Microwave assisted, palladium catalyzed aminocarbonylations of heteroaromatic bromides using solid Mo(CO)6 as the carbon monoxide source

The direct conversion of a variety of heteroaromatic bromides into heteroaromatic amides is described. This reaction utilizes Mo(CO)₆ as the carbon monoxide source and is performed using microwave heating allowing for very short reaction times. This convenient methodology allows for the preparation of a variety of heteroaromatic amides useful in medicinal chemistry applications.     

A simple phenylation of heteroaromatic compounds using diphenyliodonium triflate

In this study a novel method for direct synthesis of 2-phenyl heteroaromatic arenes was successfully developed. The title compounds were synthesized by reaction of heteroaromatic compounds with diphenylene iodonium trifluoromethanesulfonate in the presence of 5?mol% Pd(OAc)₂ under mild reaction conditions (THF, 60?°C, 24?h). The proposed reaction mechanism was studied by HPLC.     

含杂环羧酸基二苄基锡(Ⅳ)配合物的合成与表征

以二苄基二氯化锡和杂环羧酸钠为原料合成了十种新的有机锡配合物(PhCH₂)₂Sn(O₂CR)_nCl_2-n(n=1或2，R=杂环)。用元素分析、IR、 ¹H NMR和TG表征了配合物的组成和结构。     

A novel amination of aromatic and heteroaromatic compounds

Vinyl azides act as NH⁺₂ equivalents in reaction with aromatic or heteroaromatic lithium derivatives thus providing a direct method for amination of such compounds.     

Pd0‐Mediated Rapid Coupling between Methyl Iodide and Heteroarylstannanes: An Efficient and General Method for the Incorporation of a Positron‐Emitting 11C Radionuclide into Heteroaromatic Frameworks

The Pd⁰‐mediated rapid trapping of methyl iodide with an excess amount of a heteroaryl‐substituted tributylstannane has been investigated with the aim of incorporating a short‐lived ¹¹C‐labelled methyl group into the heteroaromatic carbon frameworks of important organic compounds, such as drugs with various heteroaromatic structures, in order to execute a positron emission tomography (PET) study of vital systems. The reaction was first performed by using our previously developed CH₃I/stannane/[Pd₂(dba)₃]/P(o‐CH₃C₆H₄)₃/CuCl/K₂CO₃ (1:40:0.5:2:2:2) system in DMF at 60 °C for 5 min (conditions A), however, the reaction gave low yields for various heteroaromatic compounds. Increasing the amount of phosphine ligand (conditions B) led to a significant improvement in the yield, but the conditions were still not suitable for a range of basic heteroaromatic structures. Use of the CuBr/CsF system (conditions C) also provided a result similar to that obtained under conditions B with an increased amount of the phosphine. Thus, pyridine and related heteroaromatic compounds remained less reactive substrates. The problem was overcome by replacing the DMF solvent with N‐methyl‐2‐pyrolidinone (NMP). The reaction in NMP at 60–100 °C for 5 min using a CH₃I/stannane/[Pd₂(dba)₃]/P(o‐CH₃C₆H₄)₃/CuBr/CsF (1:40:0.5:16:2:5) combination (conditions D) gave the methylated products in yields of more than 80 % (based on the reaction of CH₃I) for all of the heteroaromatic compounds listed in this study. Thus, the combined use of NMP and an increased amount of phosphine is important for promoting the reaction efficiently. The use of this general approach to rapid methylation has been well demonstrated by the synthesis of the PET tracers 2‐ and 3‐[¹¹C]methylpyridines by using [Pd₂(dba)₃]/P(o‐CH₃C₆H₄)₃/CuBr/CsF (1:16:2:5) in NMP at 60 °C for 5 min, which gives the desired products in HPLC analytical yields of 88 and 91 %, respectively.     

Ruthenium(II)-Catalyzed Transfer Hydrogenation of Aromatic and Heteroaromatic Aldehydes in Air

Aromatic and heteroaromatic aldehydes are efficiently reduced to their corresponding alcohols in the presence of [RuCl₂(p-cymene)]₂ and KOAc in 2-propanol under air at 80 °C. The presence of KOAc in the reaction is essential; in its absence no reduction takes place. A highly efficient, external-base-free reduction of aldehydes has also been reported with (η⁶-arene)ruthenium(II) complexes containing O^O chelate ligand such as [Ru(OAc)₂(p-cymene)] and [RuCl(KA)(p-cymene)], obtaining alcohol in excellent yield (OAc, acetate; KA, kojic acetate). The scope of the reaction has been extended to a broad range of aromatic and heteroaromatic aldehydes.     

Studying the reactivity of (phthalazin-1(2H)-on-2-yl)methyl trichloroacetimidate towards different C- and O-nucleophiles

A simple and efficient synthesis of phthalazin-1(2H)-one 2-substituted derivatives is achieved in very good yields via reaction of a phthalazinone-trichloroacetimidate with various C- and O-nucleophiles such as aromatic, heteroaromatic and olefinic reagents, sugars and cholesterol in CH₂Cl₂ in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf).     

The gas‐phase elimination kinetics of ethyl 2‐furoate and ethyl 2‐thiophenecarboxylate

The gas‐phase elimination kinetics of ethyl 2‐furoate and 2‐ethyl 2‐thiophenecarboxylate was carried out in a static reaction system over the temperature range of 623.15–683.15 K (350–410°C) and pressure range of 30–113 Torr. The reactions proved to be homogeneous, unimolecular, and obey a first‐order rate law. The rate coefficients are expressed by the following Arrhenius equations: ethyl 2‐furoate, log k₁ (s^?1) = (11.51 ± 0.17)–(185.6 ± 2.2) kJ mol^?1 (2.303 RT)^?1; ethyl 2‐thiophenecarboxylate, log k₁ (s^?1) = (11.59 ± 0.19)–(183.8 ± 2.4) kJ mol^?1 (2.303 RT)^?1. The elimination products are ethylene and the corresponding heteroaromatic 2‐carboxylic acid. However, as the reaction temperature increases, the intermediate heteroaromatic carboxylic acid products slowly decarboxylate to give the corresponding heteroaromatic furan and thiophene, respectively. The mechanisms of these reactions are suggested and described. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 145–152, 2009     

Palladium‐Catalyzed Carbonylative Coupling of (2‐Azaaryl)methyl Anion Equivalents with (Hetero)Aryl Bromides

Conditions for the palladium‐catalyzed coupling of (2‐pyridyl)acetones with aryl bromides have been developed. Followed by an acid‐promoted deacetylation step, the desired 1‐(het)aryl‐2‐(2‐pyridyl)ethanones were obtained in good to excellent yields with high functional group tolerance. Test reactions revealed that both the addition of MgCl₂ and a specifically positioned heteroatom in the heteroaromatic ring were crucial for product formation indicating the importance of a chelated intermediate in the reaction mechanism. The reaction conditions proved suitable for a number of 5‐ and 6‐membered heteroaromatic starting materials affording all products in good yields. The utility of the obtained 1‐(het)aryl‐2‐(2‐pyridyl)ethanones was demonstrated by the straightforward synthesis of several multiaromatic derivatives in only few additional steps.     

The mechanism of the heterogeneous catalytic monooxidation of thiophene derivatives at the S position by hydrogen peroxide

A biomimetic catalytic reaction system for hetero-oriented monooxidation of heteroaromatic compounds was developed experimentally. The system consisted of two interacting synchronous reactions of the decomposition of H₂O₂ and substrate oxidation. The problem related to the preparation, isolation, and identification of thiophene derivative S-monoxides was solved.     

Mass spectrometric study of heterogeneous catalytic monooxidation of the S-position of thiophenes with hydrogen peroxide

A biomimetic catalytic reaction system is developed experimentally for heteromonooxidation of heteroaromatic compounds. The system consists of two interacting simultaneous reactions, decomposition of H₂O₂ and oxidation of the substrate. This leads to the synthesis, isolation, and identification of the S-monoxide of thiophenes.     

Perfluoroacetylenephosphonates in Diels-Alder reactions: Synthesis of perfluoroalkylated heterocyclic and carbocyclic phosphonates

Diethyl 3,3,3-trifluoroprop-1-ynylphosphonate and diethyl 3,3,4,4,4-pentafluorobut-1-ynylphosphonate are obtained by the dehydration of the corresponding enols using P₂O₅-Et₃N system as a dehydrating agent, affording acetylenes in 50-60% yield. By the reaction of these perfluoroacetylenephosphonates with acyclic and cyclic 1,3-dienes or diene-like heteroaromatic and aromatic compounds corresponding Diels-Alder cyclo- and bicycloadducts were prepared in good yields (65-90%). The reactivity of the dienes and acetylenes which depends on their structure, as well as the regioselectivity of the reaction are established.     

Iron‐catalyzed cross‐coupling of heteroaromatic tosylates with alkyl and aryl Grignard reagents

An Fe(III)‐catalyzed cross‐coupling of N‐heteroaromatic tosylates with aryl and alkyl Grignard reagents is presented. The reaction proceeds at ?20°C to room temperature with short reaction time (15–30 min.), and the corresponding products are obtained with moderate to high yields. In particular, low‐cost and abundantly available FeCl₃ or Fe(acetylacetonate)₃ catalyze the reaction without other special ligands. All tested N‐heteroaromatic tosylates that are available including pyridine and pyrimidine derivatives were subject to the reaction, resulting in the expected products. Copyright © 2015 John Wiley & Sons, Ltd.     

Radical C−H Acylation of Nitrogen Heterocycles Induced by an Aerobic Oxidation of Aldehydes

An aerobic radical approach for the synthesis of unsymmetrical heteroaryl ketones is described herein. The reaction involves cross‐dehydrogenative coupling between aldehydes and heteroaromatic bases with molecular oxygen (O₂). The key aspect of the method is the generation of reactive acyl radical via homolytic activation of aldehyde C?H bond using O₂ as the sole oxidant. The reaction has a good substrate scope with respect to aldehydes and functionalized nitrogen heterocycles. Based on our mechanistic studies, a radical chain pathway is suggested for the reaction. A synthetic application of the method is demonstrated in the formal synthesis of natural alkaloid (±) angustureine.     

Simultaneous dehalogenation and hydrogenation reduction of halogen-heteroaromatic aldehydes

Treatment of halogen-heteroaromatic aldehydes with catalytic amount of PdCl₂ under atmosphere pressure of hydrogen in base medium (sodium acetate) leads to the corresponding dehalogenated primary alcohols. The reaction system was especially effective for the heteroaromatic compounds bearing aldehyde groups and halides (bromo- or chloro-functions).     

A Regioselective Synthesis of Benzopinacolones through Aerobic Dehydrogenative α‐Arylation of the Tertiary sp3 CH Bond of 1,1‐Diphenylketones with Aromatic and Heteroaromatic Compounds

A regioselective synthesis of symmetrical and unsymmetrical benzopinacolones through aerobic dehydrogenative α‐arylation at the tertiary sp³ C?H bond of substituted 1,1‐diphenylketones with aromatic and heteroaromatic compounds, in the presence of K₂S₂O₈ in CF₃COOH at room temperature, is described. The reaction is proposed to go via a carbocation intermediate, which could be generated directly from cleavage of the sp³ C?H bond of 1,1‐diphenylketone. Subsequent α‐arylation was achieved at the methene sp³ carbon atom of the substituted ketone. A variety of substituted aromatic and heteroaromatic compounds were compatible with this reaction. In addition, benzopinacolones were converted into sterically hindered, tetrasubstituted alkenes and polycyclic aromatic compounds.     

Synthesis and evaluation of various heteroaromatic benzamides as analogues of –ylidene-benzamide cannabinoid type 2 receptor agonists

The CB₂ receptor is an attractive target for the treatment of a wide range of diseases and pathological conditions. Compounds that selectively activate the CB₂ receptor are desirable as this avoids CB₁-mediated psychoactive effects. Heteroarylidene-benzamides have demonstrated efficacy as selective CB₂ receptor agonists. We aimed to expand the structure-activity relationship studies of this series of compounds by investigating the heteroaromatic core via the synthesis and in vitro evaluation of a small library of various heteroaromatic benzamide analogues. As heteroaromatic amides are privileged scaffolds in drug design, methods to synthesise them are of interest. Concise and reliable synthetic strategies were developed to access these novel analogues. The –ylidene-benzamide moiety is shown to be essential for CB activity as all amide derivatives exhibit no functional activity at either CB₂ or CB₁ receptors.     

Palladium-catalyzed coupling reactions of (ArCH2)Ti(O-i-Pr)3 with aromatic or heteroaromatic bromides

Three benzyltitanium compounds of (ArCH₂)Ti(O-i-Pr)₃ (Ar = Ph (1a), 4-MeOC₆H₄ (1b), 4-FC₆H₄ (1c)) were prepared and used as benzyl nucleophiles for coupling reactions with aromatic or heteroaromatic bromides. The simple catalytic system of 1 mol % Pd(OAc)₂ and 2 mol % PCy₃ worked efficiently for a wide variety of aromatic bromides, producing diarylmethanes in good to excellent yields of up to 96%. Coupling reactions of hindered aromatic bromides or aromatic bromides containing electron-withdrawing substituents were slower over longer reaction times of 3–6 h. Reactions of heteroaromatic bromides of bromopyridines, bromofurans, or bromothiophenes with benzyl reagents of 1a or 1b required either longer reaction times of 12–24 h or a higher reaction temperature of 80 °C, producing pyridyl-, furyl-, and thienyl-arylmethanes in moderate yields.     

Solvent-free sonochemical kabachnic-fields reaction to synthesize some new α-aminophosphonates catalyzed by nano-BF3•SiO2

To obtain a rapid, efficient synthesis of some new α-aminophosphonates, ultrasonic irradiation has been applied to the reaction mixtures containing amine, aromatic or heteroaromatic aldehydes and triethyl phosphite. The Kabachnik-Fields reaction was performed by using nano-BF₃?SiO₂ as a recyclable catalyst under solvent free conditions. Key advantages of this procedure consist in the eco-friendly and highly efficient reaction conditions, high yields, an easy work-up procedure, short reaction times and solvent free conditions. All title compounds were characterized by spectral and elemental analysis. They were further screened for their in vitro antioxidant activity by the DPPH, O^2? and NO methods. The majority of the title compounds showed good antioxidant activity when compared with the standard antioxidants.     

Sulfuryl Fluoride Mediated Synthesis of Amides and Amidines from Ketoximes via Beckmann Rearrangement

A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO₂F₂ gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines.