Development of Highly Selective Asymmetric Reactions

作为手性Lewis，将酒石酸二甲酯衍生的1，4-手性二醇部分引入到钛化合物中，制备了钛试剂。手性钛试剂在各种不对称反应中有着广泛的应用。在一定量的手性钛和分子筛4A的催化作用下，丙烯酸和富马酸的衍生物与二烯反应生成了具有高对映选择性的[4+2]环加合物。通过与手性钛的分子内Diels-Alder反应，合成了几乎光学纯的双环碳环。手性钛试剂还促进了丙烯酸衍生物与烯基二硫缩醛(或烯基或炔基硫化物)之间的[2+21]环加成反应。环丁烷和环丁烯的合成具有较高的对映选择性。手性钛催化不对称分子内烯反应，对映体选择性地得到环戊酮和环己酮。在手性钛的存在下，各种类型的醛与氰基三甲基硅烷在90%以上的Ee中反应生成相应的氰醇。手性醇钛作为手性催化剂可有效地用于外消旋羧酸类化合物的动力学拆分。α-芳基乙酸的拆分选择性较高。从所制备的光学活性中间体出发，以光学纯的形式合成了氧杂草素的C-类似物、格拉迪索和依西隆-杜松烯。

As a chiral Lewis, titanium reagents have been prepared by introducing a 1,4-chiral diol moiety derived from dimethyl tartrate to titanium compounds. The chiral titanium reagents have found a wide application to various asymmetric reactions.1. Acrylic acid and fumaric acid derivatives react with dienes to afford the [4+2] cycloadducts with high enantioselectivity by the combined use of a catalytic amount of the chiral titanium and Molecular Sieves 4A. Bicyclic carbocycles are synthesized in almost optically pure forms by intramolecular Diels-Alder reactions with the chiral titanium.2. The chiral titanium reagent also promotes [2+21 cycloadditions between acrylic acid derivatives and ketene dithioacetals (or alkenyl or alkynyl sulfides). Cyclobutanes and cyclobutenes are prepared in high enantioselectivity.3. Asymmetric intramolecular ene reaction is catalyzed with the chiral titanium, and cyclopentanone and cyclobexanones are obtained enantioselectively.4. Various types of aldehydes react with cyanotrimethylsilane in the presence of the chiral titanium to give the corresponding cyanohydrins in more than 90%ee.5. The chiral titanium alkoxide is efficiently employed in the kinetic resolution of racemic carboxylic acids derivatives as a chiral catalyst. alpha-Arylacetic acids are resolved in high selectivity.6. Starting from the optically active intermediates thus prepared, C-analogue of oxetanocin, grandisol and epsilon-cadinene are synthesized in optically pure forms.