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. (2)H NMR data show that these reactions using KOH in EtOH/H(2)O under non-ion-pairing conditions produce a minimum of 85-89% anti elimination on stereospecifically labeled tert-butyl (2R*,3R*)- and (2R*,3S*)-3-(3-trifluoromethylphenoxy)-2,3-(2)H(2)-butanoate, S-tert-butyl (2R*,3R*)- and (2R*,3S*)-3-(3-trifluoromethylphenoxy)-2,3-(2)H(2)-butanethioate, and the related ketones, (4R*,5R*)- and (4R*,5S*)-5-(3-trifluoromethylphenoxy)-4,5-(2)H(2)-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(2)O, with β-tosyloxy, acetoxy, and 3-trifluoromethylphenoxy nucleofuges.
Department of Chemistry, Carleton College, Northfield, Minnesota 55057, USA. jmohrig@carleton.edu
Jerry R
JR
Mohrig
Brandon G
BG
Beyer
Angela S
AS
Fleischhacker
Alex J
AJ
Ruthenburg
Seth G
SG
John
Daniel A
DA
Snyder
Paul T
PT
Nyffeler
Robert J
RJ
Noll
Nicholas D
ND
Penner
Laura A
LA
Phillips
Heidi L S
HL
Hurley
Jon S
JS
Jacobs
Corinna
C
Treitel
Thomas L
TL
James
Martha P
MP
Montgomery
D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000737:chemistry*; D011522:Protons; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014105:Tosyl Compounds / Q000737:chemistry*
D004952:Esters; D007659:Ketones; D010647:Phenyl Ethers; D011522:Protons; D013438:Sulfhydryl Compounds; D014105:Tosyl Compounds