New organic activators for the enantioselective reduction of aromatic imines with trichlorosilane
New organic activators for the enantioselective reduction of aromatic imines with trichlorosilane
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DOI：
10.1016/j.tetlet.2006.03.122
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发表时间：
2006-05
影响因子：
1.8
通讯作者：
O. Onomura;Yoshimi Kouchi;F. Iwasaki;Y. Matsumura
中科院分区：
文献类型：
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作者：
O. Onomura;Yoshimi Kouchi;F. Iwasaki;Y. Matsumura
N-吡啶甲酰基-（2S）-（二苯羟甲基）吡咯烷是一种有机活化剂，可用于氯硅氢还原芳香亚胺为相应的胺类化合物。实验结果表明，N-甲酰基并不一定是吡咯烷衍生物的N-保护基。酮1和亚胺2的不对称还原是近年来不对称合成研究的热点之一。3各种还原剂已被用于还原，但仍值得开发新的方法，可以使用廉价的还原剂在温和的条件下进行。这些试剂之一可以是三氯硅烷（Cl 3SiH），一种容易从硅工业获得的液体材料，4尽管Cl 3SiH需要一些活化剂来有效地还原酮和亚胺。5我们已经报道了手性N-甲酰基吡咯烷衍生物1作为有机活化剂在用Cl 3SiH对酮6和亚胺7的对映选择性还原中的应用。在室温下，还原反应进行顺利，具有良好的产率和对映选择性高达43%ee的酮的还原和66%ee的亚胺的还原。最近，报道了一种新的活化剂2，用于Cl_3SiH还原亚胺，具有高的对映选择性（高达92%ee）。[8]这些还原反应中值得注意的一点是，N-甲酰基取代基的存在对这些还原反应是必不可少的。在我们继续努力开发新的手性有机化合物代替1来活化Cl 3SiH，9的过程中，我们发现N-吡啶甲酰基吡咯烷衍生物3a-f在芳族亚胺4还原成胺5（Eq 1）中也用作有机活化剂。这是第一个数据表明，N-甲酰基在有机活化剂的结构中并不总是必不可少的，
N-Picolinoyl-(2S)-(diphenylhydroxymethyl) pyrrolidine was found to work as an organic activator in the reduction of aromatic imines to the corresponding amines by Cl3SiH. The highest selectivity was 80% ee. This is the first data showing that N-formyl group is not always essential as N-protecting group of pyrrolidine derivatives for the reduction of imines by Cl3SiH.Enantioselective reduction of ketones1 and imines2 has been one of recent topics in asymmetric synthesis. 3 A variety of reducing reagents have been used in the reductions but it is still worthwhile to exploit new methods which can be carried out using inexpensive reducing reagents under mild conditions. One of such reagents may be trichlorosilane (Cl3SiH), a liquid material easily available from silicon industry, 4 though some activator is necessary for Cl3SiH to efficiently reduce ketones and imines. 5 We already reported chiral N-formylpyrrolidine derivatives 1 as organic activators in the enantioselective reduction of ketones6 and imines7 with Cl3SiH. The reduction proceeds smoothly at room temperature with good yields and enantioselectivity of up to 43% ee for the reduction of ketones and 66% ee for the reduction of imines. Recently, a new activator 2 for Cl3SiH in reducing imines with high enantioselectivity (up to 92% ee) was reported. 8 The noticeable point in those reductions was that the presence of N-formyl substituent was essential for those reductions. In our continuing effort to exploit new chiral organic compounds in place of 1 to activate Cl3SiH, 9 we found N-picolinoylpyrrolidine derivatives 3a-f to also work as organic activators in the reduction of aromatic imine 4 to amine 5 (Eq 1). This is the first data showing that N-formyl group is not always essential in the structure of organic activators for