从夹子到点击反应：利用大环四嗪控制逆电子需求的狄尔斯-阿尔德反应

Clip to Click: Controlling Inverse Electron-Demand Diels-Alder Reactions with Macrocyclic Tetrazines.

作者信息

Novianti Ira, Kowada Toshiyuki, Mizukami Shin

机构信息

Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8577, Japan.

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Aoba-ku, Sendai, Miyagi 980-8577, Japan.

出版信息

Org Lett. 2022 May 6;24(17):3223-3226. doi: 10.1021/acs.orglett.2c01010. Epub 2022 Apr 21.

DOI:10.1021/acs.orglett.2c01010

PMID:35446571

Abstract

A universal strategy to control tetrazine reactivity in the inverse electron-demand Diels-Alder (IEDDA) reaction was developed as "Clip to Click". Incorporating a chemical bridge into 3,6-diphenyl-1,2,4,5-tetrazine (macrocyclic tetrazine) rendered it unreactive toward -cyclooctene. A computational study revealed that the unreactive property of macrocyclic tetrazines is mainly due to the high distortion energy of tetrazine. We demonstrated that the cleavage ("Clip") of the macrocyclic linker can activate the tetrazine moiety for the IEDDA reaction ("Click").

摘要

一种名为“Clip to Click”的通用策略被开发出来，用于在逆电子需求狄尔斯-阿尔德（IEDDA）反应中控制四嗪的反应活性。将一个化学桥引入3,6-二苯基-1,2,4,5-四嗪（大环四嗪）使其对环辛烯无反应活性。一项计算研究表明，大环四嗪的无反应活性主要归因于四嗪的高扭曲能。我们证明了大环连接基的断裂（“Clip”）可以激活四嗪部分以进行IEDDA反应（“Click”）。