Methylation is one of the most fundamental synthetic transformations in organic chemistry, but usually employs hazardous and toxic reagents, such as methyl iodide, dimethyl sulfate, diazomethane and dimethyl carbonate. In order to address sustainable development and green strategies, synthetic chemists have devoted much effort to the discovery and development of new methylating reagents, which are successfully being applied in transition metal‐catalyzed cross‐coupling reactions. In this review, recent advances in this area are summarized, mainly including C‐methylation, N‐methylation and O‐methylation. The respective reaction mechanisms are also discussed.
Since the first definition of domino reactions by Tietze in 1993, an explosive number of these fascinating reactions has been developed, allowing the easily building of complex chiral molecular architectures from simple materials to be achieved in a single step. Even more interesting, the possibility to join two or more reactions in one asymmetric domino process catalyzed by chiral metal catalysts has rapidly become one challenging goal for chemists, due to economical advantages, such as avoiding costly protecting groups and time‐consuming purification procedures after each step. The explosive development of enantioselective metal‐catalyzed domino including multicomponent reactions is a consequence of the considerable impact of the advent of asymmetric transition metal catalysis. This review aims to update the last developments of enantioselective one‐, two‐ and multicomponent domino reactions mediated by chiral metal catalysts, covering the literature since the beginning of 2006. Abbreviations: Ac: acetyl; AQN: anthraquinone; Ar: aryl; bdpp: 2,4‐bis(diphenylphosphino)pentane; BINAP: 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl; BINEPINE: phenylbinaphthophosphepine; BINIM: binapthyldiimine; BINOL: 1,1′‐bi‐2‐naphthol; BIPHEP: 2,2′‐bis(diphenylphosphino)‐1,1′‐biphenyl; Bn: benzyl; Boc: tert‐butoxycarbonyl; Box: bisoxazoline; BOXAX: 2,2′‐bis(oxazolyl)‐1,1′‐binaphthyl; BPTV: N‐benzene‐fused phthaloyl‐valine; Bu: butyl; Bz: benzoyl; Cat: catechol; Chiraphos: 2,3‐bis(diphenylphosphine)butane; cod: cyclooctadiene; Cy: cyclohexyl; DABCO: 1,4‐diazabicyclo[2.2.2]octane; dba: (E,E)‐dibenzylideneacetone; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCE: dichloroethane; de: diastereomeric excess; DHQ: hydroquinine; DHQD: dihydroquinidine; DIFLUORPHOS: 5,5′‐bis(diphenylphosphino)‐2,2,2′,2′‐tetrafluoro‐4,4′‐bi‐1,3‐benzodioxole; DIPEA: diisopropylethylamine; DMF: dimethylformamide; DMSO: dimethyl sulfoxide; DOSP: N‐p‐dodecylbenzenesulfonylprolinate; DPEN: 1,2‐diphenylethylenediamine; dtb: di‐tert‐butyl; dtbm: di‐tert‐butylmethoxy; E: electrophile; ee: enantiomeric excess; Et: ethyl; FBIP: ferrocene bis‐imidazoline bis‐palladacycle; Fc: ferrocenyl; FOXAP: ferrocenyloxazolinylphosphine; Hex: hexyl; HFIP: hexafluoroisopropyl alcohol; HMPA: hexamethylphosphoramide; iPr‐DuPhos: 1,2‐bis(2,5‐diisopropylphospholano)benzene; Josiphos: 1‐[2‐(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine ethanol adduct; L: ligand; MCPBA: 3‐chloroperoxybenzoic acid; Me: methyl; Me‐DuPhos: 1,2‐bis(2,5‐dimethylphospholano)benzene; MEDAM: bis(dimethylanisyl)methyl; MOM: methoxymethyl; Naph: naphthyl; NMI: N‐methylimidazole; MWI: microwave irradiation; Norphos: 2,3‐bis(diphenylphosphino)‐bicyclo[2.2.1]hept‐5‐ene; Ns: nosyl (4‐nitrobenzene sulfonyl); Nu: nucleophile; Oct: octyl; Pent: pentyl; Ph: phenyl; PHAL: 1,4‐phthalazinediyl; Pin: pinacolato; PINAP: 4‐[2‐(diphenylphosphino)‐1‐naphthalenyl]‐N‐[1‐phenylethyl]‐1‐phthalazinamine; Pr: propyl; Py: pyridyl; PYBOX: 2,6‐bis(2‐oxazolyl)pyridine; QUINAP: 1‐(2‐diphenylphosphino‐1‐naphthyl)isoquinoline; QUOX: quinoline‐oxazoline; Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole; Solphos: 7,7′‐bis(diphenylphosphino)‐3,3′,4,4′‐tetrahydro‐4,4′‐dimethyl‐8,8′‐bis‐2H‐1,4‐benzoxazine; SPRIX: spirobis(isoxazoline); SYNPHOS: 6,6′‐bis(diphenylphosphino)‐2,2′,3,3′‐tetrahydro‐5,5′‐bi‐1,4‐benzodioxin; Taniaphos: [2‐diphenylphosphinoferrocenyl](N,N‐dimethylamino)(2‐diphenylphosphinophenyl)methane; TBS: tert‐butyldimethylsilyl; TC: thiophene carboxylate; TCPTTL: N‐tetrachlorophthaloyl‐tert‐leucinate; TEA: triethylamine; Tf: trifluoromethanesulfonyl; TFA: trifluoroacetic acid; THF: tetrahydrofuran; TMS: trimethylsilyl; Tol: tolyl; Ts: 4‐toluenesulfonyl (tosyl); C3‐Tunephos: 1,13‐bis(diphenylphosphino)‐7,8‐dihydro‐6H‐dibenzo[f,h][1,5]dioxonin; VAPOL: 2,2′‐diphenyl‐[3,3′‐biphenanthrene]‐4,4′‐diol 相似文献
Different to the borrowing hydrogen strategy in which alcohols were activated by transition metal‐catalyzed anaerobic dehydrogenation, the direct addition of aldehydes was found to be an effective but simpler way of alcohol activation that can lead to efficient and green aldehyde‐catalyzed transition metal‐free dehydrative C‐alkylation of methyl carbinols with alcohols. Mechanistic studies revealed that the reaction proceeds via in situ formation of ketones by Oppenauer oxidation of the methyl carbinols by external aldehydes, aldol condensation, and Meerwein–Ponndorf–Verley (MPV)‐type reduction of α,β‐unsatutated ketones by substrate alcohols, affording the useful long chain alcohols and generating aldehydes and ketones as the by‐products that will be recovered in the next condensation to finish the catalytic cycle. 相似文献
A direct transition metal‐free regioselective C‐3 amidation of indoles has been developed with the commercially available N‐fluorobenzenesulfonimide (NFSI) as the amino source under external oxidant‐free conditions. This amidation requires only a catalytic amount of base and exhibits excellent functional group tolerance and regioselectivity. The C‐3 regioselectivity was proposed to realize by a free radical mechanism.
A potassium hydroxide/dimethyl sulfoxide (KOH/DMSO) superbase‐promoted method for the synthesis of 2‐substituted benzothiophenes has been developed via photoinduced intermolecular annulation of 2‐halothioanisoles with terminal alkynes at ambient temperature. The present protocol uses commercially available 2‐halothioanisoles as substrates and visible light as energy force, which offers a wide range of benzothiophenes regioselectively in moderate to good yields. Such a facile and effective transformation will provide an environment‐friendly approach to the synthesis of benzothiophene derivatives.
Amines are important building blocks possessing various applications in agrochemicals, the fine chemical industry, pharmaceuticals, materials science and biotechnology. The catalytic hydrogenation of nitriles is an important reaction for the one‐step synthesis of diverse amines. However, significant amounts of side product formation during the course of the reaction is a major issue. In recent years, an enormous amount of work has been reported using both homogeneous and heterogeneous transition metal complex catalysts for the selective reduction of nitriles. Transition metal catalysts are the most crucial factor that controls the selectivity in this reaction. Therefore, transition metal catalysts are the central point of this review. We have also briefly discussed the effect of reaction parameters, selectivity to different substrate structures and reaction mechanisms. This review provides an overview of recent developments in transition metal‐catalyzed nitrile reduction along with examples which highlight its vast potential in organic transformations.
A series of novel quinoline derivatives having a spirocyclopropyl ring can be synthesized by one‐pot, three‐component aza‐Diels–Alder reactions of arenecarbaldehydes, arylamines, and methylenecyclopropanes (MCPs) using a heterogeneous solid acid catalyst, montmorillonite KSF, under mild reaction conditions in good to excellent yields. 相似文献
In contrast to the borrowing hydrogen‐type N‐alkylation reactions, in which alcohols were activated by transition metal‐catalyzed anaerobic dehydrogenation, the addition of external aldehydes was accidentally found to be a simple and effective protocol for alcohol activation. This interesting finding subsequently led to an efficient and green, practical and scalable aldehyde‐catalyzed transition metal‐free dehydrative N‐alkylation method for a variety of amides, amines, and alcohols. Mechanistic studies revealed that this reaction most possibly proceeds via a simple but interesting transition metal‐free relay race mechanism. 相似文献
This work has established the first direct homocoupling of unactivated electron‐deficient azaarenes in the presence of TMPMgCl (2,2,6,6‐tetramethylpiperidinylmagnesium chloride) and TMEDA (tetramethylethylenediamine). In this process, no transition metal was used while freely available air was employed as the oxidant. The investigated successful substrates included quinolines, isoquinoline, 3‐phenylated pyridines, and 2‐phenylated quinoxalines, giving moderate to high yields. The homocoupling of quinolines was effectively scaled up to one gram in high yield. Additionally, an iridium complex of 6,6′‐dimethyl‐2,2′‐biquinoline was prepared and characterized as an efficient red‐emitting material.
A synthetic approach to the synthesis of novel tryptophan derivatives and benzofuran‐containing amino acids is detailed. The sequence starts from enzymatically resolved enantiopure acetylene‐containing amino acids, of which the acetylene function can be efficiently transformed into the targeted 2‐substited indole and benzofuran moieties via Sonogashira‐type coupling and metal‐catalyzed cyclization. 相似文献
Readily available 1‐(ortho‐ethynylaryl)urea derivatives undergo a selective gold/silver {[AuCl(IPr)]/AgSbF6} catalyzed N‐6‐exo‐dig or N‐5‐endo‐dig heterocyclization process in dimethylformamide (DMF) at 60 °C. Benzoxazine derivatives, i.e., the products of O‐6‐exo‐dig ring closure through the urea oxygen, could be observed under catalytic conditions only when the N‐3 basicity was substantially diminished, but were readily isolable in stoichiometric processes carried out at low temperature. The open chain amino O,O‐acetals and a series of new cyclic mixed N,O‐acetals containing the trifluoroethyl group were synthesized when the reactions were performed in ethanol or trifluoroethanol, respectively, as solvent. The procedure allows for an easy access to this versatile class of key intermediates in organic synthesis from simple starting materials. The effect of using either DMF or protic solvents on the course of the reactions is reported.
The indium‐catalyzed Barbier‐type reaction of Cbz‐protected amino aldehydes with methyl 2‐(bromomethyl)acrylate in the presence of aluminum or manganese/Me3SiCl was investigated. Best results were obtained using 0.15 equiv. InCl3 with excess aluminum. No significant differences between catalyzed and stoichiometric reaction conditions were observed. Addition of chiral auxiliaries did not improve selectivities in indium‐mediated allyl additions. 相似文献
Reaction of dialkyl disulfides or diselenides with allenes is catalyzed by a rhodium‐phosphine complex and trifluoromethanesulfonic acid giving (E)‐2‐alkylthio(seleno)‐1,3‐dienes and (E)‐2‐alkylthio(seleno)‐2‐alkenes. Unlike the reaction of alkynes, the reaction of allene is accompanied by hydride transfer. 相似文献
A transition metal‐free, facile and efficient one‐pot protocol for the synthesis of propynenitriles from readily available 3‐chloropropenals is disclosed. The reaction conditions have also been optimized for the exclusive formation and isolation of 3‐chloropropenenitriles which are important building blocks in general and are intermediates in the synthesis of propynenitriles. The hallmark of the methodology is the use of non‐toxic reagents, milder, metal‐free and economically benign reaction conditions avoiding a harsh dehydration step while achieving excellent yields.
The visible light‐induced iodine‐catalyzed oxidative cleavage of the CC bond for transforming terminal alkynes into primary amides in the presence of ammonia under aqueous conditions is described. This metal‐free protocol which ensued via initial hydroamination of the acetylene bond followed by liberation of diiodomethane (CH2I2) was found to be applicable to aromatic, heteroaromatic and aliphatic alkynes.
An efficient strategy for carbazole synthesis from arylureas and cyclohexanones under transition metal‐free conditions has been developed. The combined use of potassium iodide and iodine could significantly improve the reaction efficiency to provide 2,6‐disubstituted 9‐arylcarbazoles in moderate to good yields. In this kind of transformation, the whole carbazole moiety (except the nitrogen atom) comes from two equivalents of cyclohexanones.
The hydroamination of terminal alkynes (RCCH=phenylacetylene, 4‐methylphenylacetylene, 4‐fluorophenylacetylene, 1‐hexyne, methyl 2‐propynyl ether, prop‐2‐yn‐1‐ol) with secondary amines (piperidine, pyrrolidine, morpholine, piperazine, methylpiperazine, 4‐methylpiperidine and 3‐methylpiperidine) was achieved in high yield (up to 99%), regioselectivity (only anti‐Markovnikov product) and stereoselectivity (only E‐isomers) within a maximum of 5 h in reactions catalyzed by the tungsten tetracarbonyl complex cis‐[W(CO)4(piperidine)2] at 90 °C without any additional solvent.
