavage or the whole transformation; 3)u2005mechanistic studies (intermediate isolation, in situ NMR spectroscopic studies, competing reactions, isotopic labeling experiments) implied that: i)u2005The C-C cleavage was very efficient under these conditions; ii)u2005there is an equilibrium between the rhodacycle intermediate and the protonated byproduct phenylpyridine; iii)u2005the addition step of the rhodacycle intermediate to imines was slower than the C-C cleavage and the equilibrium between the rhodacycle and phenylpyridine; iv)u2005the whole transformation was a combination of two sequences of C-C cleavage/nucleophilic addition and C-C cleavage/protonation/C-H activation/nucleophilic addition, with the latter being perhaps the main pathway. We also demonstrated the first example of cleavage of an C(alkenyl)-C(benzyl) bond. These transformations showed the exchange (or substitution) of the alcohol group with either an amine or another alcohol group. Like the group transplant, this method offers a new concept that can be used to directly synthesize the desired products from other chemicals through reorganization of carbon skeletons.

Synthesis of Dibenzo[c,e]oxepin-5(7H)-ones from Benzyl Thioethers and Carboxylic Acids: Rhodium-Catalyzed Double CH Activation Controlled by Different Directing Groups†

A rhodium(III)-catalyzed cross-coupling of benzyl thioethers and aryl carboxylic acids through the two directing groups is reported. Useful structures with diverse substituents were efficiently synthesized in one step with the cleavage of four bonds (Cuf8ffH, Cuf8ffS, Ouf8ffH) and the formation of two bonds (Cuf8ffC, Cuf8ffO). The formed structure is the privileged core in natural products and bioactive molecules. This work highlights the power of using two different directing groups to enhance the selectivity of a double Cuf8ffH activation, the first of such examples in cross-oxidative coupling.