l-Proline-Catalyzed Three-Component Reaction of 4-Chloro-3-formylcoumarin, Sodium Sulfide, and α-Halo Ketones: A Direct Approach to Thieno[3,2-c]coumarins

Abstract

A new protocol for the synthesis of thieno[3,2-c]coumarins is disclosed herein. Following this method, 3-formyl-2-oxo-2H-chromene-4-thiolate is in-situ generated by the combination of 4-chloro-3-formylcoumarin and sodium sulfide. This chromene-4-thiolate undergoes L-proline catalyzed substitution/Knoevenagel cascade with α-haloketone to afford the desired thieno coumarins in moderate to good isolated yields. The described protocol eliminates the need for stoichiometric amounts of inorganic bases and the use of foul smelling thiols. The reaction conditions tolerate a variety of α-haloketone.

Three-Component Reaction between 3-Acetylcoumarins, Amines, and Elemental Sulfur: A Designed Approach to 3-Amino-4H-thieno[3,2-c]coumarins

“…reported an efficient strategy for the synthesis of functionalized thieno­[3,2- c ]­coumarins via a base-mediated reaction of chalcones, 4-hydroxy coumarin, and elemental sulfur . The l -proline-catalyzed reaction of 4-chloro-3-formylcoumarin, sodium sulfide, and α-halo ketones for the synthesis of thienocoumarins was illustrated by Shkoor et al . Iaroshenko et al described an approach to thienocoumarins through the base-mediated reaction of 4-chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)­coumarins with alkyl thioglycolates …”