Diastereoselective Construction of Tetrahydro-Dispiro[indolinone-3,2'-pyran-5',4?-pyrazolone] Scaffolds via an Oxa-Michael Cascade [4+2] Annulation Reaction

A straightforward metal-free oxa-Michael cascade [4 + 2] annulation reaction was established between isatin-derived Morita-Baylis-Hillman (Is-MBH) alcohols with alkylidene pyrazolones to access structural diverse tetrahydro-dispiro[indolinone-3,2 ' -pyran-5 ',4 '' -pyrazolone] scaffolds bearing two tertiary and two quaternary stereocenters. The Is-MBH alcohol was utilized as an oxa-Michael donor for the first time as a new approach in highly atom-economical transformations. This method offered a wide range of bioinspired novel tetrahydro-dispirooxindole-pyran-pyrazolone derivatives in excellent yields (up to 96%) and diastereoselectivities (up to > 20:1) in a shorter reaction time (15 min).

Automated summary

A metal-free oxa-Michael cascade reaction was developed for the synthesis of structurally diverse tetrahydro-dispiro[indolinone-3,2'-pyran-5',4''-pyrazolone] compounds with two tertiary and two quaternary stereocenters. The use of isatin-derived Morita-Baylis-Hillman alcohols as oxa-Michael donors provided a new and efficient approach for atom-economical transformations. The reaction exhibited excellent yields (up to 96%) and diastereoselectivities (up to > 20:1) within a shorter reaction time (15 min).