Organic Synthesis

Cross Coupling Reactions

  • Suzuki-Miyauri Coupling
    • In organic synthesis, Suzuki-Miyauri are very common reactions to run, due to its high efficacy, low cost, and safe reagents. Some examples of its use in industry is the drug Linifanib, a drug that inhibits angiogenic signaling pathways, preventing the growth of new blood vessels, suppressing tumor growth.

Libretexts. Suzuki-Miyaura Coupling. https://chem.libretexts.org/Bookshelves/Inorganic_Chemistry/Supplemental_Modules_and_Websites_(Inorganic_Chemistry)/Catalysis/Catalyst_Examples/Suzuki-Miyaura_Coupling (accessed 2025-04-30).

    • Not only is this reaction useful in drug synthesis, but in the synthesis of emitters for OLED displays, a technology that everyone carries with them. This example of an OLED synthesis via Suzuki coupling utilizes a one-pot, 3 step Suzuki coupling in order to achieve its product.

Dhangar, G.; Serrano, J. L.; Schulzke, C.; Gunturu, K. C.; Kapdi, A. R. Palladacycle-Catalyzed Triple Suzuki Coupling Strategy for the Synthesis of Anthracene-Based OLED Emitters. ACS Omega 2017, 2 (7), 3144–3156. https://doi.org/10.1021/acsomega.7b00725.

  • Heck Reaction

In total, the Heck reaction is used to produce up to 500 tons of fine chemicals per year, making it a very common reaction used. 

    • The Heck reaction is Used in a variety of medications, such as Chantix, a drug designed to help smokers quit. It features an intramolecular Heck Reaction.

de Vries, J. G. The Heck Reaction in the Production of Fine Chemicals. Can. J. Chem. 2001, 79 (5–6), 1086–1092. https://doi.org/10.1139/v01-033.

    • While not commonly involved in the synthesis today, the original synthesis of Naproxen, an NSAID used for arthritis pain, used a Heck reaction as well.

de Vries, J. G. The Heck Reaction in the Production of Fine Chemicals. Can. J. Chem. 2001, 79 (5–6), 1086–1092. https://doi.org/10.1139/v01-033.

    • Singulair Also Featured a Heck reaction, and is used to treat both seasonal allergies and asthma.

de Vries, J. G. The Heck Reaction in the Production of Fine Chemicals. Can. J. Chem. 2001, 79 (5–6), 1086–1092. https://doi.org/10.1139/v01-033.

    • Heck reactions are not only common in pharmaceuticals, but also in other commercial uses, such as Herbicides, specifically Prosulfuron.

de Vries, J. G. The Heck Reaction in the Production of Fine Chemicals. Can. J. Chem. 2001, 79 (5–6), 1086–1092. https://doi.org/10.1139/v01-033.

  • Negishi/Stille Couplings
    • Both Negishi and Stille couplings, while extremely useful, are not commonly used in synthesis anymore, due to the air sensitive Negishi reagents and toxic tin metal in Stille reagents. This significantly limits their use-cases to research labs, making them a useful drug discovery tool with limited commercial applications. Below is one of few examples of a Stille coupling being used commercially, which is due to the fact that the Stille coupling was the only reaction that worked in excess of 50 grams.

Haidle, A.; Kohrt, J.; Liu, F. The Stille Reaction. https://hwpi.harvard.edu/files/myers/files/11-the_stille_reaction.pdf (accessed 2025-04-30).

Asymmetric Catalysis

  • Noyori Hydrogenation
    • Noyori Hydrogenations are a poweful asymmetric reaction, and its first commercial use case was L-DOPA, commonly known as Levodopa, which is used in the treatment of Parkinsons. This discovery was so monumental that it won Knowles the 2002 Nobel Prize in Chemistry.

Myers, A. G. The Noyori Asymmetric Hydrogenation Reaction. https://hwpi.harvard.edu/files/myers/files/18-noyori_asymmetric_hydrogenation_reaction.pdf (accessed 2025-04-30).

    • It is also used in the synthesis of (R)-Warfarin, the most common anticoagulant used in America. The compound is known by its brand names Coumadin and Jantoven

Myers, A. G. The Noyori Asymmetric Hydrogenation Reaction. https://hwpi.harvard.edu/files/myers/files/18-noyori_asymmetric_hydrogenation_reaction.pdf (accessed 2025-04-30).

    • Noyori hydrogenation is also featured in Pregabalin, known as Lyrica, as an anti-convulsive agent able to treat epilepsy, neuropathic pain, and anxiety.

Myers, A. G. The Noyori Asymmetric Hydrogenation Reaction. https://hwpi.harvard.edu/files/myers/files/18-noyori_asymmetric_hydrogenation_reaction.pdf (accessed 2025-04-30).

  • Sharpless Epoxidation
    • Sharpless Asymmetric Epoxidation is an extremely useful reaction in the synthesis of pharmaceuticals, making it significantly easier to synthesize an enantiometrically pure compound. Here, it is being used to make reboxetine (Edronax), an anti-depressent. Sharpless epoxidation was introduced to this synthesis in order to drastically cut down on cost and waste. 

Assaf, G.; Checksfield, G.; Critcher, D.; Dunn, P. J.; Field, S.; Harris, L. J.; Howard, R. M.; Scotney, G.; Scott, A.; Mathew, S.; Walker, G. M. H.; Wilder, A. The Use of Environmental Metrics to Evaluate Green Chemistry Improvements to the Synthesis of (s,s)-Reboxetine Succinate. https://pubs.rsc.org/en/content/articlelanding/2012/gc/c1gc15921f (accessed 2025-04-30)