(Hive Bee)
03-23-03 23:12
No 420611
(Rated as: excellent)
From:
by F. Fringuelli, F. Pizzo and L. Vaccaro
abstract:
For the first time AlCl3 has been conveniently employed as a Lewis acid in water and efficiently catalysed regio- and stereoselective azidolysis of alpha,beta-epoxycarboxylic acids in water.
Lewis acid catalysed organic reactions in water are currently of great research interest.(1) Lanthanide triflates are the most popular *water-tolerant* Lewis acids.(2) They catalyse many reactions (1,3) and are reported to be stable in water,(3) different from common metal salts (eg. AlCl3) that decompose readily in water and therefore are thought to be unstable in aqueous medium.(3)
AlCl3 is a hard Lewis acid that coordinates hard basic centres like the oxygen atom of a carbonyl group and that of an epoxide, activating the reagent for a nucleophilic attack. Water is a hard base and therefore nucleophilic reactions catalysed by AlCl3 are recommended to be carried out in organic solvents under anhydrous conditions.
Continuing our investigations (4) on the use of water as reaction medium for organic reactions, we discovered that 1 mol% of AlCl3 effectively catalysed the azidolysis of alpha,beta-epoxycarboxylic acids in water at pH 4.0.
The results for a variety of alpha,beta-epoxycarboxylic acids in the presence and in the absence of AlCl3 are illustrated in Table 1. All experiments were carried out at pH 4.0, held constant for the whole reaction time.
The reactions carried out in the presence of AlCl3 are fast and completely regio and- diastereoselective. The beta-azido-alpha-hydroxycarboxylic acid coming from the anti attack of the azido ion was the sole reaction product, which was isolated in excellent yields. For trans-alpha,beta-epoxy-alpha-methylcinnamic acid only, 3% diol was also detected.
The comparisions between the uncatalysed (without AlCl3) and catalysed (with AlCl3) reactions, all carried out under the same acidic conditions show that in absence of AlCl3 the reactions are much slower, which indicates that under the pH conditions used, Br0nsted catalysis is not significant. For example in the presence of AlCl3 the azidolysis of alpha,beta-epoxycyclohexanecarboxylic acid at pH 4.0 after 0.25 hours gave only a 2% conversion whereas in the precense of AlCl3, after the same reaction time the reaction was complete ; and for alpha-methyl-trans-alpha,beta-epoxy-beta-phenylpropionic acid the complete conversion was reached after 20 hours in the absence of Lewis acid catalyst and in only 15 min in the presence of AlCl3.
AlCl3 is not the active catalytic species. AlCl3 dissociates in water very quickly and hydration occurs immediately with the formation of the corresponding aqua ion (Al(H2O)63+ ; pK1,1=4.97-5.5). At pH 4.0 it was estimated that about 5% hydrolysis of the aqua ion occurs and only monomeric species were present. Therefore we believe that the catalytic species is the aluminium aqua ion that coordinates the epoxycarboxylic acid and azide ion forming a reacting complex ; the nucleophile is then regio- and stereoselectively transferred to the substrate beta-carbon.
In a typical procedure the alpha,beta-epoxycarboxylic acid (1 mmol) and NaN3 (5 mmol) were dissolved in water (2 ml) with stirring at a suitable temperature in a thermostated flask equipped with a pH-stat apparatus. An 0.5 M AlCl3 aqueous solution (50 microl.) was added and the pH adjusted to 4.0 value by adding 50% H2SO4 solution (150 microl.). The mixture was stirred for a suitable time keeping the pH constant at 4.0 by a pH-stat (100 microl. of 50% H2SO4 aq. sol.). At the end, the mixture was cooled to 0°C, acidified to pH 2.0, extracted with diethyl ether and worked up as usual to give the beta-carbon adduct obtained in pure form in a 93-95% yield.
The mother liquor that remained after the work-up can be reused three times without loss of reactivity and selectivity.
To our knowledge this is also the first report on the use of AlCl3 in water to catalyse an organic reaction. The possibility of using AlCl3 in water opens new research strategies in organic synthesis, which are being studied in our laboratory.
refs:
(1): a) Li & Chang, Organic reactions in aqueous media, Wiley, NY 1997
b) Var. authors, Organic synthesis in water, Grieco, Academic and Professional, London, 1998
(2) a) Kobayashi, Synlett 1994, 689
b) Kobayashi et al, J. Am. Chem. Soc. 1998, 120, 8287
(3) Xie, Jin & Wang Chemtech 1999, 23
(4) a) Fringuelli et al J. Org. Chem. 1999, 64, 6094
b) id., Synlett 2000, 311
c) id., Synthesis 2000, 646
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