A highly efficient and shortcut synthesis of cyclitol derivatives via spiro sugar ortho esters

Preparation of cyclitol derivatives from sugar lactones via spiro sugar ort ho esters is described. The key steps are the novel enol ether formation fr om sugar ortho esters with AlMe3 and the efficient intramolecular aldol cyc lization of alkyl enol ethers with ZnCl2 in THF/H2O. Firstly, the spiro sug ar ortho eaters 3a-c were prepared from the benzyl protected sugar lactones la-e and 2,2-dimethylpropanediol (2). These ortho esters were efficiently converted into the enol ethers 5a-c by the treatment of AlMe3 in CH2Cl2. Th e initial step of this reaction was the pyran ring cleavage accompanied by the methyl anion insertion, and the second was the dioxane ring opening cau sed by the Lewis acidity of AlMe3. The resulting alkyl enol ethers were tre ated with DMSO/Ac2O, and the formed keto compounds were converted into the carbasugars 9a-c by the ZnCl2-catalyzed aldol cyclization in THF/H2O. The o verall yields of 9a, 9b, and 9c based on the corresponding lactones la-e we re 64, 64, and 54%, respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.