- Conformational Studies by Dynamic NMR. 32. Enantiomerization of Chiral Conformers in Hindered Naphthylamines and Naphthyl Nitroxides
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Observation of anisochronous NMR signals in N-alkyl-N-methyl-1-naphthylamines at low temperature indicates that these molecules adopt a twisted conformation (yielding enantiomeric conformers at the equilibrium) as opposed to the corresponding N-alkyl-N-methyl-2-naphthylamines which give two planar (thus achiral) conformers.The barriers to enantiomerization in 1-naphthylamines have been measured by line-shape analysis for those amines containing prochiral substituents.The use at low temperature of one of the Pirkle's chiral alcohols as a discriminating agent allowed these barriers to be measured even in absence of prochiral grpups.Related alkyl 1-naphthyl nitroxides were also shown to prefer a twisted conformation, but the enantiomerization barriers are too low to be measured by ESR.Examination of a much more hindered nitroxide (2-tert-butyl-1-naphthyl ethyl nitroxide) showed that the methylenic hydrogens were anisochronous even at room temperature, indicating that this radical exist as a racemic mixture.The existence of an exponential relationship between the free energies of enantiomerization in the 1-naphthylamines and the nitrogen hyperfine splittings in the analogous nitroxides allowed the barrier for N,N-dimethyl-1-naphthylamine to be estimated.This barrier could not be measured directly because of the symmetry of the amine.
- Casarini, D.,Lunazzi, L.,Placucci, G.,Macciantelli, D.
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- Continuous-Flow Amide and Ester Reductions Using Neat Borane Dimethylsulfide Complex
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Reductions of amides and esters are of critical importance in synthetic chemistry, and there are numerous protocols for executing these transformations employing traditional batch conditions. Notably, strategies based on flow chemistry, especially for amide reductions, are much less explored. Herein, a simple process was developed in which neat borane dimethylsulfide complex (BH3?DMS) was used to reduce various esters and amides under continuous-flow conditions. Taking advantage of the solvent-free nature of the commercially available borane reagent, high substrate concentrations were realized, allowing outstanding productivity and a significant reduction in E-factors. In addition, with carefully optimized short residence times, the corresponding alcohols and amines were obtained in high selectivity and high yields. The synthetic utility of the inexpensive and easily implemented flow protocol was further corroborated by multigram-scale syntheses of pharmaceutically relevant products. Owing to its beneficial features, including low solvent and reducing agent consumption, high selectivity, simplicity, and inherent scalability, the present process demonstrates fewer environmental concerns than most typical batch reductions using metal hydrides as reducing agents.
- ?tv?s, Sándor B.,Kappe, C. Oliver
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p. 1800 - 1807
(2020/02/27)
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- Homogeneous cobalt-catalyzed deoxygenative hydrogenation of amides to amines
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The first general and efficient cobalt-catalyzed deoxygenative hydrogenation of amides to amines is presented. The optimal catalytic system based on a combination of [Co(NTf2)2] and (p-anisyl)triphos (L3) in the presence of [Me3SiOTf] as acidic co-catalyst facilitates the direct hydrogenation of a broad range of amides to the corresponding amines under mild conditions. A set of control experiments indicate that, after the initial reduction of the amide carboxylic group to the well-known hemiaminal intermediate, the reaction mainly proceeds through C-O bond cleavage though other pathways might be also involved to a minor extent. This journal is
- Papa, Veronica,Cabrero-Antonino, Jose R.,Spannenberg, Anke,Junge, Kathrin,Beller, Matthias
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p. 6116 - 6128
(2020/11/03)
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- Ru-Catalyzed Deoxygenative Transfer Hydrogenation of Amides to Amines with Formic Acid/Triethylamine
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A ruthenium(II)-catalyzed deoxygenative transfer hydrogenation of amides to amines using HCO2H/NEt3 as the reducing agent is reported for the first time. The catalyst system consisting of [Ru(2-methylallyl)2(COD)], 1,1,1-tris(diphenylphosphinomethyl) ethane (triphos) and Bis(trifluoromethane sulfonimide) (HNTf2) performed well for deoxygenative reduction of various secondary and tertiary amides into the corresponding amines in high yields with excellent selectivities, and exhibits high tolerance toward functional groups including those that are reduction-sensitive. The choice of hydrogen source and acid co-catalyst is critical for catalysis. Mechanistic studies suggest that the reductive amination of the in situ generated alcohol and amine via borrowing hydrogen is the dominant pathway. (Figure presented.).
- Pan, Yixiao,Luo, Zhenli,Xu, Xin,Zhao, Haoqiang,Han, Jiahong,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
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supporting information
p. 3800 - 3806
(2019/07/12)
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- Cobalt-Catalyzed Reductive Alkylation of Amines with Carboxylic Acids
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Direct reductive alkylation of amines with carboxylic acid is carried out by using an inexpensive, air-stable cobalt/triphos catalytic system with molecular hydrogen as the reductant. This efficient synthetic method proceeds through reduction and condensation, followed by reduction of the in situ-generated imine into the amine in a green catalytic process.
- Emayavaramban, Balakumar,Chakraborty, Priyanka,Sundararaju, Basker
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p. 3089 - 3093
(2018/12/11)
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- Alanine triazole iridium-catalyzed C–N bond formation through borrowing hydrogen strategy
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An efficient synthesis of secondary amines has been described through alanine triazole iridium-catalyzed C–N bond formation of an aromatic amine and an alkyl amine using the borrowing hydrogen strategy. In addition, it was observed that alanine triazole iridium is also an efficient catalyst to promote C–N bond formation of an aromatic amine and alcohols with good to excellent yields.
- Yu, Xiaoli,Zhao, Ranran,Wan, Huida,Yang, Yongchun,Wang, Dawei
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supporting information
p. 4588 - 4591
(2016/09/23)
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- Deoxygenative Hydrogenation of Amides Catalyzed by a Well-Defined Iridium Pincer Complex
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The iridium-catalyzed highly chemoselective hydrogenation of amides to amines has been developed. Using a well-defined iridium catalyst bearing a P(O)C(O)P pincer ligand combined with B(C6F5)3, the C-O cleavage products are formed under mild reaction conditions. The reaction provides a new method for the preparation of amines from amides in good yield with high selectivity.
- Yuan, Ming-Lei,Xie, Jian-Hua,Zhu, Shou-Fei,Zhou, Qi-Lin
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p. 3665 - 3669
(2016/07/06)
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- Direct N-alkylation of aromatic amines using a microflow reactor: Enhancement of selectivity and reactivity
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A simple and highly atom-economical method for the direct N-alkylation of aromatic amines by using a microflow reactor was developed to overcome the problem of over-alkylation. In the developed method, high-yield conversion (up to 100%) was achieved in a relatively short reaction time. The ratio of mono- to di-benzylated products (3.57:1) was higher than that achieved with batch reactions conducted in a 1 L scale flask (0.87:1). The structural features of the microflow reactor meant that short-chain alkyl halides could be converted into products with high reactivity and selectivity under superheating conditions, although their boiling point was much lower than the reaction temperature. This method was successfully applied to the synthesis of a range of secondary amines including an intermediate of indobufen synthesis.
- Choi, Yong-Sung,Kim, Yoon-Jung,Shen, Liu-Lan,Lee, Yong Sup,Jeong, Jin-Hyun
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supporting information
p. 970 - 974
(2015/04/27)
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- Nickel-catalyzed amination of Aryl chlorides with ammonia or ammonium salts
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The nickel-catalyzed amination of aryl chlorides to form primary arylamines occurs with ammonia or ammonium sulfate and a well-defined single-component nickel(0) precatalyst containing a Josiphos ligand and an η2-bound benzonitrile ligand. This system also catalyzes the coupling of aryl chlorides with gaseous amines in the form of their hydrochloride salts. Simple alternative: The title reaction, which results in primary arylamines, is catalyzed by well-defined single-component nickel(0) precatalysts containing a Josiphos ligand and an η2-bound benzonitrile ligand. This system also catalyzes the coupling of aryl chlorides with gaseous amines in the form of their hydrochloride salts.
- Green, Rebecca A.,Hartwig, John F.
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supporting information
p. 3768 - 3772
(2015/03/18)
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- Palladium-catalyzed amination of aryl chlorides and bromides with ammonium salts
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We report the palladium-catalyzed coupling of aryl halides with ammonia and gaseous amines as their ammonium salts. The coupling of aryl chlorides and ortho-substituted aryl bromides with ammonium sulfate forms anilines with higher selectivity for the primary arylamine over the diarylamine than couplings with ammonia in dioxane. The resting state for the reactions of aryl chlorides is different from the resting state for the reactions of aryl bromides, and this change in resting states is proposed to account for a difference in selectivities for reactions of the two haloarenes.
- Green, Rebecca A.,Hartwig, John F.
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supporting information
p. 4388 - 4391
(2015/01/08)
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- Bicyclic core estrogens as full antagonists: Synthesis, biological evaluation and structure-activity relationships of estrogen receptor ligands based on bridged oxabicyclic core arylsulfonamides
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Compounds that block estrogen action through the estrogen receptor (ER) or downregulate ER levels are useful for the treatment of breast cancer and endocrine disorders. In our search for structurally novel estrogens having three-dimensional core scaffolds, we found some compounds with a 7-oxabicyclo[2.2.1]heptene core that bound well to the ERs. The best of these compounds, a phenyl sulfonate ester (termed OBHS for oxabicycloheptene sulfonate), was a partial antagonist on both ERα and ERβ. Although OBHS bears no structural resemblance to other estrogen antagonists, it appears to achieve its partial antagonist character by stabilizing a novel conformation of the ER that involves a significant distortion of helix-11. To enhance the antagonist properties of these oxabicyclo[2.2.1]heptane core ligands, we expanded the functional diversity of OBHS by replacing the sulfonate with secondary or tertiary sulfonamides (-SO2NR-), isoelectronic and potentially isostructural molecular replacements. An array of 16 OBHS sulfonamide analogues were prepared through a Diels-Alder reaction of a 3,4-diarylfuran using various N-aryl vinyl sulfonamide dienophiles. While the more polar secondary sulphonamides were weak ligands, certain of the tertiary sulfonamides had very good ER binding affinity. In HepG2 cell reporter gene assays, the sulphonamides had moderate potency, but they showed lower intrinsic transcriptional activity on ERα than the selective estrogen receptor modulator (SERM) hydroxytamoxifen or OBHS, and they were inverse agonists on ERβ. Thus, the behaviour of these OBH-sulfonamides more closely mirrors the activity of full antagonists like the drug fulvestrant (ICI 182780), and their greater antagonist biocharacter appears to arise from an accentuated distortion of helix-11.
- Zhu, Manghong,Zhang, Chen,Nwachukwu, Jerome C.,Srinivasan, Sathish,Cavett, Valerie,Zheng, Yangfan,Carlson, Kathryn E.,Dong, Chune,Katzenellenbogen, John A.,Nettles, Kendall W.,Zhou, Hai-Bing
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p. 8692 - 8700
(2013/01/15)
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- Reductive N-alkylation of aromatic amines and nitro compounds with nitriles using polymethylhydrosiloxane
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The potential utility of polymethylhydrosiloxane (PMHS) as a reducing agent for reductive N-alkylation of aromatic amines and nitro compounds using nitriles as an alkylating agent and Pd(OH)2/C as a catalyst is described. The application of this method for the synthesis of several heterocyclic compounds is also reported.
- Reddy, Ch. Raji,Vijeender,Bhusan, P. Bibhuti,Madhavi, P. Phani,Chandrasekhar
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p. 2765 - 2768
(2008/02/03)
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- Ruthenium-catalyzed intermolecular coupling reactions of arylamines with ethylene and 1,3-dienes: Mechanistic insight on hydroamination vs ortho-C-H bond activation
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(Chemical Equation Presented) The cationic ruthenium complex [(PCy 3)2(CO)(Cl)Ru=CHCH=C(CH3)2] +BF4- was found to be an effective catalyst for the coupling reaction of aniline and ethylene to form a ～1:1 ratio of N-ethylaniline and 2-methylquinoline products. The analogous reaction with 1,3-dienes resulted in the preferential formation of Markovnikov addition products. The normal isotope effect of kNH/kND = 2.2 (aniline and aniline-d7 at 80°C) and the Hammett ρ = -0.43 (correlation of para-substituted p-X-C6H4NH2) suggest an N-H bond activation rate-limiting step for the catalytic reaction.
- Yi, Chae S.,Sang, Young Yun
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p. 2181 - 2183
(2007/10/03)
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- Cleavage of a p-cyanobenzyl group from protected alcohols, amines, and thiols using triethylgermyl sodium
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Alcohols, amines, and thiols protected with a p-cyanobenzyl group can be easily and quantitatively deprotected using triethylgermyl sodium under mild conditions.
- Yokohama, Yasuo,Takizawa, Shuichi,Nanjo, Masato,Mochida, Kunio
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p. 1032 - 1033
(2007/10/03)
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- Stereochemistry of arylamides, 1. NMR spectra of some N-(1-naphthyl)amides
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The results of the NMR study of the conformational equilibria and dynamics at the amide group of a series of JV-(l-naphthyl)amides are reported. In the case of W-(l-naphthyl) formamides, the presence of two conformers, corresponding to the E- (carbonyi group irons to the naphthyl ring) and Z-form (carbonyl group cis to the naphthyl ring) of the amide, has been detected. In the case of isobutyryl and benzoyl amides, only one conformer (the ￡-form) was observed in solution.
- Leis, Jaan,Karelson, Mati,Scniemenz, Guenter Paulus
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p. 157 - 171
(2007/10/03)
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- Catalysts for alkoxylation reactions
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Catalysts producing a sharply peaked alkoxylation distribution during the alkoxylation of organic materials comprise mixtures of BF3 and metal alkyls or metal alkoxides, SiF4 and metal alkyls or metal alkoxides, or mixtures of these catalysts.
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- Methods of alkoxylation
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Catalysts comprising mixtures of HF and metal alkoxides and mixed metal alkoxides produce a sharply peaked alkoxylation distribution during the alkoxylation of organic materials.
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- Catalysts for alkoxylation reactions
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Catalysts and a method of using said catalysts for the alkoxylation of a variety of materials is disclosed. Catalysts so described produce alkoxylates having a very sharp alkoxylate distribution. The catalysts are supported and unsupported dialkoxy and dialkyl metal fluorides and halides and alkyl metal difluorides and dihalides.
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- Manufacture of arylamines
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Arylamines are manufactured by reacting alcohols with amines in the presence of phosphorus-III compounds. The arylamines I manufactured by the process of the invention are intermediates for the manufacture of crop protection agents, optical brighteners, especially amino-coumarin derivatives, and dyes, especially of the xanthene, pyronine, rhodamine, oxazine, azo, triphenylmethane and diphenylmethane series.
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