CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

用于对映选择性合成的手性催化剂

• 批准号: 7498720
• 负责人: Michael PATRICK Doyle
• 金额: $ 3.5万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498720
• 关键词: Acids; Aldehydes; Amides; Antidepressive Agents; Azepines; Aziridines; Carbon; Catalysis; Chemistry; Cyclopropanes; Deoxy Sugars; Development; Diels Alder reaction; Electronics; Epoxy Compounds; Esters; Funding; HIV-1 Reverse Transcriptase; Hydrogen; Imines; Isomerism; Lactones; Lignans; Metals; Methodology; Numbers; Object Attachment; One-Step dentin bonding system; Positioning Attribute; Process; Prostaglandins; Pyrroles; Pyrrolidines; Reaction; Reporting; Research; Reverse Transcriptase Inhibitors; Series; analog; aziridine; carbene; carboxylate; catalyst; cycloaddition; cyclopropane; design; novel; practical application; pyrrolidine; pyrroline; receptor; stegane; ylide

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.

本研究的长期目标是有效和高效地合成单异构体的 使用不对称催化以高产率和选择性合成生物学重要化合物。重点 手性二铑（II）羧酰胺酯引起高度立体控制的独特能力 以及在高周转数（TON）下的特殊区域选择性和化学选择性。原本 开发用于催化金属卡宾转化，现在已知这些催化剂是 有效的刘易斯酸催化的转化，并且该建议将两者都纳入其 应用.计划描述的催化对映选择性合成的stegane和 木脂素内酯的isostegan系列，用于前列腺素中的关键双环内酯中间体 合成，并控制形成较不稳定的顺式-二取代的 环丙烷化反应中异构体。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发展，我们最近 发现了环氧化物和氮丙啶、二氢呋喃和环氧化物的高度立体选择性合成 二氢吡咯和二氢氮杂卓，直接从乙烯基重氮乙酸酯和醛或亚胺经由 叶立德中间体现在是可能的，主要的努力将针对对映体控制， 阵双环吡咯及其类似物是在一步催化过程中制备的 其优势将得到进一步发挥。不对称刘易斯酸催化合成 高立体选择性的杂Diels-桤木反应、[2+2]-环加成和1，3-偶极加成 使用手性氨甲酰二铑（II）催化剂提供了潜在的显著优点， 特别是对于从通常报道的小于50的值到10，000的TON。这些研究 利用我们大量手性氨甲酰二铑（II）催化剂，因为它们的立体 有利于高反应性和选择性的电子特征在催化剂之间差异很大。 金属卡宾和刘易斯酸转化。