Ketone formation via mild nickel-catalyzed reductive coupling of alkyl halides with aryl acid chlorides

The present work highlights unprecedented Ni-catalyzed reductive coupling of unactivated alkyl iodides with aryl acid chlorides to efficiently generate alkyl aryl ketones under mild conditions.     

Carbonylative cross-coupling of ortho-disubstituted aryl iodides. convenient synthesis of sterically hindered aryl ketones

A mild and general protocol for the carbonylative cross-coupling of sterically hindered ortho-disubstituted aryl iodides is reported. Carbonylative Suzuki-Miyaura couplings of a variety of aryl boronic acids provide an array of substituted biaryl ketones in modest to excellent yield. A carbonylative Negishi coupling that utilizes alkynyl nucleophiles is also described.     

Ruthenium-catalyzed functionalization of aryl carbon-oxygen bonds in aromatic ethers with organoboron compounds

The ruthenium-catalyzed reaction of aryl ethers having a carbonyl group at the ortho position to the ether group with organoboronates (R-B(OCH2CMe2CH2O), R = aryl, alkenyl, and alkyl) resulted in site-selective C-C bond formation. Among the transition metal complexes screened, the RuH2(CO)(PPh3)3 complex showed the highest activity. Several aromatic ketones having methoxy or phenoxy groups at the ortho position can also be used in this coupling reaction. A variety of arylboronates containing electron-donating (NMe2, OMe, methyl, and vinyl) and -withdrawing (F and CF3) groups reacted with methoxy ketones to give the corresponding coupling products in high yields.     

Ligand‐free Pd/Cu‐catalyzed decarboxylative coupling of aryl iodides with α‐oxocarboxylates

This paper describes a palladium/copper‐catalyzed decarboxylative coupling of aryl iodides with α‐oxocarboxylates. The cross‐coupling reaction gives high chemical yields of aryl ketones and has wide functional group tolerance, making the transformation an attractive alternative to the traditional cross‐coupling approaches for aryl ketones. Copyright © 2014 John Wiley & Sons, Ltd.     

Unsymmetrical diaryl sulfones through palladium-catalyzed coupling of aryl iodides and arenesulfinates

[reaction: see text] The palladium-catalyzed coupling of aryl iodides and arenesulfinates provides a simple and extremely efficient new route to unsymmetrical diaryl sulfones, usually isolated in high yield. The reaction tolerates a variety of functionalized aryl iodides, including those containing ether, ester, and nitro groups. The best results have been obtained by using Pd(2)(dba)(3), Xantphos, Cs(2)CO(3), and (n)Bu(4)NCl in toluene at 80 degrees C.     

An efficient intermolecular BINAM-copper(I) catalyzed Ullmann-type coupling of aryl iodides/bromides with aliphatic alcohols

A wide range of alkyl aryl ethers are synthesized from the corresponding aryl iodides and aliphatic alcohols through Ullmann-type intermolecular coupling reactions in the presence of a catalytic amount of easily available BINAM-CuI complex. Less reactive aryl bromides have also been shown to react with aliphatic alcohols under identical reaction conditions to give good yields of the alkyl aryl ethers without increasing the reaction temperature and time.     

Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and alkyl halides

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.     

Palladium-catalyzed synthesis of aryl ketones by coupling of aryl bromides with an acyl anion equivalent

Palladium-catalyzed couplings of aryl bromides with N-tert-butylhydrazones as acyl anion equivalents to form aryl ketones are reported. The coupling process occurs at the C-position of hydrazones to form N-tert-butyl azo compounds. Isomerization of these azo compounds to the corresponding hydrazones, followed by hydrolysis, gave the desired mixed alkyl aryl ketones. The selectivity of C- versus N-arylation was strongly influenced by the substituent on nitrogen. Arylation at carbon occurred with N-tert-butylhydrazones, whereas N-arylation occurred with N-arylhydrazones. The arylation of hydrazones containing primary and secondary alkyl groups, as well as aryl groups, gave the desired ketones in good yields after hydrolysis. Functional groups on the aromatic ring, such as alkoxy, cyano, trifluoromethyl, carboalkoxy, carbamoyl, and keto groups, were tolerated. This reaction likely occurs by C-C bond-forming reductive elimination from an intermediate containing an eta1-diazaallyl ligand.     

Pd-catalyzed carbonylative reactions of aryl iodides and alkynyl carboxylic acids via decarboxylative couplings

Alkynyl carboxylic acids reacted with aryl iodides under a CO atmosphere in the presence of a palladium catalyst to produce α,β-alkynyl aryl ketones in good yields. The maximum turnover number was 16?800. The desired carbonylative coupling was formed from phenyl propiolic acid without any formation of a noncarbonylative coupling product in the absence of CuI. However, the reaction with alkyl-substituted alkynyl carboxylic acids required CuI as a cocatalyst for high yield.     

Catalysis of Kumada-Tamao-Corriu coupling by a (POCOP)Rh pincer complex

A pincer-based (P(O)C(O)P)Rh catalyst is demonstrated to be an active and well-defined catalyst for the coupling of select aryl and alkyl Grignards with aryl iodides. The proposed intermediacy of oxidative addition of aryl halides to (P(O)C(O)P)Rh(I) is supported by the isolation of the oxidative addition product.     

Direct acylation of aryl bromides with aldehydes by palladium catalysis

A new protocol for the direct acylation of aryl bromides with aldehydes is established. It appears to involve palladium-amine cooperative catalysis, affording synthetically important alkyl aryl ketones in moderate to excellent yields in a straightforward manner, and broadening the scope of metal-catalyzed coupling reactions.     

Mild ketone formation via Ni-catalyzed reductive coupling of unactivated alkyl halides with acid anhydrides

Ni-catalyzed ketone formation through mild reductive coupling of a diverse set of unactivated alkyl bromides and iodides with particularly aryl acid anhydrides was successfully developed using zinc as the terminal reductant. These conditions also allow direct coupling of alkyl iodides with aryl acids in the presence of Boc(2)O and MgCl(2).     

NiCl(2)(dppe)-catalyzed cross-coupling of aryl mesylates, arenesulfonates, and halides with arylboronic acids

An investigation of the NiCl(2)(dppe)-, NiCl(2)(dppb)-, NiCl(2)(dppf)-, NiCl(2)(PCy(3))(2)-, and NiCl(2)(PPh(3))(2)-catalyzed cross-coupling of the previously unreported aryl mesylates, and of aryl arenesulfonates, chlorides, bromides, and iodides containing electron-withdrawing and electron-donating substituents with aryl boronic acids, in the absence of a reducing agent, is reported. NiCl(2)(dppe) was the only catalyst that exhibited high and solvent-independent activity in the two solvents investigated, toluene and dioxane. NiCl(2)(dppe) with an excess of dppe, NiCl(2)(dppe)/dppe, was reactive in the cross-coupling of electron-poor aryl mesylates, tosylates, chlorides, bromides, and iodides. This catalyst was also efficient in the cross-coupling of aryl bromides and iodides containing electron-donating substituents. Most surprisingly, the replacement of the excess dppe from NiCl(2)(dppe)/dppe with excess PPh(3) generated NiCl(2)(dppe)/PPh(3), which was found to be reactive for the cross-coupling of both electron-rich and electron-poor aryl mesylates and chlorides. Therefore, the solvent-independent reactivity of NiCl(2)(dppe) provides an inexpensive and general nickel catalyst for the cross-coupling of aryl mesylates, tosylates, chlorides, bromides, and iodides with aryl boronic acids.     

Practical one-pot preparation of ketones from aryl and alkyl bromides with aldehydes and DIH via Grignard reagents

Various diaryl ketones, alkyl aryl ketones, and dialkyl ketones were efficiently prepared in good yields by the reactions of the Grignard reagents derived from aryl or alkyl bromides, followed by the reactions with aromatic or aliphatic aldehydes and the subsequent treatment with 1,3-diiodo-5,5-dimethylhydantoin and K₂CO₃, in a one-pot method. The same treatment of aromatic bromides bearing electron-withdrawing groups, such as ester, nitrile, ketone, and nitro groups with i-PrMgCl·LiCl or PhMgCl instead of Mg, also provided the corresponding diaryl and alkyl aryl ketones in good yields. The above methods are simple and practical transition-metal-free methods for the preparation of various diaryl ketones and alkyl aryl ketones bearing electron-rich aromatic groups and electron-deficient aromatic groups, as well as dialkyl ketones.     

Palladium-catalyzed cascade reaction of alpha,beta-unsaturated sulfones with aryl iodides

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions (Pd(OAc)(2) as catalyst, Ag(2)CO(3) as base in DMF at 120 (0)C) takes place mainly by a cascade process, involving one unit of the alkene and three units of the aryl iodide, to afford a substituted 9-phenylsulfonyl-9,10-dihydrophenanthrene. The dominant formation of this 3:1 coupling product, instead of the Heck trisubstituted olefin, shows that aromatic C-H bond activation processes can compete with the usually fast syn beta-hydrogen elimination step in the Heck arylation of an acyclic olefin. The structural scope of this palladium-catalyzed cascade arylation of alpha,beta-unsaturated sulfones has proved to be wide with regard to substitution at the beta-position (alkyl, aryl, or alkenyl substitution), substitution at the sulfone unit (alkyl or phenyl sulfones), and configuration at the CdoublebondC bond (trans or cis). Moreover, although less favored than in the case of the arylation of alpha,beta-unsaturated sulfones, similarly substituted 9,10-dihydrophenanthrenes have also been obtained in the case of alpha,beta-unsaturated phosphine oxides and alpha,beta-unsaturated phosphonate esters. A Pd(0)-Pd(II)-Pd(IV) mechanistic pathway involving the successive formation of highly electrophilic sigma-alkylpalladium intermediates and palladacycles is proposed for this multicomponent arylation.     

Pd-catalyzed copper-free carbonylative Sonogashira reaction of aryl iodides with alkynes for the synthesis of alkynyl ketones and flavones by using water as a solvent

The Pd-catalyzed copper-free carbonylative Sonogashira coupling reaction to synthesize alkynyl ketones from terminal alkynes and aryl iodides was achieved by using water as a solvent. The reaction was carried out at room temperature under balloon pressure of CO with Et(3)N as a base. The developed method was successfully applied to the synthesis of flavones.     

An efficient intermolecular C(aryl)-S bond forming reaction catalyzed by BINAM-copper(II) complex

A wide range of diaryl thioethers and aryl alkyl thioethers are synthesized from the corresponding aryl iodides and aromatic/aliphatic thiols through Ullmann type intermolecular coupling reactions in the presence of a catalytic amount of easily available BINAM-Cu(OTf)₂ complex. Less reactive aryl bromides have also been shown to react with thiols under identical reaction conditions to give good yields of the thioethers without increasing the reaction temperature and time.     

Palladium-catalyzed aminosulfonylation of aryl halides

The palladium-catalyzed three-component coupling of aryl iodides, sulfur dioxide, and hydrazines to deliver aryl N-aminosulfonamides is described. The colorless crystalline solid DABCO·(SO(2))(2) was used as a convenient source of sulfur dioxide. The reaction tolerates significant variation of both the aryl iodide and hydrazine coupling partners.     

N6-Arylation of 2'-deoxyadenosine via copper-catalyzed direct coupling with aryl halides

[reaction: see text] A general method for efficient N(6)-arylation of 2'-deoxyadenosine via copper-catalyzed direct coupling with aryl iodides and bromides is described. The method is useful for aryl halides with either electron-donating or electron-withdrawing groups.     

Novel C-C bond cleavage under mild, neutral conditions: conversion of electron-deficient aryl alkyl ketones to aryl carboxylic esters

A novel, unique way to cleave the carbon-carbon bond in aryl alkyl ketones under mild, neutral conditions is described. Treatment of aryl alkyl ketones in a refluxing mixture of N,N-dimethylformamide dimethyl acetal and methanol for 16 h provided aryl carboxylic esters. The scope and limitations of the reaction are discussed. Useful yields of the reaction can be obtained with electron-deficient aryl groups, and the yields are higher when the alkyl group is larger than a methyl group. Studies toward elucidation of the reaction mechanism led to a proposed mechanism that is consistent with all the observations.