CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

描述(申请人提供)：这项研究的长期目标是利用不对称催化以高产率和选择性有效地合成具有生物重要性的化合物的单一异构体。重点放在手性二氢呋喃(11)甲酰胺酸盐的独特能力，以导致高立体控制以及在高成交量(吨)时的特殊区域和化学选择性。这些催化剂最初是为催化金属卡宾转化而开发的，现在已知对Lewis酸催化转化有效，本提案在其应用中结合了这两种方法。介绍了木脂素内酯的隐形和异形系列的催化不对称合成，前列腺素合成中关键的双环内酯中间体的催化对映选择性合成，以及在环丙化反应中控制非对映选择性以形成不太稳定的顺式二取代异构体的计划。然而，我们努力的主要焦点是我们最近发现的叶立德化学和Lewis酸催化转化的新进展。通过叶立德中间体直接从乙烯基重氮乙酸酯和醛或亚胺合成环氧化物和氮杂环丙烷、二氢呋喃和二氢吡咯以及二氢氮杂卓类化合物是可能的，并将主要努力控制它们的形成。采用一步催化法合成双环吡咯及其类似物，将进一步发挥其优点。不对称Lewis酸催化的高立体选择性的异-Diels-Alder反应、[2+2]-环加成和1，3-偶极加成反应，使用手性二氢吡喃(11)碳酰胺盐催化剂，提供了潜在的显著优势，特别是从通常报道的不到50吨增加到10,000吨。这些研究利用了我们大量的手性碳酰胺二氢吡喃催化剂，因为它们的立体和电子特性有利于高反应活性和选择性，在催化金属卡宾和Lewis酸转化方面差别很大。

DESCRIPTION (provided by applicant): 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.