Favorskii reaction and the possible subsequent rearrangement
When the carbonyl is an aldehyde (R"=H), a rearrangement can occur to generate enone, although the secondary propargylic alcohol can be isolated in some cases.[2] When this rearrangement is catalyzed by an acid, it is called Meyer–Schuster rearrangement.
The metal acetylide then reacts with an aldehyde or ketone to form a propargyl alcohol. When an α-hydrogen is present (as is the case when the carbonyl is an aldehyde), it will tautomerize to the corresponding enone.[4]
The applicable substrates that undergo a Favorskii reaction are limited when compared to the conventional reaction because using an excess of hydroxide base introduces aldol condensation as a more significant competing side reaction.[3] Since enolates do not react with acetylene, the reaction can be often be a poor substitute for the conventional reaction, especially when reaction is used on aldehydes. Successful reactions with aldehydes often require special solvents to be used, such as DMSO[4]or1,2-dimethoxyethane with a trace amount of ethanol.[3] Additionally, LiOH fails to form the necessary adduct with alkynes to initiate the reaction.
Hydroxide bases are inexpensive relative to generating an alkoxide or acetylide with reagents such as elemental lithium, sodium, or potassium. Additionally, the stringent reaction conditions used by most alternatives, such as excluding moisture and atmospheric oxygen, are less important, making the reaction easier to perform.[4]
This reaction is used to protectalkynes: the alkyne is either converted with acetone to a 2-hydroxyprop-2-yl-alkyne or a protected alkyne can be directly synthesized using the commercially available 2-methyl-3-butyn-2-ol as an alkyne source.[5] The protective group can be removed by heating the compound in a solution of potassium hydroxideinpropan-2-ol (aretro-Favorskii reaction).[6]
^Favorsky, A.E. (1905). "Action of potassium hydroxide on mixtures of ketones and phenylacetylene". Zhurnal Russkago Fiziko-Khimicheskago Obshchestva. 37: 643–645., Favorsky, A.E. (1907). "Action de la potasse caustique sur les mélanges des cétones avec le phénylacétylène". Bulletin de la Société Chimique de France. 2: 1087–1088.
^ abcSobenina, L. N.; Tomilin, D. N.; Petrova, O. V.; Mikhaleva, A. I.; Trofimov, B. A. (2013). "Synthesis of secondary propargyl alcohols from aromatic and heteroaromatic aldehydes and acetylene in the system KOH-H2O-DMSO". Russian Journal of Organic Chemistry. 49 (3): 356–359. doi:10.1134/S107042801303007X. S2CID94135082.
^Kukula, H.; Veit, S.; Godt, A. (1999). "Synthesis of Monodisperse Oligo(para-phenyleneethynylene)s Using Orthogonal Protecting Groups with Different Polarity for Terminal Acetylene Units". European Journal of Organic Chemistry. 1999 (1): 277–286. doi:10.1002/(SICI)1099-0690(199901)1999:1<277::AID-EJOC277>3.0.CO;2-R.
^Wuts, Peter G. M.; Greene, Theodora W. (2007). "Chapter 8. Protection for the Alkynes". Greene's Protective Groups in Organic Synthesis (4th ed.). Hoboken, New Jersey: John Wiley & Sons, Inc. p. 932. doi:10.1002/9780470053485.ch8. ISBN9780471697541.
