Solvent-Dependent Mechanism and Stereochemistry of Mitsunobu Glycosylation with Unprotected Pyranoses
Hironori Takeuchi, Yusuke Fujimori, Y. Ueda, Hiromitsu Shibayama, Masaru Nagaishi, Tomoyuki Yoshimura, Takahiro Sasamori, Norihiro Tokitoh, Takumi Furuta, Takeo Kawabata
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.