Access to Silylated Pyrazole Derivatives by Palladium‐Catalyzed C−H Activation of a TMS group

Abstract

A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chemistry is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chemistry, the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd-catalyzed activation of a non-activated C(sp(3) )-H bond alpha to a silicon atom. The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.

Recent Advances in Transition-Metal-Catalyzed Synthetic Transformations of Organosilicon Reagents

“…A novel 1,4-silicon/halogen exchange reaction is observed by lithiation of 4-( ortho -bromophenyl)-5-trimetylsilylpyrazole 25 followed by iodination to give 26 (eq ). The net transformation is understood by bromine/lithium exchange, an intramolecular attack of phenyllithium XI to the silicon center to generate a bridged silicate XII and then pyrazolyllihtium XIII , which is quenched by I 2 to give 26 . This then undergoes palladium-catalyzed cyclization via C–H bond activation on the silylmethyl moiety in a manner similar to the case in eq to finally give a tricyclic silacycle through another C–H activation.…”

Silylative Cyclization with Dehydrogenation Leading to Benzosilole‐Fused Azulenes Showing Unique Stimuli‐Responsive Fluorescence

“…General Methods : All reactions were carried out in dry solvent under an argon atmosphere. 1‐Iodoazulene, [19] 2‐bromo‐5‐(trifluoromethyl)phenylboronic acid, [20] and 2‐borylazulene [2a,21] were prepared according to the reported methods. 1 H (400 MHz), 13 C (100 MHz), and 19 F (376 MHz) NMR spectra were recorded on a JEOL 400 MR spectrometer.…”

Transition-metal-catalyzed cleavage of silyl C(sp<sup>3</sup>)–H bonds

“…通过对钯催化的硅甲基C-H键活化过程中的 各个过渡态的能量进行仔细计算(图3), 他们认为反应 中C-H键的活化是在过渡金属的作用下, 通过碱参与 的协同的"金属化/去质子化"过程进行的 [41,42] 根据实验事实和计算结果, 林振阳等 [40] 给出了该 反应的机理. 如图4所示, 底物1中的C-Br键首先与零 图 1 硅烷基C(sp 3 )-H键活化-官能团化(网络版彩图) 2016年, Maddaluno等 [43] 报道了一例类似的反应.…”