Brønsted Acid‐Catalyzed Tandem Cyclizations of Tryptamine‐Ynamides Yielding 1H‐Pyrrolo[2,3‐d]carbazole Derivatives

Abstract

Ynamides, as versatile synthetic precursors, have attracted much attention from synthetic chemists and sparked the development of a number of methodologies for the construction of various structures. 1H-Pyrrolo[2,3-d]carbazole is a core scaffold of a series of monoterpene indole alkaloids found in Kopsia, Strychnos, and Aspidosperma, for example. In this study, 1H-pyrrolo[2,3-d]carbazole derivatives were synthesized by a Brønsted acid-catalyzed tandem cyclization starting from tryptamine-based ynamides. This strategy prevented Wagner-Meerwein rearrangement by instantaneous intramolecular nucleophilic trapping of the indoleninium to afford a tetracyclic indoline via an in situ-formed enol species induced by the formation of a more stable conjugate diene moiety. The functional group tolerances were investigated by using a series of readily available substrates. A plausible mechanism has been proposed based on the evidence of the capture of the hemiaminal intermediate. Lastly, a Büchi ketone, which is the pivotal intermediate in the synthesis of the indole alkaloid vindorosine, was synthesized by utilizing our newly developed methodology.

Construction of the Pyrrolo[2,3-d]carbazole Core of Spiroindoline Alkaloids by Gold-Catalyzed Cascade Cyclization of Ynamide

“…The subsequent addition of silyl enol ether to the resulting iminium moiety leads to the formation of intermediate C, followed by deauration and cleavage of the silyl group to produce pyrrolo[2,3d]carbazole D. During the course of this study, a related goldcatalyzed cascade cyclization was reported by Yang and coworkers, 12 where the iminium intermediate was trapped by intramolecular nucleophilic attack of hydroxy group (Scheme 1b). Quite recently, the Cheng and Liu group 14 reported an acid-catalyzed cascade reaction of ynamide for the racemic synthesis of pyrrolo[2,3-d]carbazole D using methyl ketone derivative G (Scheme 1c). Herein, we describe a goldcatalyzed cascade reaction of ynamide with silyl enol ether, leading to pyrrolo[2,3-d]carbazole D. A catalytic enantioselective version of the reaction and its application to formal synthesis of vindorosine are also presented.…”

Synthetic Approaches to Tetracyclic Indolines as Versatile Building Blocks of Diverse Indole Alkaloids

“…The latest effort to construct the tetracyclic indoline scaffold by using nucleophilic addition strategy was made by our group. We developed a Brønsted acid catalyzed tandem cyclization of tryptamine‐derived ynamides towards the tetracyclic frameworks (Scheme ) . In this approach, ynamides were utilized as significant building blocks by taking advantage of the substantial advancements in ynamide chemistry in the past decade .…”

“… A Brønsted acid‐catalyzed tandem cyclization of tryptamine‐derived ynamides strategy to tetracyclic indolines 67 (Liu and Cheng et al …”

“…We developed aB rønsteda cid catalyzed tandemc yclization of tryptamine-derived ynamides towards the tetracyclic frameworks (Scheme 7). [27] In this approach, ynamides were uti-Scheme5.Astereoselective cascade annulation protocol to tetracyclic indolines 46 and 51 (Blakey et al [24,25] ).…”

“…AM gI 2 -catalyzed Diels-Alderc ycloaddition providedt he cycloadduct 84,w hich underwent an Scheme7.ABrønsteda cid-catalyzed tandem cyclization of tryptamine-derived ynamides strategy to tetracyclic indolines 67 (Liu and Chenge tal. [27] ).…”