Catalytic asymmetric hydrogenation of 2,3,5-trisubstituted pyrroles
Catalytic asymmetric hydrogenation of 2,3,5-trisubstituted pyrroles
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DOI：
10.1021/ja7102422
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发表时间：
2008-01-23
影响因子：
15
通讯作者：
Kusano, Hiroki
中科院分区：
文献类型：
--
作者：
Kuwano, Ryoichi;Kashiwabara, Manabu;Kusano, Hiroki
采用反式螯合手性双膦PhTRAP修饰的钌催化剂，对n - boc保护的吡咯进行了高对映选择性的不对称加氢反应。在三乙胺存在下，Ru（eta 3-甲基）(2)（cod）和（S，S）-(R，R)- phtrap制备的钌催化剂对2-羧酸甲酯的不对称加氢反应最具对映选择性，得到所需的(S)-脯氨酸衍生物，ee为79%，产率为92%。此外，在5位上含有大取代基的2,3,5-三取代吡咯的氢化率为93-99.7%。对4,5-二甲基吡咯-2-羧酸酯进行不对称还原，得到全顺式异构体，并在一个过程中生成3个具有高度立体控制的手性中心。这是吡咯的第一次高度对映选择性还原。
Catalytic asymmetric hydrogenation of N-Boc-protected pyrroles proceeded with high enantioselectivity, by using a ruthenium catalyst modified with a trans-chelating chiral bisphosphine PhTRAP. The ruthenium catalyst prepared from Ru(eta 3-methallyl)(2)(cod) and (S,S)-(R,R)-PhTRAP in the presence of triethylamine was the most enantioselective for the asymmetric hydrogenation of methyl pyrrole-2-carboxylate, giving the desired (S)-proline derivative with 79% ee in 92% yield. Moreover, 2,3,5-trisubstituted pyrroles bearing a large substituent at the 5-position were hydrogenated with 93-99.7% ee. The asymmetric reduction of 4,5-dimethylpyrrole-2-carboxylate gave only all-cis isomer and created three chiral centers with high degree of stereocontrol in a single process. This is the first highly enantioselective reduction of pyrroles.