METAL CATALYSED ASYMMETRIC DIELS-ALDER REACTIONS

金属催化不对称狄尔斯-阿尔德反应

• 批准号: 3299061
• 负责人: BRICE BOSNICH
• 金额: $ 16.73万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3299061
• 关键词: Diels Alder reaction; aldehydes; alkaloids; aluminum; boron; catalyst; chemical structure function; cyclopentane; ketones; ligands; metals; molecular asymmetry; saturated /unsaturated bonds; stereochemistry; stereoisomer; stoichiometry; tin; titanium

In the synthesis of large, complex biologically active molecules, carbon-carbon bond formation is of fundamental importance. Associated with carbon-carbon bond formation is the problem of controlling the stereochemistry on which biological activity depends to a large degree. Thus, the development of new methodologies for stereo-controlled carbon-carbon bond formation is of crucial importance in the health field. This proposal is directed at refining one of the most powerful carbon-carbon forming reactions, the Diels-Alder reaction. The Diels-Alder reaction is remarkable in that it can generate up to 4 concatenated chiral centers in a single step with control of the relative stereochemistries of the 4 centers. As such, it has been used extensively in natural product synthesis. Although many of the aspects of Diels-Alder reaction have been solved to a large degree, there remains a major challenge; that it be catalytic and asymmetric. This proposal is directed at developing chiral catalysts of the elements boron, aluminum, titanium, and tin for the catalytic asymmetric Diels-Alder reaction. The proposed chiral catalysts are readily made and, on the basis of previous experience, are likely to be successful. Initially, we propose to investigate the classical Diels-Alder partners, alpha-beta- unsaturated esters, aldehydes and ketones with butadienes and cyclopentadiene. The emphasis is on the nature of the catalysis. This will involve equilibrium and kinetic studies of the catalysis and the isolation of dienophile-catalyst adducts in order to understand the origins of catalysis and of the enantioselection. A mechanistic understanding of the asymmetric catalysis will provide a basis for developing new, more refined, asymmetric catalysts. We believe that the development of effective asymmetric catalytic Diels-Alder catalysts will have a broad impact on synthetic strategies which will ultimately lead to the more efficient production of biologically active molecules.

在合成大的，复杂的生物活性分子时， 碳-碳键的形成具有根本的重要性。 与碳-碳键形成相关的问题是 控制立体化学， 在很大程度上取决于。 因此，新的发展 立体控制的碳-碳键形成方法 在卫生领域至关重要。 这项建议是 旨在提炼一种最强大的碳-碳形成 Diels-Alder反应 Diels-Alder反应是显着的，因为它可以生成 到4个串联的手性中心， 4个中心的相对立体化学。 因此， 广泛应用于天然产物的合成。 尽管许多 Diels-Alder反应的许多方面已经得到很大程度的解决， 在某种程度上，仍然存在一个重大挑战;它是催化剂， 不对称 该建议旨在开发手性 元素硼、铝、钛和锡的催化剂， 催化不对称Diels-Alder反应 提出的手性 催化剂容易制备，并且基于先前的 经验，很可能会成功。 首先，我们建议 研究经典的狄尔斯-阿尔德伙伴，α-β- 与丁二烯的不饱和酯、醛和酮， 环戊二烯。 重点是催化的性质。 这将涉及催化反应的平衡和动力学研究 以及亲二烯体-催化剂加合物的分离， 理解催化和对映选择的起源。 对不对称催化的机理理解将 为开发新的、更精细的、不对称的 催化剂的 我们认为，发展有效的不对称 催化Diels-Alder催化剂将对 综合战略，最终将导致更多的 有效生产生物活性分子。