Development of New Asymmetric Catalytic Processes

本提案的目标是开发几种重要合成反应的不对称催化版本。以双芳基配体VAPOL和VANOL为载体的不对称Diels-Alder反应和亚胺与重氮化合物的叠氮化反应的高效催化剂已被开发出来，今后将致力于确定这些现有工艺的范围、机理和合成应用。在Diels-Alder反应的研究中已经获得的信息已经被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，这些配体将被筛选用于烯丙基取代，炔的环异构化，TMM配合物的[3 + 2]环加成和氧（aza）钯化/羰基化反应。不对称叠氮化的范围将在分子间和分子内模式下对亚胺和重氮底物进行探讨。提出了氮吡啶-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叠氮化反应中合成α -氨基酸和β -氨基酸的通用方法。叠氮化反应的一些靶点包括吗啡、利托那韦的二胺部分、鞘脂和抗肿瘤药物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.