Design and application of new methods for asymmetric carbon-carbon bond formation

这项提议的目的是研究碳-碳键不对称结构的新方法。将开发新的有机催化剂和手性支架，并考察它们在不对称合成中的应用。不对称有机催化：本建议的目标之一是开发新的有机催化剂，用于基本过程，如碳亲核试剂与烯酮和硝基烯烃的立体选择性共轭加成，以及氨基二烯与丙烯酸酯或硝基烯烃的碳环化反应。将考察的催化剂类型有：a)手性胍，b)手性二胺和三胺。这些催化剂将从对映体纯氨基酸、氨基醇和萜类化合物中进行阐述，并将对手性吡咯烷类有机催化剂中氢键给体的性质和位置进行研究。这些催化剂在共轭加成和碳环化反应中的应用将被研究。将考察其在生物活性分子合成中的应用，如石蒜烷类生物碱。手性模板的不对称合成：将考察手性吗啉模板的合成和不对称官能化反应。重点是开发模板，提供良好的立体控制和手性调节剂的容易回收。将研究这些模板在立体选择性烷基化、羰基加成和氮杂环化反应中的应用。将探索构建高度功能化的碳环、氧杂环、氮杂环以及多肽异构体。这一研究将为有机化学和药物化学中有用的分子的对映选择性合成提供新的方法，并为制药行业或学术界的学生提供培训。

The objective of this proposal is to investigate new methods for the asymmetric construction of carbon-carbon bonds. New organocatalysts and chiral scaffolds will be developed and their applications in asymmetric synthesis will be examined.Asymmetric Organocatalysis: One aim of this proposal is the development of new organocatalysts for fundamental processes such as stereoselective conjugate additions of carbon nucleophiles to enones and nitroalkenes as well as carbocyclization reactions of aminodienes with acrylates or nitroalkenes. The catalyst types that will be examined are: a) chiral guanidines, b) chiral diamines and triamines. The catalysts will be elaborated from enantiomerically pure amino acids, amino alcohols and terpenoids.A study of the nature and positioning of hydrogen bond donor groups in chiral pyrrolidine-based organocatalysts will be undertaken. The utility of these catalysts in conjugate addition and carbocyclization reactions will be studied. Application to the synthesis of bioactive molecules such as the lycorane class of alkaloids will be examined.2. Asymmetric Synthesis on Chiral Templates: The synthesis and asymmetric functionalization reactions of chiral morpholine templates will be examined. The focus is the development of templates that offer good stereocontrol and easy recovery of the chiral regulator. The use of these templates in stereoselective alkylation, carbonyl addition and aziridination reactions will be studied. The construction of highly functionalized carbocycles, oxacycles and azacycles as well as peptide isosteres will be explored.The research will provide new methods for the enantioselective synthesis of molecules that are useful in organic chemistry and medicinal chemistry, and provide training to employ students in the pharmaceutical industry or in academia.