Ruthenium Catalysed Transfer Deuteration of Heteroaromatics in D2O
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...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/39627 |
| Acceso en línea: | https://aces.onlinelibrary.wiley.com/doi/epdf/10.1002/ajoc.202400462 https://hdl.handle.net/10578/39627 |
| Access Level: | acceso abierto |
| Palabra clave: | Deuterated derivatives Deuterium incorporation Formic acid/sodium formate Nitrogen-containing ring Non-D2 sources Partially hydrogenated heterocycles Pharmaceutical industry Polarity inversion (umpolung) Reaction mechanism Selective reduction Transfer deuteration |
| Sumario: | 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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