As two coexisting and fast-growing research fields in modern synthetic chemistry, the merging of organocatalysis and C–H bond functionalization is well foreseeable, and the joint force along this line has been demonstrated to be a powerful approach in making inert C–H bond functionalization more viable, predictable, and selective. In this review, we provide a comprehensive summary of organocatalysis in inert C–H bond functionalization over the past two decades. The review is arranged by types of inert C–H bonds including alkane C–H, arene C–H, and vinyl C–H as well as those activated benzylic C–H, allylic C–H, and C–H bonds alpha to the heteroatom such as nitrogen and oxygen. In each section, the discussion is classified by the explicit organocatalytic mode involved.

Organocatalysis in Inert C–H Bond Functionalization

The first phosphoric acid-catalyzed asymmetric direct arylative reactions of 2-naphthols with quinone derivatives have been developed, providing efficient access to a class of axially chiral biaryldiols in good yields with excellent enantioselectivities under mild reaction conditions. This approach is a highly convergent and functional group tolerant route to the rapid construction of axially chiral compounds from simple, readily available starting materials. The excellent stereocontrol of the process stems from efficient transfer of stereochemical information from the chiral phosphoric acid into the axis chirality of the biaryldiol products. Preliminary results demonstrate that the biaryldiols can act as efficient chiral ligands in asymmetric transformations.

Atroposelective Synthesis of Axially Chiral Biaryldiols via Organocatalytic Arylation of 2-Naphthols.

Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions

We summarize in this review the recent development of chiral phosphoric acid (CPA)-catalyzed asymmetric dearomatization reactions. A wide array of electron-rich arenes (indoles, phenols, naphthols, benzothiophenes, benzofurans, etc.) and electron-poor arenes (pyridines, quinolines, isoquinolines, etc.) has been proved reactive towards various reaction partners in the presence of a CPA catalyst, enabling asymmetric dearomatization reactions that lead to structurally-diverse polycyclic molecules. The reactions are grouped according to the roles of the arenes in the reactions (as nucleophiles or electrophiles) and the types of reaction partners. This review closes with a personal perspective on the dynamic research area of asymmetric dearomatization reactions by CPAs.

Chiral phosphoric acid-catalyzed asymmetric dearomatization reactions

The organocatalytic asymmetric arylative dearomatization of indoles was achieved through two tandem approaches involving 2,3-disubstituted indoles and quinone imine ketals. One approach utilized the enantioselective cascade 1,4 addition/alcohol elimination reaction, the other employed the one-pot tandem arylative dearomatization/transfer hydrogenation sequence. In both cases, enantiomerically pure indole derivatives that bear an all-carbon quaternary stereogenic center were generated in high yields and excellent stereoselectivities (all d.r.>95:5, up to 99 % ee).

Organocatalytic Asymmetric Arylative Dearomatization of 2,3‐Disubstituted Indoles Enabled by Tandem Reactions

Highly enantioselective [3+2] coupling of 3-substituted indoles with quinone monoimines promoted by a chiral phosphoric acid has been reported. A large variety of benzofuroindolines were prepared in moderate to good yields (up to 98%) with generally excellent enantioselectivities (up to 99 % ee).

Highly Enantioselective [3+2] Coupling of Indoles with Quinone Monoimines Promoted by a Chiral Phosphoric Acid

Green method for the synthesis of chromeno[2,3-c]pyrazol-4(1H)-ones through ionic liquid promoted directed annulation of 5-(aryloxy)-1H-pyrazole-4-carbaldehydes in aqueous media.

We report here an efficient and green method for Biginelli condensation reaction of aldehydes, β-ketoesters and urea or thiourea catalyzed by Bronsted acidic ionic liquid [Btto][p-TSA] under solvent-free conditions. Compared to the classical Biginelli reaction conditions, the present method has the advantages of giving good yields, short reaction times, near room temperature conditions and the avoidance of the use of organic solvents and metal catalyst.

https://www.mdpi.com/1420-3049/20/3/3811/pdf

Yonghong Zhang

Papers

Highly Enantioselective [3+2] Coupling of Indoles with Quinone Monoimines Promoted by a Chiral Phosphoric Acid

Green method for the synthesis of chromeno[2,3-c]pyrazol-4(1H)-ones through ionic liquid promoted directed annulation of 5-(aryloxy)-1H-pyrazole-4-carbaldehydes in aqueous media.

An efficient synthesis of 3,4-Dihydropyrimidin-2(1H)-ones and thiones catalyzed by a novel Brønsted acidic ionic liquid under solvent-free conditions.

Ionic Liquid Promoted Diazenylation of N-Heterocyclic Compounds with Aryltriazenes under Mild Conditions.

Recent Applications of Aryltriazenes in Organic Synthesis via C-N/N-N Bond Cleavage