A tandem reaction between (E)-cinnamaldehyde, 1a, and phenyllithium affording beta-substituted dihydrochalcones was recently reported. NMR spectroscopic studies on the reaction mixture, as well as isotopic exchange reactions and trapping of two intermediates, provide clues on the several mechanistic steps of this new reaction. Extended studies revealed that beta-alkyl-substituted alpha,beta-unsaturated aldehydes and aliphatic lithium reagents did not afford good yields of the tandem reaction products, while aromatic lithium reagents gave good results. The aggregation features of the aryllithium reagents and the extended charged delocalization effects are considered to promote beta-selectivity. This approach provides a convenient route for the synthesis of a wide variety of beta-alkyl-substituted dihydrochalcones.
The reaction of phenyllithium (PhLi) with E-cinnamaldehyde (1) has been fully examined. Besides the main product E-1, 3-diphenyl-2-propen-1-ol (2), three other by-products were detected: E-cinnamyl alcohol (3), Echalcone (4) and E-1,3-diphenylpropanone (5). The effect of several variables on the nature and relative yields of products was examined. In all the solvents studied, the selectivity of the reaction was higher at higher temperatures, probably owing to aggregation effects; at lower temperatures the reaction is slower and the amount of by-products increases. The addition is complete in 1 h at 0°C in THF for a [PhLi]:[1] ratio of 1:1, and longer reaction times have almost no effect, while for the reaction in toluene the amount of by-products increases when the reaction mixture is allowed to stand. The concentration of the reagents has no important effect on the reaction as long as the ratio is kept equal to 1:1. The influence of light was examined and a marked decrease in the selectivity of the reaction was observed. When the reaction was carried out in the presence of radical traps, no by-products were detected. Finally, for a [PhLi]:[1] ratio of 3:1 the main product is the dihydrochalcone 5, especially for long reaction times. All the above results could be interpreted in a reaction scheme involving electron transfer from PhLi to 1, and further reaction of the radical ions formed as well as reaction of dimeric PhLi without previous deaggregation when the ratio is 3:1.
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