Methyl Bis(2,2,2-trifluoroethoxy)phosphinylacetate

[88738-78-7]  · C7H9F6O5P  · Methyl Bis(2,2,2-trifluoroethoxy)phosphinylacetate  · (MW 318.13)

(Horner-Emmons reagent for the production of a,b-unsaturated esters with (Z) selectivity)

Alternate Name: bis(2,2,2-trifluoroethyl) (methyoxycarbonylmethyl)phosphonate

Physical Data: d 1.504 g cm-3.

Solubility: sol THF, DME, CH2Cl2.

Form Supplied in: oil; widely available.

Preparative Methods: prepared by reaction of methyl dichlorophosphonoacetate with trifluoroethanol in benzene.

Purification: silica gel chromatography.

Handling, Storage, and Precautions: irritant.

Modified Wittig Reagent.

The Horner-Emmons reaction carried out by reacting methyl bis(trifluoroethoxy)phosphinylacetate with an aldehyde in the presence of a strongly dissociated base system yields a,b-unsaturated esters with a strong preference for the (Z) geometry. The reaction is not overly sensitive to the type of aldehyde used. Examples are shown in eqs 1-3.1,2

The strongly dissociated base system is necessary to maximize the (Z) selectivity of the alkenation reaction (see eq 4).1,3

In general, the reagent is slow to react with ketones, especially aryl ketones, providing little or no reaction (eq 5).4 The majority of references to this reagent involve aldehydes as the coupling partner.5

Other Uses.

The anion of methyl bis(trifluoroethoxy)phosphinylacetate can undergo an SN2 reaction with suitable electrophiles to make a more complex trisubstituted modified Wittig reagent, which can undergo alkenation reactions.6

1. Still, W. C.; Gennari, C. TL 1983, 24, 4405.
2. Blaskovich, M. A.; Lajoie, G. A. JACS 1993, 115, 5021.
3. López Tudanca, P. L.; Jones, K.; Brownbridge, P. JCS(P1) 1992, 533.
4. Eguchi, T.; Aoyama, T.; Kakinuma, K. TL 1992, 33, 5545.
5. For recent examples, see: (a) Horton, D.; Koh, D. TL 1993, 34, 2283. (b) Hatakeyama, S.; Sugawara, K.; Takano, S. CC 1993, 125. (c) Nakata, M.; Osumi, T.; Ueno, A.; Kimura, T.; Tamai, T.; Tatsuta, K. BCJ 1992, 65, 2974. (d) Yokokawa, F.; Hamada, Y.; Shioiri, T. SL 1992, 703. (e) Spada, M. R.; Ubukata, M.; Isono, K H 1992, 34, 1147.
6. Marshall, J. A.; DeHoff, B. S.; Cleary, D. G. JOC 1986, 51, 1735.

Brad DeHoff

Syntex Technology Center, Boulder, CO, USA

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