Mechanistic Studies of the Pd- and Pt-Catalyzed Selective Cyclization of Propargyl/Allenyl Complexes

Abstract

Following the discovery of an unusual transitionmetal-catalyzed reaction, the elucidation of the underlying mechanism is essential to understand the characteristic reactivity of the metal. We previously reported a synthetic method for tricyclic indoles using Pt-catalyzed Friedel−Crafts-type C−H coupling. In this reaction, the Pt catalyst selectively formed a seven-membered ring, but the Pd catalyst only afforded a six-membered ring. However, the reasons for the different selectivities caused by Pd and Pt were unclear. We performed density functional theory (DFT) calculations and experimental studies to reveal the origin of the different behaviors of the two metals. The calculations revealed that the formation of the six-and seven-membered rings proceeds via η 1 -allenyl and η 3propargyl/allenyl complexes, respectively. A molecular orbital analysis of the η 3 -propargyl/allenyl complex revealed that, for the platinum complex, the energy required to convert the unoccupied molecular orbital on the reactive carbon into the lowest unoccupied molecular orbital (LUMO) was lower than that for the palladium complex. In addition, DFT calculations revealed that the combination of platinum and bis[2-(diphenylphosphino)phenyl] ether (DPEphos) reduced the activation energy of the sevenmembered cyclization in comparison with palladium or PPh 3 . Additional experimental studies, including NMR studies and stoichiometric reactions, support the aforementioned examination.

Synthetic Study of Dragmacidin E: Enantioselective Construction of the Seven-Membered Ring-Fused Indole Skeleton with Contiguous Stereocenters

“…The 3,4-fused tricyclic indole skeleton is a ubiquitous structure in a variety of natural products and bioactive molecules, making it an attractive target for synthetic organic chemists. , Since 2015, we have focused on developing a synthetic method for this skeleton using transition metal catalysis . As part of our ongoing studies aimed at applying the developed method to natural product synthesis, we reported a synthetic study of dragmacidin E using Pd-catalyzed cascade cyclization to construct the 3,4-fused tricyclic indole skeleton .…”