Metal-free Oxidative Coupling Research Articles

Synthesis of sulfonated naphthols via metal-free oxidative coupling of beta-tetralones and sodium sulfinates

The efficient synthesis of sulfonated naphthols was realized by dehydroaromatization of β-tetralones with sodium sulfinates under metal-free conditions. Iodine-containing reagents played an important role in this oxidative coupling process. Sodium sulfinates served as a stable and readily available sulfur source, providing sulfones in good to excellent yields. A wide range of functional groups were well tolerated in this reaction.

Metal-free oxidative coupling of aryl acetylene with elemental sulphur and amines: facile access to α-ketothioamides.

A simple and efficient oxidative coupling of aromatic alkynes with elemental sulphur and secondary amines has been reported. The iodine/DMSO system easily promoted the transformations, affording thioglyoxamides via C-S, C-O, and C-N bond formations. In this context, acetylenic C-H bond oxidation has occurred through iodination, leading to the desired products. Moreover, this metal-free, one-pot protocol is accomplished by using readily available starting materials, without external oxidants, and under aerobic conditions, providing a variety of α-ketothioamide compounds in moderate to good yields.

Metal-free photocatalysis at charged aqueous interfaces: boosting the photocatalytic oxidative coupling of arylamines to azoaromatics under ambient conditions

We have developed a sustainable metal-free photocatalytic oxidative coupling approach for the conversion of arylamines to azoaromatics at the charged aqueous interfaces of micelles under ambient air atmosphere in aqueous media.

Donor–Acceptor Type Conjugated Microporous Polymer as a Metal-Free Photocatalyst for Visible-Light-Driven Aerobic Oxidative Coupling of Amines

Developing cheap, highly efficient, metal-free heterogeneous photocatalysts remain a great challenge in photoredox reactions. Herein, we utilize a typical Suzuki coupling of low-cost triphenylamine derivative and 9,10-dibromoanthracene to synthesis a donor–acceptor type conjugated microporous polymer (denoted as PAA-CMP). As expected, heterogeneous PAA-CMP exhibits excellent photocatalytic performance, good functional group tolerance and satisfying recyclability in metal-free aerobic oxidative coupling of amines to imines driven by visible light, which is due to its absolute energy level positions and good physicochemical stability. More excitingly, PAA-CMP can enable the gram-scale air-oxidized photocatalytic conversion under natural sunlight irradiation, yielding the desired imine product with an isolated yield of 65% for 48 h. The current work provides a great application prospect for CMPs in low-cost and large-scale organic industrial production in the future. The prepared donor-acceptor (D-A) type conjugated microporous polymer (PAA-CMP) as a metal-free and heterogeneous photocatalyst enable the gram-scale air-oxidized photocatalytic conversion of benzylamine into N-benzylidenebenzylamine under natural sunlight irradiation, yielding the desired imine product with an isolated yield of 65%.

Transition-Metal-Free Strategies for the Synthesis of C-1 Aryl-Substituted Tetrahydroisoquinolines

Abstract1-Aryl-1,2,3,4-tetrahydroisoquinolines are important structural motifs and are widely found in bioactive molecules, pharmaceuticals and synthetic drugs. In view of increasing environmental awareness, the development of transition-metal-free strategies for the synthesis of these compounds is highly desirable. Metal-free oxidative coupling and lithiation methodologies have emerged as effective tools in this area as they exclude the use of transition-metal catalysts and help in reducing unwanted and toxic-metal-based chemical waste in the environment. This review highlights recent advances on the direct arylation of tetrahydroisoquinolines for the synthesis of the title compounds in the absence of a metal salt. Also, the emphasis has been placed on mechanistic considerations of these reactions.1 Introduction2 Arylation of Tetrahydroisoquinolines via Oxidative Coupling2.1 Arylation Using Grignard Reagents2.2 Arylation Using Other Organometallic Reagents2.3 Arylation Using Aryl Organoboranes or Arenes3 Arylation of Tetrahydroisoquinolines via Lithiation3.1 Intermolecular Arylation3.2 Intramolecular Arylation4 Conclusion and Outlook

Oxidative cross-dehydrogenative coupling between iodoarenes and acylanilides for C–N bond formation under metal-free conditions

A metal-free oxidative cross-dehydrogenative coupling between iodoarenes and acylanilides was developed. It gave highly para-selectivie C–N coupling products with the retention of iodine atom which enables further transformations.

Correction: Metal-free oxidative coupling of arylmethylamines with indoles: a simple, environmentally benign approach for the synthesis of 3,3′-bis(indolyl)methanes

Correction for ‘Metal-free oxidative coupling of arylmethylamines with indoles: a simple, environmentally benign approach for the synthesis of 3,3′-bis(indolyl)methanes” by Vikas D. Kadu et al., RSC Adv., 2020, 10, 23254–23262, DOI: 10.1039/D0RA03221B.

Synthetic approaches to biologically active xanthones: an update

Many xanthone structures show promising biological activities. Accordingly, a breadth of synthetic strategies toward xanthone derivatives have been developed. This review surveys these methods published from 2013 to 2019, and in an integrated manner details the biological activities of key xanthone structures. The review highlights the synthesis of xanthones via the classical and the modified Grover, Shah, and Shah reaction; the use of ytterbium, palladium, ruthenium, copper catalysis; the use of chromen-4-ones as building blocks; the use of the Friedel–Crafts reaction; Ullmann-ether coupling; metal-free oxidative coupling; intermolecular and intramolecular couplings; xanthone synthesis via the intermolecular Diels–Alder reaction; a novel decarboxylative aminocatalytic strategy; use of the Michael reaction, and the use of the Knoevenagel–Michael, Michael/Michael, Michael/Henry cycloadditions; and [4+2] cycloaddition.

Metal-free oxidative coupling of arylmethylamines with indoles: a simple, environmentally benign approach for the synthesis of 3,3'-bis(indolyl)methanes.

The efficient metal-free oxidative coupling of arylmethylamines with indoles has been developed using molecular oxygen as a green oxidant. The present reaction provides a novel route towards the synthesis of 3,3′-bis(indolyl)methanes in excellent yields of up to 95% via C–C and C–N bond formation. This attractive and environmentally friendly one-pot protocol is a simple procedure that features inexpensive acetic acid as the catalyst and molecular oxygen as the sole oxidant, and it supports a wide substrate scope with the good tolerance of functional groups.

Metal-free oxidative coupling of alkyl chlorides with thiols: An efficient access to sulfoxides

An efficient and step-economical access to sulfoxides from thiols and alkyl halides in the presence of I2O5 and DBU via direct oxidative couplings is described here. It is the first case that combined Williamson sulfide synthesis and subsequent sulfide oxidation into one step manipulation for sulfoxides preparation. This protocol features wide substrate scope, mild and metal-free conditons, the use of naturally abundant starting materials and avoidance of over-oxidation.

From Isocyanides to Iminonitriles via Silver-mediated Sequential Insertion of C(sp3)-H Bond.

SummaryHeterocycles are prevalent constituents of many marketing drugs and biologically active molecules to meet modern medical challenges. Isocyanide insertion into C(sp3)–H bonds is challenging especially for the construction of quaternary carbon centers. Herein, we describe an efficient strategy for the synthesis of α-iminonitrile substituted isochromans and tetrahydroisoquinolines (THIQs) with quaternary carbon centers through silver-triflate-mediated sequential isocyanide insertion of C(sp3)–H bonds, where isocyanide acts as the crucial “CN” and “imine” sources. The produced α-iminonitriles have extensive applications as valuable synthetic building blocks for pharmacologically interesting heterocycles. This protocol could be further applied for the synthesis of iminonitrile-decorated phenanthridines and azapyrene. Interestingly, a remarkable aggregation-induced emission (AIE) effect was first observed for an iminonitrile-decorated pyrene derivative, which may open a particular area for iminonitrile applications in materials science.

Metal-Free Oxidative Coupling of Tetrahydroisoquinolines and 3-Fluorooxindoles on Water

An efficient, metal-free oxidative coupling of tetrahydroisoquinolines and 3-fluorooxindoles on water has been developed. Using aqueous tert-butyl hydroperoxide as the oxidant, Et3N as the base, and water as the sole solvent, a variety of 3-fluorooxindoles fully substituted at the 3-position and containing a tetrahydroisoquinoline fragment has been successfully prepared in yields of up to 93% with an anti/syn stereo­selectivity of up to 99:1 under very mild and safe reaction conditions.

Iodine/potassium iodide catalyst for the synthesis of trifluoromethylated quinazolines via intramolecular cyclization of 2,2,2-trifluoro-N-benzyl-N'-arylacetimidamides.

An efficient and simple protocol for the synthesis of trifluoromethylated quinazolines has been described by I2-/KI-promoted oxidative C(sp3)-C(sp2) bond under the optimal oxidative cyclization reaction conditions. The required 2,2,2-trifluoro-N-benzyl-N'-arylacetimidamides are readily prepared from the corresponding acetimidoyl chlorides and benzylamines under a nucleophilic substitution reaction in the form of in situ. The merits of this protocol are the use of inexpensive molecular iodine, metal-free oxidative coupling and good to excellent yields.

Metal-free oxidative cross-dehydrogenative coupling of quinones with benzylic C(sp3)-H bonds.

A metal-free cross-dehydrogenative coupling of quinones with toluene derivatives has been established. A series of quinones were subjected to reaction with toluene derivatives in the presence of di-tertbutyl peroxide (DTBP) for direct synthesis of benzylquinones. The method exhibits good functional group tolerance, and desired products were obtained in moderate to good yields. Meanwhile, a radical pathway was proposed to describe the cross-dehydrogenative coupling of quinones with toluene derivatives.

Oxidative, Iodoarene-Catalyzed Intramolecular Alkene Arylation for the Synthesis of Polycyclic Aromatic Hydrocarbons.

A catalytic, metal-free and chemoselective oxidative intramolecular coupling of arene and alkene C-H bonds is reported. The active hypervalent iodine (HVI) reagent, generated catalytically in situ from iodotoluene and meta-chloroperoxybenzoic acid (m-CPBA), reacts with o-vinylbiphenyls to generate polyaromatic hydrocarbons in up to 95 % yield. Experimental evidence suggests the reactions proceed though vinyliodonium and, possibly, vinylenephenonium intermediates.

The efficient synthesis of Hantzsch 1,4-dihydropyridines via metal-free oxidative C[sbnd]C coupling by HBr and DMSO

A novel and efficient synthesis of Hantzsch 1,4-dihydropyridines through metal-free oxidative CC coupling process was described. The reaction between benzylic alcohols, 1,3-dicarbonyl compounds and ammonium hydroxide in the presence of HBr in DMSO at 75 °C led to afford 1,4-dihydropyridine in excellent yields. This protocol introduces the use of benzyl alcohols instead of aldehydes as a new modification of the Hantzsch reaction.

Construction of 3,4-Dihydroisoquinolinones and Indanones via DTBP-Promoted Oxidative Coupling of N-Allylbenzamides with Aromatic Aldehydes.

A metal-free oxidative tandem coupling of N-allylbenzamide with aryl aldehydes was realized. This method allowed the 1,2-difunctionalization of the C═C double bond in N-allylbenzamides through simultaneous formation of two C(sp2)-C(sp3) bonds. In the presence of DTBP, 4-substituted 3,4-dihydroisoquinolin-1(2 H)-ones were obtained in satisfactory isolated yields. 3-Substituted indanones could also be formed by varying the structures of the starting materials.

Metal-Free Oxidative Cross Coupling of Indoles with Electron-Rich (Hetero)arenes.

A new method for the synthesis of bi-heteroaryls is reported, based on the umpolung of indoles with benziodoxol(on)e hypervalent iodine reagents (IndoleBX). The oxidative coupling of IndoleBX with an equimolar amount of electron-rich benzenes, indoles, pyrroles, and thiophenes proceeded under mild transition-metal-free conditions. Functionalized non-symmetrical bi-indolyl heterocycles were accessed efficiently. Introduction of a new type of C2-substituted indole benziodoxole reagents further allowed extending the scope of the reaction to NH unprotected and C3-alkylated indoles. The obtained bi-heterocycles are important building blocks in synthetic and medicinal chemistry, and could be easily transformed into more complex heterocyclic systems.

Metal-free oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes leading to 3-acylated quinoxalin-2(1H)-ones

A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes has been developed under metal-free conditions. This method provided a convenient and efficient approach to various 3-acylated quinoxalin-2(1H)-ones from readily available starting materials with excellent regioselectivity. This reaction proceeded efficiently under mild conditions over a broad range of substrates and with functional group tolerance.

I2/TBHP-Promoted Approach to α-Keto Esters from Trifluoromethyl β-Diketones and Alcohols via C–C Bond Cleavage

A metal-free oxidative coupling reaction of trifluoromethyl β-diketones with alcohols for the synthesis of α-keto esters in good to excellent yields has been developed. Preliminary mechanistic studies suggest that an I2/TBHP promoted sequential iodination, C–C bond cleavage, C–O bond formation and oxidation pathway is involved in this reaction.