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Asymmetric Hydrogenation of Polysubstituted Aromatic Ketones Catalyzed by the DIPSkewphos/PICA Derivative–Ruthenium(II) Complexes
Author(s) -
Utsumi Noriyuki,
Arai Noriyoshi,
Kawaguchi Kei,
Katayama Takeaki,
Yasuda Toshihisa,
Murata Kunihiko,
Ohkuma Takeshi
Publication year - 2018
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201800848
Subject(s) - catalysis , chemistry , medicinal chemistry , alcohol , yield (engineering) , derivative (finance) , ruthenium , steric effects , noyori asymmetric hydrogenation , organic chemistry , molar ratio , materials science , economics , financial economics , metallurgy
The DIPSkewphos/PICA derivative‐Ru(II) complexes catalyzed asymmetric hydrogenation of significantly sterically hindered 2’,3’,4’,5’,6’‐pentamethylacetophenone, which was not reduced with NaBH 4 at 25 °C, with a substrate‐to‐catalyst molar ratio (S/C) of 2000 under 50 atm of H 2 in a base‐containing 2‐propanol to afford the alcohol in 99 % ee quantitatively. A series of polysubstituted aromatic ketones was smoothly reacted with an S/C of 300–10,000 under 10–50 atm of H 2 , yielding the alcoholic products in up to 99 % ee . The catalyst system achieved an industrial‐scale (50 kg) hydrogenation of 2’,6’‐dichloro‐3’‐fluoroacetophenone, affording the alcohol in 96 % isolated yield and in 98 % ee . The obtained alcoholic product is known as a key intermediate for the synthesis of the medicine crizotinib.