Catalytic asymmetric addition of β-ketoesters to various Imines by using chiral palladium complexes
Catalytic asymmetric addition of β-ketoesters to various Imines by using chiral palladium complexes
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DOI：
10.1002/anie.200462202
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Sodeoka, M
中科院分区：
文献类型：
--
作者：
Hamashima, Y;Sasamoto, N;Sodeoka, M
羰基化合物的金属烯醇化物与亚胺的加成反应，即所谓的mannich型反应，是一类重要的碳-碳成键反应反映了Mannich加合物在含氮化合物合成中的潜在用途，[2]、[3]和其他[4]已经报道了催化对映选择性Mannich型反应的有效方法然而，在我们之前的报告中，酮的预活化形成硅烯醇醚是必要的。为了满足目前对原子经济过程的需要，在亚胺中直接加入亲核试剂是非常可取的最近我们报道了手性Pd配合物1和2与1,3 -二羰基化合物（如β-酮酯）反应生成手性Pd烯醇酯（方案1）利用Pd烯醇化反应，建立了一种高效的烯酮对映选择性迈克尔催化反应。[7a]有趣的是，由1衍生的手性烯酸酯A顺利进行了Michael反应，而由2衍生的相应的Pdenolate则完全不活跃。这些结果表明，强质子酸三氟甲烷磺酸（TfOH）与Pd烯醇酸1伴随形成，并激活烯酮与Pd烯醇酸A协同作用，从而促进CÀC成键反应。如果亚胺的质子化作用大大提高了反应活性，那么上述Pd烯醇酯化学将适用于mannich型反应。据我们所知，在催化不对称Mannichtype反应中使用β-酮酯的报道只有一个，其中Jørgensen和同事[8]获得了超过90% ee的优异对映选择性。然而，只有所测试的亚胺是高活性的np -甲苯磺酰保护亚胺酯和可用的范围
Addition reactions of metal enolates of carbonyl compounds to imines, the so-called Mannich-type reaction, represent an important class of carbon–carbon bond-forming reactions.[1] Reflecting the potential utility of the Mannich adducts in the synthesis of nitrogen-containing compounds,[2] we [3] and others [4] have reported efficient methods for catalytic enantioselective Mannich-type reactions.[5] In our previous reports, however, the pre-activation of ketones to form silyl enol ethers was necessary. To meet the present need for atomeconomical processes, the direct addition of pronucleophiles to imines is highly desirable.[6] Recently we reported that chiral Pd complexes 1 and 2 reacted with 1, 3-dicarbonyl compounds, such as β-ketoesters, to give chiral Pd enolates (Scheme 1).[7] Using this Pd enolate chemistry, an efficient catalytic enantioselective Michael reaction with enones was developed.[7a] Interestingly, the chiral enolate A derived from 1 underwent the Michael reaction smoothly, whereas the corresponding Pdenolate derived from 2 was completely inactive. These results indicated that the strong protic acid, trifluoromethanesulfonic acid (TfOH), formed concomitantly with the Pd enolate from 1 and activated the enone to act cooperatively with the Pd enolate A, thereby promoting the CÀC bond-forming reaction. Provided that the reactivity of imines is greatly enhanced by protonation, the above-mentioned Pd enolate chemistry would be applicable to the Mannich-type reaction. To our knowledge there has been only one reported example of the use of β-ketoesters in a catalytic asymmetric Mannichtype reaction, where Jørgensen and co-workers [8] achieved excellent enantioselectivities of more than 90% ee. However, only the imine tested was a highly reactive Np-toluenesulfonyl-protected imino ester and the scope of the available