ASYMMETRIC SYNTHESIS AND ITS APPLICATIONS

许多具有生物学和化学意义的有机化合物， 药物、激素和维生素都是手性的，不对称催化（AC） 这些方法提供了一种高效的合成方法， 对映体纯的底物。 这项建议主要针对 设计和开发这样的AC工艺，用于四种基本的有机 反应如下。 第一部分. AC Aldol反应 两种类型的AC过程将被 探讨了(a)最近发现Sn（IV）（O-t-Bu）_4及其相关化合物 非手性物质有效地催化Mukaiyama型羟醛缩合反应， 包括醛和乙烯氧基硅烷，以提供相应的 羟醛产物。 Sn（IV）催化剂与手性配体将被检查。 (b)许多硼介导的羟醛缩合反应立体选择性地进行， 所述硼羟醛酸盐产品。 将努力使其中一些 通过从硼生成硼-烯醇化物催化反应， 通过酯基转移或金属间化合物转移而形成的羟醛酸酯。 第二部分. AC烯丙基-和（E）-和（Z）-巴豆基甲基。 两种策略 将被探索。 (a)络合物（dppeRhC 1）2刚刚被发现， 催化苯甲醛与烯丙基三丁基锡烷的烯丙基锡化反应。 这 令人兴奋的发现，第一次这样的，将是一个 广泛寻找催化金属、配体和 试剂. (b)手性双功能催化剂的使用已经高度地 成功地用乙硼烷还原了一种酮， 醛与二乙基锌的Oguni-Soai-Noyori烷基化反应。 这个设备 现已应用于烯丙基硼化反应，并取得了一定的成功。 工作 应该并将继续提高不对称诱导的程度。 第三部分. 有机试剂与有机溶剂的AC共轭加成反应 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， 致力于发现能够实现共轭加成的催化剂， 相对不反应的烷基金属，例如（RO）2BR、R2 Zn、R4 Ge和 R4 Sn。 第四部分. 过渡金属催化剂手性配体的设计 用于氢化、酮还原和氢化硅烷化。 新型 已经设计了配体来增强手性化合物之间的相互作用， 部分和进入的反应物，并将检查其效率 在AC过程中。 除了上述AC方法之外，新的手性硼的合成 具有高非对映体选择性的试剂作为第I部分 IC. 试剂对立体化学控制的需求很高， 两个手性片段的羟醛型组装，这是一个在生物技术中经常遇到的过程。 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.