Facile, Novel Methodology for the Synthesis of Spiro[pyrrolidin-3,3′-oxindoles]: Catalyzed Ring Expansion Reactions of Cyclopropanes by Aldimines

Abstract

The role of the bifunctional catalyst is decisive: The magnesium ion as Lewis acid and its nucleophilic iodide counterion contribute in synergy to the successful ring expansion of the cyclopropane 1 by aldimine 2 [Eq. (1)]. This reaction offers a novel route to spiro[pyrrolidin‐3,3′‐oxindoles] 3.

Cyclization and annulation reactions of nitrogen-substituted cyclopropanes and cyclobutanes

“…33 The reaction worked well for aromatic ketones (products 103-105), a class of substrates which has been challenging in annulation reactions with other DA cyclopropanes. 28 The formation of the diastereoisomer with the largest substituent of the ketone in cis position to the phthalimide was favoured. Tetrahydrofurylamines 106-108 were obtained in good yield and diastereoselectivity by the reaction of aliphatic aldehydes.…”

Recent applications of isatin in the synthesis of organic compounds

“…57 The unique structural array and the highly pronounced pharmacological activity displayed by the class of spirooxindole compounds have made them attractive synthetic targets ( Figure 1). [58][59][60] Figure 1 3.1. Synthesis involving two-component reactions of isatins 3.1.1.…”

Palladium(0)-Catalyzed Benzylic C(<i>sp</i>³)–H Functionalization for the Concise Synthesis of Heterocycles and Its Applications

“…A variety of different methods have been reported for the synthesis of spirooxindoles, including an intramolecular Heck, 54) oxidative rearrangement, 55) intramolecular Mannich, 56) and ring expansion reactions. 57) We previously developed a novel method for the construction of oxindole skeletons from carbamoyl chlorides, as well as a spirooxindole synthesis that proceeded via the bismetallation of 1,3-dienes. [58][59][60][61] Furthermore, this method was subsequently applied to a formal synthesis of elacomine.…”

“…In contrast, carbamoyl chlorides 19 and 21 containing cyclobutyl and cyclopentyl groups failed to afford the desired spirooxindole products 20 and 22 under the same conditions, and gave the corresponding anilines. Given that methine C(sp 3 )-H activation was rare at the time 73,74) and a spirooxindole fused with a cyclopropane moiety could be readily converted to various other fused systems, 57) we proceeded to investigate the cyclization of carbamoyl chlorides with cyclopropyl groups.…”