Fig. 2.

Scale-up development synthesis of SYNPHOS and DIFLUORPHOS ligands (38% and 33% overall yield, respectively). Reagents and conditions: (i) Mg, THF, then ClPPh₂, then H₂O₂, MeOH; (ii) Mg, THF, then ClP(O)Ph_2; (iii) lithium diisopropylamide, –78°C, THF, 3.5h; then I₂, –10°C (inverted addition); (iv) lithium diisopropylamide, –78°C, THF, 2 h; then I₂, –78°C (direct addition); (v) Cu, dimethylformamide, 120°C; (vi) obtainment of (+)-(R)-4: (–)-DBTA, CHCl₃/AcOEt, filtration, then CH₂Cl₂, filtration, then KOHaq (1 N); obtainment of (–)-(S)-4: (+)-DBTA, CHCl₃/AcOEt, filtration, then CH₂Cl₂, filtration, then KOH aq (1 N); (vii) chiral preparative HPLC, Chirose C3 column; (viii) HSiCl₃, Bu₃N, xylene, 140°C.