Abstract
The Ir-catalyzed conversion of prochiral tert-cyclobutanols to β-methyl-substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β-oxy-substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM-SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related RhI-catalyzed transformations. Supported by DFT calculations we propose the initial formation of an IrIII hydride intermediate, which then undergoes a β-C elimination (C−C bond activation) prior to reductive C−H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir-catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo-controlled synthesis of substituted chromanes related to the tocopherols and other natural products.
| Original language | English |
|---|---|
| Pages (from-to) | 4640-4652 |
| Number of pages | 13 |
| Journal | Chemistry - A European Journal |
| Volume | 27 |
| Issue number | 14 |
| DOIs | |
| State | Published - 8 Mar 2021 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH
Funding
Support of this work by the University of Cologne is gratefully acknowledged. We sincerely thank Thomas Netscher from DSM Nutritional Products for the determination of the enantiomeric purity of samples of α-tocopherol methyl ether by means of HPLC. We also thank Nils Schlörer and the local NMR facility for the excellent service and help in context of NMR-based ee measurements. Additionally, we thank the computing center of the University of Cologne (RRZK) for providing CPU time on the DFG-funded supercomputer CHEOPS. Open access funding enabled and organized by Projekt DEAL. Support of this work by the University of Cologne is gratefully acknowledged. We sincerely thank Thomas Netscher from DSM Nutritional Products for the determination of the enantiomeric purity of samples of α‐tocopherol methyl ether by means of HPLC. We also thank Nils Schlörer and the local NMR facility for the excellent service and help in context of NMR‐based measurements. Additionally, we thank the computing center of the University of Cologne (RRZK) for providing CPU time on the DFG‐funded supercomputer CHEOPS. Open access funding enabled and organized by Projekt DEAL. ee
| Funders |
|---|
| DFG-funded |
| DSM Nutritional Products |
| RRZK |
| Thomas Netscher |
| Universität zu Köln |
Keywords
- C−C bond activation
- asymmetric catalysis
- cyclobutanols
- deuteration
- iridium