Direct Catalytic Desaturation of Lactams Enabled by Soft Enolization
Direct Catalytic Desaturation of Lactams Enabled by Soft Enolization
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DOI：
10.1021/jacs.7b04722
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发表时间：
2017-06-14
影响因子：
15
通讯作者：
Dong, Guangbin
中科院分区：
文献类型：
--
作者：
Chen, Ming;Dong, Guangbin
介绍了一种在弱酸性条件下直接催化N-保护内酰胺类化合物的α，β-去饱和化反应的方法：该反应在室温下进行，并能容忍广泛的官能团，表现出与以前的去饱和方法互补的反应性。不同环大小、不同位置取代基的内酰胺类药物反应平稳。以罗利普兰的简明合成为例，说明了该方法的合成实用性。此外，线性酰胺也被证明是有效的底物，邻苯二甲酰基保护的产物可以作为一种方便的前体来获得各种共轭羧酸衍生物。这种去饱和方法避免了强碱，关键是将软烯醇化与钯催化的氧化过程相结合。
A direct catalytic method is described for the alpha,beta-desaturation of N-protected lactams to their conjugated unsaturated counterparts under mildly acidic conditions: The reaction is consistently operated at room temperature and tolerates a wide range of functional groups, showing reactivity complementary to that of prior desaturation methods. Lactams with various ring sizes and substituents at different positions all reacted smoothly. The synthetic utility of this method is demonstrated in a concise synthesis of Rolipram. In addition, linear amides also prove to be competent substrates, and the phthaloyl-protected product serves as a convenient precursor to access various conjugated carboxylic acid derivatives. Strong bases are avoided in this desaturation approach, and the key is to merge soft enolization with a Pd-catalyzed oxidation process.