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

Abstract

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′-oxindolines] bearing two adjacent β,γ-acyl quaternary carbon stereocenters, 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.

Pd-catalyzed oxa-[4 + n] dipolar cycloaddition using 1,4-O/C dipole synthons for the synthesis of O-heterocycles

“…Later, the sequential process of oxa-[4 + 3] dipolar cycloaddition of an oxa-1,4-dipole with the same substrates 55 and [1,3]-rearrangement to furnish spiro[methylene cyclopentane-1,3′-oxindolines] 57 was reported by the Chen and Cui group in 2023 (Scheme 17B). 32 During the initial investigation, the spiro-methylene cyclopentane scaffold 57 was unexpectedly obtained as a major product when the reaction was performed at 50 °C in CH 2 Cl 2 using a cooperative DABCO/Pd catalytic system. After an extensive screening of the Lewis base, ligand, and Pd catalyst, the optimal reaction conditions for the regio- and diastereoselective formation of rearrangement product 57 were found to be Pd(PPh 3 ) 4 and DMAP in CH 2 Cl 2 at 40 °C.…”

Recent Advances in Nucleophilic Lewis Base‐Catalyzed Cycloadditions for Synthesis of Spirooxindoles

“…[28] More recently, Cui, Chen and coworkers developed a cooperative tertiary amine/palladium-catalysis system, realizing a sequential [4 + 3] cyclization/[1,3]-rearrangement reaction of isatin-derived Morita-Baylis-Hillman Expansion (MBH) carbonates and tert-butyl 2-(hydroxymethyl)allyl carbonates. [29] The authors proposed a possible mechanism as outlined in Scheme 16. Initially, the intermediate 57 was generated by a DMAP-catalyzed addition-elimination process, which was then transformed to an active 1,3-allylic ylide species (58) via a deprotonation process.…”