The optimization on catalytic asymmetric intermolecular cyclopropanation of diazo acetocy acetone and styrene by using p-Nitro-Ru(II)-Diphenyl-pheox complex

Abstract

The chiral cyclopropane ring is an important pharmacophore in pharmaceuticals and bioactive natural products, making libraries of these building blocks a valuable resource for drug discovery and development. Furthermore, the cyclopropyl ketone groups are also found in natural products have important biochemical properties, but only a-diazoacetophenone has been developed as a ketone source, reported with 67% and 86% ee yields. Therefore, this study presents a process to synthesize chiral cyclopropane of diazo acetoxy acetone to styrene catalyzed by the asymmetric p-nitro-Ru-¬dialkyl-pheox complex. This procedure has also been optimized under suitable solvent and temperature conditions and achieved with high yields, excellent stereoisomer selectivity >99:1, and enantioselectivity up to 95%. This is the only published result of our group, demonstrating the effectiveness of this catalyst in the reaction to produce highly stereoselecitve cyclopropanes. In addition, the study also has sufficient evidence in the mechanisms of chiral cyclopropane formation with preferential Trans product.