CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

这项研究的长期目标是有效和高效地合成单异构体 利用不对称催化，高产率和高选择性地合成具有生物重要性的化合物。焦点 是关于手性二氢呋喃(11)羧胺酸盐的独特能力，以引起高度立体控制 再加上在高成交量(吨)时具有极高的区域和化学选择性。原来是这样的 这些催化剂是为催化金属卡宾转化而开发的，现在已知是 对Lewis酸催化的转化有效，本建议将两者都纳入其 申请。描述了催化对映体选择性合成隐形化合物和 前列腺素中关键的双环内酯中间体--木脂素内酯的异十八烷基系列 合成，并控制非对映选择性以形成较不稳定的顺式二取代物 环丙烷化反应中的异构体。然而，我们努力的主要重点是在新的 叶立德化学和刘易斯酸催化转化的最新进展 被发现了。高立体选择性合成环氧化物、氮杂环丙烷、二氢呋喃和 二氢吡咯和二氢氮杂环己烷通过乙烯基重氮乙酸酯和醛或亚胺直接合成 叶立德中间体现在是可能的，主要的努力将集中在他们的对映控制上 队形。用一步催化法合成了双环吡咯及其类似物 其优势将得到进一步发挥。不对称路易斯酸催化的合成方法 高立体选择性的Diels-Alder反应、[2+2]-环加成反应和1，3-偶极加成反应 使用手性二氢呋喃(11)羧氨酸酯催化剂提供了潜在的显著优点， 特别是从通常报告的不到50吨增加到1万吨。这些研究 充分利用我们大量的手性二氢呋喃(11)氨酸酯催化剂，因为它们的立体结构 有利于高活性和高选择性的电子特征在不同的催化剂中差别很大。 金属卡宾和路易斯酸的转化。

The long-term objective of this research is the effective and efficient synthesis of single isomers of biologically important compounds in high yields and selectivities using asymmetric catalysis. Focus is on the unique capabilities of chiral dirhodium(ll) carboxamidates to cause high stereocontrol together with exceptional regio- and chemoselectivity at high turnover numbers (TONs). Originally developed for catalytic metal carbene transformations, these catalysts are now known to be effective for Lewis acid-catalyzed transformations, and this proposal incorporates both in its applications. Plans are described for the catalytic enantioselective syntheses of the stegane and isostegan series of lignan lactones, for a key bicyclic lactone intermediate in prostaglandin syntheses, and to control diastereoselectivity for formation of the less stable cis-disubstituted isomer in cyclopropanation reactions. However, the principal focus of our efforts is in new developments from ylide chemistry and Lewis acid-catalyzed transformations that we have recently discovered. Highly stereoselective syntheses of epoxides and aziridines, dihydrofurans and dihydropyrroles, and dihydroazepines directly from vinyldiazoacetates and aldehydes or imines via ylide intermediates are now possible, and major efforts will be directed to enantiocontrol in their formation. Bicyclic pyrroles and their analogues are prepared in a one-step catalytic process whose advantages will be further developed. Asymmetric Lewis acid catalyzed approaches to highly stereoselective hetero-Diels-Alder reactions, [2+2]-cycloadditions, and 1,3-dipolar additions using chiral dirhodium(ll) carboxamidate catalysts offer potentially significant advantages, especially with TONs up to 10,000 from commonly reported values of less than 50. These studies take advantage of our large stock of chiral dirhodium(ll) carboxamidate catalysts, since their steric and electronic features conducive to high reactivity and selectivity differ greatly among catalytic metal carbene and Lewis acid transformation.