7 research outputs found
Nature and the Nazi diet
Poster for the 62nd Historia Medica lecture.https://digitalcommons.wustl.edu/historyofmedicine_historia_medica_posters/1033/thumbnail.jp
Does Activation of the Anti Proton, Rather than Concertedness, Determine the Stereochemistry of Base-Catalyzed 1,2-Elimination Reactions? Anti Stereospecificity in E1cB Eliminations of β-3-Trifluoromethylphenoxy Esters, Thioesters, and Ketones
As part of a comprehensive investigation on the stereochemical
aspects of base-catalyzed 1,2-elimination reactions, we have studied
a set of acyclic carbonyl substrates that react by an irreversible
E1cB mechanism with largely anti stereospecificity. <sup>2</sup>H
NMR data show that these reactions using KOH in EtOH/H<sub>2</sub>O under non-ion-pairing conditions produce a minimum of 85–89%
anti elimination on stereospecifically labeled <i>tert</i>-butyl (2<i>R</i>*,3<i>R</i>*)- and (2<i>R</i>*,3<i>S</i>*)-3-(3-trifluoromethylphenoxy)-2,3-<sup>2</sup><i>H</i><sub>2</sub>-butanoate, <i>S</i>-<i>tert</i>-butyl (2<i>R</i>*,3<i>R</i>*)- and (2<i>R</i>*,3<i>S</i>*)-3-(3-trifluoromethylphenoxy)-2,3-<sup>2</sup><i>H</i><sub>2</sub>-butanethioate, and the related
ketones, (4<i>R</i>*,5<i>R</i>*)- and (4<i>R</i>*,5<i>S</i>*)-5-(3-trifluoromethylphenoxy)-4,5-<sup>2</sup><i>H</i><sub>2</sub>-3-hexanone. With both diastereomers
of each substrate available, the KIEs can be calculated and the innate
stereoselectivities determined. The elimination reactions of the β-3-trifluoromethylphenoxy
substrates occur by E1cB mechanisms with diffusionally equilibrated
enolate-anion intermediates. Thus, it is clear that anti elimination
does not depend solely upon concerted E2 mechanisms. Negative hyperconjugation
provides a satisfactory explanation for the anti stereospecificity
exhibited by our carbonyl substrates, where the leaving group activates
the anti proton, leading to the enolate intermediate. The activation
of the anti proton by negative hyperconjugation may also play a role
in the concerted pathways of E2 mechanisms. We have also measured
the rates of the hydroxide-catalyzed elimination reactions of butanoate,
thiobutanoate, and ketone substrates in EtOH/H<sub>2</sub>O, with
β-tosyloxy, acetoxy, and 3-trifluoromethylphenoxy nucleofuges