Synthesis of (E)-1-Aryl Alk-1-en-3-ones by Tetraphosphine/Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides

Abstract

The tetraphosphine cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane in combination with [Pd(C 3 H 5 )Cl] 2 affords a very efficient catalyst for the Heck reaction of alk-1-en-3-ones with aryl bromides. If appropriate reaction conditions are used (NaOAc as base, hydroquinone as stabilising agent and DMF as solvent) high yields of (E)-1-aryl alk-1-en-3-one derivatives are obtained. In general, higher reaction rates were observed with electron-poor aryl bromides, but the electron-rich aryl bromides 4-N,N-dimethylaminobromobenzene and 4-bromoanisole also led to the arylated enones. Even with sterically very congested aryl bromides such as 9-bromoanthracene, 2,4,6-trimethylbromobenzene or 2,4,6-triisopropylbromobenzene, the expected (E)-1-aryl alk-1-en-3-ones were obtained in moderate to good yields. Moreover, several reactions can be performed with as little as 0.1% catalyst.The palladium-catalysed Heck vinylation is one of the most efficient methods for the formation of C-C bonds. [1][2][3][4] The reaction between aryl bromides and alk-1-en-3-ones should be a powerful method for the synthesis of 1-aryl alk-1-en-3-one derivatives. However, Heck coupling reaction using alk-1-en-3-ones are generally performed with very reactive but expensive aryl iodides. 5 The Heck vinylation with alk-1-en-3-ones and aryl bromides has attracted less attention so far. 6-12 In general, for the Heck vinylations with acrylates, better results are obtained using electron-poor aryl bromides. Surprisingly, in the literature, the coupling reactions of alk-1-en-3-ones were generally performed with electron-neutral or electron-rich aryl bromides. For example, the reaction of 2-bromo-6-methoxynaphthalene with but-1-en-3-one using 2% (PPh 3 ) 2 PdCl 2 as catalyst gave the expected arylated enone. 6 The reaction of 2-bromo-1,4-dimethoxynaphthalene and but-1-en-3-one with 20% Pd(PPh 3 ) 4 gave the coupling product in 73% yield. 7 Finally, bromobenzene, methoxybromobenzenes, bromonaphthalenes or a bromophenylcarbohydrate and an alk-1-en-3-ones using 10-20% of a Pd(OAc) 2 /PPh 3 catalyst gave the 1-aryl alk-1-en-3-ones in good yields. 9-11 To our knowledge, low-catalyst-loading Heck reactions using alk-1-en-3-one derivatives with aryl bromides have not been reported. Moreover, there still remained a need for a general protocol for this reaction especially with electron-poor aryl bromides.In order to obtain a highly stable palladium catalyst, we have prepared the tetraphosphine ligand, cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane or Tedicyp 13 (Figure 1). We have already reported the results obtained in allylic substitution, 13 for Suzuki crosscoupling 14 and for Sonogashira reaction 15 using Tedicyp as the ligand. We have also described several results obtained for Heck reaction using acrylates, 16a enol ethers, 16b simple alkenes, 16c alk-1-en-3-ols, 16d-16f acrolein ethylene acetal 16g or ethylene glycol vinyl ether. 16h Here, in order to further establish the requirements for a successful Heck reaction with...