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.