Thiomaleic Anhydride: A Convenient Building Block for the Synthesis of α-Substituted γ- and δ-Lactones through Free-Radical Addition, Nucleophilic Ring Opening, and Subsequent Thiocarboxylate Manipulation

Abstract

Iodoalkyl tert-butyl carbonates and carbamates undergo clean free radical addition to thiomaleic anhydride to give substituted thiosuccinic anhydrides in high yield on treatment with tris (trimethylsilyl)silane and a radical initiator. After removal of the tert-butyloxycarbonyl group cyclization then affords lactones or lactams substituted in the α-position by a thiocarboxylic acid residue. This group is converted to amides through reaction with electron-deficient sulfonamides, or to aldehydes and/or ketones by the reaction of derived thioesters with either thiophenol, an electrondeficient allyl phenyl sulfide, or phenyl boronic acid.

Cyclic Enecarbamates as Precursors of α,β-Unsaturated Iminium Ions: Reactivity and Synthesis of 6,6-Spirocyclic Ring Systems

“…To a solution of iodide 25 (4.13 g, 15.2 mmol) in acetone (69 mL) was added K 2 CO 3 (6.32 g, 45.7 mmol, 3.0 equiv), ethyl acetoacetate (2.90 mL, 22.8 mmol, 1.5 equiv), and DMF (3.5 mL). The mixture was stirred for 48 h, before being concentrated under reduced pressure, resuspended in EtOAc (80 mL), and diluted with sat.…”

Thiols, thioethers, and related compounds as sources of C-centred radicals

“…The thiyl radical generated via b-fragmentation during the last step of the allylation process propagates the radical chain, thus allowing allylation of acyl radicals to be carried out under tin-free conditions. 229 Spagnolo and co-workers extended this approach to the generation of carbamoyl radicals. They prepared pyrrolidinones (Scheme 102) and azetidinones via 5-exo and 4-exo cyclization of N-benzylcarbamoyl radicals.…”

Total Synthesis of the Anticancer Marine Natural Product Mycalol

“…[6] This underwent oxidation under Swern conditions followed by Corey-Chaykovsky reaction [7] to give racemic epoxide 9 in a good overall yield of 75 % (Scheme 2). [10] The synthesis of alkyne 7 is shown in Scheme 3. Epoxide 10 was opened with propylmagnesium chloride in the presence of a catalytic amount of CuI to give alcohol 11a in 82 % yield.…”