Electron-deficient Amines Research Articles

Selective Detection of Primary Aromatic Amines through Enhanced Luminescence of a 2D + 2D Inclined Polycatenated Microporous Nitro-Functionalized Metal-Organic Framework.

Detection and sensing of amines through enhanced fluorescence emission are always challenging in aqueous solution. The range of different Lewis basicities, shapes, and sizes as well as the different structural arrangements of amines is responsible for their less specificity in aqueous solution. Here, we have designed a highly fluorescent emissive 2D + 2D → 3D inclined polycatenated NO2-functionalized flexible metal-organic framework (MOF) for selective segregation of electron-rich aromatic primary amines from electron-deficient amines in aqueous solution, showing different emission behaviors. The inclined polycatenated 2D + 2D → 3D MOF having an asymmetric unit {[Cd(dim)(2-nta)(H2O)](H2O)(MeOH)}n (1) has been synthesized by a slow diffusion process and characterized thoroughly by single-crystal and powder X-ray diffraction (PXRD) as well as other physicochemical methods. The desolvated species of 1 (Ref. MOF) is found to be stable and has been characterized by PXRD and adsorption study. The fluorescence profile of the Ref. MOF shows selective enhancement in the presence of electron-rich primary aromatic amines, while the same shows quenching for electron-deficient amines in aqueous solution. The Ref. MOF reported here consists of flexible space between two 2D layers that is responsible for different orientations for different analyte primary aromatic amines (PAAs) with different sizes. The above findings are also supported by time-resolved fluorescence spectroscopy. The respective fluorescence enhancement and quenching have been explained by the interaction between the CB of the host MOF and LUMO of guest amines. Therefore, this work presents an operable method for the sensing of PAAs using a single compound, which is a polycatenated MOF.

Photosensitizer-free singlet oxygen generation via a charge transfer transition involving molecular O2 toward highly efficient oxidative coupling of arylamines to azoaromatics.

Photosensitizer (PS)-mediated generation of singlet oxygen, O2 (a1Δg) is a well-explored phenomenon in chemistry and biology. However, the requirement of appropriate PSs with optimum excited state properties is a prerequisite for this approach which limits its widespread application. Herein, we report the generation of O2 (a1Δg) via direct charge-transfer (CT) excitation of the solvent-O2 (X3Σg -) collision complex without any PS and utilize it for the catalyst-free oxidative coupling of arylamines to azoaromatics under ambient conditions in aqueous medium. Electron paramagnetic resonance (EPR) spectroscopy revealed the formation of O2 (a1Δg) upon direct excitation with 370 nm light. The present approach shows broad substrate scope, remarkably fast reaction kinetics (90 and 40 min under an open and O2 atm, respectively), high selectivity (100%), and excellent yields (up to 100%), and works well for both homo- and hetero-coupling of arylamines. The oxidative coupling of arylamines was found to proceed through the generation of amine radicals via electron transfer (ET) from amines to O2 (a1Δg). Notably, electron-rich amines show higher yields of azo products compared to electron-deficient amines. Detailed mechanistic investigations using various spectroscopic tools revealed the formation of hydrazobenzene as an intermediate along with superoxide radicals which subsequently transform to hydrogen peroxide. The present study is unique in the way that molecular O2 simultaneously acts as a light-absorbing chromophore (solvent-O2 complex) as well as an efficient oxidant (O2 (a1Δg)) in the same reaction. This is the first report on the efficient, selective, and sustainable synthesis of azo compounds in aqueous medium under an ambient atmosphere without any PCs/PSs and paves the way for further in-depth understanding of the chemical reactivity of O2 (a1Δg) generated directly via CT excitation of the solvent-O2 complex toward various photochemical and photobiological transformations.

Reagentless Chemistry "On-Water": An Atom-Efficient and "Green" Route to Cyclic and Acyclic β-Amino Sulfones via aza-Michael Addition Using Microwave Irradiation.

A reagentless, catalyst-free, and sustainable methodology was developed for facile access to cyclic and acyclic β-amino sulfones "on-water" using a microwave. A variety of aromatic and aliphatic amines undergo double aza-Michael addition on the surface of the water with water-insoluble divinyl sulfones upon microwave irradiation at 150 °C for 10 min to mostly afford solid cyclic β-amino sulfones as easily separable products in excellent yields by simple filtration avoiding any workup steps. Thus, all atoms of the substrates are reflected in the product making it a 100% atom-efficient method. Both electron-rich and electron-deficient amines participated well in the reaction as well as good functional group tolerance was observed. The competitive experiments expectedly revealed faster reaction kinetics for electron-rich amines. The methodology was extended to acyclic β-amino sulfones by interacting phenyl/ethyl vinyl sulfones with various amines in a similar manner. Expectedly, the method afforded very low environmental factors (in a range of 0.05-0.5) and a high Ecoscale score (up to 94). In an attempt toward sustainable development, this reagent-free, metal-free, organic solvent-free, cost-effective protocol is certainly a viable alternative to the available methods for β-amino sulfones.

It Is Not All about the Ligands: Exploring the Hidden Potentials of tBu3P through Its Oxidative Addition Complex as the Precatalyst

A series of oxidative addition complexes with a general formula (tBu3P)Pd(Ar)X, as a class of precatalysts, were synthesized for challenging Suzuki–Miyaura coupling involving coupling partners, such as (i) sensitive polyfluorinated arylboronic acids or their corresponding boronic esters, (ii) sterically hindered electrophiles, and (iii) sterically hindered nucleophiles. A total of 89 examples are reported, of which 39 examples are in the Supporting Information. These precatalysts, in particular (tBu3P)Pd(4-CF3Ph)Br, were demonstrated to be powerful catalytic systems in general for cross coupling reactions in comparison to the in situ systems created by mixing tBu3P ligand with a palladium precursor. The precatalysts are also superior to the other monoligated systems, such as Buchwald’s biaryl based G3 or G4 palladacycles. In addition, the (tBu3P)Pd(4-CF3Ph)Br precatalyst is also highly effective for the second most popular coupling reaction, namely the Buchwald–Hartwig coupling. In this study, hindered and electron-deficient amines were coupled with hindered (hetero)aryl bromides and chlorides with 34 examples, of which 8 are in the Supporting Information. Interestingly, the results obtained for both C–C and C–N couplings were on par with or superior to that of the “state-of-the-art” catalysts containing Ad3P and Np3P ligands for the same or similar substrates, suggesting that it is not all about the ligands.

Synthesis of amide derivatives for electron deficient amines and functionalized carboxylic acids using EDC and DMAP and a catalytic amount of HOBt as the coupling reagents

A convenient protocol for amide bond formation for electron deficient amines and carboxylic acids is described. Amide coupling of aniline derivatives has been investigated with a number of reagents under a variety of reaction conditions. The use of 1 equivalent of EDC and 1 equivalent of DMAP, catalytic amount of HOBt and DIPEA provided the best results. This method is applicable for the synthesis of a range of functionalized amide derivatives with electron deficient and unreactive amines.

Room temperature clickable coupling electron deficient amines with sterically hindered carboxylic acids for the construction of amides

A method for the synthesis of difficult-to-access amides was developed through the coupling of sterically hindered carboxylic acids and electron deficient amines via SO 2 F 2 -mediated dehydration. The method feathers with broad substrate scope, mild conditions, excellent functional group compatibility and high yields. • We synthetized the difficult-to-access amides through sterically hindered carboxylic acids and electron deficient amines. • This method is mild, simple and practical under the room temperature. • This method has the features of high efficiency, wide substrate scope, and excellent functional group compatibility.

A Metallaphotoredox Method for the Expansion of Benzyl SAR on Electron-Deficient Amines.

A metallaphotoredox reaction is described that allows for the efficient exploration of benzyl structure-activity relationships on electron-deficient amines. Typically, accessing a variety of benzyl groups on these substrates can be difficult due to the limited availability of the prerequisite building blocks, namely benzyl halides. However, the use of aryl bromides in this metallaphotoredox reaction allows for greater diversity in the benzyl piece. The reaction scope is discussed herein, including conditions for product scaleup using flow.

Controlling Dark Equilibria and Enhancing Donor-Acceptor Stenhouse Adduct Photoswitching Properties through Carbon Acid Design.

A novel library of tunable negative photochromic compounds, donor-acceptor Stenhouse adducts (DASAs), is reported. Tailoring the electron deficient "acceptor" moiety yielded DASAs that can be activated with mild visible and far red light. The effect of acceptor composition on reactivity, absorption, equilibrium, and cyclability is exploited for the design of high performance photoswitches. The structural changes to the carbon acid acceptor also provide access to new, more structurally diverse DASA derivatives by facilitating the ring-opening reaction with electron deficient amine donors.

A Simple, Broad-Scope Nickel(0) Precatalyst System for the Direct Amination of Allyl Alcohols.

The preparation of allylic amines is traditionally accomplished by reactions of amines with reactive electrophiles, such as allylic halides, sulfonates, or oxyphosphonium species; such methods involve hazardous reagents, generate stoichiometric waste streams, and often suffer from side reactions (such as overalkylation). We report here the first broad-scope nickel-catalysed direct amination of allyl alcohols: An inexpensive NiII /Zn couple enables the allylation of primary, secondary, and electron-deficient amines without the need for glove-box techniques. Under mild conditions, primary and secondary aliphatic amines react smoothly with a range of allyl alcohols, giving secondary and tertiary amines efficiently. This "totally catalytic" method can also be applied to electron-deficient nitrogen nucleophiles; the practicality of the process was demonstrated in an efficient, gram-scale preparation of the calcium antagonist drug substance flunarizine (Sibelium®).

Sulfur-Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates.

Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of "SuFExAmide": a new sulfur-fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.

Electronic and steric effects controlling efficiencies of photoaddition reactions of fullerene C60 with N-α-trimethylsilyl-N-alkyl-N-benzylamines

Single electron transfer (SET)-promoted photoaddition reactions between fullerene C60 and both various alkyl (Me, Et, i-Pr, t-Bu)- and para-substituted (p-Me, p-OMe, p-F, p-CF3) arene ring containing, N-α-trimethylsilyl-N-alkyl-N-benzylamines were explored to gain information about photoproduct profiles and how the electronic and steric nature of the amine substrates influence reaction efficiencies. The results show that visible light (λ>540nm) irradiation of 10% EtOH-toluene solutions containing C60 and N-α-trimethylsilyl-N-alkyl-N-benzylamines produce 1-aminomethyl-1,2-dihydrofullerenes as a sole photoproduct. In addition, SET-promoted photoaddition reactions of unsubstituted and para-electron donating group substituted arene ring containing N-α-trimethylsilyl-N-alkyl-N-benzylamines take place to give photoproducts more efficiently than those containing para-electron withdrawing group substituted arene rings. Moreover, although steric factors are less significant than the electronic nature of the amine substrates in governing reaction efficiencies, sterics do play a significant role in photoreactions of electron deficient amine substrates.

Substrate-Controlled Selectivity Switch in the Three-Component Coupling Involving Arynes, Aromatic Tertiary Amines, and CO2.

The transition-metal-free multicomponent coupling involving arynes, aromatic tertiary amines, and CO2 is reported. The reaction exhibits switchable selectivity depending on the electronic nature of the aromatic amines used. With amines bearing electron-releasing/neutral groups as the nucleophilic trigger, the reaction afforded 2-arylamino benzoates via a nitrogen to oxygen alkyl group migration. Employing electron-deficient amines in the reaction furnished 2-aminoaryl benzoates proceeding via the aryl to aryl amino group migration resembling a Smiles rearrangement.

ChemInform Abstract: A Protocol for Amide Bond Formation with Electron Deficient Amines and Sterically Hindered Substrates.

AbstractA method for efficient in situ coupling of sterically hindered carboxylic acids with hindered or electron deficient amines and oxazolidinones is developed.

A protocol for amide bond formation with electron deficient amines and sterically hindered substrates.

A protocol for amide coupling by in situ formation of acyl fluorides and reaction with amines at elevated temperature has been developed and found to be efficient for coupling of sterically hindered substrates and electron deficient amines where standard methods failed.

Iron oxide-silver magnetic nanoparticles as simple heterogeneous catalysts for the direct inter/intramolecular nucleophilic substitution of π-activated alcohols with electron-deficient amines

The development of bimetallic iron oxide-silver magnetic nanoparticles (Fe2O3–Ag MNPs) catalytic system provides an efficient heterogeneous synthetic pathway to allylic amines and 1,2-dihydroquinolines involving the direct inter/intramolecular nucleophilic substitution of π-activated alcohols with electron-deficient amines. The major advantages of the present method are wide substrate scope, simple product separation, low catalyst loading, and magnetically recyclable catalyst.

Direct oxidative coupling of enamines and electron-deficient amines: TBAI/TBHP-mediated synthesis of substituted diaminoalkenes under metal-free conditions.

A metal-free cross-coupling of enamines and electron-deficient amines through oxidative C(sp(2))-N bond formation has been realized by using TBAI as catalyst and TBHP as oxidant. This novel strategy allows for an efficient organocatalytic synthesis of the synthetically useful diaminoalkene derivatives and is highlighted by appealing features such as readily available of the starting materials, wide substrate scope and transition-metal-free characteristics.

Strong lone pair⋯π interactions between amine and tri-s-triazine derivatives: A theoretical investigation

For a better understanding of the interesting lone pair⋯π (lp⋯π) interaction, MP2 and CCSD(T) calculations have been carried out to investigate the nitrogen lp⋯π interactions between amine and tri-s-triazine derivatives. New strong attractive lp⋯π interactions are observed when the lone pairs of NH3 and NMe3 point toward the large π system, tri-s-triazine ring. At the CCSD(T)/6-311++G(d,p)//MP2/6-311G(d,p) level, the BSSE corrected interaction energy of the C6N7H3⋯NH3 complex is −6.3kcalmol−1,which is larger than those of the most previously reported lp⋯π systems. The substitution effects on interaction energy of the present studied systems were studied to probe how to manipulate lp⋯π interaction and obtain stronger one. The results indicate that the very strong lp⋯π interaction can form between electron-rich amines and electron-deficient large aromatic ring. But the lp⋯π interactions between the electron-deficient amine such as NF3 and aromatic ring are very weak. The C6N7F3⋯NMe3 complex has interaction energy of −9.8kcalmol−1. This interaction is much stronger than previously reported lp⋯π bindings. The AIM analysis of the nine studied complexes shows that their molecular graphs are obvious different from previously reported benzene⋯amine complexes and X–H/π systems, which may result from the tri-s-triazine ring’s characteristic.

Palladium-Catalyzed Cross-Coupling of Electron-Deficient Heteroaromatic Amines with Heteroaryl Halides

An efficient method has been developed for the Pd-catalyzed cross-coupling reactions of electron-deficient heteroaromatic amines with heteroaryl halides. The optimized reactions used Pd2(dba)3 as catalyst, 1,1′-bis(diphenylphosphino)ferrocene (DPPF) as ligand, and Cs2CO3 as base. The Pd-catalyzed cross-coupling reactions of several rarely reported electron-deficient heteroaromatic amines were successfully accomplished in good yields.

Stereoselective direct reductive amination of ketones with electron-deficient amines using Re2O7/NaPF6 catalyst

The first example of direct reductive amination (DRA) of ketones with electron-deficient amines (EDA) such as Cbz-, Boc-, EtOCO-, Fmoc-, Bz-, ArSO2-, etc. protected amines have been achieved using catalytic Re2O7/NaPF6. Excellent chemoselectivities as well as diastereoselectivity (for 2-alkyl cyclohexanones) were obtained.

Direct Substitution of Hydroxy Group of π-Activated Alcohols with Electron-Deficient Amines Using Re2O7 Catalyst

The first example of simple Re(2)O(7)-catalyzed direct dehydrative coupling between allylic alcohols with electron-deficient amines has been achieved under mild and open flask conditions. The protocol has also been successfully applied to benzylic and propargylic alcohols. The mechanistic proof for the S(N)1-type process has also been provided.