Vicinal Diamines Research Articles

Catalytic Enantio- and Diastereoselective Mannich Addition of TosMIC to Ketimines.

Chiral amines bearing a stereocenter in the α position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio- and diastereoselective addition of commercially available p-toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2-imidazolines bearing two contiguous stereocenters, one of which is fully-substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a dihydroquinine-derived N,P-ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp3 -rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.

Diastereoselective Synthesis of Vicinal Diamines by Aza-Michael Addition of Chiral Phenethylamine to Nitroalkenes

Diastereoselective Synthesis of Vicinal Diamines by Aza-Michael Addition of Chiral Phenethylamine to Nitroalkenes

Synthetic Evolution of the Multifarene Cavity from Planar Predecessors.

The stepwise evolution of curved multifarene structures from planar precursors is demonstrated, highlighting three architectural design elements: 1) employment of various aromatic units, 2) changing the hybridization of the linking atoms from sp2 to sp3 , and 3) rigidification of the system by the introduction of five-membered rings. Similar design elements have been employed to transform graphene sheets into curved carbon structures. Specifically, the stepwise synthetic evolution of multifarene[2+2], which has a curved, quite rigid structure, begins with a planar, tetraimine precursor, conversion to pairs of vicinal diamines, and the transformation of these pairs to cyclic thiourea groups. This process was probed by NMR spectroscopy and X-ray crystallography. Since varying the carbonylation conditions resulted in carbamates or thiocarbamates rather than the urea or thiourea isomers, the isomeric interconversion was studied both experimentally and by DFT computations. The carbamate versus urea preference was found to reflect either kinetic or thermodynamic control, respectively.

Cage Encapsulated Gold Nanoparticles as Heterogeneous Photocatalyst for Facile and Selective Reduction of Nitroarenes to Azo Compounds.

A discrete nanoscopic organic cage (OC1R) has been synthesized from a phenothiazine based trialdehyde treating with chiral 1,2-cyclohexanediamine building block via dynamic imine bond formation followed by reductive amination. The cage compound has been characterized by several spectroscopic methods, which advocate that OC1R has trigonal prismatic shape formed via [2 + 3] self-assembled imine condensation followed by imine reduction. This newly designed cage has aromatic walls and porous interior decorated with two cyclic thioether and three vicinal diamine moieties suitable for binding gold ions to engineer the controlled nucleation and stabilization of ultrafine gold nanoparticles (AuNPs). The functionalized confined pocket of the cage has been used for the controlled synthesis of AuNPs with narrow size distribution via encapsulation of Au(III) ions. Inductively coupled plasma mass spectrometric (ICP-MS) analysis revealed that the composite Au@OC1R has very high (∼68 wt %) gold loading. In distinction, reduction of gold salts in absence of the cage yielded structureless agglomerates. The fine-dispersed cage anchored AuNPs (Au@OC1R) have been finally used as potential heterogeneous photocatalyst for very facile and selective conversion of nitroarenes to respective azo compounds at ambient temperature in just 2 h reaction time. Exceptional chemical stability and reusability without any agglomeration of AuNPs even after several cycles of use are the potential features of this material. The composite Au@OC1R represents the first example of organic cage supported gold nanoparticles as photocatalyst.

Umpolung Synthesis of Vicinal Diamines: Diastereoselective Addition of 2-Azaallyl Anions to Davis-Ellman's Imines.

A highly regioselective and diastereoselective addition of 2-azaallyl anions to N- tert-butanesulfinylimines is reported. This methodology affords the preparation of enantiomerically and diastereomerically pure vicinal diamines bearing two adjacent stereocenters. Reactions proceed efficiently (yield up to 94%), diastereoselectively ( dr values up to 98:2:0:0), and site-selectively to deliver products with differentiated amino groups.

Charge‐Transfer Complex Promoted Regiospecific C−N Bond Cleavage of Vicinal Tertiary Diamines

AbstractA catalyst‐free, charge‐transfer complex promoted coupling of sulfonyl chlorides with vicinal tertiary diamines to generate sulfonamides is presented. Mechanistic studies showed that these reactions are proceeded via charge transfer of vicinal tertiary diamines to sulfonyl chlorides, forming the unstable sulfonyl quaternary ammonium like complexes which induced the regiospecific intramolecular C−N bond cleavage of vicinal tertiary diamines.magnified image

A general, electrocatalytic approach to the synthesis of vicinal diamines.

This protocol describes an electrochemical synthesis of 1,2-diazides from alkenes. Organic azides are highly versatile intermediates for synthetic chemistry, materials, and biological applications. 1,2-Diazides are commonly reduced to form 1,2-diamines, which are prevalent structural motifs in bioactive natural products, therapeutic agents, and molecular catalysts. The electrochemical formation of 1,2-diazides involves the anodic generation of an azidyl radical from sodium azide, followed by two successive additions of this N-centered radical to the alkene, and is assisted by a Mn catalyst. The electrosynthesis of 1,2-diazides can be carried out using various experimental setups comprising custom-made or commercially available reaction vessels and a direct-current power supply. Readily accessible electrode materials can be used, including carbon (made from reticulated vitreous carbon and pencil lead), nickel foam, and platinum foil. This protocol is also demonstrated using ElectraSyn, a standardized electrochemistry kit. Compared with conventional synthetic approaches, electrochemistry allows for the precise control of the anodic potential input, eliminates the need for stoichiometric and often indiscriminate oxidants, and minimizes the generation of wasteful byproducts. As such, our electrocatalytic synthesis exhibits various advantages over existing methods for alkene diamination, including sustainability, operational simplicity, substrate generality, and exceptional functional-group compatibility. The resultant 1,2-diazides can be smoothly reduced to 1,2-diamines in a single step with high chemoselectivity. To exemplify this, we include a procedure for catalytic hydrogenation using palladium on carbon. This protocol, therefore, constitutes a general approach to accessing 1,2-diazides and 1,2-diamines from alkenes.

Photoredox-Catalyzed Radical Relay Reaction Toward Functionalized Vicinal Diamines

A strategy has been described to synthesize β,γ-diamino­ketones. This strategy is enabled by photoredox-catalyzed and nitrogen-centered radical-triggered cascade reactions of styrenes, enamides, and O-acylhydroxylamines in DMSO. Four bonds (one C–C, one C–N, and two C–O) are constructed in a single operation. Various functionalized vicinal diamines have been furnished by the radical relay reaction.

Promoting Intermolecular C-N Bond Formation under the Auspices of Iodine(III).

The quest for the development of new protocols that provide general conditions for oxidative carbon-nitrogen bond formation has grown over recent years. Within this context, due to feasibility and benignity considerations in biochemical sciences, reactions that rely on main group oxidants as the only promoters have received particular interest. We have recently found that simple protonolysis events enable the incorporation of nitrogenated groups of the bissulfonimide family into the coordination sphere of common iodine(III) complexes such as diacetoxy iodobenzene. The products of the type ArI(OAc)(NTs2) represent rare examples of iodine(III) compounds displaying reactive iodine-nitrogen single bonds. Further protonolysis furnishes the corresponding iodine(III) compounds ArI(NTs2)2 containing two defined iodine-nitrogen single bonds for unprecedented dual transfer of both nitrogenated groups. It is of great synthetic importance that these new compounds contain iodine-nitrogen entities, which upon dissociation in solution lead to electrophilic iodine centers and nucleophilic nitrogen groups. This has enabled the development of a body of conceptually new amination reactions, which do not rely on conventional electrophilic nitrogen reagents but rather employ iodine(III) as an electrophilic activator and bissulfonimides as the source of subsequent nucleophilic amination. Additional diversification arises from the ambident nature of bissulfonimines enabling oxygenation pathways. The exciting chemistry covered in this Account comprises structural features of the reagents (including X-ray analysis), scope and limitation in synthetic amination of different hydrocarbons (including sp-, sp2-, and sp3-hybridized centers as in acetylenes, alkenes, enols, butadienes, allenes, arenes, and alkylketones), and physical-organic and theoretical analysis of the underlying reaction mechanisms. The oxidative transformations with all their rich diversifications originate from the versatile redox chemistry of the iodine(III) and iodine(I) pair, which shares several aspects of transition metal high oxidation state chemistry. For the present aryliodine(III) reagents, steric and electronic fine-tuning is possible through accurate engineering of the arene substituent. In addition to the general reactivity of the I-N bond, chiral aryliodine(III) reagents with defined stereochemical information in the aryl backbone are conceptually compatible with this approach. Thus, the development of enantioselective amination reactions with up to 99% ee was also successful. Several of the active enantioselective reagents have been isolated and structurally characterized. Following this approach for the important class of chiral vicinal diamines, an unprecedented direct diamination of alkenes could be conducted in an enantioselective catalytic manner under full intermolecular reaction control. This latter reaction is based on the precise engineering of a chiral aryliodine(III) catalyst in combination with bismesylimide as nitrogen source. It is the consequence of the precise understanding of the reaction behavior of structurally defined bisimidoiodine(III) reagents.

N-Arylamines Coupled with Aldehydes, Ketones, and Imines by Means of Photocatalytic Proton-Coupled Electron Transfer.

A photoredox-catalyzed umpolung strategy for coupling reactions between aldehydes, ketones, imines, and N-arylamines is reported. These reactions proceed by a Brønsted acid-activated proton-coupled electron transfer pathway, and the protocol was used to synthesize a broad scope of 1,2-amino alcohols and vicinal diamines, both of which are common motifs in biologically active natural products, pharmaceutically active molecules, and ligands.

Triclinic conformational polymorph of N,N,N′,N′-tetrakis(2-cyanoethyl)-1,2-ethylenediamine (TCED)

Abstract The crystal and molecular structures of two polymorphs of N,N,N′,N′-tetrakis(2-cyanoethyl)-1,2-ethylenediamine have been characterized by X-ray diffraction along with density functional theory (DFT) studies. The molecules differ from each other by conformation. N,N,N′,N′-tetrakis(2-cyanoethyl)-1,2-ethylenediamine has been synthesized by cyanoethylation of ethylenediamine. Cyanoethylation of vicinal diamines is important for the synthesis of hyperbranched polymeric materials applied as catalysts, surfactants and encapsulating agents in drug delivery systems. The molecular geometry of N,N,N′,N′-tetracyanoethyl-1,2-ethylenediamine is similar to that of homologous compounds. DFT calculations were performed to analyze the differences in the molecular geometry of the studied compounds in a crystalline state and for an isolated molecule.

Catalyst-free, efficient, and green procedure for the synthesis of 5-heterocyclic substituted 6-aminouracils

In this paper, the results of our studies on the catalyst-free synthesis of some new 6-aminouracils bearing naphthoquinone, benzo[a]phenazine, benzo[f]pyrido[2,3-b]quinoxaline, and benzo[f]quinoxaline substituents are reported. At first, 6-amino-5-(3,4-dioxo-1-naphthalenyl)uracil derivatives were synthesized from the reaction of various 6-aminouracils with 1,2-naphthoquinone in DMSO at 70 °C in good to excellent yields. Subsequently, the prepared 6-amino-5-(3,4-dioxo-1-naphthalenyl)uracils were subjected to the condensation reaction with various vicinal diamines, in chloroform under reflux conditions to synthesize 6-aminouracils bearing benzo[a]phenazine, benzo[f]pyrido[2,3-b]quinoxaline, and benzo[f]quinoxaline derivatives.

Origins of Stereoselectivity in Mannich Reactions Catalyzed by Chiral Vicinal Diamines.

The origins of the enantio- and diastereoselectivities in the Mannich reactions between aldehydes and ketimines catalyzed by chiral vicinal diamines have been determined by density functional theory calculations and distortion-interaction analysis. Computational results indicate a strong energetic preference for hydrogen-bonded nine-membered cyclic transition states. The favored transition states involve eight heavy atoms in the crown (chair-chair) conformation using the nomenclature of the analogous cyclic hydrocarbons. Energetic discrimination in the chirality-imparting step arises from pseudogauche-butane-type interactions in the disfavored transition states, as well as steric clashes between the N-Boc protecting group and the ammonium N-substituents.

Reactivity of orthophthalaldehyde with aliphatic, alicyclic and aromatic primary diamines: Electrochemical study and mechanistic considerations

The reactions of OPA with eight primary diamines were electrochemically monitored and the main products were isolated and identified. Various types of diamines were used: two non-vicinal α,ω-diaminoalkanes, four vicinal 1,2-diamino(cyclo)alkanes and two aromatic diamines. The results showed three electrochemical patterns: α,ω aliphatic diamines and both aromatic diamines exhibited only consumption of the parent OPA without observation of any electroactive intermediate or product; aliphatic and alicyclic vicinal diamines react with OPA under fast formation of reducible intermediate and its slow follow-up reaction yielding reducible product. A special case represents 1,2-trans-diaminocyclohexane exhibiting different products with regard to its cis-isomer. The main reaction products in all cases are derivatives of indano[1,2-a]benzimidazole and not bis-Schiff bases discussed in the literature.It has been found that the reaction of non-vicinal diamines with OPA is much faster than that of the vicinal diamines. The UV–vis monitoring revealed that the reaction of OPA with vicinal, as well as non-vicinal diamines results in the same type of product, hence the mentioned difference in the electrochemical pattern is caused by different kinetics. The slower reaction rate can be caused by lower nucleophilicity of vicinal diamines, where stronger electronic communication of vicinal amino groups takes place. This effect manifests itself as larger difference between the first and second pKa of the two amine groups and the comparison of HOMOs supported this interpretation.

Electrocatalytic Difunctionalization of Olefins as a General Approach to the Synthesis of Vicinal Diamines

Vicinal diamines are highly prevalent structural motifs in therapeutic agents, bioactive natural products, and molecular catalysts. However, there are currently few unified methodological approaches for making these pertinent synthetic building blocks. This Synpacts article provides an overview of selected landmark developments in the area of olefin diamination. In particular, we highlight our recent contribution on the electrocatalytic diazidation of olefins as a general, selective, and sustainable method for the synthesis of vicinal diamines.1 Introduction2 Background: Intermolecular Diamination of Olefins3 Background: Intermolecular Diazidation of Olefins4 Electrocatalytic Diazidation of Olefins

Aza-Henry reaction with perfluoroalkylated cyclic ketimines

Aza-Henry reaction of 5-, 6- and 7-membered cyclic imines bearing perfluorinated group with nitroalkanes affords the corresponding nitro amines in up to 95% yield. Subsequent reduction of nitro group gives perfluoroalkyl-equipped vicinal diamines.

Aminative Umpolung cyclization for synthesis of chiral exocyclic vicinal diamines.

Chiral exocylic vicinal diamines are biologically and chemically important compounds, but they are not easy to make. In this paper, an interesting aminative Umpolung cyclization process has been developed. Aromatic aldehydes 6 bearing an electrophilic chiral sulfinimine group underwent imine formation with 2,2-diphenylglycine (2), decarboxylation, and subsequent Umpolung cyclization, producing various trans-diamines 10 in 84-96% yields with high trans/cis ratios under very mild conditions. This work not only provides an efficient, clean, and mild method for the synthesis of chiral exocyclic vicinal diamines in one step but also represents a new application of aminative Umpolung strategy on intramolecular reactions.

Azides safely used to synthesize diamines

Academic researchers often develop organic synthesis methods that offer efficient new routes to industrially important chemicals. But many of these methods are considered untouchable in an industry setting because they involve hazardous reagents that can’t be safely handled on a larger scale or because they are cost-prohibitive to implement. Sometimes, though, a success story does come along. An industry-academic collaboration led by Hao Xu of Georgia State University and Marino Nebuloni of Italian specialty chemical company Redox Laboratory has developed a gram-scale procedure for directly adding azides to olefins to make vicinal primary diamines (Org. Process Res. Dev. 2017, DOI: 10.1021/acs.oprd.7b00312). Xu’s group first reported the mild-mannered method in late 2015, converting unfunctionalized linear and cyclic olefins to diamines at room temperature using trimethylsilyl azide, a benziodoxole oxidizing reagent, and an iron catalyst with a tridentate ligand (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201507550). The reaction drew the attention of

Removing the Mask in Catalytic Asymmetric Diamination of Alkenes

In this issue of Chem , Liu and co-workers report an extremely general and mild radical diamination protocol that permits the asymmetric synthesis of vicinal diamines in a highly enantioselective manner under a copper(I)/chiral phosphate dual-catalytic system. Notably, this work represents the first asymmetric radical alkene diamination that allows for direct alkylamine incorporation.

Process Safety Assessment of the Iron-Catalyzed Direct Olefin Diazidation for the Expedient Synthesis of Vicinal Primary Diamines.

We report herein a process safety assessment of the iron-catalyzed direct olefin diazidation for the preparation of a broad range of synthetically valuable vicinal primary diamines. Differential scanning calorimetry analysis of the corresponding reagents, intermediates, and a list of representative diazide/diaminium salt products revealed that all of them are thermal stable at the reaction temperature. The drop weight test of the diazides suggested that they are moderately impact-sensitive. Guided by this assessment, an optimized olefin diazidation/diamination procedure has been developed which allows for the gram-scale diaminium salt synthesis without purification of the diazide intermediate.