Asymmetric Hydrogenation of Ketones and Olefins

酮和烯烃的不对称氢化

基本信息

批准号：
13440188
负责人：
OHKUMA Takeshi
金额：
$ 8.64万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13440188/
关键词：
asymmetric hydrogenation chiral alcohols DPEN enantioselectivity reaction mechanism Ru(II) complexes simple ketones XylBINAP ヘテロ原子置換ケトン Xy1BINAP DAIPEN 生理活性物質

项目摘要

Homogeneous asymmetric catalysis provides a fundamental tool for the preparation of chiral building blocks for biologically important substances and advanced materials. Polymer-bound catalysts have inherent operational and economical advantages : immobilization on solid matrices facilitates the separation from reaction mixtures, recovery, and reuse of the expensive chiral compounds. Further, the solid-phase reaction offers a technical basis for diversity-oriented combinatorial synthesis. Numerous resin-supported (pre)catalysts have been developed along this line, though their practical application application is limited to only a few cases. Many of these are much less reactive than the homogeneous catalyst systems, and their stereoselectivity is often reduced, impeding practical use. We have found that RuCl_2(phosphine)_2(1,2-diamine) complexes, coupled with an alkaline base in 2-propanol, hydrogenate a C=0 function preferentially over coexisting conjugated or nonconjugated C=C linkage … More s, halogen atoms, various hetrocycles, and many other functional groups. The use of appropriate chiral diphosphines and diamines results in rapid and productive asymmetric hydrogenation of a range of achiral and chiral ketones. Their high efficiency prompted us and other groups to immobilize the BINAP/diamine RuCl_2 complexes. This reaction exhibits a turnover number (TON) as high as 12,300/batch or a total of 33,000 by repeated use. The enantioselectivity, productivity, and rate of hydrogenation using the polymer-bound catalysts are comparable to those attained under homogeneous conditions.Reaction of a chiral RuCl_2(diphosphine)(1,2-diamine) complex and NaBH_4 forms trans-RuH(η^1-BH_4)(diphosphine)(1,2-diamine)quantitatively. The TolBINAP/DPEN Ru complex has been characterized by single crystal X-ray analysis as well as NMR and IR spectra. The new Ru complexes allows for asymmetric hydrogenation of simple ketones in 2-propanol without an additional strong base. Various base-sensitive ketones are convertible to chiral alcohols in a high enantiomeric purity with a substrate/catalyst ratio of up to 100 000 under mild conditions. Configurationally unstable 2-isopropyl- and 2-methoxycyclohexanone can be kinetically resolved with a high enantiomer discrimination. This procedure overcomes the drawback of an earlier method using RuCl_2(diphosphine)(diamine) and an alkaline base, which sometimes causes undesired reactions such as ester exchange, epoxy-ring opening, (β-elimination, and polymerization of ketonic substrates. Less

同质的不对称催化为制备生物学重要物质和晚期材料的手性构建块提供了基本工具。聚合物结合的催化剂遗传了运营和经济优势：固定物质上的固定化有助于与昂贵的手性化合物的反应混合物，恢复和重复使用的分离。此外，固相反应为多样性的组合合成提供了技术基础。尽管它们的实际应用程序仅限于少数情况，但已经开发了许多树脂支持的（前）催化剂。其中许多比均质催化剂系统的反应性要小得多，并且它们的立体选择性通常会降低，从而阻碍了实际使用。我们发现Rucl_2（磷酸）_2（1,2-二胺）复合物，与2-丙醇中的合金碱偶联，氢化氢A C = 0优先效应，而不是共轭的或非共轭或非共轭的C = C = C = C链接…更多S，更多S，更多S，Halogen Anogen Anogen Anogen Anogen Anogen Anogen AnogoN Anogen AnogoN AnogoN AnogoN AnogoN AnogoN Atoms，各种杂种和许多其他功能。使用适当的手性双磷酸和二氨氨酸的使用导致一系列运动和手性酮的快速和产物不对称的氢化。他们的高效率促使我们和其他小组固定BINAP/Diamine Rucl_2复合物。通过重复使用，该反应表现出高达12,300/批次的周转数（吨）或总计33,000。 The enantioselectivity, productivity, and rate of hydrogenation using the polymer-bound catalysts are comparable to those attached under homogeneous conditions.Reaction of a chiral RuCl_2(diphosphine)(1,2-diamine) complex and NaBH_4 forms trans-RuH(η^1-BH_4)(diphosphine)(1,2-diamine)quantitatively. TOLBINAP/DPEN RU复合物的特征是单晶X射线分析以及NMR和IR光谱。新的RU复合物允许在2-丙醇中简单酮的不对称氢化，而没有额外的强碱。各种碱敏感的酮可转换为高性化合物纯度，在轻度条件下的底物/催化剂比最高可达100 000。在构型不稳定的2-异丙基和2-甲氧基环己酮上可以通过高的对映异构体歧视来动力学解决。该过程克服了使用RUCL_2（Diphasphine）（二氨基）和合金碱的早期方法的缺点，这有时会引起不受欢迎的反应，例如酯交换，环氧环开放，（β-溶解和酮症底物的聚合）。