Chemistry of 2H‐thiopyran and derivatives IV. Deprotonation and methylation of 2H‐thieno[2,3‐b]thiopyran and some derivatives

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AbstractMetallation of 2H‐thieno[2,3‐b]thiopyran 1 by strong bases under relatively apolar conditions proceeds exclusively in the 2‐position of the thiophene ring. In polar media a 2‐proton of the thiopyran ring is removed to give the anion 1b. By addition of hexamethylphosphoric triamide (HMPT) to the lithiated compound 1a conversion into 1b takes place. The anions 1a and 1b react with methyl iodide to give the compounds 2 and 3, respectively. Compound 2 can be further methylated by reaction with BuLi in tetrahydrofuran (THF)/HMPT mixtures or sodamide in liquid NH3, followed by addition of methyl iodide. The resulting compound 4 can be converted into the compounds 5, 6 or 7, depending on the base‐solvent system: Compound 5 is produced by interaction between 4 and KNH2 in liquid NH3 at − 33°, followed by methylation at − 60°. If the reaction with KNH2 is carried out at − 60°, however, methylation gives 6, this result is also obtained from 4, BuLi in THF/HMPT and CH3I. Omission of HMPT during the metallation gives rise to vinylic proton abstraction, and subsequent addition of CH3I leads to 7.