Verkhov, Valery A. and Gubanova, Alexandra N. and Tonkoglazova, Daria I. and Tupikina, Elena Yu. and Antonov, Alexander S. (2025) Flipping the Metalation of 4-Dimethylaminopyridine: Steric Repulsion versus London Dispersion Attraction. CHEMISTRY-A EUROPEAN JOURNAL, 31 (6). ISSN 0947-6539, 1521-3765
Full text not available from this repository. (Request a copy)Abstract
Non-covalent interactions, including the coordination of an organolithium reagent by a directing group and the steric hindrance from substituents, play a crucial role in determining the selectivity of metalation reactions. Here, we demonstrate the effective utilization of steric interactions for flipping the lithiation of 4-dimethylaminopyridine (DMAP). Introduction of a Me3Si substituent to the position 1 of DMAP or simple complexation with t-BuLi allows selective C3-lithiation, due to the steric hindrance of a C2-H bond by the bulky moiety at the pyridine nitrogen. This simple approach creates a convenient way to achieve the selective C3-functionalization of DMAP. In contrast, the utilization of an even bulkier i-Pr3Si substituent leads to exclusive C2-functionalization due to the dispersion interactions with organometallic bases. For the first time, it is demonstrated that the i-Pr3Si moiety can serve as a directing group, providing a new type of directed ortho-metalation effect.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PYRIDINE; LITHIATION; DENSITY; ACCESS; Dispersion interaction; Metalation; Steric hindrance; Pyridine; Organolithium |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Prof. Dr. Ruth Gschwind |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2026 07:39 |
| Last Modified: | 10 Mar 2026 07:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63875 |
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