Pd-Catalyzed Carboamination Reactions of Alkynes, Allenes, and Dienes

Pd-Catalyzed Carboamination Reactions of Alkynes, Allenes, and Dienes 

A few examples of Pd -catalyzed carboamination reactions between alkyne-tethered amines and aryl halides have also been reported [28d, 47]. For example, treatment of amino ester derivative 50 with Phi in the presence of K2CO3 using Pd(PPh3)4 as catalyst led to the formation of 51 in 80% yield with complete retention of enantiomeric purity (Eq. (1.23)) [28d]. In contrast to the Pd -catalyzed carboamination 

Several examples of Pd°-catalyzed carboamination reactions between allenes and aryl or alkenyl halides have been reported [50[. For example, treatment of allene 52 with iodobenzene in the presence of K2CO3 and 2mol% Pd(PPh3)4 afforded pyrrolidine 53 in 78% yield (Eq. (1.25)) [50a]. Mechanisms involving aikene amino-palladation (similar to the reactions of alkynes and alkenes noted above) have occasionally been invoked to explain these reactions. However, in many instances these transformations may involve intermediate Ji-allylpalladium complexes. Due to this mechanistic ambiguity, these transformations have been included in this section for comparison with the related reactions of alkenes and alkynes. Similar reactions involving allylic halides have also been described (Eq. (1-26)) [51]. 

Cross-coupling carboamination reactions between allenes and 2-haloaniline derivatives or halogenated allylic amines have also been employed for the generation of substituted indolines, and use of an appropriate chiral catalyst for these transformations leads to formation of enantioenriched products [52]. For example, Larock has described the synthesis of indoline 56 via the Pd-catalyzed reaction of aryl iodide 54 

Ma has developed a three-component allene carboamination reaction for the stereoselective synthesis of 2,5-as-disubstituted pyrrolidine derivatives [54]. A representative transformation involving allene 58, 4-iodoanisole, and imine 59 that generates 60 in 90% yield is shown below (Eq. (1.28)). The reaction is believed to proceed through the intermediate Jt-allylpalladium complex 62, which is formed by carbopalladation of the alkene to give 61 followed by addition of the malonate anion to the activated imine. Intramolecular capture of the allylpalladium moiety by the pendant nitrogen nucleophile affords the pyrrolidine product. A related asymmetric synthesis of pyrazolidines that employs azodicarboxylates as one of the electrophilic components has also been reported [55]. The pyrazolidine products are obtained with up to 84% ee when chiral bis oxazolines are employed as ligands. 

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