DOI: 10.1021/acs.orglett.6c04258 ISSN: 1523-7060
Ruthenium-Catalyzed Site-Selective Direct Deuteration of Azaarenes Using Deuterium Oxide
Nirmal Chandra Sahoo, Chidambaram GunanathanAbstract
Selective incorporation of deuterium into heteroarenes without directing groups has been a long-standing problem. Monohydrido-bridged ruthenium complex [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] catalyzes the site-selective deuteration of C–H bonds in five-membered azaarenes. Notably, active drug substances were directly deuterated under this catalytic condition. Remarkably, the reaction requires a minimal catalyst loading (0.5–1 mol %) and D2O is employed as a direct deuterium source for the deuteration of imidazole, thiazole, and indole derivatives that exhibited good to excellent deuterium incorporation.