6284-14-6Relevant articles and documents
A comprehensive examination of the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, laboratory-routine, gravity-driven column chromatography
Suzuki, Yuya,Han, Jianlin,Kitagawa, Osamu,Acea, Jos Luis,Klika, Karel D.,Soloshonok, Vadim A.
, p. 2988 - 2993 (2015)
This work explores the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, gravity-driven column chromatography as typically used in laboratory settings. The major findings of this work are: (1) the remarkable persistence and high magnitude of the SDE for the analytes under a variety of conditions, including polar solvents and different achiral stationary phases and (2) the notable generality of the SDE phenomenon as it occurs for a wide range of chiral amide substrates and even for a broad range of starting ee. This last aspect is unusual and not commonly observed. The key conclusion of this work is that it judiciously conveys the predictability of the SDE for chiral amides under the routine conditions of achiral chromatography. These results are consequently of concern for practitioners in the area of catalytic asymmetric synthesis involving chiral amides as intermediates or products and the inferents need to be taken extremely seriously by workers in the field.
Decarboxylative cross-nucleophile coupling via ligand-to-metal charge transfer photoexcitation of Cu(ii) carboxylates
Li, Qi Yukki,Gockel, Samuel N.,Lutovsky, Grace A.,DeGlopper, Kimberly S.,Baldwin, Neil J.,Bundesmann, Mark W.,Tucker, Joseph W.,Bagley, Scott W.,Yoon, Tehshik P.
, p. 94 - 99 (2022/01/11)
Reactions that enable carbon–nitrogen, carbon–oxygen and carbon–carbon bond formation lie at the heart of synthetic chemistry. However, substrate prefunctionalization is often needed to effect such transformations without forcing reaction conditions. The development of direct coupling methods for abundant feedstock chemicals is therefore highly desirable for the rapid construction of complex molecular scaffolds. Here we report a copper-mediated, net-oxidative decarboxylative coupling of carboxylic acids with diverse nucleophiles under visible-light irradiation. Preliminary mechanistic studies suggest that the relevant chromophore in this reaction is a Cu(ii) carboxylate species assembled in situ. We propose that visible-light excitation to a ligand-to-metal charge transfer (LMCT) state results in a radical decarboxylation process that initiates the oxidative cross-coupling. The reaction is applicable to a wide variety of coupling partners, including complex drug molecules, suggesting that this strategy for cross-nucleophile coupling would facilitate rapid compound library synthesis for the discovery of new pharmaceutical agents. [Figure not available: see fulltext.].
Biocatalytic, Intermolecular C?H Bond Functionalization for the Synthesis of Enantioenriched Amides
Arnold, Frances H.,Athavale, Soumitra V.,Gao, Shilong,Hirschi, Jennifer S.,Liu, Zhen,Mallojjala, Sharath Chandra
supporting information, p. 24864 - 24869 (2021/10/15)
Directed evolution of heme proteins has opened access to new-to-nature enzymatic activity that can be harnessed to tackle synthetic challenges. Among these, reactions resulting from active site iron-nitrenoid intermediates present a powerful strategy to forge C?N bonds with high site- and stereoselectivity. Here we report a biocatalytic, intermolecular benzylic C?H amidation reaction operating at mild and scalable conditions. With hydroxamate esters as nitrene precursors, feedstock aromatic compounds can be converted to chiral amides with excellent enantioselectivity (up to >99 % ee) and high yields (up to 87 %). Kinetic and computational analysis of the enzymatic reaction reveals rate-determining nitrenoid formation followed by stepwise hydrogen atom transfer-mediated C?H functionalization.
