Cyclic imine hydrogenation: effective catalysts

Cyclic imines 8 and 9 are intermediates or models of biologically active compounds and can be reduced with ee-values of 88 to 96% using Ti-ebthi, Ir-bcpm or Ir-binap in the presence of additives (entries 5.7, 5.9), as well as with the transfer hydrogenation catalyst Ru-dpenTs (entries 5.8, 5.10-5.12). As pointed out earlier, Ru-diphosphine-diamine complexes are also effective for imines, and the best results for 7 and 8a were 88% and 79% ee, respectively [36]. Azirines 10 are unusual substrates which could be transfer-hydrogenated with a catalyst prepared in situ from [RuCl2(p-cymene)]2 and amino alcohol L12, with ee-values of 44 to 78% and respectable TOFs of up to 3000 (entry 5.13). 

The activity and enantioselectivity of chiral Ir catalysts have been tested by using 2,3,3-trimethylindolenine as a model substrate. Hydrogenation of the cyclic imine with [Ir(bdpp)Hl2 2 gives the corresponding chiral amine with 80% ce (Scheme 1.99) [350]. The stereoselectivity is somewhat better than that with acyclic substrates (see Scheme 1.94). A neutral BCPM-Ir complex with Bil3 effects asymmetric hydrogenation in 91% optical yield [354], A complex of MCCPM shows similar enantioselection [354], These complexes are not applicable to the reaction of other acyclic and six-membered cyclic imines. An MOD-DIOP-Ir complex is also usable with the aid of ( -C4H9)4NI [355], An Ir complex of BICP with phthalimide effectively... 

An interesting effect of imide and amine additives was observed for Ir-bcpm and Ir-binap catalysts. The catalyst performance for the hydrogenation of im-ines 7 was affected by the addition of phthalimide or perfluorophthalimide [26]. The highest enantioselectivity were obtained with the Ir-bcpm catalyst system 87% ee with F4-phthalimide and 86% with phthalimide. Primary or secondary amines were found to be useful co-catalysts for the asymmetric hydrogenation of N-benzyl-iV-(l-methylbenzylidene)amine and the cyclic imine 6 (R=Ph) with cationic Ir-binap (or Ir-tol-binap) catalysts [27]. For example, the addition of... 

The HTR was carried out in organic solvent (dichloromethane) and in water using as hydrogen donor respectively the azeotrope HCOOH/EtsN and HCOONa. Catalytic system with ligand 31 was effective for the HTR of iV-benzyl imines in organic solvent. The corresponding amines were formed in good yields and ee (92-96% yields and 84-88% ee). In contrast, Ru complexes obtained from amphiphilic polymer 33a and 33b were found to be effeetive for the HTR of cyclic imines in water (50-95% yields 86-94% ee). The catalytic activity, in water, seemed to be controlled by the hydrophilic-hydrophobic balance in a polymer-supported catalyst. 

Wills et al. subsequently demonstrated that catalyst 4, derived from a modified TsDPEN containing a dimethylated amine, was effective in the reduction of imines but not of ketones. The same was the case with the N-methylated tethered complex 5 [33]. This result provided evidence that the frequently cited cyclic N-H hydrogen... 

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