Synthesis of multisubstituted pyrroles by nickel-catalyzed arylative cyclizations of N-tosyl alkynamides

Abstract

The synthesis of multisubstituted pyrroles by the nickel-catalyzed reaction of N-tosyl alkynamides with arylboronic acids is reported.

Nickel‐Catalyzed Arylative Cyclizations of Alkyne‐ and Allene‐Tethered Electrophiles using Arylboron Reagents

“…More recently, nickel catalysis has also been shown to be highly effective in these reactions. [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75] As well as being less expensive and more readily available than the more commonly used rhodium or palladium catalysts, nickel catalysis can offer unique possibilities in reaction development not readily available to these other catalyst systems. [76][77][78][79][80][81][82][83][84][85][86][87][88][89] This review will describe nickel-catalyzed arylative cyclizations of alkyne-and allene-tethered electrophiles using arylboron reagents, that proceed by the general mechanistic pathways shown in Scheme 1.…”

Dual Functionalization of Alkynes Utilizing the Redox Characteristics of Transition Metal Catalysts

“…[41c] Following this study, the Lam group reported Ni II /rac-Ph-PHOX mediated cyclization of Npropargyl amides 217 with boronic acids to synthesize substituted pyrrole derivatives 218 in 46-99 % yields (Scheme 33b). [42] The regioselective syn-addition of Ar 2 À NiX intermediate to the CÀ C triple bond of propargyl amides generated E-alkenylnickel species (E)-217 a, which upon reversible E/Z isomerization provided Z-alkenylnickel species (Z)-217 a. Intramolecular nucleophilic attack of (Z)-217 a into amide carbonyl, followed by eliminative aromatization afforded substituted pyrroles 218 (Scheme 33b). An electron-deficient Ntosyl group was essential for the activation of amide carbonyl moiety towards nucleophilic attack.…”

Recent Advances on Pyrrole Synthesis through Different Annulation Modes

“…In contrast, if t BuOK was used as the promoter, a selective cleavage of a C(CO)-C(sp 2 ) bond would occur during the cyclization reaction of N-propargyl β-enaminones, which could give 2,3,4-trisubstituted pyrroles in moderate to good yields (Scheme 11). [33] Scheme 11 t BuOK-mediated reaction of N-propargyl β-enaminones In 2018, Lam's group [34] also reported a nickel-catalyzed arylative cyclization of N-tosyl alkynamides affording multisubstituted pyrroles with good yields, and this method was applied for the formal synthesis of two borondipyrromethenes and a known inhibitor of bovine cyclooxygenase and 5-lipoxygenase (Scheme 12). Based on their systematic studies on ynamines, Ye and co-workers [35] developed a gold-catalyzed tandem cyclization of N-propargyl ynamides leading to a series of indeno [1,2-c]…”