Acid-Induced Rearrangement Reactions of α-Hydroxy-1,3-dithianes

Abstract

A c i d -I n d u c e d R e a r r a n g e m e n t o f a -H y d r o x y -1 , 3 -d i t h i a n e s Abstract: Secondary benzylic or aliphatic a-hydroxydithianes 1a-c rearrange to a-thioketones when treated with acid. Related tertiary alcohols 1d-g eliminate to dithioketene ketals (e.g., 2d), which are ring-opened to thiols in some cases (1e, 1f). Allylic a-hydroxydithianes 1h and 1i form the thioesters 2h and 2i (homologation), and the tertiary alcohols 1j and 1k undergo deoxygenation to 2j and 2k.Dithioacetals are useful protecting groups for carbonyl compounds due to their ease of formation and their stability under acidic and basic conditions. 1 In addition, they are also umpolung reagents that play an increasing role in natural product synthesis. 2 Recently, we have systematically reinvestigated 3 the scope and limitation of the Kuhn method for cleaving 1,3-dithianes to their parent carbonyl compounds. 4 In this procedure, the monosulfoxides of the respective 1,3-dithianes are cleaved to the carbonyl compounds by treatment with acids. It turned out that the 2-alkyl-1,3-dithianemonosulfoxides are cleaved in essentially quantitative yield under much milder conditions (20-40°C) than originally proposed by Kuhn, irrespective of steric and electronic factors in the substrates.However, a-hydroxydithianes, formed by addition of lithio-1,3-dithianes to aldehydes and ketones, are the most important intermediates in umpolung chemistry, and their cleavage under mild acidic conditions would be of great interest. It is known that a-hydroxydithianes are labile under acidic conditions and can undergo several rearrangement reactions, 5 for instance to 1,4-dithiepanes. 5bIn the course of our ongoing work on the deprotection of 1,3-dithianes, we have now investigated the reaction of some a-hydroxydithianes 1 with the discovery of a number of surprising new and mechanistically interesting rearrangement reactions of a-hydroxydithianes (Scheme 1). Scheme 1 Rearrangement of a-hydroxydithianesAll substrates 1a-k were synthesized using a modified version of the Corey and Seebach procedure. 6 The substrates and the resulting products after treatment with acid are compiled in Table 1. All reactions, carried out in acetonitrile solution under reflux with addition of aqueous 6 N HCl, were carefully monitored by TLC. The acid-catalyzed reactions of 1a-c afforded not the expected a-hydroxy carbonyl compounds, but the rearranged a-keto thiols 2a-c. To the best of our knowledge, this type of rearrangement of a-hydroxydithianes with oxidation of the hydroxy group and reduction of the dithiane is without precedent.A possible mechanism for the formation of the keto thiols is shown in Scheme 2. Thus, protonation of a sulfur atom, elimination of the b-atom from the stabilized open chain carbocation, enol formation, and tautomerization would lead to the keto thiols. 7 Scheme 2 Formation of keto thiols from a-hydroxydithianesCompounds 1d and 1g both gave elimination products. Reaction of 1d resulted in the formation of the ketene acetal 2d and cyclohe...

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