Carboxybenzyl Group as an O-Nucleophile in the C–H Allylic Oxidation: Total Synthesis of (−)-Castanospermine

Abstract

The first palladium-mediated C-H allylic oxidation with a Cbz group acting as an O-nucleophile is reported. It was found that this transformation is promoted by rare-earth metal triflates: Yb(OTf)(3) or Sc(OTf)(3). A possible catalytic cycle is proposed. This reaction was applied in the synthesis of a d-xylose derived oxazolidinon, a versatile intermediate used further in the stereoselective synthesis of unnatural (-)-castanospermine. Cyclization of the key intermediate with PhSeBr afforded the desired bicyclic scaffold. In an alternative route, hydroboration/oxidation followed by DPPA-mediated cyclization was used.

Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation

“…25 Fortunately, upon screening a variety of additives and varying the catalyst and oxidant loadings (see Supporting Information), we found that the addition of superstoichiometric quantities of water to the reaction mixture was crucial for obtaining reproducibly good yields of lactone 26 . 26,27 …”

Ruthenium-catalyzed one-pot ring-closing metathesis/syn-dihydroxylation in the synthesis of bicyclic iminosugars

“…10 After methanolysis, which afforded aminoalcohol 2, the N-acryloyl derivative 3a was obtained, along with considerable amounts (26%) of diacryloyl derivative 3b as a by-product. Subsequent ring-closing meta thesis (Scheme 3) of 3a with Grubbs-II cat.…”

Ytterbium Triflate Catalyzed Synthesis of Heterocycles

“…In 2014, during the total synthesis of a naturally occurring iminosugar, castanospermine, a palladium-catalyzed intramolecular C−H allylic oxidation with a piperidinyl Ncarbamate (as an O-nucleophile) yielded an oxazolidinonefused piperidine derivative (Scheme 130). 163 It was found that reaction was promoted by a catalytic amount of Yb(OTf) 3 . The presence of a Lewis acid was crucial; without it, only trace amounts of product were isolated.…”