Catalyzed Coupling of Organostannanes with Electrophiles

复杂分子的合成需要开发灵敏、高性价比的新试剂。有机和大分子化学项目的这项拨款支持研究导致新的催化过程，这将促进新一代抗生素的合成，这些抗生素的特征是极其复杂的立体化学相互关系。本研究的目的是利用有机锡试剂和有机亲电试剂作为偶联剂，探索合成上有用的钯催化偶联反应。该研究的一个目标是开发一种不对称合成方法，其中通过使用光学活性过渡金属催化剂在偶联位点产生手性碳。为了达到这些目标，将寻求有机锡试剂如何将有机基团转移到有机卤化adium（II）的机制理解。各种有机锡试剂与带有反式螯合膦配体的烷基钯（II）卤化物的金属化反应将进行，使金属化产物不能进行还原消除。将探索几何纯（E或Z）三氟乙烯酯的合成及其与有机锡烷，特别是乙烯基锡烷的偶联反应，以合成含有共轭二烯的化合物，共轭二烯是各种生物活性产品的重要结构特征，包括源自花生二酸的某些共轭多烯。探索三氟化芳酯的偶联反应，开发三氟化芳酯和芳卤与乙烯基锡烷的反应，合成多种吲哚类生物碱。为了扩大这一反应的范围，将寻找其他有用的亲电试剂，如乙烯基环氧化物和-卤代羰基。一些未经测试的锡试剂的有效利用应该为各种产品提供新的合成途径，包括一些拟除虫剂。这种偶联化学在应变环化合物合成中的应用也将得到发展。

The synthesis of complex molecules requires the development of sensitive, cost-effective new reagents. This grant in the Organic and Macromolecular Chemistry Program supports research leading to new catalytic processes that will facilitate synthesis of the new generation of antibiotics that are characterized by extremely complex stereochemical interrelationships. It is the object of this research to explore synthetically useful palladium-catalyzed coupling reactions utilizing an organotin reagent and an organic electrophile as coupling partners. One goal of the research is the development of an asymmetric synthesis in which a chiral carbon is generated at the coupling site by the use of optically active transition metal catalysts. In order to attain these objectives, a mechanistic understanding of how an organotin reagent transfers an organic group to an organopalladium(II) halide will be sought. The transmetallation reactions of various organotin reagents with alkylpalladium(II) halides bearing a trans-chelating phosphine ligand will be carried out such that the transmetallation product cannot undergo reductive elimination. The synthesis of geometrically pure (E or Z) vinyl triflates and their coupling reactions with organostannanes, particuarly vinylstannanes, will be explored in an effort to synthesize compounds containing the conjugated dienes, an important structural feature in a variety of biologically active products, including certain conjugated polyenes derived from arachadonic acid. The coupling reactions of aryl triflates will be explored, and the reactions of both aryl triflates and aryl halides with vinylstannane will be developed for the synthesis of a number of indole alkaloids. Other useful electrophiles for coupling, such as vinyl epoxides and alpha-halocarbonyls will be sought in order to expand the scope of this reaction. The effective use of a number of untested tin reagents should provide new synthetic pathways to a variety of products including a number of pyrethoids. The utilization of this coupling chemistry in the synthesis of strained ring compounds also will be developed.