Alkyne carbolithiation intramolecular

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. 

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... 

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). 

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. 

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