Microwave-assisted syntheses of n-heterocycles using alkenone-, alkynone- and aryl-carbonyl O-phenyl oximes: Formal synthesis of neocryptolepine

Fernando Portela-Cubillo, Jackie S. Scoto, John C. Walton

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)

Abstract

This research aimed to provide a new and "clean" synthetic method that would enable both known and novel N-heterocycles to be prepared efficiently. O-Phenyl oximes were found to be excellent precursors for iminyl radicals with a variety of acceptor side chains. Dihyropyrroles were made in good yields from O-phenyl oximes containing pent-4-ene acceptors. The analogous process with a hex-5-enyl acceptor did not yield a dihydropyridine, probably because the 6-exo-trig ring closure of the iminyl radical was too slow,to compete with H-atom abstraction. The iminyl radical from a precursor with a pent-4-yne type side chain underwent ring closure followed by rearrangement to afford a pyrrole derivative. Suitably substituted iminyl radicals ring closed readily onto aromatic acceptors, thus enabling several polycyclic systems to be accessed. Quinolines were made from 3-phenylpropanones via their O-phenyl oximes. Syntheses of phenanthridines starting from 2-formylbiphenyls were particularly efficient, and this approach enabled the natural product trisphaeridine to be made. Starting from 2-phenylnicotinaldehyde derivatives, ring closures of the derived iminyl radicals onto the phenyl rings yielded benzo[h][1,6]naphthyridines. Similarly, ring closure onto a phenyl ring from a benzothiophene-based iminyl yielded a benzo[b]thieno[2,3-c]quinoline. By way of contrast, iminyl radical ring closure onto pyridine rings was not observed. However, iminyl radicals did cyclize onto indoles, enabling indolopyridines to be prepared. The latter route was exploited in a short formal synthesis of neocryptolepine starting from 2-((1H-indol-3-yl)methyl)cyclohexanone.

Original languageEnglish
Pages (from-to)5558-5565
Number of pages8
JournalThe Journal of Organic Chemistry
Volume73
DOIs
Publication statusPublished - 18 Jul 2008

Keywords

  • FREE-RADICAL CYCLIZATIONS
  • IMINYL RADICALS
  • BIOLOGICAL-ACTIVITY
  • DERIVATIVES
  • PHOTOCYCLIZATION
  • PHENANTHRIDINE
  • TRISPHAERIDINE
  • ACETYLOXIMES
  • PYRROLE
  • ANALOGS

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