Carbopalladation/Suzuki Coupling Cascade for the Generation of Quaternary Centers: Access to Pyrrolo[1,2-b]isoquinolines

Abstract

A convergent route to pyrrolo [1,2-b]isoquinolines with a quaternary center at C-10 has been developed, which implies a sequential Pd(0)-catalyzed carbopalladation followed by cross-coupling reaction with boronic acids. The adequate catalytic system and experimental conditions, with and without the use of phosphane ligands, have been selected to control the chemoselectivity of the process, allowing a 6-exo-carbopalladation to generate a quaternary center and avoiding a direct Suzuki coupling. A variety of electron-rich and electron-deficient arylboronic acids can be used providing an efficient route to substituted pyrrolo [1,2-b]isoquinolines in moderate to good yields (up to 94%, 22 examples).

An Approach toward 17-Arylsubstituted Marginatafuran-Type Isospongian Diterpenoids via a Palladium-Catalyzed Heck–Suzuki Cascade Reaction of 16-Bromolambertianic Acid

“…In line with those previously postulated for the Pd-catalyzed domino Heck cascade reactions [23,24], we propose a plausible mechanism (Scheme 3). The oxidative addition of terpenoid bromofuran 5 to palladium(0) formed intermediate A, which was annulated through carbopalladation to form palladium(II) intermediate B.…”

“…The effect of the varying substitution pattern of the boronic acid aromatic ring, as well as the nature of the C-15 substituent in the terpenoid skeleton, will be explored. Previously, this Heck-Suzuki cascade reaction strategy has been intensely investigated in the synthesis of a variety of heterocycles, carbocycles [21][22][23][24], and also applied toward the synthesis of various natural products [25]. Due to the formation of a new chiral quaternary stereocenter, at the first stage as a result of the intramolecular Heck reaction, the products of this domino reaction are formed as a mixture of two diastereomers.…”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…Under the optimized reaction conditions wide range of electron rich and electron deficient arylboronic acids 197 were reacted to deliver pyrrolo[1,2-b]isoquinolines 294 in up to 70% yield (Scheme 171). [172] Again in 2019, Guguloth et al reported the similar protocol as reported by Verma et al [42] towards the synthesis of isoquinolines and other N-heterocycles using a hydrophilic Pd-phosphine catalyst (Scheme 172). [173] Reddy et al have improvised the strategy developed by Grübel et al [128] using Pd-catalyzed 6-exo-trig cyclization of N-(2-halobenzyl)-N-allylamines 295 to furnish C4-substituted tetrahydroisoquinolines 296 (Scheme 173).…”

“…Under the optimized reaction conditions wide range of electron rich and electron deficient arylboronic acids 197 were reacted to deliver pyrrolo[1,2‐ b ]isoquinolines 294 in up to 70% yield (Scheme 171). [172] …”

Ligand-Controlled Palladium-Catalyzed Chemoselective Multicomponent Reaction of Olefin-Tethered Aryl Halides, Isocyanides, and Carboxylic Acids: Diversified Synthesis of Imides

“…3 All of these reactions produced exclusively carbocyclization products, except in several rare cases, direct Suzuki coupling products were observed as the minor product. 4 To the best of our knowledge, there is no report of chemoselective formation of both carbocyclization products ("cyclization on" products) and direct coupling products ("cyclization off" products). Achieving this kind of chemoselectivity is a daunting challenge when considering the dramatic difference in the reaction rate between intra-and intermolecular reactions, and the difference in reactivity between alkyl-palladium complexes [C(sp 3 )-Pd] 5 and aryl-palladium complexes [C(sp 2 )-Pd].…”