Stereoselective Synthesis of All Possible Phosferrox Ligand Diastereoisomers Displaying Three Elements of Chirality: Stereochemical Optimization for Asymmetric Catalysis

All four possible diastereoisomers of phosphinoferrocenyloxazoline (Phosferrox type) ligands containing three elements of chirality were synthesized as single enantiomers. The S c configured oxazoline moiety (R = Me, i -Pr) was used to control the generation of planar chirality by lithiation, with the alternative diastereoisomer formed by use of a deuterium blocking group. In each case subsequent addition of PhPCl 2 followed by o -TolMgBr resulted in a single P -stereogenic diastereoisomer ( S c, S p, S phos and S c, R p, R phos, respectively). The alternative diastereoisomers were formed selectively by addition of o -TolPCl 2 followed by PhMgBr (( S c, S p, R phos and S c, R p, S phos, respectively). Preliminary application of these four ligand diastereoisomers, together with ( S c, S p ) and ( S c, R p ) Phosferrox (PPh 2 ), to palladium catalyzed allylic alkylation of trans -1,3-diphenylallyl acetate revealed a stepwise increase/decrease in ee, with the configuration of the matched/matched diastereoisomer as S c, S p, S phos (97% ee).