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. 2024 Jul 17;146(28):18866-18872.
doi: 10.1021/jacs.4c06246. Epub 2024 Jul 5.

Diverse Synthesis of C-Glycosides by Stereoselective Ni-Catalyzed Carboboration of Glycals

Mao-Yun Lyu  1 , Samuel A Jacobo  1 , M Kevin Brown  1
Affiliations

Diverse Synthesis of C-Glycosides by Stereoselective Ni-Catalyzed Carboboration of Glycals

Mao-Yun Lyu et al. J Am Chem Soc. .

Abstract

C-Glycosides are important structures that are common to natural products and pharmaceutical agents. Established methods for their synthesis involve the reaction of an activated anomeric carbon. In this study, we report a conceptually new approach that involves the stereoselective Ni-catalyzed carboboration of glycals. In these reactions, not only is a C-C bond formed at the anomeric carbon, but a synthetically useful C-B bond is also installed. Upon C-B oxidation, differentially protected C-glycosides to be formed. In addition, stereospecific manipulation of the C-B bond leads to diverse C-glycosides. Finally, we report the application of this method in the synthesis of established C-glycosides, such as C-glycosyl amino acids, as well as a strategy to make all possible diastereomers at C1 and C2.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Structure and Synthesis of C-Glycosides
Scheme 2.
Scheme 2.. Initial Studiesa
aYields are determined by 1H NMR of the unpurified reaction mixture with mesitylene as internal standard.
Scheme 3.
Scheme 3.. Substrate Scopec
aCorresponding alcohol isolated after oxidation with NaBO3. bReaction with Br(CH2)3Cl as the electrophile. cReactions run on 0.1 mmol scale. Yields of isolated product are shown.
Scheme 4.
Scheme 4.
Larger-Scale and Further Transformations
Scheme 5.
Scheme 5.
Additional Product Modifications
See this image and copyright information in PMC

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