Preparation and Reactions of Indoleninyl Halides: Scaffolds for the Synthesis of Spirocyclic Indole Derivatives

Abstract

The dearomatization of 2-haloindole precursors allows access to indoleninyl halides, a hitherto underexploited functional handle with broad synthetic utility. Indoleninyl iodides have been shown to react via three distinct modes: hydrolysis, nucleophilic substitution, and cross-coupling. This allows a broad array of functionalized spirocyclic indole derivatives to be generated from a common starting material. They are also useful precursors to functionalized quinolines following migratory rearrangement and subsequent derivatization reactions.

Copper(I)‐Catalyzed N‐Carboxamidation of Indoles with Isocyanates: Facile and General Method for the Synthesis of Indole‐1‐carboxamides

“…Indole derivatives have become attractively synthetic goal in organic chemistry, because the indole skeleton is an important element of both natural products and synthetic molecules that exhibit a wide range of bioactivities, such as monoterpene indole alkaloids, indole alkaloids and tryptophan‐derived substances, and their application as tubulin polymerization inhibitors was also studied The development of efficient methods for their generation has attracted increasingly attentions . Transition metal‐catalyzed (such as Pd‐, Cu‐ or Rh‐ catalysts) intramolecular cyclization of functionalized o ‐alkynylanilines is one of the most efficient approaches for the synthesis of indoles.…”

Gold-Catalyzed Synthesis of 2-Sulfenylspiroindolenines via Spirocyclizations

“…In most of the reported examples, the indole unit is substituted by a methyl or a bromide group [10][11][12][13]. The method described herein introduces the sulfenyl group as substituent at C2 of the indole and we demonstrated its compatibility with Au(I)-catalyzed cyclization processes.…”

“…Reagent-grade chemicals were obtained from diverse commercial suppliers and used as received. 1 H-NMR (500 or 300 MHz) and 13 C-NMR (125 or 75 MHz) spectra were recorded on Bruker Avance spectrometers (Bruker, Wissembourg, France) at 298 K unless otherwise stated. Chemical shifts are given in ppm (δ) and are referenced to the internal solvent signal or to TMS used as an internal standard.…”

“…When the alkyne is tethered to the 3-position of the indole and if position 2 is substituted, the compound will undergo dearomatizing cyclization [7][8][9], as illustrated by the conversion of the 2-methyltryptamine derivative 1 (X = Me) into the spiro-compound 2 [10] (Scheme 1). In this field, we have introduced the use of 2-bromotryptamines that led to spirooxindoles 3 after acidic hydrolysis of the spirobromoindolenine resulting from the protodeauration of the intermediate [11][12][13]. We reasoned that the scope of these spirocyclization reactions might expand to tryptamines with other substituents on their 2-positions and hypothesized that tryptamines substituted by a SPh group should lead to 2-sulfenylspiroindolenines 4.…”

Iodospirocyclization of Tryptamine‐Derived Isocyanides: Formal Total Synthesis of Aspidofractinine

“…In the absence of aC 2 substituent, the cascade process is completed by as econd cyclization reaction to form tetracyclic spiroindolines (6 and 8). Considering the robustness of this process and the high potential utility of efficient and selective indole spirocyclizations,w ew ondered whether other soft electrophiles could give rise to similar cascade cyclizations.G iven the diverse reactivity of imidoyl halides in general and imidoyl iodides [7] in particular,w ec onsidered electrophilic halogenation as an efficient entry into spiroindolenines 10 and 11 as flexible synthetic intermediates.T here is some precedence for reactions of isocyanides and electrophilic halogenating agents, [8] including those involving cyclization to phenanthridines [9] and oxazoles. [10] We were delighted to see quantitative formation of spiroindolenine 11 a,b within 5min after treatment of 5a (R 1 = R 2 = R 3 = H) and 5b (R 1 = R 2 = H, R 3 = Me) with Niodosuccinimide (NIS) in CDCl 3 as the solvent.…”