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Enantioselective Synthesis of (−)‐CP‐55940 via Ruthenium‐ Catalyzed Asymmetric Hydrogenation of Ketones
Author(s) -
Cheng LiJie,
Xie JianHua,
Wang LiXin,
Zhou QiLin
Publication year - 2012
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201100898
Subject(s) - chemistry , enantioselective synthesis , kinetic resolution , ruthenium , catalysis , ketone , aryl , noyori asymmetric hydrogenation , organic chemistry , asymmetric hydrogenation , medicinal chemistry , combinatorial chemistry , stereochemistry , alkyl
A new and efficient catalytic asymmetric synthesis of the potent cannabinoid receptor agonist (−)‐CP‐55940 has been developed by using ruthenium‐catalyzed asymmetric hydrogenation of racemic α‐aryl ketones via dynamic kinetic resolution (DKR) as a key step. With RuCl 2 ‐SDPs/diamine [SDPs=7,7′‐bis(diarylphophino)‐1,1′‐spirobiindane] catalysts the asymmetric hydrogenation of racemic α‐arylcyclohexanones via DKR provided the corresponding cis ‐β‐arylcyclohexanols in high yields with up to 99.3% ee and >99:1 cis ‐selectivities. Both ethylene ketal group at the cyclohexane ring and ortho ‐methoxy group at the phenyl ring of the substrates 6 have little effect on the selectivity and reactivity of the hydrogenations. Based on this highly efficient asymmetric ketone hydrogenation, (−)‐CP‐55940 was synthesized in 13 steps (the longest linear steps) in 14.6% overall yield starting from commercially available 3‐methoxybenzaldehyde and 1,4‐cyclohexenedione monoethylene acetal.