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DOI: 10.1055/s-0034-1379442
Chloromethyllithium
Publication History
Publication Date:
05 November 2014 (online)
Introduction
Chloromethyllithium (LiCH2Cl) is a synthetically useful reagent belonging to the category of carbenoids, which are known to exhibit an ambiphilic behavior ranging from nucleophilic (at low temperatures) to electrophilic (at higher temperatures). This fact can be deduced by the resonance structures represented in Scheme [1], in which the extreme ionization of the polar bonds could lead, in principle, to the carbanionic (1a) or carbocationic (1b) species.[1] Chloromethyllithium can be prepared via a halogen–lithium exchange reaction on a given dihalomethane. Iodo- and bromo-chloromethane (ICH2Cl and BrCH2Cl) are the ideal precursors jointly with methyllithium–lithium bromide complex or n-butyllithium.[2] It is highly unstable except at very low temperatures (–78 °C or below); however, performing the reaction in the presence of the electrophile (i.e. Barbier-type conditions) allows to realize efficient processes. The presence of lithium halides and the use of ethereal-type solvents (THF or diethyl ether) had beneficial effects on its stability.[3]
Interestingly, Le Floch and co-workers showed that by replacing the two hydrogens with electron-withdrawing groups, it is possible to dramatically improve the stability of the corresponding carbenoid.[4]
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References
- 1a Köbrich G, Akhtar A, Ansari F, Breckoff WE, Büttner H, Drischel W, Fischer RH, Flory K, Fröhlich H, Goyert W, Heinemann H, Hornke I, Merkle HR, Trapp H, Zündorf W. Angew. Chem. Int. Ed. 1967; 6: 41
- 1b Pace V. Aust. J. Chem. 2014; 67: 311
- 1c Capriati V, Florio S. Chem. Eur. J. 2010; 16: 4152
- 1d Boche G, Lohrenz JC. W. Chem. Rev. 2001; 101: 697
- 2a Sadhu KM, Matteson DS. Tetrahedron Lett. 1986; 27: 795
- 2b Tarhouni R, Kirschleger B, Rambaud M, Villieras J. Tetrahedron Lett. 1984; 25: 835
- 2c Matteson DS, Majumdar D. J. Am. Chem. Soc. 1980; 102: 7588
- 3 Pace V, Holzer W, Verniest G, Alcántara AR, De Kimpe N. Adv. Synth. Catal. 2013; 355: 919 . See also ref. 2b
- 4 Cantat T, Jacques X, Ricard L, Le Goff XF, Mézailles N, Le Floch P. Angew. Chem. Int. Ed. 2007; 46: 5947
- 5 Sadhu KM, Matteson DS. Tetrahedron Lett. 1986; 27: 795
- 6 Pace V, Castoldi L, Holzer W. Adv. Synth. Catal. 2014; 356: 1761
- 7a Concellón JM, Rodríguez-Solla H, Simal C. Org. Lett. 2008; 10: 4457
- 7b Concellón JM, Rodríguez-Solla H, Bernad PL, Simal C. J. Org. Chem. 2009; 74: 2452
- 8a Pace V, Castoldi L, Holzer W. Chem. Commun. 2013; 49: 8383
- 8b Pace V, Castoldi L, Mamuye AD, Holzer W. Synthesis 2014; 46: 2897
- 9a Nahm S, Weinreb SM. Tetrahedron Lett. 1981; 22: 3815
- 9b Balasubramaniam S, Aidhen IS. Synthesis 2008; 3707
- 9c Pace V, Castoldi L, Alcántara AR, Holzer W. RSC Adv. 2013; 3: 10158
- 9d Pace V, Holzer W, Olofsson B. Adv. Synth. Catal. 2014; in press (DOI: 10.1002/adsc.201400630)
- 9e Pace V, Holzer W. Aust. J. Chem. 2013; 66: 507
- 10 Pace V, Castoldi L, Holzer W. J. Org. Chem. 2013; 78: 7764
- 11 Hutchings M, Moffat D, Simpkins NS. Synlett 2001; 661
- 12 Sonawane RP, Jheengut V, Rabalakos C, Larouche-Gauthier R, Scott HK, Aggarwal VK. Angew. Chem. Int. Ed. 2011; 50: 3760
For seminal studies, see:
For recent reviews, see:
For a highlight on the activation strategies of amides towards organometallics, see: