Synthesis of Unsymmetrical Biaryls using PdCl₂(dppf) as a Catalyst

Abstract

촉매량의 dichloro[1, 1'-bis(diphenylphosphino)ferrocene]palladium(Ⅱ) [PdCl_(2)(dppf)]과 염기 존재하에서 phenylboric acid와 다양한 aryl halides를 coupling시켜 biphenyl, 4-phenyltoluene, 4-nitrobiphenyl, 4-acetylbiphenyl을 합성하였다. Phenylboric acid와 bromobenzene을 coupling시키는 반응을 이용하여 적당한 반응 조건을 찾아 unsymmetrical biaryl의 합성에 적용하였는데 coupling 반응은 촉매로 PdCl_(2)(dppf)를 사용하였을 때 좋은 효과를 보여 주었다. 반면 dichloro[1, 3-bis(diphenylphosphino)propane]nickel(Ⅱ) [NiCl_(2)(dppp)]는 낮은 수득율을 보였으며 촉매를 사용하지 않은 반응은 전혀 진행되지 않았다. 또한 K_(3)PO_(4)를 염기로 사용한 반응이 K_(2)CO_(3)를 쓴 경우 보다 높은 수득율을 보였으며 염기를 사용하지 않았을 때는 반응이 전혀 진행되지 않았다. 그러므로 이 반응에 있어서 염기의 역할에 대해 알아 보았다. phenylmagnesium chloride 또는 phenylboric acid와 4-bromotoluene의 coupling 반응에서는 phenylmagnesium chloride를 사용하였을 때 부생성물인 homo-coupling 생성물이 더 많이 형성되었다. 또한 electrowithdrawing group이 치환되어 있는 aryl halides는 oxidative addition 단계를 가속화시켜 매우 높은 수득율로 unsymmetrical biaryl을 형성하였으며, phenylboric acid가 카르보닐과 같은 작용기와 반응하는 생성물은 전혀 검출되지 않았다. 따라서 phenylboric acid의 사용은 unsymmetrical biaryl을 합성하는데 있어서 상당히 유용하다는 것을 알 수 있었다.;The cross-coupling of organic electrophiles with various organometallic reagents in the presence of transition organometallic compounds as a catalyst can be carried out a very mild and most straightforward method of forming carbon-carbon bonds. In the present study, the cross-coupling of various aryl halides with phenylboric acid in the presence of a catalytic amount of PdCl_(2)(dppf) and bases gave biphenyl, 4-phenyltoluene, 4-nitro-biphenyl and 4-acetylbiphenyl. A first series of experiments was effected with bromobenzene and phenylboric acid as partners to establish the best reaction condition. The coupling reaction worked out well with PdCl_(2)(dppf) as a catalyst in the presence of 2 equiv. of K_(3)PO_(4) in THF at 60℃. The desired cross-coupling products were not obtained in any noticeable amounts in the absence of bases or catalysts. In the reaction of organometallic reagents with 4-bromotoluene, phenylmagnesium chloride formed more homo-coupling products than in the case of phenylboric acid. The coupling reaction between phenylboric acid and 1-bromo-4-nitrobenzene or 4-bromoacetophenone gave the cross-coupling product in high yield because oxidative addition occurred with facility owing to electrowithdrawing group in the aryl ring. Fairly air stable phenylboric acid was found to be better acetyl transferring functional group in this experiment.