Palladium catalyzed hydroesterification of substituted alkenes under microwave conditions

While several catalyst systems have been utilized in the hydroesterification or methoxycarbonylation of alkenes or equivalent substrates, these reactions are conventionally performed in autoclave reactor systems under high CO pressure (20 - 70 bar) and thermal heating (70 – 110 o C). In this paper, the first methoxycarbonylation reactions performed in a microwave reactor fitted with a gas-addition accessory system are reported on and compared to the same reactions performed under conventional heating in an autoclave reactor. Thus 1-octene, styrene, allylbenzene, o - and p -methoxyallylbenzene and β-methylstyrene were subjected to methoxycarbonylation over a palladium acetate–aluminum triflate catalyst system at 12 bar and 95 o C. Results obtained indicated the methoxycarbonylation of these alkenes to be much faster under microwave conditions when compared to conventional heating and improvements in conversion ranged between 3 and 5% for the more reactive substrates (1-octene and styrene) and 6 – 20% for the allylbenzenes and β-methylstyrene.

Since it is generally known that microwave heating has the ability to accelerate some chemical reactions 18 and the hydroesterification reaction was found to be rather slow, it was decided to evaluate the effect of microwave heating on the rate of the alkoxycarbonylation of substituted alkenes over a palladium acetate catalyst system.

Results and Discussion
In order to be in a position to compare the results of the microwave mediated reactions with the results obtained under conditions of ordinary heating at 95 o C and the optimum pressure of 35 bar, as reported earlier, 5 the same Pd(II)/Al(OTf) 3 /PPh 3 catalyst system, developed by Williams et al., 19,20 was utilized during the current investigation.Furthermore, since the glass vessels of the microwave reactor are rated at 12 bar only, the reactions in an autoclave reactor were also performed at 12 bar CO pressure (95 o C), while the investigation was started with the very reactive general hydroesterification substrates, 1-octene (3) and styrene (4) (Scheme 1) for possible comparison with literature results.Scheme 1. Methoxycarbonylation of 1-octene (3) and styrene (4).l and b refers to the 'linear' and 'branched' isomers, respectively.
As indicated in Table 1, both substrates, 1-octene (3) and styrene (4) showed a substantial increase in conversion of ca.20% and 30%, respectively, even after only 10 minutes of reaction time for the microwave reaction when compared to the autoclave reaction at the same pressure (12 bar).Furthermore, virtually complete conversion of the starting material (99%) was observed after 30 minutes under microwave irradiation, while the reactions under conventional heating conditions at the same pressure (12 bar) were not fully completed (Table 1, entries 2 vs. 3 and 5 vs. 6).Even when compared to the reactions at 35 bar, the microwave equivalents showed a slight improvement over those performed with conventional heating (Table 1, entries 1 vs. 3 and 4 vs. 6).The fact that the final yields for the microwave reactions are somewhat lower than those of the reactions in the autoclave reactor under the same conditions (82% vs. 91% and 72% vs. 92%, respectively) is probably explicable in terms of unwanted side-reactions.These could include reactions like polymerization in the case of styrene (4), and/or subsequent hydrolysis of the ester products, 5, 6, 7 and 8, by water present in the methanol, due to the extended exposure to the microwave heating conditions, since the MW reactions were already 99% and 89% completed after only 10 minutes (Table 1, entries 3 and 6).When subjecting the aryl substituted alkenes, allylbenzene (9), 4-allylanisole (10), 2-allylanisole ( 11) and trans-β-methylstyrene (12) to the methoxycarbonylation reaction, it should be kept in mind that these substrates are prone to palladium catalyzed isomerization of the double bond between the internal and terminal positions, so the same products, i.e. 'linear', 'branched' and 'benzylic' isomers, could be formed from both the similarly substituted allylbenzene and β-methylstyrene derivatives (Scheme 2).
When the 1-and 2-propenylaryl substrates (Scheme 3) were subjected to the methoxycarbonylation reaction under microwave heating (150 W) over the standard catalyst system, Pd(OAc) 2 /Al(OTf) 3 /PPh 3 , it was found that all the substrates reacted much slower than 1-octene (3) and styrene (4), so reaction times of up to three hours were required to reach completion in both the MW and autoclave reactions at 35 bar.p-Methoxyallylbenzene (10) proved to be even less reactive and gave conversions of only 40-60% after the 3 hours, with the better conversion (60%) observed for the autoclave reaction at 35 bar.When comparing the reactions at 12 bar for this substrate (10), however, the MW method gave a better conversion (28% vs. 20%) even after only 1 hour (Table 2, entry 5 vs. 6).Scheme 3. Methoxycarbonylation of allylbenzenes (9 -11) and β-methylstyrene (12).
With regard to the regioselectivity of the reactions, a general decrease in selectivity was evident in the microwave reactions when compared to the conventional heating experiments at the same CO pressure (Table 2, entry 2 vs. 3, 5 vs. 6, 8 vs. 9 and 11 vs. 12).Though still the major products, the lower selectivity towards the linear products is probably explicable in terms of a more facile isomerization to the corresponding internal olefins for the allylbenzene substrates under the microwave conditions, while isomerization of the βmethylstyrene to the sterically less hindered allylbenzene isomer may be slower than the secondary terminal to internal isomerization.

Conclusions
Finally, for 1-octene (3) and styrene (4), a definite reaction rate increasing effect was observed with the conversion after 10 minutes under microwave conditions at 12 bar being almost the same or better than what was obtained after 30 minutes at 35 bar with conventional heating in an autoclave reactor.Although no dramatic reaction rate enhancing effect was observed for the other substrates, both the substituted allylbenzene analogues (10 and 11) and β-methylstyrene (12) showed improvements in conversion and yield under microwave conditions when compared to conventional heating at the same pressure.The fact that only a very slight improvement in conversion and yield could be detected for allylbenzene (9) is currently inexplicable.

Experimental Section
General.All the chemicals used were purchased from Sigma-Aldrich and used as received.Reactions were performed in a 4590 Parr autoclave reactor (25 ml vessel) with mechanical stirring (500 rpm) and a CEM Discover SP Microwave Reactor, equipped with a gas addition accessory and an internal IR temperature sensor, in a sealed tube (10 ml tube) and stirred by a magnetic stirrer bar. 1 H and 13 C NMR as well as 2D experiments were done on a 600 MHz Bruker AM FT spectrometer at 20°C at 600 MHz for 1 H NMR and 151 MHz for 13 C in CDCl 3 as solvent. 1 H NMR chemical shifts are given relative to the TMS signal at 0 ppm and 13 C NMR shifts are given relative to the CDCl 3 peak at 77.16 ppm, coupling constants are measured in Hz and chemical shifts in ppm.Mass spectrometry was performed on a Shimadzu GCMS QP-2010 instrument using electron-impact (EI) ionization.Conversions, yields and product ratios were determined on a Shimadzu 2010 GC instrument with xylene as the internal standard.Methyl nonanoate (5) and methyl 2-methyloctanoate (6)  were purified by passing the reaction mixture through a pad of silica gel, while all the other products were purified using flash column chromatography with silica gel 60 as stationary phase and obtained as mixtures of linear, branched and, in the case of the allylbenzenes, benzylic isomers.

Table 1 .
Methoxycarbonylation of 1-octene (3) and styrene(4) a Conventional heating in an autoclave reactor.b Microwave irradiation (150 W). c Determined by GC analysis with xylene as internal standard.d Combined yield determined by GC analysis (with xylene as internal standard).

Table 2 .
Methoxycarbonylation of allylbenzenes (9 -11) and β-methylstyrene(12) a Conventional heating in an autoclave reactor.b Microwave irradiation (150 W). c Determined by GC analysis with xylene as internal standard.d Combined yield determined by GC analysis (with xylene as internal standard) after 3 hours.