Ruthenium Catalysed Transfer Deuteration of Heteroaromatics in D2O
2024
Gonzalo Navarro, Carlos | Ruiz de Castañeda Álvaro, Margarita | Fidalgo, Jairo | Espino, Gustavo | Jalón Sotes, Félix Ángel | Manzano Manrique, Blanca Rosa Lourdes
There is a growing interest in deuterated derivatives in variousfields, including the pharmaceutical industry. In this industry,partially hydrogenated heterocycles are also a target. Combin-ing these two concepts, it was studied the reduction ofheterocycles with simultaneous deuterium incorporation bytransfer deuteration, a process of introducing two deuteriumatoms into an organic molecule using non-D2 sources, avoidingthe use of a gas or harmful reagents. Formic acid/sodiumformate and D2O as the sole deuterium source were used undermild conditions. The precatalyst was [RuCl(p-cym)(dmbpy)]BF4,(p-cym = p-cymene, dmbpy = 4,4’-dimethyl-2,2’-bipyridine),which is able to generate the “Ru polarity inversion process (“umpolung”). A wide range ofheterocycles were tested. Selective reduction in the nitrogen-containing ring with deuterium incorporation into the samering was achieved. The experiments were carried out in abiphasic D2O/toluene medium, which allowed excellent catalystrecycling with a simple work-up. Through detailed studies for 3-methylquinoline using DCOOD/DCOONa, the reaction mecha-nism that involves D+ incorporation at the nitrogen atom andan initial 1,2-type addition was elucidated. In single-phase D2Oexperiments, a distinct selectivity with deuterium incorporationin the non-hydrogenated ring was observed thus enabling tomodulate it by the choice of the medium.
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