Copper catalyzed carbonyl silylation of haloalkanes: efficient synthesis of acyl silanes

Acyl silane, as a practical synthetic block, is a kind of very important compound, which is widely used in the field of organic synthesis and materials Chemists have been developing new reactions to synthesize acyl silanes There are three strategies: (1) aldehydes are protected by carbonyl and deprotected to synthesize acyl silanes; (2) transition metal catalyzed silylation of carboxylic acid derivatives (scheme 1b); (3) ）Palladium catalyzed carbonylsilylation of aryl iodides (scheme 1b) However, there are some limitations in these synthesis methods: the reaction needs many steps, and the suitable substrate range is narrow In addition, the oxidative addition of alkylelectrophilic reagents is very slow, and there is a competitive elimination of β - hydrogen under the condition of carbonylation, so the carbonylation of alkylelectrophilic reagents is still challenging Recently, the Neal P mankad group of the University of Illinois at Chicago has developed a copper catalyzed carbonyl silanization of inactive haloalkanes on the basis of previous research The reaction is suitable for all kinds of haloalkanes under mild conditions and compatible with various substituent groups The results were recently published in J am Chem SOC (DOI: 10.1021 / JACS 9b12043) (photo source: J am Chem SOC.) at first, the author took 1-iodooctane as the model substrate and phme2si bpin as the silicon source, and made a preliminary exploration of the reaction under the condition of CO at 6 atmospheres (Table 1) By optimizing the conditions of catalyst, alkali and solvent used in the reaction, the author determined that the optimal conditions of the reaction were: iprcucl as catalyst, naoph as alkali, 1,4-dioxane as solvent, the substrate finally selectively obtained the target product 2a in 93% yield (photo source: J am Chem SOC.) after determining the optimal condition of reaction, the author expanded the range of reaction substrate (Table 2) The alkyl iodides substituted by different distal functional groups are suitable for the reaction, including benzyl ether, Chloroalkyl and terminal olefins The reaction is also compatible with different heterocycles, such as furan and thiophene, and the medium yield can be obtained by the substrate containing indole fragment In addition, it has good compatibility with trifluoromethyl group, ester group, cyano group and chlorine and bromine on the distal benzene ring Under the same conditions, the second-order iodoalkanes can also obtain excellent yield Increasing the steric hindrance of the substrate has no effect on the reaction The more challenging third-order haloalkanes may have elimination side reactions under alkaline conditions, among which brominated third-order alkanes have better reaction effect (photo source: J am Chem SOC.) next, the author proved the practicability of the reaction through experiments Scheme 2a and scheme 2B were used to modify estrone derivative 4 Acyl silylation products were obtained in excellent yield After increasing the reaction temperature, et 3Si bpin can also be used as the dominant silicon source (scheme 2C) for acyl silylation Under standard conditions, α - hydroxysilane (scheme 2D) can be synthesized in one pot by adding reducing agent hydrosilylate to the reaction system (photo source: J am Chem SOC.) later, the author carried out some mechanism verification experiments The free radical mechanism of the reaction was verified by the free radical capture experiment (scheme 3a), the free radical clock experiment (scheme 3b) and the coupling experiment between the equivalent silicon copper species iprcu-sime2 pH and the substrate (scheme 3C) Interestingly, in the competitive experiments of iodoalkanes at all levels, the yields of various substrates are almost the same, and the thermodynamic stable third-order iodoalkanes have no advantage in the reaction (scheme 3D) This shows that the cracking of carbon halide bond is not the decisive step of the reaction (photo source: J am Chem SOC.) finally, the author proposed a possible catalytic cycle (scheme 4) First, iprcuph is formed by iprcucl and naoph, which then reacts with phme2si bpin to obtain compound A; alkyl halide and compound a generate alkyl radicals and compound B through single electron transfer (set) pathway; alkyl radicals carbonyl with CO to obtain acyl radicals, which further reacts with compound B to obtain intermediate D; finally, D The target product was obtained by reduction and elimination (photo source: J am Chem SOC.) Summary: mankad group realized the copper catalyzed carbonyl silanization of haloalkanes The reaction conditions are mild, suitable for all levels of haloalkanes, and have good compatibility for a variety of substituents In addition, the mechanism verification experiment shows that the silicon copper intermediate can activate the alkyl iodide through the single electron transfer pathway, and generate the alkyl radical, thus realizing the carbonyl silylation reaction In this process, the fracture of carbon halide bond is not a critical step.