The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Michal Szostak - One of the best experts on this subject based on the ideXlab platform.
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metal free transamidation of secondary Amides by n c cleavage
Journal of Organic Chemistry, 2019Co-Authors: Md Mahbubur Rahman, Guangchen Li, Michal SzostakAbstract: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.
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highly chemoselective transition metal free transamidation of unactivated Amides and direct amidation of alkyl esters by n c o c cleavage
Journal of the American Chemical Society, 2019Co-Authors: Guangchen Li, Michal Szostak, Chonglei Ji, Xin HongAbstract: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 sc...
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highly selective transition metal free transamidation of Amides and amidation of esters at room temperature
Nature Communications, 2018Co-Authors: Guangchen Li, Michal SzostakAbstract:Amide chemistry has an essential role in the synthesis of high value molecules, such as pharmaceuticals, natural products, and fine chemicals. Over the past years, several examples of transamidation reactions have been reported. In general, transition-metal-based catalysts or harsh conditions are employed for these transformations due to unfavorable kinetics and thermodynamics of the process. Herein, we report a significant advance in this area and present the general method for transition-metal-free transamidation of Amides and amidation of esters by highly selective acyl cleavage with non-nucleophilic amines at room temperature. In contrast to metal-catalyzed protocols, the method is operationally-simple, environmentally-friendly, and operates under exceedingly mild conditions. The practical value is highlighted by the synthesis of valuable Amides in high yields. Considering the key role of Amides in various branches of chemical science, we envision that this broadly applicable method will be of great interest in organic synthesis, drug discovery, and biochemistry.
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transamidation of n acyl glutarimides with amines
Organic and Biomolecular Chemistry, 2018Co-Authors: Marcel Achtenhagen, Michal SzostakAbstract: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.
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a general method for two step transamidation of secondary Amides using commercially available air and moisture stable palladium nhc n heterocyclic carbene complexes
Organic Letters, 2017Co-Authors: Guangrong Meng, Michal SzostakAbstract:The first general method is reported for transamidation of secondary carboxAmides catalyzed by Pd-NHC (NHC = N-heterocyclic carbene) complexes. Commercially available, air- and moisture-stable (NHC)Pd(R-allyl)Cl complexes can effect C–N cross-coupling of a wide range of N-Boc and N-Ts Amides, obtained by selective amide N-functionalization, with non-nucleophilic anilines and sterically hindered amines in very good yields. The first use of versatile Pd-NHC complexes as catalysts is represented for transition-metal-catalyzed C(acyl)–N amination of Amides by N–C activation.
Guangchen Li - One of the best experts on this subject based on the ideXlab platform.
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metal free transamidation of secondary Amides by n c cleavage
Journal of Organic Chemistry, 2019Co-Authors: Md Mahbubur Rahman, Guangchen Li, Michal SzostakAbstract: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.
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highly chemoselective transition metal free transamidation of unactivated Amides and direct amidation of alkyl esters by n c o c cleavage
Journal of the American Chemical Society, 2019Co-Authors: Guangchen Li, Michal Szostak, Chonglei Ji, Xin HongAbstract: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 sc...
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highly selective transition metal free transamidation of Amides and amidation of esters at room temperature
Nature Communications, 2018Co-Authors: Guangchen Li, Michal SzostakAbstract:Amide chemistry has an essential role in the synthesis of high value molecules, such as pharmaceuticals, natural products, and fine chemicals. Over the past years, several examples of transamidation reactions have been reported. In general, transition-metal-based catalysts or harsh conditions are employed for these transformations due to unfavorable kinetics and thermodynamics of the process. Herein, we report a significant advance in this area and present the general method for transition-metal-free transamidation of Amides and amidation of esters by highly selective acyl cleavage with non-nucleophilic amines at room temperature. In contrast to metal-catalyzed protocols, the method is operationally-simple, environmentally-friendly, and operates under exceedingly mild conditions. The practical value is highlighted by the synthesis of valuable Amides in high yields. Considering the key role of Amides in various branches of chemical science, we envision that this broadly applicable method will be of great interest in organic synthesis, drug discovery, and biochemistry.
David Milstein - One of the best experts on this subject based on the ideXlab platform.
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direct hydrogenation of Amides to alcohols and amines under mild conditions
ChemInform, 2011Co-Authors: Ekambaram Balaraman, Boopathy Gnanaprakasam, Linda J W Shimon, David MilsteinAbstract:Amides can be selectively and directly hydrogenated to alcohols and amines for the first time.
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direct hydrogenation of Amides to alcohols and amines under mild conditions
Journal of the American Chemical Society, 2010Co-Authors: Ekambaram Balaraman, Boopathy Gnanaprakasam, Linda J W Shimon, David MilsteinAbstract:The selective, direct hydrogenation of Amides to the corresponding alcohols and amines with cleavage of the C−N bond was discovered. The expected products of C−O cleavage are not formed (except as traces in the case of anilides). The reaction proceeds under mild pressure and neutral, homogeneous conditions using a dearomatized, bipyridyl-based PNN Ru(II) pincer complex as a catalyst. The postulated mechanism involves metal−ligand cooperation by aromatization−dearomatization of the heteroaromatic pincer core and does not involve hydrolytic cleavage of the amide. The simplicity, generality, and efficiency of this environmentally benign process make it attractive for the direct transformations of Amides to alcohols and amines in good to excellent yields.
Tom D Sheppard - One of the best experts on this subject based on the ideXlab platform.
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recent developments in amide synthesis direct amidation of carboxylic acids and transamidation reactions
European Journal of Organic Chemistry, 2013Co-Authors: Rachel M Lanigan, Tom D SheppardAbstract:The synthesis of Amides is of huge importance in a wide variety of industrial and academic fields and is of particular significance in the synthesis of pharmaceuticals. Many of the well established methods for amide synthesis involve reagents that are difficult to handle and lead to the generation of large quantities of waste products. As a consequence, there has been a considerable amount of interest in the development of new approaches to amide synthesis. Over the past few years a wide range of new reagents and catalysts for direct amidation of carboxylic acids have been reported. In addition, the interconversion of amide derivatives through transamidation is emerging as a potential alternative strategy for accessing certain Amides. This microreview covers recent developments in the direct amidation of carboxylic acids and the interconversion of Amides through transamidation. The advantages and disadvantages of the various methods are discussed, as well as the possible mechanisms of the reactions.
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borate esters as convenient reagents for direct amidation of carboxylic acids and transamidation of primary Amides
Organic and Biomolecular Chemistry, 2011Co-Authors: Pavel Starkov, Tom D SheppardAbstract:Simple borates serve as effective promoters for amide bond formation with a variety of carboxylic acids and amines. With trimethyl or tris(2,2,2-trifluoroethyl) borate, Amides are obtained in good to excellent yield and high purity after a simple work-up procedure. Tris(2,2,2-trifluoroethyl) borate can also be used for the straightforward conversion of primary Amides to secondary Amidesvia transamidation.
Neil K Garg - One of the best experts on this subject based on the ideXlab platform.
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nickel catalyzed transamidation of aliphatic amide derivatives
Chemical Science, 2017Co-Authors: Jacob E Dander, Emma L Baker, Neil K GargAbstract:Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary Amides, the transamidation of secondary Amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic Amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C–N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date.
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Conversion of Amides to esters by the nickel-catalysed activation of amide C–N bonds
Nature, 2015Co-Authors: Noah F. Fine Nathel, Emma L Baker, Xin Hong, Tejas K. Shah, Yun-fang Yang, K. N. Houk, Neil K GargAbstract:Amides are common functional groups that have been studied for more than a century^ 1 . They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond^ 1 , 2 . Although Amides can readily be cleaved by enzymes such as proteases^ 3 , it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon–nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert Amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of Amides in the construction of carbon–heteroatom or carbon–carbon bonds using non-precious-metal catalysis. Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. In this paper the authors demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. They used this methodology to convert Amides to esters, which is a challenging and underdeveloped transformation. Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry; now the activation and cleavage of these bonds using nickel catalysts is used to convert Amides to esters.
