Department of Chemistry, University of Chicago , Chicago, Illinois 60637, United States.
J Am Chem Soc. 2017 Jun 14;139(23):7757-7760. doi: 10.1021/jacs.7b04722. Epub 2017 Jun 6.
A direct catalytic method is described for the α,β-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.
本文描述了一种在温和酸性条件下，通过直接催化的方法将 N-保护的内酰胺转化为其相应的共轭不饱和内酰胺的方法。该反应在室温下进行，能耐受广泛的官能团，与之前的不饱和方法具有互补的反应性。具有不同环大小和不同位置取代基的内酰胺都能顺利反应。该方法在 Rolipram 的简洁合成立体中得到了证明。此外，线性酰胺也被证明是合适的底物，而邻苯二甲酰基保护的产物则是一种方便的前体，可以用来制备各种共轭羧酸衍生物。在这种不饱和方法中避免了强碱，关键是将软烯醇化与 Pd 催化的氧化过程结合起来。
