Synthesis of Highly Functionalized 12-Membered Trifluoromethyl Heterocycles via a Nondecarboxylative Pd-Catalyzed [6 + 6] Annulation

An
efficient method for the construction of 12-membered heterocycles
with a trifluoromethyl group (3) was achieved via a nondecarboxylative
Pd-catalyzed [6 + 6] annulation of six-membered trifluoromethyl benzo­[d]­[1,3]­oxazinones (1) with four-membered vinyl
oxetanes (2). A variety of relatively large heterocycles 3 featuring a stereogenic trifluoromethylated carbon center,
an amino group, as well as an alkenyl and a carbonate moiety were
obtained. An X-ray crystallographic analysis revealed a unique 3D
architecture of the products that affords an attractive chemical space.
Whereas the method can be applicable for nonfluorinated substrates,
the trifluoromethyl group plays a vital role in this unexpected Pd-catalyzed
nondecarboxylative ring expansion.

本研究开发了一种高效构建含三氟甲基基团的12元杂环（化合物3）的方法，该方法通过六元环三氟甲基取代苯并[d][1,3]噁嗪酮（1）与四元环乙烯基氧杂环丁烷（2）之间的非脱羧钯催化[6+6]环加成反应实现。反应可得到一系列兼具手性三氟甲基化碳中心、氨基、烯基与碳酸酯基团的较大尺寸杂环化合物3。经X射线晶体衍射分析表明，该类产物拥有独特的三维立体结构，可构建出极具应用价值的化学空间。尽管该方法可拓展至非氟代底物，但三氟甲基基团在此次意外发现的钯催化非脱羧扩环反应中发挥了至关重要的作用。