21307-96-0Relevant articles and documents
Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources
Doyle, Abigail G.,Gandhi, Shivaani S.,Jiang, Shutian,Kariofillis, Stavros K.,Martinez Alvarado, Jesus I.,?urański, Andrzej M.
supporting information, p. 1045 - 1055 (2022/01/19)
Ni/photoredox catalysis has emerged as a powerful platform for C(sp2)–C(sp3) bond formation. While many of these methods typically employ aryl bromides as the C(sp2) coupling partner, a variety of aliphatic radical sources have been investigated. In principle, these reactions enable access to the same product scaffolds, but it can be hard to discern which method to employ because nonstandardized sets of aryl bromides are used in scope evaluation. Herein, we report a Ni/photoredox-catalyzed (deutero)methylation and alkylation of aryl halides where benzaldehyde di(alkyl) acetals serve as alcohol-derived radical sources. Reaction development, mechanistic studies, and late-stage derivatization of a biologically relevant aryl chloride, fenofibrate, are presented. Then, we describe the integration of data science techniques, including DFT featurization, dimensionality reduction, and hierarchical clustering, to delineate a diverse and succinct collection of aryl bromides that is representative of the chemical space of the substrate class. By superimposing scope examples from published Ni/photoredox methods on this same chemical space, we identify areas of sparse coverage and high versus low average yields, enabling comparisons between prior art and this new method. Additionally, we demonstrate that the systematically selected scope of aryl bromides can be used to quantify population-wide reactivity trends and reveal sources of possible functional group incompatibility with supervised machine learning.
A robust and stereocomplementary panel of ene-reductase variants for gram-scale asymmetric hydrogenation
Nett, Nathalie,Duewel, Sabine,Schmermund, Luca,Benary, Gerrit E.,Ranaghan, Kara,Mulholland, Adrian,Opperman, Diederik J.,Hoebenreich, Sabrina
, (2021/01/25)
We report an engineered panel of ene-reductases (ERs) from Thermus scotoductus SA-01 (TsER) that combines control over facial selectivity in the reduction of electron deficient C[dbnd]C double bonds with thermostability (up to 70 °C), organic solvent tolerance (up to 40 % v/v) and a broad substrate scope (23 compounds, three new to literature). Substrate acceptance and facial selectivity of 3-methylcyclohexenone was rationalized by crystallisation of TsER C25D/I67T and in silico docking. The TsER variant panel shows excellent enantiomeric excess (ee) and yields during bi-phasic preparative scale synthesis, with isolated yield of up to 93 % for 2R,5S-dihydrocarvone (3.6 g). Turnover frequencies (TOF) of approximately 40 000 h?1 were achieved, which are comparable to rates in hetero- and homogeneous metal catalysed hydrogenations. Preliminary batch reactions also demonstrated the reusability of the reaction system by consecutively removing the organic phase (n-pentane) for product removal and replacing with fresh substrate. Four consecutive batches yielded ca. 27 g L?1 R-levodione from a 45 mL aqueous reaction, containing less than 17 mg (10 μM) enzyme and the reaction only stopping because of acidification. The TsER variant panel provides a robust, highly active and stereocomplementary base for further exploitation as a tool in preparative organic synthesis.
Chiral phosphine-phosphoramidite ester ligand as well as preparation method and application thereof
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Paragraph 0054-0057; 0081-0084; 0087-0088, (2021/05/22)
The invention provides a method for preparing a phosphine-phosphoramidite ester ligand from a chiral beta-aminophosphine intermediate and an application of the phosphine-phosphoramidite ester ligand in an asymmetric reaction. Chiral N-(2-(phosphoryl)-1-phenethyl) amide is prepared from the chiral beta-aminophosphine intermediate through an asymmetric hydrogenation reaction of (Z)-(alpha-aryl-beta-phosphoryl) alkenyl amide, and then hydrolysis reduction. The preparation method comprises the following steps: dissolving newly-prepared chlorinated phosphite in toluene, adding a solution formed by dissolving the chiral phosphine-amine compound and triethylamine in toluene into an ice-water bath according to a molar ratio of the chiral phosphine-amine compound to the chlorinated phosphite to the triethylamine of 1: (1-2): (3-5), heating the reaction solution to 18-25 DEG C, stirring and reacting for 10-30 hours, filtering, and carrying out column chromatography to remove the solvent, and recrystallizing to obtain the required phosphine-phosphoramidite ligand. According to the present invention, the asymmetric hydrogenation reaction of the catalyst formed by the ligand and the metal precursor on the double bonds such as C = C, C = N, C = O and the like can achieve the enantioselectivity of 99%; the catalyst is high in activity, and TON reaches up to 10000.
