Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
J Org Chem. 2021 Sep 3;86(17):12008-12023. doi: 10.1021/acs.joc.1c01384. Epub 2021 Aug 3.
Pyridazines are important scaffolds for medicinal chemistry or crop protection agents, yet the selective preparation of 3-bromo-pyridazines with high regiocontrol remains difficult. We achieved the Lewis acid-mediated inverse electron demand Diels-Alder reaction between 3-monosubstituted -tetrazine and silyl enol ethers and obtained functionalized pyridazines. In the case of 1-monosubstituted silyl enol ethers, exclusive regioselectivity was observed. Downstream functionalization of the resulting 3-bromo-pyridazines was demonstrated utilizing several cross-coupling protocols to synthesize 3,4-disubstituted pyridazines with excellent control over the substitution pattern.
哒嗪是药物化学或作物保护剂的重要结构单元，但高区域选择性地制备 3-溴哒嗪仍然具有挑战性。我们实现了路易斯酸介导的 3-取代四嗪与硅基烯醇醚之间的逆电子需求 Diels-Alder 反应，得到了官能化的哒嗪。对于 1-单取代的硅基烯醇醚，观察到了独特的区域选择性。利用几种交叉偶联方案对得到的 3-溴哒嗪进行了下游官能化，以合成具有出色取代模式控制的 3,4-二取代哒嗪。
