[2136-75-6]  · C20H17OP  · Formylmethylenetriphenylphosphorane  · (MW 304.33)

(stabilized Wittig reagent used for the synthesis of a,b-unsaturated aldehydes from aldehydes; reagent for two-carbon chain homologation)

Alternate Name: (triphenylphosphoranylidene)acetaldehyde.

Physical Data: mp 187-188 °C (dec).

Form Supplied in: white solid, 97%; commercially available.

Preparative Methods: reaction of Chloroacetaldehyde and Triphenylphosphine affords formylmethyltriphenylphosphonium chloride, which furnishes the phosphorane reagent on treatment with Triethylamine in ethanol.2

Handling, Storage, and Precautions: unstable to moisture and acids. Keep dry.

(E)-a,b-Unsaturated Aldehydes.

This stabilized phosphonium ylide reacts with a wide variety of aliphatic and aromatic aldehydes to give a,b-unsaturated aldehydes, with a high predominance of the (E)-alkene.2-5 This reagent has been applied in many areas of organic synthesis including natural products, carbohydrates, and heterocycles. Thus in the synthesis of swainsonine from D-mannose the chain-extended (E)-alkene (2) was prepared from the aldehyde (1) in good yield (eq 1).6

Tandem addition of the ylide has been successfully applied to the synthesis of (E,E)-dienyl aldehydes. For example, in the synthesis of natural leukotrienes, Rokach et al. converted epoxy aldehyde (3) to intermediate (4) en route to LTA4 (eq 2).7

Reaction of the ylide with ketones is generally unsuccessful;2 however, it has been reported to react with trifluoroacetone to give the expected trisubstituted alkene in low yield (eq 3).8

Alkenation with this ylide can be effected in good yield when a free hydroxyl group is present in the aldehyde substrate,9,10 although a neighboring hydroxyl appears to detract from the normally high (E) stereoselectivity (eq 4).10

(Z)-a,b-Unsaturated Aldehydes.

In a complementary manner, Bestmann's group has shown that conversion of this ylide to a diethyl acetal in situ affords a new phosphorane that transforms aldehydes into a,b-unsaturated aldehydes with predominantly (Z) stereochemistry (86-97%).11,12 The procedure involves treatment of the ylide with EtBr, followed by NaOEt, then addition of the aldehyde; the intermediate unsaturated diethyl acetals are hydrolyzed to obtain a,b-unsaturated aldehydes (eq 5). Higher yields of unsaturated diethyl acetals were usually realized by an alternative reaction sequence that employed a different base system: 1) EtBr; 2) sodium amide; and 3) ethanol.

1. For relevant reviews on the Wittig reaction: (a) Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863. (b) Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: New York, 1979. (c) Bestmann, H. J.; Vostrowsky, O. Top. Curr. Chem. 1983, 109, 85.
2. Trippett, S.; Walker, D. M. JCS 1961, 1266.
3. Olstein, R.; Stephenson, E. F. M. AJC 1979, 32, 681.
4. Venkataraman, H.; Cha, J. K. TL 1987, 28, 2455.
5. Ku, T. W.; McCarthy, M. E.; Weichman, B. M.; Gleason, J. G. JMC 1985, 28, 1847.
6. Fleet, G. W. J.; Gough, M. J.; Smith, P. W. TL 1984, 25, 1853.
7. Rokach, J.; Young, R. N.; Kakushima, M.; Lau, C.-K.; Seguin, R.; Frenette, R.; Guindon, Y. TL 1981, 22, 979.
8. Nägele, U. M.; Hanack, M. LA 1989, 847.
9. Nishiyama, S.; Toshima, H.; Kanai, H.; Yamamura, S. TL 1986, 27, 3643.
10. Still, W. C.; Gennari, C.; Noguez, J. A.; Pearson, D. A. JACS 1984, 106, 260.
11. Bestmann, H. J.; Roth, K.; Ettlinger, M. AG(E) 1979, 18, 687.
12. Bestmann, H. J.; Roth, K.; Ettlinger, M. CB 1982, 115, 161.

David F. McComsey & Bruce E. Maryanoff

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

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