A library of chiral imidazoline-aminophenol ligands: Discovery of an efficient reaction sphere
A library of chiral imidazoline-aminophenol ligands: Discovery of an efficient reaction sphere
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DOI：
10.1002/chem.200701439
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Yanagisawa, Akira
中科院分区：
文献类型：
--
作者：
Arai, Takayoshi;Yokoyama, Naota;Yanagisawa, Akira
在固体载体上合成了咪唑啉-氨基苯酚配体文库。将手性氯甲基咪唑类化合物1和2固定在聚苯乙烯磺酰氯上后，与(R)或(S)-苯乙胺(3和4)进行亲核取代反应，得到四种聚合物支载的咪唑啉胺类配体。用水杨醛7-10进一步还原烷基化得到一系列咪唑啉-氨基苯酚配体(L9-L24)。固相催化/圆二色谱高通量筛选铜催化的Henry反应的分析表明，配体L25由(S，S)-二苯乙二胺衍生的咪唑啉，(S)-苯乙胺和二溴苯酚组成，是高效的配体，从而在95%的ee中提供了硝基甲烷和苯甲醛的加合物。立体中心的结合是促进高立体选择性反应的关键。在吲哚和硝基烯烃的FriedelCraft烷基化反应中也研究了L25的独特反应球体，得到了高达83%ee的加合物。
A library of imidazoline-aminophenol ligands was synthesized on solid supports. After immobilization of chiral chloromethylimidazolines 1 and 2 onto the polystyrylsulfonyl chloride, nucleophilic substitution with (R)or (S)-phenylethylamine (3 and 4) provided four combinations of polymer-supported imidazoline-amine ligands. Further reductive alkylation using salicylaldehydes 7-10 provided a series of imidazoline-aminophenol ligands (L9-L24). Analysis by solid-phase catalysis/circular dichroism high-throughput screening of a copper-catalyzed Henry reaction revealed that ligand L25, comprising a (S,S)-diphenylethylenediamine-derived imidazoline, (S)-phenyle-thylamine, and dibromophenol, was highly efficient, thus providing the adduct of nitromethane and benzaldehyde in 95% ee. The combination of stereogenic centers was crucial in promoting the highly stereoselective reactions. The unique reaction sphere of L25 was also examined in a FriedelCrafts alkylation of indole and nitroalkene to give the adduct in up to 83% ee.