A borrowing hydrogen methodology: palladium-catalyzed dehydrative N-benzylation of 2-aminopyridines in water
A borrowing hydrogen methodology: palladium-catalyzed dehydrative N-benzylation of 2-aminopyridines in water
复制标题
DOI：
10.1039/c8gc01028e
复制
发表时间：
2018-07-07
期刊：
影响因子：
9.8
通讯作者：
Azumaya, Isao
中科院分区：
文献类型：
--
作者：
Hikawa, Hidemasa;Imamura, Hirokazu;Azumaya, Isao
我们展示了一种更绿色的借用氢的方法，使用π-苄基钯系统，它提供了一个有效的和环境友好的脱水N-单苄基2-氨基吡啶与苄醇在碱的情况下。使用苄基-α，α-d（2）醇和3-甲基苄醇的交叉实验得到H/D混杂产物，表明在我们的催化体系中脱水N-苄基化涉及借氢途径。KIE实验表明，在苄醇的苄基位置的C-H键断裂参与的速率控制步骤（KIE = 2.9）。这种简单的无碱方案可以在温和的条件下以原子经济的方法实现，以中等至优异的产率提供所需的产物。
We demonstrate a greener borrowing hydrogen methodology using the pi-benzylpalladium system, which offers an efficient and environmentally friendly dehydrative N-monobenzylation of 2-aminopyridines with benzylic alcohols in the absence of base. The crossover experiment using benzyl-alpha,alpha-d(2) alcohol and 3-methylbenzyl alcohol afforded H/D scrambled products, suggesting that the dehydrative N-benzylation in our catalytic system involves a borrowing hydrogen pathway. KIE experiments show that C-H bond cleavage at the benzylic position of benzyl alcohol is involved in the rate-determining step (KIE = 2.9). This simple base-free protocol can be achieved under mild conditions in an atom-economic process, affording the desired products in moderate to excellent yields.