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. 2018 Aug 3;83(15):8054-8080.
doi: 10.1021/acs.joc.8b00893. Epub 2018 Jul 6.

Glycal Metallanitrenes for 2-Amino Sugar Synthesis: Amidoglycosylation of Gulal-, Allal-, Glucal-, and Galactal 3-Carbamates

Simran Buttar  1 , Julia Caine  1 , Evelyne Goné  1 , Reneé Harris  1 , Jennifer Gillman  1 , Roxanne Atienza  1 , Ritu Gupta  1 , Kimberly M Sogi  1 , Lauren Jain  1 , Nadia C Abascal  1 , Yetta Levine  1 , Lindsay M Repka  1 , Christian M Rojas  1
Affiliations

Glycal Metallanitrenes for 2-Amino Sugar Synthesis: Amidoglycosylation of Gulal-, Allal-, Glucal-, and Galactal 3-Carbamates

Simran Buttar et al. J Org Chem. .

Abstract

The rhodium(II)-catalyzed oxidative cyclization of glycal 3-carbamates with in situ incorporation of an alcohol nucleophile at the anomeric position provides access to a range of 2-amino sugars having 1,2-trans-2,3-cis stereochemistry, a structural motif present in compounds of medicinal and biological significance such as the streptothricin group of antibiotics and the Chitinase inhibitor allosamidin. All of the diastereomeric d-glycal 3-carbamates have been investigated, revealing significant differences in anomeric stereoselectivity depending on substrate stereochemistry and protecting groups. In addition, some substrates were prone to forming C3-oxidized dihydropyranone byproducts under the reaction conditions. Allal- and gulal 3-carbamates provided uniformly high stereo- and chemoselectivity, while for glucal substrates, acyclic, electron-withdrawing protecting groups at the 4 O and 6 O positions were required. Galactal 3-carbamates have been the most challenging substrates; formation of their amidoglycosylation products is most effective with an electron-withdrawing 6 O-Ts substituent and a sterically demanding 4 O-TBS group. These results suggest a mechanism whereby conformational and electronic factors determine the partitioning of an intermediate acyl nitrenoid between alkene addition, leading to amidoglycosylation, and C3-H insertion, providing the dihydropyranone byproduct. Along the amidoglycosylation pathway, high anomeric selectivity results when a glycosyl aziridine intermediate is favored over an aziridine-opened oxocarbenium donor.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Bioactive natural products and building blocks containing 2-amino sugars.
Figure 2
Figure 2
Stereochemistry determination in β−2-aminogulose oxazolidinones.
Figure 3
Figure 3
NOESY correlations in α−2-amidotalose derivative 18ca prepared from galactal 3-carbamate 14c.
Figure 4
Figure 4
Allal-, gulal-, and galactal-derived glycosyl aziridine donors.
Figure 5
Figure 5
Metallanitrene positioning in galactal 3-carbamate.
Scheme 1
Scheme 1
One-Pot Amidoglycosylation with d-Glycal 3-Carbamates 11–14, Giving Amino Sugar Derivatives 15–18 and Formation of Dihydropyranone Byproducts 19 and 20
Scheme 2
Scheme 2
Synthesis of (a) Gulal 3-Carbamates and (b) a Conformationally Flexible Allal 3-Carbamate
Scheme 3
Scheme 3
Synthesis of Acetonide-, Benzyl-, and Silylene-Protected Galactal 3-Carbamates
Scheme 4
Scheme 4
Preparation of Variously Protected Galactal 3-carbamates
Scheme 5
Scheme 5
Oxazolidinone Opening To Confirm Stereochemistry of 2-Gulosamine and 2-Allosamine Derivatives by 1H NMR
Scheme 6
Scheme 6
Mechanistic Proposal for Amidoglycosylation via an Acyl Metallanitrene
Scheme 7
Scheme 7
Influence of Conformational Flexibility on Glucal-Derived 2-Amido Glycosyl Donors
Scheme 8
Scheme 8
Stepwise Aziridine Formation from a Conformationally Flexible Glucal Precursor
Scheme 9
Scheme 9
Possible Mechanisms for C3−H Oxidation via Metallanitrene 7
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