【作者】 马梦林；

【导师】 陈华；

【作者基本信息】 四川大学 ， 有机化学， 2006， 博士

【摘要】 自1990年以来,不对称催化研究发展迅速,在基础研究和手性技术的开发与应用方面都获得了巨大的成功,成为不对称合成研究的热点。其中,手性膦配体的设计合成及其在不对称催化反应中的应用研究占有非常重要的地位。本文设计合成了一类新的长链烷氧基取代的手性双膦配体（S）-p-Alkoxy- MeO-BIPHEP(（S）-165c^S-165f),并对其在（Z）-2-乙酰胺基肉桂酸酯和芳香酮的不对称催化加氢反应中的性能进行了研究。首先,利用改进的方法合成了MeO-BIPHEP及其长链烷氧基取代的衍生物(（S）-165c^S-165f)。该方法适用于各种不同取代的MeO-BIPHEP类双膦配体的合成,同中时具有收率高、低成本和操作简便等特点。采用及时分出溴乙烷的新工艺和微波辅助合成两种方法,改进了传统无水氯化镍催化亚磷酸三乙脂和间溴茴香醚反应生成间甲氧基苯基磷酸二乙脂的反应,缩短了反应时间,提高了收率,适合于大量制备。以无水三氯化铁催化氧化偶联的“一锅煮”法,替代文献中常用的邻位锂化、碘代、Ullmann偶合反应法,制备了重要的合成中间体6, 6`-二甲氧基-1, 1`-联苯-2, 2`-二磷酸二乙酯（rac-162）。以廉价的无水三氯化铁代替昂贵的碘和活性铜粉,降低了试剂成本。同时,无水三氯化铁催化的“一锅煮”法具有操作简便、产物易纯化和后处理简单的优点,易于中间体的放大制备。通过对rac-162拆分条件的研究,成功地获得了光学纯的重要中间体（S）-162。偶联产物（S）-162经膦酰化反应,制备了光学纯的膦酰氯（S）-163,再与格氏试剂反应,以较高的收率制备了新的双膦氧化物（S）-164。其经还原得到了新更多还原

【Abstract】 Asymmetric hydrogenation has become increasingly popular for producing enantiomerically pure compounds in pharmaceutical and other chemical industries. The demand for new ligands with unique structural features and physical properties continues to grow in order to meet the requirements of a wide range of reactions and substrates. In this paper, a series of new optically active MeO-BIPHEP-type ligands, (S)-6,6`-dimethoxy-2,2`-bis(di-p-alkoxyphenylphosphine)-1,1`-biphenyl ((S)-165c ~ (S)-165f) were prepared and applied in asymmetric hydrogenation.Starting from the commercially available triethyl phosphorite and m-bromoanisole, an optically active (S)-6,6`-dimethoxybiphenyl-2,2`-diyl-bis (phosphonic acid diester) was prepared by an improved method. First, (3-Methoxyphenyl)-phosphonic acid diethyl ester 161 was prepared by the reaction of m-bromoanisole with triethyl phosphorite in the presence of anhydrous NiCl2. Removing of the by-product or microwave assistant synthesis could effectively accelerate the reaction and enhance the yield of product 161. Instead of the the Schmid’s method, a new one-pot oxidative home-coupling of 161 catalyzed by anhydrous FeCl3 was used to form rac-6,6`-dimethoxybiphenyl-2,2`-diyl-bis (phosphonic acid diethyl ester) rac-162. The new approach could avoid the preparation and purification of iodide derived from 161 and was much easier to manipulate and more cost-effective. A suitable resolution of rac-162 was studied and更多还原