82923-75-9Relevant articles and documents
Electrochemical Dearomative Dicarboxylation of Heterocycles with Highly Negative Reduction Potentials
Hayashi, Hiroki,Kanna, Wataru,Maeda, Satoshi,Mita, Tsuyoshi,Takano, Hideaki,You, Yong
supporting information, p. 3685 - 3695 (2022/03/08)
The dearomative dicarboxylation of stable heteroaromatics using CO2is highly challenging but represents a very powerful method for producing synthetically useful dicarboxylic acids, which can potentially be employed as intermediates of biologically active molecules such as natural products and drug leads. However, these types of transformations are still underdeveloped, and concise methodologies with high efficiency (e.g., high yield and high selectivity for dicarboxylations) have not been reported. We herein describe a new electrochemical protocol using the CO2radical anion (E1/2of CO2= -2.2 V in DMF and -2.3 V in CH3CN vs SCE) that produces unprecedented trans-oriented 2,3-dicarboxylic acids from N-Ac-, Boc-, and Ph-protected indoles that exhibit highly negative reduction potentials (-2.50 to -2.94 V). On the basis of the calculated reduction potentials, N-protected indoles with reduction potentials up to -3 V smoothly undergo the desired dicarboxylation. Other heteroaromatics, including benzofuran, benzothiophene, electron-deficient furans, thiophenes, 1,3-diphenylisobenzofuran, and N-Boc-pyrazole, also exhibit reduction potentials more positive than -3 V and served as effective substrates for such dicarboxylations. The dicarboxylated products thus obtained can be derivatized into useful synthetic intermediates for biologically active compounds in few steps. We also show how the dearomative monocarboxylation can be achieved selectively by choice of the electrolyte, solvent, and protic additive; this strategy was then applied to the synthesis of an octahydroindole-2-carboxylic acid (Oic) derivative, which is a useful proline analogue.
From batch to flow processing: Racemization of N-acetylamino acids under microwave heating
Dressen, Mark H. C. L.,Van De Kruijs, Bastiaan H. P.,Meuldijk, Jan,Vekemans, Jef A. J. M.,Hulshof, Lumbertus A.
experimental part, p. 888 - 895 (2010/04/22)
The racemization of N-acetylindoline-2-carboxylic acid in P-xylene revealed beneficial rate enhancements due to microwave effects, by comparing conventional and microwave heating. The magnitude of this effect was governed by the degree of heterogeneity of the reaction system. The amount of catalyst, the temperature and the amount of cosolvent played a decisive role. The microwave effect completely vanished when a homogeneous solution was heated. During the microwave-assisted heterogeneous racemization of N-acetylphenylalanine in P-xylene a comparable microwave effect was observed. The microwave effects could be rationalized by adapting selective heating in the phase boundary region of solid and liquid. Additionally, a straightforward translation was achieved from batchwise operation in a stirred reactor to a batch-loop reactor. The (heterogeneous) racemization of N-acetylindoline-2-carboxylic acid retained its microwave effect in the loop reactor. Our results demonstrated that avoiding plugging of the tubular reactor is a severe challenge in scaling up.
Fused bicyclic carboxamide derivatives and methods of their use
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Page/Page column 49, (2010/02/11)
Fused bicyclic carboxamide derivatives are disclosed. Pharmaceutical compositions containing the compounds and methods for their use are also disclosed.
