Book chapter
Radical additions to chiral hydrazones: stereoselectivity and functional group compatibility
Radicals in Synthesis III, Vol.320, pp.61-91
Topics in Current Chemistry, 320
2012
DOI: 10.1007/128_2011_163
PMID: 21842359
Abstract
Free radical additions to imino compounds offer increased synthetic accessibility of chiral amines, but lack of general methods for stereocontrol has hindered their development. This review focuses on two asymmetric amine synthesis strategies designed to address this problem, with emphasis on addition of functionalized radicals which may facilitate applications to synthesis of complex targets. First, chiral N-acylhydrazones are acceptors for intermolecular radical additions of a wide range of primary, secondary, and tertiary alkyl halides to the C=N bond, with radicals generated under manganese-, tin-, or boron-mediated conditions. A variety of aldehydes and ketones serve as viable precursors for the chiral hydrazones, and the highly stereoselective reactions tolerate electrophilic functionality in both coupling components. Second, radical precursors may be linked to chiral α-hydroxyhydrazones via a silicon tether to the hydroxyl group; conformational constraints impart stereocontrol during 5-exo radical cyclization under stannyl- or thiyl-mediated conditions. The silicon tether may later be removed to reveal the formal adducts of hydroxymethyl, vinyl, acetyl, and 2-oxoethyl radicals to the C=N bond. Methodology development and applications to biologically important targets are discussed.
Details
- Title: Subtitle
- Radical additions to chiral hydrazones: stereoselectivity and functional group compatibility
- Creators
- Gregory K Friestad - Department of Chemistry, University of Iowa, IA 52242, USA. gregory-friestad@uiowa.edu
- Resource Type
- Book chapter
- Publication Details
- Radicals in Synthesis III, Vol.320, pp.61-91
- Series
- Topics in Current Chemistry; 320
- DOI
- 10.1007/128_2011_163
- PMID
- 21842359
- eISBN
- 3642281230; 9783642281235
- ISSN
- 0340-1022
- eISSN
- 1436-5049
- Grant note
- R01-GM67187 / NIGMS NIH HHS
- Language
- English
- Date published
- 2012
- Academic Unit
- Chemistry
- Record Identifier
- 9984216716202771
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