Direct Oxidative Coupling Research Articles

Oxidative cross-dehydrogenative coupling between N-aryl tetrahydroisoquinolins and 5H-oxazol-4-ones through two methodologies: copper catalysis or a metal-free strategy.

A direct oxidative cross-dehydrogenative coupling (CDC) of N-aryl tetrahydroisoquinolins with 5H-oxazol-4-ones catalyzed by CuBr using air as the only oxidant has been developed, which could also proceed smoothly under a metal-free oxidative system with PhI(OAc)2 as the oxidant. A series of alkylated tetrahydroisoquinolin derivatives were obtained in good yields and excellent diastereoselectivities.

ChemInform Abstract: Direct N‐Acylation of Azoles via a Metal‐Free Catalyzed Oxidative Cross‐Coupling Strategy.

The KI-catalyzed N-acylation of azoles via direct oxidative coupling of C-H and N-H bonds has been developed. It could be smoothly scaled up to gram synthesis of acyl azoles. The reaction occurred by the coupling of acyl radicals and azoles to form the acyl azole radical anion, followed by its further oxidation.

Direct Oxidative Coupling of N‐Acetyl Indoles and Phenols for the Synthesis of Benzofuroindolines Related to Phalarine

AbstractInspired by the biogenetic synthesis of benzofuroindoline‐containing natural products, we designed an oxidative coupling between phenol and N‐acetyl indoles. This straightforward and direct radical process, mediated by 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone and FeCl3 allowed the regioselective synthesis of benzofuro[3,2‐b]indolines, whose structure is found in the natural product phalarine.

Direct oxidative coupling of N-acetyl indoles and phenols for the synthesis of benzofuroindolines related to phalarine.

Inspired by the biogenetic synthesis of benzofuroindoline-containing natural products, we designed an oxidative coupling between phenol and N-acetyl indoles. This straightforward and direct radical process, mediated by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and FeCl3 allowed the regioselective synthesis of benzofuro[3,2-b]indolines, whose structure is found in the natural product phalarine.

Propargylamine synthesis via direct oxidative C[sbnd]C coupling reaction between N,N-dimethylanilines and terminal alkynes under metal–organic framework catalysis

MOF-199, a highly porous metal–organic framework based on copper ions, was used as a heterogeneous catalyst for the direct oxidative CC coupling reaction via CH functionalization between N,N-dimethylaniline and phenylacetylene to form N-methyl-N-(3-phenylprop-2-ynyl)benzenamine as the principal product. The copper-catalyzed direct CC coupling transformation could proceed readily, with 96% conversion being achieved after 180min at 120°C in the presence of 5mol% MOF-199 catalyst. The Cu-MOF catalyst could be recovered and reused several times for the direct oxidative CC coupling reaction without a significant degradation in catalytic activity. The MOF-199 exhibited similar activity to other Cu-MOFs such as Cu2(BDC)2(BPY), Cu(BDC), and Cu2(BDC)2(DABCO), while Ni-MOF and Co-MOF were found to be catalytically inactive for the direct oxidative CC coupling reaction. To the best of our knowledge, this transformation using a heterogeneous catalyst was not previously mentioned in the literature.

ChemInform Abstract: Sodium Nitrite‐Catalyzed Aerobic Oxidative Csp2—Csp3 Coupling: Direct Construction of the 4‐Aryldihydroisoquinolinone Moiety.

AbstractA facile protocol using NaNO2 as the catalyst and air as the terminal oxidant enables the synthesis of the title species via direct oxidative intramolecular coupling.

Towards a zero-waste oxidative coupling of nonactivated aromatics by supported gold nanoparticles.

We show that gold nanoparticles are able to perform the direct oxidative coupling of nonactivated aromatics with O2 as the only co-reagent. In this reaction, the aromatic acts both as reactant and solvent. Biphenyl, for example, can be obtained from benzene with high selectivity and a turnover number (TON) of 230 per pass. Similarly, several substituted biaryls can be prepared. Pd performs only one TON and even when a second catalytic functionality is introduced, together with strong acidic conditions, TON is always lower than 100. Other catalysts require iodine for performing the reaction, leading to 2 kg of waste for 1 kg of biphenyl formed, whereas no waste is created by the oxidative coupling with gold nanoparticles.

Sodium Nitrite‐Catalyzed Aerobic Oxidative Csp2Csp3 Coupling: Direct Construction of the 4‐Aryldihydroisoquinolinone Moiety

AbstractA bioinspired approach for the construction of the 4‐aryldihydroisoquinolinone moiety via direct oxidative Csp2Csp3 coupling has been developed, which uses inexpensive sodium nitrite as catalyst and environmentally benign oxygen in the air as terminal oxidant.magnified image

ChemInform Abstract: Rhodium(III)‐Catalyzed Vinylic sp2 C—H Bond Functionalization: Efficient Synthesis of Pyrido[1,2‐α]benzimidazoles and Imidazo[1,2‐α]pyridines.

A simple approach for synthesis of novel aza-fused scaffolds such as pyrido[1,2-α]benzimidazoles and imidazo[1,2-α]pyridines was developed by Rh(III)-catalyzed direct oxidative coupling between alkenes and unactivated alkynes without an extra directing group. The method would allow a broad substrate scope, providing fused heterocycles with potential biological properties.

Syntheses of thiol and selenol esters by oxidative coupling reaction of aldehydes with RYYR (Y = S, Se) under metal-free conditions.

Thiol and selenol esters were synthesized by a direct oxidative coupling reaction of aldehydes with disulfides or diselenides in ethyl acetate under metal-free conditions. Among the oxidants examined, tert-butyl peroxide (TBP) was shown to give the best results. For the substrates with both electron-donating and electron-withdrawing substituents, the reaction proceeded smoothly and gave moderate to good yields. Compared with the previous method, the present route is very simple, atom-economical and environmentally friendly.

Direct N-acylation of azoles via a metal-free catalyzed oxidative cross-coupling strategy

The KI-catalyzed N-acylation of azoles via direct oxidative coupling of C-H and N-H bonds has been developed. It could be smoothly scaled up to gram synthesis of acyl azoles. The reaction occurred by the coupling of acyl radicals and azoles to form the acyl azole radical anion, followed by its further oxidation.

Synthesis of 1,3-dimethyl-3-(p-tolyl)-1H-pyrrolo[3,2-c]pyridin-2(3H)-one by Cu(II)-Mediated Direct Oxidative Coupling

The CuCl2-mediated protocol was extended to the synthesis of 3,3-disubstituted aza-oxindoles. Compounds containing the aza-oxindole structural motif exhibit biological activities such as oral anti-inflammatory activity, and potent TrkA kinase and JAK 3 kinase inhibition. This article discusses the synthesis of 1,3-dimethyl-3-(p-tolyl)-1H-pyrrolo[3, 2-c]pyridine-2,(3H)-one by Cu(II)-mediated direct oxidative coupling. Keywords: N-Methyl-N-(pyridin-4-yl)-2-(p-tolyl)propanamide, 1,3-Dimethyl-3-(p-tolyl)-1H-pyrrolo[3,2-c]pyridin-2(3H)-one, CH coupling reaction, CuCl2 mediated aza-oxindole synthesis

Regioselectivity of the oxidative C-S bond formation in ergothioneine and ovothiol biosyntheses.

Ergothioneine (5) and ovothiol (8) are two novel thiol-containing natural products. Their C-S bonds are formed by oxidative coupling reactions catalyzed by EgtB and OvoA enzymes, respectively. In this work, it was discovered that in addition to catalyzing the oxidative coupling between histidine and cysteine (1 → 6 conversion), OvoA can also catalyze a direct oxidative coupling between hercynine (2) and cysteine (2 → 4 conversion), which can shorten the ergothioneine biosynthetic pathway by two steps.

Metal‐Free Oxidative Coupling: Xanthone Formation via Direct Annulation of 2‐Aryloxybenzaldehyde using Tetrabutylammonium Bromide as a Promoter in Aqueous Medium

AbstractA metal‐free intramolecular annulation of 2‐aryloxybenzaldehydes to xanthones is disclosed, which proceeds through the direct oxidative coupling of an aldehyde CH bond and aromatic CH bonds using tetrabutylammonium bromide (TBAB) as a promoter in aqueous medium. This strategy works smoothly in the presence of both electron‐donating and electron‐withdrawing groups, and displays good tolerance towards catalytically reactive substituents, thus promising further functionalizations of xanthone products.magnified image

Highly efficient iron phthalocyanine catalyzed oxidative synthesis of imines from alcohols and amines

An efficient iron phthalocyanine catalyzed method was developed for direct oxidative coupling of alcohols with amines to afford corresponding imines. The present protocol is applicable to various substituted aromatic and aliphatic alcohols and amines. The reaction is believed to proceed via activation of alcohols by iron phthalocyanines through Lewis acid–base interaction to form aldehydes, which by nucleophilic attack of amines are converted into the corresponding imines.

ChemInform Abstract: Studies on Novel Synthetic Methodologies. Part 233. Pd(OAc)2 Catalyzed C—H Activation of 1,3,4‐Oxadiazoles and Their Direct Oxidative Coupling with Benzothiazoles and Aryl Boronic Acids Using Cu(OAc)2 as an Oxidant.

AbstractThis is the first direct oxidative coupling of 1,3,4‐oxadiazoles with benzothiazoles.

Metal‐Free Oxidative para Cross‐Coupling of Phenols

CC coupling: Direct oxidative coupling reactions are an attractive tool for environmentally benign chemistry. The oxidative biaryl coupling reaction of phenols with various arenes at the para positions with hypervalent iodine reagents may also be included in this category. The reaction proceeds under very mild conditions without metal catalysts in a very short time under ambient conditions (see scheme; HFIP=hexafluoroisopropanol). As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ChemInform Abstract: Rhodium(III)‐Catalyzed Direct Oxidative Cross Coupling at the C5 Position of Chromones with Alkenes.

AbstractThe present cross‐coupling of chromones and flavones with a broad range of alkenes proceeds selectively at the C5 position.

Pd(OAc)2 catalyzed C–H activation of 1,3,4-oxadiazoles and their direct oxidative coupling with benzothiazoles and aryl boronic acids using Cu(OAc)2 as an oxidant

The first direct oxidative coupling of 1,3,4-oxadiazoles with benzothiazoles has been accomplished using Pd(OAc)2 as a catalyst and Cu(OAc)2 as an oxidant. The similar combination of the catalyst and the oxidant has also been applied for direct arylation of 1,3,4-oxadiazoles with aryl boronic acids. Several novel oxadiazole derivatives have been prepared in high yields following both the methods.

Copper(ii) chloride mediated (aza)oxindole synthesis by oxidative coupling of Csp2–H and Csp3–H centers: substrate scope and DFT study

A CuCl2 mediated direct intramolecular oxidative coupling of Csp(2)-H and Csp(3)-H centers gives access to 3,3-disubstituted oxindoles containing aromatic, heteroaromatic and alkyl substituents as well as a heteroatom at the quaternary center in good to excellent yields. The reaction is carried out in the presence of NaOtBu and CuCl2 in DMF at 110 °C. The key step of this reaction is the formation of an amidyl radical by one electron oxidation of amide enolate followed by an intramolecular radical cyclization reaction (homolytic aromatic substitution reaction). A detailed DFT study shows that the cyclization of the amidyl radical is the rate-limiting step in the oxindole synthesis, whereas the second single electron transfer (SET) becomes the rate-determining step in the aza-oxindole formation. Computational data are in agreement with the experimentally observed relative reactivity and regioselectivity.