Oxidative Mizoroki–Heck reaction of unprotected cinnamylamines at ambient temperature under air
Oxidative Mizoroki–Heck reaction of unprotected cinnamylamines at ambient temperature under air
复制标题
未保护的肉桂胺在环境温度下空气中的氧化 MizorokiâHeck 反应
DOI：
10.1039/d3qo00778b
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发表时间：
2023
影响因子：
5.4
通讯作者：
Young, Michael C.
中科院分区：
文献类型：
--
作者：
Farinde, Olutayo N.;Satheesh, Vanaparthi;Shrestha, Kendra K.;Rhinehalt, Carmen R.;Landge, Vinod G.;Young, Michael C.
肉桂胺构成了许多重要的药物，靶向G蛋白偶联受体。虽然3，3-二芳基烯丙基胺可以通过现有的合成方法制备，但这些方法通常需要对不对称酮进行选择性差的维蒂希加成，然后进行多步序列以获得烯丙基胺产物。利用经由Mizoroki-Heck途径直接芳基加成至N-保护的肉桂基胺的方法是已知的，然而，未保护的肉桂基胺在Pd催化的芳基化条件下使用芳基碘对C-H活化和Mizoroki-Heck芳基化的混合物敏感。这导致在这些反应条件下可以实现的反式/顺式选择性降低。通过重新设想反应和使用芳基硼酸，我们在本文中已经证明了在许多情况下如何可以提高产率和E/Z选择性。原位形成的活性催化剂在这些条件下更敏感，并且观察到在升高的温度下关闭。
Cinnamylamines make-up many important drugs that target G protein-coupled receptors. While 3,3-diarylallylamines can be prepared via existing synthetic methods, these often require poorly-selective Wittig addition to unsymmetrical ketones, and multistep sequences thereafter to reach the allylamine product. Methods that make use of direct aryl addition to N-protected cinnamylamines via a Mizoroki–Heck pathway are known, however, unprotected cinnamylamines are sensitive to a mixture of C–H activation and Mizoroki–Heck arylation under Pd-catalysed arylation conditions using aryl iodides. This leads to a decrease in the trans/cis selectivity that can be achieved under these reaction conditions. By reimagining the reaction and using aryl boronic acids, we have herein demonstrated how in many cases the yield and E/Z selectivity can be improved. The in situ-formed active catalyst is more sensitive under these conditions, and was observed to shut down at elevated temperatures.