title: Stereochemistry of 1,2-elimination reactions at the E2-E1cB interface--tert-butyl 3-tosyloxybutanoate and its thioester.
abstract: Experimental data on the stereoselectivity of base-catalyzed 1,2-elimination reactions that produce conjugated carbonyl compounds are scarce in spite of the importance of these reactions in organic and biochemistry. As part of a comprehensive study in this area, we have synthesized stereospecifically-deuterated beta-tosyloxybutanoate esters and thioesters and studied the stereoselectivity of their elimination reactions under non-ion pairing conditions. With the availability of both the (2R*,3R*) and (2R*,3S*) diastereomers the innate stereoselectivity could be determined unambiguously. (1)H and (2)H NMR data show that these substrates produce 5-6% syn elimination, the usual amount for acyclic substrates undergoing E2 reactions. Contrary to earlier suggestions, activation by a carbonyl group has virtually no influence upon the stereoselectivity. Elimination of the (2R*,3R*) diastereomer of the beta-tosyloxyester and thioester produces 21-25% of the (Z)-alkene, much more than observed with a poorer beta-nucleofuge. A relatively large amount of (Z)-alkene product seems to be a good marker for an E2 pathway, in which the transition state is E1cB-like, rather than an E1cB(irrev) mechanism. Syn KIE values were higher than those for anti elimination for the esters as well as the thioesters. Experimental challenges to the synthesis of stereospecifically-deuterated beta-tosyloxyesters are discussed.
authors.affiliation: Department of Chemistry, Carleton College, Northfield, MN 55057, USA. jmohrig@carleton.edu
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mohrig
authors.forename: David G
authors.initials: DG
authors.lastname: Alberg
authors.forename: Craig H
authors.initials: CH
authors.lastname: Cartwright
authors.forename: Mary Kay H
authors.initials: MK
authors.lastname: Pflum
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Aldrich
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Anderson
authors.forename: Shelby R
authors.initials: SR
authors.lastname: Anderson
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Fimmen
authors.forename: Amy K
authors.initials: AK
authors.lastname: Snover
mesh_terms: D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014105:Tosyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002087:Butyrates; D004952:Esters; C530276:S-tert-butyl 3-tosyloxybutanethioate; D013457:Sulfur Compounds; D014105:Tosyl Compounds; C530275:tert-butyl 3-tosyloxybutanoate