Rhodium‐Catalyzed Stereoselective Deuteration of Benzylic C–H Bonds via Reversible η<sup>6</sup>‐Coordination
Qi‐Kai Kang, Yuntong Li, Kai Chen, Hui Zhu, Wen‐Qiang Wu, Yunzhi Lin, Hang Shi
Abstract
Abstract We report a convenient method for benzylic H/D exchange of a wide variety of substrates bearing primary, secondary, or tertiary C−H bonds via a reversible η 6 ‐coordination strategy. A doubly cationic [Cp CF3 Rh III ] 2+ catalyst that serves as an arenophile facilitates deprotonation of inert benzylic hydrogen atoms (p K a >40 in DMSO) without affecting other hydrogen atoms, such as those on aromatic rings or in α ‐positions of carboxylate groups. Notably, the H/D exchange reactions feature high stereoretention. We demonstrated the potential utility of this method by using it for deuterium labeling of ten pharmaceuticals and their analogues.
Topics & Concepts
ChemistryDeprotonationRhodiumCationic polymerizationCatalysisDeuteriumMedicinal chemistryHydrogen bondCarboxylateStereoselectivityPrimary (astronomy)StereochemistryPolymer chemistryMoleculeOrganic chemistryIonAstronomyPhysicsQuantum mechanicsChemical Reactions and IsotopesAsymmetric Hydrogenation and CatalysisFluorine in Organic Chemistry