Development of New Asymmetric Catalytic Processes

新型不对称催化工艺的开发

• 批准号: 6749050
• 负责人: WILLIAM Dean WULFF
• 金额: $ 24万
• 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/6749050
• 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.

该提案的目标是几种重要反应的不对称催化版本的发展。 通过拱形的双子体配体Vapol和Vanol Future Future努力，将针对这些现有过程的范围，机制和合成应用来确定，已开发出有效的促催化剂，用于非对称的Diels-Alder反应和与重氮化合物的Aziridination和Riasine一起使用。在Diels-Alder反应研究中已经获得的信息已用于设计针对八面体刘易斯酸量身定制的新配体。 Vapol配体的衍生物也将作为有机钯化学的平台探索。 如果成功，这些配体将被筛选以进行烯丙基取代，Enynes的环化体，[3 + 2] TMM复合物和氧气（AZA）Palladation / Carbonylation反应的环载条。 在分子间和分子内模式中，将探讨不对称副岛的范围。 提出了一种方法，用于第一种通用方法，用于氮岛-2-羧酸盐的烷基化。 将探索用于开发从不对称催化替依依反应中合成α-氨基酸和β-氨基酸的一般方法。 氮杂性反应的一些靶标包括吗啡，利托纳维尔的二胺部分，鞘脂和抗肿瘤剂FR-900482。