CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

用于对映选择性合成的手性催化剂

• 批准号: 6606586
• 负责人: Michael PATRICK Doyle
• 金额: $ 21.26万
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6606586
• 关键词: carbene; catalyst; chemical synthesis; cyclization; cyclopropanes; furans; high performance liquid chromatography; lignans; organometallic compounds; rhodium; stereochemistry; stereoisomer; ylide

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.

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且高效地合成生物学上重要的化合物的单一异构体。重点是手性二铑(II)甲酰胺酯的独特能力，可在高周转数 (TON) 下实现高立体控制以及卓越的区域和化学选择性。这些催化剂最初是为催化金属卡宾转化而开发的，现在已知对路易斯酸催化转化有效，并且该提案将这两种催化剂纳入其应用中。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，前列腺素合成中关键的双环内酯中间体，以及控制环丙烷化反应中不太稳定的顺式二取代异构体形成的非对映选择性。然而，我们努力的主要焦点是我们最近发现的叶立德化学和路易斯酸催化转化的新进展。现在可以通过叶立德中间体直接从重氮乙酸乙烯酯和醛或亚胺高度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庚烷，并且主要努力将针对它们形成的对映体控制。双环吡咯及其类似物采用一步催化法制备，其优点将得到进一步发挥。使用手性二铑(II)甲酰胺催化剂进行高度立体选择性杂狄尔斯-阿尔德反应、[2+2]-环加成和 1,3-偶极加成的不对称路易斯酸催化方法具有潜在的显着优势，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库存 甲酰胺酸二铑(II)催化剂，因为其有利于高反应活性和选择性的空间和电子特征在催化金属卡宾和路易斯酸转化之间存在很大差异。