Synthesis of a P-Glycoprotein Inhibitor and Its High-Energy ( Z )-Isomer by Carbenoid Eliminative Cross-Coupling.

Autor: Tanpure SD; Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, United States., El-Mansy MF; Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, United States., Blakemore PR; Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, United States.
Jazyk: angličtina
Zdroj: Organic letters [Org Lett] 2020 Apr 17; Vol. 22 (8), pp. 2999-3003. Date of Electronic Publication: 2020 Mar 31.
DOI: 10.1021/acs.orglett.0c00755
Abstrakt: To gauge the feasibility of carbenoid eliminative cross-coupling for the synthesis of polyfunctional alkenes, a P-glycoprotein inhibitor containing an ( E )-configured 4-chromanylidene-type trisubstituted olefin was prepared as well as its previously undescribed ( Z )-isomer. Stereospecific alkene synthesis required generation of functionalized enantioenriched α-metalated carbamates [R 1 R 2 CM(O 2 CN i -Pr 2 ), 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.
Databáze: MEDLINE
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