Dimethyl Chlorophosphite

[3743-07-5]  · C2H6ClO2P  · Dimethyl Chlorophosphite  · (MW 128.50)

(reactive phosphitylating agent for secondary alcohols; oxidation of the resulting phosphites provides phosphates)

Alternate Names: dimethyl phosphorochloridate; dimethyl chlorophosphonite; dimethoxychlorophosphine.

Preparative Method: obtained by reaction of Trimethyl Phosphite with Phosphorus(III) Chloride in HMPA.1

Inositol Phosphates.2

Phosphorylation of inositol derivatives is complicated by the relative unreactivity of phosphorus(V) reagents towards the secondary alcohol groups of inositol, and the tendency of the resulting phosphate triester intermediates to undergo cyclization and migration to neighboring hydroxy groups. Phosphitylation using the more reactive dimethyl chlorophosphite has avoided these problems while adding new selectivity features. For example, exhaustive phosphitylation of 1,4-dibenzoyl-myo-inositol (1) with excess dimethyl chlorophosphite3 and Diisopropylethylamine yields the tetrakis(dimethyl phosphate) (2a) after Hydrogen Peroxide oxidation of the intermediate phosphite ester (eq 1).

This suggests that it is possible to convert all the free hydroxy groups in any appropriately protected inositol to phosphate esters, including bisphosphorylation of a cis-vicinal diol. However, if less than the stoichiometric amount of dimethyl chlorophosphite (3.3 equiv) is used, partial phosphitylation of (1) is effected yielding the tris(dimethyl phosphate) (2b) after acetylation and oxidation. Only the more reactive equatorial 3-, 5-, and 6-hydroxy groups on (1) are phosphorylated.

The use of other phosphorus(III) reagents has recently been suggested for the synthesis of inositol phosphates. These include Dibenzyl N,N-Diisopropylphosphoramidite (3),4 and o-xylylene N,N-diethylphosphoramidite (4).5

The indirect method of phosphorylation using a phosphorochloridite followed by oxidation to the phosphate has also been applied in the synthesis of monophosphate esters from hindered alcohols. This has been reported using diallyl chlorophosphite, (CH2=CHCH2O)2PCl,6 and Diethyl Chlorophosphite, (EtO)2PCl.7

1. Mazour, Z. CA 1977, 87, 52 758u.
2. Potter, B. V. L. Nat. Prod. Rep. 1990, 7, 1.
3. Meek, J. L.; Davidson, F.; Hobbs, F. W., Jr. JACS 1988, 110, 2317.
4. Yu, K.-L.; Fraser-Reid, B. TL 1988, 29, 979.
5. Ozaki, S.; Kondo, Y.; Shiotani, N.; Ogasawara, T.; Watanabe, Y. JCS(P1) 1992, 729.
6. Sawabe, A.; Filla, S. A.; Masamune, S. TL 1992, 33, 7685.
7. Evans, D. A.; Gage, J. R.; Leighton, J. L. JOC 1992, 57, 1964.

Gerald B. Hammond

University of Massachusetts Dartmouth, North Dartmouth, MA, USA

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