Enantioselective hydroamination

The synthesis of a series of chiral organophosphine oxide/sulfide-substituted binaphtholate ligands has recently been reported by Marks and Yu and their corresponding lanthanide complexes characterized. These complexes, generated in situ from Ln[N(TMS)2]3, cleanly catalysed enantioselective intramolecular hydroamination/cyclisation of 1-amino-2,2-dimethyl-4-pentene albeit with a low enantioselectivity of 7% ee (Scheme 10.82). 

Based on this, asymmetric hydroamination was developed using [Ir(C2H4)4Cl] or lr(coe)2Cl]2 (coe = cyclooctene) with chiral diphosphines to give complexes (57)-(61) (Scheme 40). While (57) afforded only a low yield and poor enantiomeric excess (51% 2S) of exo-2-(phenylamino)nor-bornane, addition of up to one equivalent of fluoride ion gave a six-fold increase in chemical yield (from 12% to 81%) and a reversal of enantioselectivity. In the case of (60), addition of four equivalents of fluoride led to an ee of 95 % The role of fluoride in these reactions has still not been explained satisfactorily.175... 

In 2008, the Ackennann group reported on the use of phosphoric acid 3r (10 mol%, R = SiPhj) as a Brpnsted acid catalyst in the unprecedented intramolecular hydroaminations of unfunctionaUzed alkenes alike 144 (Scheme 58) [82], BINOL-derived phosphoric acids with bulky substituents at the 3,3 -positions showed improved catalytic activity compared to less sterically hindered representatives. Remarkably, this is the first example of the activation of simple alkenes by a Brpnsted acid. However, the reaction is limited to geminally disubstituted precursors 144. Their cyclization might be favored due to a Thorpe-Ingold effect. An asymmetric version was attempted by means of chiral BINOL phosphate (R)-3( (20 mol%, R = 3,5-(CF3)2-CgH3), albeit with low enantioselectivity (17% ee). 

At the end of 2007, Widenhoefer et al. reported the first examples of the dynamic kinetic enantioselective hydroamination of axially chiral allenes, catalyzed by a dinuclear complex of gold (Figure 8.1) and silver perchlorate [46, 47]. 

Enantioselective, multiple centers 153, 166,189 Hydroamination Intermolecular Alkene 30 Alkyne 1 Intramolecular Alkene 30 Alkyne 13,170 Hydrogen peroxide Oxidation of alcohols 26, 86 Hydrogenolysis of epoxide 1 Hydrozirconation 32... 

An yttrium(III) complex derived from ligand (100) has been shown to be a superior catalyst for enantioselective intramolecular hydroaminations of alkenes that provide cyclic amines with enantioselectivities ranging from 69 to 89% ee,132... 

The chiral organolanthanides have been especially designed for asymmetric catalysis. Thus far several enantioselective olefin transformations (hydrogenation, hydroamination/cyclization, hydrosilylation) as well as the polymerization of methyl methacrylate mediated by these chiral organolanthanide metallocenes have been investigated. 

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... 

Finally, though not strictly a hydroamination reaction, the asymmetric addition of alkynes to imines with a copper-bis(oxazoline) complex is worth briefly mentioning.[144] The nature of the ionic liquid cation has a strong effect on the enantioselectivity of the reaction and it appears that a good balance between hydrophobicity and acidity play an important role with best results obtained with [C4Ciim][Tf2N]. 

The displacement of cyclooctene or C2H4 from an iridium(I) centre by a variety of chiral phosphines (L) leads to the formation of [ (L)IrCl 2] which, in conjunction with a source of F (phosphazenium fluoride), has been used for catalytic hydroamination of olefins. This combination leads to a 6.5 fold increase in the activity of the system and a total reversal in the enantioselectivity compared to that of the chloride analogue. There is no direct evidence of formation of a metal fluoride complex, but it is proposed that it may well form in situ and that this might explain these interesting results [75]. 

Brown, A. R. Uyeda, C. Brotherton, C. A. Jacobsen, E. N. Enantioselective thiourea-catalyzed intramolecular cope-type hydroamination, 7 Am. Chem. Soc. 2013,135, 6747-6749. 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

The C2-symmetric bisoxazolinate 175 formed complexes with lanthanides for the catalysis of enantioselective intramolecular hydroamination /cyclization <03JA14768>. 

Wang, Q.W., Xiang, L., Song, H.B. et al. (2008) Synthesis of amidolanthanides with new chiral biaryl-based NNO ligands and their use as catalysts for enantioselective hydroamination/cycUzation. Inorganic Chemistry, 47, 4319. 

Hong, S., Xian, S., Metz, M.V. et al. (2003) C2-symmetric bis(oxazoUnato)lanthanide catalysts for enantioselective intramolecular hydroamination/cycUzation. Journal of the American Chemical Society, 125, 14768. 

A number of (R)- and (,S )-organolanthanide alkyl and amide complexes 1, bearing a homochi-ral substituent R on one cyclopentadienyl ring, were prepared and their catalytic activity in the enantioselective hydroamination-cyclization of 4-pentenylamines 3 was examined 11 113 These complexes are converted to the catalytically active species 2 in the presence of a large excess of the amine. Furthermore, catalyst epimerization (S)-2 to (/ )-2 or vice versa occurs and is complete in the early stages of preparative-scale reactions however, equilibrium homochiralities are frequently high, in some cases >95%. 

The organolanthanide-catalyzed alkene hydroamination has been reported. With this approach, amino alkenes (not enamines) can be cyclized to form cyclic amines, and amino alkynes lead to cyclic imine. The use of synthesized C-1 and C-2 symmetric chiral organolanthanide complexes give the amino alcohol with good enantioselectivity. 

Hydroamination. The chiral BINAP-IrCl dimer induces the enantioselective addition of aniline to norbomene (95% ee) at 75°. The reaction is facilitated by fluoride ions I activity increase by 6.5-fold). 

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