Solvent- and catalyst-dependent palladium-catalyzed switchable chemodivergent cascade cyclizations of trimethylenemethanes with ortho-formyl cinnamates

Abstract

Chemodivergent synthetic methodologies enable the efficient generation of structural diversity via simple transformations. Here we develop the palladium-catalyzed chemodivergent cascade cyclization of trimethylenemethane (TMM) with dielectrophilic ortho-formyl cinnamates by effectively regulating solvents and H-bond donor (HBD) co-catalysts. Hexahydrocyclopenta[a]inden-8-ols are obtained through a CC-selective [3 + 2] cycloaddition/aldol process catalyzed by Pd(PPh₃)₄ in DME, whereas aryl-substituted cyclopentenes are exclusively afforded by tuning the substituents of dielectrophiles. Furthermore, a CO-selective [3 + 2]/Michael process affords tetrahydro-2H-indeno[1,2-b]furan architectures enabled by palladium/urea cooperative catalysis.