- Generation of Oxyphosphonium Ions by Photoredox/Cobaloxime Catalysis for Scalable Amide and Peptide Synthesis in Batch and Continuous-Flow
-
Phosphine-mediated deoxygenative nucleophilic substitutions, such as the Mitsunobu reaction, are of great importance in organic synthesis. However, the conventional protocols require stoichiometric oxidants to trigger the formation of the oxyphosphonium i
- Chen, Xiangyang,Houk, Kendall N.,Mo, Jia-Nan,Su, Junqi,Umanzor, Alexander,Zhang, Zheng,Zhao, Jiannan
-
supporting information
(2022/01/06)
-
- Nickel-Catalyzed Amination of Aryl Chlorides with Amides
-
A nickel-catalyzed amination of aryl chlorides with diverse amides via C-N bond cleavage has been realized under mild conditions. A broad substrate scope with excellent functional group tolerance at a low catalyst loading makes the protocol powerful for synthesizing various aromatic amines. The aryl chlorides could selectively couple to the amino fragments rather than the carbonyl moieties of amides. Our protocol complements the conventional amination of aryl chlorides and expands the usage of inactive amides.
- Li, Jinpeng,Huang, Changyu,Wen, Daheng,Zheng, Qingshu,Tu, Bo,Tu, Tao
-
supporting information
p. 687 - 691
(2021/01/09)
-
- Hydrosilylative reduction of primary amides to primary amines catalyzed by a terminal [Ni-OH] complex
-
A terminal [Ni-OH] complex1, supported by triflamide-functionalized NHC ligands, catalyzes the hydrosilylative reduction of a range of primary amides into primary amines in good to excellent yields under base-free conditions with key functional group tolerance. Catalyst1is also effective for the reduction of a variety of tertiary and secondary amides. In contrast to literature reports, the reactivity of1towards amide reduction follows an inverse trend,i.e., 1° amide > 3° amide > 2° amide. The reaction does not follow a usual dehydration pathway.
- Bera, Jitendra K.,Pandey, Pragati
-
supporting information
p. 9204 - 9207
(2021/09/20)
-
- Direct Amidation of Esters by Ball Milling**
-
The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
- Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
-
supporting information
p. 21868 - 21874
(2021/09/02)
-
- Synthesis of O- tert-Butyl- N,N-disubstituted Hydroxylamines by N-O Bond Formation
-
The reaction of magnesium amides with tert-butyl 2,6-dimethyl perbenzoate in tetrahydrofuran at 0 °C provides a method for the synthesis O-tert-butyl-N,N-disubstituted hydroxylamines by direct N-O bond formation with a broad functional group tolerance. Less sterically hindered magnesium amides require ortho,ortho-disubstitution on the perester electrophile component, whereas sterically encumbered magnesium amides perform comparably with either tert-butyl perbenzoate or tert-butyl 2,6-dimethyl perbenzoate. A reaction mechanism is presented to account for the observed reactivity.
- Hill, Jarvis,Crich, David
-
supporting information
p. 6396 - 6400
(2021/08/23)
-
- DIVERSITY-ORIENTED SYNTHESIS OF N,N,O-TRISUBSTITUTED HYDROXYLAMINES FROM ALCOHOLS AND AMINES BY N-O BOND FORMATION
-
In one aspect, the disclosure relates to a method for the direct synthesis of complex N,N,O-trisubstituted hydroxylamines by N—O bond formation. In another aspect, the method can successfully be employed using a wide variety of commercially available alcohols and secondary amines and enables the construction of large fragment-based libraries of trisubstituted hydroxylamines for drug discovery purposes. Also disclosed are N,N,O-trisubstituted hydroxylamines having low basicity, high stability at ambient temperatures, and an inherent lack of reactivity towards acetylating and sulfonylating enzymes that confer mutagenicity on less-substituted hydroxylamines.
- -
-
Paragraph 0295; 0313-0314
(2021/11/26)
-
- Ammonia-borane as a Catalyst for the Direct Amidation of Carboxylic Acids
-
Ammonia-borane serves as an efficient substoichiometric (10%) precatalyst for the direct amidation of both aromatic and aliphatic carboxylic acids. In situ generation of amine-boranes precedes the amidation and, unlike the amidation with stoichiometric amine-boranes, this process is facile with 1 equiv of the acid. This methodology has high functional group tolerance and chromatography-free purification but is not amenable for esterification. The latter feature has been exploited to prepare hydroxyl- and thiol-containing amides.
- Ramachandran, P. Veeraraghavan,Hamann, Henry J.
-
supporting information
p. 2938 - 2942
(2021/05/04)
-
- Method for preparing amide from carboxylic acid under irradiation of blue light by taking iridium and cobalt complexes as catalysts
-
The invention relates to a method for preparing amide from carboxylic acid under the irradiation of blue light by taking iridium and cobalt complexes as catalysts, and belongs to the field of chemistry. The method comprises the following step of: by taking R substituted carboxylic acid and R1' and R2' substituted amines as raw materials, triphenylphosphine as a deoxidizing agent, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 as a photocatalyst and Co(dmgH)(dmgH2)Cl2 as a metal complex catalyst, reacting in dichloromethane in an inert atmosphere and under the irradiation of blue light to obtain an amide compound, wherein R is an aryl group, a heteroaryl group, a protected amino group, a substituted alkyl group, a substituted aryl group or a substituted protected amino group, R1' is a hydrogen group, a substituted alkyl group, a phenyl group or a substituted phenyl group, and R2' is a hydrogen group, a substituted alkyl group, a phenyl group or a substituted phenyl group.
- -
-
Paragraph 0085-0086
(2021/05/12)
-
- UV-Light-Induced N-Acylation of Amines with α-Diketones
-
Herein, we develop a mild method for N-acylation of primary and secondary amines with α-diketones induced by ultraviolet (UV) light. Forty-six examples with various functional groups are explored at room temperature with irradiation by three 26 W UV lamps (350-380 nm). The yield reaches 97%. The gram scale experiment product yield is 76%. Moreover, this system can be applied to the synthesis of several amino acid derivatives. Mechanistic studies show that benzoin is generated in situ from benzil under UV irradiation.
- Xu, Zhihui,Yang, Tianbao,Tang, Niu,Ou, Yifeng,Yin, Shuang-Feng,Kambe, Nobuaki,Qiu, Renhua
-
supporting information
p. 5329 - 5333
(2021/07/21)
-
- Regio- And Stereoselective (S N2) N -, O -, C - And S -Alkylation Using Trialkyl Phosphates
-
Bimolecular nucleophilic substitution (S N 2) is one of the most well-known fundamental reactions in organic chemistry to generate new molecules from two molecules. In principle, a nucleophile attacks from the back side of an alkylating agent having a suitable leaving group, most commonly a halide. However, alkyl halides are expensive, very harmful, toxic and not so stable, which makes them problematic for laboratory use. In contrast, trialkyl phosphates are inexpensive, readily accessible and stable at room temperature, under air, and are easy to handle, but rarely used as alkylating agents in organic synthesis. Here, we describe a mild, straightforward and powerful method for nucleophilic alkylation of various N -, O -, C - and S -nucleophiles using readily available trialkyl phosphates. The reaction proceeds smoothly in excellent yield, and quantitative yield in many cases, and covers a wide range of substrates. Further, the rare stereoselective transfer of secondary alkyl groups has been achieved with inversion of configuration of chiral centers (up to 98% ee).
- Banerjee, Amit,Hattori, Tomohiro,Yamamoto, Hisashi
-
-
- Pd-Catalyzed Oxidative Aminocarbonylation of Arylboronic Acids with Unreactive Tertiary Amines via C-N Bond Activation
-
An efficient synthesis of tertiary amides from aryl boronic acids and inert tertiary amines through the oxidative carbonylation via C(sp3)-N bond activation is presented. This protocol significantly restricts the homocoupling biarylketone product. It involves the use of a homogeneous PdCl2/CuI catalyst and a heterogeneous Pd/C based catalyst, which promotes C(sp3)-N bond activation of tertiary amines with aryl boronic acids. This process represents a ligand-free, base-free, and recyclable catalyst along with an ideal oxidant like molecular oxygen.
- Kolekar, Yuvraj A.,Bhanage, Bhalchandra M.
-
p. 14028 - 14035
(2021/05/29)
-
- A practical and sustainable protocol for direct amidation of unactivated esters under transition-metal-free and solvent-free conditions
-
In this paper, a NaOtBu-mediated synthesis approach was developed for direct amidation of unactivated esters with amines under transition-metal-free and solvent-free conditions, affording a series of amides in good to excellent yields at room temperature. In particular, an environmentally friendly and practical workup procedure, which circumvents the use of organic solvents and chromatography in most cases, was disclosed. Moreover, the gram-scale production of representative products3a,3wand3auwas efficiently realized by applying operationally simple, sustainable and practical procedures. Furthermore, this approach was also applicable to the synthesis of valuable molecules such as moclobemide (a powerful antidepressant), benodanil and fenfuram (two commercial agricultural fungicides). These results demonstrate that this protocol has the potential to streamline amide synthesis in industry. Meanwhile, quantitative green metrics of all the target products were evaluated, implying that the present protocol is advantageous over the reported ones in terms of environmental friendliness and sustainability. Finally, additional experiments and computational calculations were carried out to elucidate the mechanistic insight of this transformation, and one plausible mechanism was provided on the basis of these results and the related literature reports.
- Chen, Cheng,Cheng, Hua,Du, Min-Chen,Qian, Liang,Qin, Xin,Sang, Wei,Yao, Wei-Zhong,Yuan, Ye,Zhang, Rui
-
supporting information
p. 3972 - 3982
(2021/06/17)
-
- Preparation of alkylated compounds using the trialkylphosphate
-
[Problem] trialkylphosphate strong base used reaction agent, a carboxylic acid, a ketone, an aldehyde, amine, amide, thiol, ester or Grignard reagent to a variety of substrates, and/or high efficiency to generate a highly stereoselective alkylation reaction, the alkylated compounds capable of producing new means. [Solution] was used as the alkylating agent in the alkylation of compound trialkylphosphate, strongly basic reaction production use. [Drawing] no
- -
-
Paragraph 0184-0185; 0204
(2021/11/02)
-
- Homoleptic Bis(trimethylsilyl)amides of Yttrium Complexes Catalyzed Hydroboration Reduction of Amides to Amines
-
Homoleptic lanthanide complex Y[N(TMS)2]3 is an efficient homogeneous catalyst for the hydroboration reduction of secondary amides and tertiary amides to corresponding amines. A series of amides containing different functional groups such as cyano, nitro, and vinyl groups were found to be well-tolerated. This transformation has also been nicely applied to the synthesis of indoles and piribedil. Detailed isotopic labeling experiments, control experiments, and kinetic studies provided cumulative evidence to elucidate the reaction mechanism.
- Ye, Pengqing,Shao, Yinlin,Ye, Xuanzeng,Zhang, Fangjun,Li, Renhao,Sun, Jiani,Xu, Beihang,Chen, Jiuxi
-
supporting information
p. 1306 - 1310
(2020/02/22)
-
- Selective Methylation of Amides, N-Heterocycles, Thiols, and Alcohols with Tetramethylammonium Fluoride
-
We herein disclose the use of tetramethylammonium fluoride (TMAF) as a direct and selective methylating agent of a variety of amides, indoles, pyrroles, imidazoles, alcohols, and thiols. The method is characterized by operational simplicity, wide scope, and ease of purification. Our computational studies suggest a concerted methylation-deprotonation as the preferred reaction pathway.
- Cheng, Hong-Gang,Pu, Maoping,Kundu, Gourab,Schoenebeck, Franziska
-
supporting information
p. 331 - 334
(2019/12/30)
-
- Two-step continuous flow synthesis of amide via oxidative amidation of methylarene
-
A green and efficient method for the synthesis of amides has been developed through oxidative amidation between methylarenes with amines in a two-step continuous flow system. This method integrates methylarene oxidation and amide formation into a single operation which is usually accomplished separately. Oxidation with tert-butyl hydroperoxide (TBHP) as “green” oxidant, the synthesis of amides under mild reaction conditions in continuous flow system and the utilization of methylarenes as starting material make this methodology novel and environment friendly. The practical value of this method is highlighted through the synthesis of high-profile pharmaceutical agents, acetylprocainamide.
- Fang, Zheng,Guo, Kai,He, Wei,Liu, Chengkou,Shi, Tingting,Yang, Yuhang,Yang, Zhao,Zhang, Zhimin
-
supporting information
(2020/02/28)
-
- Well-defined N-heterocyclic carbene/ruthenium complexes for the alcohol amidation with amines: The dual role of cesium carbonate and improved activities applying an added ligand
-
Dehydrogenative amide bond formation from alcohols and amines has been regarded as an atom-economic and sustainable process. Among various catalytic systems, N-heterocyclic carbene (NHC)-based Ru catalytic systems have attracted growing interest due to the outstanding properties of NHCs as ligands. Herein, an NHC/Ru complex (1) was prepared and its structure was further confirmed with X-ray crystallography. In the presence of Cs2CO3, two NHC/Ru-based catalytic systems were disclosed to be active for this amide synthesis. System A, which did not contain any added ligand, required a catalyst loading of 1.00 mol%. Interestingly, improved catalytic performance was realized by the addition of an NHC precursor (L). Optimization of the amounts of L and other conditions gave rise to system B, a much more potent system with the Ru loading as low as 0.25 mol%. Moreover, an NHC-Ru-carbonate complex 6 was identified from the refluxing toluene of 1 and Cs2CO3, and further investigations revealed that 6 was an important intermediate for this catalytic reaction. Based on the above results, we claimed that the role of Cs2CO3 was to facilitate the formation of key intermediate 6. On the other hand, it provided the optimized basicity for the selective amide formation.
- Wang, Wan-Qiang,Yuan, Ye,Miao, Yang,Yu, Bao-Yi,Wang, Hua-Jing,Wang, Zhi-Qin,Sang, Wei,Chen, Cheng,Verpoort, Francis
-
-
- Highly Chemoselective, Transition-Metal-Free Transamidation of Unactivated Amides and Direct Amidation of Alkyl Esters by N-C/O-C Cleavage
-
The amide bond is one of the most fundamental functional groups in chemistry and biology and plays a central role in numerous processes harnessed to streamline the synthesis of key pharmaceutical and industrial molecules. Although the synthesis of amides is one of the most frequently performed reactions by academic and industrial scientists, the direct transamidation of tertiary amides is challenging due to unfavorable kinetic and thermodynamic contributions of the process. Herein, we report the first general, mild, and highly chemoselective method for transamidation of unactivated tertiary amides by a direct acyl N-C bond cleavage with non-nucleophilic amines. This operationally simple method is performed in the absence of transition metals and operates under unusually mild reaction conditions. In this context, we further describe the direct amidation of abundant alkyl esters to afford amide bonds with exquisite selectivity by acyl C-O bond cleavage. The utility of this process is showcased by a broad scope of the method, including various sensitive functional groups, late-stage modification, and the synthesis of drug molecules (>80 examples). Remarkable selectivity toward different functional groups and within different amide and ester electrophiles that is not feasible using existing methods was observed. Extensive experimental and computational studies were conducted to provide insight into the mechanism and the origins of high selectivity. We further present a series of guidelines to predict the reactivity of amides and esters in the synthesis of valuable amide bonds by this user-friendly process. In light of the importance of the amide bond in organic synthesis and major practical advantages of this method, the study opens up new opportunities in the synthesis of pivotal amide bonds in a broad range of chemical contexts.
- Li, Guangchen,Ji, Chong-Lei,Hong, Xin,Szostak, Michal
-
supporting information
p. 11161 - 11172
(2019/08/07)
-
- Simple and rapid p-methoxybenzylation of hydroxy and amide groups at room temperature by NaOt-Bu and DMSO
-
The p-methoxybenzylation of hydroxy and amide groups by p-methoxybenzyl chloride utilizing NaOt-Bu in DMSO is described. p-Methoxybenzylation of sterically hindered menthol using NaOt-Bu in DMSO proceeded faster than the commonly used methods which use Na
- Hamada, Shohei,Sugimoto, Koichi,Iida, Masashi,Furuta, Takumi
-
supporting information
(2019/11/13)
-
- Synthesis of Amides by Mild Palladium-Catalyzed Aminocarbonylation of Arylsilanes with Amines Enabled by Copper(II) Fluoride
-
A general Pd-catalyzed synthesis of amides by oxidative aminocarbonylation of arylsilanes under mild conditions was accomplished for the first time. The reaction is promoted by a commercially available copper(II) fluoride, which acts as a dual silane activator and mild oxidant, enabling highly efficient aminocarbonylation of versatile arylsilanes at atmospheric CO pressure. The reaction is tolerant of a wide range of arylsilanes and various sensitive halide functional groups as well as a broad scope of amines are compatible with this oxidative process using cheap CO. A significant aspect involves the increased efficiency by the catalyst system. The reaction represents a segue into the powerful Pd-catalyzed oxidative transformations of organosilanes.
- Zhang, Jin,Hou, Yanyan,Ma, Yangmin,Szostak, Michal
-
p. 338 - 345
(2019/01/10)
-
- Secondary/tertiary amide compound and synthesis method thereof
-
The invention discloses a secondary/tertiary amide compound and a synthesis method thereof. The method comprises the following steps: adding arylsilane and an amine compound, a catalyst and an additive to a solvent, introducing CO under a certain pressure, carrying out a carbonylation reaction, and carrying out separation and purification to obtain the secondary/tertiary amide. The method for preparing the secondary/tertiary amide by the carbonylation reaction has the advantages of concision, high efficiency, directness in the reaction, high atom economy, and wide sources and good stability ofa substrate. The reaction system of the invention does not require inert gas protection, and has mild conditions, and the target product is easy to separate and the yield reaches up to 92% under optimized reaction conditions.
- -
-
Paragraph 0156; 0157; 0158; 0159
(2019/01/21)
-
- Metal-Free Transamidation of Secondary Amides by N-C Cleavage
-
Transamidation reactions represent a fundamental chemical process involving conversion of one amide functional group into another. Herein, we report a facile, highly chemoselective method for transamidation of N-tert-butoxycarbonylation (N-Boc) activated secondary amides that proceeds under exceedingly mild conditions in the absence of any additives. Because this reaction is performed in the absence of metals, oxidants, or reductants, the reaction tolerates a large number of useful functionalities. The reaction is compatible with diverse amides and nucleophilic amines, affording the transamidation products in excellent yields through direct nucleophilic addition to the amide bond. The utility of this methodology is highlighted in the synthesis of Tigan, a commercial antiemetic, directly from the amide bond. We expect that this new metal-free transamidation will have broad implications for the development of new transformations involving direct nucleophilic addition to the amide bond as a key step.
- Rahman, Md. Mahbubur,Li, Guangchen,Szostak, Michal
-
p. 12091 - 12100
(2019/10/11)
-
- Amide bond synthesis via silver(I) N-heterocyclic carbene-catalyzed and tert-butyl hydroperoxide-mediated oxidative coupling of alcohols with amines under base free conditions
-
We present a base free method for amide bond construction via oxidative coupling of alcohols with amines catalyzed by Silver(I) N-heterocyclic carbenes (Ag(I)-NHCs) and mediated by tert-butyl hydroperoxide (TBHP) in ethanol. The results of controlled experiments suggest that the oxidative coupling proceeds through the formation of aldehyde, then subsequent attack by amine to give hemiaminal, which can then be oxidized to amide.
- Balaboina, Ramesh,Thirukovela, Narasimha Swamy,Vadde, Ravinder,Vasam, Chandra Sekhar
-
supporting information
p. 847 - 851
(2019/02/20)
-
- Methyl Esters as Cross-Coupling Electrophiles: Direct Synthesis of Amide Bonds
-
Amide bond formation and transition metal-catalyzed cross-coupling are two of the most frequently used chemical reactions in organic synthesis. Recently, an overlap between these two reaction families was identified when Pd and Ni catalysts were demonstrated to cleave the strong C-O bond present in esters via oxidative addition. When simple methyl and ethyl esters are used, this transformation provides a powerful alternative to classical amide bond formations, which commonly feature stoichiometric activating agents. Thus far, few redox-active catalysts have been demonstrated to activate the C(acyl)-O bond of alkyl esters, which makes it difficult to perform informed screening when a challenging reaction needs optimization. We demonstrate that Ni catalysts bearing diverse NHC, phosphine, and nitrogen-containing ligands can all be used to activate methyl esters and enable their use in direct amide bond formation.
- Zheng, Yan-Long,Newman, Stephen G.
-
p. 4426 - 4433
(2019/05/08)
-
- Base-promoted amide synthesis from aliphatic amines and ynones as acylation agents through C-C bond cleavage
-
A new protocol for the synthesis of amides via base-promoted cleavage of the C(sp)-C(CO) bond of ynones with aliphatic primary and secondary amines under transition-metal-, ligand-, and oxidant-free conditions has been developed. This method exhibits a wide substrate scope, high functional group tolerance and exclusive chemoselectivity, as well as mild reaction conditions.
- Cheng, Guolin,Lv, Weiwei,Kuai, Changsheng,Wen, Si,Xiao, Shangyun
-
supporting information
p. 1726 - 1729
(2018/02/21)
-
- Tetramethyl Orthosilicate (TMOS) as a Reagent for Direct Amidation of Carboxylic Acids
-
Tetramethyl orthosilicate (TMOS) is shown to be an effective reagent for direct amidation of aliphatic and aromatic carboxylic acids with amines and anilines. The amide products are obtained in good to quantitative yields in pure form directly after workup without the need for any further purification. A silyl ester as the putative activated intermediate is observed by NMR methods. Amidations on a 1 mol scale are demonstrated with a favorable process mass intensity.
- Braddock, D. Christopher,Lickiss, Paul D.,Rowley, Ben C.,Pugh, David,Purnomo, Teresa,Santhakumar, Gajan,Fussell, Steven J.
-
supporting information
p. 950 - 953
(2018/02/23)
-
- Diboron-Catalyzed Dehydrative Amidation of Aromatic Carboxylic Acids with Amines
-
Tetrakis(dimethylamido)diboron and tetrahydroxydiboron are herein reported as new catalysts for the synthesis of aryl amides by catalytic condensation of aromatic carboxylic acids with amines. The developed protocol is both simple and highly efficient over a broad range of substrates. This method thus represents an attractive approach for the use of diboron catalysts in the synthesis of amides without having to resort to stoichiometric or additional dehydrating agents.
- Sawant, Dinesh N.,Bagal, Dattatraya B.,Ogawa, Saeko,Selvam, Kaliyamoorthy,Saito, Susumu
-
supporting information
p. 4397 - 4400
(2018/08/09)
-
- Transamidation of: N -acyl-glutarimides with amines
-
The development of new transamidation reactions for the synthesis of amides is an important and active area of research due to the central role of amide linkage in various fields of chemistry. Herein, we report a new method for transamidation of N-acyl-glutarimides with amines under mild, metal-free conditions that relies on amide bond twist to weaken amidic resonance. A wide range of amines and functional groups, including electrophilic substituents that would be problematic in metal-catalyzed protocols, are tolerated under the reaction conditions. Mechanistic experiments implicate the amide bond twist, thermodynamic stability of the tetrahedral intermediate and leaving group ability of glutarimide as factors controlling the reactivity of this process. The method further establishes the synthetic utility of N-acyl-glutarimides as bench-stable, twist-perpendicular, amide-based reagents in acyl-transfer reactions by a metal-free pathway. The origin of reactivity of N-acyl-glutarimides in metal-free and metal-catalyzed processes is discussed and compared.
- Liu, Yongmei,Achtenhagen, Marcel,Liu, Ruzhang,Szostak, Michal
-
p. 1322 - 1329
(2018/03/06)
-
- Efficient N-Heterocyclic Carbene/Ruthenium Catalytic Systems for the Alcohol Amidation with Amines: Involvement of Poly-Carbene Complexes?
-
The atom-economic direct amidation of alcohols with amines has been recently highlighted as an attractive and promising transformation. Among the versatile reported catalytic systems, in situ generated N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic systems have demonstrated their advantages such as easy operation and use of commercial Ru compounds. However, the existing catalyst loadings are relatively high, and additional insights for the in situ catalyst generation are still not well-documented. In this work, a variety of benzimidazole-based NHC precursors were initially synthesized. Through the screening of various NHC precursors and other reaction conditions, active in situ catalytic systems were discovered for the efficient amide synthesis. Notably, the catalyst loading is as low as 0.5 mol %. Furthermore, additional experiments were performed to validate the rationale for the superiority of the current catalytic systems over our previous system. It was observed that the ligand structure is one of the reasons for the higher activity. In addition, the higher ratio of the NHC precursor/[Ru] is another important factor for the improvement. Further HR-MS analysis identified the formation of two mono-NHC-Ru species as major species and two Ru species bearing multiple NHC ligands as minor species. Hopefully, the efficient and readily-accessible catalytic systems reported herein could demonstrate great potential for further practical applications.
- Cheng, Hua,Xiong, Mao-Qian,Zhang, Ni,Wang, Hua-Jing,Miao, Yang,Su, Wei,Yuan, Ye,Chen, Cheng,Verpoort, Francis
-
p. 4338 - 4345
(2018/09/06)
-
- Ruthenium-based catalytic systems incorporating a labile cyclooctadiene ligand with N-heterocyclic carbene precursors for the atom-economic alcohol amidation using amines
-
Transition-metal-catalyzed amide-bond formation from alcohols and amines is an atom-economic and eco-friendly route. Herein, we identified a highly active in situ N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic system for this amide synthesis. Various substrates, including sterically hindered ones, could be directly transformed into the corresponding amides with the catalyst loading as low as 0.25 mol.%. In this system, we replaced the p-cymene ligand of the Ru source with a relatively labile cyclooctadiene (cod) ligand so as to more efficiently obtain the corresponding poly-carbene Ru species. Expectedly, the weaker cod ligand could be more easily substituted with multiple mono-NHC ligands. Further high-resolution mass spectrometry (HRMS) analyses revealed that two tetra-carbene complexes were probably generated from the in situ catalytic system.
- Chen, Cheng,Miao, Yang,De Winter, Kimmy,Wang, Hua-Jing,Demeyere, Patrick,Yuan, Ye,Verpoort, Francis
-
-
- In situ Generated Ruthenium Catalyst Systems Bearing Diverse N-Heterocyclic Carbene Precursors for Atom-Economic Amide Synthesis from Alcohols and Amines
-
The transition-metal-catalyzed direct synthesis of amides from alcohols and amines is herein demonstrated as a highly environmentally benign and atom-economic process. Among various catalyst systems, in situ generated N-heterocyclic carbene (NHC)-based ruthenium (Ru) halide catalyst systems have been proven to be active for this transformation. However, these existing catalyst systems usually require an additional ligand to achieve satisfactory results. In this work, through extensive screening of a diverse variety of NHC precursors, we discovered an active in situ catalyst system for efficient amide synthesis without any additional ligand. Notably, this catalyst system was found to be insensitive to the electronic effects of the substrates, and various electron-deficient substrates, which were not highly reactive with our previous catalyst systems, could be employed to afford the corresponding amides efficiently. Furthermore, mechanistic investigations were performed to provide a rationale for the high activity of the optimized catalyst system. NMR-scale reactions indicated that the rapid formation of a Ru hydride intermediate (signal at δ=?7.8 ppm in the 1H NMR spectrum) after the addition of the alcohol substrate should be pivotal in establishing the high catalyst activity. Besides, HRMS analysis provided possible structures of the in situ generated catalyst system.
- Cheng, Hua,Xiong, Mao-Qian,Cheng, Chuan-Xiang,Wang, Hua-Jing,Lu, Qiang,Liu, Hong-Fu,Yao, Fu-Bin,Chen, Cheng,Verpoort, Francis
-
p. 440 - 448
(2018/02/06)
-
- Method of preparing amides by catalyzed reaction of esters and amines
-
The invention provides a method of preparing amides by catalyzed reaction of esters and amines. Raw materials in the method are simple and easily obtainable, the method is simple to perform, has no need for adding solvents and has high yield, and the applicable range of substrates is wide. The method comprises the steps of allowing an ester of formula (I) shown in the description and an amine of formula (II) shown in the description to react under the catalysis of the catalyst alkoxy rare-earth metal cluster containing the basic metal sodium to obtain a compound of formula (III) shown in the description; alternatively, allowing the ester of formula (I) and the amine of formula (II) to react under the catalysis of the catalyst alkoxy rare-earth metal cluster containing the basic metal sodium to obtain a compound of formula (V) shown in the description, wherein R1 is selected from alkyl, aryl or heteroaryl, R2, R3 and R4 are independently selected from alkyl alcohol, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, or R3 and R4 are independently selected from alkyl alcohol and alkyl while R3, R4 and atoms connected to them form a ring. The reaction formulas are shown in the description.
- -
-
Paragraph 0126; 0128; 0129
(2018/04/27)
-
- Unique physicochemical and catalytic properties dictated by the B3NO2 ring system
-
The expansion of molecular diversity beyond what nature can produce is a fundamental objective in chemical sciences. Despite the rich chemistry of boron-containing heterocycles, the 1,3-dioxa-5-aza-2,4,6-triborinane (DATB) ring system, which is characterized by a six-membered B3NO2 core, remains elusive. Here, we report the synthesis of m-terphenyl-templated DATB derivatives, displaying high stability and peculiar Lewis acidity arising from the three suitably arranged boron atoms. We identify a particular utility for DATB in the dehydrative amidation of carboxylic acids and amines, a reaction of high academic and industrial importance. The three boron sites are proposed to engage in substrate assembly, lowering the entropic cost of the transition state, in contrast with the operative mechanism of previously reported catalysts and amide coupling reagents. The distinct mechanistic pathway dictated by the DATB core will advance not only such amidations, but also other reactions driven by multisite activation.
- Noda, Hidetoshi,Furutachi, Makoto,Asada, Yasuko,Shibasaki, Masakatsu,Kumagai, Naoya
-
p. 571 - 577
(2017/06/01)
-
- Tunable Ligand Effects on Ruthenium Catalyst Activity for Selectively Preparing Imines or Amides by Dehydrogenative Coupling Reactions of Alcohols and Amines
-
Selective dehydrogenative synthesis of imines from a variety of alcohols and amines was developed by using the ruthenium complex [RuCl2(dppea)2] (6 a: dppea=2-diphenylphosphino-ethylamine) in the presence of catalytic amounts of Zn(OCOCF3)2 and KOtBu, whereas the selective dehydrogenative formation of amides from the same sources was achieved by using another ruthenium complex, [RuCl2{(S)-dppmp}2] [6 d: (S)-dppmp=(S)-2-((diphenylphosphenyl)methyl)pyrrolidine], in the presence of catalytic amounts of Zn(OCOCF3)2 and potassium bis(trimethylsilyl)amide (KHMDS). Our previously reported ruthenium complex, [Ru(OCOCF3)2(dppea)2] (8 a), was the catalyst precursor for the imine synthesis, whereas [Ru(OCOCF3)2{(S)-dppmp}2] (8 d), which was derived from the treatment of 6 d with Zn(OCOCF3)2 and characterized by single-crystal X-ray analysis, was the pre-catalyst for the amide formation. Control experiments revealed that the zinc salt functioned as a reagent for replacing chloride anions with trifluoroacetate anions. Plausible mechanisms for both selective dehydrogenative coupling reactions are proposed based on a time-course study, Hammett plot, and deuterium-labeling experiments.
- Higuchi, Takafumi,Tagawa, Risa,Iimuro, Atsuhiro,Akiyama, Shoko,Nagae, Haruki,Mashima, Kazushi
-
p. 12795 - 12804
(2017/09/06)
-
- Carbonylative Tertiary Amide Synthesis from Aryl Iodides and Tertiary Amines via Oxidant-Free C?N Bond Cleavage Catalyzed by Palladium(II) Chloride in Polyethylene Glycol/Water
-
In this work, we have described the carbonylative synthesis of amides from aryl iodides and tertiary amines as an aminal source via oxidant-free C(sp3)?N bond cleavage using in situ formation of palladium(0) nanoparticles from palladium(II) chloride in polyethylene glycol 400/water. Notably, these reactions were performed under base-free, ligand-free conditions and do not require any oxidant for the C?N bond cleavage. The developed protocol offers the selective N-dealkylation of tertiary amines in a polyethylene glycol/water solvent system. Numerous symmetrical and unsymmetrical aliphatic, alicyclic, benzyl, as well as aromatic tertiary amines with aryl iodides were well tolerated and afforded the desired products in good yields. Furthermore, the in situ generation of palladium(0) nanoparticles in the polyethylene glycol 400 was confirmed by TEM, FEG-SEM, EDS and XRD techniques, which strongly indicate that the palladium nanoparticles are highly active species and the reaction proceeds through the classical palladium(0)/palladium(II) pathway. Additionally, the syntheses can be easily scaled up and the catalytic system can be recycled up to five times without loss of its catalytic activity and selectivity. (Figure presented.).
- Mane, Rajendra S.,Bhanage, Bhalchandra M.
-
p. 2621 - 2629
(2017/08/16)
-
- An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines
-
We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.
- H?ring, Andreas P.,Biallas, Phillip,Kirsch, Stefan F.
-
supporting information
p. 1526 - 1539
(2017/04/01)
-
- Amidation of unactivated ester derivatives mediated by trifluoroethanol
-
A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.
- McPherson, Christopher G.,Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
-
p. 3507 - 3518
(2017/04/26)
-
- Metal-Free Transamidation of Secondary Amides via Selective N-C Cleavage under Mild Conditions
-
Nonplanar, electronically destabilized amides have emerged as powerful intermediates in organic synthesis. We report a highly selective method for transamidation of common secondary amides under mild, metal-free conditions that relies on transient N-selective functionalization to weaken amidic resonance. The combination of rational modification of the amide bond with nucleophilic addition mechanism, and the thermodynamic collapse of the resultant tetrahedral intermediate constitutes a two-step procedure to accomplish a challenging transamidation of secondary amides under mild conditions.
- Liu, Yongmei,Shi, Shicheng,Achtenhagen, Marcel,Liu, Ruzhang,Szostak, Michal
-
supporting information
p. 1614 - 1617
(2017/04/11)
-
- Boronic acid-DMAPO cooperative catalysis for dehydrative condensation between carboxylic acids and amines
-
Arylboronic acid and 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO) cooperatively catalyse the dehydrative condensation reaction between carboxylic acids and amines to give the corresponding amides under azeotropic reflux conditions. This cooperative use is much more effective than their individual use as catalysts, and chemoselectively promotes the amide condensation of (poly)conjugated carboxylic acids. The present method is practical and scalable, and has been applied to the synthesis of sitagliptin and a drug candidate.
- Ishihara, Kazuaki,Lu, Yanhui
-
p. 1276 - 1280
(2016/02/05)
-
- Catalytic reductive N-alkylation of amines using carboxylic acids
-
We report a catalytic reductive alkylation reaction of primary or secondary amines with carboxylic acids. The two-phase process involves silane mediated direct amidation followed by catalytic reduction.
- Andrews, Keith G.,Summers, Declan M.,Donnelly, Liam J.,Denton, Ross M.
-
supporting information
p. 1855 - 1858
(2016/02/12)
-
- Dioxygen-promoted Pd-catalyzed aminocarbonylation of organoboronic acids with amines and CO: A direct approach to tertiary amides
-
A direct approach from organoboronic acids and amines to tertiary amides via Pd-catalyzed aerobic aminocarbonylation has been developed. The presence of O2 significantly promotes the efficiency of this transformation. This method uses commercially available organoboronic acids and cheap CO and O2 (1 atm), which renders amides an easy synthesis with broad substrate scope and high functional group tolerance.
- Ren, Long,Li, Xinwei,Jiao, Ning
-
supporting information
p. 5852 - 5855
(2016/11/29)
-
- 1-Cyanoformamidines. Formation during the RuO4-mediated oxidation of secondary amines
-
When performed in the presence of cyanide and at pH smaller than 5, the RuO4-mediated oxidation of secondary amines Bn-NH-R (1a-b; R=Me, Et) gave mainly 1-cyanoformamidines Bn-NR-C(=NH)-CN (2a-b) and their hydrolysis products Bn-NR-COCN (3a-b), Bn-NR-CN (4a-b), Bn-NR-CONH2 (5a-b). Carboxamides 5a-b can result also directly from 1a-b. (Chemical Equation Presented).
- Florea, Cristina,Stavarache, Cristina,Petride, Horia
-
p. 319 - 325
(2016/10/11)
-
- RuO4-mediated oxidation of secondary amines. Part 1. Are hydroxylamines the main intermediates?
-
The RuO4-catalyzed oxidation of secondary amines Bn-NH-CH2R (1a and b; R=H, Me) gave mainly amides, but minute amounts of nitrones PhCH=N(O)-CH2R (9a and b) and traces of Bn-N(OH)-CH2R (R=H, 4a) were also detect
- Florea, Cristina A.,Petride, Horia
-
p. 475 - 486
(2016/07/20)
-
- Copper-catalyzed and iodide-promoted aerobic C-C bond cleavage/C-N bond formation toward the synthesis of amides
-
A copper-catalyzed and iodide-promoted aerobic C-C bond cleavage/C-N bond formation reaction between ketone and simple amine was developed toward the synthesis of amides, which are useful synthetic intermediates in organic synthesis and important skeletons of biologically active molecules. Notably, the reaction conditions are very mild, and preliminary mechanistic investigations indicate that molecular oxygen might be involved in the C-C bond cleavage process.
- Wu, Kun,Huang, Zhiliang,Ma, Yiyang,Lei, Aiwen
-
p. 24349 - 24352
(2016/03/15)
-
- Copper-catalyzed one-pot oxidative amidation of alcohol to amide via C-H activation
-
A one-pot oxidative amidation of both aliphatic and aromatic alcohols with N-chloramines, prepared in situ from many types of primary and secondary amines, was developed. This cross-coupling reaction integrates alcohol oxidation and amide bond formation, which are usually accomplished separately, into a single operation. And it was green, simple and convenient, which has a wide substrate scope and makes use of cheap, abundant, and easily available reagents. The practical value of this method is highlighted through the synthesis of a high-profile pharmaceutical agent, acetylprocainamide.
- Gu, Jiajia,Fang, Zheng,Yang, Yuhang,Yang, Zhao,Wan, Li,Li, Xin,Wei, Ping,Guo, Kai
-
p. 89413 - 89416
(2016/10/03)
-
- Palladium-catalyzed carbonylation of aryl halides: An efficient, heterogeneous and phosphine-free catalytic system for aminocarbonylation and alkoxycarbonylation employing Mo(CO)6 as a solid carbon monoxide source
-
Immobilized palladium metal-containing magnetic nanoparticles (ImmPd(0)-MNPs) were synthesized and characterized as an immobilized, phosphine-free catalyst for carbonylation reactions, namely the alkoxycarbonylation and aminocarbonylation reactions. Various substituted aryl iodides tolerated the reaction conditions and a wide variety of alcohols and amines were used efficiently. The effects of the solvent, base, and temperature were studied in both the mentioned reactions. The developed catalytic system avoids the use of phosphine ligands and can be reused for up to eight consecutive cycles. The recycled catalyst was characterized by TEM and ICP analysis.
- Hajipour, Abdol-Reza,Tavangar-Rizi, Zeinab,Iranpoor, Nasser
-
p. 78468 - 78476
(2016/09/09)
-
- Design and synthesis of ruthenium(II) OCO pincer type NHC complexes and their catalytic role towards the synthesis of amides
-
The present contribution describes the synthesis and characterization of a family of robust ruthenium complexes, supported by a tridentate pincer ligand of the type bis-phenolate-N-heterocyclic carbene [ tBu(OCO) 2-] (NHC). Ruthenium(II) complexes (1-3) bearing bis-phenolate-N-heterocyclic carbene ligand were synthesized in good yields by the reaction of imidazolinium proligand (HL) with metal precursors [RuHCl(CO)(EPh3)2(B)] (E = P or As; B = PPh3, AsPh3 or Py) by transmetalation from the corresponding silver carbene complex. All the Ru(II)-NHC complexes have been characterized by elemental analyses, spectroscopic methods as well as ESI mass spectrometry. Based on the spectral results, an octahedral geometry was assigned for all the complexes. The tridentate nature of the tBu(OCO) 2- ligand as well as some level of steric protection provided by the t Bu groups may rationalize the excellent stability of the Ru-Ccarbene bond in the present systems. Moreover, for the explorations of catalytic potential of the synthesized compounds, all the three [Ru-NHC] complexes (1-3) were tested as catalysts for amidation of alcohols with amines. Notably, the complex 1 was found to be very efficient and versatile catalyst towards amidation of a wide range of alcohols with amines. [Figure not available: see fulltext.].
- Nirmala, Muthukumaran,Viswanathamurthi, Periasamy
-
-
- Practical Synthesis of Amides via Copper/ABNO-Catalyzed Aerobic Oxidative Coupling of Alcohols and Amines
-
A modular Cu/ABNO catalyst system has been identified that enables efficient aerobic oxidative coupling of alcohols and amines to amides. All four permutations of benzylic/aliphatic alcohols and primary/secondary amines are viable in this reaction, enabling broad access to secondary and tertiary amides. The reactions exhibit excellent functional group compatibility and are complete within 30 min-3 h at rt. All components of the catalyst system are commercially available.
- Zultanski, Susan L.,Zhao, Jingyi,Stahl, Shannon S.
-
supporting information
p. 6416 - 6419
(2016/06/09)
-
- Tert -Butyl Peroxybenzoate Mediated Selective and Mild N-Benzoylation of Ammonia/Amines under Catalyst- and Solvent-Free Conditions
-
A new protocol for the synthesis of amides from tert-butyl peroxybenzoate (TBPB) and ammonia/amines has been developed under catalyst- and solvent-free conditions. The ammonia, primary and secondary amines reacted smoothly with TBPB to furnish the corresponding primary, secondary, and tertiary amides in excellent yields. TBPB proved to be an efficient and highly chemoselective benzoylating reagent for aliphatic amines in the presence of aromatic amines/hydroxyl groups.
- Yadav, Dilip Kumar T.,Bhanage, Bhalchandra M.
-
supporting information
p. 1862 - 1866
(2015/08/06)
-
- A novel nickel-catalyzed synthesis of thioesters, esters and amides from aryl iodides in the presence of chromium hexacarbonyl
-
This study describes our findings on a novel and cheap NiCl2 catalytic system under ligand-free conditions for the efficient thiocarbonylation, alkoxycarbonylation and amidocarbonylation reactions of aryl iodides in the presence of Cr(CO)6 as the solid source of carbon monoxide under air. A variety of aryl iodides tolerated the reaction conditions and structurally different thiols, alcohols and amines were used efficiently. The corresponding thioesters, esters and amides were obtained in good to excellent yield at atmospheric pressure under mild reaction conditions.
- Iranpoor, Nasser,Firouzabadi, Habib,Etemadi-Davan, Elham,Nematollahi, Arash,Firouzi, Hamid Reza
-
p. 6445 - 6452
(2015/08/11)
-