Showing papers on "Alkylation published in 2009"
TL;DR: In this tutorial review, recent progress in the development of chiral Brønsted acid-catalyzed asymmetric Friedel-Crafts reactions is presented.
Abstract: The asymmetric Friedel–Crafts reaction is one of the most powerful methods to synthesize optically active aromatic compounds. Particularly, the Friedel–Crafts alkylation of arenes with unsaturated compounds activated by chiral Bronsted acids provides direct access to enantiopure aromatic derivatives with perfect atom economy. In this tutorial review, recent progress in the development of chiral Bronsted acid-catalyzed asymmetric Friedel–Crafts reactions is presented.
645 citations
TL;DR: The alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl(2)](2) with the bidentate phosphines dppf or DPEphos as the catalyst.
Abstract: The alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl2]2 with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine. N-Heterocyclization reactions of primary amines are reported, as well as alkylation reactions of primary sulfonamides. Secondary alcohols require more forcing conditions than primary alcohols but are still effective alkylating agents in the presence of this catalyst.
556 citations
TL;DR: In this paper, air-stable Ir and Ru complexes of a chelating pyrimidine-functionalized N-heterocyclic carbene were synthesized and characterized by NMR spectroscopy and single-crystal X-ray diffraction.
326 citations
TL;DR: Findings are reported on the development of such C H bond functionalization reactions, which allowed for the efficient conversion of primary and secondary alkyl halides and proved applicable to neopentyl-substituted electrophiles.
Abstract: Direct arylation of arenes by C H bond cleavage, which is attractive because of its ecologically and economically benign nature, is an increasingly viable alternative to conventional cross-coupling reactions with stoichiometric amounts of organometallic reagents. 2] However, while the development of stabilizing ligands allowed for the use of unactivated alkyl halides in traditional cross-coupling chemistry, generally applicable methodologies for intermolecular regioselective direct alkylations of arenes with alkyl halides by C H bond cleavage have proven elusive. Recently, we reported on the beneficial effect of carboxylic acids as additives in ruthenium-catalyzed direct arylation 11] with aryl bromides, chlorides, or tosylates. Given the significantly improved activity of the in situ generated catalytic system, we became interested in exploring its use for unprecedented ruthenium-catalyzed direct alkylations with unactivated alkyl halides 15] as electrophiles. Herein, we report our findings on the development of such C H bond functionalization reactions, which allowed for the efficient conversion of primary and secondary alkyl halides and proved applicable to neopentyl-substituted electrophiles. At the outset of our studies, we probed various additives in the ruthenium-catalyzed direct alkylation of 2-pyridyl benzene (1a), employing unactivated alkyl bromide 2 a in NMP as solvent (Table 1). Different phosphines did not significantly affect the outcome of the envisioned reaction (Table 1, entries 1–4). On the contrary, more promising results were obtained when catalytic amounts of carboxylic acids were used as additives (Table 1, entries 5–9). The alkylsubstituted, sterically hindered acid 1-AdCO2H gave the best results (Table 1, entry 9). Reactions performed in toluene as solvent proceeded less efficiently (Table 1, entry 10), and other solvents, such as THF, 1,4-dioxane, DMSO, or N,N-dimethylacetamide, gave considerably lower yields of desired product 3a. As an economically attractive alternative, RuCl3·n H2O [17] could be employed as catalyst precursor (Table 1, entry 11). Importantly, direct alkylation of pyridine derivative 1a could be performed at reaction temperatures as low as 60 8C with comparable efficiencies (Table 1, entries 13–15). Finally, the use of independently prepared carboxylic ester 1-AdCO2(nHex) clearly indicated that its formation was not relevant to the generation of the catalytically active ruthenium species (Table 1, entry 16). We then explored the scope of the optimized catalytic system in the direct alkylation of pyridine derivatives 1 (Table 2). A variety of unactivated alkyl bromides bearing bhydrogen atoms enabled regioselective direct alkylations (Table 2, entries 1–8). While an alkyl iodide also led to an acceptable yield of product 3a (Table 2, entry 9), the corresponding alkyl chloride turned out to be a more challenging substrate (Table 2, entry 10). Notably, our in situ generated catalytic system was not limited to the use of primary alkyl halides but also enabled the conversion of sterically more congested secondary alkyl halides, albeit with lower yield (Table 2, entry 11). Importantly, neopentyl bromide also served as starting material for a direct alkylation (Table 2, entry 12), which indicated that mechanisms relying on either a Table 1: Optimization of ruthenium-catalyzed direct alkylation.
277 citations
TL;DR: The first Pd(II)-catalyzed alkylation of aryl C–H bonds is achieved without using a co-oxidant, to give broadly useful γ– and ™– benzolactones.
Abstract: The first Pd(II)-catalyzed alkylation of aryl C–H bonds is achieved without using a co-oxidant. The alkylation reaction was followed thereafter by an intramolecular lactonization to give broadly useful γ– and ™– benzolactones.
232 citations
TL;DR: The working hypothesis deals with the choice of a suitable chiral Lewis acid promoter, which is capable of efficiently activating the hydroxy group as a leaving group without the formation of an allylic carbocationic species (SN1-type mechanism) that would preclude any stereochemical control in the course of the reaction.
Abstract: The use of p-activated alcohols in catalytic Friedel–Crafts alkylation (FCA) reactions has become a well-known and eco-sustainable reality. A large number of Lewis and Brønsted–Lowry acid catalyzed benzylation/allylation/propargylation procedures has been documented, and they allow rapid access to structural complexity in the realm of aromatic compounds. Despite efficiency, the formation of positively charged intermediates in FCA with alcohols (SN1-type mechanism) makes the stereocontrol of the process a challenging task that has not yet been overcome. As a matter of fact, at present only a handful of reports addressing such an issue have been documented. As a part of our program directed toward the development of innovative catalytic and stereoselective methodologies for the synthesis of polycyclic aromatic compounds, we describe herein the first example of direct activation of allylic alcohols in enantioselective catalytic Friedel–Crafts allylic alkylations of indoles. The methodology allows 1vinyland 4-vinyltetrahydrocarbazoles (THCs) to be readily prepared in a highly enantioselective manner. Our working hypothesis deals with the choice of a suitable chiral Lewis acid promoter, which is capable of efficiently activating the hydroxy group as a leaving group without the formation of an allylic carbocationic species (SN1-type mechanism) that would preclude any stereochemical control in the course of the reaction. Guidelines for searching for a suitable catalyst came from the intrinsic “chelating” architecture of the allylic alcohol featuring a soft p-base center (C=C bond) and a hard s-base unit (hydroxy group) that are adjacent to each other. Cationic late-transition-metal complexes (e.g. Pt, Ag, Au), which feature dual function (i.e. sand p-acidity), appeared suitable candidates to obtain conformationally rigid adducts between the FC precursors and the catalyst. In this context, chelating (monometallic catalyst) or single-point (bimetallic catalyst) interactions were envisioned (Figure 1).
231 citations
TL;DR: The elusive enantioselective catalytic alpha-alkylation of aldehydes, a widely sought transformation, was brought to execution by the use of alcohols capable of forming stabilized carbocations with respect to trifluoroacetic acid.
Abstract: Fahige Alkohole: Die schwierige enantioselektive katalytische α-Alkylierung von Aldehyden, eine lange gesuchte Umwandlung, wurde mithilfe von Alkoholen mit der Fahigkeit zur Stabilisierung von Carbokationen erreicht (siehe Schema, TFA=Trifluoressigsaure).
222 citations
TL;DR: Mix in water, stir, and that is all that is required in this new approach to sp(3)-sp(2) cross-couplings between an alkyl iodide and an aryl bromide, both potentially bearing functionality.
Abstract: Mix in water, stir. That is all that is required in this new approach to sp(3)-sp(2) cross-couplings between an alkyl iodide and an aryl bromide, both potentially bearing functionality. They react under catalysis by Pd(0) in the presence of zinc powder, aided by a nonionic amphiphile, to give the alkylated aromatic. No organic solvents and no heating; just add water.
214 citations
TL;DR: The research group has reported that modified cinchona alkaloids are outstanding catalysts for the asymmetric allylic alkylation of a,a-dicyanoolefins with MBH carbonates and the deprotonation of the acidic NH group of the MBH base.
Abstract: The indole framework represents a key structural motif in a large number of biologically active natural products and pharmaceutical compounds. Consequently, modifications on the indole structure, including the development of enantioselective variants, have triggered increasing interests. Because of the inherent nucleophilic characteristics of indole compounds, their reactions preferentially take place at the C3-position of the ring system. As a result, the majority of enantioselective reactions of indoles focus on the C3-selective addition of electron-rich indoles to electrophilic imines, epoxides, carbonyl compounds, a,b-unsaturated carbonyl compounds, and nitroalkenes etc., thus leading to the formation of diversely structured enantioenriched C3-functionalized indole derivatives. Recently, the enantioselective synthesis of C2-substituted indoles has also been realized through the asymmetric alkylation of 4,7-dihydroindoles and subsequent oxidation. In sharp contrast to the progress in enantioselective alkylation at the C3or C2-positions, the asymmetric Nalkylation of indoles has been underdeveloped: probably because of the privileged C3-chemoselectivity of indole compounds. The limited examples include the palladiumcatalyzed N-allylic alkylation of 3-substituted indoles developed by Trost et al. and the enantioselective intramolecular aza-Michael addition of tethered indole-2-carboxylates under chiral phase-transfer catalysis developed by Bandini et al. Indeed, N-alkylated indoles have been applied as useful intermediates for the synthesis of polyheterocycles and occur widely among natural products and biologically active pharmaceuticals (Scheme 1). For example, mitomycin C exhibits potent antitumour activity and is used clinically in the treatment of certain cancers. Yuremamine, which was recently isolated from the stem bark of Mimosa hostilis, shows hallucinogenic and psychoactive effects. Pyrrolo[3,2,1-ij]quinoline derivatives are active antihistamines and inhibitors of leukotriene, and they offer the possibility of a novel multimediator approach to the treatment of allergic diseases. Therefore, it would be extremely desirable to develop effective protocols to access optically pure N-alkylated indoles. Recently, the allylic alkylation of Morita-Baylis–Hillman (MBH) adducts catalyzed by a metal-free organic Lewis base has emerged as an attractive strategy to prepare multifunctional compounds. Our research group has also reported that modified cinchona alkaloids are outstanding catalysts for the asymmetric allylic alkylation of a,a-dicyanoolefins with MBH carbonates. We anticipated that, as outlined in Scheme 2, the deprotonation of the acidic NH group of the
209 citations
TL;DR: The present emerging area deals with the recent advances in the use of pi-activated alcohols in the catalytic and stereoselective construction of benzylic stereocenters.
Abstract: The direct functionalization of aromatic compounds, via Friedel–Crafts alkylation reactions with alcohols, is one of the cornerstones in organic chemistry. The present emerging area deals with the recent advances in the use of π-activated alcohols in the catalytic and stereoselective construction of benzylic stereocenters.
208 citations
TL;DR: Regioselective alkenylation and alkylation of 2-pyridone derivatives are achieved through inter- and intramolecular insertion of alkynes, 1,3-dienes, and alkenes into the C(6)-H bond by nickel/AlMe(3) catalysis.
Abstract: Regioselective alkenylation and alkylation of 2-pyridone derivatives are achieved through inter- and intramolecular insertion of alkynes, 1,3-dienes, and alkenes into the C(6)-H bond by nickel/AlMe(3) catalysis. Coordination of the heterocycles to the Lewis acid cocatalyst through their basic carbonyl oxygen is considered to be responsible for the regioselective activation of the C-H bonds, probably through oxidative addition to nickel(0).
TL;DR: A phosphoric acid derived from H8-BINOL enabled an asymmetric alpha-alkylation of enamides with indolyl alcohols to give beta-aryl 3-(3-indolyl)propanones in high yields and with excellent enantioselectivity.
TL;DR: By using loadings of a DNA-based copper catalyst as low as 0.15 mol %, good yields and excellent enantioselectivities were obtained in the reaction of alpha,beta-unsaturated 2-acyl imidazoles with heteroaromatic pi nucleophiles.
Abstract: Taking the plunge: The first example of a Lewis acid catalyzed asymmetric Friedel-Crafts alkylation with olefins in water is described. By using loadings of a DNA-based copper catalyst as low as 0.15 mol %, good yields and excellent enantioselectivities were obtained in the reaction of alpha,beta-unsaturated 2-acyl imidazoles with heteroaromatic pi nucleophiles. dmbpy = 4,4'-dimethyl-2,2'-bipyridine.
TL;DR: The high selectivity of this catalyst for the monoalkylation of aromatic amino functions has been successfully exploited for the alkylation of diamines in both symmetric and nonsymmetric fashions, providing a novel and very efficient synthetic tool for the preparation of N,N'-dialkylated aromatic diamines.
Abstract: Selective amine alkylation: A P,N-ligand-stabilized iridium complex has been used as an efficient catalyst for the alkylation of (hetero)aromatic amines with alcohols at mild reaction temperatures and catalyst loadings as low as 01 mol % Ir (see scheme) The excellent selectivity of the catalyst for monoalkylation of the amine function has also been exploited for the N,N′-dialkylation of diamines in both symmetric and nonsymmetric fashions
A P,N-ligand-coordinated iridium complex has been employed as an efficient catalyst for the selective monoalkylation of (hetero)aromatic amines with alcohols A significant improvement of this alkylation method has been achieved, such that it can be performed at a temperature of 70 °C and with catalyst loadings as low as 01 mol % Ir, while still affording excellent yields of secondary amines Furthermore, the high selectivity of this catalyst for the monoalkylation of aromatic amino functions has been successfully exploited for the alkylation of diamines in both symmetric and nonsymmetric fashions, providing a novel and very efficient synthetic tool for the preparation of N,N′-dialkylated aromatic diamines
TL;DR: The use of boron trifluoride etherate as the Lewis acid and ethylene glycol as the organocatalyst provides a highly active catalytic system, presumably via the in situ formation of alkenyl-oxocarbenium intermediates, which eliminates the need for expensive transition metal Lewis acids or the preparation of ketal substrates.
Abstract: C−H bond functionalization enables strategically new approaches to the synthesis of complex organic molecules including biologically active compounds, research probes and functional organic materials. To address the shortcomings of transition metal catalyzed processes, we have developed a new approach to direct coupling of sp3 C−H bonds and alkenes based on Lewis acid-promoted hydride transfer. Activation of α,β-unsaturated aldehydes and ketones with Lewis acid triggers intramolecular hydride transfer, leading to a zwitterionic intermediate, which in turn undergoes ionic cyclization to afford the cyclic alkylation product. The scope of this method is expanded by the generation of alkenyl-oxocarbenium species as highly activated alkene intermediates capable of abstracting a hydride from unreactive carbon centers, including benzyl-, allyl-, and crotyl-ethers, as well as primary alkyl ethers, at room temperature. The alkenyl acetal and ketal substrates show dramatically faster rates of cyclization, as well a...
TL;DR: Imines and secondary amines were synthesized selectively by controlling reaction conditions for the Pd-catalyzed one-pot reactions of benzyl alcohols with primary amines.
Abstract: Imines and secondary amines were synthesized selectively by controlling reaction conditions for the Pd-catalyzed one-pot reactions of benzyl alcohols with primary amines. The reactions did not require any additives and were effective for a wide range of alcohols and amines.
TL;DR: This work details the development of ruthenium(II) catalysts for the enantioselective alkylation of chiral racemic secondary phosphines through the intermediacy of nucleophilic phosphido species, which have low barriers to pyramidal inversion.
Abstract: This work details the development of ruthenium(II) catalysts for the enantioselective alkylation of chiral racemic secondary phosphines. The reactions proceed through the intermediacy of nucleophilic phosphido species, which have low barriers to pyramidal inversion; this allows for a dynamic kinetic asymmetric alkylation. The initially discovered [((R)-iPr-PHOX)2Ru(H)][BPh4] (6) catalyst was found to be effective in the reaction with benzylic chlorides; moreover, the alkylation displayed an unusual temperature dependence. However, the limited scope of alkylation of 6 motivated further studies which led to the development of two complementary chiral mixed ligand Ru(II) catalysts of type [L1L2Ru(H)]+. These catalysts were derived from a combination of one chiral and one achiral ligand, where a synergistic interaction of the two ligands creates an effective asymmetric environment around the ruthenium center. The (R)-MeO-BiPHEP/dmpe (dmpe = 1,2-bis(dimethylphosphino)ethane) catalyst (10) was found to be effec...
TL;DR: Preliminary mechanistic investigations suggest bridging metallaaziridine species are the catalytically active intermediates for this alpha-functionalization reaction, while monomeric imido complexes furnish azepane hydroamination products.
Abstract: Selective α-C−H activation results in the synthesis of the first bridging metallaaziridine complex for the catalytic α-alkylation of primary amines. Reaction development led to the preparation of n...
TL;DR: A new model involving two regiochemically distinct (NH) and (CO) locations for nucleofuge or nucleophile binding, may prove of broad utility for the interpretation of the selectivity in asymmetric allylic alkylation reactions catalyzed by Pd complexes of (R,R)-1 and related ligands.
Abstract: The solution-phase structures of the monomeric forms of the cationic Pd-η3-allyl and Pd-η3-cyclohexenyl complexes [Pd(R,R)-1(η3-C3H5)]+ (7+) and [Pd(R,R)-1(η3-C6H9)]+ (8+) bearing the trans-cyclohexylenediamine-based Trost ‘Standard Ligand’ (R,R)-1 have been elucidated by NMR, isotopic labeling and computation. In both complexes, (R,R)-1 is found to adopt a C1-symmetric conformation, leading to a concave shape in the 13-membered chelate in which one amide group in the chiral scaffold projects its NH unit out of the concave surface in close vicinity to one allyl terminus. The adjacent amide has a reversed orientation and projects its carbonyl group out of the concave face in the vicinity of the opposite allyl terminus. Stoichiometric and catalytic asymmetric alkylations of [8+][X−] by MCHE2 (E = ester, M = ‘escort’ counterion, X = Pd allyl counterion) show the same selectivities and trends as have been reported for in situ-generated catalysts, and a new model for the enantioselectivity has been explored co...
TL;DR: An X-ray crystal structure of the N-benzyl derivative reveals a conformation that permits hydrogen transfer through a six-membered transition state, and a transition state structure for the imine reduction process is proposed.
24 Jun 2009
TL;DR: In this paper, the authors proposed a Catalytic Enantioselective Hydroactivelation of Allenylindoles (AEH) reaction for the first time, based on the catalytic enantiorelective reaction of Friedel-Crafts reaction.
Abstract: GENERAL ASPECTS AND HISTORICAL BACKGROUND Introduction General Aspects and Historical Background Catalytic Enantioselective FC Reactions: An Introduction MICHAEL ADDITION Chelating Alpha, Beta-Unsaturated Compounds Simple Alpha, Beta-Unsaturated Substrates Nitroalkenes ADDITION TO CARBONYL COMPOUNDS Aldehydes/Ketones Imines NUCLEOPHILIC ALLYLIC ALKYLATION AND HYDROARYLATION OF ALLENES Introduction Allylic Alkylations Metallo-Catalyzed Hydroarylation of Allenes NUCLEOPHILIC SUBSTITUTION ON CSP3 CARBON ATOMS Ring-Opening of Epoxides Direct Activation of Alcohols UNACTIVATED ALKENES Introduction Early Studies Rh(I)-Catalyzed Enantioselective Hydroarylation of Iminoarenes Pt(II)-Catalyzed Enantioselective Hydroarylation of Alkenylidoles Au(II)-Catalyzed Enantioselective Hydroarylation of Allenylindoles Conclusions and Outlook Experimental: Selected Procedures CATALYTIC ASYMMETRIC FRIEDEL-CRAFTS ALKYLATIONS IN TOTAL SYNTHESIS Introduction Total Synthesis of Indole-Containing Compounds Total Synthesis of Pyrrole-Containing Compounds Friedel-Crafts Alkylation of Furan Derivatives in Total Synthesis Friedel-Crafts Alkylation of Arenes in Total Synthesis Asymmetric Synthesis of Natural Products Based on Diastereoselective Friedel-Crafts Reactions INDUSTRIAL FRIEDEL-CRAFTS IN CHEMISTRY Introduction Green Chemistry and the Friedel-Crafts Reaction Heterogeneous Catalysts for the Friedel-Crafts Reaction Large Scale Hydrocarbon Processing Conclusions and Perspectives
TL;DR: The Sc(OTf)(3)-catalyzed C-C bond formation by direct alkylation of quinolines and pyridines using simple alkanes was developed and yielded 50-91% yields in the presence of tert-butyl peroxide.
TL;DR: Sulfonic acid group (SO3H)-bearing amorphous carbon/mesoporous silica composites were studied for use as solid acid catalysts in this paper.
Abstract: Sulfonic acid group (SO3H)-bearing amorphous carbon/mesoporous silica composites were studied for use as solid acid catalysts. Sugar-derived amorphous carbon with SO3H cannot catalyze hydrophobic acid-catalyzed reactions, such as the dimerization of α-methylstyrene, because of the small surface area. However, SO3H-bearing sugar-derived amorphous carbon supported on mesoporous silica exhibits remarkable catalytic performance for the dimerization of α-methylstyrene. Under optimal conditions, the selectivity of the composite catalysts for unsaturated dimers exceeds 98%. Structural and reaction analyses revealed that SO3H-bearing carbon particles with large surface areas are formed in the mesopores and prevent intramolecular Friedel−Crafts alkylation, resulting in high catalytic activity.
TL;DR: In this paper, a chiral boronic ester (substrate control) can be used for stereocontrolled homologations with (dichloromethyl)lithium in the presence of ZnCl2.
Abstract: Organoboranes and boronic esters readily undergo nucleophilic addition, and if the nucleophile also bears an α-leaving group, 1,2-metallate rearrangement of the ate complex results. Through such a process a carbon chain can be extended, usually with high stereocontrol and this is the focus of this review. A chiral boronic ester (substrate control) can be used for stereocontrolled homologations with (dichloromethyl)lithium in the presence of ZnCl2. Subsequent alkylation by an organometallic reagent also occurs with high levels of stereocontrol. Chiral lithiated carbanions (reagent control) can also be used for the reaction sequence with achiral boronic esters and boranes. Aryl-stabilized sulfur ylide derived chiral carbanions can be homologated with a range of boranes including vinyl boranes in good yield and high diastereo- and enantioselectivity. Lithiated alkyl chlorides react with boronic esters, again with high stereocontrol, but both sets of reactions are limited in scope. Chiral lithiated carbamates show the greatest substrate scope and react with both boronic esters and boranes with excellent enantioselectivity. Furthermore, iterative homologation with chiral lithiated carbamates allows carbon chains to be "grown" with control over relative and absolute ste- reochemistry. The factors responsible for stereocontrol are discussed. © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 24-39; 2009: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20168
TL;DR: The ethyl oxazole-4-carboxylate was directly and regioselectivelyAlkenylated, benzylated and alkylated with alkenyl-, benzyl-, allyl- and alKYl halides in the presence of catalytic amounts of palladium acetate with caesium carbonate using Buchwald's JohnPhos ligand.
Abstract: The ethyl oxazole-4-carboxylate was directly and regioselectively alkenylated, benzylated and alkylated with alkenyl-, benzyl-, allyl- and alkyl halides in the presence of catalytic amounts of palladium acetate with caesium carbonate using Buchwald's JohnPhos ligand.
TL;DR: Some organoaluminum compounds, especially methylaluminoxane, are capable of AlkDF with more reactive substrates, but catalysis by alumenium offers an advantage over the uncatalyzed C-F activation in terms of both increased rate and, in some cases, a dramatically increased selectivity.
Abstract: Dialkylalumenium cation equivalents coupled with the hexabromocarborane anion function as efficient and long-lived catalysts for alkylation of aliphatic C-F bonds (alkylative defluorination or AlkDF) by alkylaluminum compounds. Only C(sp(3))-F bonds undergo AlkDF; C(sp(2))-F bonds are unaffected. Examples of compounds undergoing AlkDF include monofluoroalkanes, gem-difluorocyclopentane, and compounds containing a CF(3) group attached to either an aryl or an alkyl substituent. Conversion of C-F bonds to C-Me bonds is accomplished with high fidelity using Me(3)Al as the stoichiometric reagent. In reactions with Et(3)Al, hydrodefluorination of the C-F bonds is competitive with alkylation, indicative presumably of competitive hydride vs alkyl transfer from Et(3)Al. In a trialkylaluminum reagent, 1.1-1.4 alkyl groups per Al can be used to replace C-F bonds. Organoaluminum compounds efficiently remove water from the reaction mixture, obviating the need for rigorously dry solvents. Some organoaluminum compounds, especially methylaluminoxane, are capable of AlkDF with more reactive substrates, but catalysis by alumenium offers an advantage over the uncatalyzed C-F activation in terms of both increased rate and, in some cases, a dramatically increased selectivity.
TL;DR: It is found that the reversible process is a prerequisite to DNA alkylation, which in turn reinforces the G-quadruplex structural rearrangement.
Abstract: We have developed novel G-quadruplex (G-4) ligand/alkylating hybrid structures, tethering the naphthalene diimide moiety to quaternary ammonium salts of Mannich bases, as quinone-methide precursors, activatable by mild thermal digestion (40 °C). The bis-substituted naphthalene diimides were efficiently synthesized, and their reactivity as activatable bis-alkylating agents was investigated in the presence of thiols and amines in aqueous buffered solutions. The electrophilic intermediate, quinone-methide, involved in the alkylation process was trapped, in the presence of ethyl vinyl ether, in a hetero Diels−Alder [4 + 2] cycloaddition reaction, yielding a substituted 2-ethoxychroman. The DNA recognition and alkylation properties of these new derivatives were investigated by gel electrophoresis, circular dichroism, and enzymatic assays. The alkylation process occurred preferentially on the G-4 structure in comparison to other DNA conformations. By dissecting reversible recognition and alkylation events, we f...
TL;DR: In this paper, a variety of aromatic and heteroaromatic amines were selectively converted into the corresponding secondary amines in moderate to excellent yields without any co-catalysts such as bases and stabilizing ligands.
TL;DR: The reaction between acetylenes and sulfoxides, studied as a test case for gold-catalyzed intermolecular addition, provides the oxyarylation compounds 3 in good yields.