Synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones utilizing pyrrole Weinreb amides.
Synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones utilizing pyrrole Weinreb amides.
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DOI：
10.1021/jo2013516
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发表时间：
2011-10-21
影响因子：
3.6
通讯作者：
Pelkey, Erin T.
中科院分区：
文献类型：
--
作者：
Greger, Jessica G.;Yoon-Miller, Sarah J. P.;Bechtold, Nathan R.;Flewelling, Scott A.;MacDonald, Jacob P.;Downey, Catherine R.;Cohen, Eric A.;Pelkey, Erin T.
以1，2-二芳基-1-硝基乙烯为原料，以吡咯-2-甲酰胺（吡咯Weinreb酰胺）为关键中间体，经三步反应，实现了不对称3，4-二芳基-3-吡咯啉-2-酮的区域控制合成。研究了两种不同的方法制备所需的硝基烯烃：（1）芳基硝基甲烷与芳基亚胺的改进的亨利反应;（2）2-芳基-1-溴-1-硝基乙烯与芳基硼酸的Suzuki-Miyaura交叉偶联反应。在芳基硝基甲烷的制备中遇到了一些困难，从而导致了对交叉偶联策略的探索，该策略被证明更有用。1，2-二芳基-1-硝基乙烯与N-甲氧基-N-甲基-2-异氰基乙酰胺通过Barton-Zard吡咯环化缩合反应合成了相应的吡咯Weinreb酰胺，然后经两步反应合成了目标产物3-吡咯啉-2-酮。总的来说，该方法允许以相对于内酰胺羰基的取代基的完全区域控制来构建3，4_二芳基-3-吡咯啉-2-酮。通过制备8个不对称和对称的3，4-二芳基-3-吡咯啉-2-酮，包括选择性COX-II抑制剂罗非考昔的N-H内酰胺类似物，证明了这种合成方法的实用性。
A regiocontrolled synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones has been achieved in three steps from 1,2-diaryl-1-nitroethenes with pyrrole-2-carboxamides (pyrrole Weinreb amides) serving as the key linchpin intermediates. Two different methods for the preparation of the requisite nitroalkenes were investigated: (1) modified Henry reaction between arylnitromethanes and arylimines; and (2) Suzuki-Miyaura cross-coupling reaction of 2-aryl-1-bromo-1-nitroethenes with arylboronic acids. Some difficulty was encountered in the preparation of arylnitromethanes, thus leading to the exploration of a cross-coupling strategy that proved more useful. A Barton-Zard pyrrole cyclocondensation reaction between 1,2-diaryl-1-nitroethenes and N-methoxy-N-methyl-2-isocyanoacetamide gave the corresponding pyrrole Weinreb amides, which were then converted into the desired 3-pyrrolin-2-ones in two steps. Overall, this method allowed for the construction of 3,4-diaryl-3-pyrrolin-2-ones with complete regiocontrol of the substituents with respect to the lactam carbonyl. The utility of this synthetic methodology was demonstrated by the preparation of eight unsymmetrical and symmetrical 3,4-diaryl-3-pyrrolin-2-ones including the N-H lactam analog of the selective COX-II inhibitor, rofecoxib.
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影响因子：
3.6
作者：
Ballini, R;Barboni, L;Giarlo, G
通讯作者：
Giarlo, G
影响因子：
15
作者：
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影响因子：
3.6
作者：
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影响因子：
3.6
作者：
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通讯作者：
Pelkey, Erin T.
影响因子：
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作者：
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通讯作者：
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