Reaction of phenyllithium with E-cinnamaldehyde: survey of several variables and their influence on the mechanism of reaction and in organic synthesis

Abstract

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.

Solvent and Ligand Effects on the Tandem Addition-Lithiation-Electrophilic Substitution of Phenyllithium on α,β-Unsaturated Carbonyl Compounds

“…By-side products were E-cinnamyl alcohol (3), E-chalcone (4), and E-1,2-dihydrochalcone (5), as shown in Scheme 1. [3,7] and it shows the yields of the several reaction products determined when carrying out the reaction in three solvents, namely: ethyl ether, toluene and THF. In all cases, the time of reaction was 3h, and it can be observed that the results are quite dependable of the reaction conditions.…”

“…THF, hexane, ethyl ether and toluene were purified and dried as previously described, assuring the absence of peroxides for the ethers [7]. In all cases, they were distilled from sodium benzophenone ketyl immediately before use.…”

Tandem Addition β-Lithiation−Alkylation Sequence on α,β-Unsaturated Aldehydes

“…A thorough survey of the different parameters influencing the addition of phenyllithium to (E) -cinnamaldehyde, 1a , has been recently reported . We demonstrated that the reaction is highly sensitive to the reaction conditions and by a careful choice of them, further metalation of the β-carbon can be afforded thus providing a successful route for the synthesis of β-substituted dihydrochalcones in high yields .…”

Enantioselective Addition of Grignard Reagents to Aldehydes

“…It is based on the coordination of amines and ethers to organolithium and Grignard reagents; the efficiency of the asymmetric induction depends, among other factors, on the characteristics of the metal [2], its aggregation state [3] and on the chiral ligand structure [4].…”