Hydroamination Of Alkynes Research Articles

Thiolate-Protected Au25(SC2H4Ph)18 Nanoclusters as a Catalyst for Intermolecular Hydroamination of Terminal Alkynes

Au25(SC2H4Ph)18 nanoclusters have high catalytic activity for hydroamination of terminal alkynes. This reaction proceeds under O2 or air. The presence of molecular oxygen has a profound effect on the Au25(SC2H4Ph)18 reactivity. The catalysts can be separated from the mixture after the reaction and reused.

Single-Step Synthesis of Dinuclear Neutral Gold(I) Complexes with Bridging Di(N-heterocyclic carbene) Ligands and Their Catalytic Performance in Cross Coupling Reactions and Alkyne Hydroamination

We report on a single-step procedure for the synthesis of dinuclear gold(I) complexes with bridging di(N-heterocyclic carbene) (diNHC) ligands of general formula Au2Br2L1–9 (L = diNHC). The obtained complexes differ in the bridging group between the carbene donors and in the terminal wingtip substituents at the imidazol-2-ylidene rings. The complexes have been characterized by means of elemental analysis, NMR spectroscopy, ESI-MS spectrometry, and single-crystal X-ray structure analysis. The dinuclear gold(I) complexes have been tested as homogeneous catalysts in technologically relevant reactions such as the cross coupling between phenylboronic acid and aryl bromides and the intermolecular hydroamination of alkynes. The catalytic performance has been compared for complexes Au2Br2L1–9 and the benchmark mononuclear complex IPrAuCl.

A Practical Electrophilic Nitrogen Source for the Synthesis of Chiral Primary Amines by Copper-Catalyzed Hydroamination.

A mild and practical method for the catalytic installation of the amino group across alkenes and alkynes has long been recognized as a significant challenge in synthetic chemistry. As the direct hydroamination of olefins using ammonia requires harsh conditions, the development of suitable electrophilic aminating reagents for formal hydroamination methods is of importance. Herein, we describe the use of 1,2-benzisoxazole as a practical electrophilic primary amine source. Using this heterocycle as a new amino group delivery agent, a mild and general protocol for the copper-hydride-catalyzed hydroamination of alkenes and alkynes to form primary amines was developed. This method provides access to a broad range of chiral α-branched primary amines and linear primary amines, as demonstrated by the efficient synthesis of the antiretroviral drug maraviroc and the formal synthesis of several other pharmaceutical agents.

N-Silylenamines as Reactive Intermediates: Hydroamination for the Modular Synthesis of Selectively Substituted Pyridines.

A modular and selective synthesis of mono-, di-, tri-, tetra-, and pentasubstituted pyridines is reported. Hydroamination of alkynes with N-silylamine using a bis(amidate)bis(amido)titanium(IV) precatalyst furnishes the regioselective formation of N-silylenamines. Addition of α,β-unsaturated carbonyls to the crude mixtures followed by oxidation affords 47 examples of pyridines in yields of up to 96%. This synthetic route allows for the synthesis of diverse pyridines containing variable substitution patterns, including pharmaceutically relevant 2,4,5-trisubstituted pyridines, using this one-pot protocol.

Synthesis of an anionic Au(I) hydroamination precatalyst supported by charged hydrido-carboranyl phosphine ligands

Herein is reported the synthesis of an anionic gold complex bearing two charged hydrido carboranyl phosphine ligands. The compound is fully characterized by multinuclear NMR spectroscopy, high resolution mass spectrometry, as well as a single crystal X-ray diffraction study. In addition, we probe this compound’s ability to catalyze the hydroamination of alkynes and compare its behavior to a related highly active catalyst supported by a perchlorinated carboranyl phosphine.

Substrate-Controlled Regio- and Stereoselective Synthesis of ( Z)- and ( E)- N-Styrylated Carbazoles, Aza-carbazoles, and γ-Carbolines via Hydroamination of Alkynes.

We report herein the substrate-controlled regio- and stereoselective hydroamination of carbazoles, aza-carbazoles, and γ-carbolines with functionalized aromatic as well as aliphatic alkynes in a KOH/DMSO system in good yields. The electronic effect of the substrates governs the stereochemistry of the product. Electron-donating alkynes provided ( Z)-stereoselective products, and electron-withdrawing alkynes provided ( E)-stereoselective products. This approach also provides an easy route for the synthesis of mono- and bis-hydroaminated product. The deuterium-labeling studies were also conducted to support the mechanistic pathway.

Synthesis and Structure of a Bis(indolyl)-Coordinated Titanium Diamido Complex, and Its Catalytic Applications in the Intermolecular Hydroamination of Alkynes

Abstract Titanium bis(diethylamido) complex 1, which contains a carbon-bridged bis(indolyl) ligand, was obtained in 69% yield from the reaction of Ti(NEt2)4 with the corresponding bis(indole) ligand. Its molecular structure in the crystal was unequivocally determined by a single-crystal X-ray diffraction analysis. Furthermore, we examined applications of 1 as a catalyst for the intermolecular hydroamination of alkynes. When using phenylacetylene or 1-hexyne as alkynes, the Markovnikov products were obtained selectively, while the reaction with 1-phenyl-1-propyne afforded an imine of phenylacetone.

Pd(II)–Ni(II) Pyrazolate Framework as Active and Recyclable Catalyst for the Hydroamination of Terminal Alkynes

Well-dispersed [Pd(NH3)4]2+ sites have been introduced in the defective nickel pyrazolate porous framework, known as K@NiBDP. The resulting porous crystalline material shows a superior catalytic behavior for C–N bond formations than [Pd(NH3)4]2+ containing zeolite HY. The palladium exchanged catalyst, Pd@NiBDP, is able to promote both intra- and intermolecular hydroamination of terminal alkynes with excellent activity, reusability and selectivity towards the corresponding indole or imine versus the hydration of the alkyne. The same Pd species introduced in the microporous acid HY zeolite favors the hydration of the terminal alkyne towards the corresponding ketone, instead of the addition of the amine to the triple bond.

A stereoselective organic base-catalyzed protocol for hydroamination of alkynes under solvent-free conditions

The hydroamination of alkynes is a straightforward and atom-economical process for the synthesis of substituted nitrogen-containing alkenes. Herein we report a novel protocol that involves for the first time solvent-free conditions (SolFC) and the use of an organic base, namely 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) to stereoselectively promote the process. The scope of this metal-free protocol has been evaluated through an extensive study that has led to the conclusion that in most cases the yield and stereoselectivity values are very high (14 examples, up to 95% yield, Z/E up to 99%).

Synthesis of P-Stereogenic Benzoazaphosphole 1-Oxides via Alkynylation of P-Stereogenic ortho-Aurated and ortho-Iodo Phosphinic Amides.

An efficient methodology for the synthesis of P-stereogenic dihydrobenzoazaphosphole 1-oxides via intramolecular 5-exo-dig alkyne hydroamination promoted by tetrabutylammonium fluoride is herein described. The required chiral o-alkynylphosphinic amide starting materials were prepared in high yields under very mild reaction conditions through alkynylation of P-stereogenic (O^C)-cyclometalated (phosphinic amide)dichlorogold(III) complexes and Sonogashira cross-coupling of ortho-iodo P-stereogenic phosphinic amide.

Alkyne Hydroamination Catalyzed by Silica-Supported Isolated Zn(II) Sites

Hydroamination is an atom-economical reaction to form C–N bonds, which are ubiquitous in organic compounds. Hydroamination has seen prolific advancements and has mostly focused on the development of homogeneous catalysts based on lanthanides or transition metals. Here, we have developed silica-supported, site-isolated Zn(II) sites through a combined surface organometallic chemistry (SOMC) and thermolytic molecular precursor (TMP) approach and show that they catalyze the intramolecular hydroamination of alkynes. This material is applicable to a broad range of substrates. On the basis of kinetics and in situ IR spectroscopic studies, we propose that the mechanism involves coordination of the aminoalkyne onto Zn(II) followed by the heterolytic activation of the N–H bond and subsequent cyclization and proton transfer.

One-pot Sonogashira coupling, hydroamination of alkyne and intramolecular C[sbnd]H arylation reactions toward the synthesis of indole-fused benzosultams

A one-pot Sonogashira coupling, hydroamination of alkyne and CH arylation reactions for the synthesis of indole-fused benzosultams are described. This method allows access to a variety of indole-fused seven membered benzosultams in good to excellent yields. The free indolyl nitrogen containing indole-fused benzosultams are also prepared by this method. The structures of the synthesized compounds are confirmed by single crystal XRD studies.

Regio- and Stereoselective Hydroamination of Alkynes Using an Ammonia Surrogate: Synthesis of N-Silylenamines as Reactive Synthons.

An anti-Markovnikov selective hydroamination of alkynes with N-silylamines to afford N-silylenamines is reported. The reaction is catalyzed by a bis(amidate)bis(amido)Ti(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting N-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines.

Rhodium Catalyzed Asymmetric Hydroamination of Internal Alkynes with Indoline: Mechanism, Origin of Enantioselectivity, and Role of Additives.

A comprehensive mechanistic study on the title reaction by using DFT(B3LYP-D3) computational method is reported. Explicit consideration of mono- (m-xylylic) and dicarboxylic acid (phthalic) in the key transition states reveals active participation of the carboxylic acid, beginning with the generation of a monomeric Rh(I) active catalyst and in the ensuing catalytic steps. In the early catalytic event, uptake of alkyne is predicted to take place only after the oxidative addition of the Rh(I) active catalyst to the carboxylic acid. The hydrometalation of the alkyne bound to the Rh(III)-H intermediate then generates a Rh(III)-vinyl intermediate, which in turn converts to a Rh(III)-allyl species. The inclusion of m-xylylic acid results in a two-step pathway to Rh(III)-allyl species via Rh-allene intermediate. A number of weak noncovalent interactions (hydrogen bonding and C-H···π) between the catalyst and the substrates and that involving m-xylylic acid are found to have a direct impact on the regiochemical preference toward the branched product and the enantiocontrolling hydroamination step involving C-N bond formation leading to the major enantiomer (S-allylic amine). The chiral induction is enabled by cumulative effect of noncovalent interactions, which is an insight that could aid future developments of chiral ligands for asymmetric hydroamination.

PdII Complexes with N‐(Diadamantylphosphanyl)diaminocarbene and Related Ligands: Synthesis and Catalytic Applications in Intermolecular Alkyne Hydroaminations

A new N‐diadamantylphosphanyldiaminocarbene 5 is prepared, isolated, and characterized. The carbene appears to be much more stable than previously reported di‐tert‐butyl congeners. The molecular structure of the carbene is determined by X‐ray diffraction analysis. A new (diisopropylamino)(diadamantylphosphanyl)carbene 8 is also prepared in situ, but not isolated, since in this case, the adamantyl groups do not render the carbene more stable, with respect to previously known carbenes with di‐tert‐butyl substitution. Carbene 8 reacts in situ with phenylazide to give iminophosphane 9, which is also accessible from carbene 5 upon rearrangement under heating. Stable chelate PdII complexes are synthesized using both carbene 5 and iminophosphane 9 as ligands. The complex with ligand 9 displays very promising catalytic performance in the intermolecular hydroamination of alkynes with primary arylamines.

Neutral and cationic cyclic (alkyl)(amino)carbene mercury [cAAC-Hg(ii)] complexes: scope of hydroamination of alkynes with organomercury compounds.

This study demonstrates the first synthesis of cyclic (alkyl)(amino)carbene (cAAC) adducts of Hg(ii), [cAACMe·HgBr(μ-Br)]2 (1a) and [cAACcy·HgBr(μ-Br)]2 (1b). Adduct 1b catalyzes intermolecular hydroamination of aromatic alkynes and amines under mild conditions to afford aromatic imines. The quest to prepare an electrophilic Hg(ii) complex resulted in the synthesis of cationic [(cAACcy)2Hg(H2O)]2+2[NO3]- (3) by reacting 1b with AgNO3.

Heterogeneous Hydroamination over Supported Ionic Liquid‐ Stabilized Copper Ions and Its Mechanistic Study

AbstractCuII ions immobilized on supported ionic liquid phase (Cu@SILP), using imidazolium‐based ionic liquids grafted on functionalized multiwalled carbon nanotubes and efficiently utilised as catalyst in selective heterogeneous hydroamination of aromatic terminal alkynes with anilines. Large turnover numbers (TON) and selectivity (> 99%) towards Markovnikov's addition product was achieved. To recognize the structure‐activity relationship, the catalyst was characterized using Transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), Fourier transform infra‐red (FT‐IR) spectroscopy, solid state NMR. Further mechanistic pathway of hydroamination with Cu@SILP has been predicted by performing Density Functional Theory (DFT).

Synthesis and Catalytic Benefits of Tetranuclear Gold(I) Complexes with a C4-Symmetric Tetratriazol-5-ylidene

The facile preparation of a C4-symmteric tetratriazolium salt and its subsequent metalation to generate a series of tetranuclear mesoionic carbene gold(I) complexes is presented. The complete structural characterization of the metallic carbenes and the benefits of cooperative catalysis in the processes of hydroamination and hydrohydrazination of terminal alkynes are discussed.

Catalytic Asymmetric 1,3-Dipolar Cycloaddition/Hydroamination Sequence: Expeditious Access to Enantioenriched Pyrroloisoquinoline Derivatives.

A three-step reaction sequence has been developed to prepare a variety of enantioenriched pyrroloisoquinoline derivatives. The process involves a catalytic asymmetric azomethine ylide 1,3-dipolar cycloaddition followed by an intramolecular AuI-catalyzed alkyne hydroamination and enamine reduction.

Cu/Cu2O nanoparticle interface: Rational designing of a heterogeneous catalyst system for selective hydroamination

One pot highly uniform Cu(0)-Cu(I) oxide nanoparticles (5–10nm) have been synthesized on nitrogen rich mesoporous carbon nanospheres (Cu-NCN) and efficiently utilized as a heterogeneous catalyst towards hydroamination of aromatic terminal alkynes with aniline derivatives. The catalyst bed provides Cu2O nanoparticles stabilized by nitrogen functionalities in the carbon nanospheres, which triggers the catalytic system with significantly large Turn over number (TON) and >99% selectivity towards Markovnikov addition product. The structure and morphology of the copper nanoparticles engraved carbon spheres have been studied by performing nitrogen physisorption studies (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) characterization techniques.