Synthesis of benzobicyclo[3.2.1]octanes involving inversion of configuration via an N to O acetyl migration

Gary L. Grunewald, Qizhuang Ye

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Two conformationally defined analogues of phenylethanolamine, 8-amino-6,7,8,9-tetrahydro-5,8-methano-5H-benzocyclohepten-endo-9-ol (5) and 8-amino-6,7,8,9-tetrahydro-5,8-methano-5H-benzocyclohepten-exo-9-ol (6), have been synthesized. The benzobicyclo[3.2.1]octane skeleton was constructed by an intramolecular cyclization of 3-phenylcyclopentane-1,1-dicarboxylic acid (10). The sodium borohydride reduction of 8-amino-9-oxo-6,7,8,9-tetrahydro-5,8-methano-5H-benzocycloheptene (12) gave the endo alcohol 5. The greater stability of the exo alcohol 6 compared to 5 was confirmed by AM1 calculations. The exo alcohol 6 was obtained from 5 by an N to O acetyl migration. A possible mechanism for this migration in the inversion of the stereochemistry at C-9 is discussed. Structural assignments using 2-D NMR spectra and an NOE difference spectrum are presented.

Original languageEnglish (US)
Pages (from-to)4021-4026
Number of pages6
JournalJournal of Organic Chemistry
Volume53
Issue number17
StatePublished - 1988
Externally publishedYes

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Octanes
Alcohols
Benzocycloheptenes
Dicarboxylic Acids
Stereochemistry
Cyclization
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis of benzobicyclo[3.2.1]octanes involving inversion of configuration via an N to O acetyl migration. / Grunewald, Gary L.; Ye, Qizhuang.

In: Journal of Organic Chemistry, Vol. 53, No. 17, 1988, p. 4021-4026.

Research output: Contribution to journalArticle

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N2 - Two conformationally defined analogues of phenylethanolamine, 8-amino-6,7,8,9-tetrahydro-5,8-methano-5H-benzocyclohepten-endo-9-ol (5) and 8-amino-6,7,8,9-tetrahydro-5,8-methano-5H-benzocyclohepten-exo-9-ol (6), have been synthesized. The benzobicyclo[3.2.1]octane skeleton was constructed by an intramolecular cyclization of 3-phenylcyclopentane-1,1-dicarboxylic acid (10). The sodium borohydride reduction of 8-amino-9-oxo-6,7,8,9-tetrahydro-5,8-methano-5H-benzocycloheptene (12) gave the endo alcohol 5. The greater stability of the exo alcohol 6 compared to 5 was confirmed by AM1 calculations. The exo alcohol 6 was obtained from 5 by an N to O acetyl migration. A possible mechanism for this migration in the inversion of the stereochemistry at C-9 is discussed. Structural assignments using 2-D NMR spectra and an NOE difference spectrum are presented.

AB - Two conformationally defined analogues of phenylethanolamine, 8-amino-6,7,8,9-tetrahydro-5,8-methano-5H-benzocyclohepten-endo-9-ol (5) and 8-amino-6,7,8,9-tetrahydro-5,8-methano-5H-benzocyclohepten-exo-9-ol (6), have been synthesized. The benzobicyclo[3.2.1]octane skeleton was constructed by an intramolecular cyclization of 3-phenylcyclopentane-1,1-dicarboxylic acid (10). The sodium borohydride reduction of 8-amino-9-oxo-6,7,8,9-tetrahydro-5,8-methano-5H-benzocycloheptene (12) gave the endo alcohol 5. The greater stability of the exo alcohol 6 compared to 5 was confirmed by AM1 calculations. The exo alcohol 6 was obtained from 5 by an N to O acetyl migration. A possible mechanism for this migration in the inversion of the stereochemistry at C-9 is discussed. Structural assignments using 2-D NMR spectra and an NOE difference spectrum are presented.

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