Iridium-Catalyzed Asymmetric Hydrogenation of 2,3-Diarylallyl Amines with a Threonine-Derived P-Stereogenic Ligand for the Synthesis of Tetrahydroquinolines and Tetrahydroisoquinolines.

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.

BOM-Phosphinite as an Electrophilic P-Stereogenic Transfer Reagent for the Synthesis of Bulky Phosphines: Synthesis of tert-Butyl(3,5-di-tert-butylphenyl)BisP.

BOM-tert-butylmethylphosphinite borane is an efficient electrophilic P-stereogenic transfer reagent for the synthesis of bulky tertiary phosphines. The novel methodology relies on a one-pot deprotection/substitution on the trivalent phosphinite that takes place with very high stereospecificity. The potential of this strategy is demonstrated with the synthesis of a wide scope of tertiary phosphines in excellent enantiomeric excess. The methodology was applied to the synthesis of a bulky P-stereogenic BisP* ligand analogue.

P-Stereogenic and Non-P-Stereogenic Ir-MaxPHOX in the Asymmetric Hydrogenation of N-Aryl Imines. Isolation and X-ray Analysis of Imine Iridacycles.

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.