Expedient and Divergent Tandem One-Pot Synthesis of Benz[e]indole and Spiro[indene-1,3′-pyrrole] Derivatives from Alkyne-Tethered Chalcones/Cinnamates and TosMIC

Abstract

An efficient solvent-dependent regioselective [3 + 2]-cycloaddition/iodocyclization cascade reaction of alkyne-tethered chalcones/cinnamates and TosMIC has been developed. The reaction represents a novel protocol for the expedient and divergent one-pot synthesis of benz[e]indoles and spiro[indene-1,3'-pyrroles] from acyclic common precursors at room temperature.

Synthesis of Multi-Substituted Pyrrole Derivatives Through [3+2] Cycloaddition with Tosylmethyl Isocyanides (TosMICs) and Electron-Deficient Compounds

“…As shown in Scheme 3 , the electron-withdrawing groups may be esters, amides, ketones, nitros, cyanos, aryls, etc. [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Based on the different types of electron-withdrawing group attached to the alkenes, they are classified and described in order ( Scheme 3 ).…”

“…In 2015, our group developed an expedient and divergent tandem one-pot synthesis of benz[ e ]indole derivative 53 (79%) and spiro[indene-1,3’-pyrrole] derivative 54 (6%) from alkyne-tethered chalcones/cinnamates 51 and TosMIC 16 . The formation of intermediate 52 in this reaction involves a [3+2] cycloaddition with TosMIC 16 and electron-deficient ester 51 ( Scheme 14 ) [ 34 ]. To our knowledge this reaction is the first example of intramolecular electrophilic cyclizations of alkynes with in-situ generated pyrroles.…”

TosMIC: A Powerful Synthon for Cyclization and Sulfonylation

“…The structure of prototype spiro compound was confirmed by X-ray diffraction study and subsequent derivatives were characterized by spectroscopic analysis. [51] A plausible mechanism was proposed based on the spiro product generated. Initially, the formal […”

[3+2] Cycloaddition of Tosylmethyl Isocyanide with Styrylisoxazoles: Facile Access to Polysubstituted 3-(Isoxazol-5-yl)pyrroles

“…Although the stepwise synthesis of dihydropyrroles from styrylisoxazoles was developed [ 41 ], to our knowledge, the [3+2] cycloaddition reaction of styrylisoxazoles with TosMIC for the synthesis of isoxazolylpyrroles has not been reported so far. As part of our continued efforts to develop the heterocyclization of TosMIC [ 42 , 43 , 44 , 45 , 46 , 47 ], we report herein an expedient and convenient one-pot synthesis of isoxazole-substituted pyrrole derivatives from [3+2] cycloaddition of 3-methyl-4-nitro-5-styrylisoxazoles with TosMIC and analogs ( Scheme 1 , Equation (4)). Under basic conditions, various styrylisoxazoles reacted smoothly with TosMIC and analogs to deliver a wide range of polysubstituted isoxazolylpyrroles at ambient temperature.…”