(1,3-Dioxolan-2-ylmethyl)triphenylphosphonium Bromide

[52509-14-5]  · C22H22BrO2P  · (1,3-Dioxolan-2-ylmethyl)triphenylphosphonium Bromide  · (MW 429.31)

(generation of the nonstabilized ylide (1,3-dioxolan-2-ylmethylene)triphenylphosphorane for Wittig alkenation; synthesis of masked a,b-unsaturated aldehydes from aldehydes; reagent for two-carbon chain homologation1)

Physical Data: mp 193-195 °C.

Form Supplied in: white solid, 98%.

Preparative Method: from 2-bromomethyl-1,3-dioxolane and triphenylphosphine at 100 °C (36 h).2

Purification: recrystallized from methylene chloride/ether.2

a,b-Unsaturated Aldehydes.

This phosphonium salt reacts with base to give (1,3-dioxolan-2-ylmethylene)triphenylphosphorane, which is used in situ. Wittig reaction of this nonstabilized phosphorus ylide with aldehydes affords a,b-unsaturated acetals; acidic hydrolysis then provides the corresponding aldehydes. The alkene stereochemistry obtained is highly dependent on the base or solvent used. (E)-Alkenes are predominant with lithium methoxide or potassium carbonate in DMF (e.g. eq 1).2-6 Reactions of the ylide with ketones are generally poor.

Fraser-Reid and co-workers studied the stereoselectivity of this reagent in reactions with benzaldehyde involving different bases. When the phosphorane was prepared in THF with n-Butyllithium, only the (E)-alkene is formed. With dimsylsodium (Sodium Methylsulfinylmethylide) in DMSO a 3:1 ratio of (Z)- to (E)-isomers is obtained, while addition of THF to the DMSO reaction results in a 8:1 preference for the (Z)-isomer.7 These reaction conditions have been applied to ansamycin precursors (eq 2).7-9

Also, whereas a-alkoxy aldehydes usually furnish (E)-alkenes almost exclusively with Formylmethylenetriphenylphosphorane, Sakai et al. found that (1,3-dioxolan-2-ylmethylene)triphenylphosphorane, generated from the phosphonium reagent by using Sodium Hydride in THF-HMPA, gives mainly (Z)-alkenes (eq 3).10 Replacing the THF with DMF reduces this preference to ca. 75:25.

The Bestmann protocol with formylmethylenetriphenylphosphorane, which involves treatment with EtBr and NaOEt to form a diethyl acetal intermediate, offers a similar means for elaboration of aldehydes into a,b-unsaturated aldehydes chain-extended by two carbons, with high (Z) stereoselectivity.11,12 Related ylide reagents have also been used for such two-carbon homologations.13


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.
2. Cresp, T. M.; Sargent, M. V.; Vogel, P. JCS(P1) 1974, 37.
3. Ojima, J.; Ejiri, E.; Kato, T.; Kuroda, S.; Hirooka, S.; Shibutani, M. TL 1986, 27, 2467.
4. Tanner, D.; Wennerström, O.; Olsson, T. TL 1983, 24, 5407.
5. Nishitani, S.; Kurata, N.; Sakata, Y.; Misumi, S.; Migata, M.; Okada, T.; Mataga, N. TL 1981, 22, 2099.
6. Deng, Y.; Li, H.; Wu, W.; Tan, Z.; Hu, X.; Hu, H. CA 1989, 110, 38687g.
7. Fraser-Reid, B.; Molino, B. F.; Magdzinski, L.; Mootoo, D. R. JOC 1987, 52, 4505.
8. Molino, B. F.; Magdzinski, L.; Fraser-Reid, B. TL 1983, 24, 5819.
9. Fraser-Reid, B.; Magdzinski, L.; Molino, B. JACS 1984, 106, 731.
10. Sakai, T.; Kohda, K.; Tsuboi, S.; Utaka, M.; Takeda, A. BCJ 1987, 60, 2911.
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.
13. (a) Brugidou, J.; Poncet, J.; Chiche-Trinh Bich, H.; Christol, H. TL 1981, 22, 4709. (b) Spangler, C. W.; McCoy, R. K. SC 1988, 18, 51. (c) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P. T 1988, 44, 2021.

David F. McComsey & Bruce E. Maryanoff

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



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