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 Sc 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 PhPCl2 followed by o-TolMgBr resulted in a single P-stereogenic diastereoisomer (Sc,Sp,Sphos and Sc,Rp,Rphos, respectively). The alternative
diastereoisomers were formed selectively by addition of o-TolPCl2 followed by PhMgBr ((Sc,Sp,Rphos and Sc,Rp,Sphos, respectively). Preliminary application
of these four ligand diastereoisomers, together with (Sc,Sp) and (Sc,Rp) Phosferrox (PPh2), 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 Sc,Sp,Sphos (97% ee).