Palladium catalysts carboamination

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. 

Intramolecular carbonylative carboamination of unsaturated amines, converted in the presence of palladium catalysts and carbon monoxide, gives nitrogen heterocycles9-10. Medium to low E Z stereoselectivities have been reported for conversions of this type using amino allenes 211 or similar systems26. 

Balme has reported a one-pot threecomponent alkene carboamination between propargylic amines, alkylidene malonates, and aryl halides [43]. For example, treatment of N-methyl propargylamine (2 equiv), dimethyl benzylidene malonate (2 equiv) and 1,4-diiodobenzene (1 equiv) with n-BuLi and a palladium catalyst provided 43 as a single diastereomer (Eq. (1.20)) [43a]. The formation of the C—N bond in this process does not appear to be metal catalyzed. Instead, initial conjugate addition of the nitrogen nucleophile to the activated alkene affords a malonate anion, which undergoes carbopalladation followed by reductive elimination to afford the pyrrolidine product. 

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. 

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