Development of a bifunctional urea based catalyst

双功能尿素催化剂的研制

• 批准号: 6836703
• 负责人: Kian Tan
• 金额: $ 4.11万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-02 至 2006-08-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836703
• 关键词: catalyst; chemical addition; chemical structure function; chemical synthesis; combinatorial chemistry; imines; postdoctoral investigator; stereoisomer; technology /technique development; urea

DESCRIPTION (provided by applicant): This proposal discusses the design and development of a bifunctional chiral organic catalyst that will promote the addition of a variety of nucleophiles into imine substrates. The products of these reactions are functionalized chiral amines, which are important components in natural products and drug candidates. A 50- member catalyst library will be synthesized on solid support and then screened for catalyst efficiency and enantioselectivity in the reaction of allyl- and crotylsilane additions as well as the additions of dialkylzinc reagents to imines. The catalyst will incorporate a Lewis acidic urea group and a Lewis basic group (tertiary amines or phosphine oxides). These electrophiles were chosen due to their susceptibility to Lewis basic activation and the importance of the chiral amine products to drug discovery. With the discovery of an active catalyst, rigorous control experiments will be used to determine if the catalyst is behaving bifunctionally. The overall goal of the project is to elucidate whether the chiral urea functionality is a privileged catalyst structure. Such a catalyst would make a significant contribution to the field of asymmetric catalysis.

描述（由申请人提供）：该提案讨论了双功能手性有机催化剂的设计和开发，该催化剂将促进各种亲核试剂添加到亚胺底物中。这些反应的产物是功能化的手性胺，是天然产物和候选药物的重要成分。将在固体载体上合成 50 元催化剂库，然后筛选烯丙基和巴豆基硅烷加成反应以及二烷基锌试剂与亚胺加成反应中的催化剂效率和对映选择性。该催化剂将结合路易斯酸性脲基团和路易斯碱性基团（叔胺或氧化膦）。选择这些亲电子试剂是因为它们对路易斯碱活化的敏感性以及手性胺产物对药物发现的重要性。随着活性催化剂的发现，将使用严格的控制实验来确定催化剂是否具有双功能。该项目的总体目标是阐明手性尿素功能是否是一种特殊的催化剂结构。这种催化剂将为不对称催化领域做出重大贡献。