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

54 Citations (Scopus)

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
StatePublished - Jan 1 1995

Fingerprint

Osmium
Pyrroles
Cycloaddition
Cycloaddition Reaction
Alkaloids
Stereochemistry
Heptane
epibatidine
Crystal structure
Ligands
Nitrogen
Acrylonitrile
Acids
Electrons
Cyclopentanes
Dicarboxylic Acids
Metals
Anhydrides

ASJC Scopus subject areas

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

Cite this

Osmium-Promoted Dipolar Cycloadditions with Pyrroles : An Efficient, Stereoselective Synthesis of 7-Azanorbornanes. / Gonzalez, Javier; Koontz, Jason I.; Hodges, L. Mark; Nilsson, Kent R; Sabat, Michal; Harman, W. Dean; Neely, Linda K.; Myers, William H.

In: Journal of the American Chemical Society, Vol. 117, No. 12, 01.01.1995, p. 3405-3421.

Research output: Contribution to journalArticle

Gonzalez, Javier ; Koontz, Jason I. ; Hodges, L. Mark ; Nilsson, Kent R ; Sabat, Michal ; Harman, W. Dean ; Neely, Linda K. ; Myers, William H. / Osmium-Promoted Dipolar Cycloadditions with Pyrroles : An Efficient, Stereoselective Synthesis of 7-Azanorbornanes. In: Journal of the American Chemical Society. 1995 ; Vol. 117, No. 12. pp. 3405-3421.
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title = "Osmium-Promoted Dipolar Cycloadditions with Pyrroles: An Efficient, Stereoselective Synthesis of 7-Azanorbornanes",
abstract = "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).",
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T2 - An Efficient, Stereoselective Synthesis of 7-Azanorbornanes

AU - Gonzalez, Javier

AU - Koontz, Jason I.

AU - Hodges, L. Mark

AU - Nilsson, Kent R

AU - Sabat, Michal

AU - Harman, W. Dean

AU - Neely, Linda K.

AU - Myers, William H.

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N2 - 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).

AB - 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).

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