Lithium Pyrrolidide

[4439-90-1]  · C4H8LiN  · Lithium Pyrrolidide  · (MW 77.07)

(reduction of nonenolizable ketones;3 carbonylation;5 nucleophilic additions6,8 and substitutions4,9)

Physical Data: white, amorphous solid, [(CH2)4NLi]n; mp 150 °C (dec); X-ray structures of [((CH2)4NLi)3.PMDETA]2 and [((CH2)4NLi)2.TMEDA]2 have been reported.1

Solubility: sol THF, Et2O; insol pentane, hexane (at rt).

Preparative Method: prepared from Pyrrolidine (dried over and distilled from CaH2) and Methyllithium or n-Butyllithium in Et2O or THF usually at 0 °C for 30 min.3,4

Handling, Storage, and Precautions: unstable in THF solution at rt, forming LiH after a short period of time.2 Best prepared in situ immediately prior to use. Use in a fume hood.

Reduction.

In 1971, Wittig3 reported that treatment of nonenolizable ketones with lithium pyrrolidide (2 equiv) leads to alcohols in good yields (eq 1).

Carbonylation.

Treatment of lithium pyrrolidide with CO at atmospheric pressure leads to a carbamoyllithium species which, when quenched with R3SnCl, affords amidostannanes (eq 2).5 These may be cross-coupled with alkenyl, aryl, and heteroaryl halides under Pd0 catalysis to give acylpyrrolidines. Trimethyltin derivatives are the most effective cross-coupling partners. This procedure was developed for the introduction of 11C (from 11CO) into molecules for biological and clinical studies.

Nucleophilic Addition.

Treatment of 1-chloro-2-phenylacetylene with lithium pyrrolidide yields 1-(1-pyrrolidinyl)-2-phenylacetylene (eq 3), which may be used as an electron-rich partner in [2 + 2] cycloaddition reactions with heterocyclic compounds.6 In general, ynamines are versatile reagents.7

Addition of lithium pyrrolidide to activated alkynes leads to (Z)/(E) mixtures of synthetically useful vinyllithium species (eq 4).8 Yields given correspond to the protonated products obtained by quenching with MeOH.

Nucleophilic Substitution.

The reaction of lithium pyrrolidide with Dimethyl Disulfide in pentane gives the corresponding sulfenamide (eq 5).9 This reaction fails in THF. Sulfenamides have been used as sulfenyl-group transfer reagents.10

Treatment of 1,2-dimethoxybenzene with lithium pyrrolidide leads to displacement of only one methoxy group (eq 6)4 in a reaction which appears not to proceed via a benzyne intermediate.

Related Reagents.

Lithium Diethylamide; Lithium Diisopropylamide; Lithium Hexamethyldisilazide; Lithium Piperidide; Lithium 2,2,6,6-Tetramethylpiperidide.


1. Armstrong, D. R.; Barr, D.; Clegg, W.; Hodgson, S. M.; Mulvey, R. E.; Reed, D.; Snaith, R.; Wright, D. S. JACS 1989, 111, 4719.
2. Rathman, T., FMC Corporation, personal communication, February, 1994.
3. Wittig, G.; Hesse, A. LA 1971, 746, 149.
4. ten Hoeve, W.; Kruse, C. G.; Luteyn, J. M.; Thiecke, J. R. G.; Wynberg, H. JOC 1993, 58, 5101.
5. Lindsay, C. M.; Widdowson, D. A. JCS(P1) 1988, 569.
6. Reinhoudt, D. N.; Kouwenhoven, C. G. RTC 1976, 95, 67.
7. Viehe, H. G. Chemistry of Acetylenes; Dekker: New York, 1969; p 889.
8. Feit, B.-A.; Dickerman, S.; Masrawe, D.; Fishman, A. JCS(P1) 1988, 927.
9. Nelsen, S. F.; Steffek, D. J.; Cunkle, G. T.; Gannett, P. M. JACS 1982, 104, 6641.
10. Davis, F. A.; Nadir, U. K. OPP 1979, 11, 33.

Markus Wicki & Victor Snieckus

University of Waterloo, Ontario, Canada



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