Showing papers in "Synthesis in 2003"
TL;DR: A review of solution-phase multi-component procedures for the synthesis of heterocyclic compounds can be found in this paper, where the authors give an overview of the progress made in the past decade.
Abstract: Following the increased interest from the pharmaceutical industry for the generation of diverse libraries of heterocyclic compounds, scientific efforts have become more and more focused on the development of novel multi-component procedures as a means of gaining rapid access to such compounds. Initially, the development of solid-phase procedures received considerable attention. However, current efforts are increasingly concerned with the development of solution-phase procedures. The latter will be the subject of discussion in this review, which aims to give an overview of the progress made in the past decade. After a general introduction, non-catalyzed, acid-catalyzed, and transition metal-catalyzed solution-phase multi-component procedures for the preparation of a wide range of heterocycles will be discussed. The last chapter discusses the role of cycloaddition reactions in the development of novel MCRs for the synthesis of heterocyclic compounds. In spite of their important role in the synthesis of heterocyclic compounds, MCRs involving isocyanides are not discussed in this review, since the topic has been exhaustively reviewed several times. 1 Introduction 2 Non-Catalyzed MCRs 3 Acid-Catalyzed MCRs 4 Transition Metal-Catalyzed or -Mediated MCRs 5 MCRs Involving Cycloaddition Reactions 6 Conclusions and Outlook.
854 citations
TL;DR: Enyne metathesis combines an alkene and an alkyne into a 1,3-diene as mentioned in this paper. But the first enyne reaction catalyzed by a ruthenium carbene complex was reported in 1994.
Abstract: Enyne metathesis combines an alkene and an alkyne into a 1,3-diene. The first enyne metathesis reaction catalyzed by a ruthenium carbene complex was reported in 1994. This review covers the advances in this transformationduring the last eight years with particular emphasis on methodology development and synthetic applications.
341 citations
TL;DR: The application of Lawesson's reagent [2,4-bis(p-methoxyphenyl)-1, 3-dithiaphosphetane-2, 4-disulfide] in organic and organometallic syntheses is described in this article.
Abstract: This review, including 245 references, describes the application of Lawesson's reagent [2,4-bis(p-methoxyphenyl)-1,3-dithiaphosphetane-2,4-disulfide] LR in organic and organometallic syntheses. Thionations of carbonyl-containing compounds as well as unexpected reactions are shown for different applications (e.g. cyclizations, rerrangements, syntheses of heterocyclic compounds etc.). Syntheses of novel organometallic compounds by LR are also discussed.
253 citations
TL;DR: In this paper, the various applications of indium in organic synthesis are highlighted, especially Barbier-type reactions, especially allyl additions to carbonyl compounds, and Reformatsky reactions.
Abstract: The various applications of indium in organic synthesis are highlighted in this review. Major fields are Barbier-type reactions, especially allyl additions to carbonyl compounds, and Reformatsky reactions. Special emphasis is placed on reactions, which have been examined only recently, i.e. reductions of various functionalities, indium-catalyzed reactions and palladium/indium-mediated reactions.
221 citations
TL;DR: In this article, a mixture of a 1,2-phenylenedi-amine and an aldehyde in wet DMF at room temperature is used to synthesize benzimidazoles.
Abstract: Addition of oxone ® to a mixture of a 1,2-phenylenedi- amine and an aldehyde in wet DMF at room temperature results in rapid formation of benzimidazoles under very mild conditions. The reaction is applicable to a wide range of substrates including ali- phatic, aromatic and heteroaromatic aldehydes, and is not signifi- cantly affected by steric or electronic effects. In most cases, crude products are isolated in good to excellent yields (59-95%) and ho- mogeneities (86-99%) by simple precipitation or extraction from the reaction mixture and do not require additional purification. Lim- itations to the scope of this methodology were encountered in cases where aldehydes were sensitive to oxone ® under the acidic reaction conditions. The features of this methodology make it particularly well suited for the high-throughput, solution-phase synthesis of benzimidazole libraries. The low cost and simplicity of this proce- dure makes it equally attractive for preparative-scale syntheses where safety and environmental issues are of greater concern.
201 citations
TL;DR: In this article, the development and scope of catalytic enanti-lective addition of aromatic and heteroaromatic C-H bonds to α,β-unsaturated alkenes, carbonyl compounds, and imines is presented.
Abstract: The development and scope of catalytic enantioselective addition of aromatic and heteroaromatic C-H bonds to α,β-unsaturated alkenes, carbonyl compounds, and imines are presented. α,β-Unsaturated alkenes, 4-substituted 2-oxo-3-butenoate esters and alkylidene malonates react with indoles, furans and electron-rich aromatic compounds in the presence of chiral bisoxazoline-copper(II) complexes to give the Friedel-Crafts alkylation adduct in moderate to high yields and with up to >99.5% ee. Chiral bisoxazoline-copper(II) complexes can also catalyze the enantioselective addition of especially electron-rich aromatic compounds to activated carbonyl compounds such as glyoxylates and trifluoropyruvate to give e.g. optically active aromatic mandelic acid esters in good yields and enantioselectivities. Electron-rich aromatic compounds and heteroaromatic compounds react in an enantioselective fashion with activated N-protected α-imino esters to give optically active aromatic and heteroaromatic u-amino acid derivatives using chiral BINAP-copper(I) complexes as the catalyst.
197 citations
TL;DR: In this article, a one-pot synthesis of alkynes from aldehydes is described, using a new in situ preparation of dimethyldiazomethylphosphonate.
Abstract: A highly convenient way to perform the synthesis of alkynes from aldehydes is reported. The procedure utilizes a new in situ preparation of dimethyldiazomethylphosphonate. As a consequence a commercially available reagentcan now be used, circumventing a disadvantage of earlier protocols. The easy one-pot procedure avoids the use of strong bases, low temperatures and inert gas techniques.
179 citations
TL;DR: An overview of the synthesis and applications of a range of heterocyclic boronic acids can be found in this article, with a focus on the synthesis of biphenyls via a palladium(0) catalysed cross-coupling reaction with aryl halides.
Abstract: Boronic acids are valued by organic chemists for their important role in the synthesis of biphenyls via a palladium(0) catalysed cross-coupling reaction with aryl halides (Suzuki reaction). Despite their synthetic utilityand known biological activities heterocyclic boronic acids feature less frequently often due to difficulties in their synthesis. This paper provides an overview of the synthesis and applications of a range of heterocyclic boronic acids.
135 citations
TL;DR: In this paper, the use of (trifluoromethyl)trimethylsilane has been broadened to the synthesis of trifluorsulfide sulfides, especially those that are bio-active.
Abstract: Apart from the use of (trifluoromethyl)trimethylsilane, the scope of which has been broadened to the synthesis of trifluoromethyl sulfides, especially those that are bio-active, new and mild processes for the nucleophilictrifluoromethylation of non-enolizable carbonyl compounds or disulfides have been discovered from fluoroform or hemiaminals of trifluoroacetaldehyde and their derivatives. Very stable hemiaminals of fluoral (as well as their silyl ethers), readily prepared from commercially available hemiketals, have been designed as new trifluoromethylating agents. Besides their trifluoromethylating ability, they can be transformed into silyl or methyl ethers, which behave, as efficient generators of α-(tri-fluoromethyl)iminiums salts and equivalents of difluoromethylcarboxyl anions, respectively.
133 citations
122 citations
TL;DR: This review examines the subtle electronic, steric and conformational effects that in turn have profound impacts on reaction paths and selectivity for Rhodium catalyzed reactions of diazo compounds.
Abstract: Rhodium catalyzed reactions of diazo compounds form a powerful set of tools for synthetic organic chemists. Reactivity modes include cyclopropanation, C-H insertion, X-H insertion, and ylide formation. A myriad of factorsinfluences the mode of reaction, selectivity, and yield for these reaction processes. This review examines the subtle electronic, steric and conformational effects that in turn have profound impacts on reaction paths and selectivity. 1 Introduction 2 Achiral Rhodium(II) Catalysts 2.1 Effect of Catalyst Electrophilicity on Selectivity 2.2 Effect of Diazo Substitution on Selectivity 2.3 Effect of Substrate Substitution on Selectivity 3 Chiral Rhodium(II) Catalysts 3.1 Carboxylate Ligands 3.2 Carboxamidate Ligands 3.3 Phosphate Ligands 3.4 Phosphine Ligands 4 Conclusions.
TL;DR: In this article, the synthesis of diversely substituted 1,3,5-substituted pyrazoles from the reaction of acetylenic ketones with substituted hydrazines is reported.
Abstract: The synthesis of diversely substituted 1,3,5-substituted pyrazoles from the reaction of acetylenic ketones with substituted hydrazines is reported. The reactions were shown to be highly regioselective regardless of the nature of the substituents in the substrates and afforded essentially single pyrazole isomers in excellent yields.
TL;DR: In the late 1980's, a new process based on an intramolecular palladium-mediated cyclisation coupled with a carbon-carbon bond forming reaction appeared in the literature as mentioned in this paper.
Abstract: In the late 1980's, a new process based on an intramolecular palladium-mediated cyclisation coupled with a carbon-carbon bond forming reaction appeared in the literature. Since the first report, many novel ring systems have been synthesized using this methodology. The aim of this present review article is to summarise a number of synthetic applications of this new process developed over the last fifteen years.
TL;DR: In this article, an efficient synthesis of an array of quinazolin-4(3 H)- ones from anthranilic acid, ortho esters (or formic acid) and amines using Yb(OTf)3 in one-pot under solvent-free conditions is de- scribed.
Abstract: An efficient synthesis of an array of quinazolin-4(3 H)- ones from anthranilic acid, ortho esters (or formic acid) and amines using Yb(OTf)3 in one-pot under solvent-free conditions is de- scribed. Compared with the classical reaction conditions, this new synthetic method has the advantage of excellent yields (75-99%), shorter reaction time (few minutes) and reusability of the catalyst.
TL;DR: Aryl nitriles have been found to participate in cross-coupling and amination reactions via nickel-catalyzed activation of the C-CN bond.
Abstract: Aryl nitriles have been found to participate in cross-coupling and amination reactions via nickel-catalyzed activation of the C-CN bond. With the development of these synthetically useful transformations, aryl nitriles can now be considered along with aryl halides and sulfonates as viable substrates for these types of reactions.
TL;DR: An improved one-pot procedure for the preparation of N-acylbenzotriazoles involves mild reaction conditions and allows the Preparation of several derivatives not accessible by the previously reported methods.
Abstract: An improved one-pot procedure for the preparation of N-acylbenzotriazoles involves mild reaction conditions and allows the preparation of several derivatives not accessible by the previously reported methods.
TL;DR: The terdentate ligand 2,2':6',2"-terpyridine (tpy) has increasingly become one of the most popular ligands in coordination chemistry as mentioned in this paper.
Abstract: The terdentate ligand 2,2':6',2"-terpyridine (tpy) has increasingly become one of the most popular ligands in coordination chemistry. A variety of substituents are utilised to tailor the properties of its metal complexes.2,2":6",2"-Terpyridine was reacted with almost all transition metals to form complexes. Among a series of tpy ligand derivatives, those containing substituents at the C(4') position are of especial interest. Metal-bonded tpy ligands with spacers at C(4') provide a means of directionality, and thus a means of linear communication, it means that electronic communication can occur along the coordination axis. In addition, the insertion of a single substituent at the C(4')-position of the tpy ligand results in no enantiomeric derivatives, as the derivative retains its plane of symmetry. The synthetic strategies used to prepare tpy ligands are reviewed comprehensively.
TL;DR: In this paper, two families of biarylphosphine ligands were prepared for use in the Pd-catalyzed amination reaction, one derived from N-phenylpyrroles, and the other derived from n-pyrrole pyrazoles.
Abstract: Two families of biarylphosphine ligands were prepared for use in the Pd-catalyzed amination reaction. The first series investigated was derived from N-phenylpyrroles, and the second, was derived from N-phenylpyrazoles. While the pyrrole ligands were not as general in substrate scope, one of the readily prepared pyrazole ligands (R = t-Bu) was found to have a fairly broad substrate scope.
TL;DR: In this article, high yielding syntheses of mercapto terminated monodisperse dimer, trimer, and tetramer ethyleneoxide oligomers and of p-hydroxyphenethyl thiol via an alcohol-tosylate-thiol route are reported.
Abstract: High yielding syntheses of mercapto terminated monodisperse dimer, trimer, and tetramer ethyleneoxide oligomers and of p-hydroxyphenethyl thiol via an alcohol-tosylate-thiol route are reported. Comparisons are made with the more conventional alcohol-bromide-thiol route.
TL;DR: The Dutch resolution is the term given to the use of mixtures (families) of resolving agents in classical resolutions as mentioned in this paper, and it is the most common method for resolving agents.
Abstract: Dutch Resolution is the term given to the use of mixtures (families) of resolving agents in classical resolutions. In this status report an overview is given of the latest results and new (possible) families of resolving agents are introduced. The concept of families is discussed as well as the factors that come into play on use of fam- ilies. Practical aspects of Dutch Resolution in particular and resolu- tions in general are discussed.
TL;DR: In this article, a reduction of nitroarenes with nanosized activated metallic iron powder in water at 210 °C (near-critical water) was developed, which generated the corresponding aromatic amines in excellent yields.
Abstract: A practical reduction of nitroarenes with nanosized activated metallic iron powder in water at 210 °C (near-critical water) has been developed. The reduction generates the corresponding aromatic amines in excellent yields.
TL;DR: In this article, the identification and development of a catalyst for the enantioselective nucleophilic addition of a trifluoromethyl anion to a ketone is described.
Abstract: The identification and development of a catalyst for the enantioselective nucleophilic addition of a trifluoromethyl anion to a ketone is described. An easily prepared cinchonine-derived catalyst was used in amounts as low as 4 mol% to afford enantiomeric excess as high as 92%.
TL;DR: In this paper, a review summarizes the efforts towards the synthesis of chiral neolignans, racemic and optically active, and provides a brief outlook for future developments.
Abstract: Neolignans, dehydrodimers of phenylpropenes, are important natural products with high structural diversity and various biological properties. Several diastereo- and enantioselective synthesis of neolignans have been developed in the past, either specific for each of the various neolignan skeletons or randomized. This review summarizes the efforts towards the synthesis of chiral neolignans, racemic and optically active, and provides a brief outlook for future developments.
TL;DR: A solventless Suzuki coupling reaction has been developed which utilizes a commercially available potassium fluoride alumina mixture and palladium powder as discussed by the authors, which is convenient, environmentally friendly, and generates good yields of the coupled products.
Abstract: A solventless Suzuki coupling reaction has been developed which utilizes a commercially available potassium fluoride alumina mixture and palladium powder. The new reaction is convenient, environmentally friendly, and generates good yields of the coupled products. Aryl iodides react faster than the bromides or chlorides; aryl groups are also more reactive than alkenyl groups. which react faster than alkyl groups. The use of microwave irradiation accelerates the reaction, decreasing reaction times from hours to minutes. The palladium powder catalyst can be recycled using a simple filtration and washing sequence without loss of catalytic activity.
TL;DR: In this paper, a simple and flexible general procedure for the regiospecific annulation of the trifluoromethylpyridine ring to electron-rich amino heterocycles was proposed.
Abstract: The reaction of 4,4,4-trifluoro-3-oxobutanoates with the corresponding electron-rich amino heterocycles was investigated. A simple and flexible general procedure for the regiospecific annulation of the trifluoromethylpyridine ring to electron-rich amino heterocycles was proposed. A set of CF 3 -containing fused pyridines in almost quantitative yield was obtained.
TL;DR: The moisture and air stable ionic liquids 1-butyl-3-methylimidazonium tetrafluoroborate [bmim]BF4 and 1butyl 3methyloridazium hexafluorophosphate [BMim]PF6 were used as "green" recyclable alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds RE
Abstract: The moisture and air stable ionic liquids 1-butyl-3-methylimidazonium tetrafluoroborate [bmim]BF4 and 1-butyl-3-methylimidazonium hexafluorophosphate [bmim]PF6 were used as ‘green' recyclable alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds. Both aldehydes and ketones gave satisfactory results. The ionic liquids containing catalyst EDDA were recycled several times with no decreases in yields and reaction rates. In the case of 2-hydroxybenzaldehyde, the reactions led to the formation of 3-substituted coumarins under standard reaction conditions.
TL;DR: The transformation of aldehydes into nitriles is an important process in organic chemistry as discussed by the authors, which can be converted to amides, carboxylic acids, amines, ketones, and esters.
Abstract: The transformation of aldehydes into nitriles is an important process in organic chemistry.1,2 Nitriles are very useful starting materials for the synthesis of various bioactive molecules.3 The former can be converted to amides, carboxylic acids, amines, ketones, and esters.2 Nitriles can be obtained by dehydration of aldoximes prepared from the corresponding aldehydes.4 Several procedures are available for the one-step conversion of aldehydes into nitriles using different chemical reagents.5–8 However, most of these methods suffer from serious drawbacks which include use of hazardous and expensive or commercially nonavailable reagents, long reaction time, low yields, drastic reaction conditions, and tedious workup procedure.
TL;DR: In this paper, the deprotonation of HC(pz) 3 with n-butyllithium followed by reaction with methyl iodide, benzyl bromide and chlorotrimethylsilane produced the respective substituted ligands RC(pZ) 3 [R = CH 3, C 6 H 5 CH 2, (CH 3 ) 3 Si] in good yield.
Abstract: The deprotonation of HC(pz) 3 with n-butyllithium followed by reaction with methyl iodide, benzyl bromide and chlorotrimethylsilane produced the respective substituted ligands RC(pz) 3 [R = CH 3 , C 6 H 5 CH 2 , (CH 3 ) 3 Si] in good yield Analogous chemistry starting with HC(3-Phpz) 3 was only successful in high yield when the deprotonation step was carried out with LiN(Si(CH 3 ) 3 ] 2 , added at low temperature, and led to the syntheses of RC(3-Phpz) 3 [R = CH 3 , (CH 3 ) 3 si, CH 2 =CHCH 2 , C 6 H 5 CH 2 ] In contrast, the alcohol derivatives HOCH 2 C(pz) 3 and HOCH 2 C(3-Phpz) 3 were prepared using potassium tort-butoxide for the deprotonation step followed by paraformaldehyde For HC(3-t-Bupz) 3 , deprotonation with n-butyllithium at low temperature was most successful and led to the syntheses of RC(3-t-Bupz) 3 [R = CH 3 , (CH 3 ) 3 Si, HOCH 2 ] The compound HOCH 2 C(pz) 3 was converted into t-BuPhCH 2 OCH 2 C(pz) 3 by reaction with sodium hydride and (tertbutyl)benzyl bromide These synthetic routes have made a variety of functionalized tris(pyrazolyl)methane ligands available for studies of their coordination chemistry
TL;DR: In this paper, the reaction time of secondary benzylic alcohols with an alkyl chain is increased by substituting a bulky phenyl ring such as benzhydrol and 9-hydroxyfluorene.
Abstract: Secondary benzylic alcohols with an alkyl chain are oxidized faster than simple benzyl alcohols. However the reaction time is prolonged, when the alkyl chain is replaced by a bulky phenyl ring such as benzhydrol and 9-hydroxyfluorene. All the benzyl and benzylic alcohols give yields >90%. Allylic alcohols without steric hindrance react faster to give excellent yield (>80%). The present method is superior to others currently available due to its relatively short reaction times and excellent yields.