223553-87-5Relevant academic research and scientific papers
Decarboxylative sp 3 C-N coupling via dual copper and photoredox catalysis
Liang, Yufan,Zhang, Xiaheng,MacMillan, David W. C.
, p. 83 - 88 (2018/07/24)
Over the past three decades, considerable progress has been made in the development of methods to construct sp 2 carbon-nitrogen (C-N) bonds using palladium, copper or nickel catalysis 1,2 . However, the incorporation of alkyl substrates to form sp 3 C-N bonds remains one of the major challenges in the field of cross-coupling chemistry. Here we demonstrate that the synergistic combination of copper catalysis and photoredox catalysis can provide a general platform from which to address this challenge. This cross-coupling system uses naturally abundant alkyl carboxylic acids and commercially available nitrogen nucleophiles as coupling partners. It is applicable to a wide variety of primary, secondary and tertiary alkyl carboxylic acids (through iodonium activation), as well as a vast array of nitrogen nucleophiles: nitrogen heterocycles, amides, sulfonamides and anilines can undergo C-N coupling to provide N-alkyl products in good to excellent efficiency, at room temperature and on short timescales (five minutes to one hour). We demonstrate that this C-N coupling protocol proceeds with high regioselectivity using substrates that contain several amine groups, and can also be applied to complex drug molecules, enabling the rapid construction of molecular complexity and the late-stage functionalization of bioactive pharmaceuticals.
Nickel-Catalyzed Reductive Addition of Aryl/Benzyl Halides and Pseudohalides to Carbodiimides for the Synthesis of Amides
Panahi, Farhad,Jamedi, Fereshteh,Iranpoor, Nasser
, p. 780 - 788 (2017/01/18)
A Nickel-catalyzed reductive process is described for the direct amidation of benzyl and aryl halides using carbodiimides as the amidating agent. Moreover, aryl and benzyl C–O electrophiles such as triflate, acetate, tosylate, trityl ether, and pivalate were converted into amides using this method. The in-situ-generated Ni0acts as a catalyst for the reaction at room temperature for benzylic substrates, and 70 °C for aryl electrophiles. This new nickel-catalyzed reductive coupling protocol provides a general and operationally simple method for the synthesis of diverse amides using carbodiimides. Amides bearing bulky substituents can be synthesized by this strategy in high yield, which demonstrates its effectiveness in amide synthesis.
Copper-catalyzed intermolecular amidation and imidation of unactivated alkanes
Tran, Ba L.,Li, Bijie,Driess, Matthias,Hartwig, John F.
supporting information, p. 2555 - 2563 (2014/03/21)
We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding N-alkyl products. The reactions lead to functionalization at secondary C-H bonds over tertiary C-H bonds and even occur at primary C-H bonds. [(phen)Cu(phth)] (1-phth) and [(phen)Cu(phth)2] (1-phth2), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of 1-phth and 1-phth2 with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and tBuOOtBu for the generation of N-alkyl product. Neither 1-phth nor 1-phth2 reacted with excess cyclohexane at 100 C without tBuOOtBu. However, the reactions of 1-phth and 1-phth2 with tBuOOtBu afforded N-cyclohexylphthalimide (Cy-phth), N-methylphthalimide, and tert-butoxycyclohexane (Cy-OtBu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a tert-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr4, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)Cu(phth)2] with tBuOOtBu and (Ph(Me)2CO) 2 at 100 C without cyclohexane afforded N-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and d12-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C-H cleavage of cyclohexane by a tert-butoxy radical. These mechanistic data imply that the tert-butoxy radical reacts with the C-H bonds of alkanes, and the subsequent alkyl radical combines with 1-phth2 to form the corresponding N-alkyl imide product.
Magnetite-supported sulfonic acid: A retrievable nanocatalyst for the Ritter reaction and multicomponent reactions
Gawande, Manoj B.,Rathi, Anuj K.,Nogueira, Isabel D.,Varma, Rajender S.,Branco, Paula S.
supporting information, p. 1895 - 1899 (2013/09/24)
Magnetite-sulfonic acid (Nanocat-Fe-OSO3H), prepared by the wet-impregnation method, serves as a magnetically retrievable sustainable catalyst for the Ritter and multicomponent reactions. The as synthesized catalyst can be used in several reaction cycles without any loss of activity.
Pd(ii)-catalyzed decarboxylative cross-coupling of oxamic acids with potassium phenyltrifluoroborates under mild conditions
Li, Mingzong,Wang, Cong,Fang, Ping,Ge, Haibo
supporting information; experimental part, p. 6587 - 6589 (2011/06/25)
A novel Pd-catalyzed decarboxylative cross-coupling of oxamic acids with potassium phenyltrifluoroborates has been realized under mild reaction conditions. This method provides an efficient access to N-mono- or N,N-disubstituted benzamides and benzoates.
Controlled and chemoselective reduction of secondary amides
Pelletier, Guillaume,Bechara, William S.,Charette, Andre B.
supporting information; experimental part, p. 12817 - 12819 (2010/11/05)
This communication describes a metal-free methodology involving an efficient and controlled reduction of secondary amides to imines, aldehydes, and amines in good to excellent yields under ambient pressure and temperature. The process includes a chemoselective activation of a secondary amide with triflic anhydride in the presence of 2-fluoropyridine. The electrophilic activated amide can then be reduced to the corresponding iminium using triethylsilane, a cheap, rather inert, and commercially available reagent. Imines can be isolated after a basic workup or readily transformed to the aldehydes following an acidic workup. The amine moiety can be accessed via a sequential reductive amination by the addition of silane and Hantzsch ester hydride in a one-pot reaction. Moreover, this reduction tolerates various functional groups that are usually reactive under reductive conditions and is very selective to secondary amides.
Indium-mediated mild and facile method for the synthesis of amides
Cho, Dae Hyan,Jang, Doo Ok
, p. 2285 - 2287 (2007/10/03)
Indium-mediated coupling reactions of acyl chlorides and amines for the synthesis of amide bonds are described. The reaction afforded high yields of the desired amides under mild and neutral conditions, and it was applicable also to the preparation of peptides without epimerization.
Fused pyridine derivatives
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Example 273, (2010/01/30)
The present provides a condensed pyridine compound (I) represented by the following formula: (wherein, R2represents ring A represents benzene ring, pyridine ring, thiophene ring or furan ring; and B represents its pharmaceutically acceptable salt or hydrates thereof, which is a clinically useful medicament having a serotonin antagonism, in particular, that for treating, ameliorating or preventing spastic paralysis or central muscle relaxants for ameliorating myotonia.
A mild and efficient procedure for the preparation of acid chlorides from carboxylic acids
Jang, Doo Ok,Park, Doo Jin,Joonggon, Kim
, p. 5323 - 5326 (2007/10/03)
Various carboxylic acids are converted into the corresponding acid chlorides by treatment with trichloroacetonitrile and triphenylphosphine in methylene chloride at room temperature. Aryl acids show higher reactivity than alkyl acids under the conditions.
