Efficient allylation of carbonyl compounds with allyl chlorides in water

A novel mediation system, Zn-InCl 3 (cat.)/NH 4 Cl was employed in the Barbier–type allylation. As a result, the allylation with allyl chloride in water took place smoothly under mild conditions. Various aldehydes and even ketones could be employed to afford the corresponding alcohols in high yields. The stereochemistry of the allylation reactions was also briefly discussed.


Introduction
Recently, organic reactions in aqueous media have attracted more and more attention in organic synthesis because of their environmental benefits and the favorable effects of water on organic transformations. 1 Among the reactions in aqueous media, allylations of carbonyl compounds with allylic organometallic compounds or allyl halides are of particular interest because they are the convenient method to form C-C bond and to generate homoallylic alcohols, which are important building blocks in natural product synthesis. 2Many metals such as Mg, 3 Zn, 4 Sn, 5 In, 6 Bi 7 have been employed as the mediators to promote the allylation under mild conditions.In these reactions, the allyl halides used were generally allyl bromides.Allyl chlorides, which are cheaper and more stable than allyl bromidse, are hardly effective. 8Therefore, it is important to develop the allylation methods with allyl chlorides under mild conditions.Herein we report a new and facile allylation method with allyl chloride in water (Scheme 1).A variety of carbonyl compounds were then allylated under the above optimized condition and the results are summarized in Table 2.Both aldehydes and ketones were converted smoothly to the corresponding homoallylic alcohols in good to excellent yields.No pinacol coupling products or reduced products were observed.The results showed that the substituents on phenyl ring, whether electron-donating or electron-withdrawing, had almost no influence on the allylations (entries 1-6, Table 2).Moreover, the allylation with crotyl chloride gave the corresponding adducts in excellent yields regardless of whether the substrate is an aldehyde or a ketone (entries 15-19, Table 2).To the best of our knowledge, no report on the corresponding allylation of ketone with crotyl chloride in water was found.Only a few examples with allyl bromide were reported, in which the corresponding allylations hardly took place or gave the corresponding adducts in low yields and the reactions took long time. 11It is interesting to note that the substrates with a hydroxyl group such as 2-hydroxylbenzaldehyde, 2-hydroxyl-5methoxybenzaldehyde and 3-hydroxybuta-2-one gave slightly higher yields probably because of their better solubility in water (entries 8, 9, 14, Table 2).
With crotyl chloride, the reactions were highly regioselective (entries 15-19, Table 2).The allylation gave the corresponding γ adducts exclusively except for benzaldehyde, in which the ratio of γ to α adduct was around 33 : 1.In all the cases, syn-isomers were favored over the antiisomers.These results are different from those reported in the literature in which no stereoselectivity was observed 12 or the anti-isomers were favored. 13The reason for the differences in the stereoselectivities is still unclear.In conclusion, we have developed a novel mediation system for the allylation of carbonyl compounds with the more popular and less expensive allyl chlorides, giving the corresponding homoallylic alcohols in good to excellent yields.Both aldehydes and ketones can be allylated smoothly.Further investigation on the role of InCl 3 is in progress in our laboratory.

Experimental Section
General Procedures.All the chemicals were commercially available and directly used without further purification.IR spectra were performed on a Bruker FT-IR spectrometer. 1 H NMR and 13 C NMR spectra were measured on a Brucker-300MHz spectrometer with CDCl 3 as the solvent and TMS as the internal standard.HRMS data were collected on a Micromass GCT mass spectrometer with an EI mode.

Table 2 .
Alllylation of carbonyl compounds with allyl chlorides in sat.NH 4 Cl

Table 2 .
Continued Allyl bromide was used.c Combined yields.The ratio was determined by 1 H NMR. d The yield was estimated by 1 HNMR.