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


Journal Article

A series of 7-azabicyclo[2.2.1]hept-5-ene complexes are prepared from [Os(NH3)5(η2-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). © 1995, American Chemical Society. All rights reserved.

Full Text

Duke Authors

Cited Authors

  • Gonzalez, J; Koontz, JI; Hodges, LM; Nilsson, KR; Sabat, M; Harman, WD; Neely, LK; Myers, WH

Published Date

  • January 1, 1995

Published In

Volume / Issue

  • 117 / 12

Start / End Page

  • 3405 - 3421

Electronic International Standard Serial Number (EISSN)

  • 1520-5126

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja00117a010

Citation Source

  • Scopus