Asymmetric intramolecular carbolithiation

Methods for the enantioselective synthesis of 3-substituted indolines by means of the asymmetric intramolecular carbolithiation of 2-bromo-A,-allylanilines in the presence of (-)-sparteine were reported simultaneously by Bailey <00JA6787> and Groth <00JA6789>. Thus, addition of 89 to 2.2 equiv of /BuLi in the presence of the chiral ligand generates the lithium intermediate 90 which upon quenching with methanol affords the chiral indoline 91 in a process that is highly solvent dependent. 

Hoppe, D. Woltering, M. J. Oestreich, M. Frohlich, R. (-)-Sparteine-mediated asymmetric intramolecular carbolithiation of alkenes synthesis of enantiopure cyclopentanes with three consecutive stereogenic centers. Helv. Chim. Acta 1999, 82, 1860-1877. 

More recently, asymmetric intramolecular carbolithiation was described, either with a remote chiral center in a suitable position to promote a diastereofacial differentiation of the olefin [130] or with a chiral organolithium derivative [131]. In the former case, alkylation... 

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. 

Scheme 10.57 Asymmetric synthesis of substituted pyrrolidines by an intramolecular carbolithiation reaction [47].

Inter- and intramolecular enantioselective carbolithiation reactions in the presence of a chiral ligand for lithium, such as (—)-sparteine 13BJ0313. New application progress of chiral bis(oxazoline) ligands in asymmetric catalysis 13CJ02283. 

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