Catalytic Stereoselective Olefin Metathesis Reactions

催化立体选择性烯烃复分解反应

基本信息

批准号：
8608535
负责人：
AMIR H HOVEYDA
金额：
$ 53.68万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-03-01 至 2016-01-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：烯烃存在于大量生物活性分子中，并用于一些最广泛使用的转化中以获取它们（例如氢化、环氧化、硼氢化、二羟基化、环丙烷化、烯丙基取代、加氢甲酰化）和环加成）。许多烯烃以 E 或更高能量的 Z 异构体存在。因此，能够以高选择性和成本效益的方式高效、可靠、高选择性地获得每种异构体形式的方法对于化学、生物学和医学具有重要意义。特别有价值的是用于立体选择性形成烯烃的催化方法；然而，这种方法并不常见。特别稀缺的是提供 Z 烯烃的催化方案。该项目的研究重点是设计、合成和开发一系列钼基和钨基催化剂，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。这项由美国国立卫生研究院 (NIH) 资助的项目最初构想的各种概念将用于引入可以在空气中操作的催化剂，并且在存在底物的情况下置于溶液中时提供卓越的反应性和选择性。这种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。将开发烯烃复分解催化剂，促进烯丙醚、环氧化物、硼酸酯、硅烷以及乙烯醇酸酯、二烯和1,2-不饱和羰基化合物的Z选择性交叉复分解反应。引入的催化剂将使化学家能够制备Z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因为不需要的立体异构体而损失近一半的有价值的材料。新的催化剂和方法将产生通常被合成化学家视为“面包和黄油”的实体，但它们的制备通常需要漫长且不切实际的路线。拟议研究中出现的概念、策略、催化剂和方案的特殊用途将通过有效合成具有生物学意义的分子的方法来强调，例如抗突变的falcarindiol、抗病毒的氯磺脂、细胞毒性地索拉唑C1、赤霉素生物合成抑制剂cladospolide B、抗菌药物和抗癌剂 nakadomarin A，以及抗癌剂埃坡霉素 B 和 Neopeltolide。