METAL CATALYSED ASYMMETRIC DIELS-ALDER REACTIONS

在合成大的、复杂的生物活性分子方面， 碳-碳键的形成至关重要。 与碳-碳键形成相关的问题是 控制生物活性的立体化学 这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 在卫生领域具有至关重要的作用。这项建议是 旨在提炼最强大的碳之一--碳的形成 反应，Diels-Alder反应。 Diels-Alder反应的显著之处在于它可以产生UP 一步得到4个串联的手性中心，控制 4个中心的相对立体化学。因此，它已经 广泛应用于天然产物的合成。虽然很多人 Diels-Alder反应的一些方面已经得到了很大的解决 学位，仍然是一个重大挑战；它是催化和 不对称。这项提议是针对开发手性的 硼、铝、钛和锡等元素的催化剂 催化的不对称Diels-Alder反应。建议的手性 催化剂很容易制造，并且在以前的基础上 经验，都有可能成功。最初，我们建议 研究经典的Diels-Alder伙伴，α-β- 丁二烯和丁二烯的不饱和酯、醛和酮 环戊二烯。重点放在催化的性质上。 这将涉及到催化的平衡和动力学研究。 以及亲双烯催化剂加合物的分离，以便 了解催化和对映体选择的起源。 对不对称催化意志的机理理解 为开发新的、更精致的、不对称的 催化剂。我们认为，有效的发展不对称 催化Diels-Alder催化剂将对 综合战略，最终将导致更多 高效生产生物活性分子。

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.