Cooperative Tertiary Amine/Palladium-Catalyzed Sequential [4+3] Cyclization/[1,3]-Rearrangement for Stereoselective Synthesis of Spiro [Methylenecyclopentane-1,3′-oxindolines]

A cooperative tertiary amine/palladium-catalyzed sequential reaction process, proceeding via a [4 + 3] cyclization of isatin-derived Morita-Baylis-Hillman Expansion (MBH) carbonates and tert-butyl 2-(hydroxymethyl)allyl carbonates followed by a [1,3]-rearrangement, has been found and developed. A range of structurally diverse spiro[methylene cyclopentane-1,3 '-oxindo-lines] bearing two adjacent beta,gamma-acyl quaternary carbon stereo-centers, which are difficult to obtain by conventional strategies, were obtained in good yields. Further synthetic utility of this protocol is highlighted by its excellent regio-and stereocontrol as well as the large-scale synthesis and diverse functional transformations of the synthetic compounds. Moreover, the control experiments probably established the plausible mechanism for this sequential [4 + 3] cyclization/[1,3]-rearrangement process.

Automated summary

A cooperative tertiary amine/palladium-catalyzed sequential reaction process has been developed for the synthesis of spiro[methylene cyclopentane-1,3 '-oxindo-lines]. This process involves a [4 + 3] cyclization of isatin-derived Morita-Baylis-Hillman Expansion (MBH) carbonates and tert-butyl 2-(hydroxymethyl)allyl carbonates, followed by a [1,3]-rearrangement. The synthetic compounds obtained exhibit excellent regio- and stereocontrol, and this protocol has potential for large-scale synthesis and diverse functional transformations.