One-pot conversion of aromatic bromides and aromatics into aromatic nitriles via aryllithiums and their DMF adduct

Various aromatic bromides and iodides were smoothly converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH₃. The same treatment of typical aromatics and heteroaromatics with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH₃ also provided the corresponding aromatic nitriles in good yields. Moreover, the same treatment of aromatic bromides and aromatics with half amount of DIH (1,3-diiodo-5,5-dimethylhydantoin) instead of molecular iodine worked effectively to give the corresponding aromatic nitriles, respectively, in good yields. These reactions are novel and environmentally benign one-pot methods for the preparation of aromatic nitriles from aromatic bromides and aromatics, respectively, through the formation of aryllithiums and their DMF adducts.     

Facile preparation of aromatic ketones from aromatic bromides and arenes with aldehydes

Aromatic ketones were efficiently prepared in good yields by the reactions of aryl bromides with n-BuLi, followed by the reactions with aromatic aldehydes or aliphatic aldehydes and the subsequent treatment with molecular iodine and K₂CO₃, in a one-pot method. The same treatment of arenes, instead of aromatic bromides, also provided the corresponding aromatic ketones in good yields. Using these methods, various diaryl ketones and alkyl aryl ketones bearing electron-rich aromatics and electron-deficient aromatics could be prepared efficiently by a simple, transition-metal-free, and therefore environmentally benign experimental procedure.     

Transformation of aromatic bromides into aromatic nitriles via formations of grignard reagents and their DMF adducts

Various aromatic bromides were efficiently transformed into the corresponding aromatic nitriles in good yields via the formations of Grignard reagents and subsequently N,N-dimethyl formamide (DMF) adducts, followed by treatment with molecular iodine (I₂) in aq NH₃ at room temperature. The present reaction is an easy and practical method for the preparation of aromatic nitriles from aromatic bromides with less toxic reagents, such as Mg, DMF, I₂, and aq NH₃.     

Practical one-pot conversion of aryl bromides and β-bromostyrenes into aromatic nitriles and cinnamonitriles

Various aryl bromides were efficiently converted into the corresponding aromatic nitriles in good yields by the treatment with Mg turnings and subsequently DMF, followed by treatment with molecular iodine and aq NH₃. The same treatment of aryl bromides, which are weakly reactive to Mg turnings, with ⁱPrMgCl·LiCl and subsequently DMF, followed by the treatment with molecular iodine and aq NH₃ also afforded the corresponding aromatic nitriles in good yields. On the other hand, when N-formylpiperidine was used instead of DMF, p-substituted β-bromostyrenes were converted into the corresponding p-substituted cinnamonitriles, i.e., α,β-unsaturated nitriles, in good to moderate yields by the same procedure. The reactions were carried out by means of a simple experimental procedure and did not require any toxic metal cyanides or expensive rare metals. Therefore, the present reactions are practical and environmentally benign one-pot methods for the preparation of aromatic nitriles, cinnamonitriles, and aliphatic nitriles from aryl bromides, β-bromostyrenes, and alkyl bromides, respectively, through the formation of Grignard reagents and their DMF or N-formylpiperidine adducts.     

Practical one-pot transformation of electron-rich aromatics into aromatic nitriles with molecular iodine and aq NH3 using Vilsmeier–Haack reaction

Various electron-rich aromatics could be efficiently transformed into the corresponding aromatic nitriles in good to moderate yields by treatment with DMF and POCl₃, followed by the reaction with molecular iodine or 1,3-diiodo-5,5-dimethylhydantoin (DIH) in aq NH₃. Some of less reactive aromatics, such as anisole, 1,2-dimethoxybenzene, 1,4-dimethoxybenzene, and mesityrene, could be also transformed into the corresponding aromatic nitriles in good to moderate yields using N-methylformanilide and O(POCl₂)₂, followed by the reaction with molecular iodine in aq NH₃. Moreover, propiophenone derivatives could be successfully transformed into the corresponding β-chlorocinnamonitriles by the reaction with DMF and POCl₃, followed by the reaction with molecular iodine and aq NH₃. These reactions are novel metal-free one-pot methods for the preparation of aromatic nitriles from electron-rich aromatics and β-chlorocinnamonitriles from propiophenones.     

Facile one-pot preparation of 5-aryltetrazoles and 3-arylisoxazoles from aryl bromides

The successive treatment of aryl bromides with n-BuLi, DMF, hydroxylamine hydrochloride, and finally diphenylphosphoryl azide provided efficiently the corresponding 5-aryltetrazoles in good to moderate yields. Similarly, the successive treatment of aryl bromides with n-BuLi, DMF, hydroxylamine hydrochloride, and finally diethyl acetylenedicarboxylate and Oxone^® provided efficiently the corresponding diethyl 3-arylisoxazole-4,5-dicarboxylates in good to moderate yields. Aromatic aldoximes are the key intermediates in both reactions, and 5-aryltetrazoles and 3-arylisoxazoles could be obtained from aryl bromides in one pot under transition-metal-free conditions.     

Practical synthesis of pinacolborane for one-pot synthesis of unsymmetrical biaryls via aromatic C-H borylation-cross-coupling sequence

A method for practical preparation of pinacolborane from borane-diethylaniline and pinacol was newly developed. Aromatic C-H borylation of arenes with pinacolborane or bis(pinacolato)diboron catalyzed by 1/2[Ir(OMe)(COD)]₂-(4,4′-di-tert-butyl-2,2′-bipyridine) at 25 °C in hexane to give arylboronic esters was directly followed by cross-coupling with aromatic bromides at 60 °C in the presence of PdCl₂(dppf) (3.0 mol %) and K₃PO₄ in DMF. This one-pot, two-step procedure provided a variety of unsymmetrical biaryls in high yields.     

Transformation of aromatic bromides into aromatic nitriles with n-BuLi,pivalonitrile, and iodine under metal cyanide-free conditions

Various aromatic nitriles could be obtained in good yields by the treatment of aryl bromides with n-butyllithium and then pivalonitrile, followed by the treatment with molecular iodine at 70 °C, without metal cyanides under transition-metal-free conditions. The present reaction proceeds through the radical β-elimination of imino-nitrogen-centered radicals formed from the reactions of imines and N-iodoimines under warming conditions. © 2019 Elsevier Science. All rights reserved.     

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.     

Efficient homo-coupling reactions of heterocyclic aromatic bromides catalyzed by Pd(OAc)2 using indium

Homo-coupling reactions of heterocyclic aromatic bromides smoothly proceeded with cat-Pd(OAc)₂, indium, and LiCl in DMF to afford exclusively symmetric biaryls possessing heterocyclic aromatic ring in good to excellent yields.     

Selective arylation of 1,1-disubstituted olefins using a biphenyl-based phosphine in Heck coupling reactions

The biphenyl-based phosphine, 2-diphenylphosphino-2′-methylbiphenyl is an effective ligand for palladium-catalyzed terminal arylation of 1,1-disubstituted olefins with aryl bromides in DMF and K₂CO₃ as base. The yields of products are independent of the electronic properties of the aryl bromides, however, the nature of the olefin has a major effect.     

New method for synthesis of aromatic diimide dicarboxylic acid diallyl esters

New method is suggested for synthesis aromatic diimide dicarboxylic acid diallyl esters from the corresponding acids under the action of allyl halides in aprotic polar solvents in the presence of anhydrous K₂CO₃.     

Metalation in hydrocarbon solvents: the mechanistic aspects of substrate-promoted ortho-metalations

The methoxy-substituted aromatic reagents 1,2- and 1,3-dimethoxybenzene (1,2-DMB and 1,3-DMB) and 1,2,4-trimethoxybenzene (1,2,4-TMB) each undergo directed ortho-metalation in high yield in n-BuLi/hydrocarbon media without the aid of a catalyst. These reactions, coined ‘substrate-promoted ortho-metalations’, proceed with the methoxy aromatic substrate functioning as both the directing metalation group (DMG) and as the deoligomerization agent. Evidence that the substrates themselves serve to deoligomerize n-BuLi comes from ¹³C NMR. The relative extent of metalated product formed as a function of time for each of the three aromatics directly correlates with the substrate's time-dependent ability to coordinate to n-BuLi as measured by ¹³C NMR. The interpretation of NMR results from experiments involving 1,2,4-TMB is consistent with the metalation proceeding via the activated complex [(1,2,4-TMB)₂·(n-BuLi)₂]. Finally, conclusions from solubility experiments are that for every substrate-promoted metalation investigated, a precipitate forms in the hydrocarbon solvent, and this precipitate mostly contains the ortho-lithiated aryl intermediate.     

Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

Aryl hydrazones, the precursor of Fischer indole synthesis, were easily obtained by nucleophilic addition of aryllithium reagents to diazo esters. The aryl hydrazones were converted into indoles in good yields by heating with thionyl chloride in alcohol. Grignard reagent was also a good nucleophile, whereas organozinc reagent did not react with diazo esters. Aryllithium reagents were prepared by reacting aryl bromides having various substitutions at 2-, 3-, 4-, or multi positions with n-BuLi. The addition of nucleophiles derived from bromopyridines to diazo esters also gave hydrazones.     

Highly stereoselective synthesis of trans-4-trifluoromethylsulfonyl-2,3-dihydrofurans from arsonium ylides and (E)-α-trifluoromethylsulfonyl-α,β-unsaturated ketones

The reactions of arsonium bromides with (E)-α-trifluoromethylsulfonyl-α,β-unsaturated ketones in the presence of Cs₂CO₃ or K₂CO₃ proceeded smoothly under refluxing condition in dichloromethane (DCM) to give the corresponding trifluoromethylated trans-2,3-dihydrofurans in good to excellent yields with high stereoselectivity.     

Metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into aromatic amides with molecular iodine in aq ammonia, and hydrogen peroxide

Various primary alcohols, particularly benzylic alcohols, could be converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq. NH₃, followed by reaction with ∼30% aq H₂O₂. Similarly, various benzylic halides could be also converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq NH₃, followed by reaction with ∼30% aq H₂O₂. The present reactions involve the metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into the corresponding aromatic amides, respectively.     

Preparation of Polyfunctionalized Aromatic Nitriles from Aryl Oxazolines

A selective ortho,ortho’-functionalization of readily available aryl oxazolines by two successive magnesiations with sBu₂Mg in toluene followed by trapping reactions with electrophiles, such as (hetero)aryl iodides or bromides, iodine, tosyl cyanide, ethyl cyanoformate or allylic bromides (39 examples, 62–99 % yield) is reported. Treatment of these aryl oxazolines with excess oxalyl chloride and catalytic amounts of DMF (50 °C, 4 h) provided the corresponding nitriles (36 examples, 73–99 % yield). Conversions of these nitriles to valuable heterocycles are reported, and a tentative mechanism is proposed.     

A novel approach for the one-pot synthesis of linear and angular fused quinazolinones

A convenient and inexpensive one step methodology has been developed for the synthesis of linear and angular fused quinazolinones. The protocol, which uses amino heterocycles and o-bromo benzyl/naphthyl bromides as reactants, CuI as catalyst, Cs₂CO₃ as base, l-proline as ligand, and DMF as solvent, proceeds via nucleophilic aromatic substitution of the N-heteroaromatic cationic intermediate followed by in situ aerial oxidation at the benzylic position to the quinazolinone scaffold.     

Highly efficient copper(0)-catalyzed Suzuki-Miyaura cross-coupling reactions in reusable PEG-400

Readily available copper powder with K₂CO₃ as the base was extremely effective catalyst for Suzuki-Miyaura coupling reaction performed in PEG-400, which afforded almost quantitative coupling products of aryl iodides. Using iodine as additive, coupling products of aryl bromides or chlorides could be obtained with moderate to good yields.     

Facile transformation of esters to nitriles

Various esters were efficiently converted into the corresponding nitriles in good yields by the treatment with sodium diisobutyl-tert-butoxyaluminium hydride (SDBBA-H), followed by treatment with molecular iodine in aq ammonia. The present one-pot method is very efficient and practical for the conversion of various aromatic and aliphatic esters into the corresponding nitriles.