CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

描述（由申请人提供）：本研究的长期目标是使用不对称催化以高产率和选择性有效和高效地合成生物重要化合物的单一异构体。重点关注手性二铑（II）甲酰胺酯在高转换数（TON）下引起高立体控制以及出色的区域和化学选择性的独特能力。这些催化剂最初是为催化金属卡宾转化而开发的，现在已知它们对刘易斯酸催化转化是有效的，并且该提议在其应用中结合了两者。计划描述的stegane和isostegan系列的木脂素内酯，前列腺素合成中的关键双环内酯中间体的催化对映选择性合成，并控制非对映选择性形成的不太稳定的顺式-二取代的异构体在环丙烷化反应。然而，我们努力的主要重点是在叶立德化学和刘易斯酸催化的转变，我们最近发现的新发展。从乙烯基重氮乙酸酯和醛或亚胺通过叶立德中间体直接高立体选择性地合成环氧化物和氮丙啶、二氢呋喃和二氢吡咯以及二氢氮杂卓现在是可能的，并且主要的努力将针对其形成中的对映体控制。一步催化法合成双环吡咯及其类似物，其优点将得到进一步发挥。使用手性氨甲酰二铑（II）催化剂的高度立体选择性的杂-Diels-桤木反应、[2+2]-环加成和1，3-偶极加成的不对称刘易斯酸催化方法提供了潜在的显著优点，特别是TON从通常报道的小于50的值高达10，000。这些研究利用了我们大量的手性氨甲酰二铑（II）催化剂，因为它们有利于高反应性和选择性的空间和电子特征在催化金属卡宾和刘易斯酸转化之间差异很大。

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.