TitleSynthesis of a P-Glycoprotein Inhibitor and Its High-Energy ()-Isomer by Carbenoid Eliminative Cross-Coupling.
Publication TypeJournal Article
Year of Publication2020
AuthorsTanpure SD, El-Mansy MF, Blakemore PR
JournalOrg Lett
Volume22
Issue8
Pagination2999-3003
Date Published2020 04 17
ISSN1523-7052
KeywordsAlkenes, ATP Binding Cassette Transporter, Subfamily B, Member 1, Molecular Structure, Stereoisomerism
Abstract

To gauge the feasibility of carbenoid eliminative cross-coupling for the synthesis of polyfunctional alkenes, a P-glycoprotein inhibitor containing an ()-configured 4-chromanylidene-type trisubstituted olefin was prepared as well as its previously undescribed ()-isomer. Stereospecific alkene synthesis required generation of functionalized enantioenriched α-metalated carbamates [RRCM(OCN-Pr), M = Li or Bneo], and problems associated with incorrect lithiation regioselectivity and unexpected organolithium configurational lability were encountered. Solutions to these difficulties are described together with a method for ee determination of α-carbamoyloxyboronates.

DOI10.1021/acs.orglett.0c00755
Alternate JournalOrg Lett
PubMed ID32227909