Hydroaminations Using Achiral Catalysts

The diastereoselective cyclization of chiral aminoalkenes, such as a substituted hex 

5 enylamines, can be utilized in the synthesis of piperidine based alkaloids, such as 

Organolithium mediated cycloisomerization of chiral aminoalkenes may proceed with high diastereoselectivities when favored by the substrate geometry. The last step ofthe enantioselective synthesis of ( ) codeine (80), reported by Trost and Tang [121], consisted of an intramolecular hydroamination. Treatment of amine 79 with LDA or wBuLi in refluxing THF left the starting material unreacted. However, irradiation of the amine/LDA solution with a 150 W tungsten lamp led to diastereoselective cycloisomerization to form ( ) codeine (80) (Eq. 11.11). 

Equation 11.11. Synthesis of ( ) codeine (80) via base catalyzed hydroamination/ cyclization [121]. 

While no catalytic intermolecular asymmetric hydroamination of allenes has 

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Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

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