Three-Component 1,3-Difunctionalization of Carbonyl Ylides with Water and Azadienes for the Synthesis of Dihydroisobenzofurans

Multicomponent reactions are an efficient and widely employed synthetic strategy, known for their capability to rapidly and effectively construct complex molecular architectures from multiple starting materials. This work presents a chemo- and diastereoselective three-component reaction for the 1,3-difunctionalization of transient carbonyl ylides with H2O and azadienes, facilitated by the synergistic catalysis of Rh2(OAc)4 and phosphoric acid. This strategy provides an efficient protocol for the synthesis of highly functionalized dihydroisobenzofurans in high yields (up to 94%) and good diastereoselectivities (up to 91:9 dr). Additionally, subsequent transformations with nucleophiles enable the synthesis of structurally diverse compounds with enhanced diastereoselectivities (dr >95:5).