Gold(III)‐Catalyzed Site‐Selective and Divergent Synthesis of 2‐Aminopyrroles and Quinoline‐Based Polyazaheterocycles

Abstract

Af acile,s ite-selective,a nd divergent approach to construct 2-aminopyrroles and quinoline-fused polyazaheterocycles enabled by as imple gold(III) catalyst from ynamides and anthranils under mild reaction conditions is described. This one-pot strategy uses readily available starting materials, proceeds in ahighly step-and atom-economical manner,w ith broad substrate scope and scale-up potential. The key element for success in this tandem reaction is ac atalyst-directed preferred quenchingo ft he in situ generated gold carbene intermediates by an ucleophilic benzyl/2-furylmethyl moiety on the ynamides as an alternative to the knownC ÀH annulation leading to indoles. Scheme 1. Different site-selectivereaction patterns of a-amino gold carbene intermediates.

Anthranils: versatile building blocks in the construction of C–N bonds and N-heterocycles

“…55 In this transformation, the carbene complex 111a underwent a regioselective insertion into the C-H bond of the o-aryl group to generate the iminophenanthrene intermediate 111b, which evolved towards the final products via a Friedel-Crafts-type cyclization. In addition, the annulation reactions of anthranils with N-benzyl ynamides, 56 N-aryl ynamides, 57 aryloxyethynes and aryl propargyl ethers 58 have been explored for the construction of various useful condensed N-heterocycles.…”

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

“…This reaction was further used for total synthesis of three natural alkaloids with this scaffold including norcryptotackeine, neocryptolepine, and 11-methylneocryptolepine. By using Nbenzyl ynamides and anthranils as substrates, Hashmi's group (Zeng et al, 2018) developed a gold(III)-catalyzed synthesis of polyazaheterocycles with a unique dihydroisoquinolinequinoline fused framework. Interestingly, when N-furanylmethyl ynamides are used, functionalized pyrroles, and 1H-pyrrolo[2,3b]quinolines can be obtained via a different reaction pathway involving ring-opening reaction of furan.…”

Skeletal reorganization divergence of N-sulfonyl ynamides

“…Ynamides are a type of N-substituted electron-rich alkynes that exhibit unique chemical properties and serve as versatile synthons in organic synthesis [33][34][35][36][37][38][39][40][41][42] . For example, ynamides could act as flexible cyclization partners in heterocycle synthesis [43][44][45] , carbene precursors [46][47][48][49] and enamide precursors 50,51 , racemization-free coupling reagents for peptide and macrolide synthesis [52][53][54] and C2 building blocks of multicomponent reactions) [55][56][57] . In recent years, the intramolecular cyclizations of ynamides, including transition-metal-catalysed and Brønsted acid-catalysed nucleophilic cyclizations, anionic cyclizations and radical cyclizations, have been extensively investigated for the synthesis of N-heterocycles ( Fig.…”