Hydroamination enantioselective processes

More recently chiral organolanthanide precatalysts of the type [Me2SiCp"(R Cp)]LnCH(SiMe3)2 and [Me2SiCp"(R Cp)]LnN(SiMe3)2 (R = ( + )-neomenthyl, (— )-menthyl Ln = Y, La, Sm, Lu) have been used for efficient regio- and enantioselective olefin hydroamination/cyclization processes. For example, a > 95% diasteroselectivity at 15 °C was achieved with... 

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. 

The intermolecialar hydroamination has also received some attention and studies in this area have focussed on the use of iridium and nickel catalysts. Enan-tioselectivities for the intermolecular process are also generally moderate with ees observed between 60 and 70%. The highest enantioselectivities for this reaction have been obtained during the hydroamination of norbornene (2.145) with aniline in the presence of the iridium complex (2.184) and the fluoride ion source... 

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... 

Almost at the same time, Liu and Che independently applied the same strategy to the synthesis of chiral secondary amines through a domino intermolecular hydroamination-transfer hydrogenation of alkynes using a gold(i) complex in combination with a chiral phosphoric acid." This domino process has a broad substrate scope since a wide variety of aryl, alkenyl, and aliphatic allq nes could be coupled with anilines with different electronic properties to afford chiral amines in excellent enantioselectivities of up to 94% ee, as shown in Scheme 7.31. 

Almost at the same time, Liu and Che published a cascade intermolecular hydroamination/asymmetric reduction sequence, which included achiral Au complex-catalyzed hydroamination of aryl amines and chiral phosphoric acid-promoted Hantzsch ester reduction to afford secondary aryl amines [70], More recently, the same group reported a tandem one-pot assembly of functionalized tetrahydroquino-lines from amino aldehyde and alkynes by combining Au and chiral phosphoric acid catalysis [71], The reaction was initiated by Au-promotedquinololine 210 generation, followed by an enantioselective HEH-incorporated transfer hydrogenation process (Scheme 9.67). 

Similar to alkali metals, only few chiral alkaline earth metal complexes have been apphed in asymmetric hydroaminations of nonactivated aminoalkenes [155, 244—248] and one of the greatest challenges has been the development of a chiral catalyst system that can resist facile ligand redistribution processes leading to achiral catalytically active species. Therefore, it is not too surprising that many systems are plagued with low enantioselectivities (Fig. 18, Table 18). 

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