490025-33-7Relevant academic research and scientific papers
Inter- and intramolecular stereoselective protonation of enols
Zimmerman, Howard E.,Wang, Pengfei
, p. 9216 - 9226 (2007/10/03)
Kinetic control of the stereoselectivity of protonation of enolates and other delocalized species commonly affords the less stable diastereomer as a consequence of the considerable exothermicity and resulting sp2 transition-state hybridization of the α-carbon. Protonation then is from the less hindered face of the enolate. The present study is aimed at reversing this phenomenon by intramolecular delivery of the proton. The approach employed required the synthesis of two enolate precursors, one with a 2-pyridyl group strategically close to the α-carbon and the other with a phenyl group in the same location. The synthesis required 15 steps and involved new methodology. Intramolecular proton transfer, reversing the usual stereoselectivity, was successful. The selectivity proved to depend on several factors including the exo versus endo configuration of the diastereomer reacting, the proton donor employed, and the concentration of the proton donor. A kinetic analysis permitted the determination of the relative reaction orders of the protonation on the two faces of the enolate.
