DBU-Promoted Three-Component Cascade Annulations to Access Multiply Substituted 3-Cyano-thiophenes

Metal-free [2+2+1] three-component cascade annulations for the one-pot synthesis of multiply substituted 3-cyano-thiophenes from 3-oxo-nitriles, enones and elemental sulfur are described. This DBU-promoted protocol features good functional group tolerance, and provides high value 3-cyano-thiophenes in moderate to good yields under simple reaction conditions. This approach also enables late-stage modifications of structurally complex bioactive molecules and drugs, which exhibits potential applications in medicinal chemistry.

Automated summary

The metal-free [2+2+1] three-component cascade annulations described in this study allow for the efficient synthesis of multiply substituted 3-cyano-thiophenes with good functional group tolerance and simple reaction conditions, showing potential applications in medicinal chemistry through late-stage modifications of structurally complex bioactive molecules and drugs.