One-pot, multicomponent reactions via indolium ion intermediates: synthesis of spiropyrans and pyrroloindolines

Abstract

Nitrogen-containing heterocylces such as indoles, pyrroloindolines and spiropyrans are a common motif in a variety of diverse, natural products, which exhibit interesting physical and biological properties. Accessing these structures has inspired numerous synthetic procedures. Herein, we have developed a one-pot, 4-component synthesis of spiropyrans based on a Fischer Indolisation, tandem, alkylation-condensation cascade promoted by para-toluene sulfonic acid, starting from hydrazine, ketone, alkyl-bromide and salicylaldehyde starting materials, under mild conditions in environmentally benign solvents, ethanol and water. Our procedure produced 23 diverse spiropyran compounds with unique and useful functional groups for further elaboration, and steric control of the spiropyran-merocyanine isomerism. Furthermore, we have developed a microwave assisted, one-pot, 2-step, solvent free, [3+2] dearomative cycloaddition cascade in the synthesis of pyrolloindolines from 1,2,3-trimethylindole and N-tosylaziridines. This procedure consistently produced simple methyl substituted pyrolloindoline scaffolds in a solvent and catalyst free manner. We then expanded the scope of this process to encompass alternative aziridines, thereby generating phenyl stablised pyrolloindolines.