Showing papers on "Alkylation published in 2014"
TL;DR: The homogeneous, iron-catalysed, direct alkylation of amines with alcohols is described, which includes the monoalkylation of anilines and benzyl amine with a wide range of alcohols, and the use of diols in the formation of five, six- and seven- membered nitrogen heterocycles, which are privileged structures in numerous pharmaceuticals.
Abstract: The selective conversion of carbon-oxygen bonds into carbon-nitrogen bonds to form amines is one of the most important chemical transformations for the production of bulk and fine chemicals and pharma intermediates. An attractive atom-economic way of carrying out such C-N bond formations is the direct N-alkylation of simple amines with alcohols by the borrowing hydrogen strategy. Recently, transition metal complexes based on precious metals have emerged as suitable catalysts for this transformation; however, the crucial change towards the use of abundant, inexpensive and environmentally friendly metals, in particular iron, has not yet been accomplished. Here we describe the homogeneous, iron-catalysed, direct alkylation of amines with alcohols. The scope of this new methodology includes the monoalkylation of anilines and benzyl amines with a wide range of alcohols, and the use of diols in the formation of five, six- and seven- membered nitrogen heterocycles, which are privileged structures in numerous pharmaceuticals.
325 citations
TL;DR: A novel method for sulfone derivatives by oxidative coupling with sodium sulfinates and oxime acetates using copper as catalyst is reported, which resulted in various sulfonylvinylamines and β-ketosulfones being obtained in good to excellent yields under the optimized reaction conditions.
Abstract: Sulfone derivatives are important synthetic intermediates. However, the general method for their preparation is through traditional coupling reaction: the alkylation of sodium sulfinates with phenacyl halides. Based on our previous work on sodium sulfinates and oxime acetates, we herein report a novel method for sulfone derivatives by oxidative coupling with sodium sulfinates and oxime acetates using copper as catalyst. The sulfonylvinylamine products could be formed in excellent yields. Upon hydrolysis by silica gel in CH2 Cl2 , β-ketosulfones could also be efficiently constructed. Various sulfonylvinylamines and β-ketosulfones were obtained in good to excellent yields under the optimized reaction conditions. Mechanistic studies indicated that this transformation involved copper-catalyzed N-O bond cleavage, activation of a vinyl sp(2) C-H bond, and C-S bond formation. The oxime acetates act as both a substrate and an oxidant, thus the reaction needs no additional oxidants or additives.
258 citations
TL;DR: The direct alkylation of unactivated sp(3) C-H bonds of aliphatic amides was achieved via nickel catalysis with the assist of a bidentate directing group and shows a predominant preference for sp( 3) C(H) bonds of methyl groups via a five-membered ring intermediate over the sp(2)C-H Bonds of arenes in the cyclometalation step.
Abstract: The direct alkylation of unactivated sp3 C–H bonds of aliphatic amides was achieved via nickel catalysis with the assist of a bidentate directing group. The reaction favors the C–H bonds of methyl groups over the methylene C–H bonds and tolerates various functional groups. Moreover, this reaction shows a predominant preference for sp3 C–H bonds of methyl groups via a five-membered ring intermediate over the sp2 C–H bonds of arenes in the cyclometalation step.
251 citations
TL;DR: A practical and unified strategy has been described for the preparation of mono- and difluoromethylated phenanthridine derivatives using a visible-light-promoted alkylation and decarboxylation sequence from biphenyl isocyanides with ethyl bromofluoroacetate (EBFA) or ethylbromodifluoro acetate (EBDFA).
213 citations
TL;DR: Development of a ketone-alkylation strategy using simple olefins as the alkylating agents and the pH/redox neutral and byproduct-free nature of this dual-activation approach shows promise for large-scale syntheses.
Abstract: Alkylation of carbonyl compounds is a commonly used carbon-carbon bond-forming reaction. However, the conventional enolate alkylation approach remains problematic due to lack of regioselectivity, risk of overalkylation, and the need for strongly basic conditions and expensive alkyl halide reagents. Here, we describe development of a ketone-alkylation strategy using simple olefins as the alkylating agents. This strategy employs a bifunctional catalyst comprising a secondary amine and a low-valent rhodium complex capable of activating ketones and olefins simultaneously. Both cyclic and acyclic ketones can be mono-α-alkylated with simple terminal olefins, such as ethylene, propylene, 1-hexene, and styrene, selectively at the less hindered site; a large number of functional groups are tolerated. The pH/redox neutral and byproduct-free nature of this dual-activation approach shows promise for large-scale syntheses.
211 citations
TL;DR: Cationic half-sandwich scandium alkyl complexes bearing monocyclopentadienyl ligands embedded in chiral binaphthyl backbones act as excellent catalysts for the enantioselective C-H bond addition of pyridines to various 1-alkenes, leading to formation of a variety of enantioenriched alkylated pyridine derivatives in high yields and excellent enantiOSElectivity.
Abstract: Cationic half-sandwich scandium alkyl complexes bearing monocyclopentadienyl ligands embedded in chiral binaphthyl backbones act as excellent catalysts for the enantioselective C–H bond addition of pyridines to various 1-alkenes, leading to formation of a variety of enantioenriched alkylated pyridine derivatives in high yields and excellent enantioselectivity (up to 98:2 er).
203 citations
TL;DR: The Rh(III)-catalyzed C-8 selective direct alkylation and alkynylation of quinoline N-oxides has been developed and demonstrates the synthetic utility of the N-oxide directing group as a stepping stone for remote C-H functionalized quinolines.
198 citations
TL;DR: The reaction of 1,1-bis(pinacolboronate) esters with alkyl halides can be effected by metal alkoxides and provides a strategy for the construction of organoboronate compounds.
Abstract: The reaction of 1,1-bis(pinacolboronate) esters with alkyl halides can be effected by metal alkoxides and provides a strategy for the construction of organoboronate compounds. The reaction is found to occur by alkoxide-induced deborylation and generation of a boron-stabilized carbanion.
193 citations
TL;DR: The first catalytic and enantioselective C-H alkylation of ferrocene derivatives with various alkenes was achieved using a cationic iridium complex.
Abstract: The first catalytic and enantioselective CH alkylation of ferrocene derivatives with various alkenes was achieved. A cationic iridium complex, having a chiral diene ligand, and an isoquinolyl moiety as a directing group are essential for regioselective and enantioselective CH bond activation.
173 citations
TL;DR: A versatile transition-metal-catalyzed approach to monoalkylation of primary amides, compatible with a variety of functional groups, and it has been applied to the synthesis of an opioid receptor antagonist.
Abstract: The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (ie, poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C–N bond formation at room temperature The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that inclu
172 citations
TL;DR: Several bisbenzoxazolyl iridium(III) complexes have been synthesized and characterized through X-ray crystallography as discussed by the authors, and these complexes exhibit excellent catalytic activity in C-C and C-N bond formation reactions.
Abstract: Several new bisbenzoxazolyl iridium(III) complexes have been synthesized and characterized through X-ray crystallography. These complexes exhibit excellent catalytic activity in C–C and C–N bond formation reactions from the alkylation of amine with amine, amine with alcohol, ketone with alcohol, and alcohol with alcohol through a borrowing hydrogen reaction. Moreover, these iridium(III) complexes are effective catalysts for the alkylation of amine with alcohol and ketone with alcohol under solvent-free conditions. The catalytic activity of these complexes is greatly enhanced by noncoordinating, while the experiments have excluded the possibility of a “silver effect” (bimetallic catalysis or silver-assisted metal catalysis) from the experiments.
TL;DR: For the first time, a successful Ir(III)-catalyzed intermolecular insertion of arene C-H bonds into α-diazo compounds is reported.
Abstract: A Rh(III)-catalyzed procedure for the C7-selective C-H alkylation of various indolines with α-diazo compounds at room temperature is reported. The advantages of this process are: 1) simple, mild, and pH-neutral reaction conditions, 2) broad substrate scope, 3) complete regioselectivity, 4) no need for an external oxidant, and 5) N2 as the sole byproduct. Furthermore, alkylation and bis-alkylation of carbazoles at the C1 and C8 positions have also been developed. More significantly, for the first time, a successful Ir(III)-catalyzed intermolecular insertion of arene C-H bonds into α-diazo compounds is reported.
TL;DR: These catalyst-free autocatalyzed alkylation methods can efficiently afford useful alkylated ketone or alcohol products in a one-pot manner and on a large scale by C�C bond formation of the in situ generated intermediates with subsequent controllable and selective Meerwein-Pondorf-Verley-Oppenauer-type redox processes.
Abstract: Direct dehydrative α-alkylation reactions of ketones with alcohols are now realized under simple, practical, and green conditions without using external catalysts. These catalyst-free autocatalyzed alkylation methods can efficiently afford useful alkylated ketone or alcohol products in a one-pot manner and on a large scale by CC bond formation of the in situ generated intermediates with subsequent controllable and selective Meerwein–Pondorf–Verley–Oppenauer-type redox processes.
TL;DR: In this paper, a simple CuAlOx catalyst was used to synthesize N-methyl or N-dimethyl amines with up to 96% yields by applying amine, nitrobenzene and nitrile as starting materials.
Abstract: CO2/H2 was successfully employed in alkylation reactions by performing CO2 reduction and amine N-methylation in one-pot. In the presence of a simple CuAlOx catalyst, N-methyl or N,N-dimethyl amines with different structures can be selectively synthesized with up to 96% yields by applying amine, nitrobenzene and nitrile as starting materials.
TL;DR: The synthesis of both classes of compounds starting from aromatic diamines and alcohols (benzimidazoles) or diols (quinoxalines) is reported, with the highest catalytic activity for both reactions.
Abstract: Benzimidazoles and quinoxalines are important N-heteroaromatics with many applications in pharmaceutical and chemical industry. Here, the synthesis of both classes of compounds starting from aromatic diamines and alcohols (benzimidazoles) or diols (quinoxalines) is reported. The reactions proceed through acceptorless dehydrogenative condensation steps. Water and two equivalents of hydrogen are liberated in the course of the reactions. An Ir complex stabilized by the tridentate P^N^P ligand N(2) ,N(6) -bis(di-isopropylphosphino)pyridine-2,6-diamine revealed the highest catalytic activity for both reactions.
TL;DR: Investigations indicate that catalysts suitable for hydrogen autotransfer or borrowing hydrogen chemistry might also be suitable for acceptor-less dehydrogenative condensation reactions.
Abstract: A novel family of iridium catalysts stabilised by P,N-ligands have been introduced. The ligands are based on imidazo[1,5-b]pyridazin-7-amines and can be synthesised with a broad variety of substitution patterns. The catalysts were synthesised quantitatively from the protonated ligands and a commercially available iridium precursor. The catalysts mediate the alkylation of amines by alcohols under mild conditions (70 °C). In addition, the synthesis of quinolines from secondary or primary alcohols and amino alcohols is reported. This sustainable synthesis proceeds through the liberation of two equivalents of water and two equivalents of dihydrogen. The investigations indicate that catalysts suitable for hydrogen autotransfer or borrowing hydrogen chemistry might also be suitable for acceptor-less dehydrogenative condensation reactions.
TL;DR: Alkenes, arenes, and heteroarenes possessing an 8-quinolylamide group as the directing group are alkylated with primary and secondary alkyl tosylates, mesylate, and halides in the presence of Fe(acac)3/diphosphine as a catalyst and ArZnBr as a base.
Abstract: Alkenes, arenes, and heteroarenes possessing an 8-quinolylamide group as the directing group are alkylated with primary and secondary alkyl tosylates, mesylate, and halides in the presence of Fe(acac)3/diphosphine as a catalyst and ArZnBr as a base. The reaction proceeds stereospecifically for alkene substrates and takes place without loss of regiochemical integrity of the starting secondary tosylate, but with loss of the stereochemistry of the chiral center.
TL;DR: In this article, the first asymmetric catalytic alkylation of unmodified ketones with alkyl halides was reported, which requires light in order to proceed, providing a rare example of highly enantioselective photochemical catalytic processes.
Abstract: We report here the first asymmetric catalytic alkylation of unmodified ketones with alkyl halides. This metal-free approach, which requires light in order to proceed, provides a rare example of highly enantioselective photochemical catalytic processes. An easily available cinchona-based primary amine catalyst guides both the stereoselectivity-defining event and, through the transient formation of photon-absorbing chiral electron donor–acceptor complexes, the photo-activation of the substrates.
TL;DR: 9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3)–H and C(Sp2,–H) alkylation of simple amides with various alkyl iodides.
Abstract: 9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3)–H and C(sp2)–H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.
TL;DR: Stabilization of oil/oil Pickering emulsions using robust and recyclable catalytic amphiphilic silica nanoparticles bearing alkyl and propylsulfonic acid groups allows fast and efficient solvent-free acetalization of immiscible long-chain fatty aldehydes with ethylene glycol.
Abstract: Stabilization of oil/oil Pickering emulsions using robust and recyclable catalytic amphiphilic silica nanoparticles bearing alkyl and propylsulfonic acid groups allows fast and efficient solvent-free acetalization of immiscible long-chain fatty aldehydes with ethylene glycol.
TL;DR: Using 8-aminoquinoline-based aryl carboxamides, the direct ortho-alkylation can be achieved in high yields in the presence of an iron source, 1,2-bis(diphenylphosphino)ethane (dppe) and phenylmagnesium bromide and provide high levels of regioselectivity.
Abstract: Using 8-aminoquinoline-based aryl carboxamides, the direct ortho-alkylation can be achieved in high yields in the presence of an iron source, 1,2-bis(diphenylphosphino)ethane (dppe) and phenylmagnesium bromide. The reactions proceed without overalkylation and provide high levels of regioselectivity. The benzylation reactions can be performed in air with reagent-grade THF, while the alkylation works well with unactivated secondary bromides and iodides in 2-methyltetrahydrofuran. Moreover, the reactions only require 5–10 min.
TL;DR: Various β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-amino acids were prepared by sequential C(sp(3))-H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural β-disubstituted α-aminos acids.
Abstract: The alkylation of unactivated β-methylene C(sp(3))-H bonds of α-amino acid substrates with a broad range of alkyl iodides using Pd(OAc)2 as the catalyst is described. The addition of NaOCN and 4-Cl-C6H4SO2NH2 was found to be crucial for the success of this transformation. The reaction is compatible with a diverse array of functional groups and proceeds with high diastereoselectivity. Furthermore, various β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-amino acids were prepared by sequential C(sp(3))-H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural β-disubstituted α-amino acids.
TL;DR: A general alkylation of heterocycles using a simple palladium catalyst is reported, and an alkyl radical addition to neutral heteroarenes is most likely involved.
Abstract: A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.
TL;DR: In this paper, the phase-transfer catalysts for asymmetric alkylation of sulfenate anions to various sulfoxides with high enantioselectivities and yields were reported.
Abstract: We report halogenated pentanidiums as phase-transfer catalysts for the asymmetric alkylation of sulfenate anions to various sulfoxides with high enantioselectivities (up to 99 % ee) and yields (up to 99 %). This approach gives access to enantioenriched heterocyclic sulfoxides that might not be compatible with strong oxidants or organometallic reagents. Computational studies have revealed that the multiple noncovalent interactions such as halogen bonds and nonclassical hydrogen bonds are involved.
TL;DR: The results of this study revealed the unique potential of Cp*Ir complexes bearing a functional bipyridonate ligand for the development of C-C bond-forming reactions with the activation of primary alcohols as electrophiles.
Abstract: A Cp*Ir complex bearing a functional bipyridonate ligand was found to be a highly effective and versatile catalyst for the α-alkylation of ketones with primary alcohols under extremely environmentally benign and mild conditions (0.1 equiv of Cs2CO3 per substrate, reflux in tert-amyl alcohol under an air atmosphere for 6 h). Furthermore, this complex also exhibited a high level of catalytic activity for the α-methylation of ketones with methanol. The mechanistic investigation revealed that the carbonyl group on the ligand is of critical importance for catalytic hydrogen transfer. Notably, the results of this study revealed the unique potential of Cp*Ir complexes bearing a functional bipyridonate ligand for the development of C–C bond-forming reactions with the activation of primary alcohols as electrophiles.
TL;DR: Sunlight-induced direct regioselective β-alkylation of cyclopentanones with electron-deficient alkenes withelectrolysis using tetrabutylammonium decatungstate (TBADT) as the catalyst gave the three-component β-acylation product in good yield.
Abstract: Sunlight-induced direct regioselective β-alkylation of cyclopentanones with electron-deficient alkenes was accomplished by using tetrabutylammonium decatungstate (TBADT) as the catalyst. The regiochemistry can be rationalized by a polar transition state for an SH2 reaction. In the presence of CO, the reaction gave the three-component β-acylation product in good yield.
TL;DR: Using a simple amino amide ligand, ruthenium-catalyzed one-pot alkylation of primary and secondary amines with simple alcohols was carried out under a wide range of conditions, with high conversion and selectivity.
Abstract: Using a simple amino amide ligand, ruthenium-catalyzed one-pot alkylation of primary and secondary amines with simple alcohols was carried out under a wide range of conditions. Using the alcohol as solvent, alkylation was achieved under mild conditions, even as low as room temperature. Reactions occurred with high conversion and selectivity in many cases. Reactions can also be carried out at high temperatures in organic solvent with high selectivity using stoichiometric amounts of the alcohol.