Transition asymmetric alkene hydroamination

As already mentioned, there has been significant progress in the development of chiral catalysts for asymmetric hydroamination reactions over the last decade. However, significant challenges remain, such as asymmetric intermolecular hydro aminations of simple nonactivated alkenes and the development of a chiral catalyst, which is applicable to a wide variety of substrates with consistent high stereochemical induction and tolerance of a multitude of functional groups as well as air and moisture. Certainly, late transition metal based catalysts show promising leads that could fill this void, but to date, early transition metal based catalysts (in particular, rare earth metals) remain the most active and most versatile catalyst systems. 

Catalytic asymmetric hydroamination of alkenes can be achieved using early and late transition metal catalysts and lanthanide-based catalytic... 

Hydroamination is an atom-economical process for the synthesis of industrially and pharmaceutically valuable amines. The hydroamination reaction has been studied intensively, including asymmetric reactions, and a variety of catalytic systems based on early and late transition metals as well as main-group metals have been developed." However, Group 5 metal-catalysed hydroaminations of alkenes had not been reported until Hultzsch s work in 2011. Hultzsch discovered that 3,3 -silylated binaphtho-late niobium complex 69 was an efficient catalyst for the enantioselective hydroaminoalkylation of iV-methyl amine derivatives 70 with simple alkenes 71, giving enantioselectivities up to 80% (Scheme 9.30). Enantiomerically pure (l )-binaphtholate niobium amido complex 69 was readily prepared at room temperature in 5 min via rapid amine elimination reactions between Nb(NMe2)5 and l,l-binaphthyl-2-ol possessing bullqr 3,3 -silyl substituents. Since the complex prepared in situ showed reactivity and selectivity identical... 

Protected nitrogen substrates in combination with late transition metal catalysts have proven exceptionally useful for addressing the aforementioned substrate scope problems when trying to mediate hydroamination with unactivated alkene substrates. In asymmetric variants of this reaction, early work by Yamamoto showed that protected aminoalkynes could be used as cydohydroamination substrates to yield chiral heterocydes with vinyl substituents [108, 225). Here the chiral chelating phosphine ligand 66 ((J ,J )-RENOPHOS) in combination with a Pd(0) precursor and benzoic acid yielded the desired products in good yield with up to 91% ee (Table 15.26). Unfortunately, to obtain these optimized enantiomeric excesses,... 

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