Journal article
Preparation of alpha-phosphono lactams via electrophilic phosphorus reagents: an application in the synthesis of lactam-based farnesyl transferase Inhibitors
Journal of organic chemistry, Vol.67(16), pp.5709-5717
08/09/2002
DOI: 10.1021/jo020119l
PMID: 12153273
Abstract
Conversion of N-alkyl lactams to the corresponding alpha-phosphono lactams has been investigated through procedures that involve formation of the lactam enolate and reaction with a phosphorus electrophile. With N-octylpyrrolidinone, the enolate could be trapped efficiently on oxygen by reaction with diethyl phosphorochloridate, and the resulting vinyl phosphate rearranges smoothly to the desired phosphonate upon treatment with additional LDA. Attempts to apply the same protocol to N-farnesyl lactams met with limited success. Studies with an isolated alpha-phosphono N-farnesyl lactam have shown that the farnesyl group is not stable to the excess of strong base required for rearrangement of a vinyl phosphate. However, a series of N-farnesyl lactams and imides was converted to the desired phosphonates through formation of the lactam enolate, reaction with diethyl phosphorochloridite, and subsequent oxidation of the phosphorus intermediate to the P(V) state.
Details
- Title: Subtitle
- Preparation of alpha-phosphono lactams via electrophilic phosphorus reagents: an application in the synthesis of lactam-based farnesyl transferase Inhibitors
- Creators
- Yanming Du - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USADavid F Wiemer
- Resource Type
- Journal article
- Publication Details
- Journal of organic chemistry, Vol.67(16), pp.5709-5717
- DOI
- 10.1021/jo020119l
- PMID
- 12153273
- NLM abbreviation
- J Org Chem
- ISSN
- 0022-3263
- eISSN
- 1520-6904
- Publisher
- United States
- Language
- English
- Date published
- 08/09/2002
- Academic Unit
- Neuroscience and Pharmacology; Chemistry
- Record Identifier
- 9983985888602771
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