Alkenes anionic cyclisation onto

The first cyclisations to be put to synthetic use were those of aryl lithiums onto carbonyl compounds, imines and epoxides. These are known as Parham cyclisations , and the method for transforming an aryl bromide to an aryllithium the Parham protocol , after W. E. Parham, who developed the reaction. We will survey the use of Parham cyclisations in synthesis, before assessing intramolecular attack of other electrophiles. The most important of these are the alkenes, and the usefulness of anionic cyclisations onto unactivated double bonds compares very favourably with radical cyclisations, particularly with regard to stereochemical control. 

Since the sulfide substituents can be removed reductively, the cyclisations of 273 and 276 are synthetically equivalent to cyclisations onto disubstituted double bonds, giving compounds such as 275.142>143 Like the corresponding cyclisations onto monosubstituted alkenes they are highly stereoselective, with the sense of stereoselectivity being solvent-dependent the products 274 and 277 are trans as shown for a cyclisation conducted in THF in pentane complete cis selectivity is obtained. Similar cyclisations onto vinyl sulfides have been used to explore the stereochemical course of the anionic cyclisation reaction, and are discussed below.146... 

Krief has applied selenium chemistry to some anionic cascade cyclisations.128 For example, 293 can be cyclised in two successive 5-exo reactions to give a mixture of the stereoisomers of 297. If 294 is warmed to 0 °C, an alternative sort of tandem process occurs after cyclisation onto the alkene, the organolithium 295 undergoes an intramolecular displacement, stereoselectively generating the 5,3-fused system of 296. Similar intramolecular cyclopropanations (of a-bromo organolithiums) have been described by Hoffmann151 but are probably mediated by carbenes rather than a sequential cyclisation-substitution sequence. 

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