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

这项工作的标题为“Construction of Aldol Structure with Variously Fluorinated Methyl Groups Using Sugars As Chiral Templates”，是基于从单一中间体制备甲基上含氟的前所未有的Aldol结构的概念进行的。γ，γ-二氟代烯丙醇作为常用中间体，因为该化合物不仅可以通过Red-Al还原转化为相应的单氟代化合物，而且可以通过S_N2'型DAST还原转化为三氟甲基化物质。此外，考虑到将两个氟原子引入这种中间体γ，γ-二氟化烯丙醇将通过相应的光学活性α-羟基酮的Wittig型二氟烯烃化来实现，而光学活性α-羟基酮又优选具有相对刚性的构象以获得氢化时的高非对映选择性，D-葡萄糖被确定为最佳起始原料。基于上述计划，1996-1997年期间进行了详细的研究，成功地开发了以高效和非对映选择性的方式获得具有两种氟代甲基的羟醛结构的新路线，当2，3位羟基，或使用了4个位置。通过分子轨道计算，阐明了异头甲氧基的空间和/或电子效应在非对映选择性氢化反应中的重要作用。

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.