Asinex, 20 Geroev Panfilovtsev St., 125480 Moscow, Russia.
Enikolopov Institute of Synthetic Polymeric Materials, a Foundation of the Russian Academy of Sciences, 70 Profsoyuznaya St., 117393 Moscow, Russia.
J Org Chem. 2021 Jan 1;86(1):1037-1052. doi: 10.1021/acs.joc.0c02292. Epub 2020 Dec 15.
A new three-component reaction leading to 1-α-(pyridyl-2-[1,2,4]triazolyl)-2-alkyl-ethanones has been discovered while studying the reactivity of monosubstituted 3,3-difluorocyclopropenes in an inverse electronic demand Diels-Alder (IEDDA) cycloaddition-cycloreversion sequence with -tetrazines. The reaction involving the above-mentioned reactants and (benzo)pyridine as a third component results in a complex transformation proceeding in mild conditions in a stoichiometric ratio of reactants and has high functional group tolerance (phenols, amides, ethers, carboxylic acids, ketones, and acrylic esters). As a result, simple pyridines are selectively functionalized at the α-position in good isolated yields. The reaction mechanism includes a rare azaphilic [4 + 2]-cycloaddition step between -tetrazine and intermediate 1-hydroxyindolizine, suggested after byproduct identification and tracked with a deuterium label. To date, it is only the third known example of skewed azaphilic cycloaddition of tetrazine. The reaction is truly three-component and cannot be effectively performed stepwise.
在研究单取代的 3,3-二氟环丙烯与 -四嗪进行逆向电子需求 Diels-Alder（IEDDA）环加成-环回转化序列的反应活性时，发现了一种新的三组分反应，生成了 1-α-（吡啶-2-[1,2,4]三唑基）-2-烷基-乙酮。该反应涉及上述反应物和（苯并）吡啶作为第三组分，在温和条件下以反应物的化学计量比进行复杂转化，具有高官能团容忍度（酚、酰胺、醚、羧酸、酮和丙烯酸酯）。结果，简单的吡啶在α-位被选择性官能化，收率良好。反应机理包括 -四嗪和中间体 1-羟基吲哚嗪之间罕见的亲氮[4+2]-环加成步骤，这是在确定副产物并使用氘标记跟踪后提出的。迄今为止，这仅是第三个已知的四嗪倾斜亲氮环加成的例子。该反应确实是三组分的，不能有效地分步进行。
