Fluorinated cyclitols. An improved synthesis of 5-deoxy-5-fluoro- myo-inositol, its deuterium labeling, and synthesis of a 5,5- gem-difluoro analogue

Abstract

An improved synthesis of 5-deoxy-5-fluoro- myo-inositol is provided via the reaction of diethylaminosulfur trifluoride (DAST) with the versatile intermediate, 1,4,6-tri- O-benzyl-2,3- O-cyclohexylidene- neo-inositol (I), followed by appropriate deprotection reactions. Reaction of DAST with the 5- keto analogue of I gave the gem-difluoro compound, which upon deprotection afforded 5-deoxy-5,5-difluoro- myo-inositol. A 1H-n.m.r. study of the deuteration of 5-deoxy-5-fluoro- myo-inositol with Raney nickel-deuterium oxide revealed that the equatorial H-2 proton was most rapidly exchanged, followed by the sterically identical H-1 and H-3 protons, which exchanged at a significantly slower rate.