Highly selective catalyst- and additive-free iodosulfonylation of cyclopropenes in water

The construction of functionalized cyclopropanes is a hot topic in synthetic chemistry as they are important 3C starting materials and privileged structures in medicinal chemistry. By treating the readily available cyclopropenes with sulfonyl iodides in water, beta-iodo cyclopropyl sulfones were diastereoselectively formed via a syn-addition process in high yields. Employment of water as the sole solvent, avoidance of transition metals and air-sensitive reagents, and chromatography-free purification of the products make this transformation quite operationally convenient and environmentally benign. This method could be extended to various styrenes and alkynes, and the reactions with alkynes exhibited excellent anti-addition selectivity. It should be noted that post-modification of several natural products and drugs has been achieved, and this transformation has been successfully applied as a key step in the synthesis of a quinolinone MAT2A inhibitor and in the formal synthesis of a dipeptide renin inhibitor.

Automated summary

By reacting readily available cyclopropenes with sulfonyl iodides in water, beta-iodo cyclopropyl sulfones were selectively formed, which are important 3C starting materials with privileged structures in medicinal chemistry. This method is operationally convenient and environmentally friendly with water as the sole solvent, avoiding transition metals and air-sensitive reagents, and chromatography-free purification. It can be extended to various styrenes and alkynes, with excellent anti-addition selectivity in reactions with alkynes. Additionally, it has been successfully applied in the post-modification of natural products and drugs, as well as the synthesis of quinolinone MAT2A inhibitor and dipeptide renin inhibitor.