Construction of Aldol Structure with Variously Fluorinated Methyl Groups Using Sugars As Chiral Templates

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This work, titled as "Construction of Aldol Structure with Variously Fluorinated Methyl Groups Using Sugars As Chiral Templates" was carried out on the basis of the concept that unprecedented aldol structures containing fluorine (s) on the methyl group would be prepared from a single intermediate. gamma, gamma-Difluorinated allylic alcohols were employed as the common intermediate because this compound could be converted not only into the corresponding monofluorinated counterpart by the Red-Al reduction but also into the trifluoromethylated materials by S_N2' type DAST fluorination. Moreover, considering the fact that introduction of two fluorine atoms to such intermediary gamma, gamma-difluorinated allylic alcohols would be realized by Wittig type difluoroolefination of the corresponding optically active alpha-hydroxyketones which, in turn, were preferable to possess relatively rigid conformations for attainment of high diastereofacial selectivity on hydrogenation, D-glucose was decided as the best starting material. Its low cost and ready availability as well as many reports on the regioselective protection of its hydroxy groups were also the important factor.Based on the above plan, investigation was carried out in detail during 1996-1997 to successfully develop the novel routes to access aldol structures with either types of fluorinated methyl groups in highly efficient as well diastereoselective manners when a hydroxy group at 2,3, or 4 positions was utilized. It was also clarified that the steric and/or electronic effect of the anomeric methoxy group playd an important role in the diastereoselective hydrogenation based on the molecular orbital calculations.