Gold-Catalyzed Intermolecular Ynamide Amination-Initiated Aza-Nazarov Cyclization: Access to Functionalized 2-Aminopyrroles

Abstract

A novel gold-catalyzed intermolecular ynamide amination-initiated aza-Nazarov cyclization has been developed, allowing the facile and efficient synthesis of various 2-aminopyrroles in moderate to good yields. Furthermore, a mechanistic rationale for this tandem sequence, especially for the observed high regioselectivity, is also well supported by DFT (density functional theory) computations. The high flexibility, broad substrate scope, and mild nature of this reaction render it a viable alternative for the construction of 2-aminopyrroles.

Gold-catalyzed heterocyclic syntheses through α-imino gold carbene complexes as intermediates

“…Final protodeauration and aromatization steps could drive to the formation of the same -carboline derivatives 66 as starting from the regioisomeric indoles 64.Finally, it is worth to mention the formation of pyrrole derivatives 73 from enynamides 71. This research, by Lu, Ye et al,39 is closely related to the intramolecular version reported by other authors in 2012.…”

Recent Progress in N-Heterocyclic Carbene Gold-Catalyzed Reactions of Alkynes Involving Oxidation/Amination/Cycloaddition

“…Following this work, the same group developed a novel mode of NHC gold-catalyzed intermolecular alkyne amination-initiated aza-Nazarov cyclization when enynes replaced ordinary alkynes as the substrates [99]. Enynes 44 with 3 equivalent of 3-bromobenzyl azide 45a could be converted smoothly into the breadth of 2-aminopyrroles 46 by using IPrAuNTf 2 (5 mol%) as the catalyst (Scheme 24).…”

Gold-catalyzed intermolecular reaction of ynamides with 3-indolyl azides via an unexpected 1,2-alkyl migration

“…As a result, this chemistry has evolved into a robust and reliable method for the construction of versatile 2aminoindoles and 3-amino-b-carbolines (Scheme 2a) [49]. On the basis of this work, we further developed the relevant goldcatalyzed intermolecular ynamide amination initiated aza-Nazarov cyclization [50] and C-H functionalization [51], leading to the efficient synthesis of highly functionalized 2aminopyrroles and 2-aza-1,3-butadienes, respectively. Inspired by these results, we envisioned that the synthesis of 2-amino-ccarbolines might be accessed directly through such a goldcatalyzed intermolecular reaction of ynamides with 3-indolyl azides (Scheme 2b).…”