Reductive amination with iridium catalysts

Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared from [IrCl(cod)]2, (S)-BINAP, NBu 4 BH4, gives with high enantioselectivity the corresponding A-hydroxylamines which are important biologically active compounds and precursors of amines (480). Further reduction of hydroxylamines to secondary amines or imines can be realized upon treatment with Fe/AcOH (479), or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature (481). 

Aqueous organometalHc catalysis allows the use of NH3-solutions in water for the direct synthesis of amines from olefins in a combined hydroformylation/reductive amination procedure (Scheme 4.19). The hydroformylation step was catalyzed by the proven Rh/TPPTS or Rh/BINAS (44) catalysts, while the iridium complexes formed from the same phosphine ligands and [ IrCl(COD) 2] were found suitable for the hydrogenation of the intermediate imines. With sufficiently high NH3/olefin ratios (8/1) high selectivity towards the formation of primary amines (up to 90 %) could be achieved, while in an excess of olefin the corresponding... 

An interesting variation of hydroformylation with a great potential for the industrial preparation of primary amines is hydroaminomethylation. In this process two catalytic reactions are combined, a hydroformylation and a reductive amination of the resulting aldehyde. Although first described more than 60 years ago a really successful procedure was only published recently [78]. To ensure the success of this sequence a rhodium catalyst for the hydroformylation was combined with an iridium catalyst for the imine reduction in a two-phase system, similar to the Ruhrchemie/Rhone-Poulenc process for the hydroformylation. It was demonstrated that less polar solvents such as toluene in combina-... 

Another application of this reaction is in a synthesis of the alkaloid xenovenine 9.150 (Scheme 9.46), one of many isolated from tropical frogs, which acquire the compound from their diet. While asymmetric allylation provided the original stereogenic centre, Suzuki coupling, the Wittig reaction and reductive amination were each employed for key bond-forming reactions. Additional syntheses of xenovenine can be found in Section 6.2. The readily available allylic carbonate 9.152 was reacted with the diacylammo-nia derivative 9.153 in the presence of an iridium complex and the chiral pre-catalyst (Scheme 9.47). The... 

Chiral amines have been conveniently prepared also by asymmetric reductive amination of ketones using iridium catalysts and intriguing results with up to 96% ee have been obtained by Zhang and co-workers employing a catalytic system based on Ir./-binaphane in the presence of Ti(OPr )4 and iodine (Scheme 61). Water-soluble aquo complexes [Cp lr(H20)3](0Tf)2 494, [CpP Ir(H20)2](0Tf)2 504, and [Cp Ir(bpy)(H20)](0Tf)2 505 have been used to catalyze the reductive amination of hydrosoluble aldehydes and ketones as well as the dehalogenation of alkyl halides. The activity is markedly pH dependent and inactivation of the catalyst takes place reversibly on increasing the solution basicity due to Ir(H20), deprotonation and formation of mono- or dinuclear hydroxo complexes which are catalytically inactive. The structure of one of these compounds, [Cp Ir(bpy)(OH)]OTf 506, which reversibly forms from 494 around pH 6.6, is presented in Figure 42. 

Cationic complex 72, related to Crabtree s catalyst, was one of the first NHC complexes used for TH of ketones, alkenes and nitro compounds in refluxing isopropanol (Figure 13.8). Related neutral complexes 73 were also very active in the reduction of acetophenone in KOH/i-PrOH. Oro and co-workers prepared the cationic Rh and Ir complexes 74 and 75 with O-donor-func-tionalized NHC ligands (Figure 13.8). The iridium complexes were found to be efficient pre-catalysts for the TH of cyclohexanone in KOH/i-PrOH with TOFs < 4600 h. Cationic triazol-5-ylidene complexes 76 were highly active for the TH of C=0 and C=C functions as well as for reductive amination of aldehydes. ... 

Earher mechanistic studies by Milstein on a achiral Ir catalyst system indicated that the iridium catalyzed norbornene hydroamination involves amine activation as a key step in the catalytic cycle [27] rather than alkene activation, which is observed for most other late transition metal catalyzed hydroamination reactions [28]. Thus, the iridium catalyzed hydroamination of norbornene with aniline is initiated by an oxidative addition of aniline to the metal center, followed by insertion of the strained olefin into the iridium amido bond (Scheme 11.4). Subsequent reductive elimina tion completes the catalytic cycle and gives the hydroamination product 11. Unfor tunately, this catalyst system seems to be limited to highly strained olefins. 

In this chapter, I outline our recent progress in asymmetric reductive and oxidative transformations with bifunctional molecular catalysts based on ruthenium, rhodium, and iridium complexes bearing chiral chelating amine ligands. 

Zirconium Intermolecular hydroamination of both terminal and internal alkynes R C=CR with primary amines R NH2 to produce (after subsequent reduction) saturated secondary amines RiCH2-CH(NHR )R can be attained with the in situ generated zirconium catalysts (Me2N)4Zr (5 mol%) and sulfonamide (10 mol%). " Zirconium-catalysed intramolecular hydroamination (225) (226) has been studied theoretically " as for the analogous iridium-catalysed cyclization of (177) discussed (g) earlier " and similar conclusions have been reached regarding the hydrogen bonding, and so on. 

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