Corey-Fuchs Reaction

The Corey-Fuchs reaction refers to the transformation of an aldehyde into a terminal alkyne through a two-step process: first, the aldehyde reacts with carbon tetrabromide (CBr₄) and triphenylphosphine (PPh₃) to form a dibromoolefin, which is then treated with n-butyllithium (n-BuLi) to yield the terminal alkyne. This reaction is named after the American chemists E. J. Corey and Philip L. Fuchs.

As an efficient organic synthetic method, the Corey-Fuchs reaction holds significant value in the synthesis of terminal alkynes. It plays an important role in simplifying synthetic routes, expanding organic synthesis strategies, and applications in medicinal chemistry, making it one of the most widely used classic reactions in organic chemistry.

Reagents: Carbon tetrabromide (CBr₄), triphenylphosphine (PPh₃), zinc (Zn), n-butyllithium (n-BuLi)
Reactants: Aldehydes
Products: Alkynes
Reaction Type: Substitution reaction

Experimental Tips:

• In the first step, the use of zinc powder can reduce the amount of triphenylphosphine required, resulting in higher yields and easier purification.

• For sensitive substrates, triethylamine may be used as an alternative to zinc.

• By selecting an appropriate base, the reaction can often be stopped at the 1-bromoalkyne stage, which may serve as a useful intermediate for further transformations.

Reaction Mechanism:
The Corey-Fuchs reaction proceeds via the formation of a dibromoolefin intermediate, followed by double dehydrobromination to generate the terminal alkyne.

Original Literature:
Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, *13*, 3769–3772.

Popular Applications:

• Modular and Stereodivergent Approach to Unbranched 1,5,9,n-Polyenes: Total Synthesis of Chatenaytrienin-4. The Journal of Organic Chemistry. 2016, *81* (18), 8175–8186.

• Toward the Stereochemical Assignment and Synthesis of Hemicalide: DP4f GIAO-NMR Analysis and Synthesis of a Reassigned C16–C28. Chem. Commun. 2016, *52* (18), 4632-4635.

• DBU-Mediated Synthesis of Aryl Acetylenes or 1-Bromoethynylarenes from Aldehydes. Advanced Synthesis & Catalysis, 2019, *361* (3), 611-616.