CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

描述（由申请人提供）：本研究的长期目标是利用不对称催化以高收率和高选择性有效和高效地合成生物学上重要化合物的单异构体。重点是手性镉（ll）羧酰胺类化合物在高周转率(t)下具有高立体控制和特殊的区域选择性和化学选择性的独特能力。这些催化剂最初是为催化金属碳转化而开发的，现在已知它们对刘易斯酸催化的转化是有效的，本提案将两者结合在其应用中。计划描述了木脂素内酯的甾烷和异甾烷系列的催化对映选择性合成，前列腺素合成中的关键双环内酯中间体，以及控制环丙烷反应中形成不稳定的顺式二取代异构体的非对映选择性。然而，我们努力的主要焦点是我们最近发现的乙烷化学和刘易斯酸催化转化的新进展。现在可以直接由乙烯基重氮乙酸酯和醛或亚胺通过酰化物中间体合成高度立体选择性的环氧化物和叠氮醚、二氢呋喃和二氢吡啶以及二氢氮卓类化合物，并将主要努力在其形成过程中控制对映体。双环吡咯及其类似物是一步法合成的，其优点有待进一步开发。不对称Lewis酸催化的高立体选择性杂diols - alder反应、[2+2]-环加成和1,3-偶极加成的方法使用手性dihodium (ll) carboxamidate催化剂具有潜在的显著优势，特别是当吨从通常报道的小于50的值增加到10,000时。这些研究利用了我们大量的手性羰基甲酸二钠催化剂，因为它们的空间和电子特征有利于高反应活性和选择性，在催化金属羰基和路易斯酸转化方面有很大的不同。

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.