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

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 pi-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 pi-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 pi-facial selectivity control. DFT computational methods are able to correctly predict the reactivity, regioselectivity, and pi-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.

Origins of Stereoselectivity in Diels−Alder Cycloadditions Catalyzed by Chiral Imidazolidinones

“…Increasing solvent polarity weakens these CH···O interactions. 33,34 Single point calculations performed with the CPCM solvation model gave an endo:exo ratio of 1:2.4 in benzene for the reaction of 7 with cyclopentadiene at 0 °C, that is, the exo preference decreases with respect to the same reaction in the gas phase. In water, a selectivity reversal occurs, and the calculated endo:exo ratio is 1.2:1.…”

Electrophilicity Index

“…The main classes of reactions for which the mechanisms have been analyzed in terms of global and local electrophilicities comprise 1,3-dipolar cycloaddition reactions, − specific cycloaddition reactions such as Diels−Alder reactions ,− with varied diene−dienophile pairs, and other cycloaddition reactions. − A typical Diels−Alder reaction will follow a nonpolar pericyclic mechanism if the electrophilicity difference between the diene and the dienophile is small whereas a polar mechanism will be followed for a large value of this difference.…”

“…Polar regioselective reactions between nitrile/azomethine ylide and methyl acrylate/propiolate have been properly accounted for by the relative global and local electrophilicities between dipoles and dipolarophiles . The regio- and stereoselectivity of various 1,3-dipolar cycloaddition reactions, such as that between hindered thiocarbonyl ylides and tetracyanoethylene, nitrile oxide and anthracene/acridine, C -(methoxy carbonyl)- N -methyl nitrone and methyl acrylate/vinyl acelate, 5-ethoxy-3-p-(S)-tolylsulfinyl furan-2(5H)-ones and diazoalkanes, etc., have been shown to be in conformity with those predicted by the relative electrophilicity patterns. This approach is found to be more reliable 279 than the frontier molecular orbital theory.…”

m-CPBA/KOH: An Efficient Reagent for Nucleophilic Epoxidation of gem-Deactivated Olefins

“…In the course of our research on 1,3-dipolar reactions of diazoalkanes with activated vinylsulfoxides, we were interested in the synthesis of cyclopropanes by thermal extrusion of nitrogen from pyrazolines. In refluxing toluene, sulfinylpyrazolines 1 evolved into olefins instead of cyclopropanes, but other sulfonylpyrazolines could be transformed into cyclopropanes despite the fact that their corresponding sulfinyl derivatives only evolved into complex mixtures.…”