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 system from the tetranuclear Ru−H complex [(PCy 3 )(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 2hydroxybenzaldehydes 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-C 6 H 4 CHO (X = OMe, Me, H, Cl, CF 3 ) 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.

Nickel-Catalyzed Three-Component Unsymmetrical Bis-Allylation of Alkynes with Alkenes: A Density Functional Theory Study

“…Yet, Ni-based MCRs still face many challenges such as (1) overcoming competitive and side reactions among multiple components and (2) effective control of chemo-, regio-and stereo-selectivities of the reaction [13,14]. Detailed computational characterizations provide atomistic details from which to raise awareness and understanding of MCRs towards helping overcome these challenges [15][16][17]. Yet, even for seasoned computational scientists, accurate determinations of structure and energetics along the reaction profiles of the putative mechanisms, towards predicting selectivities of MCRs, require significant computational resources, replete with technical difficulties and non-facile interpretation of the result trends.…”