Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Nat Commun. 2016 Dec 23;7:13780. doi: 10.1038/ncomms13780.
α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N-sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure.
α-手性胺在药物化学、不对称合成和材料科学中具有重要意义，但高效合成它们的方法却很少。特别是，具有挑战性的四取代碳立体中心的α-手性胺的合成是一个长期存在的问题，而催化不对称加成有机金属试剂到酮亚胺上可以直接得到这些分子的方法还不够发达。在这里，我们报道了一种通过廉价、易于处理且易于获得的格氏试剂与硅基酮亚胺加成来高效对映选择性合成 N-磺酸保护的α-手性硅基胺的方法。成功的关键是我们能够通过识别一种廉价的手性 Cu 配合物作为催化活性结构，抑制任何非选择性的背景加成反应和副还原途径。
