The practicalities of the asymmetric hydrogenation of acetophenone derivatives are addressed. The catalysts used, derived fromthe precatalysts [(xylylPhanePhos)RuCl
2(DPEN)] (
S)-(
R,
R)-
1and (
R)-(
S,
S)-
1, were shown to possess very high reactivity. 4'-Fluoroacetophenone was hydrogenated at a molar substrate-to-catalyst ratio (S/C) of 100,000 with complete conversioneffected in as little as 80 min (average turnover ~1200 min
-1,peak turnover ~2500 min
-1). The catalysts are tolerant of arange of commercial grade substrates, in most cases a S/C of5000-10000 was achieved without the need to purify the ketone.Using precatalyst
1 enantioselectivities of 95
99% ee wereachieved. The high selectivity and catalyst activity, plus thesimplicity of the process, offers significant advantages over otherenantioselective ketone reductions.