Development of a Phosphorus (III)-Mediated Asymmetric Reductive C-N and C-O Bond Forming Method
- Miller, Eric
- [University Park, Pennsylvania] : Pennsylvania State University, 2016.
- Physical Description:
- 1 electronic document
- Additional Creators:
- Radosevich, Alexander Thomas
- Restrictions on Access:
- Open Access.
- Synthetic methods leading to the formation of carbonyl derivatives with [alpha]- heterofunctionality are valuable for the synthesis of important molecular targets. The research described in this thesis details the development of a new nonmetal approach to the preparation of [alpha]-heterofunctionalized carbonyl derivatives from readily available and bench-stable precursors. Specifically, the method involves the direct reductive coupling of diverse [alpha]-ketoesters with a range of protic pro-heteronucleophiles (i.e. O-H, N-H, and S-H derivatives) under the action of tris(dimethylamino)phosphorus to yield the corresponding [alpha]-alkoxy, -amino-, and -thio esters. More than thirty assorted examples of this reaction demonstrate the broad scope of reactivity. Mechanistically, the reductive coupling is believed to be initiated by a formal [4+1] cycloaddition of the trivalent phosphorus compound with the [alpha]-dicarbonyl substrate to give a 10-P-5 dioxaphospholene intermediate (i.e. a Ramirez reaction). Subsequent decomposition of this pentacoordinate intermediate via protonolysis and displacement by the heteronucleophile then yields the target product with concomitant formation of water-soluble hexamethylphosphoramide as the sole by-product. By employing a stereochemically defined phosphorus triamide, a stereoselective reaction sequence yields optically active [alpha]-heterofunctionalized carbonyl derivatives with enantiomeric excesses approaching 98% ee. In short, the method described serves as a mild and selective route for the preparation of [alpha]- heterofunctionalized carbonyl derivatives, representing a useful complement to known protocols.
- Dissertation Note:
- M.S. Pennsylvania State University 2016.
- Reproduction Note:
- Library holds archival microfiches negative and service copy. 3 fiches. (Micrographics International, 2016)
- Technical Details:
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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