A CONVENIENT METHOD FOR LACTONIZATION OF α-ALLYL ESTERS USING IODINE IN DIMETHYLSULPHOXIDE

A simple method for the synthesis of α-γ-disubstituted-γ-butyrolactones by cyclization of α-allyl esters using iodine in dimethylsulphoxide is reported. This method is efficient and operationally simple in comparison to methods using transition metal complexes.


INTRODUCTION
γ-Butyrolactones are important building blocks in the synthesis of many natural products [1].Saturated γ-lactones are encountered frequently in large number of natural products especially flavour components and plant growth regulators [2].γ-Lactones are also very useful in the synthesis of nucleosides and related bioactive compounds.In particular, some aryl substituted γlactones have shown cancer preventive and anti-inflammatory properties [3].
Several routes to prepare γ-lactones and lactone derivatives have been reported [4].Numerous synthetic methods [5] have been developed for the synthesis of chiral α-methylene butyrolactones, often using transition metals or their [6].
Yamazaki et al. reported the use of the allyl group as a protecting group for the acidic hydrogen in malonic ester [7].Iodine is available as a crystalline solid and is easy to handle and not particularly toxic.The DMSO-I 2 reagent has been used in the oxidative cyclization of 2'hydroxy chalcones to flavones [8], the oxidation of flavanones to flavones [9], isoxazolines to isoxazoles [10], and pyrazolines to pyrazoles [11].It has also been used for the deprotection of allyl carboxylic esters [12].Very recently we reported the selective deallylation of allyl ethers and esters using iodine in polyethylene glycol-400 [13].Allyl ethers of phenols are selectively deprotected using iodine in dimethyl sulphoxide [14].
Initial results of the use of iodine in dimethylsulphoxide for oxidative cyclization of 2'allyloxy chalcones to flavones encouraged us to use this reagent system for the cyclization of αallyl esters.2'-Allyloxy chalcones with iodine (20%) in dimethylsulphoxide result in attack of the allyloxy oxygen towards reactive alkene group.This results in the deallylation of 2'-allyloxy chalcones followed by cyclization to give six membered flavone rings.In α-allylphenyl acetate, the allyl group is attached to a carbon which is bonded to an aryl ring and a carbonyl group.This carbon is sufficiently acidic to give the deallylated product.To study C-deallylation, α-allyl esters were reacted with iodine (20%) in dimethylsulphoxide reagent.But under the initial conditions, it was observed that the oxygen of the ester group attacks the allyl group to form the corresponding γ-butyrolactone.We herein report the results of a study involving the reaction of α-allyl esters with I 2 -DMSO to yield α-γ-disubstituted-γ-butyrolactones.

EXPERIMENTAL
General procedure for cyclization of α-allyl esters to α-γ-disubstituted-γ-butyrolactones (2a-o).To a solution of α-allyl ester 1 (1 mmol) in dimethylsulphoxide (3 mL) was added iodine (0.2 mmol).The reaction mixture was heated in an oil bath at 80-90 °C for 2 hours.After cooling, the reaction mixture was diluted with water and iodine was removed by addition of a saturated solution of sodium thiosulphate followed by a water wash.The product was extracted into ethyl acetate, washed with water, dried over anhydrous Na 2 SO 4, and the solvent removed using a rotary evaporator.The product was purified by column chromatography (hexane/ethyl acetate, 9:1).

RESULTS AND DISCUSSION
Earlier we reported the use of DMSO-I 2 for the synthesis of flavones from 2'-allyloxy chalcones [16] in which the allyl group is first deprotected and the resulting 2'-allyloxychalcones then oxidatively cyclized to flavones.We thought this type of cyclization would be possible in α-allyl esters using the same reagent.To test this hypothesis, α-allyl carboxylic esters (1) were reacted with iodine (20%) in dimethyl sulphoxide in order to generate the γ-butyrolactone.The reaction was complete in 3-4 hours at 80-90 °C.It was observed that the reaction resulted in cyclization to give the product α-γ-disubstituted-γ-butyrolactone (2) (Scheme 1).There are different methods reported for allyl cyclization using iodine.In most cases, iodocyclization gives the desired product [17].In the synthesis of flavones from 2'hydroxychalcones, Silva and co-worker reported that traces of HI were observed [18].In the presence of HI, our cyclization method results in generation of γ-methyl-butyrolactones. Presumably, this reaction is initiated by the HI which is formed in situ [19].The generation of HI can be explained by the following reaction (Scheme 2).A possible mechanism for cyclization of α-allyl carboxylic esters (1) to α-γ-disubstituted-γbutyrolactone (2) is presented below (Scheme 3).
α-Butyl-γ-methyl-butenolide can be used as a precursor for the synthesis of blastmycinone, blastmycinolactol.
Previous studies reported the synthesis of flavones from 2'-allyloxy chalcones [16].In this reaction, deallylation with oxidative cyclization of 2'-allyloxy chalcones gives flavones at 130 °C in 30 min.The same reaction can be accomplished at 60 °C in presence of a drop of concentrated sulphuric acid.In order to examine the effect of acid in reducing the temperature of the cyclization reaction of α-allyl carboxylic esters (1), a drop of concentrated sulfuric acid was added to the iodine in dimethylsulphoxide (Scheme 2).The reaction was completed in 3 h giving 40% yield.The plausible mechanism for the formation of α-substituted-γ-methylbutenolide from α-allyl carboxylic esters (1) is shown in Scheme 4.   In conclusion, we report a method for preparing α-γ-disubstituted-γ-butyrolactones by cyclization of α-allyl esters using iodine in dimethylsulphoxide.The efficiency, ready availability, and ease of handling encourages using the reagent for lactonization of various αallyl-esters.The DMSO-I 2 reagent in the presence of a catalytic amount of H + is useful for the synthesis of α-substituted-γ-methyl-butenolides.
a Isolated yields of the product.b Products are characterized by spectral analysis.
a Isolated yields of the product.b Products are characterized by spectral analysis.

Table 3 .
Effect of Quantity of iodine.
a Isolated yields of the product.b Products are characterized by spectral analysis.