Scope and Mechanistic Studies on the Ruthenium-Catalyzed Multicomponent Deaminative C–H Coupling Reaction of Phenols with Aldehydes and Enamines for the Formation of Xanthene and Dioxacyclic Derivatives

The in situ generated catalytic system
from the
tetranuclear Ru–H complex [(PCy3)(CO)RuH]4(O)(OH)2 (1) with 3,4,5,6-tetrachloro-1,2-benzoquinone
(L1) has been found to mediate a multicomponent deaminative
coupling reaction of phenols with aldehydes and enamines to form xanthene
products. The multicomponent C–H coupling reaction of phenols
with 2-hydroxybenzaldehydes and cyclic enamines efficiently installed
the tricyclic 1,3-dioxacin derivatives, while the analogous coupling
reaction of phenols with 2-hydroxybenzaldehydes and triethylamine
selectively formed bicyclic 1,5-dioxacyclic derivatives. The density
functional theory (DFT) calculations established two energetically
viable mechanistic pathways for the formation of xanthene products,
in which both pathways identified the C–O bond cleavage step
as the turnover limiting step. A Hammett plot from the coupling reaction
of 3,5-dimethoxyphenol with an enamine and para-substituted
benzaldehydes p-X-C6H4CHO (X
= OMe, Me, H, Cl, CF3) showed a negative slope (ρ
= −0.98). The calculated energy analysis showed a similar trend
(ρ = −0.59) for the mechanism via the C–O cleavage
rate-limiting step. The combined experimental and DFT computational
results support a mechanistic path that involves the dehydrative C–H
coupling of phenol with aldehyde, followed by the deaminative coupling
reaction with an enamine in forming the xanthene product.