α‐Keto Thioesters as Building Blocks for Accessing γ‐Hydroxybutenolides and Oxazoles

Abstract

Abstractα‐Keto thioesters, with two electrophilic carbon centres, have been found to react differently with β‐keto esters and isocyanoacetates. They undergo base induced Knoevenagel‐type condensation on the keto carbonyl group with β‐keto esters, followed by intramolecular cyclization and water addition leads to highly substituted γ‐hydroxybutenolides. On the other hand, substituted oxazole derivatives have been obtained using isocyanoacetates via nucleophilic displacement on the thioester carbonyl followed by intramolecular cyclization. Further functionalization of the γ‐hydroxybutenolides is also demonstrated via a BF3.OEt2‐mediated cation‐driven nucleophilic addition of terminal alkynes to access multiply substituted butenolides.magnified image

Recent Advances in the Synthesis and Applications of α‐Ketothioesters

“…Building on their experience with cascade sequences or successive reactions of α‐ketothioesters adorned with two reactive centres, they developed two independent methodologies for the reaction of α‐ketothioesters with different active methylene compounds, such as β‐ketoesters 56 a and isocyanoacetates 56 b , as shown in Scheme 32 [61] . They found that the substrates exhibited different site selectivity in reaction with these active methylene compounds.…”

Recent Advances in the Chemistry of Isocyanides with Activated Methylene Group

“…Das and Mal employed α ‐keto thioesters 108 , with two electrophilic carbon centers, as component for nucleophilic displacement on the thioester carbonyl followed by intramolecular cyclization with isocyanoacetates 1 . [ 66 ] Substituted oxazole derivatives 109 were obtained using K 2 CO 3 as a base in DMF with the yields of 55–93 %. To determine whether α ‐keto ester could be also available substrate in this cyclization reaction, authors performed the reaction of oxo esters 110 with isocyanoacetates 1 .…”

Direct Access to 2‐Thioxooxazolidin‐4‐ones and Oxazolidine‐2,4‐diones from α‐Keto Thioesters through Thiolate Transfer

“…3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 Thiocyanate and cyanate salts have been recognized as one of the most efficient and versatile reagents for accessing diverse heterocycles. [6] In the course of our continuing efforts, [7] the reactivity of aketo thioesters with these salts was investigated. We observed that a-keto thioesters underwent nucleophilic displacement with thiocyanate/cyanate on the thioester carbonyl, followed by intermolecular thiolate addition to the carbonyl carbon, and subsequent intramolecular CÀO heterocyclization to afford 2thioxooxazolidin-4-one and oxazolidine-2,4-dione derivatives, respectively (Scheme 1c).…”