Lithium t-Butoxide


[1907-33-1]  · C4H9LiO  · Lithium t-Butoxide  · (MW 80.07)

(weakly basic and nucleophilic metal alkoxide)1

Physical Data: crystalline solid, subl over 170-205 °C/760 mmHg; dec above 250 °C.2

Form Supplied in: commercially available as a white powder.

Preparative Methods: the crystalline material is prepared using a Schlenk apparatus by reaction of t-BuOH with a small excess of Lithium sand in PhMe at rt for 24 h;2 the excess metal is removed by filtration and the solvent is removed in vacuo; the remaining solid is sublimed at 110-120 °C/0.01 mmHg. In situ preparation is accomplished by adding a solution of anhyd t-BuOH in THF to 1.6 M n-Butyllithium in hexane,1a or by slowly adding a 1.55 M solution of n-BuLi in hexane to an excess of the anhyd alcohol under N2;1b the reaction is exothermic, and a water bath should be used to keep the temperature of the mixture near rt.

Handling, Storage, and Precautions: use same procedure as for Potassium t-Butoxide, i.e. handle and conduct reactions in a fume hood under an inert atmosphere; for critical experiments, it is recommended that the reagent be freshly prepared.

Preparation of t-Butyl Esters.

t-BuOLi reacts with acid chlorides of hindered carboxylic acids to give the corresponding t-butyl esters in high yields (eq 1).1 The ester product shown in eq 1 is not obtained by the more conventional method of reacting the acid chloride with t-BuOH in the presence of PhNMe2.3

Oxidation of Alcohols.

Alkoxymagnesium bromides of secondary alcohols and allylic and benzylic alcohols are oxidized to the corresponding ketones or aldehydes with N-Chlorosuccinimide in the presence of t-BuOLi.4 The method is ineffective for primary saturated and some unsaturated alcohols, but oxidations of the former substrates to aldehydes occur readily if t-Butoxymagnesium Bromide is substituted for t-BuOLi.5 Secondary alcohols (eq 2) and primary benzylic (eq 3) and allylic alcohols are oxidized to the corresponding carbonyl compounds in good yields using 2-3 equiv of a 1:1 mixture of Copper(II) Bromide-t-BuOLi in THF at rt.6 However, the reagent is not effective for the conversion of primary aliphatic alcohols to aldehydes.

Condensation Reactions.

In the presence of dipolar aprotic additives, e.g. Hexamethylphosphoric Triamide (eq 4) or 12-Crown-4, which reduce the degree of aggregation, t-BuOLi catalyzes the Michael addition of methyl cyanoacetate to benzylideneacetophenone.7 A similar yield of the Michael adduct is obtained if t-BuOK is used as the base, and no additive is required.

Additions to Hindered Ketones.

In the absence of various additive salts, the reaction of i-Pr2Mg with t-Bu2CO leads mainly to simple reduction of the carbonyl group.8 In the presence of t-BuOLi, addition to the carbonyl group occurs in good yield (eq 5).8 t-BuOLi, MeOK, and (Me2CH)2CHOK are more effective than MeONa or quaternary ammonium salts in preventing the reduction process. The exact role of the additive in favoring addition to the hindered ketone over reduction is unknown.

b-Elimination Reactions.

1-Methoxyacenaphthene undergoes loss of MeOH via an E1cB mechanism.9 t-BuOLi/t-BuOH favors exchange and elimination of the proton syn to the methoxy group much more than do other alkali metal alkoxides. It has been suggested that the strong tendency of the lithium cation of the base ion pair (or an aggregate) to coordinate with the ether oxygen of the substrate accounts for this.9

1. (a) Kaiser, E. M.; Woodruff, R. A. JOC 1970, 35, 1198. (b) Crowther, G. P.; Kaiser, E. M.; Woodruff, R. A.; Hauser, C. R. OSC 1988, 6, 259.
2. Chisholm, M. H.; Drake, S. R.; Naiini, A. A.; Streib, W. E. Polyhedron 1991, 10, 805.
3. Hauser, C. R.; Hudson, B. E.; Abramovitch, B.; Shivers, J. C. OSC 1955, 3, 142.
4. Mukaiyama, T.; Tsunoda, M.; Saigo, K. CL 1975, 691.
5. Narasaka, K.; Morikawa, A.; Saigo, K.; Mukaiyama, T. BCJ 1977, 50, 2773.
6. Yamaguchi, J.; Yamamoto, S.; Takeda, T. CL 1992, 1185.
7. Cossentini, M.; Strzalko, T.; Seyden-Penne, J. BSF(2) 1987, 531.
8. Richey, H. G., Jr.; DeStephano, J. P. JOC 1990, 55, 3281.
9. Hunter, D. H.; Shearing, D. J. JACS 1971, 93, 2348.

Drury Caine

University of Alabama, Tuscaloosa, AL, USA

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