Catalytic Stereoselective Olefin Metathesis Reactions

描述（由申请人提供）：烯烃存在于许多生物活性分子中，并用于一些最广泛使用的转化中（如氢化，环氧化，硼化氢，二羟基化，环丙烷化，烯丙基取代，氢甲酰化和环加成）。许多烯烃以E或更高能量的Z异构体存在。因此，能够以高效、可靠、高选择性和具有成本效益的方式获得每种异构体形式的工艺对化学、生物学和医学具有重大意义。特别有价值的是烯烃立体选择性形成的催化过程；然而，这种方法并不常见。尤其缺乏的是能产生Z烯烃的催化方案。该项目的研究重点是设计、合成和开发一系列基于钼和钨的催化剂，这些催化剂可用于最强大、最有效的烯烃合成方法之一：催化烯烃复分解。这个由美国国立卫生研究院资助的项目最初设想的各种概念，将用于引入催化剂，这些催化剂可以在空气中操作，但当放置在有底物存在的溶液中时，却能提供出色的反应性和选择性。这样的催化剂将使化学家获得完全无法达到的反应性和/或选择性水平。烯烃复分解催化剂将用于促进烯丙醚、环氧化物、硼酸盐、硅烷以及乙烯基硼酸盐、二烯和1,2-不饱和羰基的z选择性交叉复分解反应。催化剂将被引入，使化学家能够制备二取代或三取代的大环烯烃，而不必在多步全合成的后期阶段丧失近一半的有价值的材料作为不需要的立体异构体。新的催化剂和方法将产生通常被视为合成化学家“面包和黄油”的实体，然而它们的制备往往需要漫长而不切实际的路线。这些概念、策略、催化剂和方案的特殊用途将通过有效的方法来合成具有重要生物学意义的分子，如抗诱变的falcarindiol、抗病毒的氯硫脂、细胞毒性的disorazole C1、赤霉素生物合成抑制剂cladospolide B、抗菌和抗癌的nakadomarin A、抗癌药物epothilone B和neopeltolide。

DESCRIPTION (provided by applicant): Alkenes are found in a great number of biologically active molecules and are employed in some of the most widely used transformations used to access them (such as hydrogenations, epoxidations, hydroborations, dihydroxylations, cyclopropanations, allylic substitutions, hydroformylations and cycloadditions). Many olefins exist as E or higher energy Z isomers. Processes that allow access to each isomeric form efficiently, reliably, with high selectivity and in a cost-effective fashion are therefore of substantial significance to chemistry, biology and medicine. Especially valuable are catalytic procedures for stereoselective formation of alkenes; however, such methods are uncommon. Particularly scarce are catalytic protocols that deliver Z alkenes. Research in this program is focused on the design, synthesis and development of a range of molybdenum- and tungsten-based catalysts that can be used for one of the most powerful and efficient methods for olefin synthesis: catalytic olefin metathesis. A variety of concepts, originally conceived in this NIH-funded program, will be used to introduce catalysts that can be manipulated in air and yet offer exceptional reactivity and selectivity when placed in solution in the presence of a substrate. Such catalysts will allow chemists to obtain reactivity and/or selectivity levels that remain entirely out of reach. Olefin metathesis catalysts will be developed that promote Z-selective cross-metathesis reactions of allylic ethers, epoxides, boronates, silanes as well as vinylbornates, dienes and 1,2-unsaturated carbonyls. Catalysts will be introduced that will allow chemists to prepare Z di- or trisubstituted macrocyclic alkenes, without having to forfeit nearly half of their valuable materials as the undesired stereoisomer at the late stages of a multi-step total synthesis. The new catalysts and methods will generate entities commonly viewed as the "bread and butter" of synthetic chemists, and yet their preparation often requires long and impractical routes. The special utility of the concepts, strategies, catalysts and protocols that will emerge from the proposed investigations will be highlighted through efficient approaches to syntheses of biologically significant molecules such as antimutagenic falcarindiol, antiviral chlorosufolipids, cytotoxic disorazole C1, gibberellin biosynthesis inhibitor cladospolide B, antibacterial and anticancer nakadomarin A, and anticancer agents epothilone B and neopeltolide.