Sequential Nucleophilic C(sp3)‐Benzylation/C(sp2)–H Arylation for the Synthesis of Spiro[oxindole‐3,5′‐pyrrolo[2,1‐a]isoquinolines]

• Published in: European journal of organic chemistry 2017-06, Vol.2017 (22), p.3179-3186
• Main Authors: Zhang, Tinglei, Cui, Baodong, Han, Wenyong, Wan, Nanwei, Bai, Mei, Chen, Yongzheng
• Format: Article
• Language: English
• Subjects: Alkylation; Aromatic compounds; Bromides; Cascade chemical reactions; Catalysis; Chemical reactions; Derivatives; Domino reactions; Nitrogen heterocycles; Palladium; Series (mathematics); Spiro compounds; Synthesis
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201700533

An efficient strategy for the synthesis of spirocyclic indolizidine derivatives that have a 3,3′‐disubstituted oxindole framework has been described. By using sequential nucleophilic C(sp3)‐benzylation and palladium‐catalyzed C(sp2)–H arylation reactions of 3‐pyrrolyloxindoles and 2‐(bromomethyl)aryl bromides, a series of spiro[oxindole‐3,5′‐pyrrolo[2,1‐a]isoquinolines] were smoothly obtained in up to 92 % yield. A synthetic application of this method was also demonstrated by the transformation of 3u into functionalized compound 4. Moreover, the catalytic cycle of this cascade reaction was proposed on the basis of results of control experiments. A cooperative base and palladium system was employed for the sequential nucleophilic C(sp3)‐benzylation and C(sp2)–H arylation reactions of 3‐pyrrolyloxindoles and 2‐(bromomethyl)aryl bromides. This protocol was used for the construction of spirocyclic indolizidine derivatives that incorporate a 3,3′‐disubstituted oxindole framework. TFA = trifluoroacetate; DMF = N,N‐dimethylformamide.