A Radical Reaction for the Synthesis of 3‐Substituted Dihydrothiopyrans under Photosensitized Conditions

Abstract

We report the synthesis of thiopyran derivatives under photosensitized conditions. This method is of interest for its reactionm echanism andi sanovel synthetic route to heterocycles.Cyclic ether moietiesa re often found not only in sugars but also in av ariety of bioactive compounds. [1] Studies on compoundsw ith tetrahydrofuran or tetrahydropyran scaffolds are generallyd eemed valuable. [2] In contrast, S-containing heterocycles are not well understood compared to O-heterocycles because cyclic sulfides are encountered much lessf requently than cyclic ethers. [3] However,r ecent reports revealed that some thiopyrans-the sulfur analogues of pyrans-exhibit unique biological activities, attracting increasing interest from researchers in the pharmaceutical industry. [4] Someu seful pharmaceutical agents possessing thiopyran scaffolds have been reported, including cephalosporins [4a] and dithiathromboxane A 2 . [4c] Furthermore,t he chemical behavior of S-containing heterocycles often differs greatlyf rom that of O-analogues. For example, in the Diels-Alder reaction, furan can be involved as a diene substrate under mild conditions; [5] harsh conditions of high temperature and high pressure are required for thiophene because of its aromaticity. [6] These results show that Sanalogues of useful cyclic ethers can presentu nexpected and interesting properties.Severala pproaches can be used for the synthesis of S-containing heterocycles, including thia-Prins cyclization, [7] Michael/ aldol reaction, [8] thionium-ene cyclization reaction, [9] oxidative CÀHb ond functionalization, [10] and so forth. [11] In this context, an ovel approach was proposed using radical reactions because it is well known that radicalr eactions show different reactivity and selectivity compared with ordinary ionic reactions. [12] Accordingly,wef ocused on the radical reaction to synthesize dihydrothiophenes or dihydrothiopyrans reported by Journet'sg roup around 20 years ago (Scheme 1). [13] Their Scheme1.Synthesis of S-containing heterocycles using the double radical addition-b-cleavage process.EWG = electron-withdrawing group; AIBN = 2,2'-azobis(2-methylpropionitrile).