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）：这项研究的长期目标是使用不对称催化在高产量和选择性中对生物学重要化合物的单个异构体的有效合成。重点是手性dirhodium（LL）羧化剂的独特功能引起高立体控制，并在高转让数（TONS）下具有出色的区域和化学选择性。这些催化剂最初是为催化金属碳烯转化而开发的，现在已知对刘易斯酸催化的转化有效，并且该提案在其应用中都包含了这两种建议。描述了Stegane和Isostegan系列木烷内酯系列的催化对映选择性合成的计划，用于前列腺素合成中的一个重要的双环内酯中间体，并控制映映选择性，以形成不太稳定的CIS-DisubStitated同构体在自旋opopanations中的形成。但是，我们努力的主要重点是我们最近发现的YLIDE化学和刘易斯酸催化转化的新发展。高度立体选择性的环氧化物和氮杂氨酸，二氢呋喃和二氢吡咯并直接从Vinyldiazoacetates和醛或亚胺或亚胺通过Ylide Intermediates直接从Vinyldiazoacetates和醛或亚胺中进行的，现在有可能，并且将有可能进行重大努力。双环吡咯及其类似物是在一个步骤催化过程中制备的，其优势将进一步发展。不对称刘易斯酸催化了高度立体选择性的杂音alder反应，[2+2] - 循环载体和使用手性羧酰胺（LL）羧酰胺催化剂的1,3-二极添加的方法，尤其是在较大的库中提供的10,000个研究值，而不是50个研究的量库。 Dirhodium（LL）羧化型催化剂，因为它们的空间和电子特征有助于高反应性和选择性在催化金属碳和刘易斯酸转化中有很大差异。