Carboamination palladium-alkene reactions

The first Pd-catalyzed carboamination and carboetherification reactions of y-amino or y-hydroxy alkenes with aryl halides were described by Wolfe in 2004 [ 100]. As shown below, treatment of these substrates with aryl or heteroaryl bromides in the presence of NaOfBu and a palladium catalyst provides substituted tetrahydrofuran or pyrrolidine products. 

Two recent reports have described Pd"-catalyzed carboamination reactions involving two alkenes that afford pyrrolidine products. Building on early work by Oshima that employed stoichiometric amounts of palladium [44], Stahl has developed an inter-molecular Pd-catalyzed coupling of N-allylsulfonamide derivatives with enol ethers or styrene derivatives that affords substituted pyrrolidines in high yields with moderate diastereoselectivity [45]. For example, treatment of 44 with styrene in the presence of Pd" and Cu" co-catalysts, with methyl acrylate added for catalyst stability, provided 45 in 97% yield with 1.9 1 dr (Eq. (1.21)). This reaction proceeds through intermolecular aminopalladation of styrene to afford 46. Intramolecular carbopalla-dation then provides intermediate 47, and subsequent P-hydride elimination yields product 45. 

Wolfe JP (2008) Stereoselective synthesis of saturated heterocycles via palladium-catalyzed alkene carhoetherification and carboamination reactions. Synlett 2913-2937... 

Nakhla JS, Schultz DM, Wolfe JP. Palladium-catalyzed alkene carboamination reactions for the synthesis of substituted piperazines. Tetrahedron 2009 65(33) 6549-6570. 

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