Carbolithiation alkynes

Due to its high ionic character, the carbon-lithium bond is very reactive and adds under mild conditions to ethylene or dienes and under more severe conditions to other alkenes. Some functionalized alkenes can be used, and high regio- and stereo-selectivity is usually observed in these carbolithiation reactions, especially if a precoordination of the lithium organometallic with the alkene is possible. Intramolecular carbolithiations of alkenes proceed under mild conditions and allow the preparation of several stereochemically well defined mono- and bi-cyclic compounds. Alkynes are too reactive, and can lead, with organolithium derivatives, to several side reactions, and seldom afford the desired carbolithiated product in good yield. 

Fig. 16.17. Mechanism of the carbocupration of acetylene (R = H) or terminal alkynes (R H) with a saturated Gilman cuprate. The unsaturated Gilman cuprate I is obtained via the cuprolithiation product E and the resulting carbolithiation product F in several steps—and stereoselectively. Iodolysis of I leads to the formation of the iodoalkenes J with complete retention of configuration. Note The last step but one in this figure does not only afford I, but again the initial Gilman cuprate A B, too. The latter reenters the reaction chain "at the top" so that in the end the entire saturated (and more reactive) initial cuprate is incorporated into the unsaturated (and less reactive) cuprate (I). - Caution The organometallic compounds depicted here contain two-electron, multi-center bonds. Other than in "normal" cases, i.e., those with two-electron, two-center bonds, the lines cannot be automatically equated with the number of electron pairs. This is why only three electron shift arrows can be used to illustrate the reaction process. The fourth red arrow—in boldface— is not an electron shift arrow, but only indicates the site where the lithium atom binds next.

It has been reported that carbolithiation of ether-substituted alkynes such as 17 is catalysed by iron(III), a method which has allowed the remarkable stereoselective construction of tetrasubstituted double bonds such as that of 18.19... 

The carbolithiation of alkenes and alkynes is a useful transformation for the generation of a new carbon—carbon bond, specially when the alkenes and alkynes are activated by conjugation to carbonyl and related electron-withdrawing groups. Similarly to the intramolecular carbolithiation, it is possible to carry out this reaction with high diastere-o selectivity. 

Major advances have been made in the intermolecular carbolithiation of unactivated alkenes (such as 128) and alkynes in recent years. Wei and Taylor designed a tandem intermolecular-intramolecular carbolithiation sequence, giving rise to cyclic products, 129 (Scheme 42), using organolithium reagents as difunctional reagents106. 

The first stereoselective intramolecular carbolithiation of alkynes was recently achieved by Hoppe and coworkers109. Several 4-functionalized 5-hexynyl carbamates, e.g. (5-145), were efficiently cyclized in the presence of the chiral base (—)sparteine, to 146Z, providing... 

Negishi and coworkers have shown that trialkylsilylalkynes are able to trap intramolec-ularly alkyl-, vinyl-, allenyl- and aryllithiums126. For instance, allene 366 cyclizes to cyclopentane derivative 367 under treatment with f-BuLi and TMEDA. This is a remarkable example of a carbolithiation reaction initiated by a deprotonation that affords allenyl-lithium 368 which cyclizes onto the alkyne (Scheme 96). 

On the other hand, the cyclization reaction of a vinyllithium onto an acetylenic unit provides an efficient route to five- and six-membered bis-exocyclic 1,3-dienes, which react stereoselectively with a wide range of dienophiles157. The 5-exo carbolithiation reaction of vinyllithiums 369, derived from the corresponding vinyl bromides, is syw-stereospecific giving, after hydrolysis, the /(-isomer of five-membered outer-ring dienes 370 and tolerates aryl-, silyl- or alkyl-substituents at the distal acetylenic carbon (Scheme 97). However, the alkyl-substituted alkynes are far more resistant to rearrangement than the aryl- or silyl-substrates and the addition of TMEDA and longer reaction times are needed for the latter... 

The intramolecular carbolithiation of a series of chloro-substituted alkynes led to exocyclic alkylidene carbenoids, of which both nucleophilic and electrophilic characters could be derived (14CEJ10249). 

Scheme 10.76 Synthetic application of the iron-catalyzed carbolithiation of unactivated alkynes [62].

Frequently seen are Parham cyclizations onto alkene side chains. For example, bromoalkene 39 undergoes cyclization and electrophilic trapping to afford 40. A series of allyl 2-lithioaryl ethers undergo a tandem Parham cyclization-y-elimination to afford 2-cyclopropylphenols, e.g., 41- 42. Intramolecular carbolithiation reactions of alkenes have led to 2-azabenzonorbomanes and tetrahydroisoquinolines. Similarly, carbolithia-tions of alkyne and allene side chains have been reported. Thus, both 43 and 45 undergo iodine-lithium exchange and cyclization to provide benzofuran 44 and fiiropyridine 46, respectively. 

Iron-catalyzed carbolithiation of the internal alkyne 186, bearing an alkoxy group at the homopropargylic position, led to the vinyllithium compound 187,... 

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