Yb(OTf)3 Anchored on Crosslinked Chitosan Microsphere: A Green Heterogenized Catalyst for the Synthesis of Bispiro-Fused Heterocycles

Using renewable biomass chitosan as a raw material, crosslinked chitosan microsphere (CCM) was prepared by inverse suspension, which was then immersed in the ethanol solution of Yb(OTf)₃ to fabricate CCM-supported Yb(OTf)₃ (Yb(OTf)₃@CCM). The three-component 3+2] cycloaddition of isatins, tetrahydroisoquinolines and 5-alkenyl rhodanines was developed with Yb(OTf)₃@CCM as a green heterogeneous catalyst, which gave access to a suite of architecturally complex bispiro-fused heterocycles merging four pharmacophores with moderate to excellent yields (50–96 %) and diastereoselectivities (up to 99 : 1 dr). The reaction mechanism was preliminarily clarified by controlled experiments and dynamic high-resolution mass spectrometry studies. The synthetic potential of this protocol was proved by a gram-scale reaction which furnished the product with comparable results (85 % yield and 72 : 28 dr). Moreover, the catalyst could be recovered just through filtering, washing and drying process, and reused five times with the catalytic activity remaining in an acceptable range (from 93 % to 73 % yield).