Tris(dimethylamino)phosphine-Carbon Tetrachloride1

(Me2N)3P-CCl4
((Me2N)3P)

[1608-26-0]  · C6H18N3P  · Tris(dimethylamino)phosphine-Carbon Tetrachloride  · (MW 163.24) (CCl4)

[56-23-5]  · CCl4  · Tris(dimethylamino)phosphine-Carbon Tetrachloride  · (MW 153.81)

(reagent combination for the conversion of hydroxyl groups to the corresponding chlorides; hydroxyl group activation; dehydrations)

Alternate Name: hexamethylphosphorous triamide-carbon tetrachloride.

Physical Data: (Me2N)3P: bp 55-58 °C/15 mmHg; d 0.898 g cm-3. CCl4: mp -23 °C; bp 77 °C; d 1.594 g cm-3.

Solubility: sol CCl4, MeCN, CH2Cl2, THF.

Preparative Methods: reactive species is generated in situ by reaction of (Me2N)3P and CCl4.

Handling, Storage, and Precautions: (Me2N)3P is an irritant and is flammable. It is best kept under a nitrogen atmosphere. CCl4 is toxic and a cancer suspect agent. All solvents used must be carefully dried because the intermediates are all susceptible to hydrolysis. The hexamethylphosphoramide produced as a byproduct is a cancer suspect agent. This reagent should be handled in a fume hood.

General Considerations.

The use of Hexamethylphosphorous Triamide in place of Triphenylphosphine in the phosphine-carbon tetrachloride reaction has a number of advantages. The separation of the triphenylphosphine oxide from the product can sometimes be problematic. The byproduct of the hexamethylphosphorous triamide reaction, Hexamethylphosphoric Triamide, is water soluble which allows for simple separation from the desired product. The aminophosphine is more nucleophilic, resulting in milder reaction conditions. Also, the alkoxyphosphonium intermediates can sometimes be isolated.1

Activation of Hydroxyl Groups.

The combination of hexamethylphosphorous triamide and CCl4 with an alcohol is a very effective method for the activation of the hydroxyl group for displacement by a variety of nucleophiles. In the absence of any external nucleophiles, the chloride ion formed in the reaction will react with the intermediate alkoxyphosphonium ion to produce the alkyl chloride (eq 1).2

Other nucleophiles are capable of effectively competing with chloride ion for the alkoxyphosphonium ion. If Sodium Azide, Potassium Iodide, or Potassium Cyanide is added to the reaction mixture, the corresponding azide, iodide, or nitrile will be formed in good yield (eq 2).3

Sometimes it is advantageous to replace the chloride counterion with less nucleophilic counterions such as BF4-,4 ClO4-,5 or PF6-.6 This technique sometimes allows the alkoxyphosphonium salts to be isolated as stable crystalline solids (eq 3).5 Weaker nucleophiles, such as amines (eq 4), can then be used to displace the alkoxyphosphonium ion.5

Deoxygenations.

The removal of oxygen functionality can be achieved via activation of hydroxyl groups with this reagent. The reduction of the alkoxyphosphonium ion by Lithium Triethylborohydride provides a route to deoxy sugars (eq 5).7

The preparation of glycals from lactols can be achieved by initial activation of the anomeric hydroxyl and subsequent Li/NH3 reduction (eq 6).8

Anomeric Hydroxyl Activation.

Anomeric hydroxyl group activation can be utilized to prepare a number of glycosyl derivatives. Activation followed by reaction with Mesityloxytris(dimethylamino)phosphonium Azide affords glycosyl azides (eq 7).9

For the preparation of disaccharides, the intermediate alkoxyphosphonium ions are reacted with Silver(I) p-Toluenesulfonate prior to the addition of the second sugar (eq 8).10

Dehydrations.

The reaction of 1,2-diols with this reagent combination can lead to the formation of epoxides (eq 9) or spirophosphoranes (eq 10). The course of the reaction is dependent on the stereochemistry of the starting diol. The reaction of meso-hydrobenzoin affords the epoxide while the threo stereoisomer provides the spirophosphorane. The trans-diol of cyclohexane was unaffected.11

The selective monofunctionalization of a 1,3-diol is possible. Following activation, the monoalkoxyphosphonium ion can be displaced with various nucleophiles such as iodide or azide (eq 11).12 Alternatively, if the alkoxyphosphonium ion was reacted with base, the oxetane was formed (eq 12).13

Dichloroalkenes.

Aldehydes and the intermediate trichloromethylcarbinols can be converted to dichloroalkenes.14 Even certain g-lactones will undergo this transformation. Treatment of the g-lactone (eq 13) with hexamethylphosphorous triamide produced the dichloroalkene in 79% yield. The use of Ph3P was ineffective for this transformation. Attempts to use CBr4 in place of CCl4 resulted in the formation of complex mixtures.14


1. Castro, B. R. OR 1983, 29, 1.
2. Downie, I. M.; Lee, J. B.; Matough, M. F. S. CC 1968, 1350.
3. Castro, B.; Selve, C. BSF 1971, 2296.
4. (a) Castro, B.; Chapleur, Y.; Gross, B.; Selve. C. TL 1972, 5001. (b) Castro, B.; Chapleur, Y.; Gross, B. BSF 1973, 3034.
5. (a) Castro, B.; Selve, C. BSF 1971, 4368. (b) Castro, B.; Chapleur, Y.; Gross, B. TL 1974, 2313. (c) Chapleur, Y.; Castro, B.; Gross, B. SC 1977, 7, 143.
6. Downie, I. M.; Heaney, H.; Kemp, G. T 1988, 44, 2619.
7. Simon, P.; Ziegler, J.-C.; Gross, B. S 1979, 951.
8. Ireland, R. E.; Thaisrivongs, S.; Vanier, N.; Wilcox, C. S. JOC 1980, 45, 48.
9. Chretien, F.; Castro, B.; Gross, B. S 1979, 937.
10. Chretien, F.; Chapleur, Y.; Castro, B.; Gross, B. JCS(P1) 1980, 381.
11. Boigegrain, R.; Castro, B. T 1976, 32, 1283.
12. Castro, B.; Ly, M.; Selve, C. TL 1973, 4455.
13. Castro, B.; Selve, C. TL 1973, 4459.
14. Combret, J. C.; Villiéras, J.; Lavielle, G. TL 1971, 1035.
15. Chapleur, Y. CC 1984, 449.

Michael J. Taschner

The University of Akron, OH, USA



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