Indole Editing Enabled by HFIP‐Mediated Ring‐Switch Reactions of 3‐Amino‐2‐Hydroxyindolines

Abstract

This work reports the novel reactivity of hemiaminal as a precursor for indole editing at the multi-site. The HFIPpromoted indole editing of indoline hemiaminals affords 2arylindoles through a ring-switch sequence. The key to success of this transformation is to use a cyclic hemiaminal as an α-amino aldehyde surrogate under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance. The utility of this transformation is presented through the one-pot protocol and the synthesis of isocryptolepine.

Concise Synthesis of Thiazolo[4,5‐b]indoles via Ring Switch/Cyclization Sequences

“…First, the indole-2,3-epoxide 6 [10,15] generated in situ undergoes nucleo- philic attack by phenylthioamide 2 a to afford benzimidothioate 7. Transient tautomeric control [9] would afford aldehyde 8, and subsequent cyclization by the imidate moiety/protonation furnish 2,5-diaryl-4-hydroxythiazoline 3 aa. [18] These sequences delineates the first example of construction of thiazoline from the indoles through the ring-switch reaction.…”

“…Recently, we described the synthesis of 2-arylindoles via a ring-switch reaction of the 3-amino-2-hydroxyindolines under the transient tautomeric control of the hemiaminals, [9] which could be derived from HITAB (1, 2-hydroxyindoline-3-triethylammonium bromide) [10] and anilines (Scheme 1C). In order to develop the ring-switch reaction of indoles via the C2À N1 bond breaking transformations, [11][12][13][14] we herein wish to disclose the unprecedented reactions of indoline hemiaminals affords 2,5diaryl-4-hydroxythiazolines through a thioamidation/ring switch sequence under the transient tautomeric control (sp 3 -and sp 2type: Scheme 1D).…”

Aluminum-Catalyzed Cross Selective C3–N1′ Coupling Reactions of N-Methoxyindoles with Indoles

“…Over the past five years, our group has had an intensive focus on the development and application of umpoled indole surrogates [33][34][35][36][37][38][39][40][41][42][43][44]. These results led us to find that in situ generated 3-methoxyindoles act as a C3-electrophilic reagent that can be harnessed for C-N, C-O, and C-C bond-forming SNAr reactions under indium catalysts [45,46].…”

“…By analogy to our indium-catalyzed SNAr reaction, we hypothesized that N-alkoxy indoles might be suitable competent substrate as a N1-electrophilic indole precursor by a Lewis acid activation of alkoxy group through an elimination of ROH, thereby producing a C3-N1′ bisindole (Scheme 2). In this hypothesis, N-alkoxyindole is first combined with Lewis acids (LA) to form an LA-indole complex, which shows an N-electrophilic character by N-O bond activation along with reducing C3-nucleophilicity by coordinating at the C2-C3 π-bond [47- Over the past five years, our group has had an intensive focus on the development and application of umpoled indole surrogates [33][34][35][36][37][38][39][40][41][42][43][44]. These results led us to find that in situ generated 3-methoxyindoles act as a C3-electrophilic reagent that can be harnessed for C-N, C-O, and C-C bond-forming S N Ar reactions under indium catalysts [45,46].…”

First Total Synthesis of Reassigned Echinosulfonic Acid D

“…We recently reported a new class of bench-stable indoline reagents that serve as an umpoled indole synthon for the formal cross-nucleophile coupling to afford 3-substituted indoles. , Using our umpoled indole reagent, α-monoindolyl carbonyl compounds were able to be synthesized from the active methylene compounds, which are difficult to obtain by other methods . Based on these results, we hypothesized a new synthetic route for bisindolylacetic acids; the desired strategy should be accomplished by a double indolization of dimethylbarbituric acid as a dinucleophile with our umpoled indole reagent as an electrophile followed by dehydration and hydrolysis of the barbituric acid moiety.…”