The role of steric and electronic interactions in the stereocontrol of the asymmetric 1,3-dipolar reactions of 5-ethoxy-3-p-(S)-tolylsulfinylfuran-2(5H)-ones with diazoalkanes: Theoretical calculations and experimental evidences

José L. García Ruano, Alberto Fraile, Gemma González, M. Rosario Martín, Fernando R. Clemente, Ruth Gordillo

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45 Scopus citations

Abstract

The addition of diazomethane and diazoethane to (5S,SS)- and (5R,SS)-5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones (1a and 1b) and their 4-methylderivatives (2a and 2b) proceeded in almost quantitative yields and complete regioselectivity. The observed π-facial selectivity is determined by the configurations at both C-5 and the sulfinyl group, the later being the most important. The syn adducts were almost exclusively obtained from 1a and 2a in apolar solvents but the π-facial selectivity was strongly decreased in more polar solvents. On the other hand, the major adducts from 1b and 2b were the anti ones and such predominance was slightly increased with solvent polarity. The exo-selectivity was complete in all the cases except for the anti approach to compounds 2a (in polar solvents) and 2b. The role of the sulfinyl group in this behavior was inferred by comparison of these results with those obtained in reactions of diazoalkanes with 5-methoxyfuran-2(5H)-one (3). Steric interactions seem to be the main ones responsible for the observed exo selectivity of reactions with diazoethane, but electronic factors, which can be modulated by the solvent, are also significant in the π-facial selectivity control. DFT computational methods are able to correctly predict the reactivity, regioselectivity, and π-facial selectivity exhibited by 5-alkoxyfuranones as well as their changes with the solvent polarity. A C-H⋯O hydrogen bond, involving the oxygen atom of the 5-alkoxy group at dipolarophiles and the endo-hydrogen atom at dipoles, seems to play a key role in the electronic interactions influencing the stereochemical course of these reactions.

Original languageEnglish (US)
Pages (from-to)6522-6534
Number of pages13
JournalJournal of Organic Chemistry
Volume68
Issue number17
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Organic Chemistry

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