Synthesis and resolution of 1-(2-diphenylphosphino-1-naphthyl)isoquinoline; a PN chelating ligand for asymmetric catalysis.

A multistep synthesis resulting in a good yield of the title compound has been developed based on the Pd-catalysed coupling of 1-chloroisoquinoline and 2-methoxy-1-naphthylboronic acid (5). The product is converted into the corresponding trifluoromethanesulphonate (10) by successive demethylation and treatment with (CF3CO)2O, followed by a further Pd-catalysed coupling with Ph2P(O)H. The resulting phosphine oxide (11) was cleanly reduced with HSiCl3. Resolution of the phosphinamine (4) was carried out with the Pd complex derived from (R)-(+)-dimethyl(1-(1-naphthyl)ethyl)amine and PdCl2; the diastereomers were of different stabilities and solubilities and were therefore readily separated. The resolved phosphinamine, [α]D22 ± 153 (c = 1, CHCl3), was enantiomerically stable on heating to 65°C for 24h. X-ray crystal structures of the adduct (16) and the Pd dimer (7) isolated during the initial coupling reaction are presented.