[reaction: see text] Rhodium and copper acyl nitrenoids are likely intermediates in amidoglycosylation reactions of allal 3-carbamates. Iodine(III)-mediated nitrenoid formation, interaction of this species with the glycal enol ether pi-system, and highly beta-stereoselective glycosylation occur in a one-pot process that requires no additional Lewis acid activation.

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In the Rh 2 (OAc) 4 -catalyzed amidoglycosylation of glucal 3-carbamates, anomeric stereoselectivity and the extent of competing C3-H oxidation depend on the 4O and 6O protecting groups. Acyclic protection permits high α-anomer selectivity with further improvement in less polar solvents, while electron-withdrawing protecting groups limit C3-oxidized byproducts. Stereocontrol and bifurcation between alkene insertion and C3-H oxidation reflect an interplay of conformational, stereoelectronic, and inductive factors.2-Amino sugars having a 2,3-cis stereo array include N-acetylmannosamine (ManNAc, 1), which is the biosynthetic precursor of the sialic acids, 1 and 2-allosamine, a constituent of the potent chitinase inhibitor allosamidin (2) 2 and a useful ligand scaffold (3) 3 for asymmetric catalysis. The challenge of stereoselective C2-N bond construction is acute in these systems, and control of anomeric configuration in the preparation of glycoside derivatives is desirable. Synthetic methods based on intermolecular additions to glycals typically place the C2-N group trans to the C3-oxygen substituent. 4 Gin's activated-sulfoxide-mediated acetamidoglycosylation 5 of glucals is an exception, producing ManNAc structures, though with N-acetylglucosamine (GlcNAc) byproducts. 5cAs an alternative, 6 we have used intramolecular nitrogen atom delivery from allal 3-azidoformates, 7 allal 3-carbamates, 8 and glucal 3-carbamates 9 to establish the 2,3-cis relationship. With the 3O-carbamoyl glycals, we extended Du Bois's C-H amidation method 10 to alkene insertion, 11,12 a new reaction of allylic carbamates. 13 Mechanistic studies 14 imply that these conditions produce rhodium nitrenoids having reactivity strikingly analogous to metal carbenoids. 15 With iodosobenzene (PhIO) 16 instead of PhI(OAc) 2 as the oxidant, we achieved in situ glycosylation of alcohols without nucleophilic competition from acetate, an overall amidoglycosylation process. 8,9,17 Allal frameworks (e.g., 4, Scheme 1) provided high 1,2-trans selectivity, offering a concise route to β-linked 2-amido allopyranosides as found in allosamidin. 7,8 However, in the C3-epimeric series, our one-pot amidoglycosylation process applied to glucal 3-carbamates 6a and 6b, having 4O,6O acetonide or di-tert-butylsilylene protection, gave anomeric mixtures only slighly favoring the 1,2-trans products 7-α and also generated dihydropyranone byproducts 8a and 8b via oxidation at the C3-H bond (Table 1, entries 1 and 5). 9 Using 4-penten-1-ol as the acceptor, we were able to stereoconvergently advance either anomer of n-pentenyl glycoside 18 7a, but the lack of amidoglycosylation selectivity stymied direct access to α-linked ManNAc derivatives. 9Herein we report that proper choice of 4O and 6O protecting groups and solvent enables high levels of stereocontrol and chemoselectivity in amidoglycosylation of glucal 3-carbamates. Our studies also illuminate electronic and conformational aspects of both amidoglycosylation and the competing C3-H oxidation.For comparison, we be...

[reaction: see text] Glucal 3-carbamates 1 and 7 underwent oxidative cyclization with iodobenzene diacetate or iodosobenzene in the presence of Rh2(OAc)4, providing mannosamine 2-N,3-O-oxazolidinones. With iodosobenzene, incorporation of 4-penten-1-ol provided a readily separable anomeric mixture of n-pentenyl glycosides, with the anomers exhibiting pronounced differences in reactivity as glycosyl donors. N-acylation of the sugar oxazolidinones led to alpha-selective glycosyl donors for the elaboration of various 2-mannosamine frameworks. Alternatively, the anomeric n-pentenyl glycosides of N-Cbz 2-mannosamine oxazolidinones were converted separately to oxazolidinone-opened derivatives 28alpha and 28beta. These served as stereoconvergent glycosyl donors, and the alpha-linked products were readily advanced to a variety of N-acetylmannosamine (ManNAc) frameworks, using an intramolecular O-->N acetyl transfer as the final step.