Abstract

Abstract New indole synthesis starting with o-methylphenyl isocyanides such as o-tolyl, 2,4-xylyl, and 2,6-xylyl isocyanide is described in full detail. Treatment of o-tolyl isocyanide with LDA in diglyme at −78 °C generated selectively o-(lithiomethyl)phenyl isocyanide in an almost quantitative yield, which on warming up to room temperature was cyclized to indole after aqueous workup. Similary, 2,4-xylyl and 2,6-xylyl isocyanides were cyclized to 5-methylindole and 7-methylindole quantitatively. The o-(lithiomethyl)phenyl isocyanides reacted with electrophiles such as alkyl halides and alkylene oxides to give o-alkylphenyl isocyanides, which were cyclized via the lithiation at the orthobenzylic carbon to afford 3-substituted indoles. On the other hand, the o-(lithiomethyl)phenyl isocyanides generated in situ at −78 °C was first warmed up to room temperature and then treated with electrophiles to furnish 1-substituted indoles. The o-(lithiomethyl)phenyl isocyanides were acylated in a fairly good yield with N-acylaziridines to give o-(acylmethyl)phenyl isocyanides, which were readily alkylated in the presence of sodium hydride to produce o-(1-acylalkyl)phenyl isocyanides. On acid hydrolysis followed by neutralization, o-(1-acylalkyl)phenyl isocyanides were converted to 2,3-disubstituted indoles.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.