ASYMMETRIC SYNTHESIS AND ITS APPLICATIONS

许多具有生物和化学价值的有机化合物，如 药物、激素和维生素是手性的，不对称催化(AC) 工艺提供了一种高效的合成方法 对映体纯底物。这项建议主要是针对 四种基本有机物的AC工艺设计与开发 反应，如下所列。 第一部分AC-Aldol反应。将有两种类型的交流工艺 探索过了。(A)最近发现，锡(IV)(O-t-Bu)4和有关 非手性物种有效催化Mukaiyama类型的Aldol反应 涉及乙醛和聚氧乙烯氧基硅烷，以提供相应的 Aldol产品。我们将考察具有手性配体的锡(IV)催化剂。 (B)许多硼介导的羟醛反应以立体选择性进行，以获得 硼醛酸盐产品。将努力实现其中的一些 由硼生成硼烯醇酸盐的反应是催化的 通过酯交换或金属交换生成的醛类化合物。 第二部分：AC-烯丙基和(E)-和(Z)-克洛基金属作用。两种策略 将会被探索。(A)刚刚发现络合物(DppeRhC1)2 催化苯甲醛与烯丙基三丁基锡烷的烯丙基锡化反应。这 这是第一个令人兴奋的发现，紧随其后的是 广泛地寻找一组最佳的催化金属、配体和 试剂。(B)手性双功能催化剂的使用 成功地完成了酮与二硼烷的Isuno-Corey还原反应 醛与二乙基锌的烷基化反应。这个设备 现在已被应用于烯丙基硼反应，并取得了一定的成功。这项工作 应该并将继续提高不对称诱导的程度。 第三部分：有机金属试剂的AC共轭加成 α，β-不饱和羰基体系。我们在这方面的主要努力 将涉及(A)铜酸盐的手性配体的设计和合成 和(B)锌酸盐催化剂。此外，(C)将进行探索性搜索 用来发现能够实现共轭加成的催化剂 相对不活泼的烷基金属，如(RO)2Br、R2Zn、R4Ge和 R4Sn. 第四部分过渡金属催化剂手性配体的设计 用于氢化、酮还原和硅氢化。新类型的 配体已经被设计成增强手性之间的相互作用 并将检查它们的效率 在交流工艺中。 除上述AC工艺外，新的手性硼的合成 第一部分包括具有高非对映面选择性的试剂 IC.对试剂的需求很高，需要用来进行立体化学控制 两个手性片段的羟醛类型组装，这是一种经常在 收敛的天然产物合成。

Many organic compounds of biological and chemical interest such as medicines, hormones, and vitamins are chiral, and asymmetric catalytic (AC) processes provide a highly efficient means of synthesizing enantiometrically pure substrates. This proposal is aimed mainly at the design and development of such AC processes for four fundamental organic reactions, as itemized below. Part I. The AC Aldol Reaction. Two types of AC processes will be explored. (a) It has been found recently that Sn(IV) (O-t-Bu)4 and related achiral species efficiently catalyze the Mukaiyama-type aldol reaction that involves an aldehyde and a vinyloxysilane to provide the corresponding aldol product. Sn(IV) catalysts with a chiral ligand will be examined. (b) Many boron-mediated aldol reactions proceed stereoselectively to afford the boron aldolate products. Efforts will be made to render some of these reactions catalytic by generating the boron-enolates from the boron aldolates through transesterification or transmetallation. Part II. AC Allyl- and (E)- and (Z)-Crotylmetallation. Two strategies will be explored. (a) The complex (dppeRhC1)2 has just been found to catalyze allylstannation of benzaldehyde with allytributylstannane. This exciting discovery, the first of this kind, will be followed by an extensive search for an optimum set of catalytic metal, ligand, and reagent. (b) The use of a chiral bifunctional catalyst has been highly successful in the Itsuno-Corey reduction of a ketone with diborane and Oguni-Soai-Noyori alkylation of an aldehyde with diethylzinc. This device has now been applied to allylboration with moderate success. The work should and will be continued to enhance the degree of asymmetric induction. Part III. The AC Conjugate Addition of Organometallic Reagents to the alpha,beta-unsaturated Carbonyl System. Our major efforts in this area will concern the design and synthesis of chiral ligands for (a) the cuprate and (b) zincate catalysts. In addition, (c) an exploratory search will be made to discover catalysts capable of effecting conjugate addition of relatively unreactive alkylmetals exemplified by (RO)2BR,R2Zn,R4Ge and R4Sn. Part IV. Design of Chiral Ligands for Transition Metal Catalysts Which Are Used in Hydrogenation, Ketone Reduction, and Hydrosilylation. New types of ligands have been designed to enhance the interaction between the chiral moiety and an incoming reactant and will be examined for their efficiency in the AC processes. In addition to the above AC processes, the synthesis of new chiral boron reagents of high diastereofacial selectivity is included in Part I as Part Ic. The reagents are in high demand for stereochemical control of the aldol-type assembly of two chiral fragments, a process often encountered in convergent natural product syntheses.