Synthesis and resolution of the biaryl-like diphosphine (S)-Me2-CATPHOS, preparation of a derived rhodium precatalyst and applications in asymmetric hydrogenation

Abstract

This protocol describes the synthesis of a representative example of the enantiopure biaryl-like CATPHOS class of diphosphines, (S)-9,9'-dimethyl-9,9',10,10'-tetrahydro-9,10,9',10'-biethenobianthracene-11,11'-bis(diphenylphosphino)-12,12'-diyl ((S)-Me(2)-CATPHOS), and its derived cationic rhodium-based hydrogenation precatalyst. The C(2)-symmetric framework of Me(2)-CATPHOS is the result of a regioselective Diels-Alder cycloaddition between 1,4-bis(diphenylphosphinoyl)buta-1,3-diyne and 9-methylanthracene, such that the bulky methyl-substituted bridgehead carbon atoms are attached to C2 and C3 of the 1,3-butadiene tether. Enantiopure Me(2)-CATPHOS is obtained in an operationally straightforward three-step procedure and isolated in ∼50-60% overall yield and <99% enantiopurity, after diastereoselective resolution with (2R,3R)-(-)-2,3-O-dibenzoyltartaric acid. The derived rhodium complex forms a highly effective catalyst for the asymmetric hydrogenation of a range of dehydroamino acid derivatives, as well as (E)-β-aryl-(enamido)phosphonates, giving ee values in excess of 99%, the highest to be reported for the latter class of substrate. The total time required for the synthesis of (S)-Me(2)-CATPHOS, including resolution, reduction and crystallizations, is 130 h and preparation of the corresponding rhodium precatalyst requires an additional 24-26 h.