Switchable C–H Silylation of Indoles Catalyzed by a Thermally Induced Frustrated Lewis Pair

It
is a challenging task to achieve regioselective C–H silylation
of indoles with Ph2SiH2, as bis­(indol-3-yl)-substituted
silanes are always obtained along with the C3-silylated indoles. Without
adding any additive, we developed an Al­(C6F5)3-based catalyst system for the synthesis of C3-selective
silylated indoles under mild conditions and propose here the reaction
mechanism on the basis of systematic studies including detailed experimental
data, characterization of key reaction intermediates, and isotope-labeled
experiments. The adduct 8a generated from the coordination
of indoline with Al­(C6F5)3 at room
temperature could activate silanes such as 2a to form
a thermally induced frustrated Lewis pair (FLP) under heated conditions,
which could efficiently catalyze the regioselective C–H silylation.
The direct use of 8a as catalyst enabled us to successfully
inhibit the formation of different indoline byproducts without the
specific requirement of indole substrates and any additive, achieving
up to 99% yields of C3-silylated indoles. More importantly, this Al­(C6F5)3-based thermally induced FLP catalyst
system realized the precise control of C–H silylation process
by switching the external thermal stimuli on/off.

以二苯基硅烷(Ph₂SiH₂)实现吲哚(indole)的区域选择性C-H硅基化是一项极具挑战性的研究课题，因为反应体系中总会同时生成双(吲哚-3-基)取代硅烷副产物与C3位硅基化吲哚。在不添加任何添加剂的前提下，我们开发了基于三(五氟苯基)铝[Al(C₆F₅)₃]的催化体系，可在温和条件下合成C3位选择性硅基化吲哚；同时基于包含详细实验数据、关键反应中间体表征以及同位素标记实验在内的系统性研究，我们提出了该反应的机理。室温下吲哚啉(indoline)与Al(C₆F₅)₃配位生成的加合物8a，在加热条件下可活化硅烷（如2a），形成热诱导受阻路易斯对(frustrated Lewis pair, FLP)，该催化物种能够高效催化区域选择性C-H硅基化反应。直接以加合物8a作为催化剂，可在无需对吲哚底物提出特殊要求且不添加任何添加剂的情况下，有效抑制各类吲哚啉副产物的生成，使C3位硅基化吲哚的产率最高可达99%。更为关键的是，这套基于Al(C₆F₅)₃的热诱导FLP催化体系，可通过启停外部热刺激，精准调控C-H硅基化反应的进程。