Ortho-Deuteration of Aromatic Aldehydes via a Transient Directing Group-Enabled Pd-Catalyzed Hydrogen Isotope Exchange
Junhua Kong, Zhi‐Jiang Jiang, Jiayuan Xu, Yan Li, Hong Cao, Yanan Ding, Bencan Tang, Jia Chen, Zhanghua Gao
Abstract
A practical and scalable ortho-selective deuteration of aromatic aldehydes was accomplished by Pd-catalyzed hydrogen isotope exchange with deuterium oxide as an inexpensive deuterium source. The use of tert-leucine as a transient directing group facilitates the exchange, affording a wide range of ortho-deuterated aromatic aldehydes with deuterium incorporation up to 97%. The control experiments suggest that the addition of silver trifluoroacetate resists the unexpected reduction of Pd(II), while the theoretical study indicates a rapid reversible concerted metalation-deprotonation process.
Topics & Concepts
ChemistryDeuteriumDeprotonationMetalationCatalysisHydrogenKinetic isotope effectHydrogen–deuterium exchangePhotochemistryOxideMedicinal chemistryOrganic chemistryPhysicsQuantum mechanicsIonChemical Reactions and IsotopesAsymmetric Hydrogenation and CatalysisCoordination Chemistry and Organometallics