Chemo-enzymatic synthesis of (R)-5-hydroxymethyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate, a potential chiral building block for multicyclic terpenoids

Abstract The chemo-enzymatic synthesis of ( R )-5-hydroxymethyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate, a potential chiral building block for polycyclic terpenoids containing a five–membered ring having isopropyl and angular methyl substituents, such as erinacin A and dolatriol, was achieved over 11 steps from ethyl 2-oxocyclopentane-1-carboxylate. The key synthetic precursor for this triflate was ethyl (1 S ,2 R )-2-hydroxycyclopentanecarboxylate (>99% ee), which was prepared by a lipase-catalyzed enantioselective hydrolysis of the corresponding racemic acetate. The antipodal ( S )-triflate is expected to be the synthetic intermediate for another group of terpenoids involving hamigeran B and stolonidiol. Enantiomerically pure (1 R ,2 S )-hydroxyester (>99% ee) was prepared in high yield using the asymmetric reduction of the oxoester with commercially available carbonyl reductase, “Chiralscreen® OH”-E001.