The Favorskii reaction refers to the nucleophilic addition of terminal alkynes to carbonyl compounds in the presence of a basic medium (e.g., anhydrous potassium hydroxide or sodium amide), yielding propargylic alcohols. The reaction is named after Russian chemist Alexei Yevgrafovich Favorskii, who first reported it.

The reaction mechanism involves deprotonation of the terminal hydrogen atom on the alkyne, generating a nucleophilic acetylide anion. This anion subsequently undergoes nucleophilic addition to an aldehyde or ketone to form a propargylic alcohol.

• Reagents: Base

• Reactants: Terminal alkyne, carbonyl compound

• Products: Propargylic alcohols

• Reaction Type: Nucleophilic addition

Experimental Tips:

• If an aldehyde is used as the carbonyl compound, rearrangement to an enone may occur.

• The reaction is useful for synthesizing 1,3-butadiene frameworks.

• It can also be used for alkyne protection. An alkyne can be protected by converting it into a 2-hydroxyprop-2-yl alkyne via reaction with acetone, or by using commercially available 3-methyl-1-butyn-3-ol.
  The protecting group can be removed by heating the compound in a potassium hydroxide solution in isopropanol, a process known as the reverse Favorskii reaction [1].

Reaction Mechanism

Key References:

• Original Publication
  Favorsky, A.E., Zh. Russ. Fiz.-Khim. Obshch., 1905, 37, 643–645.

• Notable Citations

  • A convenient synthesis of hetarylethynyl ketones from hetarylcarbaldehydes and acetylene, Chem. Heterocycl. Comp., 2013, 49(37), 341–344.

• Additional Reference

  • Wuts, P. G. M.; Greene, T. W., Greene’s Protective Groups in Organic Synthesis (4th ed.), Hoboken, New Jersey: John Wiley & Sons, Inc., 2007, Chapter 8. Protection for the Alkynes.