Highly Diastereoselective Synthesis of 2,2-Disubstituted Cyclopentane-1,3-diols via Stepwise Ketone Reduction
Jingyao Gong1,2, Jianjiong Li2, Xi Chen2
1Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
Abstract:
A series of 2,2-disubstituted trans,cis-cyclopentane-1,3-diols were synthesized in >99% dr through enzymatic reduction of enantiopure 2,2-disubstituted 3-hydroxycyclopentane-1-ones, which were prepared by highly stereoselective enzymatic reduction of the corresponding cyclodiketones. For 2-benzyl-2-methyl-3-oxocyclopentyl acetate, acetylation of the hydroxyl group significantly affected the reduction stereoselectivity, giving trans,cis-, trans,trans-, and cis,cis-2-benzyl-2-methyl-cyclopentane-1,3-diols in stereomerically pure form. This efficient and environmentally friendly method provides a practical approach to the synthesis of these chiral building blocks in single stereoisomeric form, demonstrating the power of biocatalysis in the concise chirality construction of complex chiral molecules.
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