Catalytic intermolecular hydroaminations of unactivated olefins with secondary alkyl amines.
ABSTRACT: The intermolecular hydroamination of unactivated alkenes with simple dialkyl amines remains an unsolved problem in organic synthesis. We report a catalytic protocol for efficient additions of cyclic and acyclic secondary alkyl amines to a wide range of alkyl olefins with complete anti-Markovnikov regioselectivity. In this process, carbon-nitrogen bond formation proceeds through a key aminium radical cation intermediate that is generated via electron transfer between an excited-state iridium photocatalyst and an amine substrate. These reactions are redox-neutral and completely atom-economical, exhibit broad functional group tolerance, and occur readily at room temperature under visible light irradiation. Certain tertiary amine products generated through this method are formally endergonic relative to their constituent olefin and amine starting materials and thus are not accessible via direct coupling with conventional ground-state catalysts.
Project description:We report here a photocatalytic method for the intermolecular anti-Markovnikov hydroamination of unactivated olefins with primary alkyl amines to selectively furnish secondary amine products. These reactions proceed through aminium radical cation (ARC) intermediates and occur at room temperature under visible light irradiation in the presence of an iridium photocatalyst and an aryl thiol hydrogen atom donor. Despite the presence of excess olefin, high selectivities are observed for secondary over tertiary amine products, even though the secondary amines are established substrates for ARC-based olefin amination under similar conditions.
Project description:A new strategy to access linear amines from terminal olefin precursors is reported. This two-step, one-pot hydroamination methodology employs sequential oxidation and reduction catalytic cycles. The formal hydroamination transformation proceeds with excellent regioselectivity, and only the anti-Markovnikov product is observed. Up to 70% yield can be obtained from styrenes or aliphatic olefins and either primary or secondary aromatic amines. Additionally, the scope is broad with respect to the olefin and accommodates a variety of functionalities; we demonstrate that amines with removable aryl protecting groups may be utilized to allow access to a more diverse array of hydroamination adducts.
Project description:Herein we report a metal-free method for the direct anti-Markovnikov hydroamination of unsaturated amines. Irradiation of the amine substrates with visible light in the presence of catalytic quantities of easily synthesized 9-mesityl-10-methylacridinium tetrafluoroborate and thiophenol as a hydrogen-atom donor furnished the nitrogen-containing heterocycles with complete regiocontrol. Two examples of intermolecular anti-Markovnikov alkene hydroamination are also disclosed.
Project description:A one-pot anti-Markovnikov hydroamination of alkenes is reported. The synthesis of primary and secondary amines from unactivated olefins was accomplished in the presence of a variety of functional groups. Hydrozirconation, followed by amination with nitrogen electrophiles, provides exclusive anti-Markovnikov selectivity. Most products are isolated in high yields without the use of column chromatography.
Project description:Here we report a catalytic method for the intermolecular anti-Markovnikov hydroamination of unactivated alkenes using primary and secondary sulfonamides. These reactions occur at room temperature under visible light irradiation and are jointly catalyzed by an iridium(III) photocatalyst, a dialkyl phosphate base, and a thiol hydrogen atom donor. Reaction outcomes are consistent with the intermediacy of an N-centered sulfonamidyl radical generated via proton-coupled electron transfer activation of the sulfonamide N-H bond. Studies outlining the synthetic scope (>60 examples) and mechanistic features of the reaction are presented.
Project description:Highly regio- and enantioselective intermolecular hydroamination of alkenes is a challenging process potentially leading to valuable chiral amines. Hydroamination of alkenes via metal-catalyzed hydrogen atom transfer (HAT) with good regioselectivity and functional group tolerance has been reported, however, high enantioselectivity has not been achieved due to the lack of suitable ligands. Here we report a ligand-promoted cobalt-catalyzed Markovnikov-type selective radical hydroamination of alkenes with diazo compounds. This operationally simple protocol uses unsymmetric NNN-tridentate (UNT) ligand, readily available alkenes and hydrosilanes to construct hydrazones with good functional group tolerance. The hydrazones can undergo nitrogen-nitrogen bond cleavage smoothly to deliver valuable amine derivatives. Additionally, asymmetric intermolecular hydroamination of unactivated aliphatic terminal alkenes using chiral N-imidazolinylphenyl 8-aminoquinoline (IPAQ) ligands has also been achieved to afford chiral amine derivatives with good enantioselectivities.
Project description:Disclosed herein is a general catalytic system for the intermolecular anti-Markovnikov hydroamination of alkenes. By using an organocatalytic photoredox system, ?- and ?-substituted styrenes as well as aliphatic alkenes undergo anti-Markovnikov hydroamination. Heterocyclic amines were also successfully employed as nitrogen nucleophiles, thus providing a direct route to heterocyclic motifs common in medicinal agents.
Project description:We report a Rh-catalyzed hydroamination of 1,3-dienes to generate homoallylic amines. Our work showcases the first case of anti-Markovnikov selectivity in the intermolecular coupling of amines and 1,3-dienes. By tuning the ligand properties and Brønsted acid additive, we find that a combination of rac-BINAP and mandelic acid is critical for achieving anti-Markovnikov selectivity.
Project description:A highly enantio- and regioselective copper-catalyzed hydroamination reaction of alkenes has been developed using diethoxymethylsilane and esters of hydroxylamines. The process tolerates a wide variety of substituted styrenes, including trans-, cis-, and ?,?-disubstituted styrenes, to yield ?-branched amines. In addition, aliphatic alkenes coupled to generate exclusively the anti-Markovnikov hydroamination products.
Project description:In comparison to the extensively studied metal-catalyzed hydroamination reaction, hydroaminomethylation has received significantly less attention despite its considerable potential to streamline amine synthesis. State-of-the-art protocols for hydroaminomethylation of alkenes rely largely on transition-metal catalysis, enabling this transformation only under highly designed and controlled conditions. Here we report a broadly applicable, acid-mediated approach to the hydroaminomethylation of unactivated alkenes and alkynes. This methodology employs cheap, readily available, and bench-stable reactants and affords the desired amines with excellent functional group tolerance and impeccable regioselectivity. The broad scope of this transformation, as well as mechanistic investigations and in situ domino functionalization reactions are reported.