Intramolecular carbolithiation reactions alkenes

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. 

Krief and coworkers have also shown that vinyl sulphides are useful traps for the intramolecular carbolithiation reactions. Interestingly, as the sulphide substituent can be reductively removed, the cyclization reactions of benzyllithiums derived from 73 and 75 are synthetically equivalents to cyclizations onto disubstituted double bonds, giving rise by complementary routes to compound 74 (Scheme 20)46. Like the corresponding carbolithiation reactions onto monosubstituted alkenes they are highly stereoselective but dependent on the solvent used, i.e. the derivatives in which the methyl- and the phenylthio groups are cis (THF) or trans (pentane) one to the other are selectively formed. 

As shown in Scheme 11, Hoppe and coworkers have accomplished the first enantios-elective intramolecular carbolithiation reaction of alkenes by fusion of the concepts of the intramolecular carbolithiation reaction and the asymmetric deprotonation. The efficiency of this method has been demonstrated by the extension to other substrates by these and other authors78. However, this topic has been excellently reviewed by Hoppe and Christoph in Chapter 17 of Vol. 1 of The Chemistry of Organolithium Compounds and therefore it will not be treated in this chapter. 

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. 

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. 

The carbolithiation of unactivated alkenes has also proven very successful for the synthesis of complex polycyclic systems. This has typically been achieved by reaction sequences utilizing an intramolecular carbolithiation process to generate a variety of carbocycles185 and heterocycles186. To achieve the intermolecular carbolithiation reaction required to initiate a controlled cascade reaction sequence for the generation of indole ring scaffold, Kessler and coworkers44 have expanded the synthetic utility of the styrene... 

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