Traceless Solid-Phase Preparation of Thiomorpholin-3-ones

Significance

Preparation of thiomorpholin-3-ones 10 using a traceless solid-phase approach was described. Thus, the reaction of benzyl chloride on Merrifield resin 1 with 2 gave the corresponding products 3 that were converted into N,N-disubstituted 2-nitrobenzenesulfonamides 5 under Mitsunobu conditions with 4. Compounds 5 were transformed into the key intermediates 8 by removal of the Ns group followed by acylation with chloroacetic acids 7. The key cyclization of 8 was carried out with CsI (1 equiv) in aqueous dioxane to afford thiomorpholin-3-ones 10 via cyclic sulfonium salts 9. Six-, seven-, and eight-membered products 10 were obtained in 47-74% yield with 95-100% purity.