A small library of Ir-MaxPHOX catalysts has been applied to the asymmetric hydrogenation of N-aryl imines. A structure-activity analysis of the three-chiral-center MaxPHOX ligand has been performed. Using complex 1b, the hydrogenation of N-aryl imines took place with up to 96% enantiomeric excess at atmospheric pressure of hydrogen and low temperature. The impact of the stereochemical information at the phosphorus center is small with respect to the selectivity, but large with respect the catalyst activity. Non-P-stereogenic analogs of MaxPHOX were also synthesized and tested, but they provided lower selectivity. The selectivity observed could be explained by taking into account that the actual catalysts were cyclometalated imine complexes formed in situ. [IrHCl(MaxPHOX)(imine)] complexes 9 and 10 were synthesized and characterized by X-ray crystallography. These complexes, via chloride abstraction, provided the active catalytic species with the same levels of selectivity. Finally, the influence of the counterion on the catalyst performance was also studied.

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Chiral compounds containing nitrogen heteroatoms are fundamental substances for the chemical, pharmaceutical and agrochemical industries. However, the preparation of some of these interesting scaffolds is still underdeveloped. Herein we present the synthesis of a family of P-stereogenic phosphinooxazoline iridium catalysts from L-threonine methyl ester and their use in the asymmetric hydrogenation of N-Boc-2,3-diarylallyl amines, achieving very high enantioselectivity. Furthermore, the synthetic utility of the 2,3-diarylpropyl amines obtained is demonstrated by their transformation to 3-aryl-tetrahydroquinolines and 4-benzyl-tetrahydroisoquinolines, which have not yet been obtained in an enantioselective manner by direct reduction of the corresponding aromatic heterocycles. This strategy allows the preparation of these types of alkaloids with the highest enantioselectivity reported up to date.

The synthesis of optically and diastereomerically pure P-stereogenic phosphine-imidazole ligands is reported. The new ligands contain either a benzoimidazole or a 4-phenylimidazole as a N-donor fragment. The ligands have been coordinated to iridium and the structure of the corresponding cationic COD complexes has been determined by X-ray analysis. The combination of the chiral phosphorus atom and the imidazole substituents generate a strong chiral environment around the metal 2 center. Preliminary hydrogenation reactions with a model cyclic -enamide are also reported. RESULTS AND DISCUSSIONLigand Synthesis. Phosphino imidazole ligands have been synthetized according to the retrosynthetic analysis shown in Scheme 1. Condensation of valine with orthophenylenendiamine and 2-bromoacetophenone should provide the corresponding chiral protected benzo-and 4-phenylimidazole amines. N-Alkylation and Boc deprotection would provide the corresponding primary amines. These will be coupled with either enantiomer of the optically pure tert-butylmethylphosphinous acid borane in a SN2 reaction at the stereogenic P-center (SN2@P) to afford the desired ligands. Scheme 1: Retrosynthetic plan for the synthesis of phosphino imidazole ligands. The synthesis of free (R)-2-methyl-1-(1-methylbenzoimidazol-2-yl)propan-1-amine 4 was conducted as shown in Scheme 2. Condensation of N-Boc valine with orthophenylenendiamine was carried out through a two-step procedure as described in the literature. 15 Isobutyl chlorocarbonate-mediated amide coupling and cyclization with AcOH at 65 ºC provided the desired N-Boc protected benzoimidazole 2 in 54% yield. Next, N-methylation of the benzoimidazole heterocycle was carried selectively with MeI and NaOH pellets in acetonitrile. This cleanly afforded 3 in 90% yield. Finally, Boc deprotection was performed in MeOH/HCl(aq) which afforded the desired benzoimidazole amine 4 in excellent yield and purity.