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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意义的物质和先进材料的手性构件提供了基本工具。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、回收和重复使用昂贵的手性化合物。此外，该固相反应为以多样性为导向的组合合成提供了技术基础。许多树脂负载(前)催化剂已经沿着这条线被开发出来，尽管它们的实际应用仅限于少数几种情况。其中许多催化剂的活性比均相催化体系低得多，而且它们的立体选择性往往降低，阻碍了实际应用。我们发现RuCl2(膦)2(1，2-二胺)配合物与异丙醇中的碱性碱偶联，优先氢化C=0的功能，而不是共存的共轭或非共轭C=C键…较多的有S、卤素原子、各种杂环等多种官能团。适当的手性双膦和二胺的使用导致了一系列非手性和手性酮的快速和有效的不对称氢化。它们的高效率促使我们和其他基团固定化了BINAP/二胺RuCl2络合物。该反应的周转数(吨)高达12,300个/批次，重复使用总计33,000个。手性RuCl2(双膦)(1，2-二胺)络合物与NaBH4反应生成trans-RuH(η^1-BH_4)(diphosphine)(1，2-diamine)quantitatively.用单晶X-射线分析、核磁共振和红外光谱对TolBINAP/DPEN-Ru络合物进行了表征。新的Ru络合物允许单酮在异丙醇中的不对称氢化，而不需要额外的强碱。在温和的条件下，各种碱敏酮可以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-甲氧基环己酮可以以较高的对映体识别率进行动力学拆分。该方法克服了以前使用RuCl2(双膦)(二胺)和碱性碱的方法的缺点，该方法有时会引起酯交换、环氧环开环、(β-消除)和酮底物聚合等不良反应。较少