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Rapid Hydrogenation under Low Pressure

March 12, 2014

discoversp_gas_add.pngDifficult hydrogenations traditionally require high pressure and forcing conditions in order to produce the desired reduced products. Asymmetric hydrogenations pose the same challenges, plus the added concern to produce the desired stereochemistry. Arena and coworkers were able to use less rigorous conditions and maintain the desired stereochemistry of their (E)-enol acetate carboxylic acids through the use of microwave irradiation.

Utilizing the Gas Addition Accessory for the Discover microwave synthesis system, the authors were able to easily purge the reaction vessel, add the required amount of hydrogen (or other gaseous reagent as desired) and perform the reaction. The Gas Addition Accessory can be used with any of the Discover-based microwave systems.

discoversp_web.png Arena and coworkers first optimized the conditions using conventional, non-microwave conditions. The optimized conditions included 30 bar of hydrogen, 10% catalyst ([Rh(S)-Phanephos(cod)]BF4), MeOH, and Et3N at 60 oC for 16 hours. The authors wanted to increase the efficiency of the process and decided to try microwave conditions. They were able to reduce the catalyst loading to only 5%, reduce the amount of hydrogen required from 30 bar to only 5 bar, and maintain comparable yield and ee. While a higher temperature was required (80 oC vs 60 oC), the amount of time was substantially reduced (only 30 minutes, as opposed to 16 hours). The reaction was found to be scalable up to 6 grams of product.

Once the microwave conditions were optimized, the authors performed a direct comparison to conventional (non-microwave) conditions. Heating the sample to 80 oC in a preheated oil bath with 5 bar of hydrogen for 60 minutes gave no conversion to product. Allowing the transformation to continue for a total of 24 hours did not result in any conversion to the desired product. A 45% conversion to product (with a high ee) could be obtained by increasing the catalyst loading to 15%.

The authors noted:
The use of microwaves as a heating source allowed a drastic reduction of time, H2 pressure and catalyst loading required for reduction, confirming that the technique is highly suitable also for asymmetric catalytic reactions.


For more information on the Gas Addition Accessory, Discover Microwave System, or Arena and co-workers work, use the attached links.

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