Theoretical Evaluation of Epimerization in Diels-Alder Cycloadductsla

Osman F. Guner, Koop Lammertsma, Peter V. Alston, Raphael M. Ottenbrite, Donald D. Shillady

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7 Citations (Scopus)


Four Diels-Alder reactions of trans-1,3-pentadiene (trans-piperylene) with acetone, methyl vinyl ketone, methyl acrylate, and acrylonitrile were selected for this study due to their varying epimerization rates previously reported (J. Org. Chem. 1988, 53, 5348). The reaction coordinate of the epimerization process for each reaction is evaluated for thermal and Lewis acid catalyzed conditions. The theoretical calculations are carried out by semiempirical (AM1) and ab initio (HF/STO-3G,3-21G) methods, and the computational results were found to be in agreement with the experimentally observed substituent effects on the relative rates for epimerizations. Due to the enhancement of epimerization by silica gel, the possibility of inadvertently altering the product distribution of a Diels-Alder reaction by GC and column chromatography is also discussed. The positions of equilibrium, established by acid catalysis, between diastereomeric cis- and trans-5-(phenylthio)-(7), 5-(phenylsulfinyl)- (8), 5-(phenylsulfonyl)- (9), 5-(cyclohexylthio)- (10), 5-(cyclohexylsulfinyl)- (11), and 5-(cyclohexylsulfonyl)-2-tert-butyl-1,3-dioxanes (12) are reported and compared with published data for the 5-(methylthio)- (1), 5-(methylsulfinyl)- (2), 5-(methylsulfonyl)- (3), 5-(tert-butylthio)- (4), 5-(tert-butylsulfinyl)-(5), and 5-(tert-butylsulfonyl)-2-isopropyl- 1,3-dioxanes (6). Although AG° values for sulfides 1, 4, and 7 are very similar, there exist significant differences in the conformational behavior of the sulfoxides and the sulfones, which result from the relative steric, electrostatic, and torsional effects arising from each substituent. The information at hand (XH and 13C NMR spectroscopic data, X-ray crystallographic analysis, etc.) shows that, while sulfone cis-6 has the S-ferf-butyl group outside the ring, with both sulfonyl oxygens above the dioxane ring and eclipsing the endocyclic C-C bonds, the alkyl and aryl substituents in cis-3, cis-9, and cis-12 point inside the ring. The phenylsulfonyl- inside rotamer in czs-9 leads to steric and electron/electron repulsion that overcomes the electrostatic attractive interactions between the (negative) endocyclic oxygens and the (positive) sulfur in the sulfonyl group, so that equatorial trans-9 predominates at equilibrium, AG° = -0.44 kcal/mol. All sulfoxides place both the sulfinyl oxygen and the substituent outside the dioxane ring.

Original languageEnglish
Pages (from-to)28-33
Number of pages6
JournalJournal of Organic Chemistry
Issue number1
Publication statusPublished - 1990
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry


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