Sn/I 2 Mediated allylation of carbonyl compounds with allyl (crotyl) halide in water

A novel mediator (Sn/I 2 ) has been developed and employed in the allylation and crotylation of various aldehydes and ketones with allyl (crotyl) halide in water. With a catalytic amount of I 2 and less than stoichiometric amounts of Sn, allyl (crotyl) bromide reacts with carbonyl compounds to produce the corresponding alcohols in quantitative yield. Even the inert allyl chloride and crotyl chloride can react with aldehydes to give the corresponding alcohols. The diastereoselectivity and regioseletivity of the reaction have also been studied. Sn/I 2 mediated allylations of aldehydes with crotyl bromide produced dominant γ -adducts with minor α -isomers while Sn/I 2 mediated allylations of aldehydes with crotyl chloride afforded dominant α -adducts with minor γ -isomers.


Introduction
Organic reactions in aqueous media is a significant branch of green chemistry utilizing a variety of organometallic reagents to accomplish Barbier-type carbonyl allylation in water. 1 As a typical Barbier-type allylation, metal-mediated allylation in aqueous media is studied widely.Metals such as indium 2 , zinc 3 , gallium 4 , iron 5 and tin 6 are always used as mediators.However, in order to improve the reaction yield, more than stoichiometric amount of metals, long reaction time, the vast use of inorganic salt 7 (e.g.NH 4 Cl, SnCl 2 ), an organic co-solvent 8 or ultrasonic irradiation 9 are often involved.These facts prompted us to investigate a novel allylation reaction, which is very convenient to use, has a low cost, and does not require difficult techniques.Here, we discovered a novel mediator (Sn/I 2 ) for the allylation reaction in water.Using this new mediator, the dosage of tin metal can be decreased and the scope of substrates was extended.Even allyl chloride and crotyl chloride, which were inert to allylation in most cases, can be activated in the

Entries Substrates
Products Time (h) Yield %

Tin & iodine mediated crotylation of various aldehydes and crotyl halides
The crotylation can also be promoted by this new mediator regardless of the use of crotyl bromide or crotyl chloride, affording the corresponding product in good yields (Table 3).
ARKAT USA, Inc.  b The ratio of α to γ was determined by 1 H NMR, 13 C NMR.
As shown in Table 3, using only a catalytic amount of iodine, the carbonyl crotylation by crotyl bromide can be carried out smoothly to generate the corresponding alcohols with excellent to quantitative yields in 6-12 hours (entries 1-7, Table 3).Under these conditions, the reaction preferred the syn-isomer in dominant γ-adduct.When crotyl chloride was employed in the carbonyl crotylation, a bigger amount of iodine (0.5 mmol) was needed to mediate the crotylation, perhaps due to the low reactivity of crotyl chloride.The Sn/I 2 promoted crotylation using crotyl chloride produced the corresponding alcohols with good to excellent yields (entries 8-12, Table 3).Compared to the allylation of crotyl bromide, the crotylation of crotyl chloride gave α-adducts as the predominant products.For 4-methoxybenzaldehyde or 2methoxybenzaldehyde, when 0.5 of mmol I 2 was used to promote the crotylation of crotyl chloride, side reactions increased.Nevertheless, the suitable reduction of the iodine dosage had little influence on the allylation for these two substrates.When the amount of I 2 was reduced to 0.2 mmol in order to eliminate the side reactions, the γ-adduct product was obtained as the predominant product (entries 13-14, Table 3).
Plausible mechanisms are shown in Scheme 1.The γ-anti product likely forms via the usual six-membered cyclic chair transition state (C).The stannous intermediate (A) behaves as a Lewis acid 10 and coordinates with the carbonyl oxygen.When a catalytic amount of iodine was added in the reaction, iodine can coordinate with the stannous bromide to afford an intermediate (B), in which the Lewis acidity of stannous is reduced while the steric hindrance of the α-C of the allylic halide is increased due to the iodine coordination.As a result, the nucleophilicity of the γ-C in the allylic halide is enhanced and this γ-C attacks a substrate aldehyde directly to afford an acyclic antiperiplanar transition (D).This acyclic antiperiplanar transition, in which the steric hindrance is reduced most, leads to a γ-syn product 11 .With the addition of iodine, the amount of stannous iodide is increased and the excess of iodine maybe results in the formation of iodonium.Either this iodonium or stannous iodide can promote the formation of a chair-formed sixmembered cyclic transition state (E), in which the γ-position is occupied by iodine and the electron density of the α-C is increased, resulting in the α-nucleophilic attack to afford the αadduct product.6g The iodine in iodonium is inclined to bind to a neighboring stannic iodide, which pushes the methyl group to the same side as that of the α-C, as shown in (E) and prefers the formation of a Z-isomer in an α-adduct product.According to this proposed mechanism, the experimental results and the diastereoselectivity can be explained to some extent.

Conclusions
In conclusion, Sn/I 2 efficiently mediates the Barbier-type allylation of carbonyl compounds with crotyl (allyl) halide (Br or Cl) in water afford the corresponding homoallylic alcohols with good to excellent yields.The addition of iodine led to the reduction of the mediator loading of the Experimental Section General Procedures.A mixture of benzaldehyde (0.10 mL, 1.0 mmol, 1 equiv.),tin powder (0.10 g, 0.9 mmol), I 2 (25mg, 10% mmol) and allyl bromide (0.14 mL, 1.5 mmol) in water (2-4 mL) was stirred in a 10 mL round-bottom flask equipped with a glass septum at room temperature for several hours.Then the reaction mixture was extracted with ethyl acetate (3×10ml).The combined organic layer was washed with 10 mL of water and 10 mL of brine respectively, and dried over anhydrous magnesium sulfate.The mixture was then filtered.Pure product was obtained after evaporating the solvent with a yield of 99% (160mg).

Table 1 .
Allylation of carbonyl compounds and allyl bromide mediated by Sn/I 2 in water

Table 2 .
Allylation of aldehydes/ketones and allyl chloride mediated by tin and iodine in water

Table 3 .
Regio-and diastereoselectivity for tin/iodine mediated allylations of aldehydes with crotyl halide in water