Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/Linked-BINOL complex:: Synthesis of either anti- or syn-β-amino alcohols
Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/Linked-BINOL complex:: Synthesis of either anti- or syn-β-amino alcohols
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DOI：
10.1021/ja0482435
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发表时间：
2004-07-21
影响因子：
15
通讯作者：
Shibasaki, M
中科院分区：
文献类型：
--
作者：
Matsunaga, S;Yoshida, T;Shibasaki, M
详细描述了乙二锌/(S，S)连接的联二醇络合物直接催化羟基酮的不对称Mannich反应的全部细节。通过在亚胺氮上选择合适的保护基团，在相同的锌催化下，反-β-氨基醇和合成的β-氨基醇都能以良好的非对映异构体比率、产率和良好的对映体过量得到。N-二苯基膦(DPP)亚胺3的反/SYN=98/2，产率达99%，ee达99.5%，而Boc-亚胺4得抗/SYN=5/95，产率达99%，ee达99.5%。催化剂的高周转数(吨)也值得注意。催化剂负载量成功地降低到0.02摩尔%(TON=4920)和0.05摩尔%(TON=1760)，用于反选择反应。Et2Zn/(S，S)连接的二异氰酸酯络合物的催化性能远远好于以往报道的不对称曼尼奇反应。阐明了催化剂效率高的原因以及Mannich加合物的转化机理。
Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.