Diastereoselective synthesis hydroamination

Scheme 11.25 Diastereoselective synthesis of pyrrolidine ( + ) 197B via hydroamination/...

Scheme 11.26 Diastereoselective synthesis of ( + ) xenovenine via hydroamination/bicyclization ofthe aminoallene alkene 77 [120],...

The carbon-carbon unsaturated substrates have now expanded from aminoalkenes to aminoalkynes, aminoallenes, and aminodienes, and the hydroamination/cyclization reactions of these substrates have produced functionalized nitrogen-containing heterocycles. It is worth noting that the aminoallene hydroamination/cyclization reactions are highly diastereoselective, and can provide concise routes to the synthesis of some natural products (Figure 8.38) [126]. 

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). 

Recently, an elegant synthesis of hyacinthacine A2 was proposed by Fox and colleagues in which the pyrrolizidine skeleton was elaborated through a trans-annular hydroamination of a 5-aza-trans-cyclooctene such as XIV, in mm obtained via a diastereoselective photoisomerization of a c/s-octene XV (Scheme 24) [32]. The enantiopure cyclooctene was obtained from the chiral ketone 96, prepared via a three steps sequence from sucrose disaccharide [33]. 

The aminoaUene hydroamination/cyclization reactions are highly diastereoselective and can provide concise routes to synthesize some natural products (Scheme 3). Using chiral organolanthanide complexes as catalysts, enantioselec-tive hydroamination/cychzation reactions are achieved, which provide a convenient route for the synthesis of chiral amines from simple, readily available prochiral substrates in a single step. 

A relay catalytic hydroamination/redox reaction for the synthesis of cyclic aminals 83 from tertiary amine-substituted 3-en-l-yne derivatives 81 and various aniline derivatives 82 was recently developed by Gong and coworkers (Scheme 12.40) [43]. The gold carbene complex [(IPrlAuNTfj] and TfOH were found to be optimal cocatalysts for this cascade reaction. In their preliminary studies, the authors found that this reaction could be carried out in a highly enantioselective manner, despite that 2 equiv. of an expensive chiral phosphoric acid are required. Interestingly, the diastereoselectivity for a particular substrate appears to be independent of the catalyst or ee. This suggests that the enantioselectivity may result from the ring-closure step, rather than the hydride shift step. 

Asymmetric hydroamination has served as an important strategy for the synthesis of pyrrolidine and piperidine derivatives. Moreover, it has been found to be useful for the synthesis of other five- and six-membered heterocyclic compounds having more than one hetero atom. Asymmetric hydroamination and diastereoselective hydroamination have been found to be extremely useful for the synthesis of natural products and pharmaceutical agents. It is important to note that diastereoselective hydroamination has been... 

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