A Structure-Reactivity Relationship of the Tandem Asymmetric Dihydroxylation on a Biologically Relevant Diene: Influence of Remote Stereocenters on Diastereofacial Selectivity

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The Sharpless asymmetric dihydroxylation (AD) finds widespread use in natural product and drug molecule syntheses, in part, due to its efficiency and predictability. However, the tandem AD of dienes is much less studied, but important in complex molecular synthesis. Herein, a biologically relevant tandem AD is reported, and several anomalies are discovered with the accepted model. These include the formation of unpredicted diastereoisomers, with matched and mismatched stereocenters contradicting the Sharpless mnemonic device. From a structural analysis of the tandem AD, we present a strategy to improve asymmetric induction in sterically hindered alkenes using double diastereodifferentiation from a 9-bond distant stereocenter. A theoretical justification for the unpredicted stereoselectivity, accounting for the influence of steric hindrance and pre-installed chirality, is proposed.


Original languageEnglish
Pages (from-to)7568-7577
Number of pages10
JournalEuropean Journal of Organic Chemistry
Issue number46
Early online date6 Nov 2019
Publication statusPublished - 15 Dec 2019


  • Asymmetric dihydroxylation, sharpless, tandem, diastereodifferentiation, stereofacial selectivity