170,570 research outputs found
Regioselective Direct C-5 arylation of Imidazoles: synthetic protocols and applications
No full textArylazoles are ubiquitous features of natural products, pharmaceutics, agrochemicals and fluorescent dyes and this, undoubtedly, plays a key role in the continuing search for the development of new, efficient and cost-effective methods to synthesize these heterocycles. Recently, the transition metal-promoted direct C–H arylation of heteroarenes with (hetero)aryl halides has emerged as an attractive strategy for the effective formation of heteroaryl–(hetero)aryl bonds. In fact, this strategy, unlike the traditional metal-catalyzed cross-coupling procedures involving the use of preformed organometallic reagents, enables the direct elaboration of the heterocyclic cores without the need of preactivating both the coupling partners.
In this context, we have been interested in studies aimed to develop efficient protocols for the highly regioselective synthesis of (hetero)aryl azoles by palladium-catalyzed intermolecular direct (hetero)arylation of azoles with (hetero)aryl halides.1 Our studies in this field allowed us the design and development of convenient procedures for the highly regioselective Pd(OAc)2/(2-furyl)3P-catalyzed direct C-5 arylation of 1-aryl-1H-imidazoles, 1-methyl-, 1-benzyl- and 1-methoxymethyl-1H-imidazole with (hetero)aryl iodides and bromides.
These arylation reactions were successfully used as key steps of efficient and highly regioselective syntheses of 1,5-, 2,4(5)-, 4,5-diaryl-1H-imidazole derivatives and 2,4,5-triaryl-1H-imidazoles.
Interestingly, these new synthetic protocols also allowed us to prepare some interesting bioactive arylazole derivatives, which include several cis-restricted analogues of Combretastatin A-4, a potent and selective antitumor derivative.
1) For a review, see: Bellina, F.; Cauteruccio, S.; Rossi, R. Curr. Org. Chem. accepted for publication
Bellina Robineau-Desvoidy 1863
No full text<p> <b>55</b>. <b>Bellina Robineau-Desvoidy</b>, <b>1863b</b>: <b>194</b>.</p> <p> ORIGINALLY INCLUDED SPECIES: <i>Bellina melanura</i> Robineau-Desvoidy, 1863.</p> <p> TYPE SPECIES: <i>Bellina melanura</i> Robineau-Desvoidy, 1863, by monotypy.</p> <p> CURRENT STATUS: Valid genus [<i>teste</i> Crosskey (1977: 591)].</p> <p>FAMILY: TACHINIDAE.</p>Published as part of <i>Evenhuis, Neal L., O'Hara, James E., Pape, Thomas & Pont, Adrian C., 2010, 2373, pp. 1-265 in Zootaxa 2373</i> on page 4
A new protocol for the direct C-2 arylationj of azoles, including free (NH)-imidazole, -benzimidazole and -indole
No full textRecently, in the course of our investigations on the synthesis of vicinal diaryl-substituted 1H-imidazoles by transition metal-catalyzed direct arylation procedures via C–H bond activation,1,2 we reported a new, reliable and convenient method for the regioselective Pd- and Cu-mediated direct C-2 arylation of azoles, including free (NH)–imidazole, –benzimidazole and –indole, under base-free and ligandless conditions.3 The preliminary results obtained in this context encouraged us to perform a more in-depth study in order to determine the most suitable reaction conditions for performing efficiently the Pd- and Cu-mediated direct C-2 arylation of various kinds of azoles. Thus, we found that 1-aryl-1H-imidazoles, 1-methyl-1H-imidazole, 1H-imidazole, thiazole, 1H-benzimidazole, 1-benzyl-1H-imidazole and benzothiazole can undergo regioselective C-2 arylation by reaction with 2 equiv of an aryl iodide in DMF at 140°C for 48 h in the presence of 5 mol % Pd(OAc)2 and 2 equiv of CuI, under base-free and ligandless conditions, to provide the required 2-arylazoles in satisfactory to excellent yields. DMA and DMPU could also be used as solvents, but the arylation in toluene or dioxane didn’t proceed at all. The arylation reaction could also be performed using 5 mol % Pd/C and 2 equiv of CuI in DMF at 140 °C, and under these conditions the required azoles were prepared in yields similar to those obtained via reactions performed under homogeneous conditions, although the reaction times were longer (ca. 72 h). We also found that the best results for the C-2 arylation of indole could be obtained when the reaction was performed by treatment of the azole with 2 equiv of an aryl iodide in the presence of 5 mol % Pd(OAc)2 and 2 equiv of CuI in DMA at 160 °C instead of in DMF at 140 °C. However, also using these modified experimental conditions the required 2-aryl-1H-indoles were obtained in modest yields. Modified reaction conditions were also used to prepare in a good yield 2-(4-methoxyphenyl)oxazole which we previously obtained in a low yield.3 In fact, when 3 equiv of oxazole were reacted with 1 equiv of iodoanisole in DMF at 140°C for 74 h in the presence of 5 mol % Pd(OAc)2 and 2 equiv of CuI, the required 2-arylazole was obtained in 74 % yield. Interestingly, aryl bromides could also be used as electrophiles in the Pd- and Cu-mediated C-2 arylation of the above mentioned heterocycles, provided that 4 equiv of NaI were added to the reagents. 1,2-Diphenyl-1H-imidazole was so prepared in 47 % yield from 1-phenyl-1H-imidazole and 2 equiv of bromobenzene. Our new C-2 arylation method was then applied for preparing some bioactive heterocycle derivatives such as 4-methyl-2-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)-1H-imidazole, which is a selective COX-2 inhibitor,4 and 2-(4-nitrophenyl)-1H-benzimidazole, which is a key intermediate for the synthesis of heparanase inhibitors,5 in 78 and 89 % yield, respectively. At present, we are performing studies on the synthesis of 2,4(5)-diaryl-1H-imidazoles via reaction sequences involving the Pd- and Cu-mediated C-2 arylation of 4(5)-aryl-1H-imidazoles or 5-aryl-1-benzyl-1H-imidazoles under base-free and ligandless conditions
Regioselective functionalization of the imidazole ring via transition metal-catalyzed C–N and C–C bond forming reactions
No full textFunctionalized imidazole derivatives in- clude compounds that are known to possess a broad range of significant biological properties or are im- portant templates in medicinal chemistry. In the light of the importance of these heteroaromatic com- pounds a great deal of attention has been given to their synthesis and, in the past years, a number of methods has been described in the literature allow- ing for the construction of the heteroaromatic core of these substances by cyclization protocols. Howev- er, in recent years, much more attention has been fo- cused on the design and development of efficient protocols that are based on the selective functionali- zation of the imidazole ring at the N-1, C-2, C-4 or C-5 position via transition metal-catalyzed reactions and enable the synthesis of imidazole derivatives, in- cluding bioactive and/or naturally occurring com- pounds, which cannot be accessed by other means. This critical review with 439 references covers devel- opments in this hot area of research up to July 2009 and includes a description of synthetically important, regioselective transition metal-catalyzed Csp2-N, Csp-N, Csp3-N, Csp2-Csp2, and Csp-Csp2 bond form- ing methods, their applications, and limitations
Real Metal-Free C–H Arylation of (Hetero)arenes: The Radical Way
No full textSynthetic methodologies involving the formation of carbon-carbon bonds from carbon-hydrogen bonds are of significant synthetic interest, both for efficiency in terms of atom economy and for their undeniable usefulness in late-stage functionalization approaches. Combining these aspects with being metal-free, the radical C-H intermolecular arylation procedures covered by this review represent both powerful and green methods for the synthesis of (hetero)biaryl systems. 1 Introduction 2 Arylation with Arenediazonium Salts and Related Derivatives 2.1 Ascorbic Acid as the Reductant 2.2 Hydrazines as Reductants 2.3 Gallic Acid as the Reductant 2.4. Polyanilines as Reductants 2.5 Chlorpromazine Hydrochloride as the Reductant 2.6 Phenalenyl-Based Radicals as Reductants 2.7 Electrolytic Reduction of Diazonium Salts 2.8 Visible-Light-Mediated Arylation 3 Arylation with Arylhydrazines: Generation of Aryl Radicals Using an Oxidant 4 Arylation with Diaryliodonium Salts 5 Arylation with Aryl Halides 6 Conclusions
Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides
No full textThe Pd- and Cu-mediated reaction of a large variety of p-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylhetero- cycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a heparanase inhibitor
Transition Metal-Catalyzed Direct Arylation of Substrates with Activated sp3-Hybridized C–H Bonds and Some Their Synthetic Equivalents with Aryl Halides and Pseudohalides
No full textA study was conducted to demonstrate transition metal-catalyzed direct arylation of substrates with activated sp3-hybridized C-H bonds and some of their synthetic equivalents with aryl halides and pseudohalides. The study also focused on the catalyst system and experimental conditions used for the regioselective synthesis of α-arylated compounds through transition metal-catalyzed arylation of synthetic equivalents of carbonyl compounds. The synthetic equivalents of carbonyl compounds included silyl enol ethers and enol ethers of ketones and silyl ketone acetals using aryl halides or pseudohalides as electrophiles. The investigations also highlighted the utility of these experimentally simple reactions that proceeded without requiring preparation of stoichiometric amounts of organometallics
Total synthesis of rubrolide M and some of its unnatural congeners
No full textTwo protocols have been developed for the Pd-catalyzed regioselective synthesis of 4-aryl-3-chloro-2(5H)-furanones starting from 3,4-dichloro-2(5H)-furanone. These monochloro derivatives have then been used as precursors to (Z)-4-aryl-5-[I(aryl)methylidenel-3-chloro-2(5H)-furanones including naturally-occurring rubrolide M. (C) 2002 Elsevier Science Ltd. All rights reserved
Synthesis of 4-alkyl-3-bromo-2(5H)-furanones and unsymmetrically disubstituted 3,4-dialkyl-2(5H)-furanones by palladium-catalyzed cross-coupling reactions
No full textEasily available 3,4-dibromo-2(5H)-furanone undergoes a regioselective cross-coupling reaction with alkylboronic acids in the presence of catalytic amounts of PdCl2( MeCN)(2) and AsPh3 and a large molal excess of Ag2O to provide the corresponding 4-alkyl-3-bromo-2(5H)-furanones in satisfactory yields. These monobromo derivatives have proven to be useful precursors to unsymmetrically substituted 3,3-dialkyl-2(5H)-furanones which include the racemic form of naturally occurring seiridin. (C) 2001 Elsevier Science Ltd. All rights reserved
A new, selective and functional group tolerant method for the synthesis of 1-aryl-1H-indoles and 9-aryl-9H-carbazoles
No full textSeveral methods have been described for the N-arylation of 1H-indoles and 9H-carbazoles, but some problems limit their synthetic utility. In fact, the Ullmann-type reactions suffer from a limited substrate scope, moderate yields, have been preferentially conducted with aryl halides activated by electron-withdrawing groups and involve the use of expensive phosphine ligands.
On the other hand, even the Cu-catalyzed N-arylation of 1H-indoles is not entirely satisfactory since the use in this methods of a ligand entails an increase of the cost of the reaction and problems in the isolation of the required chemically pure products. Furthermore, the experimental conditions of the Ullmann-type coupling and the Pd- or Cu-catalyzed N-arylations, that involve the use of a base, cause an intolerance of base sensitive groups such as the phenolic hydroxy group.
Recently, in the course of our studies on the development of new and efficient protocols for the highly regioselective arylation of azoles we found that the CuOAc-mediated N-arylation of 1H-indole derivatives and 9H-carbazole with aryl iodides in DMA at 160 °C under base-free and ligandless conditions provides with complete N-selectivity the required N-arylazoles in moderate to good yields (eqs. 1 and 2).This inexpensive new version of the classical Ullmann reaction allows an unprecedented tolerance of functional groups both in the 1H-indoles and aryl iodides and works well with electron-rich and electron-poor aryl iodides. Moreover, the experimental conditions of this protocol facilitate the work-up of the reaction mixtures and the isolation of the required chemically pure N-aryl derivatives
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