Carbenoid Functionalization Research Articles

Rhodium-catalyzed site-selective cross-couplings of indoles and pyridotriazoles through carbene insertion

The switchable cross-coupling of indoles and pyridotriazoles through carbene insertion at C2- or C3-positon has been developed in this paper. This highly site-selective C−H carbenoid functionalization is determined by both the Rh-catalyst species and auxiliary groups. [Cp*RhCl2]2 and coordinating pyrimidyl group direct the C−H carbenoid functionalization to occur at the C2-position, while Rh2OAc4 and non-coordinating benzyl group lead the reaction to occur at the C3-position of the indoles. This regioselective C−H functionalization strategy is of significant importance for the discovery of indole drugs.

Selective Gram-Scale C–H Carbenoid Functionalization of N-Sulfonylarylamides with a Rhodium Catalyst

This work describes an effective Cp*RhIII-catalyzed C-H carbenoid functionalization of N-sulfonylarylamides. Compared to the previous late-stage C-H modification methods of N-sulfonylarylamide analogues, this method efficiently achieves the gram-scale transformation with 2.5 mol % Rh-catalyst loading at 0 °C or with a 0.1 mol % Rh-catalyst loading at room temperature. The reaction medium has a great influence on the reaction rate. Methanol is optimal, and adding a nonpolar solvent (such as toluene or 1,2-dichloroethane) causes the rate to decrease. Experiments and density functional theory calculations were performed to rationalize the mechanism of rate control by a polar medium.

Synthetic and Computational Studies on RhIII-Catalyzed Redox-Neutral Cascade of Carbenoid Functionalization and Dephosphonylative Annulation.

A Rh(III)-catalyzed regioselective redox-neutral cascade process of carbenoid functionalization followed by dephosphonylative annulation of benzoic acids with α-diazo-β-keto phosphonate has been realized, which led to the direct synthesis of a privileged 3-substituted isocoumarin scaffold. To the best of our knowledge, this is the first report of a complete redox neutral method to synthesize isocoumarins using C-H functionalization strategy. In the catalytic cycle of this reaction, there are two possible pathways for the C-C coupling between ortho-positioned carbon atom of benzoic acid and the diazo carbon atom: (i) concerted 1,2-aryl shift and (ii) stepwise metal-carbene formation followed by migratory insertion. DFT study has predicted that the concerted pathway has lower activation energy as compared to the stepwise pathway by 1.5 kcal/mol.

Rh(III)-Catalyzed Csp2-Csp3 σ-Bond Enolation of α-Indolyl Alcohols.

A Rh(III)-catalyzed Csp2-Csp3 σ-bond carbenoid functionalization of α-(2-indolyl)alcohols with acceptor/acceptor diazo compounds has been developed. This transformation provides an efficient strategy to assemble stable C2-enolated indole skeletons via Csp2-Csp3 σ-bond cleavage.

Iridium-catalyzed selective ortho C[sbnd]H carbenoid functionalization of N-aryl-7-azaindoles with diazotized Meldrum’s acid

An iridium-catalyzed selective ortho CH carbenoid functionalization of N-aryl-7-azaindoles with α-diazotized Meldrum’s acid was developed, affording a series of 7-azaindole containing aryl acetates in excellent to good yields. This procedure is simple, mild with high regioselectivity and broad substrate scope.

Cp*RhIII-Catalyzed Sulfonamide-Directed Ortho Arene C-H Carbenoid Functionalization with Pyridotriazoles.

In this Letter, triazoles as carbene reagents were used for sulfonamide-directed C-H insertion carbenoid functionalization to construct benzylpyridine sulfonamide dual-pharmacophore compounds. This method is simple and efficient and can be used for the late-stage modification of sulfonamide drugs.

Rhodium(iii)-catalyzed sulfonamide directed ortho C-H carbenoid functionalization via metal carbene migratory insertion.

A rhodium(iii)-catalyzed sulfonamide directed ortho C-H carbenoid functionalization has been developed with good yields. This method is attractive due to its broad substrate scope, and enables derivation of diverse biologically active sulfonamide structures and late-stage modification of sulfa drugs.

Synthesis of Isoquinoline from Benzimidates via Ru(II)‐Catalyzed C–H Alkylation/Annulations with Diazo Compounds

AbstractA Ru(II)‐catalyzed C–H alkylation/annulations of benzimidate with diazo compounds have been developed for the synthesis of functionalized isoquinoline. The reaction proceeds under mild condition and exhibit broad functional group tolerance. This strategy also provides a direct approach to isoquinolines and 3,4‐dihydrophenanthridin synthesis. Moreover, Ru(II)‐catalyzed C−H carbenoid functionalization of benzimidate with diazodiester is also demonstrated.

Rhodium-Catalyzed Relay Carbenoid Functionalization of Aromatic C-H Bonds toward Fused Heteroarenes.

A rhodium-catalyzed annulation between ethyl benzimidates and α- aroyl sulfur ylides was developed, affording a series of pyrano[4,3,2-ij]isoquinoline derivatives in moderate to good yields with good functional group compatibility. The procedure featured dual ortho-C-H functionalization and dual cyclization in one pot. The optoelectronic properties of those fused heteroarenes were tested by UV/vis and fluorescence spectrometers.

Selective Synthesis of 2- and 7-Substituted Indole Derivatives via Chelation-Assisted Metallocarbenoid C–H Bond Functionalization

Functionally substituted indole derivatives are important intermediates for the synthesis of new potential drug candidates exhibiting strong bioactivities. Over the past few years, significant progress has been made in the direct C–H functionalization of the indole ring through the usage of metal-catalyzed intermolecular cross-coupling with diazo compounds. Directing group strategy provides a unique possibility for selective insertion of carbenes catalytically generated from diazo compounds into challenging indole C2–H and C7–H bonds. This short review summarizes recent advances in carbenoid functionalization of indole derivatives under chelation-controlled metal catalysis.1 Introduction2 Indole C2 Alkylation with α-Diazotized Meldrum’s Acid3 Indole C2 Alkylation with Diazomalonate Derivatives and Related Compounds4 Indole C7 Alkylation with Diazomalonates and Related Compounds5 Tandem Indole C2–H Alkylation/Cyclization6 Indoline C7 Alkylation with Diazomalonates and Related Compounds7 Tandem Indoline C7–H Alkylation/Cyclization8 Conclusion

Synthesis of oxindole from acetanilide via Ir(iii)-catalyzed C-H carbenoid functionalization.

Herein we disclose the first report on the synthesis of oxindole derivatives from acetanilide via Ir(iii)-catalyzed intermolecular C-H functionalization with diazotized Meldrum's acid. A broad range of substituted anilides were found to react smoothly under the Ir(iii)-catalytic system to afford the corresponding N-protected oxindoles. The N-protecting groups, such as Ac, Bz or Piv, can be easily removed to furnish the oxindole. Various synthetic applications of the synthesized oxindole were also demonstrated.

ChemInform Abstract: Ir(III)‐Catalyzed Carbenoid Functionalization of Benzamides: Synthesis of N‐Methoxyisoquinolinediones and N‐Methoxyisoquinolinones.

AbstractDiazotized Meldrum′s acid and various other α‐diazocarbonyl compounds are employed for the carbenoid functionalization of benzamides, heterocyclic amides and aroylamides to give isoquinolinediones, isoquinolinones, and pyridones.

ChemInform Abstract: Rh(III)‐Catalyzed Aromatic C—H Bond Carbenoid Functionalization of Triazenes by α‐Diazomalonate.

Abstract A Rh(III)-catalyzed aromatic C–H bond carbenoid functionalization of triazenes by α-diazomalonates has been developed, with features of mild reaction condition and high efficiency. Furthermore, the functionalized triazenes could be subject to divergent synthesis.

Ir(III)-Catalyzed Carbenoid Functionalization of Benzamides: Synthesis of N-Methoxyisoquinolinediones and N-Methoxyisoquinolinones.

A mild and efficient Ir(III)-catalyzed C-H carbenoid functionalization strategy has been developed to access N-methoxyisoquinolinediones and N-methoxyisoquinolinones. The reaction proceeds efficiently in high yield at room temperature over a broad range of substrates without requirement of any additional oxidants or a base.

Rh(III)-catalyzed relay carbenoid functionalization of aromatic C-H bonds: access to π-conjugated fused heteroarenes.

A novel Rh(III)-catalyzed relay cross-coupling/cyclization cascade between arylketoimines and diazoesters is described. This transformation provides a concise access to unique π-conjugated 1-azaphenalenes (1-APLEs) via a double aryl Csp(2)-H bond carbenoid functionalization process. As illustrative examples, the 1-APLE-based π-conjugated molecules which possess low-lying HOMO levels could be converted to promising organic optoelectronic materials.

Rh(III)-catalyzed aromatic C–H bond carbenoid functionalization of triazenes by α-diazomalonate

A Rh(III)-catalyzed aromatic C–H bond carbenoid functionalization of triazenes by α-diazomalonates has been developed, with features of mild reaction condition and high efficiency. Furthermore, the functionalized triazenes could be subject to divergent synthesis.

ChemInform Abstract: Cu‐Catalyzed Carbenoid Functionalization of Indoles by Methyl 3,3,3‐Trifluoro‐2‐diazopropionate.

AbstractThe title reaction allows the regioselective introduction of CF3 and carboxylate functions into the 2‐ or 3‐position of the indole core.

ChemInform Abstract: Rhodium(III)‐Catalyzed C2‐Selective Carbenoid Functionalization and Subsequent C7‐Alkenylation of Indoles.

AbstractThe first example of a Rh(III)‐catalyzed and alcohol‐mediated direct C2‐selective carbenoid insertion functionalization of indoles (I) using the pyrimidyl function as a directing group is reported.

Cu‐Catalyzed Carbenoid Functionalization of Indoles by Methyl 3,3,3‐Trifluoro‐2‐diazopropionate

AbstractAn efficient protocol for the direct CH‐functionalization of indole and its derivatives has been developed by using Cu(F3‐acac)2‐catalyzed insertion of CF3‐carbene derived from methyl 3,3,3‐trifluoro‐2‐diazopropionate. The reaction proceeds with high regioselectivity within a few minutes under low catalyst loading and allows the introduction of CF3 and carboxylate functions simultaneously into the 3‐ or 2‐position of the indole core. This method can be successfully applied for the synthesis of trifluoromethyl‐containing paullones, which are new members of the known family of potent inhibitors of cyclin‐dependent kinases.

Rhodium(III)-catalyzed C2-selective carbenoid functionalization and subsequent C7-alkenylation of indoles.

Here a new, mild and versatile method for efficient synthesis of a diverse range of 2-acetate substituted indoles via Rh(III)-catalyzed and alcohol-mediated C2-selective carbenoid insertion functionalization of indoles by α-diazotized Meldrum's acid has been developed. Furthermore, for the first time, a Rh(III)/Cu(II)-catalyzed direct C7-alkenylation of such functionalized products has also been demonstrated.