Development of a bifunctional urea based catalyst

描述（由申请人提供）：本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手性胺，是天然产物和候选药物的重要成分。在固体载体上合成了一个50元催化剂库，并对烯丙基硅烷和丁基硅烷加成反应以及二烷基锌试剂对亚胺加成反应的催化剂效率和对映选择性进行了筛选。催化剂将包含路易斯酸性尿素基团和路易斯碱性基团（叔胺或氧化膦）。选择这些亲电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。这种催化剂将对不对称催化领域做出重大贡献。

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.