Asymmetric conjugate addition of nitromethane to enones catalyzed by chiral N,N'-dioxide-scandium(III) complexes.
Asymmetric conjugate addition of nitromethane to enones catalyzed by chiral N,N'-dioxide-scandium(III) complexes.
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DOI：
10.1002/chem.201000688
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发表时间：
2010-07
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通讯作者：
Liwei Wang;Qi Zhang;Xin Zhou;Xiaohua Liu;Lili Lin;B. Qin;Xiaoming Feng
中科院分区：
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作者：
Liwei Wang;Qi Zhang;Xin Zhou;Xiaohua Liu;Lili Lin;B. Qin;Xiaoming Feng
硝基烷烃与a，b-不饱和酮的催化共轭加成是有机合成中最重要的过程之一，因为相应的产物是合成各种更复杂结构的中间体，如氨基烷烃、氨基羰基、内酯和吡咯烷。在过去的几十年里，人们在这方面付出了巨大的努力；然而，据我们所知，大多数这些合成是由有机催化剂或相转移催化剂促进的，尽管手性金属配合物催化的反应，如杂双金属手性催化剂、三联萘氧化镧和saln - al配合物，也有报道。此外，在以往的研究中，催化剂通常受到底物范围的限制，这意味着它们只对一种特定类型的烯酮有效，而对查尔酮和“肉桂酮”衍生物都高效的催化剂很少有报道。因此，寻找一种简单，高效的合成这两种类型的烯酮，具有高对映选择性和广泛的底物范围，仍然是具有挑战性和有趣的。在此，我们报道了ScACHTUNGTRENNUNG(OTf)3/N,N ' - 2配合物有效地促进了硝基甲烷到烯酮的Michael加成，以优异的收率（高达99%）和优异的对映异构体过量（查尔酮高达99%，肉桂酮衍生物高达98%）提供了所需的加合物。以查尔酮与硝基甲烷的反应为模型反应，对反应条件进行了优化。对不同金属的筛选表明，Sc ACHTUNGTRENNUNG(OTf)3在给予产品方面优于任何其他金属（表1，条目5与1 - 4）。随后，研究了N，N ' -二氧化氮配体的结构（L1-L5）。结果表明，在苯胺官能的邻位上具有大体积基团的配体，如异丙基，提供了良好的结果（表1，条目8与6和7）。对于手性骨架，如果用(S)雷米普利衍生的N，N ' -二氧化二氮代替l-脯氨酸或(S)-细果酸衍生的N，二氧化二氮，结果略有改善（>99% ee；表1，第9项）。为了进一步提高反应效率，考察了添加剂和溶剂等几种反应条件，[a]王磊，张琪，周晓霞，刘晓霞博士，林玲博士，秦斌博士，冯晓霞教授，四川大学化学学院绿色化学与技术教育部重点实验室，四川成都610064传真：（+86）28-8541-8249电子邮件：xmfeng@scu.edu.cn qinbo@163.com本文的支持信息可在WWW的http://dx.doi.org/10.1002/chem.201000688下找到。表1。硝基甲烷与查尔酮的不对称迈克尔加成。
The catalytic conjugate addition of nitroalkanes to a,b-unsaturated ketones is one of the most important processes in organic synthesis, since the corresponding products are very useful intermediates for the synthesis of a variety of more elaborate structures, such as amino alkanes, amino carbonyls, lactones, and pyrrolidines. In the past decades, tremendous effort has been devoted to this area; however, to the best of our knowledge, most of these syntheses are promoted by organocatalysts or phase-transfer catalysts, although reactions catalyzed by chiral metal complexes, such as heterobimetallic chiral catalysts, lanthanum trisbinaphthoxide, and a salen–Al complex, have also been reported. Furthermore, catalysts in previous studies generally suffer from limitations in substrate scope that mean they are only effective for one particular type of enone and catalysts with high efficiency for both chalcone and “cinnamone” derivatives have rarely been reported. Therefore, finding a simple, efficient synthesis for both of these types of enone, with high enantioselectivity and broad substrate scope, is still challenging and interesting. Herein, we report that a ScACHTUNGTRENNUNG(OTf)3/N,N’-dioxide complex efficiently promotes the Michael addition of nitromethanes to enones, providing the desired adducts in excellent yields (up to 99%) and excellent enantiomeric excesses (up to>99% for chalcone and up to 98% for “cinnamone” derivatives). The reaction between chalcone and nitromethane was selected as the model reaction for optimizing the conditions. A screening of different metals revealed that Sc ACHTUNGTRENNUNG(OTf)3 was superior to any other at giving the product (Table 1, entry 5 vs. 1–4). Subsequently, the structure of the N,N’-dioxide ligand was studied (L1–L5). It was shown that ligands with bulky groups at the ortho position of the aniline functionality, such as isopropyl groups, provide good results (Table 1, entry 8 vs. 6 and 7). As for the chiral backbone, if an (S)ramipril-derived N,N’-dioxide was used instead of those derived from l-proline or (S)-pipecolic acid, the result was slightly improved (>99% ee ; Table 1, entry 9). To further improve the efficiency of the reaction, several other reaction conditions, such as additives and solvents, [a] L. Wang, Q. Zhang, X. Zhou, Dr. X. Liu, Dr. L. Lin, Dr. B. Qin, Prof. Dr. X. Feng Key Laboratory of Green Chemistry & Technology Ministry of Education, College of Chemistry Sichuan University, Chengdu 610064 (China) Fax: (+86)28-8541-8249 E-mail : xmfeng@scu.edu.cn qinbo@163.com Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201000688. Table 1. Asymmetric Michael addition of nitromethane to chalcone.