Dimethyl 3-Bromo-2-ethoxy-1-propenylphosphonate1

[73542-48-0]  · C7H14BrO4P  · Dimethyl 3-Bromo-2-ethoxy-1-propenylphosphonate  · (MW 273.08) (E)

[87278-14-6] (Z)


(reagent for effecting cyclopentenone annulations2,3)

Physical Data: colorless liquid; distillation temperature (bulb-to-bulb) 110 °C/0.05 mmHg.

Solubility: sol THF, CHCl3, EtOAc, and other common organic solvents.

Preparative Method: is readily prepared in two steps from the commerically available keto phosphonate (1).2b Reaction of (1) with Triethyl Orthoformate in the presence of FeCl3.6H2O, followed by allylic bromination of the resultant enol ether (2), provides the title reagent (3) in 71% overall yield (eq 1).

Handling, Storage, and Precautions: should be used shortly after its preparation and should be handled only in a well-ventilated fume hood.

Cyclopentenone Annulations.

The use of (3) for the synthesis of 2-cyclopentenones involves three steps, as shown in general terms in eq 2. Alkylation of carbonyl substrates (4) with reagent (3),4 followed by mild acid hydrolysis of the resultant products (5), affords the diketo phosphonates (6). Subjection of the latter substances to intramolecular Horner-Emmons processes5 provides the annulation products (7).

A variety of functionalized ketones have been alkylated successfully with reagent (3).2,6-10 In those cases in which this process is sluggish or inefficient, the use of the iodo reagent (8) is beneficial.11-14

Conversion of (5) into (6) (eq 2) is typically accomplished by treatment of (5) with dilute aqueous HCl in acetone at rt.2,6-14 Under these conditions, groups that are potentially acid sensitive (acetals,2,8 esters,2,10,11 conjugated diene system12) are (normally) stable, although cleavage of a primary TBDMS ether has been noted.13

The intramolecular Horner-Emmons reaction (eq 2) has been effected via a variety of procedures, including the use of Sodium Hydride in DME,2,6,13-18 THF,8,15 or DMF11 at various temperatures, Potassium Carbonate in the presence of 18-Crown-6 in benzene7,9 or toluene,19 phase-transfer conditions employing Tetra-n-butylammonium Hydroxide-water in benzene20 or toluene,10 and MeSOCH2Na in THF.12 While the use of NaH as base is usually satisfactory, this protocol fails to convert (9) into bicyclo[3.3.0]oct-1-en-3-one (10).16 This transformation is readily achieved, however, as shown in eq 3.20

Compared with other procedures for effecting cyclopentenone annulations,3 the method under discussion (eq 2) has several advantages. The overall process is convergent in nature, is generally efficient, and, importantly, the final step (internal Horner-Emmons reaction) can be achieved under conditions that do not isomerize the initially formed product (7). The synthetic utility of this method is illustrated by the examples given in eqs 4 and 5.9,14

Related Reagents.

Allyl Chloride; 2,3-Dichloropropene; Methallyl Chloride.

1. Minami, T.; Motoyoshiya, J. S 1992, 333.
2. (a) Piers, E.; Abeysekera, B. Scheffer, J. R. TL 1979, 3279. (b) Piers, E.; Abeysekera, B. CJC 1982, 60, 1114.
3. (a) Paquette, L. A. Top. Curr. Chem. 1979, 79, 41; 1984, 119, 1. (b) Paquette, L. A.; Doherty, A. M. Polyquinane Chemistry: Synthesis and Reactions; Springer: Berlin, 1987. (c) Ramaiah, M. S 1984, 529. (d) Hudlicky, T.; Price, J. D. CRV 1989, 89, 1467.
4. For the overall conversion of (4) into diketo phosphonates structurally related to (6), employing diethyl 3-bromo-1-propenylphosphonate and diethyl 3-iodo-1-propynylphosphonate as the initial alkylating agents, see Poss, A. J.; Smyth, M. S. SC 1987, 17, 1735 and Poss, A. J.; Belter, R. K. JOC 1987, 52, 4810.
5. For cyclopentenone annulation sequences involving the use of intramolecular Wittig reactions, see Altenbach, H.-J. AG(E) 1979, 18, 940 and Trost, B. M.; Curran, D. P. JACS 1980, 102, 5699.
6. Bornack, W. K.; Bhagwat, S. S.; Ponton, J.; Helquist, P. JACS 1981, 103, 4647.
7. Aristoff, P. A. SC 1983, 13, 145.
8. Paquette, L. A.; Leone-Bay, A. JACS 1983, 105, 7352.
9. Liu, H.-J.; Llinas-Brunet, M. CJC 1988, 66, 528.
10. (a) Keese, R. AG(E) 1992, 31, 344. (b) Hirschi, D.; Luef, W.; Gerber, P.; Keese, R. HCA 1992, 75, 1897.
11. Callant, P.; De Wilde, H.; Vandewalle, M. T 1981, 37, 2079.
12. Dewanckele, J. M.; Zutterman, F.; Vandewalle, M. T 1983, 39, 3235.
13. Paquette, L. A.; Vanucci, C.; Rogers, R. D. JACS 1989, 111, 5792.
14. Paquette, L. A.; Moriarty, K. J.; McKinney, J. A.; Rogers, R. D. OM 1989, 8, 1707.
15. Clark, R. D.; Kozar, L. G.; Heathcock, C. H. SC 1975, 5, 1.
16. (a) Begley, M. J.; Cooper, K.; Pattenden, G. TL 1981, 22, 257. (b) Begley, M. J.; Cooper, K.; Pattenden, G. T 1981, 37, 4503.
17. Iwata, C.; Yamashita, M.; Aoki, S.; Suzuki, K.; Arakawa, H.; Tanaka, T. CPB 1986, 34, 4947.
18. Moriarty, K. J.; Rogers, R. D.; Paquette, L. A. OM 1989, 8, 1512.
19. Aristoff, P. A. JOC 1981, 46, 1954.
20. Davidsen, S. K.; Heathcock, C. H. S 1986, 842.

Edward Piers & Christine Rogers

University of British Columbia, Vancouver, BC, Canada

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.