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Pd/Xu-Phos-catalyzed asymmetric elimination of fully substituted enol triflates into axially chiral trisubstituted allenes

Jie Han, Siyuan Liu, Huanan Wang, Jie Wang, Hui Qian, Zhiming Li, Shengming Ma, Junliang Zhang

2023Science Advances34 citationsDOIOpen Access PDF

Abstract

The β-H elimination, as one of the most important elementary reactions in transition metal chemistry, is a key step in quenching the carbon-palladium bond for the Heck reaction. However, the β-H elimination of the alkenyl palladium species leading to allene is an energetically unfavored process, and therefore, it has been a long-standing challenge in control of this process via enantioselective manner. We developed a concise and efficient methodology to construct trisubstituted chiral allenes from stereodefined fully substituted enol triflates by the enantioselective β - H elimination of the alkenyl palladium species under mild conditions. The identified Xu-Phos play a crucial role in the chemoselectivity and enantioselectivity. Multiple linear regression analysis shows the important steric effect on enantioselectivity. DFT computation results allow us to propose an intramolecular base ( − OAc)–assisted deprotonation mechanism for this progress. Distortion-interaction and energy decomposition analysis indicate that the difference in electrostatic energy ( E elec ) of the two intramolecular base-assisted deprotonation transition states dominates the stereoselectivity.

Topics & Concepts

ChemistryEnolIntramolecular forceAlleneEnantioselective synthesisDeprotonationPalladiumTransition stateStereoselectivitySteric effectsCatalysisOxidative additionMedicinal chemistryCombinatorial chemistryStereochemistryOrganic chemistryIonAsymmetric Hydrogenation and CatalysisAxial and Atropisomeric Chirality SynthesisCatalytic C–H Functionalization Methods