Ru-Catalyzed Reductive Dehydration of Amides to Enamines: Catalyst-Loading-Controlled Selectivity

Herein, we report a Ru 3 (CO) 12 -catalyzed reductive dehydration of amides to enamines using 1,1,3,3-tetramethyldisiloxane (TMDSO) that proceeds under mild conditions with high chemoselectivity and broad functional group tolerance. Notably, the enamine over amine selectivity is governed solely by the catalyst loading: low Ru 3 (CO) 12 loadings selectively afford pure enamines in good yields, whereas higher loadings of the same catalyst under otherwise identical conditions promote complete reduction to the corresponding amines. This catalyst-loading-controlled selectivity enables easily programmable access to distinct reduction products without any changes to catalyst structure, reductant, or other reaction components. Mechanistic studies indicate that the observed selectivity arises from the kinetic competition between α-C–H deprotonation and further reduction of an iminium intermediate, with low catalyst loading kinetically trapping the enamine product.