Development of a new and practical route to chiral 3,4-disubstituted cyclopentanones: asymmetric alkylation and intramolecular cyclopropanation as key C-C bond-forming steps.
An efficient and practical asymmetric synthesis of (+)-trans-3-hydroxymethyl-4-(3-fluorophenyl)cyclopentanone (1) is described. An asymmetric Mo-catalyzed alkylation reaction was used to establish the first stereocenter and a Cu-catalyzed intramolecular diastereoselective cyclopropanation reaction was used to set the second stereocenter. The last step involved a one-pot ring-opening/deprotection/hydrolysis/decarboxylation sequence that furnished the desired product in good yield.
Palucki
Michael
M
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. michael_palucki@merck.com
Um
Joann M
JM
Yasuda
Nobuyoshi
N
Conlon
David A
DA
Tsay
Fuh-Rong
FR
Hartner
Frederick W
FW
Hsiao
Yi
Y
Marcune
Benjamin
B
Karady
Sandor
S
Hughes
David L
DL
Dormer
Peter G
PG
Reider
Paul J
PJ
D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry*; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry*; D007202:Indicators and Reagents; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D003517:Cyclopentanes; D003521:Cyclopropanes; D007202:Indicators and Reagents; C007201:cyclopentanone