Homolytic Aromatic Substitution Research Articles

Ligand-controlled chemoselectivity in potassium tert-amylate-promoted direct C–H arylation of unactivated benzene with aryl halides

Direct C–H arylation of unactivated benzene with aryl halides under various simple ligands (EDA, DMEDA, ethylene glycol, etc.) in the presence of potassium tert-amylate (t-AmOK) base at mild temperature (80 °C) have been developed. This transition-metal-free radical cross-coupling offers an efficient way to synthesize various biaryls in good yields through base-promoted homolytic aromatic substitution. And mechanistic investigations have provided insight into the chemoselectivity of couplings between haloiodobenzenes and benzene and showed that phenanthroline and its derivatives not only initiate these radical reactions like most of other ligands (EDA, DMEDA, ethylene glycol, etc.), but also participate in the electron transfer process of biaryl radical anion intermediates.

ChemInform Abstract: 9‐Silafluorenes via Base‐Promoted Homolytic Aromatic Substitution (BHAS) — The Electron as a Catalyst.

AbstractThe reaction proceeds efficiently for diphenyl substituted silanes, but not for dialkyl substituted silanes.

Synthesis of 3,3-disubstituted oxindoles from anilines nitrosated in situ: a radical-promoted reaction of aromatic amines with N-arylacrylamides

A mild and efficient synthesis of 3,3-disubstituted oxindoles is achieved. The corresponding diazonium salts are generated in situ from aromatic amines before these salts undergo a homolytic bond cleavage to produce the aryl radicals. Various oxindoles are obtained by homolytic aromatic substitution and radical cyclization. This procedure is an alternative method to oxindole synthesis.

Potassium ethoxide/phenanthroline promoted chemoselective direct C–H arylation of unactivated arenes with aryl iodides

Simple and cheap potassium ethoxide (EtOK) and a catalytic amount of phenanthroline can efficiently promote the direct C–H arylation of unactivated arenes with aryl iodides at 80 °C. This transition-metal-free base-promoted homolytic aromatic substitution offers a chemoselective approach to synthesize biaryls bearing active halo substituents (I, Br, Cl, etc.) in good yields.

CuBr/proline‐catalyzed cross‐coupling of unactivated benzene with aryl halides

Direct CH arylation of unactivated benzene with aryl halides was achieved using a readily available copper catalyst. The reaction was carried out at 80 °C, using CuBr as catalyst, proline as ligand and t‐BuOK as base. This radical cross‐coupling reaction between unactivated benzene and aryl iodides proceeds via homolytic aromatic substitution and offers an efficient method for the synthesis of various biaryls in good to excellent yields. Copyright © 2015 John Wiley & Sons, Ltd.

ChemInform Abstract: Base‐Promoted Dehydrogenative Coupling of Benzene Derivatives with Amides or Ethers.

AbstractBenzene derivatives, e.g. (I), (V), (IX), and (XIII), bearing electron‐withdrawing groups as well as aromatic hydrocarbons, such as (XVI) and (XVIII), are introduced into the dehydrogenative coupling via homolytic aromatic substitution.

Visible‐Light‐Promoted Iminyl‐Radical Formation from Acyl Oximes: A Unified Approach to Pyridines, Quinolines, and Phenanthridines

AbstractA unified strategy involving visible‐light‐induced iminyl‐radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac‐[Ir(ppy)3] as a photoredox catalyst, the acyl oximes were converted by 1 e− reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N‐containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible‐light‐induced iminyl‐radical formation was successfully applied to a five‐step concise synthesis of benzo[c]phenanthridine alkaloids.

Visible-light-promoted iminyl-radical formation from acyl oximes: a unified approach to pyridines, quinolines, and phenanthridines.

A unified strategy involving visible-light-induced iminyl-radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac-[Ir(ppy)3 ] as a photoredox catalyst, the acyl oximes were converted by 1 e(-) reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N-containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible-light-induced iminyl-radical formation was successfully applied to a five-step concise synthesis of benzo[c]phenanthridine alkaloids.

ChemInform Abstract: Silver‐Catalyzed 2‐Isocyanobiaryls Insertion/Cyclization with Phosphine Oxides: Synthesis of 6‐Phosphorylated Phenanthridines.

Abstract A silver-catalyzed 2-isocyanobiaryls insertion/cyclization with phosphine oxides was described for the construction of the 6-phosphorylated phenanthridines through radical addition of in situ formed P-centered radical to 2-isocyanobiphenyls and homolytic aromatic substitution process. The reactions could proceed smoothly to give the desired 6-phosphorylated phenanthridines promoted by AgOAc (20 mol %) with PhI(OAc)2 (3.0 equiv).

Preparation of phenanthrenes from ortho-amino-biphenyls and alkynes via base-promoted homolytic aromatic substitution.

A transition-metal-free phenanthrene synthesis starting from readily accessible ortho-amino-biaryls is presented. The biarylamines are in situ transformed into the corresponding diazonium salts which upon single electron reduction give the corresponding aryl radicals. Addition to an alkyne and subsequent base promoted homolytic aromatic substitution (BHAS) provide phenanthrenes in moderate to good yields.

Metal-free oxidative decarbonylative coupling of aromatic aldehydes with arenes: direct access to biaryls.

A metal-free oxidative decarbonylative coupling of aromatic aldehydes with electron-rich or electron-deficient arenes to produce biaryl compounds was developed. This novel coupling was proposed to proceed via a non-chain radical homolytic aromatic substitution (HAS) type mechanism, based on the substrate scope, ortho-regioselectivity, radical trapping experiments and DFT calculation studies. With the ready availability of aromatic aldehydes and arenes, metal-free conditions should make this coupling attractive for the biaryl synthesis.

Multi-bond forming and iodo-selective base-promoted homolytic aromatic substitution

Base-promoted homolytic aromatic substitution (BHAS) has been applied as a means to effect multi-bond forming reactions.

Formal base-free homolytic aromatic substitutions via photoredox catalysis

We developed a simple and convenient method to assemble biaryls exploiting a photoredox catalyst and visible light.

9-Silafluorenes via base-promoted homolytic aromatic substitution (BHAS)--the electron as a catalyst.

Transition-metal-free intramolecular radical silylation of 2-diphenylsilylbiaryls via base-promoted homolytic aromatic substitution (BHAS) to give 9-silafluorenes is reported. 2-Diphenylsilylbiaryls are readily prepared, and cross dehydrogenative silylation occurs with tert-butylhydroperoxide (TBHP) as a cheap stoichiometric oxidant in the presence of a small amount of tetrabutylammonium iodide (TBAI) as an initiator. These cyclizations are catalyzed by the electron.

Consecutive Aromatic Carbon–Fluorine Bond and Carbon–Hydrogen Bond Activations by Iridium Porphyrins

Consecutive aromatic C–F bond and C–H bond activations of aryl fluorides were achieved by iridium porphyrins to initially give aryl and finally fluoroaryl iridium porphyrins. The C–F bond activation product is generated first, which is the precursor for the C–H bond activation. Both experimental and theoretical results support that the C–F bond is cleaved by iridium porphyrin anion through nucleophilic aromatic substitution, and the C–H bond cleavage is through homolytic aromatic substitution by iridium porphyrin radical followed by hydrogen atom abstraction. Moreover, the meta-fluorophenyl iridium porphyrin is the most thermodynamic stable regioisomers.

ChemInform Abstract: An Approach to 6‐Trifluoromethyl‐phenanthridines Through Visible‐Light‐Mediated Intramolecular Radical Cyclization of Trifluoroacetimidoyl Chlorides.

A mild and efficient visible light-mediated intramolecular radical cyclization of trifluoroacetimidoyl chlorides is developed for the synthesis of 6-(trifluoromethyl)phenanthridine derivatives. The reaction involves the generation of radical intermediates from C(sp2)–Cl bonds and a homolytic radical aromatic substitution (HAS) process.

ChemInform Abstract: Arylative Cyclization of 2‐Isocyanobiphenyls with Anilines: One‐Pot Synthesis of 6‐Arylphenanthridines via Competitive Reaction Pathways.

A transition-metal-free method for the synthesis of C6 phenanthridine derivatives by arylative cyclization of 2-isocyanobiphenyls with arylamines in one pot was developed. Mechanistic studies suggest that electrophilic aromatic substitution (SEAr) of a nitrilium intermediate and homolytic aromatic substitution (HAS) of an imidoyl radical intermediate are two competitive reaction pathways involved in the annulation step.

A Direct CH Arylation of Unactivated Arenes Promoted by Mixed Potassium Alkoxides

AbstractAn intermolecular CH arylation of unactivated arenes with aryl iodides is made viable through a transition‐metal‐free approach. This simple and efficient process obviates the common use of diamines or diols as the promoters. With the aid of only mixed potassium alkoxides, a number of unactivated arene CH bonds can be directly arylated through a homolytic aromatic substitution (HAS) pathway.

P-Toluenesulfonohydrazide as highly efficient initiator for direct C-H arylation of unactivated arenes.

p-Toluenesulfonohydrazide (PTSH) was shown to promote the highly efficient direct arylation of unactivated arenes with aryl iodides, bromides, or chlorides in the presence of potassium tert-butoxide without the assistance of any transition metals. The reaction proceeds through base-promoted homolytic aromatic substitution (BHAS) involving aryl radicals and arylradical anions as intermediates.

The electron is a catalyst.

The electron is an efficient catalyst for conducting various types of radical cascade reaction that proceed by way of radical and radical ion intermediates. But because electrons are omnipresent, catalysis by electrons often passes unnoticed. In this Review, a simple analogy between acid/base catalysis and redox catalysis is presented. Conceptually, the electron is a catalyst in much the same way that a proton is a catalyst. The 'electron is a catalyst' paradigm unifies mechanistically an assortment of synthetic transformations that otherwise have little or no apparent relationship. Diverse radical cascades, including unimolecular radical substitution reactions (SRN1-type chemistry), base-promoted homolytic aromatic substitutions (BHAS), radical Heck-type reactions, radical cross-dehydrogenative couplings (CDC), direct arene trifluoromethylations and radical alkoxycarbonylations, can all be viewed as electron-catalysed reactions.