Study On Synthesis Of The Haloallenes Catalyzed By R₃P And Its Suzuki Cross-Coupling Reaction

Haloallenes which has been recognized as important fundamental organic units are often used as intermediates for the preparation of natural products and pharmaceuticals due to their high reactivity in substitution, addition, coupling and other reactions. However, the reported methods for the synthesis of haloallenes have many disadvantages such as low-yield, poor selectivity, complex manipulation and serious pollution problems. Especially, dichlorosulfoxide, concentrated hydrochloric acid and other halogenated reagents have caused severe damage to the environment. Recently, the field of enzyme catalysis and organocatalysis has been rapidly developing and attracted an increasing number of research groups around the world. Chemical transformations in this field generally possess advantages such as high efficiency, good selectivity and mild conditions, thus the synthesis of halo-allenes directed by the concept of organocatalysis is according to green chemistry concepts and would be an ideal strategy.The reaction of propargyl alcohols with N-halogenated succinimide under the NCX/PPh3 system providing chloroallenes or bromoallenes via three stages including halogenation, oxidation and isomerization was firstly studied. It is found that PPh3 not only facilitate the step of halogenation but also act as a deoxidant. Base on this result, we proposed the triphosphine/ 1,4-hydroquinone/NXS as an novel organocatalytical system for the halogenation reaction. In this catalytical system, propargyl alcohols could be halogenated by NCS in presence of only 5 mol% of triphosphine to afford chloroallenes in one step. This method possesses a series of merits containing good selectivity, high yield, simple manipulation and limited pollution which is better than reported methods.Triphosphines was found to be catalyst in the employed systerms, and demonstrates that Cy3P is the best catalyst, PPh3 as the second one. The research on the mechanism reveals that the triphosphine acts as catalyst and deoxidant at the same time. Generally, the oxygen atom of the propargyl alcohols can not be absorbed by reductant directly. However, the deoxidant can reduce triphenylphosphine oxide to triphenylphosphine which achieves the catalytical cycles.. Polyphenols were the effective reductant and 1,4-dihydroxybenzene was the best one.Based on the obtained results, a proposed mechanism of the halogenation of propargyl alcohols under the HQ/NCS/PPh3 system was tentatively given. In this mechanism:hydroxyl was halogenated by Cl-PPh3 cation as the active intermediate generated by the reaction of triphenylphosphine with N-halogenated succinimide. Then the oxygen atom in hydroxyl was removed by triphenylphosphine giving triphenylphosphine oxide. At last, triphenylphosphine oxide was reduced to triphenylphosphine by 1,4-dihydroxybenzene and start a new catalytical cycle.The optimized condition in the absence of reductant:propargyl alcohol (1.0 mmol), NXS (1.55 mmol), triphenylphosphine (1.50 mmol), CH2Cl2 (5 mL) and stirred for 1 h under-15 to 25℃. Under this condition, up to 88% and 86% yields can be obtained for chloroallene and bromoallene, respectively. In the presence of reductant:propargyl alcohol (1.0 mmol), NCS (1.55 mmol), HQ (1.5 mmol), triphenylphosphine (5 mmol%), CH2Cl2 (5 mL) and stirred for 24 h under room temperature. All the chloroallenes and bromoallenes are new compounds.Suzuki cross-coupling reaction is one of the most important methods in modern organic synthesis. An investigation of the Suzuki cross-coupling reaction of haloallenes to synthesize natural products and pharmaceuticals containing allene structure was extraordinary significance. However, up to now only a few reports could be found in this area. Thus, suzuki cross-coupling of bromoallene and arylboric acid was studied and found that di[2-(diphenylphosphino)acetic acid] palladium was an very effective catalyst, even under room temperature the yield can reach up to 93%. It was found that C-Br on bromoallene rather than on benzene ring readily took part in Suzuki cross-coupling reaction between 1-bromo-l-butyl- (4-bromophenyl)-1,2-propadiene and aryl boric acid catalyzed by di[2-(diphenylphosphino)acetic acid] palladium.NiCl2(Ph2PCH2CH2O)2 was also found to be a effective catalyst for the Suzuki reaction and led up to 87% yield.All cross-coupling products of bromoallene are new compounds.