Development of Chiral Organocatalyst and Application to Asymmetric Synthesis

手性有机催化剂的研制及其在不对称合成中的应用

基本信息

批准号：
16390006
负责人：
TAKEMOTO Yoshiji
金额：
$ 6.53万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

1. We synthesized a new class of bifunctional thiourea catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. The thiourea bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon-center with high enantioselectivity by the Michael reaction.2. Bifunctional thiourea catalyzed aza-Henry reaction of nitroalkanes to N-Boc-imines, giving syn-β-nitroamines with good to high diastereo- and enantioselectivity. The reaction of N-Boc-imine with various nitroalkanes gave (R)-adducts as major products, whereas the same reaction of N-phosphonoylimines furnished the corresponding (S)-adducts. Synthetic versatility of the addition products was demonstrated by the transformation to chiral piperidine derivatives such as CP-99,994.3. The PEG-bound thiourea showe … More d better catalytic activity than those of the carboxypolystyrene HL resin- and TentaGel carboxy resin-bound ones.4. Successive treatment of γ,δ-unsaturated β-ketoesters and nitroalkenes with a bifunctional thiourea and TMG promoted the tandem Michael addition, giving rise to highly functionalized cyclohexanones with high diastereo-and enantioselectivity (up to >99% de and 92% ee). The reaction was applied to the asymmetric synthesis of (-)-epibatidine.5. A thiourea-catalyzed asymmetric Michael addition of activated methylene compounds such as malononitrile, methyl α-cyanoacetate, and nitromethane to α,β-unsaturated imides derived from 2-pyrrolidinone and 2-methoxybenzamide was developed. The Michael adducts were obtained with up to 93% ee.6. The organocatalytic α-hydrazination of β-keto esters with azodicarboxylates using a bifunctional urea proceeded in high yields and with good enantioselectivity. The scope of the reaction was demonstrated for various substrates and the urea catalyst was revealed to be superior to thiourea.7. Intermolecular alkyl radical addition to ketimines having 2-phenolic hydroxy group proceeded effectively in aqueous media, providing the novel method for construction of all-substituted sp^3-hybridized carbon center. Less

1。我们合成了一类新的双功能硫脲催化剂，并在手性支架上带有硫脲部分和一个氨基组。 3-二氨基化合物还向硝基烯丁求发。神与各种硝基烷的反应。例如CP-99,994.3。双功能硫脲和TMG促进了串联迈克尔的添加，使高度功能化的环己酮具有高映射和对映选择性（最高> 99％的DE和92％的EE）从2-吡raldine和2-甲氧基苯甲酰胺中添加了非对称的甲基化合物，例如甲基因腈，甲基α-氰乙酸和硝基甲烷，β-β-无饱和度使用双功能尿素的β-酮酯对各种底物的α-酮酯进行了尿素，并在水性培养基中催化了尿素，从而在水性培养基中进行了成熟的销售，从而提供了新颖的方法，用于分解所有叠加的SP^3- 3-杂交碳中心。