Mechanistic Investigation of the Palladium-Catalyzed Decarboxylative Cyclization of gamma-Methylidene- delta-valerolactones with lsocyanates: Kinetic Studies and Origin of the Site Selectivity in the Nucleophilic Attack at a (pi-Allyl)palladium

• Published in: Journal of the American Chemical Society Vol. 132; no. 21; pp. 7508 - 7513
• Main Authors: Shintani, Ryo, Tsuji, Takaoki, Park, Soyoung, Hayashi, Tamio
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 02.06.2010
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; KETENE SILYL ACETAL; ETA-3-ALLYL COMPLEXES; ASYMMETRIC ALLYLIC ALKYLATION; CENTRAL CARBON; VINYLIC OXIRANES; CYCLOPROPANATION; EFFECTIVE ROUTE; REGIOSELECTIVE 3+2 CYCLOADDITION; ALKENYL ISOCYANATES; ACTIVATED OLEFINS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja1023223

Mechanistic studies for the palladium-catalyzed decarboxylative cyclization reactions of gamma-meth-ylidene-delta-valerolactones 1 with isocyanates 2 are described. The reactions can be effectively catalyzed by palladium triarylphosphine complexes to give piperidones 3 and/or azaspiro[2.4]heptanones 4. Through kinetic studies using NMR spectroscopy, it has been determined that the oxidative addition of lactones 1 to palladium(0) is the turnover-limiting step of the catalytic cycle. By changes in the electronic properties of the triarylphosphine ligands, the product distribution between 3 and 4 can be easily controlled, and an explanation for the origin of this selectivity is provided. The selectivity between 3 and 4 is also influenced by the nature of the nitrogen substituent on isocyanates 2, and more electron-rich substituents tend to give higher selectivity toward azaspiro[2.4]heptanones 4. These studies represent the first systematic investigation into the selectivity between terminal attack and central attack at (pi-allyl)palladium species by nitrogen-based nucleophiles.