Direct Cupration of Fluoroform

We have found the first reaction of direct cupration of fluoroform, the most attractive CF3 source for the introduction of the trifluoromethyl group into organic molecules. Treatment of CuX (X = Cl, Br, I) with 2 equiv of MOR (M = K, Na) in DMF or NMP produces novel alkoxycuprates that readily react with CF3H at room temperature and atmospheric pressure to give CuCF3 derivatives. The CuCl and t-BuOK (1:2) combination provides best results, furnishing the CuCF3 product within seconds in nearly quantitative yield. As demonstrated, neither CF3– nor CF2 mediate the Cu–CF3 bond formation, which accounts for its remarkably high selectivity. The fluoroform-derived CuCF3 solutions can be efficiently stabilized with TREAT HF to produce CuCF3 reagents that readily trifluoromethylate organic and inorganic electrophiles in the absence of additional ligands such as phenanthroline. A series of novel Cu(I) complexes have been structurally characterized, including K(DMF)[Cu(OBu-t)2] (1), Na(DMF)2[Cu(OBu-t)2] (2), [K8Cu6(OBu-t)12(DMF)8(I)]+ I– (3), and [Cu4(CF3)2(C(OBu-t)2)2(μ3-OBu-t)2] (7).

本研究首次实现了三氟甲烷（fluoroform）的直接铜化反应——三氟甲烷是将三氟甲基（trifluoromethyl group）引入有机分子的最具吸引力的CF3源。将卤化亚铜CuX（X=Cl、Br、I）与2当量的醇盐MOR（M=K、Na）在N,N-二甲基甲酰胺（DMF）或N-甲基吡咯烷酮（NMP）中反应，可生成新型烷氧基铜酸盐，该类化合物可在室温及常压下与三氟甲烷（CF3H）快速反应，得到三氟甲基铜（CuCF3）衍生物。其中CuCl与叔丁醇钾（t-BuOK）按1:2摩尔比组合的效果最优，可在数秒内以近乎定量的产率得到CuCF3产物。实验证实，三氟甲基负离子（CF3–）与二氟物种CF2均未介导Cu-CF3键的形成，这正是该反应具备极高选择性的原因。经TREAT HF处理后，由三氟甲烷衍生得到的CuCF3溶液可得到有效稳定，所制得的CuCF3试剂可在无需额外配体（如菲咯啉（phenanthroline））的条件下，便捷地对有机及无机亲电试剂进行三氟甲基化修饰。已有一系列新型一价铜（Cu(I)）配合物完成结构表征，包括K(DMF)[Cu(OBu-t)2]（1）、Na(DMF)2[Cu(OBu-t)2]（2）、[K8Cu6(OBu-t)12(DMF)8(I)]+ I–（3）以及[Cu4(CF3)2(C(OBu-t)2)2(μ3-OBu-t)2]（7）。