Frank, Eduard and Park, Sooyoung and Harrer, Elias and Fluegel, Jana L. and Fischer, Marcel and Nuernberger, Patrick and Rehbein, Julia and Breder, Alexander (2024) Asymmetric Migratory Tsuji-Wacker Oxidation Enables the Enantioselective Synthesis of Hetero- and Isosteric Diarylmethanes. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 146 (50). pp. 34383-34393. ISSN 0002-7863, 1520-5126
Full text not available from this repository. (Request a copy)Abstract
Diarylmethanes play, in part, a pivotal role in the design of highly potent, chiral, nonracemic drugs whose bioactivity is typically affected by the substitution pattern of their arene units. In this context, certain arenes such as para-substituted benzenes or unsubstituted heteroarenes cause particular synthetic challenges, since such isosteric residues at the central methane carbon atom are typically indistinguishable for a chiral catalyst. Hence, the stereoselective incorporation of isosteric (hetero)arenes into chiral methane scaffolds requires the use of stoichiometrically differentiated building blocks, which is typically realized through preceding redox-modifying operations such as metalation or halogenation and thus associated with disadvantageous step- and redox-economic traits. As a counter-design, we report herein a generalized enantioselective synthesis of chiral diarylmethanes by means of an asymmetric migratory Tsuji-Wacker oxidation of simple stilbenes. The title protocol relies on the well-adjusted interplay of aerobic photoredox and selenium-pi-acid catalysis to allow for the installation of a broad variety of arenes, including isosteric ones, into the methane core. Facial differentiation and regioselectivity are solely controlled by the selenium catalyst, which (a) renders the E/Z-configuration of the stilbene substrates inconsequential and (b) permits the stereodivergent synthesis of both product enantiomers from a single catalyst enantiomer, simply by employing constitutionally isomeric starting materials. Altogether, this multicatalytic platform offers the target structures with high levels of enantioselectivity in up to 97% ee, which has also been successfully exploited in expedited syntheses of antihistaminic (R)- and (S)-neobenodine.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DYNAMIC-KINETIC RESOLUTION; C(SP(3))-H BONDS; SELENIRANIUM IONS; RING ENLARGEMENT; AB-INITIO; ARYLATION; REARRANGEMENT; BETA; FUNCTIONALIZATION; HYDROGENATION; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Prof. Dr. Alexander Breder |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jul 2025 09:10 |
| Last Modified: | 25 Jul 2025 09:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63777 |
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