Pd-Catalyzed Hydroamination Reactions of Alkenes and Alkynes

The hydroamination of alkenes and alkynes has been of longstanding interest in organometallic chemistry [26]. Much of the early work in this area focused on early transition metal or lanthanide metal catalyst systems. However, much recent progress has been made in late-metal catalyzed hydroamination chemistry, and several interesting hydroamination reactions that afford nitrogen heterocycles have been developed using palladium catalysts. 

Palladium-catalyzed intramolecular hydroamination reactions of alkynes that afford pyrrolidine derivatives were initially reported by Yamamoto in 1998 [27] and have been the subject of detailed investigation over the past ten years [28]. In a 

Although Pd-catalyzed intramolecular hydroamination reactions of alkynes have been known for ten years, analogous transformations of unactivated alkenes have only recently been developed [33]. Key to the success of these studies was the use of a cationic palladium complex bearing a pyridine-derived P-N-P pincer ligand (29). For example, treatment of 26 with catalytic amounts of 29, AgB F4, and Cu(OTf)2 led to the formation of pyrrolidine 27 in 88% yield with 4 1 dr (Eq. (1.13)). Detailed mechamstic studies have indicated these transformations proceed via alkene coordination to the metal complex followed by outer-sphere aminopaUadation to provide 28. Protonolysis ofthe metal-carbon bond with acid generated in situ leads to formation of the product with regeneration of the active catalyst. 

An interesting tandem intermolecular/intramolecular hydroamination reaction of cycloheptatriene with substituted anilines has been developed by Hartwig for the synthesis oftropene derivatives [34]. As shown in Eq. (1.14), the coupling of 30 with 31 provided 32 in 73% yield. The mechanism of this transformation is believed to involve acid-assisted formation of an q -pentadienylpalladium complex 33, which is then captured by the aniline nucleophile to afford the allylpalladium intermediate 34. Intramolecular attack of the aniline nitrogen on the allylpalladium moiety affords the observed heterocycle. 

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