Palladium-Catalyzed Cross Coupling

Overview

Source: Vy M. Dong and Faben Cruz, Department of Chemistry, University of California, Irvine, CA

This experiment will demonstrate the concept of a palladium-catalyzed cross coupling. The set-up of a typical Pd-catalyzed cross coupling reaction will be illustrated. Pd-catalyzed cross coupling reactions have had a profound effect on how synthetic chemists create molecules. These reactions have enabled chemists to construct bonds in new and more efficient ways. Such reactions have found widespread applications in the fine chemical and pharmaceutical industries. Pd-catalyzed cross coupling reactions add another tool to the chemist's toolbox for constructing carbon-carbon bonds, which are central to organic chemistry. The combination of the importance of making carbon-carbon bonds and the impact of Pd-catalyzed cross coupling have resulted in these reactions being the subject of the 2010 Nobel Prize in Chemistry. Ei-ichi Negishi, one of the recipients of the 2010 Nobel Prize in chemistry, explained in his Nobel lecture that one of his motivations for developing this chemistry was to develop "widely applicable straightforward Lego-like methods for hooking up two different organic groups".

Procedure

Add 4-iodoacetophenone (246 mg, 1 equivalent, 1 mmol), acrylic acid (100 μL, 1.5 equivalents, 1.5 mmol), sodium carbonate (Na₂CO₃, 318 mg, 3 equivalents, 3 mmol), PdCl₂(2 mg, 0.01 equivalents, 0.01 mmol), and water (5 mL, 0.2 M) to a round bottom flask (~ 20 mL) equipped with a magnetic stir bar.
Heat the reaction to approximately 100 °C and stir until complete consumption of 4-iodoacetoph

Results

The product should be a solid with the follow ¹H NMR spectrum: ¹H NMR (400 MHz, DMSO-d₆): δ (ppm) 2.60 (s, 3H), 6.67 (d, J = 16.0 Hz, 1H), 7.65 (d, J = 16.0 Hz, 1H). 7.83 (d, J = 8.4 Hz, 2H). 7.97 (d, J = 8.4 Hz, 2H).

Application and Summary

These Pd-catalyzed cross coupling reactions have changed the way molecules are synthesized in academic and industrial settings. The impact of this technology can be seen in how chemists construct complex structures for pharmaceuticals, agriculture chemicals, and materials. Beyond Pd-catalyzed cross couplings, transition metal catalysis has changed (and is continuing to change) the way synthetic chemists prepare molecules that can have an impact on society through their potential therapeutic use.