Intermolecular Asymmetric Hydroamination

While no catalytic intermolecular asymmetric hydroamination of allenes has... 

Intermolecular asymmetric hydroamination provides chiral acyclic amines, whereas intramolecular asymmetric hydroamination provides chiral cyclic amines. 

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. 

Although this chapter is formally not covering recent achievements in rare earth chemistry, it must be mentioned that the first examples of asymmetric intermolecular alkene hydroamination have been reported by Hultzsch and coworkers (Scheme 15.13) [85]. Using a bulky binaphtholate yttrium complex at high temperatures with excess alkene substrate, the first examples of this challenging and highly sought after reaction have been realized with unactivated alkenes. 

Scheme 15.13 Y-catalyzed asymmetric intermolecular alkene hydroamination.

Zhou J, Hartwig JF. Intermolecular, catalytic asymmetric hydroamination of bicychc alkenes and dienes in high yield and enantioselectivity. J. Am. Chem. Soc. 2008 130(37) 12220-12221. 

Although hydroamination reactions are regiospecific in most cases, the stereoselective synthesis of pharmaceutically relevant chiral amines via hydroamination remains challenging despite significant progress for asymmetric intramolecular reactions and some initial reports on asymmetric intermolecular hydroamination. Selected examples of asymmetric hydroamination will be covered in this chapter due to the volume limitations, and the reader should refer to available specialized reviews for a more comprehensive coverage of the stereoselective aspects [8-15]. 

Scheme 15.84 Au(l)-catalyzed asymmetric intermolecular hydroamination with allenes.

Organolanthanide complexes are known to be highly active catalysts for a variety of organic transformations, which can be either intramolecular or intermolecular in character. Successful intramolecular transformations include hydroelementation processes, which is the addition of a H-E (E = N, O, P, Si, S, H) bond across unsaturated C-C bonds, such as hydroamination, hydroalkoxylation, and hydrophosphination. Intermolecular transformations include a series of asymmetric syntheses, the amidation of aldehydes with amines, Tishchenko reaction, addition of amines to nitriles, aUcyne dimerization, and guanylation of terminal aUcynes, amines, and phosphines with carbodiimides. 

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). 

The asymmetric intermolecular hydroamination is arguably the most challenging transformation in the context of hydroamination chemistry. Despite significant progress over the last two decades in the development of hydroamination catalysts in general, this particular area has seen little to no progress for early and late... 

Table 20 Asymmetric intermolecular hydroamination of unactivated aUcenes...

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