[733-90-4]  · C19H15Li  · Triphenylmethyllithium  · (MW 250.28)

(sterically hindered strong base; can function as a nucleophile)

Form Supplied in: red solution in THF, DME, and toluene; diethyl ether solution is colorless.

Analysis of Reagent Purity: the concentration of colored solutions can be determined by titration with a standard solution of 2-butanol to a colorless endpoint.2

Preparative Methods: solutions in ether solvents (containing some hexane) are most conveniently prepared by adding commercial solutions of n-Butyllithium in hexane to a solution of triphenylmethane in the ether, usually with ice-water cooling.1 Crystals of the diethyl ether complex may be obtained as red needles by removal of the solvent.3 Preparative methods up to 1959 have been reviewed.4

Handling, Storage, and Precautions: the red color of the reagent is rapidly discharged on exposure to air or water. Solutions in THF and diethyl ether are stable indefinitely,3 but solutions in DME slowly lose titer at room temperature and form Ph3CH, LiOMe, and CH2=CHOMe.2

Reaction as a Base.

Triphenylmethyllithium is a strong base (the pKa of Ph3CH is 31.5) and rapidly converts a number of carbonyl compounds into the corresponding lithium enolates. The reagent played an important role in pioneering studies of enolate chemistry, but the more recently developed lithium dialkylamides possess significant advantages including greater base strength and faster rates of proton removal. A considerable advantage is the easier separation of dialkylamine, compared to Ph3CH, from reaction mixtures. It has been observed that triphenylmethyllithium is now rarely used, in favor of the amide bases.5 Nevertheless, triphenylmethyllithium has several unique characteristics which may make it the base of choice for some applications. The bright red color of triphenylmethyllithium together with the colorless nature of Ph3CH allows a simple check for the completion of proton transfer as well as a rough estimation of the rate. For some applications, this advantage can be gained for other bases by addition of small quantities of Ph3CH as an indicator.6 Triphenylmethane is a relatively inert material compared to secondary amines and this fact may be advantageous for transformations subsequent to proton transfer. Quenching lithium amide-generated enolate solutions with D2O often results in less than quantitative incorporation of deuterium because of the readily exchangeable protons of secondary amines. Of eight bases examined, triphenylmethyllithium gave the highest incorporation of deuterium in compound (1), an intermediate in the synthesis of the antibiotic Fludalanine (eq 1).7

Triphenylmethyllithium can react with conjugated enones by single electron transfer,2 and this can provide an alternate mechanism for the formation of conjugated enolates (eq 2).8 This may account for the occasional reports of superior yields,9 or different regiochemistry,10 obtained for proton removal with triphenylmethyllithium in such systems.

Reaction as a Nucleophile.

Triphenylmethyllithium can function as a surprisingly efficient nucleophile, especially in cases where proton transfer is not possible. Addition reactions with nonenolizable aldehydes and ketones,4 and conjugate addition with enones, have been reported.2,8 The reaction with organic halides and tosylates, in some cases at least, proceeds with inversion.11,12

1. Gilman, H.; Gaj, B. J. JOC 1963, 28, 1725.
2. House, H. O.; Weeks, P. D. JACS 1975, 97, 2785.
3. Bauer, W.; Lochmann, L. JACS 1992, 114, 7482.
4. Tomboulian, P. JOC 1959, 24, 229.
5. Heathcock, C. COS 1991, 2, Chapter 1.6.
6. House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972; pp 551-552.
7. Reider, P. J.; EichenConn, R. S.; Davis, P.; Grenda, V. J.; Zambito, A. J.; Grabowski, E. J. J. JOC 1987, 52, 3326.
8. Lee, R. A.; Reusch, W. TL 1973, 12, 969.
9. Barton, D. H. R.; Hesse, R. H.; Pechet, M. M.; Wiltshire, C. CC 1972, 1017.
10. Bauman, J. G.; Barber, R. B.; Gless, R. D.; Rapoport, H. TL 1980, 21, 4777.
11. Screttas, C. G.; Micha-Screttas, M. JOC 1982, 47, 3008.
12. Lee, K-W.; San Fillippo, J., Jr. OM 1982, 1, 1496.

Michael Rathke & Robert Elghanian

Michigan State University, East Lansing, MI, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.