Regiospecific metallation of furyl-4,5-dihydrooxazoles: preparation of 2,5-disubstituted and 2,3,5-trisubstituted furans

Abstract

Regiospecific metallation at C-5 of 2-(2-furyl)-4,4-dimethyl-4,5-dihydrooxazole 1 has been carried out using butyllithium in tetrahydrofuran (THF) and hexamethylphosphoramide (HMPA) as co-solvent. Reaction of the metallated species 1a with various electrophiles allowed us to prepare the disubstituted furans 3–13. The metallation of (5-alkyl- or 5-trialkylsilyl-2-furyl)-4,5-dihydrooxazoles 3, 4, 8, 9 or 10 with butyllithium in THF led to regiospecific metallation at C-3 and reaction with electrophiles provided the expected trisubstituted furans. C-3 Lithiation of (5-trialkylsilyl-2-furyl)-4,5-dihydrooxazoles 3 and 4 is a potential route to 2,3-disubstituted furans. All these reactions took place with generally good yields.