Amide enolate additions to acylsilanes: In situ generation of unusual and stereoselective homoenolate equivalents

Robert B. Lettan, Chris V. Galliford, Chase C. Woodward, Karl A. Scheidt

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The synthesis of β-hydroxy carbonyl compounds is an important goal due to their prevalence in bioactive molecules. A novel approach to construct these structural motifs involves the multicomponent reaction of acylsilanes, amides, and electrophiles. The addition of amide enolates to acylsilanes generates β-silyloxy homoenolate reactivity by undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ can then undergo addition to alkyl halides, aldehydes, ketones, and imines. The γ-amino-β-hydroxy amide products derived from the addition of these homoenolates to N-diphenylphosphinyl imines are generated with excellent diastereoselectivity (≥20:1) and can be efficiently converted to highly valuable γ-lactams. Finally, the use of optically active amide enolates delivers β-hydroxy amide products with high levels of diastereoselectivity (≥10:1).

Original languageEnglish (US)
Pages (from-to)8805-8814
Number of pages10
JournalJournal of the American Chemical Society
Volume131
Issue number25
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Amide enolate additions to acylsilanes: In situ generation of unusual and stereoselective homoenolate equivalents'. Together they form a unique fingerprint.

Cite this