Zinc-Graphite1

Zn-Gr

[7440-66-6]  · Zn  · Zinc-Graphite  · (MW 65.39)

(very highly activated form of zinc, able to convert halides into organozinc species under mild conditions;2,3 eliminates a-oxy halides to alkenes4)

Solubility: insol in all common solvents; compatible with THF and other ethereal solvents.

Preparative Methods: Potassium-Graphite is prepared by reaction between Potassium metal and degassed graphite at 150 °C. When cool the potassium graphite is suspended in THF. Zinc Chloride is added and a very vigorous reaction ensues before the THF is heated to reflux to ensure complete reaction. Zinc/silver-graphite is prepared by the addition of 10 mol % Silver(I) Acetate to the zinc chloride mixture. These preparations have only been reported on a 15 mmol scale; because molten potassium is used and the reduction of zinc chloride is highly exothermic, great caution should be exercised in any scale-up.3,5

Handling, Storage, and Precautions: the reagent consists of highly active metal particles; it should be handled under argon and used immediately after preparation.

Introduction.

The reagent prepared by reduction of zinc chloride with potassium graphite does not consist of intercalated zinc; instead, very fine particles of zinc are deposited upon the graphite, which serves as an inert carrier.1a A comparison of the conditions required to condense ethyl bromoacetate with cyclohexanone was used to demonstrate that more active zinc is formed by this method than by other activation methods. The superiority of zinc/silver-graphite over simple zinc-graphite is also apparent (Table 1).5

The advantages of using zinc-graphite are that the workup of the reaction is simple, substrates formerly considered as poor may be converted to zinc reagents in good yield and, because low temperatures are used, stereocontrol may be better. Graphite may be removed from the reaction mixtures after quenching by simple filtration, in contrast to the soluble reagents like naphthalene used in Rieke and similar methods, which are usually removed by chromatography.

Organozinc Reagents.

Zinc-graphite and zinc/silver-graphite have been used to generate organozinc reagents from a-chloro2,3 and a-bromo2,3 esters and lactones, g-bromo crotonates,3,5 allylic bromides,3,6 and 2-bromomethyl-2-propenoates.3,7

One class of substrate where the high reactivity of zinc/silver-graphite has been used to effect a previously difficult transformation is a,a-dihaloacetates. Use of zinc/silver-graphite allows the synthesis of a-halo-b-hydroxy esters in excellent yield.8 If Potassium Carbonate is added during workup, then glycidic esters may be isolated directly (eq 1).8

Examples of the improved stereoselectivity achievable by the use of zinc/silver-graphite have been found in the reactions of 2-bromomethyl-2-propenoates with chiral ketones (eq 2).5,7

Eliminations.

The use of zinc/silver-graphite for the synthesis of glycals and eliminative ring opening of sugar derivatives has been reviewed.1a The advantages of using zinc/silver-graphite are that yields are high and, because low temperatures are used, most protecting groups are compatible.

The conversion of glycosyl bromides to glycals is typical of these reactions (eq 3). This reaction can not be carried out using Rieke zinc. In the presence of azido groups, either in the substrate or in another compound in the flask, the mechanism changes and reduction occurs (eq 3). This type of elimination has found application in a novel unmasking reaction used by Ireland in an approach to FK506 synthesis.9

Related Reagents.

Nickel-Graphite; Palladium-Graphite; Zinc; Zinc/Copper Couple; Zinc/Nickel Couple; Zinc/Silver Couple.


1. (a) Fürstner, A. AG(E) 1993, 32, 164. (b) Erdik, E. T 1987, 43, 2203.
2. Csuk, R.; Fürstner, A.; Weidmann, H. CC 1986, 775.
3. Boldrini, G. P.; Savoia, D.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. JOC 1983, 48, 4108.
4. Csuk, R.; Fürstner, A.; Glänzer, B. I.; Weidmann, H. CC 1986, 1149.
5. Fürstner, A. S 1989, 571.
6. Marceau, P.; Gautreau, L.; Béguin, F.; Guillaumet, G. JOM 1991, 403, 21.
7. (a) Csuk, R.; Fürstner, A.; Sterk, H.; Weidmann, H. J. Carbohydr. Chem. 1986, 5, 459. (b) Csuk, R.; Hugener, M.; Vasella, A. HCA 1988, 71, 609.
8. Fürstner, A. JOM 1987, 336, C33.
9. Ireland, R. E.; Highsmith, T. K.; Gegnas, L. D.; Gleason, J. L. JOC 1992, 57, 5071.

Matthew W. D. Perry

Fisons Pharmaceuticals, Loughborough, UK



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