- Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL
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While the biochemistry of rhomboid proteases has been extensively studied since their discovery two decades ago, efforts to define the physiological roles of these enzymes are ongoing and would benefit from chemical probes that can be used to manipulate the functions of these proteins in their native settings. Here, we describe the use of activity-based protein profiling (ABPP) technology to conduct a targeted screen for small-molecule inhibitors of the mitochondrial rhomboid protease PARL, which plays a critical role in regulating mitophagy and cell death. We synthesized a series of succinimide-containing sulfonyl esters and sulfonamides and discovered that these compounds serve as inhibitors of PARL with the most potent sulfonamides having submicromolar affinity for the enzyme. A counterscreen against the bacterial rhomboid protease GlpG demonstrates that several of these compounds display selectivity for PARL over GlpG by as much as two orders of magnitude. Both the sulfonyl ester and sulfonamide scaffolds exhibit reversible binding and are able to engage PARL in mammalian cells. Collectively, our findings provide encouraging precedent for the development of PARL-selective inhibitors and establish N-[(arylsulfonyl)oxy]succinimides and N-arylsulfonylsuccinimides as new molecular scaffolds for inhibiting members of the rhomboid protease family.
- Andrews, Charlotte L.,Cardozo, Joaquin M.,Chow, Alyssa S.,Crainic, Jennifer A.,Parsons, William H.,Rutland, Nicholas T.,Sheehan, Brendan K.
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supporting information
(2021/08/04)
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- Visible Light-Driven Efficient Synthesis of Amides from Alcohols using Cu?N?TiO2 Heterogeneous Photocatalyst
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Amides were synthesized from alcohols and amines in high yields using an in situ generated active ester of N-hydroxyimide with our developed Cu?N?TiO2 catalyst at room temperature using oxygen as a sole oxidant under visible light. The catalyst can be easily prepared, robust, and recycled four times without a considerable change in catalytic activity. This developed protocol applies to a wide substrate scope and has good functional group tolerance. The application of this amidation reaction has been successfully demonstrated for the synthesis of moclobemide, an antidepressant drug, and an analog of the itopride drug on a gram scale.
- Singha, Krishnadipti,Ghosh, Subhash Chandra,Panda, Asit Baran
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supporting information
p. 657 - 662
(2021/02/02)
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- tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides
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A synthetically practical transition metal/catalyst/halogen-free dehydrogenative coupling of aldehydes with N-hydroxyimides promoted solely by tert-butyl nitrite under mild conditions was developed. tert-Butyl nitrite generates two radicals (tBuO and NO) and thus works as a twofold hydrogen abstractor. A diverse array of N-hydroxyimide esters were prepared from either aliphatic or aromatic aldehydes. Benzoyl-substituted aldehydes such as 2-oxo-2-phenylacetaldehyde are also suitable.
- Dai, Peng-Fei,Wang, Yi-Ping,Qu, Jian-Ping,Kang, Yan-Biao
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supporting information
p. 9360 - 9364
(2021/12/09)
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- Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride
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Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO2F2-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30-80percent yields, and esters, amides, and thioesters in 72-96percent yields without reoptimization for each nucleophile.
- Foth, Paul J.,Malig, Thomas C.,Yu, Hao,Bolduc, Trevor G.,Hein, Jason E.,Sammis, Glenn M.
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supporting information
p. 6682 - 6686
(2020/09/02)
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- N-Doped Yellow TiO2 Hollow Sphere-Mediated Visible-Light-Driven Efficient Esterification of Alcohol and N-Hydroxyimides to Active Esters
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Herein we report a simple synthetic protocol for N-doped yellow TiO2 (N-TiO2) hollow spheres as an efficient visible-light-active photocatalyst using aqueous titanium peroxocarbonate complex (TPCC) solution as precursor and NH4OH. In the developed strategy, the ammonium ion of TPCC and NH4OH acts as nitrogen source and structure-directing agent. The synthesized N-TiO2 hollow spheres are capable of promoting the synthesis of active esters of N-hydroxyimide and alcohol through simultaneous selective oxidation of alcohol to aldehyde followed by cross-dehydrogenative coupling (CDC) under ambient conditions upon irradiation of visible light. It is possible to develop a novel and cost-effective one-pot strategy for the synthesis of important esters and amides on gram scale using the developed strategy. The catalytic activity of N-TiO2 hollow spheres is much superior to that of other reported N-TiO2 samples as well as TiO2 with varying morphology.
- Singha, Krishnadipti,Ghosh, Subhash Ch.,Panda, Asit Baran
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p. 3205 - 3212
(2019/09/09)
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- A visible light-driven minisci-type reaction with N-hydroxyphthalimide esters
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A visible light-promoted protocol for the redox-neutral coupling of N-hydroxyphthalimide esters with different N-heterocyclic compounds is described. The reaction proceeds through an alkyl radical intermediate generated by reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the original Minisci protocol, polyalkylation can largely be avoided. Mechanistic investigations revealed a radical chain mechanism which in some cases can proceed even if no photocatalyst is added. This valuable and functional group-tolerant reaction produces substituted heterocycles in moderate to excellent yield. The use of inexpensive starting materials and LEDs as the light source are key features of this C–C bond formation.
- Kammer, Lisa Marie,Rahman, Aliyaah,Opatz, Till
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- Method for preparing aliphatic alcohol from aliphatic carboxylic acid through decarboxylation
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The invention relates to a method for preparing aliphatic alcohol from aliphatic carboxylic acid through decarboxylation. The method comprises the following steps of converting aliphatic carboxylic acid into aliphatic N-(acyl oxy)phthalimide; then, performing photocatalysis decarboxylation reaction to convert the material into aliphatic N-(oxy)2, 2,6,6-tetramethylpiperidine nitrogen-oxygen free radicals; finally, reducing the materials into aliphatic alcohol. The method provided by the invention has the advantages that good chemical selectivity is realized; the wide and easy-to-obtain materialsources are realized. The defects of harsh reaction conditions and high energy consumption such as high temperature and high pressure of aliphatic carboxylic acid conversion by a conventional heat conversion method are avoided; the reaction process is simple and convenient; the operation is easy; the repeated extraction is avoided; in addition, the additional introduction of high-purity hydrogengas is not needed; the reaction energy consumption and the raw material consumption are greatly reduced; the green and environment-friendly effects are achieved; the environment pollution is small; the wide application prospects are realized.
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Paragraph 0027-0029
(2018/11/04)
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- A photoinduced cross-dehydrogenative-coupling (CDC) reaction between aldehydes and N-hydroxyimides by a TiO2-Co ascorbic acid nanohybrid under visible light irradiation
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In this study, we performed a visible light-mediated aerobic photo-cross dehydrogenative coupling (CDC) reaction between aldehydes and N-hydroxyimides using TiO2-AA-Co as a photocatalyst for the synthesis of active esters. The synergistic and selective effects of the cobalt ascorbic acid complex (Co-AA) and TiO2 nanoparticles on the visible-light photocatalytic activity were explored. The method possesses some advantages such as environmentally friendly conditions, easy work-up procedure, reusability, and scalability.
- Feizpour, Fahimeh,Jafarpour, Maasoumeh,Rezaeifard, Abdolreza
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supporting information
p. 807 - 811
(2018/02/06)
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- Isonicotinate Ester Catalyzed Decarboxylative Borylation of (Hetero)Aryl and Alkenyl Carboxylic Acids through N-Hydroxyphthalimide Esters
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Decarboxylative borylation of aryl and alkenyl carboxylic acids with bis(pinacolato)diboron was achieved through N-hydroxyphthalimide esters using tert-butyl isonicotinate as a catalyst under base-free conditions. A variety of aryl carboxylic acids possessing different functional groups and electronic properties can be smoothly converted to aryl boronate esters, including those that are difficult to decarboxylate under transition-metal catalysis, offering a new method enabling use of carboxylic acid as building blocks in organic synthesis. Mechanistic analysis suggests the reaction proceeds through coupling of a transient aryl radical generated by radical decarboxylation with a pyridine-stabilized persistent boryl radical. Activation of redox active esters may proceed via an intramolecular single-electron-transfer (SET) process through a pyridine-diboron-phthalimide adduct and accounts for the base-free reaction conditions.
- Cheng, Wan-Min,Shang, Rui,Zhao, Bin,Xing, Wei-Long,Fu, Yao
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supporting information
p. 4291 - 4294
(2017/08/23)
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- Transition-Metal-Free, Visible-Light-Enabled Decarboxylative Borylation of Aryl N-Hydroxyphthalimide Esters
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Herein, we report a conceptually novel borylation reaction proceeding via a mild photoinduced decarboxylation of redox-activated aromatic carboxylic acids. This work constitutes the first application of cheap and easily prepared N-hydroxyphthalimide esters as aryl radical precursors and does not require the use of expensive transition metals or ligands. The reaction is operationally simple, scalable, and displays broad scope and functional group tolerance.
- Candish, Lisa,Teders, Michael,Glorius, Frank
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supporting information
p. 7440 - 7443
(2017/06/13)
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- Copper nitrate-catalyzed oxidative coupling of unactivated C(sp3)-H bonds of ethers and alkanes with: N -hydroxyphthalimide: Synthesis of N -hydroxyimide esters
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A copper nitrate-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) and ethers/alkanes has been described. The reaction is accomplished smoothly by using simple and green molecular oxygen as the oxidant, providing an alternative for the efficient synthesis of N-alkoxyphthalimides. In addition, it was found that when tert-butyl ethers were used as substrates, unexpected N-hydroxyimide ester derivatives were obtained in moderate to excellent yields. To further understand this unusual transformation, control experiments were performed and a plausible mechanism was proposed.
- Xu, Xiaohe,Sun, Jian,Lin, Yuyan,Cheng, Jingya,Li, Pingping,Yan, Yiyan,Shuai, Qi,Xie, Yuanyuan
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supporting information
p. 9875 - 9879
(2017/12/12)
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- Iron-Nitrate-Catalyzed Oxidative Esterification of Aldehydes and Alcohols with N-Hydroxyphthalimide: Efficient Synthesis of N-Hydroxyimide Esters
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An Fe(NO3)3·9H2O-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) or N-hydroxysuccinimide (NHSI) and aldehydes or alcohols in air is described. This transformation represents an efficient approach to the preparation of N-hydroxyimide ester derivatives in moderate to excellent yields, and has a wide substrate scope.
- Xu, Xiaohe,Sun, Jian,Lin, Yuyan,Cheng, Jingya,Li, Pingping,Jiang, Xiaoying,Bai, Renren,Xie, Yuanyuan
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supporting information
p. 7160 - 7166
(2017/12/28)
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- Atmospheric oxidative catalyst-free cross-dehydrogenative coupling of aldehydes with N-hydroxyimides
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Cross-dehydrogenative coupling (CDC) reactions of aldehydes with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI) under catalyst-free conditions is described. Moreover, the desired products can be obtained simply by recrystallization from ethanol. This method is also applicable to the synthesis of amides in excellent yields. A radical mechanism of the type shown in Scheme 4 is proposed based upon the inhibition of the reaction in the presence of TEMPO.
- Xu, Xiaohe,Li, Pingping,Huang, Yingyi,Tong, Chuo,Yan, YiYan,Xie, Yuanyuan
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supporting information
p. 1742 - 1746
(2017/04/13)
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- Copper-Catalyzed Highly Efficient Esterification of Aldehydes with N -Hydroxyphthalimide via Cross-Dehydrogenative Coupling in Water at Room Temperature
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A copper-catalyzed cross-dehydrogenative coupling reaction between N -hydroxyphthalimide and aldehydes using PhI(OAc) 2 as an oxidant is described. It is reported for the first time to synthesize NHPI esters in water, providing the corresponding NHPI esters in moderate to good yields. This facile and efficient method is eco-friendly and possesses the advantages of mild conditions, short reaction time, and broad substrate scope.
- Guo, Zhicheng,Jiang, Xinpeng,Jin, Can,Zhou, Jiadi,Sun, Bin,Su, Weike
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supporting information
p. 1321 - 1326
(2017/06/27)
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- Metal-free intermolecular C-O cross-coupling reactions: Synthesis of: N -hydroxyimide esters
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Selectfluor-mediated intermolecular C-O cross coupling reaction for the synthesis of N-hydroxyimide esters was developed for the first time. The reaction is applicable to the coupling of readily available aryl and alkyl aldehydes with N-hydroxyphthalimide (NHPI) and N-hydroxysuccinimide (NHSI). The resulting active esters can be directly converted into amides in one pot.
- Lv, Yunhe,Sun, Kai,Pu, Weiya,Mao, Shukuan,Li, Gang,Niu, Jiejie,Chen, Qian,Wang, Tingting
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p. 93486 - 93490
(2016/10/21)
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- Ruthenium-catalyzed ortho -C-H mono- and di-imidation of arenes with n -tosyloxyphthalimide
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The Ru(II)-catalyzed imidation of the o-C-H bond in arenes with N-tosyloxyphthalimide is realized with the assistance of a methyl phenylsulfoximine (MPS) directing group. This method is applicable to access the hitherto difficult o-C-H di-imidation produc
- Yadav, M. Ramu,Shankar, Majji,Ramesh,Ghosh, Koushik,Sahoo, Akhila K.
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supporting information
p. 1886 - 1889
(2015/04/27)
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- Cross dehydrogenative coupling (CDC) of aldehydes with N-hydroxyimides by visible light photoredox catalysis
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A photoinduced cross-dehydrogenative-coupling (CDC) reaction between aldehydes and N-hydroxyimides has been developed for the synthesis of ester derivatives. Using 2 mol% [Ru(bpy)3]Cl2 in dry acetonitrile at room temperature with an LED light bulb, we were able to synthesize N-hydroxyesters in good yields. The ester derivatives are very useful synthetic intermediates, which were transformed to amide and oxazole building blocks in excellent yields. This journal is
- Dinda, Milan,Bose, Chandan,Ghosh, Tridev,Maity, Soumitra
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p. 44928 - 44932
(2015/06/02)
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- A very mild and selective method for O-benzoylation of hydroxamic acids
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Selective O-benzoylation of hydroxamic acids is achieved by the treatment of BPO and DABCO. Aliphatic alcohols are not reactive under these conditions. Various radical or oxidation sensitive functional groups are compatible with this protocol, and no anhydrous reagents or solvents are required for the high yields of the benzoylations.
- Zheng, Yongsheng,Liu, Muqiong,Yuan, Yu
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supporting information
p. 4404 - 4406
(2014/07/22)
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- N-acyloxyphthalimides as nitrogen radical precursors in the visible light photocatalyzed room temperature C-H amination of arenes and heteroarenes
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This paper reports a room temperature visible light photocatalyzed method for the C-H amination of arenes and heteroarenes. A key enabling advance in this work is the design of N-acyloxyphthalimides as precursors to nitrogen-based radical intermediates for these transformations. A broad substrate scope is presented, including the selective meta-amination of pyridine derivatives. A radical aromatic substitution mechanism is proposed.
- Allen, Laura J.,Cabrera, Pablo J.,Lee, Melissa,Sanford, Melanie S.
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supporting information
p. 5607 - 5610
(2014/05/06)
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- Pd-NHC-catalyzed synthesis of diaryl ketones
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With N-hetereocyclic carbene and palladium catalysis, diaryl ketones with a variety of functional groups that span from electron withdrawing to electron donating substitutions can be conveniently synthesized using the corresponding aryl boronic acid and N-acyloxyphthalimide.
- Gao, Feng,Feng, Huangdi,Sun, Zhihua
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supporting information
p. 6451 - 6454
(2014/12/10)
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- Iodide-catalyzed amide synthesis from alcohols and amines
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An efficient method to prepare amides by a cascade strategy was developed. Using nBu4NI or NaI as the catalyst and tert-butyl hydroperoxide as the oxidant, various alcohols reacted with N-hydroxysuccinimide or N-hydroxyphthalimide affording corresponding active esters in moderate to good yield. The resulting active esters were converted into amides smoothly in one pot. The Royal Society of Chemistry 2013.
- Wang, Gao,Yu, Qing-Ying,Wang, Jian,Wang, Shan,Chen, Shan-Yong,Yu, Xiao-Qi
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p. 21306 - 21310
(2013/11/06)
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- Organocatalytic amidation and esterification of aldehydes with activating reagents by a cross-coupling strategy
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Formation on demand: An organocatalytic cross-coupling reaction of aldehydes with N-hydroxyimides, hexafluoroisopropyl alcohol, and sulfonimides has been developed. The resulting active intermediates can be directly converted into amides or esters in one pot. This simple method makes use of readily available starting materials, and the newly discovered activating reagents should find broad application in the synthesis of amides and esters. Copyright
- Tan, Bin,Toda, Narihiro,Barbas III, Carlos F.
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supporting information
p. 12538 - 12541
(2013/02/22)
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- CATALYSTS COMPRISING N-SUBSTITUTED CYCLIC IMIDES AND PROCESSES FOR PREPARING ORGANIC COMPOUNDS WITH THE CATALYSTS
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A catalyst of the invention includes an imide compound having a N-substituted cyclic imide skeleton represented by following Formula (I): wherein R is a hydroxyl-protecting group. Preferred R is a hydrolyzable protecting group. R may be a group obtained from an acid by eliminating an OH group therefrom. Such acids include, for example, carboxylic acids, sulfonic acids, carbonic acid, carbamic acid, sulfuric acid, nitric acid, phosphoric acids and boric acids. The catalyst may include the imide compound and a metallic compound in combination. In the presence of the catalyst, (A) a compound capable of forming a radical is allowed to react with (B) a radical scavenging compound and thereby yields an addition or substitution reaction product of the compound (A) and the compound (B) or a derivative thereof. This catalyst can produce an organic compound with a high selectivity in a high yield as a result of, for example, an addition or substitution reaction under mild conditions.
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- A New Method for the Preparation of Active Esters Using Di-2-pyridyl Carbonate
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The use of di-2-pyridyl carbonate in the presence of a catalytic amount of 4-dimethylaminopyridine is found to be very effective in the preparation of various active esters.
- Kim, Sunggak,Ko, Young Kwan
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