51713-72-5Relevant academic research and scientific papers
CATALYTIC SYSTEMS FOR STEREOSELECTIVE SYNTHESIS OF CHIRAL AMINES BY ENANTIODIVERGENT RADICAL C-H AMINATION
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Paragraph 0201; 0242-0243; 0250, (2020/11/27)
In one aspect, the disclosure relates to a mode of asymmetric induction in radical processes based on sequential combination of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution. Also disclosed is an asymmetric system for stereoselective synthesis of strained 5-membered cyclic sulfamides via radical 1,5-C—H amination of sulfamoyl azides. The disclosed metalloradical system can control the degree and sense of asymmetric induction in the catalytic radical C—H amination in a systematic manner. The disclosed system is applicable to a broad scope of substrates with different types of C(sp3)-H bonds and exhibits reactivity and selectivity, providing access to both enantiomers of useful 5-membered cyclic sulfamides in a highly enantioenriched form. Also disclosed are catalysts useful in these processes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
Asymmetric Induction and Enantiodivergence in Catalytic Radical C-H Amination via Enantiodifferentiative H-Atom Abstraction and Stereoretentive Radical Substitution
Lang, Kai,Torker, Sebastian,Wojtas, Lukasz,Zhang, X. Peter
supporting information, p. 12388 - 12396 (2019/08/20)
Control of enantioselectivity remains a major challenge in radical chemistry. The emergence of metalloradical catalysis (MRC) offers a conceptually new strategy for addressing this and other outstanding issues. Through the employment of D2-symmetric chiral amidoporphyrins as the supporting ligands, Co(II)-based MRC has enabled the development of new catalytic systems for asymmetric radical transformations with a unique profile of reactivity and selectivity. With the support of new-generation HuPhyrin chiral ligands whose cavity environment can be fine-tuned, the Co-centered d-radicals enable to address challenging issues that require exquisite control of fundamental radical processes. As showcased with asymmetric 1,5-C-H amination of sulfamoyl azides, the enantiocontrol of which has proven difficult, the judicious use of HuPhyrin ligand by tuning the bridge length and other remote nonchiral elements allows for controlling both the degree and sense of asymmetric induction in a systematic manner. This effort leads to successful development of new Co(II)-based catalytic systems that are highly effective for enantiodivergent radical 1,5-C-H amination, producing both enantiomers of the strained five-membered cyclic sulfamides with excellent enantioselectivities. Detailed deuterium-labeling studies, together with DFT computation, have revealed an unprecedented mode of asymmetric induction that consists of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution.
Synthesis of Symmetric and Unsymmetric Secondary Amines from the Ligand-Promoted Ruthenium-Catalyzed Deaminative Coupling Reaction of Primary Amines
Arachchige, Pandula T. Kirinde,Lee, Hanbin,Yi, Chae S.
, p. 4932 - 4947 (2018/05/08)
The catalytic system generated in situ from the tetranuclear Ru-H complex with a catechol ligand (1/L1) was found to be effective for the direct deaminative coupling of two primary amines to form secondary amines. The catalyst 1/L1 was highly chemoselective for promoting the coupling of two different primary amines to afford unsymmetric secondary amines. The analogous coupling of aniline with primary amines formed aryl-substituted secondary amines. The treatment of aniline-d7 with 4-methoxybenzylamine led to the coupling product with significant deuterium incorporation on CH2 (18% D). The most pronounced carbon isotope effect was observed on the α-carbon of the product isolated from the coupling reaction of 4-methoxybenzylamine (C(1) = 1.015(2)). A Hammett plot was constructed from measuring the rates of the coupling reaction of 4-methoxyaniline with a series of para-substituted benzylamines 4-X-C6H4CH2NH2 (X = OMe, Me, H, F, CF3) (ρ = -0.79 ± 0.1). A plausible mechanistic scheme has been proposed for the coupling reaction on the basis of these results. The catalytic coupling method provides an operationally simple and chemoselective synthesis of secondary amine products without using any reactive reagents or forming wasteful byproducts.
Comparative molecular field analysis of fenoterol derivatives interacting with an agonist-stabilized form of the β2-adrenergic receptor
Plazinska, Anita,Pajak, Karolina,Rutkowska, Ewelina,Jimenez, Lucita,Kozocas, Joseph,Koolpe, Gary,Tanga, Mary,Toll, Lawrence,Wainer, Irving W.,Jozwiak, Krzysztof
, p. 234 - 246 (2014/01/17)
The β2-adrenergic receptor (β2-AR) agonist [3H]-(R,R′)-methoxyfenoterol was employed as the marker ligand in displacement studies measuring the binding affinities (Ki values) of the stereoisomers of a series of 4′-methoxyfenoterol analogs in which the length of the alkyl substituent at α′ position was varied from 0 to 3 carbon atoms. The binding affinities of the compounds were additionally determined using the inverse agonist [3H]-CGP-12177 as the marker ligand and the ability of the compounds to stimulate cAMP accumulation, measured as EC50 values, were determined in HEK293 cells expressing the β2-AR. The data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the α′ position. The results also indicate that the Ki values obtained using [3H]-(R,R′)-methoxyfenoterol as the marker ligand modeled the EC50 values obtained from cAMP stimulation better than the data obtained using [3H]-CGP-12177 as the marker ligand. The data from this study was combined with data from previous studies and processed using the Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting the binding to the β2-AR conformation probed by [3H]-(R,R′)-4′-methoxyfenoterol. The CoMFA model of the agonist-stabilized β2-AR suggests that the binding of the fenoterol analogs to an agonist-stabilized conformation of the β2-AR is governed to a greater extend by steric effects than binding to the [3H]-CGP-12177-stabilized conformation(s) in which electrostatic interactions play a more predominate role.
Tandem synthesis of amides and secondary amines from esters with primary amines under solvent-free conditions
Lee, Jeongbin,Muthaiah, Senthilkumar,Hong, Soon Hyeok
, p. 2653 - 2660 (2014/09/17)
An iridium(III)-catalyzed tandem synthesis of amides and amines from esters under solvent-free conditions is described. A commercially available iridium(III) complex, [Cp*IrCl2]2, with sodium acetate showed the best activity for the synthesis of amides and secondary amines. The amide was formed by ester-amide exchange which generates an alcohol in situ which is subsequently transformed to a secondary amine via hydrogen autotransfer. This synthetic protocol with high atom economy generates water as the sole by-product and can afford amides and amines from various esters in a one-pot reaction, expanding the synthetic versatility of ester transformations.
Bis(amidate)bis(amido) titanium complex: A regioselective intermolecular alkyne hydroamination catalyst
Yim, Jacky C.-H.,Bexrud, Jason A.,Ayinla, Rashidat O.,Leitch, David C.,Schafer, Laurel L.
, p. 2015 - 2028 (2014/04/03)
An efficient and selective bis(amidate)bis(amido) titanium precatalyst for the anti-Markovnikov hydroamination of alkynes is reported. Hydroamination of terminal and internal alkynes with primary alkylamines, arylamines, and hydrazines is promoted by 5-10 mol % of Ti catalyst. Various functional groups are tolerated including esters, protected alcohols, and imines. The in situ generated complex shows comparable catalytic activity, demonstrating its synthetic versatility for benchtop application. Applications of this catalyst for the synthesis of amino alcohols and a one-pot procedure for indole synthesis are described. A mechanistic proposal that invokes turnover-limiting protonolysis is presented to rationalize the observed regioselectivities.
Heavier alkaline earth catalysts for the intermolecular hydroamination of vinylarenes, dienes, and alkynes
Brinkmann, Christine,Barrett, Anthony G. M.,Hill, Michael S.,Procopiou, Panayiotis A.
supporting information; experimental part, p. 2193 - 2207 (2012/03/10)
The heavier group 2 complexes [M{N(SiMe3)2} 2]2(1, M = Ca; 2, M = Sr) and [M{CH(SiMe3) 2}2(THF)2] (3, M = Ca; 4, M = Sr) are shown to be effective precatalysts for the intermolecular hydroamination of vinyl arenes and dienes under mild conditions. Initial studies revealed that the amide precatalysts, 1 and 2, while compromised in terms of absolute activity by a tendency toward transaminative behavior, offer greater stability toward polymerization/oligomerization side reactions. In every case the strontium species, 2 and 4, were found to outperform their calcium congeners. Reactions of piperidine with para-substituted styrenes are indicative of rate-determining alkene insertion in the catalytic cycle while the ease of addition of secondary cyclic amines was found to be dependent on ring size and reasoned to be a consequence of varying amine nucleophilicity. Hydroamination of conjugated dienes yielded isomeric products via η3-allyl intermediates and their relative distributions were explained through stereoelectronic considerations. The ability to carry out the hydroamination of internal alkynes was found to be dramatically dependent upon the identity of the alkyne substituents while reactions employing terminal alkynes resulted in the precipitation of insoluble and unreactive group 2 acetylides. The rate law for styrene hydroamination with piperidine catalyzed by [Sr{N(SiMe3) 2}2]2 was deduced to be first order in [amine] and [alkene] and second order in [catalyst], while large kinetic isotope effects and group 2 element-dependent ΔS? values implicated the formation of an amine-assisted rate-determining alkene insertion transition state in which there is a considerable entropic advantage associated with use of the larger strontium center.
When bigger is better: Intermolecular hydrofunctionalizations of activated alkenes catalyzed by heteroleptic alkaline earth complexes
Liu, Bo,Roisnel, Thierry,Carpentier, Jean-Francois,Sarazin, Yann
supporting information; experimental part, p. 4943 - 4946 (2012/07/13)
New alkaline-earth amido complexes catalyze the regioselective intermolecular hydroamination (see scheme; Ae=alkaline earth) and hydrophosphination of styrene and isoprene with unprecedented activities. The catalytic performances increased linearly with the size of the metal. Copyright
Heavier group 2 metals and intermolecular hydroamination: A computational and synthetic assessment
Barrett, Anthony G. M.,Brinkmann, Christine,Crimmin, Mark R.,Hill, Michael S.,Hunt, Patricia,Procopiou, Panayiotis A.
scheme or table, p. 12906 - 12907 (2009/12/05)
(Chemical Equation Presented) A density functional theory assessment of the use of the group 2 elements Mg, Ca, Sr, and Ba for the intermolecular hydroamination of ethene indicated that the efficiency of the catalysis is dependent upon both the polarity and the deformability of the electron density within the metal-substituent bonds of key intermediates and transition states. The validity of this analysis was supplemented by a preliminary study of the use of group 2 amides for the intermolecular hydroamination of vinyl arenes. Although strontium was found to provide the highest catalytic activity, in line with the expectation provided by the theoretical study, a preliminary kinetic analysis demonstrated that this is possibly a consequence of the increased radius and accessibility of this cation rather than a reflection of a reduced barrier for rate-determining alkene insertion.
An easy-to-use, regioselective, and robust bis(amidate) titanium hydroamination precatalyst: Mechanistic and synthetic investigations toward the preparation of tetrahydroisoquinolines and benzoquinolizine alkaloids
Zhang, Zhe,Leitch, David C.,Lu, Man,Patrick, Brian O.,Schafer, Laurel L.
, p. 2012 - 2022 (2008/02/04)
Amidate-supported titanium amido complexes are efficient and regioselective precatalysts for intermolecular hydroamination of terminal alkynes with primary amines. The synthesis and characterization of the first his(amidate)-supported titanium-imido complex is reported. Its role as the active catalytic species is suggested in the course of product distribution studies using deuteratcd substrates. The bis(amidate)-supported prccatalysts exhibit good functional-group tolerance, even performing hydroaminations in the presence of ester and amide groups. This functional-group tolerance was exploited in the synthesis of a variety of 1-substituted tetrahydroisoquinoline alkaloids and a one-pot hydroaminative procedure for the high yielding preparation of the benzo[a]quinolizine skeleton.
