SYNTHESIS OF AMINOCYCLITOLS BY INTRAMOLECULAR REDUCTIVE COUPLING OF CARBOHYDRATE-DERIVED DELTA-FUNCTIONALIZED AND EPSILON-FUNCTIONALIZED OXIME ETHERS PROMOTED BY TRIBUTYLTIN HYDRIDE OR SAMARIUM DIIODIDE

The intramolecular reductive coupling of a series of simple or polyoxy genated oxime ethers delta- or epsilon-functionalized with bromide, al pha,beta-unsaturated ester, aldehyde, or ketone groups is reported. Th e cyclization of a nitrile-tethered aldehyde is also studied. These re ductive couplings are promoted by tributyltin hydride or samarium diio dide. The reactions proceed under mild conditions, in good chemical yi eld, and with high stereoselectivity. When applied to highly functiona lized substrates derived from carbohydrates, this approach provides a selective entry to enantiomerically pure aminocyclitols of varying reg io- and stereochemistry. In particular, the reductive coupling reactio n of carbonyl-tethered oxime ethers promoted by samarium diiodide can be performed in a one-pot sequence, following a Swern oxidation step, allowing the direct transformation of hydroxyl-tethered oxime ethers i nto the corresponding aminocyclitols. Moreover, the resultant O-benzyl hydroxylamine products of these cyclizations can be further reduced in situ with excess samarium diiodide, in the presence of water, to the corresponding amino alcohols in excellent yields. Some transformations of these compounds are discussed.