Asymmetric hydroamination

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). 

Han Z-Y, Xiao H, Chen X-H, Gong L-Z. Consecutive intramolecular hydroamination/asymmetric transfer hydrogenation under relay catalysis of an achiral gold complex/chiral brpnsted acid binary system. J. Am. Chem. Soc. 2009 131 9182-9183. 

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... 

Transition metal complex-catalyzed carbon-nitrogen bond formations have been developed as fundamentally important reactions. This chapter highlights the allylic amination and its asymmetric version as well as all other possible aminations such as crosscoupling reactions, oxidative addition-/3-elimination, and hydroamination, except for nitrene reactions. This chapter has been organized according to the different types of reactions and references to literature from 1993 to 2004 have been used. 

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). 

Ruthenium complexes mediate the hydroamination of ethylene with pyridine.589 The reaction, however, is not catalytic, because of strong complexation of the amine to metal sites. Iridium complexes with chiral diphosphine ligands and a small amount of fluoride cocatalyst are effective in inducing asymmetric alkene hydroamination reaction of norbomene with aniline [the best enantiomeric excess (ee) values exceed 90%].590 Strained methylenecyclopropanes react with ring opening to yield isomeric allylic enamines 591... 

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. 

The third part of this chapter reviews previously described catalytic asymmetric reactions that can be promoted by chiral lanthanoid complexes. Transformations such as Diels-Alder reactions, Mukaiyama aldol reactions, several types of reductions, Michael addition reactions, hydrosilylations, and hydroaminations proceed under asymmetric catalysis in the presence of chiral lanthanoid complexes. 

Figure 50. Proposed mechanism for catalytic asymmetric hydroamination/cyclization.

Asymmetric hydroamination using a chiral PIGIPHOS-Ni(II) complex has also been achieved in ionic liquids, as shown in Scheme 9.38.11431 A number of different imidazolium and picolinium ionic liquids were tested and relative to THF, much higher turnover numbers (300 vs. 20) were observed in the reaction between methacrylonitrile and morpholine at comparable selectivity (64% ee vs. 69%). Moreover, the catalyst in the ionic liquid solution is less sensitive to air and moisture so that non-distilled reagents can be used. 

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 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. 

Gribkov, D.V., Hultzsch, K.C., and Hampel, F. (2006) 3,3 -Bis(trisarylsilyl)-substituted binaphtholate rare earth metal catalysts for asymmetric hydroamination. Journal of the American Chemical Society, 128, 3748. 

Aillaud, I., Lyubov, D., Collin, J. et al. (2008) Chiral amido alkyl rare earth complexes a new family of asymmetric intramolecular hydroamination catalysts. Organometallics, 27, 5929. 

In 2002, Trost and Tang reported the chiral total synthesis of (-)-codeine in short reaction steps using a palladium-catalyzed asymmetric allylic alkylation (AAA) [53] as the key transformation [54], In 2005, a detailed full account of their synthesis was published [55]. The key features of their synthesis are (1) a preparation of an aryl ether with high optical purity by the Pd-catalyzed AAA reaction, (2) the intramolecular Heck reaction to generate the A-C-E benzofuran skeleton, (3) the second intramolecular Heck reaction of Z-vinyl bromide providing the phenan-throfuran core, and (4) the intramolecular hydroamination for the construction of D-ring by the action of LDA and visible light. 

Fig. 4 Cl-symmetric chiral lanthanocene catalysts for asymmetric hydrogenation, hydrosUylation, and hydroamination [27-29]...

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