ENANTIOSELECTIVE HYDROGENATION REACTIONS WITH A FULL SET OF PREFORMED AND PREPARED IN-SITU CHIRAL DIPHOSPHINE-RUTHENIUM(II) CATALYSTS

The new class of 2-methylallyl ruthenium chiral diphosphines 1 are efficient in asymmetric hydrogenation of alpha beta unsaturated acids and allylic alcohols. The related chiral halogen-containing ruthenium catalysts 2 are prepared from 1 or in situ from (COD)Ru(eta(3)(CH2)(2)CHCH3)(2) by ligand exchange with the chelating diphosphine followed by protonation (HX) in acetone. This procedure allows rapid screening of chiral phosphines, such as Diop, Chiraphos, Cbd, Bppm, Binap, beta-glucophos, Biphemp, MeO-Biphep, Me-Duphos, in ruthenium mediated hydrogenations of prochiral substrates. A high efficiency is displayed by Ru-catalysts having atropisomeric ligands (e.e. up to 99%), and a C-2 symmetric bis(phospholane) has also emerged as a valuable ligand (Me-Duphos, e.e. up to 87% not optimized). Asymmetric hydrogenation of beta-keto esters can be conducted under quite mild conditions (4 atm. of H-2, 50 degrees C, e.e. up to 99%), beta-keto esters having a disubstituted double bond are also hydrogenated chemoselectively to unsaturated chiral alcohols under controlled conditions with excellent optical purities.