权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

均相不对称催化为制备具有重要生物学意义的物质和先进材料的手性结构单元提供了基本工具。聚合物结合的催化剂具有固有的操作和经济优势：固定在固体基质上有利于从反应混合物中分离、回收和再利用昂贵的手性化合物。此外，固相反应为面向多样性的组合合成提供了技术基础。沿着这条线开发了许多树脂负载（预）催化剂，尽管它们的实际应用仅限于少数情况。其中许多催化剂的反应性比均相催化剂体系低得多，并且它们的立体选择性通常会降低，从而阻碍了实际应用。我们发现，RuCl_2(膦)_2(1,2-二胺)络合物与 2-丙醇中的碱性碱偶联，比共存的共轭或非共轭 C=C 键、卤素原子、各种杂环和许多其他官能团优先氢化 C=0 官能团。使用适当的手性二膦和二胺可以快速、高效地对一系列非手性和手性酮进行不对称氢化。它们的高效率促使我们和其他小组固定 BINAP/二胺 RuCl_2 配合物。该反应的周转数 (TON) 高达 12,300/批，或重复使用总计 33,000。使用聚合物结合催化剂的对映选择性、生产率和氢化速率与均相条件下获得的氢化反应相当。手性RuCl_2(二膦)(1,2-二胺)配合物与NaBH_4反应定量形成反式-RuH(η^1-BH_4)(二膦)(1,2-二胺)。 TolBINAP/DPEN Ru 络合物已通过单晶 X 射线分析以及核磁共振和红外光谱进行了表征。新的Ru配合物允许简单酮在2-丙醇中进行不对称氢化，无需额外的强碱。各种碱敏感酮可在温和条件下转化为高对映体纯度的手性醇，底物/催化剂比高达 100 000。构型不稳定的 2-异丙基-和 2-甲氧基环己酮可以通过高对映异构体区分度进行动力学拆分。该过程克服了早期使用 RuCl_2(二膦)(二胺) 和碱性碱的方法的缺点，该方法有时会导致不良反应，如酯交换、环氧开环、(β-消除和酮底物聚合)。