Optimization of a Resolution Process Allowing Access to Both Enan-tiomers of the Versatile Chiral Phosphine Ligand sSPhos on Scale

Broadly-effective, chiral monodentate phosphine ligands in asymmetric catalysis are relatively rare. sSPhos is a versatile, axi-ally chiral phosphine which, is capable of inducing high levels of enantioselectivity in a number of palladium-catalyzed trans-formations, including atroposelective Suzuki-Miyaura cross-coupling, arylative dearomatization and carboetherification reac-tions. We have previously reported the chiral resolution of sSPhos by salt formation with quinidine, permitting isolation of the (R) enantiomer. That process possessed several limitations including relatively small scale, inability to access the (S) enantio-mer, the requirement to pre-synthesize a trifluoroacetate salt of the dihydroquinine and a maximum ee of 98% of (R)-sSPhos. In this work we report further optimization and development of that procedure to permit it to be performed on large scale. This simplified process permits the protonated, zwitterionic form of (R)-sSPhos to be obtained in >99% ee and (S)-sSPhos in 98% ee. The new modified procedure included a resolution of racemic sSPhos by crystallization and was demonstrated on 80 g scale to give access to both enantiomers of sSPhos in high ee and good yield. It is notable that the (S)-sSPhos enantiomer had previously been only available through preparative separation. We anticipate that this will assist incorporation of sSPhos as a chiral ligand in screening libraries and facilitate industrial application.