Rh2(II)-catalyzed intramolecular aliphatic C-H bond amination reactions using aryl azides as the N-atom source

Rhodium(II) dicarboxylate complexes were discovered to catalyze the intramolecular amination of unactivated primary, secondary, or tertiary aliphatic C-H bonds using aryl azides as the N-atom precursor. While a strong electron-withdrawing group on the nitrogen atom is typically required to achieve this reaction, we found that both electron-rich and electron-poor aryl azides are efficient sources for the metal nitrene reactive intermediate.     

Sigma-chelation-directed C-H functionalizations using Pd(II) and Cu(II) catalysts: regioselectivity, stereoselectivity and catalytic turnover

Recent progress in sigma-chelation directed C-H functionalization from the authors' group is described to illustrate the challenges and opportunities in the development of synthetically-useful catalytic reactions involving C-H activation as the key step. Emphasis is placed on strategies for developing catalysis under mild conditions and controlling regio- and stereoselectivity.     

Pd(II)-catalyzed cross-coupling of sp3 C-H Bonds with sp2 and sp3 boronic acids using air as the oxidant

O-Methyl hydroxamic acids, readily available from carboxylic acids, are found to be extremely reactive for beta-C-H activation by Pd(OAc)2. This reactivity is exploited to develop the first example of cross-coupling sp3 C-H bonds with sp3 boronic acids. Air was shown to be a suitable stoichiometric oxidant for the catalytic oxidative coupling reaction. A biologically active natural product is readily converted to its novel analogues through this coupling reaction.     

Synthesis of 1,2- and 1,3-dicarboxylic acids via Pd(II)-catalyzed carboxylation of aryl and vinyl C-H bonds

A Pd(II)-catalyzed reaction protocol for the direct carboxylation of benzoic and phenylacetic acid derivatives to form dicarboxylic acids has been developed. The reaction conditions are also applicable for the carboxylation of vinyl C-H bonds. The first C-H insertion Pd-aryl complex from carboxylic acids has been characterized by X-ray crystallography.     

Chelation-assisted palladium-catalyzed acyloxylation of benzyl sp C-H bonds using PhI(OAc)2 as oxidant

A chelation-assisted palladium-catalyzed acyloxylation of the sp³ C-H bond of benzyl by carboxylic acid is described, which employs PhI(OAc)₂ as a stoichiometric oxidant. The procedure tolerates a series of functional groups, such as methoxyl, chloro, bromo, iodo, vinyl, formyl, phenolic hydroxyl, nitro, and cyano groups, providing the acyloxylation products in moderate to good yields.     

Mizoroki-Heck type reaction of organoboron reagents with alkenes and alkynes. A Pd(II)-catalyzed pathway with Cu(OAc)2 as an oxidant

[reaction: see text]. In contrast to the Pd(0)-catalyzed mechanism by Uemura, Mizoroki-Heck type reaction of boronic acids is found to proceed under a Pd(II)-mediated pathway using a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2 as an oxidant. Treatment of a variety of alkenes with boronic acids, boronates, and sodium tetraphenylborate furnishes beta-arylated and alkenylated products in good to excellent yields. The reactions with norbornene, norbornadiene, and diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.     

Cu(II)-catalyzed C-H (SP3) oxidation and C-N cleavage: base-switched methylenation and formylation using tetramethylethylenediamine as a carbon source

Base-switched methylenation and formylation using tetramethylethylenediamine (TMEDA) as a carbon source have been achieved under mild conditions, catalyzed by CuCl(2), with atmospheric oxygen as oxidant. Bisindolylmethanes, diphenylmethanes and 3-formylindoles were synthesized with excellent regioselectivity and good yield.     

Cu(OAc)2-catalyzed N-arylations of sulfoximines with aryl boronic acids

[reaction: see text] A simple and mild copper salt-catalyzed N-arylation of sulfoximines in high yields is reported. Cu(OAc)(2) activates aryl boronic acids for the reaction with NH-sulfoximines without additional base or heating. Furthermore, this new method allows the preparation of N-arylated sulfoximines, which have previously been more difficult to access.     

Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes

Systematic ligand development has led to the identification of novel mono-N-protected amino acid ligands for Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. A diverse range of organoboron reagents can be used as coupling partners, and the reaction proceeds under mild conditions. These results provide a new retrosynthetic disconnection for the construction of enantioenriched cis-substituted cyclopropanecarboxylic acids.     

Rhodium(II)-catalyzed enantioselective C-H functionalization of indoles

A catalytic, enantioselective method for the C-H functionalization of indoles by diazo compounds has been achieved. With catalytic amounts of Rh(2)(S-NTTL)(4), the putative Rh-carbene intermediates from α-alkyl-α-diazoesters react with indoles at C(3) to provide α-alkyl-α-indolylacetates in high yield and enantioselectivity. From DFT calculations, a mechanism is proposed that involves a Rh-ylide intermediate with oxocarbenium character.     

Iterative multifunctionalization of unactivated C-H bonds in piperidines by way of intramolecular Rh(II)-catalyzed aminations

Efficient stereocontrolled synthesis of di-, tri-, tetra-, and pentasubstituted piperidines from simple 2-sulfamoyloxymethyl piperidine derivatives has been performed by way of intramolecular Rh-catalyzed amination of saturated C-H bonds. In this process, the sulfamoyloxymethyl arm was directly or indirectly involved in the functionalization of every saturated methylene group of the piperidine ring at C-3, C-4, C-5, and C-6. Direct application to the total synthesis of iminosugars and related compounds demonstrated the synthetic potential of this strategy.     

Copper(II)-catalyzed conversion of bisaryloxime ethers to 2-arylbenzoxazoles via C-H functionalization/C-N/C-O bonds formation

A copper(II)-catalyzed conversion of bisaryloxime ethers to 2-arylbenzoxazoles has been developed. The reaction involves a cascade C-H functionalization and C-N/C-O bond formation under oxygen atmosphere.     

Allylic C-H activations using Cu(II) 2-quinoxalinol salen and tert-butyl hydroperoxide

Using a Cu(II) 2-quinoxalinol salen complex as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant, allylic activations of olefin substrates can be converted to the corresponding enones or 1,4-enediones. Excellent yields can be achieved (up to 99%) within a very short reaction time and with great tolerance for additional functional groups. Possible mechanistic pathways have been characterized using Raman spectroscopy, cyclic voltammetry, and theoretical calculations.     

Pd(O)-catalyzed electro-reductive coupling of aryl halides

An efficient electro-reductive coupling of aryl bromides and iodides into biaryls has been performed by the electrolysis with Pd(O)-and/or Pd(II)-catalysts in a DMF-ET₄NOTs-(Pb cathode) system. 4-Bromo-and 2-bromopyridines were also converted into the corresponding bipyridyls, respectively.     

C-H bond functionalizations with palladium(II): intramolecular oxidative annulations of arenes

Oxidative annulations for the synthesis of carbocycles were developed using a catalytic palladium(II) system. Indoles with pendant olefin tethers were oxidatively cyclized to form annulated products. Electron-rich aromatic systems were also investigated, culminating in the synthesis of benzofurans and dihydrobenzofurans by a similar protocol. These reactions were demonstrated to proceed by an initial C-H bond functionalization event, followed by olefin insertion and β-hydride elimination.     

Rhodium(III)-catalyzed intermolecular direct amination of aromatic C-H bonds with N-chloroamines

A Rh(III)-catalyzed direct aromatic C-H amination is achieved using N-chloroamines as a reagent. Furthermore, we also developed a one-pot amination protocol involving in situ chlorination of the secondary amines. The catalytic amination operates at mild conditions with excellent functional group tolerance and regioselectivity.     

Cu(II)-catalyzed oxidation of sulfides

A variety of sulfides and disulfides were converted into the corresponding sulfoxide derivatives with 70% t-BuOOH (water) as the oxidant in the presence of catalytic quantity of CuBr₂. The method described does not involve cumbersome work-up, has wide range of applicabilities, exhibits chemoselectivity, and proceeds under mild reaction conditions, and the resulting products are obtained in good yields within reasonable time.     

Nickel(0)-catalyzed Heck cross-coupling via activation of aryl C-OPiv bonds

Using a Ni(dppf) catalyst generated in situ, Heck cross-coupling of aryl pivalates with a variety of olefin partners has been accomplished. This method represents one of the first examples of a C-C cross-coupling via activation of a strong C-O bond with a nonorganometallic coupling partner. It enables the transformation of phenol-based substrates into styrenyl products without generation of a halogenated byproduct or the use of expensive triflate groups.