Study On Synthesis Of The Bromophenyl Substituted Bromoallenes And Its Chemoselective Suzuki-Miyaura Cross-Coupling Reaction

Suzuki-Mayaura coupling reaction is an effective method of building new C-C bond by the reaction of organoboron reagents with organic halides. It could be extensively applied in synthesis of natural products, polymer, advanced materials, liquid crystal, medicines, agrochemicals and bioactive molecules. When the starting molecule has more than one substituent of the halogen atom, selectivity is a critical issue to the cross-coupling reactions because the remaining halo group in the product of the cross-coupling reaction can be further converted into another group through a subsequent synthetic procedure.Chemoselective cross-coupling has thus become an attractive approach in the synthetic chemistry, and consequently it is of great value to develop such site-selective cross-coupling reactions.Bromophenyl substituted bromoallenes not only contain bromophenyl but also include high reactivity of bromoallenyl, which has been recognized as important fundamental organic units due to their high reactivity in substitution, addition, coupling and other reactions.This paper decides to develop a facile and practical preparation of bromophenyl substituted bromoallenes and study on its chemoselective suzuki-miyaura coupling reaction.We researched preparation of bromoallenes and found that propargyl alcohols could be easily converted to corresponding bromoallenes by a reagent combination of N-bromosuccinimide and dimethyl sulfide under a mild condition for the fist time. In this paper, we report this efficient, convenient new method.The optimized condition:propargyl alcohol (1.0mmol), NBS (1.5mmol), CH3SCH3(1.2mmol), CH2Cl2(7mL) and stirred for3h at room temperature. Under this condition, up to91%yields can be obtained for bromoallene. Part of bromoallenes are new compounds.The result of chemoselective suzuki-miyaura coupling of bromophenyl substituted bromoallenes with arylboronic acids indicates that it can catalyze the C-Br bond on bromoallenes instead of the C-Br bond on the bromine phenyl. The optimal reaction conditions:bromophenyl substituted bromoallenes (1.0mmol), arylbornoc acids (1.2mmol), solvent3ml of THF:H2O=1:1,3%mmol2-(diaryl phosphonite acetic acid)-palladium and stirred for8h at room temperature. Under this condition the coupling product have the best chemoselective and good yeild. Prodcuts of different arylboronic acids coupling with bromophenyl substituted bromomoallenes show the structure of fragrance boric acid has no significant effect on the chemoselective of reaction but arylboronic acid with methoxyl-or nitro-will cause products instable. The structure of bromophenyl substituted bromoallenes has no effect on the chemoselective of reaction. The site of C-Br bond on bromophenyl in3 No. of carbon will cause products instable. All of cross-coupling products of bromoallenes are new compounds.The causes of the reaction chemoselective were preliminary explained by theoretical computations. Theoretical computations indicate that intermediates of palladium oxdative addition with C-Br bond on the bromoallene are more stable than palladium oxdative addition with C-Br bond on the Bromophenyl.