Direct Acylation of Aryl Bromides with Aldehydes by Palladium Catalysis
Preparation of aryl ketones is becoming easier with the new palladium-mediated coupling protocols.
The importance of arylketones does not need to be stressed. These compounds are common starting materials for very different compounds, and synthetic methods for them are always welcome. The classic method is of course the old Friedel–Crafts acylation, but coupling methods have been around for some years, although unfortunately they are sometimes troublesome and involve toxic metals. In the second issue of our newsletter, we selected a paper reporting conditions for the synthesis of aryl ketones from boronic acids and enol ethers.
The method reported by the research group of Xiao (Liverpool, UK) uses aryl bromides as starting materials, but more interestingly, the source of the carbonyl compound is an aldehyde. The standard conditions involve the reaction of an aryl bromide with the aldehyde using Pd(dba)2, dppp, pyrrolidine, and molecular sieves in DMF at 115 °C for 6 h. Examples include the coupling of aliphatic, benzylic, and homobenzylic aldehydes with aryl bromides. The yields are usually excellent. The only heteroaryl bromide reported (2-bromothiophene) gives a modest 58% yield. Once again, it is a great step forward from the days of thallium to prepare alkyl aryl ketones.
J. Am. Chem. Soc., 2008, 130 (32), pp. 10510–10511. See: 10.1021/ja804351z