Iron‐Catalyzed Mild and Selective Hydrogenative Cross‐Coupling of Nitriles and Amines To Form Secondary Aldimines

The first example of a base‐metal‐catalyzed homogeneous hydrogenative coupling of nitriles and amines to selectively form secondary cross‐imines is reported. The reaction is catalyzed under mild conditions by a well‐defined (iPr‐PNP)Fe(H)Br(CO) pincer pre‐catalyst and catalytic t BuOK.     

A Metalloenzyme‐Like Catalytic System for the Chemoselective Oxidative Cross‐Coupling of Primary Amines to Imines under Ambient Conditions

The direct oxidative cross‐coupling of primary amines is a challenging transformation as homocoupling is usually preferred. We report herein the chemoselective preparation of cross‐coupled imines through the synergistic combination of low loadings of Cu^II metal‐catalyst and o‐iminoquinone organocatalyst under ambient conditions. This homogeneous cooperative catalytic system has been inspired by the reaction of copper amine oxidases, a family of metalloenzymes with quinone organic cofactors that mediate the selective oxidation of primary amines to aldehydes. After optimization, the desired cross‐coupled imines are obtained in high yields with broad substrate scope through a transamination process that leads to the homocoupled imine intermediate, followed by dynamic transimination. The ability to carry out the reactions at room temperature and with ambient air, rather than molecular oxygen as the oxidant, and equimolar amounts of each coupling partner is particularly attractive from an environmentally viewpoint.     

Disulfonimide‐Catalyzed Asymmetric Reduction of N‐Alkyl Imines

A chiral disulfonimide (DSI)‐catalyzed asymmetric reduction of N‐alkyl imines with Hantzsch esters as a hydrogen source in the presence of Boc₂O has been developed. The reaction delivers Boc‐protected N‐alkyl amines with excellent yields and enantioselectivity. The method tolerates a large variety of alkyl amines, thus illustrating potential for a general reductive cross‐coupling of ketones with diverse amines, and it was applied in the synthesis of the pharmaceuticals (S)‐Rivastigmine, NPS R‐568 Hydrochloride, and (R)‐Fendiline.     

MnO2/graphene oxide: A highly efficient catalyst for imine synthesis from alcohols and amines

α‐MnO₂ nanocrystals supported on graphene oxide (α‐MnO₂/GO) was prepared through a soft chemical route and evaluated for the first time as a novel, eco‐friendly and efficient catalyst in the coupling reaction of alcohols and amines to imines. The well‐organized α‐MnO₂/GO was characterized using various techniques. The results show that MnO₂ nanocrystals are highly dispersed on the GO sheets and interconnected with each other, leading to large available surface area, which greatly enhances the catalytic performance of conventional MnO₂. Under mild conditions, the catalyst exhibits excellent catalytic activity and selectivity with O₂ serving as terminal oxidant. Various imines can be smoothly obtained in good to excellent yield. Importantly, the catalyst is easily recovered and can be reused six times with no significant loss of activity.     

Copper Catalyzed C−H Activation

Activation of C?H bonds and their application in cross coupling chemistry has received a wider interest in recent years. The conventional strategy in cross coupling reaction involves the pre‐functionalization step of coupling reactants such as organic halides, pseudo‐halides and organometallic reagents. The C?H activation facilitates a simple and straight forward approach devoid of pre‐functionalization step. This approach also addresses the environmental and economical issues involved in several chemical reactions. In this account, we have reported C?H bond activation of small organic molecules, for example, formamide C?H bond can be activated and coupled with β‐dicarbonyl or 2‐carbonyl substituted phenols under oxidative conditions to yield carbamates using inexpensive copper catalysts. Phenyl carbamates were successfully synthesized in moderate to good yields by cross dehydrogenative coupling (CDC) of phenols with formamides using copper catalysts in presence of a ligand. We have also prepared unsymmetrical urea derivatives by oxidative cross coupling of formamides with amines using copper catalysts. Synthesis of N,N‐dimethyl substituted amides, 5‐substituted‐γ‐lactams and α‐acyloxy ethers was carried out from carboxylic acids using recyclable CuO nanoparticles. Copper nanoparticles afforded N‐aryl‐γ‐amino‐γ‐lactams by oxidative coupling of aromatic amines with 2‐pyrrolidinone. Reusable transition metal HT‐derived oxide catalyst was used for the synthesis of N,N‐dimethyl substituted amides by the oxidative cross‐coupling of carboxylic acids and substituted benzaldehydes. Overview of our work in this area is summarized.     

氧化铝负载的银纳米颗粒高选择性催化合成亚胺(英)

The oxidative dehydrogenation of alcohols to aldehydes catalyzed by Ag nanoparticles supported on Al₂O₃ was studied.The catalyst promoted the direct formation of imines by tandem oxidative dehydrogenation and condensation of alcohols and amines.The reactions were performed under mild conditions and afforded the imines in high yield（up to 99%） without any byproducts other than H₂O.The highest activity was obtained over 5 wt%Ag/Al₂O₃ in toluene with air as oxidant.The reactions were also performed under oxidant-free conditions where the reaction was driven to the product side by the production of H₂ in the gas phase.The use of an efficient and selective Ag catalyst for the oxidative dehydrogenation of alcohol in the presence of amines gives a new green reaction protocol for imine synthesis.     

Nickel(0)‐Catalyzed Hydroalkenylation of Imines with Styrene and Its Derivatives

A nickel(0)‐catalyzed hydroalkenylation of imines with styrene and its derivatives is described. A wide range of aromatic and aliphatic imines directly coupled with styrene and its derivatives, thus providing various synthetically useful allylic amines with up to 95 % yield. The reaction offers a new atom‐ and step‐economical approach to allylic amines by using alkenes instead of alkenyl‐metallic reagents. Experiments and DFT calculations showed that TsNH₂ promotes the proton transfer from the coordinated olefin to the imine, accompanied by a new C?C bond formation.     

Continuous‐Flow Oxidative Cyanation of Primary and Secondary Amines Using Singlet Oxygen

Primary and secondary amines can be rapidly and quantitatively oxidized to the corresponding imines by singlet oxygen. This reactive form of oxygen was produced using a variable‐temperature continuous‐flow LED‐photoreactor with a catalytic amount of tetraphenylporphyrin as the sensitizer. α‐Aminonitriles were obtained in good to excellent yields when trimethylsilyl cyanide served as an in situ imine trap. At 25°C, primary amines were found to undergo oxidative coupling prior to cyanide addition and yielded secondary α‐aminonitriles. Primary α‐aminonitriles were synthesized from the corresponding primary amines for the first time, by an oxidative Strecker reaction at –50 °C. This atom‐economic and protecting‐group‐free pathway provides a route to racemic amino acids, which was exemplified by the synthesis of tert‐leucine hydrochloride from neopentylamine.     

Asymmetric control in Diels–Alder cycloadditions of chiral 9-aminoanthracenes by relay of stereochemical information

Two approaches to the synthesis of chiral 9-amino anthracenes are described. The first, by nucleophilic addition of organolithium reagents to imines promoted by BF₃·OEt₂, unexpectedly provided stable aminoboranes as products. The second approach, using palladium catalysed cross coupling, was more successful for primary amines, and the key 9-(α-methylbenzylamino)anthracene subjected to cycloadditions with N-methyl maleimide and maleic anhydride. Excellent reactivity was achieved with good levels of diastereoselectivity, through a favourable combination of electrostatic and hydrogen bonding effects. Trial studies of the retro Diels–Alder reaction of these cycloadducts were also performed.     

Direct synthesis of imines by 9-azabicyclo-[3,3,1]nonan-N-oxyl/KOH-catalyzed aerobic oxidative coupling of alcohols and amines

A simple and efficient method for preparation of imines by the oxidative coupling of alcohols and amines using ABNO/KOH as the catalysts, and air as the economic and green oxidant was developed.     

Ruthenium‐Catalyzed Reductive Methylation of Imines Using Carbon Dioxide and Molecular Hydrogen

The use of the well‐defined [Ru(triphos)(tmm)] catalyst, CO₂ as C₁ source, and H₂ as reducing agent enabled the reductive methylation of isolated imines, as well as the direct coupling of amines with aldehydes and the subsequent reductive methylation of the in situ formed imines. The method, which afforded the corresponding N‐methyl amines in very good to excellent yields, was also used for the preparation of the antifungal agent butenafine in one step with no apparent waste, thus increasing the atom efficiency of its synthesis.     

Highly selective oxidation of amines to imines by Mn2O3 catalyst under eco-friendly conditions

Enhancing the selectivity of imines for the oxidative self-coupling of primary amines was found to be challenging in the heterogeneous catalysis. Three different manganese oxides (M-3, M-4, M-5) were synthesized by controlling the calcination temperature using a simple template-free oxalate route. The prepared manganese oxides were systematically characterized using XRD, N₂ sorption, SEM, TEM, XPS, H₂-TPR techniques. M-4 gave 96.2% selectivity of imine at 100% conversion of benzylamine, which was far more superior than other existing protocols. Mn³⁺/Mn⁴⁺ ratio was found to affect the selectivity of the imines. The probable reaction pathway for amines oxidation catalyzed by manganese oxides was proposed for the first time.     

Pt-Sn/γ-Al2O3-catalyzed highly efficient direct synthesis of secondary and tertiary amines and imines

Versatile syntheses of secondary and tertiary amines by highly efficient direct N‐alkylation of primary and secondary amines with alcohols or by deaminative self‐coupling of primary amines have been successfully realized by means of a heterogeneous bimetallic Pt–Sn/γ‐Al₂O₃ catalyst (0.5 wt % Pt, Pt/Sn molar ratio=1:3) through a borrowing‐hydrogen strategy. In the presence of oxygen, imines were also efficiently prepared from the tandem reactions of amines with alcohols or between two primary amines. The proposed mechanism reveals that an alcohol or amine substrate is initially dehydrogenated to an aldehyde/ketone or NH‐imine with concomitant formation of a [PtSn] hydride. Condensation of the aldehyde/ketone species or deamination of the NH‐imine intermediate with another molecule of amine forms an N‐substituted imine which is then reduced to a new amine product by the in‐situ generated [PtSn] hydride under a nitrogen atmosphere or remains unchanged as the final product under an oxygen atmosphere. The Pt–Sn/γ‐Al₂O₃ catalyst can be easily recycled without Pt metal leaching and has exhibited very high catalytic activity toward a wide range of amine and alcohol substrates, which suggests potential for application in the direct production of secondary and tertiary amines and N‐substituted imines.     

Synthesis of Heterodinuclear Hemisalen Complexes on a Hexaarylbenzene Scaffold and their Application for the Cross‐Pinacol Coupling Reaction

Intermolecular cross‐pinacol coupling reaction between aliphatic and aromatic aldehydes by using heterodinuclear hemisalen complexes 1 _cis with vanadium(V) and titanium(IV) on a hexaarylbenzene scaffold is reported. Our ligand design is based on the individual activation of two aldehydes by vanadium and titanium, which are positioned with a suitable space on the rigid scaffold. Ligands such as 1 _cis were synthesized by Diels–Alder addition and decarbonylation reaction, followed by condensation of dialdehyde 3 _cis with various aminophenols. The influence of the substituents on the ligands on the pinacol coupling reaction was investigated. As a result, the reductive coupling reaction between aliphatic and aromatic aldehydes by using a catalytic amount of 1 _cis in the presence of Me₃SiCl and Zn provided the corresponding cross‐coupled 1,2‐diol in good yields with high cross‐selectivity.     

A Highly Versatile Catalyst System for the Cross‐Coupling of Aryl Chlorides and Amines

The syntheses of 2‐(di‐tert‐butylphosphino)‐N,N‐dimethylaniline ( L1 , 71 %) and 2‐(di‐1‐adamantylphosphino)‐N,N‐dimethylaniline ( L2 , 74 %), and their application in Buchwald–Hartwig amination, are reported. In combination with [Pd(allyl)Cl]₂ or [Pd(cinnamyl)Cl]₂, these structurally simple and air‐stable P,N ligands enable the cross‐coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl‐ and arylamines, cyclic and acyclic secondary amines, N? H imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5–0.02 mol % Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross‐coupling reactions involving 1,4‐bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)₂, PdCl₂, [PdCl₂(cod)] (cod=1,5‐cyclooctadiene), [PdCl₂(MeCN)₂], or [Pd₂(dba)₃] (dba=dibenzylideneacetone) in combination with L1 or L2 , or by use of [Pd(allyl)Cl]₂ or [Pd(cinnamyl)Cl]₂ with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortho‐dimethylamino fragment. Given current limitations associated with established ligand classes with regard to maintaining high activity across the diverse possible range of C? N coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross‐coupling of aryl chlorides and amines.     

Mimicking the environment of living organisms to achieve the oxidative coupling of amines to imines catalyzed by water-soluble metalloporphyrins

Highly efficient procedure for preparing imines from the oxidative coupling of amines catalyzed by metalloporphyrins using water as the only solvent has been developed. Manganese porphyrin showed an excellent activity for the oxidative coupling of a wide range of amines under mild conditions. Further investigations of the oxidative coupling reaction led to the elucidation of the possible mechanism.     

Transition‐Metal‐Free Oxidative Cross‐Coupling of Tetraarylborates to Biaryls Using Organic Oxidants

Readily prepared tetraarylborates undergo selective (cross)‐coupling through oxidation with Bobbitt's salt to give symmetric and unsymmetric biaryls. The organic oxoammonium salt can be used either as a stoichiometric oxidant or as a catalyst in combination with in situ generated NO₂ and molecular oxygen as the terminal oxidant. For selected cases, oxidative coupling is also possible with NO₂/O₂ without any additional nitroxide‐based cocatalyst. Transition‐metal‐free catalytic oxidative ligand cross‐coupling of tetraarylborates is unprecedented and the introduced method provides access to various biaryl and heterobiaryl systems.     

Cross‐Coupling of Alkyl Redox‐Active Esters with Benzophenone Imines: Tandem Photoredox and Copper Catalysis

Alkyl amines are an important class of organic compounds in medicinal and materials chemistry. Until now very have been very few methods for the synthesis of alkyl amines by metal‐catalyzed cross‐coupling of alkyl electrophiles with nitrogen nucleophiles. Described here is an approach to employ tandem photoredox and copper catalysis to enable the cross‐coupling of alkyl N‐hydroxyphthalimide esters, readily derived from alkyl carboxylic acids, with benzophenone‐derived imines. Hydrolysis of the coupling products furnish alkylated primary amines. Primary, secondary, and tertiary alkyl groups can be transferred, and the coupling tolerates a diverse set of functional groups. The method allows rapid functionalization of natural products and drugs, and can be used to expedite syntheses of pharmaceuticals from readily available chemical feedstocks.     

Magnetized inorganic–bioorganic nanohybrid [nano Fe3O4‐SiO2@Glu‐Cu (II)]: A novel nanostructure for the efficient solvent‐free synthesis of thiazolidin‐2‐imines

In this research, a solvent‐free four‐component one‐pot reaction of phenyl isothiocyanate, phenylacetylene, various kinds of aldehydes, and amines was interpreted to obtain the desired five‐membered heterocycles named thiazolidin‐2‐imines. The promotor of this transformation is a novel magnetite‐based multilayered inorganic–bioorganic nanohybrid prepared via embedding glutamic acid on the magnetized silica followed by anchoring Cu (II) [nano Fe₃O₄‐SiO₂@Glu‐Cu (II)]. The newly synthesized nanostructure is characterized through Fourier‐transform infrared (FT‐IR), field‐emission scanning electron microscopy (FESEM), energy dispersive X‐ray analysis (EDAX), transmission electron microscopy (TEM), X‐ray fluorescence (XRF), thermogravimetric analysis or derivative thermogravimetric (TGA/DTG), vibrating sample magnetometer (VSM), X‐ray photoelectron spectroscopy (XPS), and Brunauer–Emmett–Teller (BET) techniques. This protocol is a straightforward one‐step procedure to obtain thiazolidin‐2‐imines without requirement to propargylamines or imines as substrates. In addition, easy work‐up procedure, high yields of products, absence of organic solvents in the reaction media, recovery and reusability of nano Fe₃O₄‐SiO₂@Glu‐Cu ( II) to promote the reaction at least for three runs without activity lost, simple separation of the catalyst from reaction mixture via an external magnet, and regioselectivity of the method are some highlighted aspects of the approach.     

Nitro group reduction and Suzuki reaction catalysed by palladium supported on magnetic nanoparticles modified with carbon quantum dots generated from glycerol and urea

Glycerol and urea were used as green and cheap sources of carbon quantum dots (CQD) for modifying Fe₃O₄ nanoparticles (NPs). The obtained CQD@Fe₃O₄ NPs were used for the stabilization of palladium species and the prepared catalyst, Pd@CQD@Fe₃O₄, was characterized using various techniques. This magnetic supported palladium was applied as an efficient catalyst for the reduction of aromatic nitro compounds to primary amines at room temperature using very low palladium loading (0.008 mol%) and also for the Suzuki–Miyaura cross‐coupling reaction of aryl halides as well as challenging heteroaryl bromides and aryl diazonium salts with arylboronic acids and with potassium phenyltrifluoroborate. This magnetically recyclable catalyst was recovered and reused for seven consecutive runs in the reduction of 4‐nitrotoluene to p‐toluidine and for ten consecutive runs in the reaction of 4‐iodoanisole with phenylboronic acid with small decrease of activity. The catalyst reused in the Suzuki reaction was characterized using transmission electron microscopy, vibrating sample magnetometry and X‐ray photoelectron spectroscopy. Using experiments such as hot filtration and poisoning tests, it has been shown that the true catalyst works under homogeneous conditions according to the release–return pathway of active palladium species.