Corey—Fuchs reaction

Corey-Fuchs reaction is a two step reaction converting an aldehyde to an alkyne by one-carbon homologation of the aldehyde. The Wittig-like reaction of aldehyde 1 and dibromocarbene forms dibromoalkene 2. The treatment of dibromoalkene 2 with two equivalent of -BuLi form a lithium alkynylide, quenched by eletrophiles, such as proton, CO2, aldehydes, ketones, and alkyl halides to form alkyne 3. 

This transformation was first disclosed by Corey and Fuchs in 1972. Three aldehydes, an aromatic, a linear aliphatic and a cyclic aliphatic aldehyde were chosen to show the generality of this reaction. For all three aldehydes, the reaction proceeded well. 

Two procedures were developed for the first step. The aldehyde (1 equiv) was added to a mixture of PPha (4 equiv) and CBr4 (2 equiv) in CH2CI2 at 0 °C with a reaction time of 5 min. Alternatively, the aldehyde (1 equiv) was added to the mixture, prepared by the reaction of Zn dust (2 equiv), PPhs (2 equiv) and CBr4 (2 equiv) at 23 °C for 24-30 h, for a reaction time of 1-2 h. The advantage of the first procedure is very short total reaction time for the second procedure, the isolation procedure is simpler, especially for those non-polar alkynes, since less PPhs is used and unreacted 

PPh3 could eluent together with non-polar alkynes during flash column chromatography. 

Corey-Fuchs alkyne synthesis can be seen as a cousin of the Wittig olefin synthesis. 

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Terminal alkenylstannanes can be prepared after homologation of aldehydes via the Corey-Fuchs reaction.95... 

The olefination of cyclobutanones with the tetrabromomethane/triphenylphosphane reagent (Corey-Fuchs reaction) affords the dihaloalkene in the usual manner.241,242... 

A modification of the Corey-Fuchs Reaction involves the reaction of the intermediate alkynyllithium with an electrophile prior to aqueous work-up, giving a chain extension product ... 

Another common method for the conversion of an aldehyde into an alkyne is the transformation of the aldehyde via a Corey-Fuchs reaction into a geminal vinyl dibromide followed by reaction with nbutyllithium and aqueous work-up.22... 

Steps 1-2 Corey-Fuchs reaction aldehyde to terminal alkyne transformation. 

Steps 1-2 Conversion of a ketone to a terminal alkyne (compare with Corey-Fuchs reaction where an aldehyde is converted to a terminal alkyne). Step 4 Me2CuLi adds to the acetylenic ester in a conjugate manner to provide (Z)-olefin. 

The total synthesis of Galubulimima alkaloid 4,4a-didehydrohimandravine, using an intramolecular Diels-Alder reaction and a Stille coupling as the key steps, was accomplished in the laboratory of M.S. Sherburn. The required vinylstannane intermediate for the Stille coupling was prepared via the one-pot Corey-Fuchs reaction, followed by radical hydrostannylation. 

W.J. Kerr and co-workers carried out the total synthesis of (+)-taylorione starting from readily available (+)-2-carene and using a modified Pauson-Khand annulation with ethylene gas as the key step. The key terminal alkyne intermediate was prepared by the Corey-Fuchs reaction. Interestingly, the ketal protecting group was sensitive to the excess of CBr4, so the addition of this reagent had to be monitored carefully to cleanly transform the aldehyde to the desired dibromoolefin. 

A bonanza of Heck reactions was used by Tietze25 in the synthesis of cephalostatin analogues. Corey-Fuchs reaction on the aldehyde 167 gives the alkene 168 from which the trans Br atom is stereoselectively removed by Pd-catalysed tin hydride reduction to give the Z-vinyl bromide 169. This reaction is discussed below under Stille coupling. 

Amdt-Eistert homologation Baylis-Hillman reaction Benzoin condensation Corey-Fuchs reaction Henry reaction (Nitroaldol reaction)... 

Examples of allylation [39a] and vinylation [39b] are shown in Scheme 24. The dichlorovinylation is especially interesting since the products are immediate precursors of alkynes via the Corey-Fuchs reaction. The process is also applicable to aliphatic iodides, exchange of iodine replacing the exchange of xanthate in the mechanistic manifold in Scheme 22 [39b,c[. 

A general one-pot procedure for the synthesis of alkynes from aldehydes (Corey-Fuchs reaction) that involves the synthesis of the triphenylphosphonium dibromomethane reagent has been explored by Michel and coworkers. In general, the base of choice is f-BuOK, but in case of the N-Boc piperidine, use of BuLi in order to avoid unwanted side reactions between the carbamate and the acetylide function provides a cleaner reaction at low temperature (eq 64). 

Other references related to the Corey-Fuchs reaction are cited in the literature. 

Caronaldehyde hemiacetal can be transformed in a simple manner by the Corey-Fuchs reaction [107] into permethric acid, and as well its bromo-analogue deltamethric acid. Instead of triphenylphosphane, tris-(dimethylamino) phos-phane may also be used. 

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