Shi Yao, Derasp Joshua S, Guzman Sara M, Patrick Brian O, Hein Jason E
Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
Department of Chemistry, University of Bergen, Allégaten 41, N-5007 Bergen, Norway.
ACS Catal. 2024 Aug 7;14(16):12671-12680. doi: 10.1021/acscatal.4c02407. eCollection 2024 Aug 16.
The Suzuki-Miyaura cross-coupling (SMC) remains one of the most widely used transformations available to chemists. Recently, robust new conditions achieving rapid reactivity under homogeneous aprotic conditions enabled by the use of potassium trimethylsilanolate (TMSOK) as a base were reported. However, the strong inhibitory effect of TMSOK restricts the generality of such conditions. Moreover, the basic nature of TMSOK impedes the use of protic heterocycles as substrates, as these latter anionic species are even more potent catalyst inhibitors. Herein, we report a thorough mechanistic study of these novel SMC conditions. Halide salt additives were found to provide a dramatic rate acceleration and mitigate the inhibitory effect of TMSOK. NMR experiments revealed that this is largely achieved by impacting the unexpected formation of inactive [LnPd(Ar)(μ-OH)], favoring the formation of active LnPd(Ar)(X) instead. These findings enabled an impressive substrate scope even at low catalyst loadings (0.1 mol %). Finally, halide additives were observed to enable the use of protic heterocyclic substrates, which could otherwise completely inhibit reactivity.
铃木-宫浦交叉偶联反应（SMC）仍然是化学家可用的最广泛使用的转化反应之一。最近，有报道称，通过使用三甲基硅醇钾（TMSOK）作为碱，在均相非质子条件下实现了快速反应性的稳健新条件。然而，TMSOK的强抑制作用限制了此类条件的通用性。此外，TMSOK的碱性性质阻碍了质子杂环作为底物的使用，因为这些阴离子物种是更强效的催化剂抑制剂。在此，我们报告了对这些新型SMC条件的深入机理研究。发现卤化物盐添加剂可显著加速反应速率并减轻TMSOK的抑制作用。核磁共振实验表明，这主要是通过影响无活性的[LnPd(Ar)(μ-OH)]的意外形成来实现的，转而有利于活性LnPd(Ar)(X)的形成。这些发现即使在低催化剂负载量（0.1 mol%）下也能实现令人印象深刻的底物范围。最后，观察到卤化物添加剂能够使用质子杂环底物，否则这些底物会完全抑制反应性。
