Solvent-Dependent Mechanism and Stereochemistry of Mitsunobu Glycosylation with Unprotected Pyranoses

  • Org Lett. 2020 Jun 19;22(12):4754-4759. doi: 10.1021/acs.orglett.0c01549.
Hironori Takeuchi  1 ,  Yusuke Fujimori  1 ,  Yoshihiro Ueda  1 ,  Hiromitsu Shibayama  1 ,  Masaru Nagaishi  1 ,  Tomoyuki Yoshimura  1 ,  Takahiro Sasamori  1 ,  Norihiro Tokitoh  1 ,  Takumi Furuta  1 ,  Takeo Kawabata  1
Affiliations
  • 1. Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
PMID: 32496806 DOI: 10.1021/acs.orglett.0c01549
Abstract

An SN2 mechanism was proposed for highly stereoselective glycosylation of benzoic acid with unprotected α-d-glucose under Mitsunobu conditions in dioxane, while an SN1 mechanism was indicated for nonstereoselective glycosylation in DMF. The SN2-type stereoselective Mitsunobu glycosylation is generally applicable to various unprotected pyranoses as glycosyl donors in combination with a wide range of acidic glycosyl acceptors such as carboxylic acids, Phenols, and imides, retaining its high stereoselectivity (33 examples). Glycosylation of a carboxylic acid with unprotected α-d-mannose proceeded also in an SN2 manner to directly afford a usually less accessible 1,2-cis-mannoside. One- or two-step total syntheses of five simple natural glycosides were performed using the glycosylation strategy presented here using unprotected α-d-glucose.

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