Catalytic asymmetric synthesis of spirocyclobutyl oxindoles and beyond <i>via</i> [2+2] cycloaddition and sequential transformations

Abstract

Efficient asymmetric synthesis of a collection of small molecules with structural diversity is highly important to drug discovery. Herein, three distinct types of chiral cyclic compounds were accessible by enantioselective catalysis and sequential transformations. Highly regio- and enantioselective [2+2] cycloaddition of (<i>E</i>)-alkenyloxindoles with the internal C[double bond, length as m-dash]C bond of <i>N-</i>allenamides was achieved with <i>N</i>,<i>N</i>'-dioxide/Ni(OTf)₂ as the catalyst. Various optically active spirocyclobutyl oxindole derivatives were obtained under mild conditions. Moreover, formal [4+2] cycloaddition products occurring at the terminal C[double bond, length as m-dash]C bond of <i>N-</i>allenamides, dihydropyran-fused indoles, were afforded by a stereospecific sequential transformation with the assistance of a catalytic amount of Cu(OTf)₂. In contrast, performing the conversion under air led to the formation of γ-lactones <i>via</i> the water-involved deprotection and rearrangement process. Experimental studies and DFT calculations were performed to probe the reaction mechanism.