(Methoxycarbonylmethylene)triphenylphosphorane1

Ph3P=CHCO2Me

[2605-67-6]  · C21H19O2P  · (Methoxycarbonylmethylene)triphenylphosphorane  · (MW 334.37)

(stabilized phosphorane reagent useful for Wittig alkenation reactions to give methyl acrylate esters on reactions with carbonyl compounds1 and ozonides;2 formation of heterocyclic rings3)

Alternate Name: methyl (triphenylphosphoranylidene)acetate.

Physical Data: mp 169-171 °C.

Solubility: sol CHCl3 (26 g 100 mL-1); slightly sol EtOH (2.7 g 100 mL-1), THF (3.8 g 100 mL-1); insol water (<0.5 g 100 mL-1).

Form Supplied in: white crystalline powder; commercially available.

Preparative Methods: readily prepared by mild base treatment of (methoxycarbonylmethyl)triphenylphosphonium bromide (pKa 8.8) (eq 1).4,5

Handling, Storage, and Precautions: storage at 5 °C in a tightly sealed bottle is recommended for prolonged periods. The compound decomposes to triphenylphosphine oxide in MeOH-water 1:1 (t1/2 ca. 1.5 h) and in weakly basic aqueous solution (0.5 mM NaOH in MeOH-water 1:1) (t1/2 ca. 1 h).

Weakly Basic Phosphorus Ylide.

(Methoxycarbonylmethylene)triphenylphosphorane is slightly less stable than the corresponding ethyl ester, but is widely used in a similar manner for Wittig alkenations and other reactions (see (Ethoxycarbonylmethylene)triphenylphosphorane). As with the ethyl ester, this reagent exists in solution as a 3:1 mixture of cis/trans ylide/enolates (eq 2).4,6 X-ray structure determination shows the cis form to have a short P-C bond and considerable C-C double bond character.7 There is increasing exchange of the two forms at higher temperatures, and also in the presence of trace amounts of a proton source such as water.6 Wittig reactions with the reagent work best as the exchange rate increases, due to the presence of greater amounts of the reactive ylide tautomer, so that it can be counterproductive to be overly scrupulous in drying these reactions.6

Wittig Alkenation Reactions.

Among the many examples of the use of this reagent in synthesis,1 only a few will be highlighted here. Typical reactions with aldehydes produce primarily the (E)-alkene, as in the condensation with PhCHO to give methyl cinnamates (eq 3).8 Although Wittig reaction intermediates have not been observed by spectroscopic means,9 it is expected that such reactions proceed through a four-membered oxaphosphetane prior to formation of products. The stereocontrol can be altered by the choice of solvent, temperature, and other factors.1

Treatment of MeC(O)CF3 with Ph3P=CHCO2Me results in formation of largely the (E) product (E:Z = 95:5), whereas condensation with the related Horner-Wadsworth-Emmons (HWE) reagent (MeO)2P(O)CHCO2Me-Na+ is not particularly stereoselective.10 Larger amounts of the (Z)-isomer are often observed in reactions with aldehydes bearing adjacent hydroxy or alkoxy groups, such as those derived from carbohydrates.1a For example, reaction of a galactose-derived aldehyde with the phosphorane gives mainly the (Z)-alkene (eq 4); many other related systems have been examined.11 The reactions of a-hydroxy carbonyl compounds are faster than those in which the hydroxy groups are protected.12

In cases where reactions are sluggish, such as those involving hindered carbonyls, the use of Bu3P=CHCO2Me can prove advantageous.1,12 In addition, this reagent often reacts with higher levels of (E) stereocontrol.1,13

Wittig/Michael reactions on the anomeric hemiacetals of sugars can lead directly to a C-glycoside structure. For example, an arabinose derivative was condensed with the phosphorane to give an anomeric mixture of C-glycosides (eq 5).14 When this reaction is carried out using Ph3P=CHCO2-t-Bu, a 2:3 mixture of (E):(Z) noncyclized alkene isomers is observed.15

Imides react with the phosphorane to produce N-vinyl amides.16 Thioimides react in a thio-Wittig reaction, albeit in low yields (eq 6).17 The (Z)-isomer converts to the (E)-isomer upon a silica gel chromatography.

The phosphorane reacts with anhydrides to give enol lactones.16 With highly substituted anhydrides the condensation occurs at the least hindered carbonyl; however, other factors come into play with only moderate steric hindrance. For example, 2-methyl- and 2-phenylsuccinic anhydrides suffer considerable attack at the 1-carbonyl.16,18 This effect is particularly pronounced in the case of 2-methoxysuccinic anhydride, in which case complexation of the oxygen is thought to direct the phosphorane to the 1-carbonyl (eq 7).18

Alkenations of Ozonides.

Ozonides react directly with the phosphorane in the preparation of trans-acrylate esters (eq 8).2 The sequence can be applied to a one-pot homologation of alkenes to (E)-acrylate esters.2 Trapping experiments have shown that it is the ozonide itself, and not opened species such as a carbonyl ylide, which is the reactive partner.2b

Heterocyclic Ring Formation.

Several different ring systems can be prepared using stabilized phosphoranes, as they have both ylide and ester reactive sites (see (Ethoxycarbonylmethylene)triphenylphosphorane). One example specifically involving (methoxycarbonylmethyl)triphenylphosphorane is the preparation of 2-chromenes from o-acyloxybenzyl bromide (eq 9).3 In this condensation the ylide is first benzylated with the benzyl halide functionality, followed by intramolecular Wittig reaction with the o-acetoxy group.

Condensation with benzoquinones involves initial Wittig reaction, followed by Michael addition of a second phosphorane. Elimination of triphenylphosphine and cyclization of the ester affords coumarin derivatives (eqs 10 and 11).19

Alkylation.

The reagent is sufficiently nucleophilic to be alkylated with reactive electrophiles to produce phosphorus reagents often suitable for further reactions.1 Hydrolysis of the triphenylphosphorus and ester moieties after alkylation affords the corresponding carboxylic acids (eq 12).19

Alternatively, alkylation of the phosphorane with an a-halo ketone is followed immediately by elimination of triphenylphosphine to give an a,b-unsaturated g-keto ester.20 This reaction has been used in the synthesis of isocardenolides (eq 13).21

The ylide can be halogenated22 or sulfenylated23 to prepare more complex ylides, which can then undergo Wittig reactions to yield vinyl halides or vinyl sulfides, respectively. Treatment of the phosphorane with a strong base in the absence of an added electrophile, followed by addition of Chlorotrimethylstannane, leads to Ph3P=C=C=O,24 which is a useful reagent for the construction of certain heterocyclic rings.25


1. (a) Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863. (b) Gosney, I.; Rowley, A. G. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; p. 17. (c) Schlosser, M. Top. Stereochem. 1970, 5, 1. (d) Johnson, A. W. Ylid Chemistry; Academic: New York, 1966. (e) Hudson, R. F. Structure and Mechanism in Organo-Phosphorus Chemistry, Academic: New York, 1965. (f) Maercker, A. OR 1965, 14, 270. (g) Trippett, S. QR 1963, 17, 406.
2. (a) Hon, Y.-S.; Chu, K.-P.; Hong, P.-C.; Lu, L. SC 1992, 22, 429. (b) Hon, Y.-S.; Lu, L.; Li, S.-Y. CC 1990, 1627.
3. Hercouet, A.; Le Corre, M. TL 1979, 2995.
4. Kayser, M. M.; Hatt, K. L.; Hooper, D. L. CJC 1991, 69, 1929.
5. Elemes, Y.; Foote, C. S. JACS 1992, 114, 6044.
6. Kayser, M. M.; Hooper, D. L. CJC 1990, 68, 2123.
7. Cherepinskii-Malov, V. D.; Aleksandrov, G. G.; Gusev, A. I.; Struchkov, Y. T. Zh. Strukt. Khim. 1972, 13, 273.
8. McEwen, W. E.; Sullivan, C. E.; Day, R. O. OM 1983, 2, 420.
9. Maryanoff, B. E.; Reitz, A. B.; Mutter, M. S.; Inners, R. R.; Almond, H. R., Jr.; Whittle, R. R.; Olofson, R. A. JACS 1986, 108, 7664.
10. Camps, F.; Canela, R.; Coll, J.; Messeguer, A.; Roca, A. T 1978, 34, 2179.
11. Valverde, S.; Martin-Lomas, M.; Herradon, B.; Garcia-Ochoa, S. T 1987, 43, 1895.
12. Garner, P.; Ramakanth, S. JOC 1987, 52, 2629.
13. Bissing, D. E. JOC 1965, 30, 1296.
14. Maryanoff, B. E.; Nortey, S. O.; Inners, R. R.; Campbell, S. A.; Reitz, A. B.; Liotta, D. Carbohydr. Res. 1987, 171, 259.
15. Wilcox, C. S.; Gaudino, J. J. JACS 1986, 108, 3102.
16. Murphy, P. J.; Brennan, J. CSR 1988, 17, 1.
17. Bishop, J. E.; O'Connell, J. F.; Rapoport, H. JOC 1991, 56, 5079.
18. Kayser, M. M.; Breau, L. CJC 1989, 67, 1401; and references cited therein.
19. (a) Bestmann, H. J.; Lang, H. J. TL 1969, 2101. (b) Bestmann, H. J.; Schulz, H. CB 1962, 95, 2921.
20. Bestmann, H. J.; Seng, F.; Schulz, H. CB 1963, 96, 465.
21. Pettit, G. R.; Green, B.; Das Gupta, A. K.; Whitehouse, P. A.; Yardley, J. P. JOC 1970, 35, 1381.
22. Speziale, A. J.; Ratts, K. W. JACS 1963, 85, 2790; and references cited therein.
23. Galli, R. JOC 1987, 52, 5349.
24. (a) Buckle, J.; Harrison, P. G. JOM 1974, 77, C22. (b) see also: Appel, R.; Winkhaus, V.; Knoch, F. CB 1986, 119, 2466.
25. Zbiral, E. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979; p. 223.

Allen B. Reitz & Mark E. McDonnell

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA



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