A systematic investigation of quaternary ammonium ions as asymmetric phase-transfer catalysts. Synthesis of catalyst libraries and evaluation of catalyst activity

Scott E. Denmark, Nathan D. Gould, Larry M. Wolf

Research output: Contribution to journalArticle

Abstract

Despite over three decades of research into asymmetric phase-transfer catalysis (APTC), a fundamental understanding of the factors that affect the rate and stereoselectivity of this important process are still obscure. This paper describes the initial stages of a long-term program aimed at elucidating the physical organic foundations of APTC employing a chemoinformatic analysis of the alkylation of a protected glycine imine with libraries of enantiomerically enriched quaternary ammonium ions. The synthesis of the quaternary ammonium ions follows a diversity-oriented approach wherein the tandem inter[4 + 2]/intra[3 + 2] cycloaddition of nitroalkenes serves as the key transformation. A two-part synthetic strategy comprised of (1) preparation of enantioenriched scaffolds and (2) development of parallel synthesis procedures is described. The strategy allows for the facile introduction of four variable groups in the vicinity of a stereogenic quaternary ammonium ion. The quaternary ammonium ions exhibited a wide range of activity and to a lesser degree enantioselectivity. Catalyst activity and selectivity are rationalized in a qualitative way on the basis of the effective positive potential of the ammonium ion.

Original languageEnglish (US)
Pages (from-to)4260-4336
Number of pages77
JournalJournal of Organic Chemistry
Volume76
Issue number11
DOIs
StatePublished - Jun 3 2011

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Ammonium Compounds
Catalyst activity
Ions
Catalysts
Catalysis
Stereoselectivity
Imines
Cycloaddition
Catalyst selectivity
Enantioselectivity
Alkylation
Scaffolds
Glycine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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abstract = "Despite over three decades of research into asymmetric phase-transfer catalysis (APTC), a fundamental understanding of the factors that affect the rate and stereoselectivity of this important process are still obscure. This paper describes the initial stages of a long-term program aimed at elucidating the physical organic foundations of APTC employing a chemoinformatic analysis of the alkylation of a protected glycine imine with libraries of enantiomerically enriched quaternary ammonium ions. The synthesis of the quaternary ammonium ions follows a diversity-oriented approach wherein the tandem inter[4 + 2]/intra[3 + 2] cycloaddition of nitroalkenes serves as the key transformation. A two-part synthetic strategy comprised of (1) preparation of enantioenriched scaffolds and (2) development of parallel synthesis procedures is described. The strategy allows for the facile introduction of four variable groups in the vicinity of a stereogenic quaternary ammonium ion. The quaternary ammonium ions exhibited a wide range of activity and to a lesser degree enantioselectivity. Catalyst activity and selectivity are rationalized in a qualitative way on the basis of the effective positive potential of the ammonium ion.",
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