Diureas as Ligands in Asymmetric Reduction of Ketones
Diureas as Ligands in Asymmetric Reduction of Ketones
复制标题
双脲作为酮不对称还原的配体
DOI：
10.1021/jo960574f
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发表时间：
1996
影响因子：
3.6
通讯作者：
M. Lemaire
中科院分区：
文献类型：
--
作者：
P. Gamez;B. Dunjić;M. Lemaire
虽然膦在过去的三十年里受到了更多的关注，但最近的论文证明了含氮配体在不对称催化中的有用性。Sharpless 1和Jacobsen 2很好地说明了这种配体在CO键形成中的潜在用途。最近，Pfaltz，3 Noyori，4 Mukaiyama，5以及我们实验室的报告6表明，含氮配体可用于不对称还原，其对映体选择性与最佳手性膦相似或甚至更高。酮的氢化物转移还原反应是其中一种使用酮的反应。7我们最近报道了在酮的多相还原中成功地利用聚脲作为配体和载体。8基于这些结果，我们选择制备和评价聚合物的单体类似物（即，二脲），目的是实现溶液相化学。事实上，考虑到二脲作为氢化物转移还原的有效配体的功能，将不同的市售二异氰酸酯与二胺缔合的可能性允许快速制备大量的新配体。通过方案1中描述的顺序制备二脲。二胺1或2在异氰酸酯（2当量）存在下在二氯甲烷中在氩气下处理过夜，得到80-95%产率的二脲3。9使用3a和3b作为配体对一系列芳族酮进行不对称还原（方案2），结果收集在表1中。表1-4（表1）强调了铑-配体3a络合物作为催化剂的利用。苯乙酮的还原（表1，条目1）导致43%ee的（R）-1-苯基乙醇。用苯丙酮（表1，条目2）获得最好的结果，其被还原80%ee。除了2，2-二甲基苯丙酮（表1，条目4），（S，S）配体构型导致（R）-醇（氢化物加成通过酮的Si面发生）。该结果可以通过大体积叔丁基迫使基质通过其Re面接近铑催化剂来解释（方案3，A和B）。在苯丙酮的还原中使用配体3b（表1，条目5）显示出对映选择性从80%降低到37%，尽管注意到更好的催化效率（表1，条目2和5）。这种较低的对映选择性可能是由于萘基的空间效应导致铑的弱络合。用苯丙酮探索了使用铱作为金属的尝试（表1，条目6），表明催化铱络合物的活性和对映选择性都较低。我们还评估了由二胺1和2和光学纯异氰酸酯合成的二脲。这种非对映异构体配体的使用使我们能够研究
Although phosphines have received more attention during the last three decades, recent papers have demonstrated the usefulness of nitrogen-containing ligands in asymmetric catalysis. Sharpless1 and Jacobsen2 have nicely illustrated the potential uses of such ligands in CO bond formation. More recently, Pfaltz, 3 Noyori, 4 Mukaiyama, 5 as well as reports from our laboratory6 have shown that nitrogen-containing ligands can be used in asymmetric reductions with similar or even higher enantioselectivities than those obtained with the best chiral phosphines. The hydride transfer reduction of ketones is one of the reactions where they have been used. 7 We recently reported on the successful utilization of polyureas as ligands and as supports in a heterogeneous reduction of ketones. 8 On the basis of these results, we chose to prepare and evaluate the monomeric analogs of the polymers (ie, diureas) with the aim of attaining solution phase chemistry. Indeed, considering the diurea function as an efficient ligand for hydride transfer reduction, the possibility to associate different commercially available diisocyanates with diamines allows a rapid preparation of a great number of new ligands. Diureas were prepared by the sequence depicted in Scheme 1. Treatment of diamine 1 or 2 in the presence of an isocyanate (2 equiv) in dichloromethane overnight under argon gave diureas 3 in 80-95% yields. 9 Asymmetric reductions using 3a and 3b as ligands were performed on a series of aromatic ketones (Scheme 2), and the results are collected in Table 1. Entries 1-4 (Table 1) highlight the utilization of a rhodium-ligand 3a complex as catalyst. Reduction of acetophenone (Table 1, entry 1) led to a 43% ee of (R)-1-phenylethanol. The best result was obtained with propiophenone (Table 1, entry 2), which was reduced in 80% ee. Except for the 2, 2-dimethylpropiophenone (Table 1, entry 4), a (S, S) ligand configuration resulted in (R)-alcohols (the hydride addition occurs by the Si face of the ketones). This result can be explained by a bulky tert-butyl group forcing the substrate to approach the rhodium catalyst by its Re face (Scheme 3, A and B). The use of ligand 3b in the reduction of propiophenone (Table 1, entry 5) showed a decrease of enantioselectivity from 80 to 37%, although better catalytic efficacy (Table 1, entries 2 and 5) was noted. This lower enantioselectivity may be due to a steric effect of the naphthyl group leading to a weak complexation of rhodium. An attempt using iridium as the metal was explored with propiophenone (Table 1, entry 6) showing that the catalytic iridium complex was both less active and enantioselective. We also evaluated the diureas synthesized from diamines 1 and 2 and optically pure isocyanates. The use of such diastereoisomeric ligands permitted us to study