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A Structure‐Reactivity Relationship of the Tandem Asymmetric Dihydroxylation on a Biologically Relevant Diene: Influence of Remote Stereocenters on Diastereofacial Selectivity
Author(s) -
Gill Daniel M.,
Male Louise,
Jones Alan M.
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901474
Subject(s) - stereocenter , chemistry , steric effects , dihydroxylation , sharpless asymmetric dihydroxylation , stereochemistry , asymmetric induction , tandem , stereoselectivity , diastereomer , enantioselective synthesis , natural product , chirality (physics) , selectivity , combinatorial chemistry , organic chemistry , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark , materials science , composite material
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.