Insights into the Oxidative Palladium‐Catalyzed Regioselective Synthesis of 3‐Arylindoles from N−Ts‐Anilines and Styrenes: A Computational Study

Abstract

Palladium (Pd)‐catalyzed intermolecular oxidative annulation represents as an attractive approach to regioselective synthesis of 2/3‐arylindoles, but the unexpected regioselectivity remains to be one of the most challenging questions in this field. Herein, we present a systematically theoretical study on the Pd‐catalyzed regioselective synthesis of 3‐arylindoles from N−Ts‐anilines and styrenes with the presence of oxidant, special ligand, and benzoquinone (BQ) additive. A refined mechanism, in which the single six‐membered ring CMD‐type transition state was involved in the C−H activation of styrenes, is obviously more energetically favorable than the proposed pathway associated with the [6‐6] palladacyclic transition state in the experimental report (Youn et al., Angew. Chem. Int. Ed. 2017, 56, 1–6). The preferred reaction pathway consists of N−H deprotonation, CMD‐type C−H bond activation of styrenes, carbopalladation, BQ‐assisted β‐C−H activation, α‐C−H bond activation, and reductive elimination. With BQ additive, the carbopalladation is the key step for controlling the regioselectivity, and the favorable Pd−O coordinating bond interaction between Pd and BQ as well as the less distortion degree of styrene in the C3‐regioselective transition state determine the observed regioselectivity. The obtained computational insights should be valuable for understanding and rational design of the transition metal‐catalyzed oxidative annulation reactions with special regioselectivity.

Activation Pathway of C‐H and C–C Bonds of Ethane by Pd Atom with CO2 as a Soft Oxidant

“…Researchers are more concerned about Pt due to its excellent catalytic performance, but Pt is too expensive to industrial production. Pd and Pt are in the same group, have similar chemical properties, are more economical, and can be used for the activation of C−H bonds . In this study Pd was chosen as catalyst to explore the different reaction pathway of ethane/CO 2 .…”

Relative Strength of Common Directing Groups in Palladium-Catalyzed Aromatic C−H Activation

“…However, experimental results show that the activation takes place on the carbon A ortho to the nitrogen. A recent computational study on a similar palladium catalyst suggested that the activation does indeed proceed through the nitrogen coordination to palladium (Qiao et al., 2019). The following acetate-mediated N−H deprotonation leads to a four-member transition state that directs the reaction to position A.…”

Theoretical insights into phosphine‐catalyzed [4 + 2] annulation of allenoates with thiazolone‐derived alkenes

“…(3) Which step is the stereoselectivity‐determining step of chiral phosphine‐catalyzed [4 + 2] reaction? In order to solve the above mentioned problems, we intend to carry out a theoretical study on this kind of reaction by using the DFT method, which has been proved to be an effective and powerful tool for the mechanistic study of organocatalytic, [ 36–43 ] transition‐metal catalyzed [ 44–46 ] reactions.…”