Jia-Qiang Wu

Cp*Co(III)-Catalyzed Annulations of 2-Alkenylphenols with CO: Mild Access to Coumarin Derivatives

Cp*Co(III)-catalyzed annulations of 2-alkenylphenols with CO for the synthesis of coumarin derivatives have been developed. The reaction features mild reaction conditions, broad substrate scope, and good functional group tolerance. Preliminary mechanistic studies were conducted, suggesting that C-H activation is the turnover limiting step. Furthermore, the efficiency of this reaction was demonstrated by the rapid total synthesis of three natural products herniarin, xanthyletin, and seselin.

Experimental and Theoretical Studies on Rhodium-Catalyzed Coupling of Benzamides with 2,2-Difluorovinyl Tosylate: Diverse Synthesis of Fluorinated Heterocycles

Fluorinated heterocycles play an important role in pharmaceutical and agrochemical industries. Herein, we report on the synthesis of four types of fluorinated heterocycles via rhodium(III)-catalyzed C-H activation of arenes/alkenes and versatile coupling with 2,2-difluorovinyl tosylate. With N-OMe benzamide being a directing group (DG), the reaction delivered a monofluorinated alkene with the retention of the tosylate functionality. Subsequent one-pot acid treatment allowed the efficient synthesis of 4-fluoroisoquinolin-1(2H)-ones and 5-fluoropyridin-2(1H)-ones. When N-OPiv benzamides were used, however, [4 + 2] cyclization occurred to provide gem-difluorinated dihydroisoquinolin-1(2H)-ones. Synthetic applications have been demonstrated and the ready availability of both the arene and the coupling partner highlighted the synthetic potentials of these protocols. Mechanistically, these two processes share a common process involving N-H deprotonation, C-H activation, and olefin insertion to form a 7-membered rhodacycle. Thereafter, different reaction pathways featuring β-F elimination and C-N bond formation are followed on the basis of density functional theory (DFT) studies. These two pathways are DG-dependent and led to the open chain and cyclization products, respectively. The mechanistic rationale was supported by detailed DFT studies. In particular, the origins of the intriguing selectivity in the competing β-F elimination versus C-N bond formation were elucidated. It was found that β-F elimination is a facile event and proceeds via a syn-coplanar transition state with a low energy barrier. The C-N bond formation proceeds via a facile migratory insertion of the Rh-C(alkyl) into the Rh(V) amido species. In both reactions, the migratory insertion of the alkene is turnover-limiting, which stays in good agreement with the experimental studies.

Mild Rhodium(III)-Catalyzed C–H Allylation with 4-Vinyl-1,3-dioxolan-2-ones: Direct and Stereoselective Synthesis of (E)-Allylic Alcohols

A rhodium(III)-catalyzed C-H direct allylation reaction with 4-vinyl-1,3-dioxolan-2-ones has been developed. The reaction provides a facile and stereoselective access to substituted-(E)-allylic alcohols under mild and redox-neutral reaction conditions. Olefinic C-H activation is applicable, giving multifunctionalized skipped dienes in good yields. Minimal double-bond migration was observed.

Manganese(I)‐Catalyzed Regio‐ and Stereoselective 1,2‐Diheteroarylation of Allenes: Combination of C−H Activation and Smiles Rearrangement

Heteroarenes are important structural motif in functional molecules. A MnI -catalyzed 1,2-diheteroarylation of allenes via a C-H activation/Smiles rearrangement cascade is presented. The reaction occurred under additive-free or even solvent-free conditions, which allowed the creation of two C-C and one C-N bonds in a single operation. A series of structurally diverse bicyclic or tricyclic compounds bearing an exocyclic double bond were constructed in good to excellent efficiency. The decarboxylative ring-opening of the products led to the facile synthesis of vicinal biheteroaryls. Synthetic applications were demonstrated and preliminary mechanistic studies were conducted.

Palladium-Catalyzed Remote C(sp3)–H Arylation of 3-Pinanamine

3-Pinanamine is a prevalent motif in medicinal chemistry and asymmetric synthesis. In line with the pursuit of novel 3-pinanamine based anti-influenza virus A agent, the direct functionalization of 3-pinanamine was achieved by using Pd-catalyzed C(sp(3))-H activation logic. Good substrate scope and functional group tolerance were observed. The reaction represents a rare example of a direct functionalization of an aliphatic amine at the remote δ position.

Polycyclization Enabled by Relay Catalysis: One-Pot Manganese-Catalyzed C-H Allylation and Silver-Catalyzed Povarov Reaction

In this study, a MnI /AgI -based relay catalysis process is described for the one-pot synthesis of polycyclic products by a formal [3+2] and [4+2] cycloaddition reaction cascade. A manganese(I) complex catalyzed the first example of directed C-H allylation with allenes, setting the stage for an in situ Povarov cyclization catalyzed by silver(I). The reaction proceeds with high bond-forming efficiency (three C-C bonds), broad substrate scope, high regio- and stereoselectivity, and 100 % atom economy.

Palladium-catalyzed methylene C(sp3)–H arylation of the adamantyl scaffold

The adamantyl group is prevalent as a key pharmacophore element in drugs. We describe herein a palladium-catalyzed C–H functionalization logic for the methylene C(sp3)–H arylation of the adamantyl scaffold with the assistance of an amide group. The resulting arylated adamantyl amide was smoothly converted to an amine, providing facile access to the memantine analog.

Three-Component Catalytic Carboxygenation of Activated Alkenes Enabled by Bimetallic Rh(III)/Cu(II) Catalysis

A novel cascade Cp*Rh(III)-catalyzed C-H alkylation/Cu(II)-promoted α-oxygenation which enabled a three-component carboxygenation of activated alkene is reported. Mild reaction conditions, broad substrate scope, and good functional group tolerance were observed. The synthetic utility of the protocol was showcased by the facile transformations of the product to a variety of structurally diverse molecules. Preliminary mechanistic studies were conducted.