Huy Peter H, Mbouhom Christelle
Saarland University , Institute of Organic Chemistry , P. O. Box 151150 , D-66041 Saarbruecken , Germany . https://www.peterhuylab.de/ ; Email:
Chem Sci. 2019 Jun 17;10(31):7399-7406. doi: 10.1039/c9sc02126d. eCollection 2019 Aug 21.
A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
基于甲酰基吡咯烷（FPyr）作为路易斯碱催化剂，提出了一种新颖、广泛适用的酰胺C-N键和酯C-O键形成方法。在此，使用了三氯三嗪（TCT），它是用于羟基活化的最具成本效益的试剂，相对于起始原料（100 mol%）的用量≤40 mol%。这种新方法具有出色的成本效益、废物平衡（-因子降至3）和可扩展性（高达>80 g）。此外，还展示了高水平的官能团兼容性，包括对酸不稳定的缩醛和硅醚，甚至可以形成肽C-N键。与报道的使用TCT的酰胺化方法相比，产率有了显著提高（例如从26%提高到91%），并且首次以合成有用的产率促进了酯化反应。这些显著的改进通过使用酰氯而不是亲电性较弱的酸酐中间体进行活化来解释。
