Oxindoles spirocyclic, preparation

Beckwith and Storey have developed a tandem translocation and homolytic aromatic substitution sequence en route to spiro-oxindoles [95CC977]. Treatment of the bromoaniline derivative 122 with tin hydride at 160 °C generated the aryl radical 123 which underwent a 1,5-hydrogen atom transfer to give intermediate 124. Intramolecular homolytic aromatic substitution and aromatization gave the spiro-oxindole 125. Intramolecular aryl radical cyclization on to a pyrrole nucleus has been used to prepare spirocyclic heterocycles [95TL6743]. 

Pummerer-like cyclization reactions were utilized to prepare spirocyclic oxindole derivatives <04OL1869, 04OL2849>. For example, treatment of 2-sulfenylindole 215 with an iodonium reagent in the presence of 2,6-lutidine produced thioimidate 216. Oxidation of the latter with cerium ammonium nitrate (CAN) gave spirooxindole 217. 

The synthetic and kinetic regularities of the amino-Claisen rearrangement were studied for the transformation of 2,5-dimethyl-Af-(pent-3-en-2-yl)aniline." The products are obtained via conversion of a binary r-complex formed by the reaction of N-alkenylaniline hydrochloride with the hydrochloride of the solvent (2,5-dimethylaniline). Spirocyclic oxindoles have been prepared from iodoindoles via a sequential intramolecular Ullmann coupling and Claisen rearrangement." Nucleophilic ort/io-propargylation of aryl sulfoxides has been reported to occur by intermolecular delivery of the nucleophile to sulfur followed by an intramolecular relay to carbon in a... 

General Procedure for the Preparation Spirocyclic Compounds 59 by Rios [30] In a small flask, oxindole 58 (0.25 mmol, 1 equiv) and a,p-unsaturated aldehyde 16 (0.75 mmol, 1.5 equiv) were stirred in toluene at room temperature in the presence of catalyst I (0.05 mmol, 0.2 equiv) and benzoic acid (0.05 mmol, 0.2 equiv). The reaction was stirred overnight, monitored by NMR. Then, the crude mixture was purified by column chromatography to afford the spiro compounds 59. 

Direct coupling of vinyl halides and phenols under Ullman-type reaction conditions can be useful for the preparation of aryl vinyl ethers, and intramolecular version of this process has been applied to the synthesis of spirocyclic oxindoles through a sequence of intramolecular Ullman coupling and Claisen rearrangement reactions (eq 58). ... 

In 2010, Jaegli et al. reported a novel palladium-catalyzed intramolecular domino spirocyclization process for the preparation of biologically relevant spiropyrroUdine-3,3 -oxindoles 86 [32] (Scheme 6.19). Oxidative addition of the aryl halide to Pd(0) aminopalladation via the coordinated intermediate 84 leads to palladacycle 85 reductive elimination of complex 85 generates the final product. Both Heck reaction and aminopalladation processes were viable pathways from amide 83, and the route that occurs is dependent on the ligand chosen. The use of tBuMePhos as the ligand is required for the successful formation of spirooxindoles. 

Recently, Chen et al. reported on a one-pot, three-component tandem reaction sequence to prepare piperidine containing spirocyclic oxindoles 345 using chiral orga-nocatalyst 341 (Scheme 40.75). 

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