A General Strategy for the Construction of Functionalized Azaindolines via Domino Palladium-Catalyzed Heck Cyclization/Suzuki Coupling

Abstract

The preparation of substituted azaindolines utilizing a domino palladium-catalyzed Heck cyclization/Suzuki coupling is described. The approach is amenable for the construction of all four azaindoline isomers. A range of functional groups such as esters, amides, ketones, sulfones, amines, and nitriles are all tolerated under the reaction conditions.

Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes

“…The path c should be ruled out principally because of the dramatic difference in ee between the Heck dearomative carbocyclization Suzuki products (3y-3ab) and the Heck-Suzuki byproducts (3y′-3ab′). Since the electron-withdrawing group on arylboronic acids might accelerate the rate of transmetalation, 51,52 a reasonable assumption was that the domino dearomative reaction proceeded through path a or path d, while the side Heck-Suzuki reaction proceeded through path b. Indeed, the intermediate E could not have been involved in the formation of dearomative product 3 according to the halide effect investigation, because different ee values of 3a were observed when Br and I were employed in the reaction (Scheme 3, entries 2 and 3).…”

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…A range of functional groups such as esters, amides, ketones, sulfones, amines, and nitriles are all tolerated under these reaction conditions. 16 Scheme 9. Synthesis of 3,3-azaindolines.…”

Suzuki-Miyaura Coupling Enabled by Aryl to Vinyl 1,4-Palladium Migration

“…Later, direct C-H bond activation by palladium(II) becomes a second important route (Chen et al, 2006;Giri et al, 2007;Shi et al, 2007;Wang et al, 2008;Yang et al, 2008). Compared with these direct generation modes, the organopalladium(II) intermediate can also be produced via an indirect manner, which has been far less developed and mainly focused on the generation via a migratory insertion of organopalladium to olefins (Grigg et al, 1997;Schempp et al, 2017;Zhang et al, 2019) or alkynes (Couty et al, 2004;Monks and Cook, 2012) ( Figure 1A).…”