Development of New Asymmetric Catalytic Processes

新型不对称催化工艺的开发

• 批准号: 6542473
• 负责人: WILLIAM Dean WULFF
• 金额: $ 27.37万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-05 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6542473
• 关键词: Diels Alder reaction; alkylation; antineoplastics; aziridines; chemical synthesis; cyclization; diazo compound; drug design /synthesis /production; imines; morphine; organometallic compounds; palladium; ritonavir; sphingolipids; stereochemistry

This proposal has as its goal the development of asymmetric catalytic versions of several synthetically important reactions. Efficient catalysts for asymmetric Diels-Alder reactions and aziridination of imines with diazo compounds have been developed with the vaulted biaryl ligands VAPOL and VANOL Future efforts will be directed to determining the scope, mechanism and synthetic applicstions of these existing processes. The information that has already been gained in the study of the Diels-Alder reaction has been used to design new ligands that are tailored for octahedral Lewis acids. Derivatives of the VAPOL ligand will also be explored as a platform for organo-palladium chemistry. If successful, these ligands will be screened for allylic substitutions, cycloisomerizations of enynes, [3 + 2] cycloadditions of TMM complexes and oxy(aza) palladation / carbonylation reactions. The scope of the asymmetric aziridination will be explored with respect to the imine and diazo substrates in both inter- and intramolecular modes. A method is proposed for the first general method for the alkylation of aziridine -2-carboxylates. Methods will explored for the development of a general method for the synthesis of both alpha-amino acids and beta-amino acids from the asymmetric catalytic aziridination reaction. Some of the targets for the aziridination reaction include morphine, the diamine portion of ritonavir, sphingolipids and the antitumor agent FR-900482.

该提案的目标是开发几个重要合成反应的不对称催化版本。 使用拱形联芳基配体 VAPOL 和 VANOL 开发了用于不对称 Diels-Alder 反应和亚胺与重氮化合物氮丙啶化的高效催化剂。未来的努力将致力于确定这些现有过程的范围、机制和合成应用。在第尔斯-阿尔德反应研究中获得的信息已用于设计适合八面体路易斯酸的新配体。 VAPOL 配体的衍生物也将作为有机钯化学的平台进行探索。 如果成功，将筛选这些配体的烯丙基取代、烯炔的环异构化、TMM 配合物的[3 + 2]环加成和氧(氮杂)钯化/羰基化反应。 将在分子间和分子内模式下针对亚胺和重氮底物探索不对称氮丙啶化的范围。 提出了一种用于氮丙啶-2-羧酸酯烷基化的第一个通用方法。 将探索开发从不对称催化氮丙啶化反应合成 α-氨基酸和 β-氨基酸的通用方法的方法。 氮丙啶化反应的一些靶标包括吗啡、利托那韦的二胺部分、鞘脂和抗肿瘤剂 FR-900482。