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

Abstract

The in situ generated catalytic systemfrom thetetranuclear 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 deaminativecoupling reaction of phenols with aldehydes and enamines to form xantheneproducts. The multicomponent C-H coupling reaction of phenolswith 2-hydroxybenzaldehydes and cyclic enamines efficiently installedthe tricyclic 1,3-dioxacin derivatives, while the analogous couplingreaction of phenols with 2-hydroxybenzaldehydes and triethylamineselectively formed bicyclic 1,5-dioxacyclic derivatives. The densityfunctional theory (DFT) calculations established two energeticallyviable mechanistic pathways for the formation of xanthene products,in which both pathways identified the C-O bond cleavage stepas the turnover limiting step. A Hammett plot from the coupling reactionof 3,5-dimethoxyphenol with an enamine and para-substitutedbenzaldehydes p-X-C6H4CHO (X= OMe, Me, H, Cl, CF3) showed a negative slope (& rho;= -0.98). The calculated energy analysis showed a similar trend(& rho; = -0.59) for the mechanism via the C-O cleavagerate-limiting step. The combined experimental and DFT computationalresults support a mechanistic path that involves the dehydrative C-Hcoupling of phenol with aldehyde, followed by the deaminative couplingreaction with an enamine in forming the xanthene product.