Triisopropyl Phosphite1


[116-17-6]  · C9H21O3P  · Triisopropyl Phosphite  · (MW 208.27)

(corresponding phosphonate esters afford high (E) selectivity in Wadsworth-Emmons alkenations4,5)

Physical Data: bp 63-64 °C/11 mmHg; nD 1.411; d 0.844 g cm-3; fp 67 °C.

Solubility: sol organic solvents.

Form Supplied in: clear liquid; widely available.

Purification: by distillation at reduced pressure to avoid decomposition by Michaelis-Arbuzov reaction.

Handling, Storage, and Precautions: moisture sensitive, toxic (RTECS# TH2800000). Stable at rt for extended periods of time. Use in a fume hood.

Phosphonate/Phosphate Formation.

The reactions of the triisopropyl ester of P(OH)3 are only marginally different from those of the triethyl or trimethyl esters. It may be used advantageously in situations which require a higher reaction temperature or a more sterically congested center (e.g. to prevent dealkylation of phosphonate esters). It can be used as a source of phosphonates (Michaelis-Arbuzov reaction)1 for Wadsworth-Emmons alkenation reactions.2 Control of the stereochemistry of the a,b-unsaturated ester may be possible by proper choice of the phosphonate ester. In contrast to the high (Z) selectivity observed3 using the bis(trifluoroethyl) phosphonate, diisopropyl phosphonates4,5 afford high (E) selectivity in some cases (eq 1).5 This has been attributed to the increased bulk of the phosphorus ester, but other reports6 dispute this and attribute the improved stereoselectivity to other factors.

Reaction with a-halo ketones affords enol phosphates (Perkow reaction),7 which can be converted to alkenes (eq 2).6

Like all phosphites, triisopropyl phosphite can be used as a reagent for removal of O,8 S,9 Hal,10 etc. from organic substrates (e.g. epoxides, episulfides, thiadiazolines). Like most reactions of trivalent phosphorus derivatives (phosphites or phosphines) with organic substrates, these reactions begin by formation of an alkoxyphosphonium salt or a derivative. Subsequent decomposition of the addition products leads to various products, depending on the functional groups involved. The use of triisopropyl phosphite as a ligand for transition metals is common. The much larger cone angle of triisopropyl phosphite11 relative to the ethyl and methyl esters can be advantageous. Phosphites are less basic and less nucleophilic than phosphines (trialkyl or triaryl).

Reduction of Carbonyl Groups.

Triisopropyl phosphite has been used as a simple alternative to the Clemmensen or Wolff-Kischner reductions.12 Refluxing the aldehyde or ketone with excess phosphite affords the deoxygenated reduced product in good yield under essentially neutral conditions (eq 3). A mechanism similar to the Meerwein-Pondorf-Verley reduction was proposed.

Related Reagents.

Triethyl Phosphite; Triethyl Phosphonoacetate; Trimethyl Phosphite; Trimethyl Phosphonoacetate.

1. Bhattacharya, A. K.; Thyagarajan, G. CRV 1981, 81, 415.
2. Wadsworth, W. S. OR 1977, 25, 73.
3. Still, W. C.; Gennari, C. TL 1983, 24, 4405.
4. Nagaoka, H.; Kishi, Y. T 1981, 37, 3873.
5. Roush, W. R.; Harris, D. J.; Lesur, B. M. TL 1983, 24, 2227.
6. Marshall, J. A.; DeHoff, B. S.; Cleary, D. G. JOC 1986, 51, 1735.
7. Lichtenthaler, F. W. CRV 1961, 61, 607.
8. Rowley, A. G. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; p 295.
9. Mackie, R. K. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; p 351.
10. Mackie, R. K. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; p 433.
11. Tolman, C. A. CRV 1977, 77, 313.
12. Olah, G. A.; Wu, A.-h. SL 1990, 54.

John M. McIntosh

University of Windsor, Ontario, Canada

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