Regio- and stereoselective formation of 1,3-Oxathiolanes by reactions of thiocarbonyl compounds with oxiranes

Lewis acid-catalyzed reactions of oxiranes with a variety of C=S compounds yield 1,3-oxathiolanes. The ring enlargement of monosubstituted oxiranes occurs regioselectively via cleavage of the O,C(3) bond of alkyl substituted oxiranes and the O,C(2) bond of phenyl oxirane. Furthermore, the reaction proceeds with inversion of the configuration at the center of the nucleophilic attack by the S-atom. The formation of thiocarbonylium ions as intermediates is supported by Wagner–Meerwein-type rearrangements. Enolized thioketones react with oxiranes to give enesulfanyl alcohols, which undergo an acid-catalyzed cyclization to yield 1,3-oxathiolanes. DOI: https://doi.org/10.1080/10426500590912240 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-77376 Accepted Version Originally published at: Fu, Changchun; Blagoev, Milen; Linden, Anthony; Heimgartner, Heinz (2005). Regioand stereoselective formation of 1,3-Oxathiolanes by reactions of thiocarbonyl compounds with oxiranes. Phosphorus, Sulfur and Silicon and the Related Elements, 180(5-6):1309-1313. DOI: https://doi.org/10.1080/10426500590912240 REGIOAND STEREOSELECTIVE FORMATION OF 1,3-OXATHIOLANES BY REACTIONS OF THIOCARBONYL COMPOUNDS WITH OXIRANES Changchun Fu, Milen Blagoev, Anthony Linden, and Heinz Heimgartner Institute of Organic Chemistry, University of Zürich Winterthurerstrasse 190, CH-8057 Zürich, Switzerland E-mail: [email protected] Abstract Lewis acid-catalyzed reactions of oxiranes with a variety of C=S compounds yield 1,3oxathiolanes. The ring enlargement of monosubstituted oxiranes occurs regioselectively via cleavage of the O,C(3) bond of alkyl substituted oxiranes and the O,C(2) bond of phenyl oxirane. Furthermore, the reaction proceeds with inversion of the configuration at the center of the nucleophilic attack by the S-atom. The formation of thiocarbonylium ions as intermediates is supported by Wagner-Meerwein type rearrangements. Enolized thioketones react with oxiranes to give enesulfanyl alcohols, which undergo an acid-catalyzed cyclization to yield 1,3-oxathiolanes. INTRODUCTION In general, 1,3-oxathiolanes are prepared by the reaction of carbonyl compounds with 2sulfanylalkan-1-ols. Alternatively, 1,3-dipolar cycloadditions of carbonyl ylides with C=S and thiocarbonyl ylides with C=O compounds, respectively, lead to the same heterocyclic system (cf. refs. cited in [1]). Some years ago, we discovered that the Lewis acid-catalyzed reaction of oxiranes with 4,4-disubstituted 1,3-thiazole-5(4H)-thiones and trithiocarbonates, respectively, offers another convenient access to 1,3-oxathiolanes [1,2]. For example, 1,3dithiolane-2-thione (1) and 2-ethyloxirane (2a) in 1,2-dichloroethane and TiCl4 at –20°C gave the spirocyclic 1,3-oxathiolanes 3a and 4a (R = Et) in a ratio of 15:1 (Scheme 1). On the other hand, the ratio 3b/4b (R = Ph) was determined to be 1:20 [2]. Scheme 1Lewis acid-catalyzed reactions of oxiranes with a variety of C=S compounds yield 1,3oxathiolanes. The ring enlargement of monosubstituted oxiranes occurs regioselectively via cleavage of the O,C(3) bond of alkyl substituted oxiranes and the O,C(2) bond of phenyl oxirane. Furthermore, the reaction proceeds with inversion of the configuration at the center of the nucleophilic attack by the S-atom. The formation of thiocarbonylium ions as intermediates is supported by Wagner-Meerwein type rearrangements. Enolized thioketones react with oxiranes to give enesulfanyl alcohols, which undergo an acid-catalyzed cyclization to yield 1,3-oxathiolanes. INTRODUCTION In general, 1,3-oxathiolanes are prepared by the reaction of carbonyl compounds with 2sulfanylalkan-1-ols. Alternatively, 1,3-dipolar cycloadditions of carbonyl ylides with C=S and thiocarbonyl ylides with C=O compounds, respectively, lead to the same heterocyclic system (cf. refs. cited in [1]). Some years ago, we discovered that the Lewis acid-catalyzed reaction of oxiranes with 4,4-disubstituted 1,3-thiazole-5(4H)-thiones and trithiocarbonates, respectively, offers another convenient access to 1,3-oxathiolanes [1,2]. For example, 1,3dithiolane-2-thione (1) and 2-ethyloxirane (2a) in 1,2-dichloroethane and TiCl4 at –20°C gave the spirocyclic 1,3-oxathiolanes 3a and 4a (R = Et) in a ratio of 15:1 (Scheme 1). On the other hand, the ratio 3b/4b (R = Ph) was determined to be 1:20 [2]. Scheme 1 RESULTS Treatment of a mixture of a 1,3-thiazole-5(4H)-thione 5 and 1,2-epoxycyclopentane (6) in dichloroethane at –78°C with BF3⋅Et2O gives the two diastereoisomeric 1,3-oxathiolanes 7 and 8 in 74-84% yield (ratio ca. 3:1) [3] (Scheme 2). Another efficient catalyst is SnCl4. Both isomers show a trans-fusion of the cyclopentane and 1,3-oxathiolane ring. Analogous results are obtained with 1,2-epoxycyclohexane [3] and cisand trans-2,3-dimethyloxirane [4]. Obviously, the opening of the oxirane ring occurs by nucleophilic attack of the S-atom under S S S O R +