Diastereoselective Syntheses of Spiro[indoline-3,4′-pyridin]-2-yl Carbamates via AgOTf/Ph₃P-Catalyzed Tandem Cyclizations of Tryptamine-Ynesulfonamides

Abstract

Spiro­[indoline-3,4′-piperidine] is a significant structural scaffold in numerous polycyclic indole alkaloids with a variety of bioactivities. In this study, a synthetic strategy was developed to access spiro­[indoline-3,4′-pyridin]-2-yl carbamate via an AgOTf/PPh3-catalyzed tandem cyclization of tryptamine-ynesulfonamides. The unique feature of this strategy is the efficient intermolecular capturing of the in situ generated spiroindoleninium intermediates with carbamates, leading to the diastereoselective syntheses of spiro­[indoline-3,4′-pyridin]-2-yl carbamate derivatives. A broad scope of this cyclization was demonstrated by a variety of tryptamine-ynesulfonamide substrates and several carbamates. A plausible mechanism of this reaction was proposed.

Facile synthesis of the spiro-pyridoindolone scaffoldviaa gold-catalysed intramolecular alkynol cyclisation/hydroindolylation

“…4,5 Likewise, the addition of carbon centred nucleophiles to the C2 of indole was explored by the Ohno, Huang, and Liu groups. 6–8…”

Ag(i)/PPh3-catalyzed diastereoselective syntheses of spiro[indole-3,4′-piperidine] derivatives via cycloisomerizations of tryptamine-ynamides

“…The importance of tryptamine-ynamides as versatile building blocks in organic synthesis, especially in the construction of indoline scaffolds, has been established by many elegant pioneering works due to the development of synthetic methods of tryptamine-ynamide. 7 Most cases reported to date relied on the electron-donating ability of nitrogen, leading to the regioselective addition of nucleophiles to the α-carbons of ynamides and the formation of spiro[indole-3,3′-pyrrolidine]. 7 a , b , d , e , h Ye and our group reported the opposite regioselectivity via a umpolung-type additions of indole to ynamides controlled by the chelating group of nitrogen under the catalysis of metal such as copper and silver salts, resulting in formation of azepino[4,5- b ]indole derivatives.…”

Lewis Acid-Catalyzed Diastereoselective Domino Reaction of Ene-Ynamide with Trimethylsilyl Cyanide to Construct Spiroindolines

“…As a result, there have been a few reports on the synthesis of spiroindolines using tryptamine-derived ynamides (Scheme ). However, during the synthesis of spiroindolines from tryptamine-derived ynamides, a carbon bond is formed at C-2 via rapid Wagner–Meerwein rearrangement. Previous research has reported the requirement of intramolecular traps with an appropriate nucleophile to prevent this.…”