Osmium-Promoted Dipolar Cycloadditions with Pyrroles: An Efficient, Stereoselective Synthesis of 7-Azanorbornanes

Javier Gonzalez, Jason I. Koontz, L. Mark Hodges, Kent R. Nilsson, Michal Sabat, W. Dean Harman, Linda K. Neely, William H. Myers

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

A series of 7-azabicyclo[2.2.1]hept-5-ene complexes are prepared from [Os(NH3)52-L)]2+ (L = pyrrole, 1-methylpyrrole, 2,5-dimethylpyrrole, 1,2,5-trimethylpyrrole, or 1-(trimethylsilyl)pyrrole) and various dipolarophiles (e.g., acrylonitrile, methyl acrylate, α-methylene-γ-butyrolactone, dimethyl maleate, dimethyl fumarate, N-phenyl maleimide, cyclopentene-1,2-dicarboxylic acid anhydride, and (E)- and (Z)-methyl 3-(3'-pyridyl)acrylate). The cycloaddition is promoted by coordination of the pyrrole with [Os(NH3)5]2+ across C3 and C4, transforming the uncoordinated portion of the pyrrole nucleus into an azomethine ylide capable of undergoing 1,3-dipolar cycloadditions. The metal serves not only to activate the pyrrole ring but also to stabilize the resulting 7-azabicyclo[2.2.1]heptene ligands. A number of organic 7-azabicyclo[2.2.1]heptanes, including analogs of the alkaloid epibatidine, have been synthesized by this methodology. For the cases examined, the cycloaddition favors exo stereochemistry of the electron-withdrawing substituent when the pyrrole nitrogen is unsubstituted. Crystal structures have been determined for the complexes obtained from the reactions of pyrrole with N-phenylmaleimide (8a), 2,5-dimethylpyrrole with dimethyl maleate (13a), and 2,5-dimethylpyrrole with α-methylene-γ-butyrolactone (22a).

Original languageEnglish (US)
Pages (from-to)3405-3421
Number of pages17
JournalJournal of the American Chemical Society
Volume117
Issue number12
DOIs
Publication statusPublished - Mar 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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