Allylic Amination Reaction Research Articles

Regioselective intermolecular carboamination of allylamines via nucleopalladation: empowering three-component synthesis of vicinal diamines.

An intermolecular carboamination reaction of allyl amines under Pd(ii)-catalysis is reported, expediting the synthesis of valuable vicinal diamines embedded in a functionally enriched linear carbon framework with high yields and exclusive Markovnikov selectivity. Central to our approach is the strategic use of a removable picolinamide auxiliary, which directs the regioselectivity during aminopalladation and stabilizes the crucial 5,5-palladacycle intermediate. This stabilization facilitates oxidative addition to carbon electrophiles, enabling the simultaneous incorporation of diverse aryl/styryl groups as well as important amine motifs, such as sulfoximines and anilines, across carbon-carbon double bonds. The protocol features broad substrate compatibility, tolerance to various functional groups, and scalability. The utility of this method is further demonstrated by the site-selective diversification of pharmaceutical agents. Additionally, these products serve as versatile intermediates for synthesizing heterocycles and function as effective ligands in catalytic transfer hydrogenation reactions. Notably, this work represents a rare instance of nucleopalladation-guided intermolecular carboamination of allylamines.

Asymmetric Allylic Amination of Alkyl-Substituted Allylic Carbonates with Pyridones Catalyzed by the Krische Iridium Complex.

An efficient Ir-catalyzed asymmetric allylic amination reaction of alkyl-substituted allylic carbonates is disclosed. With the Krische iridium complex as the catalyst, asymmetric allylic amination of alkyl-substituted allylic carbonates with pyridones proceeds effectively, affording pyridone derivatives containing a stereocenter α to the nitrogen atom in excellent yields and enantioselectivity (up to 99% yield, 95% ee). This catalytic system broadens the substrate scope of the reaction compared with that of the known catalytic systems. This reaction can also be conducted on a gram scale, further enhancing its potential for synthetic application.

Acyclic nucleosides via allylic amination of 2-methylidenetrimethylene carbonate with N-heteroaromatics

A highly efficient Pd-catalyzed allylic amination reaction using N-heteroaromatics to react with 2-methylidenetrimethylene carbonate was achieved (24 examples, up to 95 % yield, up to >20:1 N9/N7 selectivities). The presented strategy offers an efficient and convenient approach to construct acyclic nucleosides with a double bond in side chain.

Iridium-catalysed reductive allylic amination of α,β-unsaturated aldehydes.

Allylic amination is a powerful tool for constructing N-allylic amines widely found in bioactive molecules. Generally, allylic alcohols and unsaturated hydrocarbons have been considered for allylic amination reactions to minimize waste production. Herein, we present an iridium-catalysed method for reductive allylic amination of α,β-unsaturated aldehydes with amines to afford N-allylic amines under air conditions. This protocol is demonstrated to provide products from many substrates (41 examples) in moderate-to-excellent yields. This synthetic methodology is also highlighted by the synthesis of drug molecules, optically pure products, as well as scale-up experiments.

Mechanism and origins of regioselectivity of selenium-catalyzed allylic amination reactions

The mechanism of selenium-catalyzed allylic amination reactions with different ligands has been explored using density functional theory calculations.

Highly enantioselective allylic amination reaction through aerobic oxidative organo–organo dual catalytic system

An NHC/chiral tertiary amine dual catalytic system for the aerobic oxidation/allylic amination reaction has been developed. The combination of NHC with organo-catalysts especially with tertiary amine catalysts remains an underexplored area.

Allylic Amination of Highly Substituted Alkenes Enabled by Photoredox Catalysis and Cu(II)-Mediated Radical-Polar Crossover.

Allylic amination reactions enable the conversion of alkene feedstocks into value-added products with significant synthetic versatility. Here we describe a method for allylic amination involving photoredox activation and Cu(II)-mediated radical-polar crossover. A range of structurally varied allylic amines can be accessed using this strategy. The regioselectivity of this process is complementary to those of conventional methods for allylic amination.

Upcycling of Polybutadiene Facilitated by Selenium‐Mediated Allylic Amination

AbstractAccumulation of end‐of‐life plastics presents ongoing environmental concerns. One strategy to solve this grand challenge is to invent new techniques that modify post‐consumer waste and impart new functionality. While promising approaches for the chemical upcycling of commodity polyolefins and polyaromatics exist, analogous approaches to repurpose unsaturated polymers (e.g., polybutadiene) are scarce. In this work, we propose a method to upcycle polybutadiene, one of the most widely used commercial rubbers, via a mild, metal‐free allylic amination reaction. The resulting materials have tunable thermal and surface wetting properties as a function of both sulfonamide identity and grafting density. Importantly, this approach maintains the parent alkene microstructure without evidence of olefin reduction, olefin transposition, and/or chain scission. Based on these findings, we anticipate future applications in the remediation of complex elastomers and vulcanized rubbers.

Upcycling of Polybutadiene Facilitated by Selenium-Mediated Allylic Amination.

Accumulation of end-of-life plastics presents ongoing environmental concerns. One strategy to solve this grand challenge is to invent new techniques that modify post-consumer waste and impart new functionality. While promising approaches for the chemical upcycling of commodity polyolefins and polyaromatics exist, analogous approaches to repurpose unsaturated polymers (e.g., polybutadiene) are scarce. In this work, we propose a method to upcycle polybutadiene, one of the most widely used commercial rubbers, via a mild, metal-free allylic amination reaction. The resulting materials have tunable thermal and surface wetting properties as a function of both sulfonamide identity and grafting density. Importantly, this approach maintains the parent alkene microstructure without evidence of olefin reduction, olefin transposition, and/or chain scission. Based on these findings, we anticipate future applications in the remediation of complex elastomers and vulcanized rubbers.

Metal-Free Allylic C-H Amination

Allylic amination reactions of alkenes are useful tools to construct N-functionalized molecules and now one of the main research targets in the field of allylic oxidation reaction. Although many reactions using transition metal catalysts have been developed, the examples of metal-free systems are relatively limited. This short review focuses on recent reports about metal-free allylic C-H amination, and three types of the reactions, (1) enantioselective reactions using organobase catalysts, (2) iodine-mediated reaction systems, and (3) selenium-catalyzed reactions will be described.

The Adjustability of Physicochemical Properties: Comparison of 1-Vinyl-5H-tetrazole and 1-Allyl-5H-tetrazole as Ligands in 3d Metal Energetic Coordination Compounds

Energetic coordination compounds (ECCs) show promising properties to be used as potential substitutes for highly toxic lead-containing primary explosives. The concept is to combine the three building blocks: (i) ligand, (ii) transition metal, and (iii) anion, acting as (i) fuel, (ii) matrix, and (iii) oxidizer (e.g., ClO4-, NO3-, ClO3-) or energetic component (e.g., DN-, N3-, picrate, styphnate, trinitrophloroglucinate). By variation of the ligands, the complexes' properties can be adjusted toward their desired performance and sensitivities. In the present study, 1-vinyl-5H-tetrazole (1-VTZ, 1) and 1-allyl-5H-tetrazole (1-ATZ, 2) were used as nitrogen-rich endothermic ligands to form 3d metal (Mn2+, Fe2+, Cu2+, Zn2+, Co2+, Ni2+)-based ECCs. The influence of the introduction of an unsaturated C-C bond (1-ETZ vs 1-VTZ and 1-PTZ vs 1-ATZ) on the performance and sensitivity of the complexes is discussed, as is the lengthening of the alkenyl chain (1-VTZ vs 1-ATZ). For further insights, the novel complexes were compared to literature-known complexes based on N1-substituted C2- and C3-derived tetrazole ligands, respectively. The ligand 1-VTZ (1) was prepared by elimination of hydrogen chloride from 1-(2-chloroethyl)-5H-tetrazole in methanolic KOH solution. 1-ATZ (2) was obtained by a heterocyclization reaction of allylamine with triethyl orthoformate and sodium azide in an acetic acid medium. All compounds were intensively characterized with analytical methods such as XRD, IR, EA, DTA, TGA, and sensitivity measurements (IS and FS). The energetic performances were visibly evaluated in fast heating experiments. Furthermore, PETN initiation and laser ignition experiments were carried out for promising ECCs.

Progress and Prospects in the Ruthenium Catalyzed Allylic Amination Reactions

Abstract: Ruthenium-catalyzed amination reactions have gained much attention in recent times. Due to the low cost and versatile nature of ruthenium, its chemistry is expanding rapidly. The amination reaction provides an efficient pathway to synthesize organonitrogen compounds. These reactions are highly regio- and stereoselective and exhibit wide substrate scope. This review gives an overview of the ruthenium-catalyzed allylic amination reactions covering literature up to 2021.

Fe-Catalyzed Amidation of Allylic Alcohols by Borrowing Hydrogen Catalysis.

Allylic amines are useful building blocks in organic synthesis, so the development of green and efficient methods for the preparation of allylic amines are of great importance. An Fe-catalyzed amidation of allylic alcohols with chiral tert-butylsulfinamide has been developed. With water as the only by-product, a range of synthetically useful chiral sulfinamide olefin derivatives (30 examples) were obtained under mild reaction conditions. The reaction can be performed on a gram-scale, and the products could serve as chiral ligands for asymmetric catalysis. Mechanistic studies suggest that the reaction proceeds by an Fe-catalyzed borrowing hydrogen process, which is different from most of the reported allylic amination reactions.

Inherently Chiral 6,7-Diphenyldibenzo[ e,g ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Inherently Chiral 6,7-Diphenyldibenzo[ <i>e,g</i> ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

‘In-water’, nickel-catalyzed mild preparation of allylic amines employing alcohols: application to ‘all-water’ synthesis of pharmaceuticals

Reported here is a nanomicelle-enabled, ‘in-water’, nickel-catalyzed allylic amination reaction using allylic alcohols under mild conditions (in the absence of additives/bases/activators).

Phosphine-Catalyzed Asymmetric Tandem Isomerization/Annulation of Allyl Amines with Allenoates: Enantioselective Annulation of a Saturated C-N Bond.

Under catalysis by chiral phosphine, an asymmetric isomerization/annulation cascade reaction of allylamines with allenoates was realized. A wide range of γ-substituted allenoates were tolerated to afford chiral pyrroline derivatives in high yields with excellent enantioselectivities. In the reaction, isomerization of readily available N-allylamines to reactive aliphatic imines through a 1,4-proton shift is a key step, which circumvents the isolation of highly unstable alkyl N-sulfonylimines.

Rhodium-Catalyzed Regio- and Enantioselective Allylic Amination of Racemic 1,2-Disubstituted Allylic Phosphates.

Alkynylphosphines are rarely used as ligands in asymmetric metal catalysis. We synthesized a series of chiral bis(oxazoline)alkynylphosphine ligands and used them in Rh-catalyzed highly regio- and enantioselective allylic amination reactions of 1,2-disubstituted allylic phosphates. Chiral 1,2-disubstituted allylic amines were synthesized in up to 95% yield with >20:1 branched/linear (b/l) ratio and 99% ee from racemic 1,2-disubstituted allylic precursors. The sterically smaller linear alkynyl group on the P atom in the bis(oxazoline)alkynylphosphine ligands was the key to fit the new requirements of the introduction of bulky 2-R' groups.

Counteranion-controlled regioselectivity in palladium-catalyzed allylic amination of dienyl allylic carbonates

a bstract A regioselective Pd-catalyzed allylic amination reaction of dienyl allylic carbonates and aromatic amines has been developed by means of phosphoramidite-palladium catalysis. The regioselectivity could be altered by the counterion of the π-allylpalladium intermediate. As a result, either branched Z-dienyl allylic amines or linear conjugated allylic amines were generated in high levels of regioselectivity from the same substrates by tuning the reaction conditions.

Borrowing Carbonate-Enabled Allylic Amination Reactions under Additive- and Reductant-Free Nickel Catalysis Employing Allylic Alcohols

A “borrowing carbonate”-enabled allylic cross-amination reactions employing allylic alcohol were discovered via merging acyl/allyl C–O bonds activation under nickel catalysis. The key component of this protocol is the ability of nickel [Ni(II)-Ni(0)] to execute a relay process via the nucleophilic trapping of the generated acyl Ni complex, resulting from the acyl C–O bond cleavage of dialkyl carbonates, followed by selective allylic C–O bond activations (allylic C–O vs alkyl C–O vs acyl C–O) to yield π-allylNi-complexes. The finding truly represents Ni-catalyzed green allylic amination reactions under additive(s)-free conditions with excellent chemo- (N vs O), regio- (linear vs branched), and stereoselectivity (E vs Z) with a wide range of fundamentally challenging N-heterocycles and allylic alcohols. The reaction is scalable, does not require harmful reaction media and a globe box, and is successfully applied to the scale-up synthesis of pharmaceuticals (cinnarizine, flunarizine, and naftifine) with promising yields.

Strain-release C-C bond cleavage enables the [2,3]-sigmatropic rearrangement of tertiary allylamines.

A new strategy has been established for the [2,3]-sigmatropic rearrangement of quaternary allylammonium ylides, generated in situ from tertiary allylamines and a bicyclo[1.1.0]butane via strain-release C-C bond cleavage. A range of tertiary allylamines with an acidic α-C-H bond participated in the 1-sulfonylbicyclo[1.1.0]butane-mediated [2,3]-sigmatropic rearrangement, delivering structurally diverse N-cyclobutyl homoallylamines in moderate to excellent yields.