Metal-complexed nitrene intermediates generated from glycal 3-carbamates provide one-pot, stereocontrolled C2–N bond formation as well as incorporation of a nucleophile at the anomeric center.  All four D-glycal 3-carbamate diastereomers have been investigated, leading to a range of 2-amino sugar derivatives bearing a cis-2N,3O-oxazolidinone group.  In developing this methodology, we discovered that the nitrene intermediate partitions between the desired alkene addition reaction (which leads to amidoglycosylation via a presumed glycosyl aziridine donor) and a competing C3–H oxidation that leads to a dihydropyranone byproduct.  We have developed solutions to this chemoselectivity problem both through substrate control (varying the electronic, steric, and conformational properties of the glycals via the 4O,6O protecting groups) and catalyst control (use of Rh-, Cu-, Ag-, and Fe-complexed nitrenes).  The reaction tolerates C6-azido functionality as well as a range of glycosyl acceptor alcohols.  The resulting 2-amino sugar oxazolidinones can be further derivatized by N-arylation and also advanced to the fully deprotected free reducing sugars for dehydrative couplings with aglycons.

Chemoselective amidoglycosylation of all four D-glycal 3-carbamate diastereomers: Synthesis of stereo-varied 2-amino sugar oxazolidinones

255th National Meeting (2018)

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