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

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.

Radical Beckmann Rearrangement and Its Application in the Formal Total Synthesis of Antimalarial Natural Product Isocryptolepine via C-H Activation.

The Beckmann rearrangement of ketoximes, mediated by ammonium persulfate-dimethyl sulfoxide as a reagent, has been achieved under neutral conditions. Based on the radical trapping and (18)O-labeling experiments, the transformation follows a mechanism involving a radical pathway. The scope and generality of the developed protocol has been demonstrated by 19 examples.

Radical-mediated dehydrative preparation of cyclic imides using (NH4)2S2O8-DMSO: application to the synthesis of vernakalant.

Ammonium persulfate-dimethyl sulfoxide (APS-DMSO) has been developed as an efficient and new dehydrating reagent for a convenient one-pot process for the synthesis of miscellaneous cyclic imides in high yields starting from readily available primary amines and cyclic anhydrides. A plausible radical mechanism involving DMSO has been proposed. The application of this facile one-pot imide forming process has been demonstrated for a practical synthesis of vernakalant.