Showing papers on "Alkylation published in 2004"
TL;DR: Recent developments in the design and use of catalytic and stereoselective strategies for the alkylation of aromatic systems and synthesis of a wide range of polyfunctionalized enantiomerically enriched compounds are reviewed.
Abstract: After more than 125 years, the Friedel-Crafts alkylation is still one of the most studied and most utilized reactions in organic synthesis. What is the secret of this astonishing success? Perhaps the great versatility in scope and applicability continues to justify its crucial role in the synthesis of more and more complex molecules. However, it has taken more than a century for asymmetric catalytic versions of this reaction to be developed and subsequently extended to a range of aromatic compounds and alkylating agents. Herein we review recent developments in the design and use of catalytic and stereoselective strategies for the alkylation of aromatic systems and synthesis of a wide range of polyfunctionalized enantiomerically enriched compounds.
591 citations
TL;DR: O-Alkyl N-anthracenylmethyl derivatives of Cinchona alkaloids can function as enantioselective phase-transfer catalysts, resulting in the development of a new highly selective catalyst and opening up the potential of further expanding the range of alpha-amino acid derivatives that can be prepared.
Abstract: O-Alkyl N-anthracenylmethyl derivatives of Cinchona alkaloids can function as enantioselective phase-transfer catalysts. By employing these catalysts in the asymmetric alkylation of glycine imines, one can generate a range of α-amino acid derivatives with high levels of enantiomeric excess. It is also possible to generate the catalysts in situ from commercially available chiral amines, which offers the opportunity to evaluate libraries of related structures. This latter approach has been successfully applied to a series of biphenyl quaternary ammonium salts resulting in the development of a new highly selective catalyst and opening up the potential of further expanding the range of α-amino acid derivatives that can be prepared.
461 citations
TL;DR: The total synthesis of linear and/or macrocyclic natural polyamines can be accomplished efficiently using nitrobenzenesulfonamides as both a protecting and activating group.
391 citations
TL;DR: In this paper, a reduction of single-walled carbon nanotubes (SWNTs) using lithium and alkyl halides in liquid ammonia yields sidewall functionalized SWNTs that are soluble in common organic solvents.
Abstract: Reductive alkylation of single-walled carbon nanotubes (SWNTs) using lithium and alkyl halides in liquid ammonia yields sidewall functionalized nanotubes that are soluble in common organic solvents. Atomic force microscopy (AFM) and high-resolution tunneling electron microscopy (HRTEM) of dodecylated SWNTs prepared from raw HiPco nanotubes show that extensive debundling has occurred. GC-MS analysis of the byproduct hydrocarbons demonstrates that alkyl radicals are intermediates in the alkylation step.
309 citations
TL;DR: A detailed analysis of the preparative results suggests that iron-catalyzed C-C bond formations can occur via different pathways and it is likely that reactions of methylmagnesium halides involve iron-ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)(2)](n) generated in situ.
Abstract: Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)3 are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C−C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron−ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)2]n generated in situ. Control experiments using the ate-complex [Me4Fe]Li2 corroborate this inter...
286 citations
TL;DR: Very high enantioselectivity has been achieved both in the copper-catalystzed alkylation of allylic substrates by Grignard and organozinc reagents and in the iridium-catalyzed amination of cinnamyl carbonate by employing a very efficient phosphoramidite ligand.
Abstract: Very high enantioselectivity has been achieved both in the copper-catalyzed alkylation of allylic substrates by Grignard and organozinc reagents and in the iridium-catalyzed amination of cinnamyl carbonate by employing a very efficient phosphoramidite ligand
265 citations
TL;DR: This is the first colloidal system shown to display such a high enantioselectivity besides the well-known Pt/cinchonidine system.
Abstract: Palladium nanoparticles (4 nm, fcc) were prepared through decomposition of [Pd2(dba)3] by H2 in the presence of a chiral xylofuranoside diphosphite. These particles catalyze the allylic alkylation of rac-3-acetoxy-1,3-diphenyl-1-propene with dimethyl malonate leading to an almost total conversion of the (R) enantiomer and almost no reaction with the (S). This gives rise to 97% ee for the alkylation product and a kinetic resolution of the substrate recovered with ca. 90% ee. This behavior was compared to that of a molecular catalyst at various dilutions, and the differences between the two systems are discussed. This is the first colloidal system shown to display such a high enantioselectivity besides the well-known Pt/cinchonidine system.
246 citations
TL;DR: The first highly enantioselective catalytic reaction involving aromatic C-H bond activation is communicated and the identified catalyst system enables the intramolecular alkylation reaction to be performed at temperatures 75 degrees C lower than the previously reported achiral system.
Abstract: The first highly enantioselective catalytic reaction involving aromatic C−H bond activation is communicated. Enantioselective cyclization of aromatic ketimines containing alkenyl groups tethered at the meta position of an imine directing group has been achieved using 5 mol % [RhCl(coe)2]2 and 15 mol % of an (S)-binol-derived phosphoramidite ligand. Selectivities of up to 96% ee and up to quantitative yields were obtained. Moreover, the identified catalyst system enables the intramolecular alkylation reaction to be performed at temperatures 75 °C lower than our previously reported achiral system. The reaction can even be performed at room temperature for one of the optimal substrates.
237 citations
TL;DR: The activity of the cationic monoalkyls in catalytic ethene polymerization was found to vary by over 2 orders of magnitude depending on the metal ionic radius, the intermediate metal sizes being found to be the most effective.
Abstract: Using a sterically demanding amidinate ancillary ligand and an in situ alkylation procedure, neutral mono(amidinate) dialkyl and cationic mono(amidinate) monoalkyl complexes were prepared for metals spanning the full size range of the group 3 and lanthanide metals. The activity of the cationic monoalkyls in catalytic ethene polymerization was found to vary by over 2 orders of magnitude depending on the metal ionic radius, the intermediate metal sizes being found to be the most effective.
236 citations
TL;DR: This novel Ru-grafted hydrotalcite (Ru/HT) efficiently catalyzed alpha-alkylation of nitriles with primary alcohols through the cooperative catalysis between the Ru species and the surface base sites.
Abstract: Treatment of a hydrotacite, Mg6Al2(OH)16CO3, with an aqueous solution of RuCl3·nH2O afforded a monomeric Ru(IV) species on the surface of the hydrotalcite. This novel Ru-grafted hydrotalcite (Ru/HT...
227 citations
TL;DR: alpha-Alkylation of ketones was successfully achieved by the reaction of ketone with alcohols catalyzed by iridium complexes in the presence of a small amount of base.
Abstract: α-Alkylation of ketones was successfully achieved by the reaction of ketones with alcohols catalyzed by iridium complexes in the presence of a small amount of base. For example, 2-octanone was allowed to react with butanol under the influence of [Ir(cod)Cl]2/PPh3/KOH to give 6-dodecanone in good yield. The reaction was found to proceed by using a 1:1 mixture of ketone and alcohol without use of any solvent.
TL;DR: A simultaneous redox, alkylation, self-assembly reaction under solvothermal conditions afforded a novel copper(I) chain polymer constructed of luminescent Cu3I4- and unprecedented EtS-4-C5H4N+Et components (Et = CH3CH2).
Abstract: A simultaneous redox, alkylation, self-assembly reaction under solvothermal conditions afforded a novel copper(I) chain polymer constructed of luminescent Cu3I4- and unprecedented EtS-4-C5H4N+Et components (Et = CH3CH2).
TL;DR: In this paper, (S)-alpha-methyl proline catalyzes the intramolecular alkylation of various halo aldehydes to the corresponding formyl cyclopentanes, -cyclopropanes, or -pyrrolidines in excellent yields and enantioselectivities.
Abstract: The development of a general catalytic asymmetric aldehyde alpha-alkylation reaction constitutes a major challenge in organic synthesis. Here, we report the first and successful approach toward its solution: (S)-alpha-methyl proline catalyzes the intramolecular alkylation of various halo aldehydes to the corresponding formyl cyclopentanes, -cyclopropanes, or -pyrrolidines in excellent yields and enantioselectivities. Most remarkably, racemization, aldolization, or catalyst alkylation do not occur to any significant extend, further illustrating the power, mildness, and profound selectivity of enamine catalysis.
TL;DR: The present report provides the first precedent for efficient Cu-catalyzed allylic alkylations with chiral NHC ligands with high enantioselectivity to afford tertiary as well as quaternary carbon centers.
Abstract: Cu-catalyzed addition of alkylzinc reagents to a range of allylic phosphates is promoted efficiently and with high enantioselectivity to afford tertiary as well as quaternary carbon centers (up to 98% ee). Reactions proceed to completion with 0.5−5 mol % catalyst loading and are best promoted by commercially available CuCl2·2H2O. The X-ray structure of the chiral NHC−Ag(I) complex used in the study as well as that of a catalytically active NHC−Cu(II) complex are also reported; both complexes are air-stable and are formed in ≥95% isolated yield. The isolated Cu complex, which can be handled in air, is catalytically active. The present report provides the first precedent for efficient Cu-catalyzed allylic alkylations with chiral NHC ligands.
TL;DR: In this paper, the catalytic reaction of 1-methy-2-(4-pentenyl)indole with a catalytic amount of PtCl2 in dioxane that contained a trace of HCl (5 mol %) at 60 °C for 24 h led to the isolation of 4,9-dimethyl-2,3,4,9tetrahydro-1H-carbazole (2) in 92% yield.
Abstract: Reaction of 1-methy-2-(4-pentenyl)indole (1) with a catalytic amount of PtCl2 (2 mol %) in dioxane that contained a trace of HCl (5 mol %) at 60 °C for 24 h led to the isolation of 4,9-dimethyl-2,3,4,9-tetrahydro-1H-carbazole (2) in 92% yield. Platinum-catalyzed cyclization of 2-(4-pentenyl)indoles tolerated substitution at each position of the 4-pentenyl chain. Furthermore, the protocol was applicable to the synthesis of tetrahydro-β-carbolinones and was effective for cyclization of unprotected indoles. 2-(3-Butenyl)indoles underwent platinum-catalyzed cyclization with exclusive 6-endo-trig regioselectivity. Mechanistic studies established a mechanism for the platinum-catalyzed cyclization of 2-alkenyl indoles involving nucleophilic attack of the indole on a platinum-complexed olefin.
TL;DR: A detailed study of the alkylation of isobutane with 2-butene in ionic liquid media has been conducted using 1-alkyl-3-methylimidazolium halides-aluminum chloride encompassing various alkyl groups (butyl-, hexyl-, and octyl-) and halides (Cl, Br, and I) on its cations and anions, respectively as mentioned in this paper.
TL;DR: Observations suggest a mechanism involving the cyclization of the more reactive pi-allyl palladium diastereomeric intermediate as the enantiodiscriminating step (Curtin-Hammett conditions).
Abstract: The Pd-catalyzed asymmetric allylic alkylation (AAA) of phenol allyl carbonates serves as an efficient strategy to construct the allylic C−O bond allowing access to chiral chromans in up to 98% ee. The effect of pH and the influence of olefin geometry, as well as substitution pattern on the ee and the absolute configuration of the chiral chromans were explored in detail. These observations suggest a mechanism involving the cyclization of the more reactive π-allyl palladium diastereomeric intermediate as the enantiodiscriminating step (Curtin−Hammett conditions). This methodology led to the enantioselective synthesis of the vitamin E core, the first enantioselective total synthesis of (+)-clusifoliol and (−)-siccanin, and the synthesis of an advanced intermediate toward (+)-rhododaurichromanic acid A.
TL;DR: In this article, an efficient, general procedure for highly chemoselective reductive mono-alkylation of ammonia with ketones is reported, followed by in situ sodium borohydride reduction, and a straightforward workup afforded primary amines in good yield.
TL;DR: In this article, large-pore zeolites X and Y in their acidic form were explored as catalysts for isobutane/butene alkylation in order to understand the principal requirements for successful solid acid catalysts.
TL;DR: A review of reductive aminations using borohydride and borane reducing agents can be found in this article, where the authors focus on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel.
Abstract: Reductive amination is an important tool for synthetic organic chemists in the construction of carbon-nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent. A wide variety of substrates can be used including aliphatic and aromatic aldehydes and ketones, and even benzophenones. A range of amines from ammonia to aromatic amines, including those with electron-withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful.
This chapter focuses on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel. This review is restricted to reductive aminations using borohydride and borane reducing agents. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron-containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced, through the middle of 1999. In addition to reductive aminations of aldehyde and ketone substrates, reactions of related structures including acetals, aminals, ketals, carboxylic acids, nitriles, and dicarbonyls that form a nitrogen-containing ring are reviewed. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. The intramolecular variant is a useful method for preparing cyclic amines. All of the various boron-containing hydride sources in reductive aminations, including labeled metal hydrides, are reviewed. Instances of reductive aminations that failed are described. Applications of this method to a solid support in parallel synthesis in combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as reductive lactamizations are discussed.
Keywords:
organic reaction(s);
organic synthesis;
reaction(s);
synthesis;
reductive amination;
condensation;
alkylation;
reductive alkylation;
reduction;
amination;
carbonyl;
amine;
reducing agent(s);
borohydride;
borane;
carbon-nitrogen bond(s);
CN bond(s)
TL;DR: New S-alkylated 5-(2-,3- and 4-methoxyphenyl)-4H-1,2,4-triazole-3-thiols and 5-(1,3-benzodioxol-5-yl)-2-bromo-1-ethanone, which exhibit anti-inflammatory activity, are synthesized.
Abstract: New S-alkylated 5-(2-,3- and 4-methoxyphenyl)-4H-1,2,4-triazole-3-thiols (5a–c, 6a–c) and 5-(2-,3- and 4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols (7a–c, 8a–c, 9a–c) were synthesized by the alkylation of 3-(2-,3- and 4-methoxyphenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (3a–c) or 3-(2-,3- and 4-methoxyphenyl)-4-phenyl-4,5-dihydro-1H-1,2,4-triazole-5-thiones (4a–c) with 1-iodobutane or 1-(1,3-benzodioxol-5-yl)-2-bromo-1-ethanone, 2-bromo-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-ethanone and 2-bromo-1-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-1-ethanone. Compounds 3a–c and 4a–c were synthesized by the acylation of thiosemicarbazide or 4-phenyl-3-thiosemicarbazide with 2-, 3- and 4-methoxybenzoyl chlorides and further cyclization of the obtained acylderivatives 1a–c and 2a–c. The synthesized compounds 4a–c, 5a, 6a–c, 7a–c, 8a–c, 9b,c exhibit anti-inflammatory activity.
TL;DR: The protocol uses a catalytic amount of [PdCl(pi-allyl)](2)/phosphine as a promoting agent, providing allylindoles in excellent yields, providing a flexible route to fused indole alkaloids.
TL;DR: Elimination of the need for desalting of samples after reaction raised the possibility of automation of the procedure for liquid samples, which is difficult with conventional reduction and alkylation chemistries.
TL;DR: In this article, the authors summarize some examples of novel industrial processes, based on new catalysts that are environmentally friendly, for the production of ethylbenzene and cumene, two of the most important chemicals produced by alkylation/transalkylation.
TL;DR: Catalytic enantioselective alkylation promoted by a quaternary ammonium salt from cinchonine as a phase transfer catalyst is described, resulting in moderate to excellent yields with high enantiomeric excesses.
Abstract: Catalytic enantioselective alkylation promoted by a quaternary ammonium salt from cinchonine as a phase transfer catalyst is described. Treatment of cyclo beta-keto esters with alkyl halide under mild reaction conditions afforded the corresponding alpha-alkylated beta-keto esters in moderate to excellent yields with high enantiomeric excesses
TL;DR: The in vitro anticancer assay indicated 5- methylated derivatives 14a, 15a, 16a are more cytotoxic than their respective 6-methylated counterparts 14b, 15b, 16b and 6H-indolo[2,3-b]quinoline precursors 11, 12, 13.
TL;DR: DFT calculations in the gas phase and in water bulk on the binol and benzo quaternary ammonium salts 2 and 4 evidence structural and electrostatic features of the binl derivative which might offer a rationalization of its promising high photo-cross-linking efficiency.
Abstract: The photogeneration and detection of new binol quinone methides undergoing mono- and bisalkylation of free nucleophiles was investigated by product distribution analysis and laser flash photolysis in water solution using binol quaternary ammonium derivatives 2 and 12 as photoactivated precursors. The alkylation processes of N and S nucleophiles are strongly competitive with the hydration reaction. DNA cross-linking potency of the water-soluble binol quaternary ammonium salt 2 was investigated as a pH function and compared to that of other quaternary ammonium salts capable of benzo-QM (QM = quinone methide) photogeneration by gel electrophoresis. DFT calculations in the gas phase and in water bulk on the binol and benzo quaternary ammonium salts 2 and 4 evidence structural and electrostatic features of the binol derivative which might offer a rationalization of its promising high photo-cross-linking efficiency.
TL;DR: A mild protocol for the synthesis of cis-aziridines is described that employs a catalytic amount of Brønsted acid and high levels of relative stereocontrol are also possible when forming the Schiff base from a chiral nonracemic aldehyde.
Abstract: A mild protocol for the synthesis of cis-aziridines is described that employs a catalytic amount of Bronsted acid. Despite the potential for diazo compound decomposition via alkylation or homocoupling upon exposure to a proton source, these pathways are slow relative to [2 + 1] annulation in the presence of a Schiff base, leading to aziridine product. The process uses no metals or reagents that must be removed chromatographically, exhibits rapid turnover rates, and produces only atomic nitrogen as a coproduct. High levels of relative stereocontrol are also possible when forming the Schiff base from a chiral nonracemic aldehyde.
TL;DR: Lewis acids are shown to cleave the carbon-carbon bond of activated aziridines at ambient temperature, and the derived metal-coordinated azomethine ylides undergo cycloaddition reactions with electron-rich alkenes.
Abstract: Lewis acids are shown to cleave the carbon−carbon bond of activated aziridines at ambient temperature. The derived metal-coordinated azomethine ylides undergo cycloaddition reactions with electron-rich alkenes. Cyclic alkenes afford products that are formally [4+2] adducts most likely derived from a Mannich-type addition to the ylide, followed by intramolecular Friedel−Crafts alkylation. Alternatively, acyclic alkenes undergo [3+2] cycloaddition to give new pyrrolidine products.