Amination Of Alkenes Research Articles

Direct Allylic C–H Amination of Alkenes with Amines to Branched Allylic Amines under Dual Catalysis

Direct Allylic C–H Amination of Alkenes with Amines to Branched Allylic Amines under Dual Catalysis

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Photoredox-Catalyzed Alkene Amination: C(sp2)-H/N-H Radical-Radical Cross Dehydrogenative Coupling.

Direct alkene C-H/N-H cross dehydrogenative coupling is an infrequent, highly challenging transformation. Herein, a photoredox radical-radical cross-coupling reaction between ketene dithioacetal as a persistent alkene radical cation and azole nitrogen center radical (NCR) was developed. This direct alkene amination proceeded through a synergistic photoredox and cobalt catalysis, with only H2 evolution. The reaction showed excellent tolerance and highly regio- and stereospecific manner, expanding the scope of C(sp2)-N construction methods and radical cross-coupling modes.

Cooperative Cu/azodiformate system-catalyzed allylic C–H amination of unactivated internal alkenes directed by aminoquinoline

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

Iodine-catalyzed intermolecular 1,2-thio (seleno)amination of alkenes with 1,2,3-triazoles and disulfides (diselenides) in air

Iodine-catalyzed 1,2-thio (seleno)amination of alkenes via direct N- and C-centered radical cross-coupling was established to elicit highly regioselective β-triazolized thioalkyl compounds.

Shining light on nitrogen: Alkene amination with N-heteroaromatic radicals via energy transfer

Shining light on nitrogen: Alkene amination with N-heteroaromatic radicals via energy transfer

Selenated NHC-Pd(II) Pincer Complex Catalyzed, Temperature-Dependent Selective Hydroamination and Oxidative Amination of Olefins: Formation of Enamine Esters and β-Amino Esters under Solvent-Free and Aerobic Conditions.

NHC-Pd(II) pincer catalyzed oxidative amination and hydroamination of olefins is developed under solvent-free aerobic conditions. Reaction offered a temperature-controlled synthesis of (Z)-enamine and β-amino esters to provide easy access and remarkable functional group tolerance for a variety of enamines. The developed approach renders an opportunity of scalability and flexibility, and besides this, the produced enamines can be transformed into many N-containing heterocycles, underscoring its potential usage in synthetic and pharmaceutical chemistry. Moreover, it is the first report for coupling of aniline with styrene.

Palladium-Catalyzed E-Selective Oxidative Amination of Aromatic Amine with 3-Butenoic Acid.

A palladium-catalyzed oxidative amination of inactive olefins with an aromatic amine was developed using a copper acetate oxidant to yield corresponding secondary and tertiary enamines in moderate to good yields. This new procedure outlines an efficient approach for the construction of enamine skeletons.

Amine-Functionalized Polybutadiene Synthesis by Tunable Postpolymerization Hydroaminoalkylation.

Early transition metal-catalyzed hydroaminoalkylation is a powerful single-step method to selectively add amines to polybutadienes, offering an efficient strategy to access amine-functionalized polyolefins. Aryl and alkyl secondary amines were used with a tantalum catalyst to functionalize both 28 wt% (PBD13) and 70 wt% (PBD50) 1,2-polybutadiene polymers. The degree of amination was controlled by modifying amine and catalyst loading in both small- and multigram-scale reactions. The vinyl groups of 1,2-polybutadiene were aminated with ease, and unexpectedly the hydroaminoalkylation of challenging internal alkenes of the 1,4-polybutadiene unit was observed. This unanticipated reactivity was proposed to be due to a directing group effect. This hypothesis was supported with small-molecule model substrates, which also showed directed internal alkene amination. Increasing degrees of amination resulted in materials with dramatically higher and tunable glass transition temperature (Tg) values, due to the dynamic cross-linking accessible to hydrogen-bonding, amine-containing materials. Primary amine-functionalized polybutadiene was also prepared, demonstrating that a broad new class of amine-containing polyolefins can be accessed by postpolymerization hydroaminoalkylation.

Palladium Catalyzed Aerobic Oxidative Amination of Alkenes

AbstractAmines are widely applied in the chemical and pharmaceutical industries, and the development of synthetic methods for their preparation is driven by their importance. The amination of alkenes is a direct and efficient method for the construction of amines, of which oxidative amination is more valuable because it can give the desired products with greater functionality and flexibility. In oxidative amination, using molecular oxygen (O2) as a terminal oxidant has promising industrial application prospects. In recent years, the palladium‐catalyzed aerobic oxidation of alkenes has seen significant progress, and its related research has also been extended to the aerobic oxidative amination of alkenes. The corresponding oxidation systems have been developed from early research involving the introduction of cocatalysts to the more recent systems which utilize auxiliary ligands instead of cocatalysts. In this review, the advancements in the palladium‐catalyzed aerobic oxidative amination of monoalkenes and conjugated dienes over the last two decades are discussed, with emphasis on aerobic oxidation process and their associated mechanisms.

Palladium-Catalyzed Oxidative Amination of Unactivated Olefins with Primary Aliphatic Amines

Direct coupling of unactivated olefins with primary alkylamines is considered to be an efficient but unknown method for the construction of complex amines. Herein we report a catalytic intermolecular oxidative amination of unactivated olefins with primary aliphatic amines based on the combination of a palladium catalyst, a bidentate phosphine ligand, and duroquinone. A range of secondary allylic amines were obtained in good yields with excellent regio- and stereoselectivity. Mechanistic control experiments revealed that the reaction proceeds by allylic C(sp3)-H activation and nucleophilic amination. The utility of the protocol is further demonstrated with the late-stage modification and streamlined synthesis of drug molecules.

Metal-Free Intermolecular Allylic C–H Amination of Alkenes Using Primary Carbamates

The allylic C–H amination of alkenes is a powerful method for the regioselective formation of new C–N bonds. Though many methods for introducing a wide range of nitrogen groups intermolecularly have been developed, few of these utilize carbamates, which are an important class of bioactive compounds and are commonly used as protecting groups for free amines. Here, we report a convenient metal-free protocol for intermolecular allylic C–H amination using unactivated primary carbamates as the nitrogen source. A sterically hindered NHC-selenium catalyst was found to be critical to obtaining high yields. A wide range of trisubstituted and 1,1-disubstituted alkenes were regioselectively aminated, including terpenoid natural products. A range of common carbamate-protecting groups such as Cbz, Teoc, and Alloc could be successfully incorporated into alkene substrates. Additionally, trifluoroacetamide was shown to be a viable nitrogen source. The observed regio- and stereoselectivities can be explained by a sequential ene reaction/[2,3]-sigmatropic rearrangement mechanism in which cis C–H bonds are preferentially activated, but subsequent rearrangement results in selective formation of trans alkene products.

Palladium-Catalyzed Enantioselective Allylic C–H Amination of Alkenes Induced by Blue Light

Palladium-Catalyzed Enantioselective Allylic C–H Amination of Alkenes Induced by Blue Light

Mechanism and Reaction Channels of Iron-Catalyzed Primary Amination of Alkenes by Hydroxylamine Reagents

Iron-catalyzed N-transfer by hydroxylamine-derived reagents has emerged as an appealing method for the straightforward synthesis of unprotected primary amines. Here, we studied the detailed reaction mechanism of the FePc-catalyzed aminofunctionalization of styrene with AcO-NH3OTf and PivO-NH3OTf by quantum chemical calculations and mass spectrometry experiments. An inner-sphere heterolytic N–O cleavage mechanism was proposed for the hydroxylamine activation. It affords an unprotected iron-amido species ([PcFeNH2]+), which has been detected by mass spectrometry. The iron-amido species acts as the active aminating intermediate and reacts with styrene to form a radical intermediate, followed by nucleophilic addition with methanol to generate the product. Electronic structure analysis revealed σ- and π-channels in the N-transfer process for the iron-amido species. This reported iron–nitrogen complex resembles the iron-oxo species to possess both σ- and π-channels, unveiling the mechanistic connections with iron-oxo chemistry.

Asymmetric intermolecular allylic C-H amination of alkenes with aliphatic amines.

Aliphatic allylic amines are found in a great variety of complex and biorelevant molecules. The direct allylic C-H amination of alkenes serves as the most straightforward method toward these motifs. However, use of widely available internal alkenes with aliphatic amines in this transformation remains a synthetic challenge. In particular, palladium catalysis faces the twin challenges of inefficient coordination of Pd(II) to internal alkenes but excessively tight and therefore inhibitory coordination of Pd(II) by basic aliphatic amines. We report a general solution to these problems. The developed protocol, in contrast to a classical Pd(II/0) scenario, operates through a blue light-induced Pd(0/I/II) manifold with mild aryl bromide oxidant. This open-shell approach also enables enantio- and diastereoselective allylic C-H amination.

Aminium-Radical-Mediated Intermolecular Hydroamination of Nonactivated Olefins

AbstractAminium radicals are attractive intermediates in synthetic chemistry that readily participate in a series of C–N bond-forming processes. Here, we briefly discuss strategies for generating aminium radicals from various precursors in the context of intermolecular alkene amination, and we highlight recent advances in aminium-radical-mediated hydroaminations of nonactivated olefins to directly approach alkylamines.1 Introduction2 Intermolecular Hydroamination of Nonactivated Alkenes with Alkylamines under Photoredox Catalysis3 Intermolecular Hydroamination of Nonactivated Alkenes with Aliphatic Azides4 Conclusions

Dual photoredox and cobalt catalysis enpowers site-selective allylic amination

The development of a highly efficient, selective and atom-economical method for the construction of allylic amines are a challenge in green synthetic chemistry. In a recent work published in Nature Catalysis, Lei, Qi, and co-workers reported that the combination of a photoredox catalyst and cobaloxime catalyst enables site-selective allylic amination of various olefins with secondary alkyl amines, affording the valuable tertiary aliphatic allylamines, without the need for external oxidants.

Site-Selective Allylic C–H Amination of Alkenes Enabled by Formation of an Aminium Radical Cation

Site-Selective Allylic C–H Amination of Alkenes Enabled by Formation of an Aminium Radical Cation

Palladium-catalysed selective oxidative amination of olefins with Lewis basic amines.

Amines are prominent in natural products, pharmaceutical agents and agrochemicals. Moreover, they are synthetically valuable building blocks for the construction of complex organic molecules and functional materials. However, amines, especially aliphatic and aromatic amines with free N-H bonds, tend to coordinate with transition metals and deactivate the catalyst, posing a tremendous challenge to applying Lewis basic amines in the amination of olefins. Here we present an example of oxidative amination of simple olefins with various Lewis basic amines. The combination of a palladium catalyst, 2,6-dimethyl-1,4-benzoquinone and a phosphorous ligand leads to the efficient synthesis of alkyl and aryl allylamines. A series of allylamines were obtained with good yields and excellent regio- and stereoselectivities. Intramolecular amination to synthesize tetrahydropyrrole and piperidine derivatives was also realized. Mechanistic investigations reveal that the reaction undergoes allylic C(sp3)-H activation and subsequent functionalization.

Electrochemical Organoselenium-Catalyzed Intermolecular Hydroazolylation of Alkenes with Low Catalyst Loadings.

The organoselenium-catalyzed amination of alkenes is a promising way to construct functionalized amines. However, the use of chemical oxidants and the unavoidable formation of allylic amine or enamine are the two main limitations of these methodologies. Against this background, we herein report an electro-selenocatalytic regime for the hydroazolylation of alkenes with azoles under external oxidant-free conditions with low catalyst loadings. Moreover, this protocol enables the generation of amines without vinyl substituents.