Transition Metal Mediated Routes--Heterocycles/Carbocycl

过渡金属介导的路线——杂环/碳环

• 批准号: 7016442
• 负责人: JANIS LOUIE
• 金额: $ 28.1万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016442
• 关键词: catalyst; chemical addition; chemical structure function; chemical synthesis; cyclization; heavy metals; heterocyclic compounds; hydrocarbons; method development; molecular rearrangement; nickel; organic chemicals; pyridine; pyrones

DESCRIPTION (provided by applicant): The objective of this research program is to develop new reaction methodology for synthesizing economically important and biologically relevant carbocyclic and heterocyclic molecules. Studies will focus on the elaboration and advancement of nickel-catalyzed annulations and cyclizations that function under user-friendly conditions and employ benign starting materials. These reactions will include regioselective cycloadditions of unsaturated hydrocarbons with heterocumulenes and new cyclization-based molecular rearrangements. These reactions will find utility in the synthesis of a variety of pharmaceuticals and biologically active substrates for which current synthetic approaches are either non-existent or inefficient. The initial phases will build upon previous accomplishments involving nickel-based catalysts for mediating carbon dioxide/diyne and isocyanate/diyne annulations to produce 2-pyrones and 2-pyridones, respectively. The substrate scope of this particular system will be expanded to include other heterocumulenes and other unsaturated hydrocarbons. Ultimately, this should afford a rich array of complex carbocyclic, heterocyclic, and fused-ring compounds. Key mechanistic steps will be explored through the use of model compounds permitting concomitant catalyst re-design (e.g., through use of new ligands and/or metals) to enhance reaction performance and scope. Parallel efforts will focus on nickel-catalyzed cyclization rearrangements of readily accessible unactivated cyclopropylen-ynes as atom-economical syntheses of heterocycles and carbocycles under mild conditions. Throughout the proposal, opportunities are described for preparing biologically or commercially important substrates or related analogues and will be pursued. This research program will reverberate across the scientific disciplines of organic and organometallic chemistry, chemical biology, and medicinal chemistry.

描述（由申请人提供）：该研究计划的目的是开发新的反应方法，以综合经济重要和生物学相关的碳循环和杂环分子。研究将重点介绍在用户友好条件下运作并采用良性的起始物质的镍催化环境和环化的详细和进步。这些反应将包括具有杂量和新的基于环化的分子重排的不饱和烃的区域选择性环节。这些反应将在合成各种药物和生物活性底物的合成中找到效用，而当前合成方法不存在或效率低下的生物活性底物。最初的阶段将基于涉及基于镍的催化剂的成就，用于介导二氧化碳/二氧化物和异氰酸酯/二烷酸/二烷酸/diyne环境，分别产生2-吡咯和2-吡啶酮。该特定系统的底物范围将扩展到包括其他杂环和其他不饱和烃。最终，这应该提供一系列复杂的碳环，杂环和融合环化合物。通过使用允许催化剂重新设计（例如，通过使用新的配体和/或金属）来增强反应性能和范围的模型化合物，将探索关键机械步骤。平行的努力将集中于镍催化的环化重排，该重排在轻度条件下作为异环和碳循环的原子经济合成，作为原子经济合成。在整个提案中，都描述了在生物学或商业上重要的底物或相关类似物中准备的机会，并将被追求。该研究计划将在有机和有机金属化学，化学生物学和药物化学的科学学科中回荡。