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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，在手性支架上带有硫脲和氨基。研究了带有3，5-二（三氟甲基）苯和二甲氨基的硫脲对1，3-二羰基化合物生成硝基烯烃的不对称Michael反应的影响。此外，我们还通过Michael反应开发了一条新的（R）-（-）-巴氯芬的合成路线，并得到了一个具有高对映选择性的手性季碳中心.双功能基硫脲催化硝基烷烃与N-叔丁氧羰基亚胺的aza-Henry反应，得到了高选择性的顺式β-硝基胺。N-叔丁氧羰基亚胺与各种硝基烷烃反应，主要产物为（R）-加合物，而N-膦酰亚胺反应则得到相应的（S）-加合物。通过转化为手性哌啶衍生物如CP-99，994.3证明了加成产物的合成通用性。PEG结合硫脲显示， ...更多信息 d比羧基聚苯乙烯HL树脂和TentaGel羧基树脂结合的催化剂具有更好的催化活性.用双官能团硫脲和TMG连续处理γ，δ-不饱和β-酮酯和硝基烯烃，促进了串联Michael加成反应，得到了具有高非对映体和对映体选择性的高度官能化的环己酮（高达> 99%de和92%ee）。将该反应应用于（-）-epibatidine的不对称合成.以硫脲为催化剂，研究了活性亚甲基化合物丙二腈、α-氰基乙酸甲酯和硝基甲烷与2-吡咯烷酮和2-甲氧基苯甲酰胺衍生的α，β-不饱和酰亚胺的不对称Michael加成反应。Michael加成物的ee值高达93%。用双官能团脲催化偶氮二羧酸酯与β-酮酯的α-肼化反应，产率高，对映选择性好。反应的范围被证明为各种底物和尿素催化剂被揭示是上级硫脲。在水溶液中，烷基自由基与含2-酚羟基的酮亚胺的分子间加成反应得以有效进行，为构建全取代sp^3-杂化碳中心提供了新的方法.少