Polysubstituted allyl groups, for example, the prenyl group, are valuable synthetic handles and widely encountered in bioactive compounds. Reported herein is a manganese(I)-catalyzed direct C–H coupling with allenes for the efficient assembly of allylated arenes. The protocol offers an extremely high level of atom-economy and is particularly suited for the introduction of 1,1-disubstitiuted allyl groups, as exemplified by the quantitative syntheses of a variety of prenylated indoles. The practicality of this method was evidenced by a gram-scale synthesis with a lower catalyst loading of manganese(I) (2.5 mol %, 95% yield). Experimental mechanistic studies were conducted, and a possible reaction mechanism was proposed.

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.

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.

Group 9 Cp*M(III) (M = Co, Rh, Ir) complexes have been extensively investigated as catalysts in a variety of C–H activation reactions. Typically, late metal-based silver or copper salt was used (while needed) as oxidant in these catalytic systems. Herein, we report our discovery of a potentially general type of N–O bond-containing oxidants, which allowed the mild and efficient syntheses of isocoumarins, isoquinolines, isoquinolinone, and styrenes via C–H activation catalyzed by group 9 Cp*M(III) complexes. By using Cp*Rh(III)-catalyzed isocoumarin synthesis as a model reaction, experimental and theoretical mechanistic studies were conducted. The results concluded that the Rh(III)–Rh(I)–Rh(III) rather than the Rh(III)–Rh(V)–Rh(III) pathway is more likely involved in the mechanism, and both the C–H activation and oxidation of the Cp*Rh(I) species were involved in the turnover-limiting step.Keywords: Cp*M(III); C−H activation; heterocycle; N−O bond; oxidation;

A redox-neutral bimetallic Rh(III)/Ag(I) relay catalysis allowed the efficient construction of 3-alkylidene isoindolinones and 3-alkylidene isobenzofuranones. The Rh(III) catalyst was responsible for the C–H monofluoroalkenylation reaction, whereas the Ag(I) salt was an activator for the follow-up cyclization. The methodology developed was applied as a key step in the rapid total synthesis of the natural product aristolactam BII.

AbstractThe direct trifluoromethylthiolation of arenes was realized via (pentamethylcyclopentadienyl)cobalt(III)-catalyzed C(sp2)-H activation and coupling with AgSCF3 under the assistance of a directing group. The reaction features redox-neutrality, mild conditions, broad substrate scope, and good functional group tolerance. Preliminary mechanistic studies have been conducted.

AbstractHeteroarenes 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.

AbstractHeteroarenes 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.

AbstractThe individual molecules of α-chloroalkenyl boronates include both an electrophilic C−Cl bond and a nucleophilic C−B bond, which makes them intriguing organic synthons. Reported herein is a stereodivergent synthesis of both E and Z α-chloroalkenyl N-methyliminodiacetyl (MIDA) boronates through the direct chlorination of alkenyl MIDA boronates using tBuOCl and PhSeCl reagents, respectively. Both reaction processes are stereospecific and the use of sp3-B MIDA boronate is the key contributor to the reactivity. The synthetic value of the boronate products was also demonstrated.

Tandem catalysis by Rh(III)/Pd(II) was realized, enabling rapid access to two important N-heterocycles that bear a synthetically valuable vinyl substituent. The reaction occurred under mild reaction conditions and was easy to handle. Good substrate scope and high regio- and stereoselectivities were observed. The vinyl group was demonstrated to be a reliable handle for functional group interconversions. The alkene effect was found to be the key factor for the success of this process.Keywords: C−H bond activation; N-heterocycles; palladium(II); rhodium(III); tandem catalysis

A tandem Cp*Rh(III)-catalyzed C–H activation/Brønsted acid-catalyzed intramolecular cyclization allows a facile synthesis of carbazoles from readily available indoles. The reaction proceeds under rather mild reaction conditions with the generation of water and N2 as the only byproducts. Broad substrate scope, excellent functional group tolerance, and high yields were observed. The benzannulation of pyroles for the synthesis of indoles is also feasible using the same protocol.Keywords: Brønsted acid; carbazoles; C−H bond activation; rhodium(III); tandem catalysis

Cp*Rh(III)- and Cp*Ir(III)-catalysed direct C–H arylation with quinone diazides as efficient coupling partners is disclosed. This redox-neutral protocol offers a facile, operationally simple and environmentally benign access to arylated phenols. The reaction represents the first example of Cp*Ir(III)-catalysed C–H direct arylation reaction.

Succession of C–H activation and C–C activation was achieved by using a single rhodium(III) catalyst. Vinylcyclopropanes were used as versatile coupling partners. Mechanistic studies suggest that the olefin insertion step is rate-determining and a facile β-carbon elimination is involved, which represents a novel ring opening mode of vinylcyclopropanes.

A simple and efficient method for the synthesis of diaryl 1,2-diketones has been developed. The reaction represents the first example of diaryl 1,2-diketones that are synthesized directly from arylboronic acids and arylpropiolic acids by a radical pathway in moderate to good yields. This reaction proceeds under mild reaction conditions and with good tolerance of a variety of functional groups. Preliminary mechanistic studies were conducted.

Cp∗Co(III)-catalyzed intermolecular C(sp2)–C(sp3) assembly of (hetero)arenes with α-diazomalonates using a direct C–H functionalization logic was developed. A series of (hetero)arenes underwent alkylation efficiently under the assistance of pyrazolyl and pyrimidyl directing groups under relatively mild and operationally simple reaction conditions. Good functional group tolerance, satisfactory yields, and excellent regioselectivity were found.

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(sp3)–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.

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.

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.

Succession of C–H activation and C–C activation was achieved by using a single rhodium(III) catalyst. Vinylcyclopropanes were used as versatile coupling partners. Mechanistic studies suggest that the olefin insertion step is rate-determining and a facile β-carbon elimination is involved, which represents a novel ring opening mode of vinylcyclopropanes.

A redox-neutral bimetallic Rh(III)/Ag(I) relay catalysis allowed the efficient construction of 3-alkylidene isoindolinones and 3-alkylidene isobenzofuranones. The Rh(III) catalyst was responsible for the C–H monofluoroalkenylation reaction, whereas the Ag(I) salt was an activator for the follow-up cyclization. The methodology developed was applied as a key step in the rapid total synthesis of the natural product aristolactam BII.

Cp*Rh(III)- and Cp*Ir(III)-catalysed direct C–H arylation with quinone diazides as efficient coupling partners is disclosed. This redox-neutral protocol offers a facile, operationally simple and environmentally benign access to arylated phenols. The reaction represents the first example of Cp*Ir(III)-catalysed C–H direct arylation reaction.

A mild and convenient oxidative radical cyclization of aryl alkynoate esters for the synthesis of 3-trifluoromethylthiolated and 3-thiocyanated coumarins has been developed using AgSCF3 and AgSCN as the corresponding radical sources, respectively. This protocol is characterized by readily available starting materials, excellent functional group tolerance and good yields.