title: Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery(1)(,)(2).
abstract: Four decades ago, we noted that for delocalized carbanions and enols the protonation transition state is close to sp(2) hybridized and that, as a consequence, under kinetic control protonation takes place from the less hindered approach, most often with formation of the less stable of two possible stereoisomers. The initial report was followed by an extensive series of examples. Nevertheless, a major question remained, namely whether it was possible to deliver the proton to the more hindered face of such a species using intramolecular proton transfer. To this end, silyl ether precursors to the enols of 3-benzoyl-endo-6-phenyl-exo-6-pyridylbicyclo[3.1.0]hexane and its endo-6-pyridyl-exo-6-phenyl stereoisomer were synthesized. The corresponding enols were generated with fluoride anion. The endo-phenyl enol stereoisomers, on kinetic protonation, led stereoselectively to the endo-3-benzoyl product resulting from the less hindered protonation. In stark contrast, the endo-6-pyridyl enol isomer led stereoselectively to the exo-3-benzoyl ketone by intramolecular proton delivery. However, the kinetic orders of the stereochemistries differ; the intramolecular process requires additional proton donor molecules. The log of the ratio of the two stereochemistries is linear with the log of the proton donor concentration with the slope giving the difference in kinetic orders. An aromatic cyclic 14 electron Hückel transition state is proposed. Additionally, the roles of acyl, nitro and cyano delocalizing groups were analyzed with ab initio computations.
authors.affiliation: Chemistry Department, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Howard E.
authors.initials: HE
authors.lastname: Zimmerman
authors.forename: Alexey
authors.initials: A
authors.lastname: Ignatchenko