Lithium hydride as an efficient reagent for the preparation of 1,2-anhydro inositols: Does the reaction proceed through ‘axial rich’ conformation?

• Published in: Carbohydrate research 2018-06, Vol.463, p.32-36
• Main Authors: Sarkar, Nitai, Sardessai, Richa S., Shashidhar, Mysore S., Tamboli, Majid I., Gonnade, Rajesh G.
• Format: Article
• Language: English
• Subjects: Cyclitol; Epoxide; Halohydrin; Inositol; Lithium hydride
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2018.04.014

scyllo-Inositol derived 1,2-trans-diequatorial halohydrins can be efficiently converted to the corresponding epoxides in the presence of lithium hydride. The structure of one of the epoxides was determined by single crystal X-ray diffraction analysis. This provides a potential route for the preparation of ring modified inositol derivatives. DFT calculations suggest that this epoxide formation could be proceeding through the intermediacy of the cyclohexane ring-inverted axial-rich conformer (1,2-trans-diaxial halohydrin). This is supported by the results of DFT calculations on the formation of inositol orthoformate, where the product is locked in the axial-rich conformation, while the starting inositol has the equatorial-rich conformation. Inositol derived trans-diequatorial halohydrins cyclize to yield the corresponding epoxides in the presence of lithium hydride. [Display omitted] •Lithium hydride converts halohydrins to epoxides efficiently.•Inositol derived halohydrin flips to axial-rich conformation prior to reaction.•DFT calculations support 1,2-anhydro inositol formation via axial-rich conformation.