Cyclic imine hydrogenation: effective

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). 

A RhCp complex (S,S)-6 (Cp =pentamethylcyclopentadienyl), which is iso-lobal with Ru(rj6-arene) complex (S,S)-5 (Scheme 13), effected the transfer hydrogenation of a cyclic imine substituted by an isopropyl group with an S/C of 200 in the presence of a 5 2 mixture of formic acid and triethylamine to give the R amine in 99% ee (Scheme 13) [31]. When the reaction was performed with an S/C of 1,000, the optical yield decreased to 93%. The methyl imine was reduced with a 91% optical yield. Reduction of a cyclic sulfonimide resulted in the R sul-tam in 81% ee. 

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... 

Strong iodide effects were also observed for the hydrogenation of J -benzyl-N-(l-methylbenzylidene)amine and of the cyclic imine 5 with [Ir(cod)Cl2] and diop and bppm (and analogs thereof) as ligands. In the presence of n-Bu Nl and Bilj as promoters and an s/c ratio of 200, complete conversion were achieved for both substrates with ees up to 91% for imine 5 [30]. 

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. 

Secondary Amines.—The reduction of imines to the corresponding secondary amines can be effected by various methodologies. New additions are the sodium triacyloxyborohydrides (easily obtainable from sodium borohydride and AT-acyl derivatives of optically active amino-acids), which are used for the asymmetric reduction of cyclic imines. Also now available is a highly stereoselective reduction of N-benzylimines derived from substituted cyclohexanones, with alkali-metal borohydrides, in particular L-selectride. A fiuther addition is the first report of the reduction of aldimines by hydrogen transfer from propan-2-ol,... 

Between 360°C (680°F) and 400°C (750°F), the solvent power of various solvent types has been found to decrease in the following order amines, phenols, cyclic hydrocarbons, aliphatic hydrocarbons, but the substitution of hydrogen for functions such as imine (=NH) or amino (-NHj) may increase the solvent power. With aliphatic amines at lower temperatures, the reverse is true. Insertion of a carbonyl group in the para position causes a sharp increase in effectiveness. 

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... 

---