Unusual regioselectivity in nucleophilic addition to η 3 - р - allylpalladium complex in conventional heating and under microwave irradiation

Nucleophilic attack of 3-hydroxycoumarin on η 3 - р -allylpalladium complex formed from substituted cinnamyl alcohols and acetates in the presence of palladium acetylacetonate and triphenylphosphine resulted normal addition product like 4-(3´-phenylallyl)-3-hydroxycoumarin, except for cinnamyl acetate, which provided an unusual product 4-(1´-phenylallyl)-3- hydroxycoumarin by conventional and microwave heating.


Introduction
Palladium-catalyzed allylic substitution reactions [1][2][3][4][5] have been receiving a great deal of attention in recent years, utilizing a wide range of nucleophiles.Since the coumarin moiety has several biological activities 6,7 and has been utilized as therapeutic agents in different diseases, 3hydroxycoumarin has been exploited for the first time as nucleophile in η 3 -р-allylpalladium complex mediated reaction by us.Several substituted cinnamyl alcohols and acetates have been chosen for this reaction.The reactions were carried out not only by conventional heating but also under microwave irradiation.MORE 8 (Microwave -induced Organic Reaction Enhancement) chemistry is the most emerging trend in global perspective.Microwave irradiation has provided a versatile method to speed up many chemical reactions 9,10,11 delivering high yields in a few minutes.The process is not only rapid but also energy-efficient, cost-effective.So we have carried out allylic substitution reaction under microwave irradiation also.

Results and Discussion
Treatment of cinnamyl alcohol with 3-hydroxycoumarin in toluene (at 80 o C for 8 hours / 10 min., MW) in the presence of palladium acetylacetonate and triphenylphosphine under argon atmosphere resulted in 4-(3´-phenylallyl)-3-hydroxycoumarin (1a) as the only product in good yield (70% in conventional heating, 78% under microwave irradiation) (Scheme 1).The structure of the addition product (1a) was established by the presence of nine aromatic protons at δ 7.57-7.12ppm, two olefinic protons at δ 6.47 and 6.23 as doublet (J = 15.8Hz) and double triplet (J = 15.8 and 6.2 Hz) for 3´-H and 2´-H respectively in 1 H NMR spectrum.Two 1´-H protons appear as doublet (J = 6.2 Hz) at δ 3.69.In 13 C NMR besides the usual aromatic ring carbons, olefinic carbons appear at δ 132.6 and 125.0 ppm and C-1´ carbon resonates at δ 28.1.
But surprisingly, when cinnamyl acetate was treated under identical condition, only a regioselective unexpected product was obtained in appreciable amount (62% by conventional heating and 60% under microwave irradiation) with the structure 4-(1´-phenylallyl)-3hydroxycoumarin (2).Its structure was evidenced by the appearance of nine aromatic protons at δ 7.44-7.01ppm, three olefinic protons, one at δ 6.46 (2´-H) as multiplet and two at δ 5.24 (3´-H) as double doublet (J = 13.5, 6.5 Hz) and one methine proton at δ 5.39 (1´-H) as doublet (J = 7.8 Hz) in 1 H NMR spectrum.In 13 C NMR spectrum, carbons of coumarin moiety and aromatic carbons of cinnamyl residue appear at usual range.Two olefinic carbons, C-2´ and C-3´ appear at δ 136.2 and 118.6 ppm respectively and C-1´ carbon shows signal at δ 46.0 ppm which evidences the structure 2 2 .

Scheme 3. Mechanism of reaction for Scheme 1.
But the formation of the unusual product 2 can be explained by a direct nucleophilic attack of the hydroxycoumarin on the internal double bond carbon followed by double bond shift and elimination of the acetoxy group (Scheme 4).

Scheme 4. Formation of 2.
This may be a reasonable possibility not involving an η3-р-allylpalladium complex intermediate.The formation of 2 can also be rationalised by Claisen type sigmatropic rearrangement (Scheme 5).

Scheme 5. Formation of 2 via Claisen type rearrangement.
Reactions of the other substituted cinnamyl acetates resulted in usual products (1b and 1c) presumably due to the electron-releasing effect of these substituents.The electron-releasing effect of these substituents make the attack on the double bond more difficult, thus favouring the formation of the allyl complex.

Experimental Section
General Procedures.IR spectra were recorded on a Perkin-Elmer FTIR-RXI spectrophotometer and 1 H and 13 C NMR spectra were run on Bruker AM 300L spectrometer operating at 300 MHz and 75 MHz respectively.The chemical shifts were referenced to TMS as internal standard using d-chloroform as solvent.Microwave oven used was BPL, 800T / MM 261 EEP.
Experimental procedure for conventional heating method.A mixture of 3-hydroxycoumarin (0.324 g, 2 mmol), cinnamyl alcohol or acetate (2 mmol), palladium acetylacetonate (0.39 g, 1.28mmol) and triphenylphosphine (0.104 g, 0.397mmol) in toluene (5 ml) was taken in a sealed pyrex tube under argon atmosphere and heated at 80 o C for 8 hours.The reaction mixture was cooled and poured into ice cold water.Then it was extracted with ethyl acetate (3x3 ml), washed with brine and dried over anhydrous sodium sulphate.Evaporation of the solvent followed by the filtration on a short silica gel column afforded the coupled product.Experimental procedure under microwave irradiation.The same mixture (conventional heating method) was subjected to microwave irradiation for the specified time (Table 1).It was poured into ice cold water and worked up as usual.The NMR spectroscopic data of the products are given in the Table 2 and Table 3.

Table 1 .
Reactions under microwave irradiation