Synthesis of Furans, Pyrroles and Thiophenes Using Ynolate Building Blocks

Significance

Reported here is a synthetic protocol for the preparation of multisubstituted furans, pyrroles and thiophenes using a reaction of α-acyl­oxy-, α-acylamino-, and α-acylthioketones respectively with ynolates as ketene anion equivalents. An interesting pathway for the formation of C2-C3 and C3-C4 bonds via formal [4+1] annulation which involves cycloaddition, cyclization, decarboxylation, and dehydration is proposed. For furans and thiophenes, the initial cyclo­addition-cyclization steps were best effected at -78 °C and the intermediate bicyclic compound of type A was isolated; its treatment with TsOH afforded the tetrasubstituted heterocyclic products. For acid-sensitive products (e.g., X = S; R¹ = Me; R² = Ph; 2-thienyl; R³ = Me; R⁴ = (E)-styryl, Ph), the decarboxylation was carried out with or without heating in the absence of acid. In contrast, for pyrroles the initial steps were carried out at -20 °C and treatment with acid was not necessary to produce the final product pyrroles. The scope of the reaction was well explored.