Novel syn intramolecular pathway in base-catalyzed 1,2-elimination reactions of beta-acetoxy esters.
As part of a comprehensive investigation of electronic effects on the stereochemistry of base-catalyzed 1,2-elimination reactions, we observed a new syn intramolecular pathway in the elimination of acetic acid from beta-acetoxy esters and thioesters. 1H and 2H NMR investigation of reactions using stereospecifically labeled tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2-butanoate (1) and its (2R*,3S*) diastereomer (2) shows that 23 +/- 2% syn elimination occurs. The elimination reactions were catalyzed with KOH or (CH3)4NOH in ethanol/water under rigorously non-ion-pairing conditions. By contrast, the more sterically hindered beta-trimethylacetoxy ester produces only 6 +/- 1% syn elimination. These data strongly support an intramolecular (Ei) syn path for elimination of acetic acid, most likely through the oxyanion produced by nucleophilic attack at the carbonyl carbon of the beta-acetoxy group. The analogous thioesters, S-tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2-butanethioate (3) and its (2R*,3S*) diastereomer (4), showed 18 +/- 2% syn elimination, whereas the beta-trimethylacetoxy substrate gave 5 +/- 1% syn elimination. The more acidic thioester substrates do not produce an increased amount of syn stereoselectivity even though their elimination reactions are at the E1cb interface.
Mohrig
Jerry R
JR
Department of Chemistry, Carleton College, Northfield, Minnesota 55057, USA. jmohrig@carleton.edu
Carlson
Hans K
HK
Coughlin
Jane M
JM
Hofmeister
Gretchen E
GE
McMartin
Lea A
LA
Rowley
Elizabeth G
EG
Trimmer
Elizabeth E
EE
Wild
Andrew J
AJ
Schultz
Steve C
SC
D019342:Acetic Acid / Q000737:chemistry; D000468:Alkalies / Q000737:chemistry*; D002087:Butyrates / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D012997:Solvents / Q000737:chemistry; D013194:Staining and Labeling; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013696:Temperature
D000468:Alkalies; D002087:Butyrates; D004952:Esters; C518688:S-tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2-butanethioate; D012997:Solvents; D013438:Sulfhydryl Compounds; C518687:tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2-butanoate; D019342:Acetic Acid