Development of New Asymmetric Catalytic Processes

这项提议的目标是开发几个合成上重要的反应的不对称催化形式。利用拱形联芳基配体VAPOL和VANOL开发了用于亚胺与重氮化合物的不对称Diels-Alder反应和氮杂环化反应的高效催化剂。未来的努力将集中在确定这些现有工艺的范围、机理和合成应用上。在Diels-Alder反应的研究中已经获得的信息已经被用来设计为八面体Lewis酸量身定做的新配体。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，这些配体将被筛选为烯丙基取代、烯炔的环异构化、TMM络合物的[3 2]环加成反应和氧(氮)甲基化/羰化反应。不对称氮杂环化的范围将在分子间和分子内两种模式下针对亚胺和重氮底物进行探索。提出了氮杂环丙烷-2-羧酸酯烷基化反应的第一种通用方法。将探索从不对称催化氮杂环化反应合成α-氨基酸和β-氨基酸的一般方法。氮杂环化反应的一些靶点包括吗啡、利托那韦的二胺部分、鞘磷脂和抗肿瘤药物FR-900482。

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.