Versatile Transformations of α,β-Dibromoesters and Ketones in Basic Media under Microwave Irradiation

Abstract

Depending on the reaction medium, a,b-dibromoesters under microwave irradiation may selectively lead to a-bromoalkenes, to alkenes or to (E)-b-bromostyrenes. The corresponding ketones give selectively the a-bromoketones.We have previously reported the synthesis of functionalised aziridines 1 starting from a,b-dibromoesters or ketones 1 and primary amines over bentonite as solid support. This first study has shown that coupling of this reaction with microwave irradiation promoted the formation of a-bromoalkenes 4 (Scheme 1). Scheme 1In order to form selectively the a-bromoalkenes, we studied the behaviour of these a,b-dibromo compounds under various conditions 2 and we found that treatment with KF supported on alumina under microwave irradiation led to an elimination reaction which produced functionalised abromoalkenes in fair yields, but at high temperatures the formation of the debrominated alkenes 5 competed (Scheme 2).These results led us to extend the investigation related to these eliminations in various conditions with the aim of getting better selectivities.For this purpose, we chose methyl or ethyl-2,3-dibromo-3-phenylpropanoate (RS,SR), 2,3-dibromo-4-phenylbutanone (RS,SR) and their p-substituted phenyl derivatives.We found that in the presence of piperidine or Et 3 N without solvent, under thermal or microwave activation (MWI), the a,b-dibromoesters lead exclusively to a-bromoalkenes 4-(Z) and 4-(E) (Scheme 3) with very good yields in very short times (5-15 min) (Tables 1 and 2). Scheme 3All the compounds are already described in the literature resulting from various methods which need longer reaction times, are less straightforward and involve less ecofriendly procedures. [3][4][5][6][7] Although the yields were quantitative with both amines, it is noteworthy that the Z selectivity was higher with piperidine and that higher temperatures promote isomerisation.We realised a comparison between microwave activation and conventional heating by using an oil bath previously set at the temperature used under irradiation and found no difference between the two activation modes. Nevertheless the microwave experiments are much easier to set up.We were also interested in the debromination reactions for the synthesis of alkenes. This reaction is known in the literature using DMF coupled with a reducing agent 9-11 or as shown later with DMF alone. [12][13][14] In the latter case, the temperature was usually 150-160 °C under N 2 during 90 minutes.We readily achieved the debromination using 8.5 equivalents of DMF under microwave irradiation at a monitored temperature of 150 °C. In these conditions, we could observe the formation of the alkenes 5 in 5-15 minutes in good yields (Scheme 4 and Table 3).It is noteworthy that an electron-donating substituent on the phenyl group (1c and 2c) leads to a lower yield of 5 Br X R H Br H N R 1 1 2 3 4 X: ester or ketone Scheme 2 R X Br Br X R H Br H MWI R Br X R X + X: ester or ketone KF/Al 2 O 3 + 1 4 (Z) 4(E) 5Downloaded by: Nanyang Technological University NTU. Copyrighted mate...