A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1990, 68, 138
DOI: 10.15227/orgsyn.068.0138
Submitted by Sandro Cacchi1, Enrico Morera2, and Giorgio Ortar2.
Checked by Sean Kerwin, Christopher Schmid, and Clayton H. Heathcock.
Discussion Addendum: Org. Synth. 2011, 88, 260
1. Procedure
A. Cholesta-3,5-dien-3-yl trifluoromethanesulfonate. A dry, 250-mL, two-necked, round-bottomed flask, equipped with a magnetic stirring bar, a rubber septum, and a pressure-equalizing 100-mL dropping funnel fitted with a calcium chloride drying tube, is charged with 4.62 g (22.5 mmol) of 2,6-di-tert-butyl-4-methylpyridine (Note 1) and 60 mL of dry dichloromethane (Note 2). Then 3.08 mL (18.75 mmol) of trifluoromethanesulfonic anhydride (Note 3) is added rapidly from a syringe and 5.77 g (15 mmol) of cholest-4-en-3-one (Note 4) diluted 40 mL of dry dichloromethane is added through the dropping funnel, dropwise and with stirring, during 15–20 min. The mixture is stirred for an additional 1 hr at room temperature. During this period the solution turns slightly pink and a white precipitate separates. The solvent is removed with a rotary evaporator and the residue is combined with 100 mL of diethyl ether. The white pyridinium trifluoromethanesulfonate salt is filtered off and washed with additional diethyl ether (3 × 50 mL). The ethereal solution is washed with cold 2 N hydrochloric acid (2 × 100 mL) and saturated sodium chloride solution (3 × 100 mL), dried over anhydrous potassium carbonate, and concentrated at reduced pressure. The solid residue (7.21–7.40 g) is recrystallized from hexane to give 6.46–6.72 g (83–87%) of cholesta-3,5-dien-3-yl trifluoromethanesulfonate as white crystals (Note 5), mp 125–126°C (Note 6).
B. Cholesta-3,5-diene. A 50-mL, two-necked, round-bottomed flask, equipped with a magnetic stirring bar and a reflux condenser with a nitrogen inlet at the top, is charged with 5.00 g (9.68 mmol) of cholesta-3,5-dien-3-yl trifluoromethanesulfonate (1), 6.92 mL (29.03 mmol) of tributylamine (Note 7), 0.043 g (0.19 mmol) of palladium acetate, 0.100 g (0.38 mmol) of triphenylphosphine, and 20.2 mL of N,N-dimethylformamide. The mixture is gently flushed with nitrogen for 1–2 min. and capped with a rubber septum. Formic acid, 99%, 0.73 mL (19.42 mmol), is added from a syringe dropwise and with swirling during 2–3 min. The resulting mixture is warmed in an oil bath at 60°C for 1 hr with continuous stirring under nitrogen. During this period the mixture becomes black. The contents of the flask are poured into 50 mL of 2 N hydrochloric acid and extracted with two 75-mL portions of ethyl ether. The combined organic phases are then washed with 50 mL of 2 N hydrochloric acid, 15 mL of saturated sodium bicarbonate solution, and two 10-mL portions of saturated sodium chloride solution, and are then dried over anhydrous magnesium sulfate. The drying agent is removed by filtration, the ether is evaporated at reduced pressure, and the solid residue (3.92–4.16 g) is purified by open-column chromatography on 100 g of basic aluminum oxide (Note 8) using hexane as eluent to give 3.12–3.22 g of nearly pure cholesta-3,5-diene, which is recrystallized from acetone to give a first crop (2.92–3.00 g) as white needles (Note 9), mp 81.5–82.5°C (lit.3 mp 79.5–80°C) (Note 6) and a second crop (0.11–0.15 g, 85–88% overall yield), mp 79.5–80.5°C (Note 6).
2. Notes
1. A commercial sample of 2,6-di-tert-butyl-4-methylpyridine from Fluka AG was purified through a short column of silica gel by eluting with hexane. Alternatively, it may be prepared according to the procedure reported in Organic Syntheses.4
2. Reagent-grade dichloromethane is dried by passing over a column of aluminum oxide (activity I).
3. Trifluoromethanesulfonic anhydride from Fluka AG was stirred over phosphorus pentoxide for 18 hr and distilled. It can also be prepared from trifluoromethanesulfonic acid (Fluka AG) according to the procedure described in Organic Syntheses.5
4. Cholest-4-en-3-one was purchased from Fluka AG and used without further purification.
5. Spectral data are as follows: 1H NMR (90 MHz, CDCl3) δ: 0.69 (s, 3 H, 13-CH3), 0.82 (s, 3 H, 10-CH3), 5.62 (m, 1 H, C-6 H), 6.02 (m, 1 H, C-4 H); MS m / e: 516 (M+).
6. Melting points are uncorrected and were determined with a Köfler hot-stage apparatus.
7. Tributylamine, palladium acetate, triphenylphosphine from Fluka AG and N,N-dimethylformamide, and formic acid from Farmitalia Carlo Erba Chemicals were used without further purification.
8. Basic aluminum oxide (activity I) is available from Merck & Company, Inc.
9. This compound has the following physical properties: 1H NMR (90 MHz, CDCl3) δ: 0.69 (s, 3 H, 13-CH3), 0.82 (s, 3 H, 10-CH3), 5.4 (m, 1 H, C-6 H), 5.59 (m, 1 H, C-3 H), 5.71 (d, 1 H, J = 10, C-4 H); [α]D (CHCl3, 1%) −115° (lit.3 [α]D −123°).
3. Discussion
The present preparation illustrates a general and convenient method for a two-step deoxygenation of carbonyl compounds to olefins.6 Related procedures comprise the basic decomposition of p-toluenesulfonylhydrazones,7 the hydride reduction of enol ethers,8 enol acetates,9 enamines,10 the reduction of enol phosphates (and/or enol phosphorodiamidates) by lithium metal in ethylamine (or liquid ammonia),11 the reduction of enol phosphates by titanium metal under aprotic conditions,12 the reduction of thioketals by Raney nickel,13 and the reduction of vinyl sulfides by Raney nickel in the presence of isopropylmagnesium bromide.14
Following our first report on the palladium-catalyzed reaction of vinyl triflates with olefins15 (Heck-type reaction), oxidative insertion of palladium(0) into the carbon–oxygen bond of easily available vinyl and aryl triflates16 has proved to be a general method for the generation of σ-vinyl and σ-aryl palladium intermediates that can react with a variety of nucleophiles such as olefins,15 17 18 19 1-alkynes,20 disubstituted alkynes,21 allenes,22 dialkyl phosphites,23 triphenylphosphine,24 silyloxycyclopropanes,25 cyanide,26 carbon monoxide in the presence of alcohols,27 amines,27 alkynes,28 and silyloxycyclopropanes.29
Palladium-catalyzed cross-coupling of vinyl and aryl triflates with organotion,30 organozinc,31 organoboron,32 organoaluminum,33 and organosilicon34 reagents has also been reported.
Reviews dealing with some aspects of the palladium chemistry of vinyl and aryl triflates have been published.35
σ-Vinyl palladium triflates are smoothly reduced to alkenes with trialkylammonium formate, usually in high yield. Some advantages of this reduction procedure should be noted. The trialkylammonium formate–palladium reducing system is very simple to use.36 Clean reduction of vinyl triflates to olefins is observed, and no overreduction is detected. Since vinyl triflates with defined regiochemistry can be easily synthesized,37 the method is of use in the regioselective synthesis of alkenes and dienes. Ketones, alcohols, ethers, aromatic systems, and presumably a variety of other functional groups are unaffected by the reduction conditions. When the reaction is carried out by using DCOOD, this method allows the regioselective and quantitative introduction of a deuterium atom.
The reaction has been successfully extended to the reduction of aryl triflates38,39,40,41 and fluoroalkanesulfonates39,42 to arenes.
Some selected examples of palladium-catalyzed reduction of vinyl and aryl triflates are summarized in Table I.




% yield



























aDCOOD was used.

bDPPF refers to 1, 1'-bis(diphenylphosphino)ferrocene.

cDPPP refers to 1,3-bis(diphenylphosphino)propane.

References and Notes
  1. Dipartimento di Studi di Chimica e Technologia delle Sostanze Biologicamente Attive, Università degli studi "La Sapienza," P.le A. Moro 5, 00185 Roma, Italy.
  2. Dipartimento di Studi Farmaceutici, Università degli Studi "La Sapienza," P.le A. Moro 5, 00185 Roma, Italy.
  3. O'Connor, G. L.; Nace, H. R. J. Am. Chem. Soc. 1952, 74, 5454.
  4. Anderson, A. G.; Stang, P. J. Org. Synth., Coll. Vol. VII 1990, 144.
  5. Stang, P. J.; Deuber, T. E. Org. Synth., Coll. Vol. VI 1988, 757.
  6. Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 25, 4821.
  7. Shapiro, R. H. Org. React. 1976, 23, 405, and references cited therein.
  8. Larson, G. L.; Hernandez, E.; Alonzo, C.; Nieves, I. Tetrahedron Lett. 1975, 4005; Pino, P.; Lorenzi, G. P. J. Org. Chem. 1966, 31, 329.
  9. Caglioti, L.; Cainelli, G.; Maina, G.; Selva, A. Gazz. Chim. Ital. 1962, 92, 309; Chem. Abstr. 1962, 57, 12572c.
  10. Lewis, J. W.; Lynch, P. P. Proc. Chem. Soc. London 1963, 19; Coulter, J. M.; Lewis, J. W.; Lynch, P. P. Proc. Chem. Soc. London 1963, 19; Coulter, J. M.; Lewis, J. W.; Lynch, P. P. Tetrahedron 1968, 24, 4489.
  11. Ireland, R. E.; Pfister, G. Tetrahedron Lett. 1969, 2145; Fetizon, M.; Jurion, M.; Anh, N. T. J. Chem. Soc., Chem. Commun. 1969, 112; Ireland, R. E.; Kowalski, C. J.; Tilley, J. W.; Walba, D. M. J. Org. Chem. 1975, 40, 990; Ireland, R. E.; Muchmore, D. C.; Hengartner, U. J. Am. Chem. Soc. 1972, 94, 5098; Ireland, R. E.; O'Neil, T. H.; Tolman, G. L. Org. Synth., Coll. Vol. VII 1990, 66.
  12. Welch, S. C.; Walters, M. E. J. Org. Chem. 1978, 43, 2715.
  13. Ben-Efraim, D. A.; Sondheimer, F. Tetrahedron 1969, 25, 2823; Fishman, J.; Torigoe, M.; Guzig, H. J. Org. Chem. 1963, 28, 1443.
  14. Trost, B. M.; Ornstein, P. L. Tetrahedron Lett. 1981, 22, 3463.
  15. Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 25, 2271;
  16. Stang, P. J.; Treptow, W. Synthesis 1980, 283; Hassdenteufel, J. R.; Hanack, M. Tetrahedron Lett. 1980, 21, 503; Stang, P. J.; Fisk, T. E. Synthesis 1979, 438.
  17. Harnisch, W.; Morera, E.; Ortar, G. J. Org. Chem. 1985, 50, 1990;
  18. Scott, W. J.; Pena, M. R.; Swärd, K.; Stoessel, S. J.; Stille, J. K. J. Org. Chem. 1985, 50, 2302;
  19. Arcadi, A.; Marinelli, F.; Cacchi, S. J. Organomet. Chem. 1986, 312, C27; Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1987, 28, 3039.
  20. Cacchi, S.; Morera, E.; Ortar, G. Synthesis 1986, 320.
  21. Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. R. J. Org. Chem. 1992, 57, 976.
  22. Friess, B.; Cazes, B.; Gore, J. Tetrahedron Lett. 1988, 29, 4089.
  23. Petrakis, S. K.; Nagabhushan, T. L. J. Am. Chem. Soc. 1987, 109, 2831; Holt, D. A.; Erb, J. M. Tetrahedron Lett. 1989, 30, 5393.
  24. Hinkle, R. J.; Stang, P. J.; Kowalski, M. H. J. Org. Chem. 1990, 55, 5033.
  25. Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. J. Am. Chem. Soc. 1988, 110, 3296.
  26. Piers, E.; Fleming, F. F. J. Chem. Soc., Chem. Commun. 1989, 756; Takagi, K.; Sakakibara, Y. Chem. Lett. 1989, 1957.
  27. Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1985, 26, 1109; Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1986, 27, 3931.
  28. Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1991, 32, 6449.
  29. Aoki, S.; Nakamura, E. Synlett. 1990, 741.
  30. Stille, J. K.; Tanaka, M. J. Am. Chem. Soc. 1987, 109, 3785; Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478; Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1988, 110, 1557.
  31. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. Tetrahedron Lett. 1986, 27, 955; McCague, R. Tetrahedron Lett. 1987, 28, 701; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1990, 31, 1889; Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. Synlett. 1990, 47.
  32. Oh-e, T.; Miyaura, N.; Suzuki, A. Synlett. 1990, 221.
  33. Saulnier, M. G.; Kadow, J. F.; Tun, M. M.; Langley, D. R.; Vyas, D. M. J. Am. Chem. Soc. 1989, 111, 8320; Hirota, K.; Isobe, Y.; Maki, Y. J. Chem. Soc., Perkin Trans. 1989, 2513.
  34. Hatanaka, Y.; Ebina, Y.; Hiyama, T. J. Am. Chem. Soc. 1991, 113, 7075.
  35. Scott, W. J.; McMurry, J. E. Acc. Chem. Res. 1988, 21, 47; Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508; Huang, W.-Y.; Chen, Q.-Y. "The Chemistry of Sulphonic Acids, Esters and Their Derivatives," Patai, S.; Rappoport, Z., Eds.: Wiley: New York, 1991, Chapter 21.
  36. Weir, J. R.; Patel, B. A.; Heck, R. F. J. Org. Chem. 1980, 45, 4926; Cacchi, S.; Palmieri, G. Synthesis 1984, 575; Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1986, 27, 6397; Tsuji, J.; Sugiura, T.; Minami, I. Synthesis 1987, 603.
  37. Crisp, G. T.; Scott, W. J. Synthesis 1985, 335.
  38. Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1986, 27, 5541;
  39. Chen, Q.-Y.; He, Y.-B.; Yang, Z.-Y. J. Chem. Soc., Chem. Commun. 1986, 1452;
  40. Peterson, G. A.; Kunng, F.-A.; McCallum, J. S.; Wulff, W. D. Tetrahedron Lett. 1987, 28, 1381.
  41. Saa, J. M.; Dopico, M.; Martonell, G.; Garcia-Raso, A. J. Org. Chem. 1990, 55, 991.
  42. Chen, Q.-Y.; He, Y.-B. Synthesis 1988, 896.
  43. Dolle, R. E.; Schmidt, S. J.; Erhard, K. F.; Kruse, L. I. J. Am. Chem. Soc. 1989, 111, 278.

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)


vinyl triflates


σ-Vinyl palladium triflates




potassium carbonate (584-08-7)

hydrochloric acid (7647-01-0)

ammonia (7664-41-7)

ethyl ether,
diethyl ether (60-29-7)

carbon monoxide (630-08-0)

sodium bicarbonate (144-55-8)

sodium chloride (7647-14-5)

formic acid (64-18-6)

nitrogen (7727-37-9)

Raney nickel (7440-02-0)

acetone (67-64-1)

palladium(0) (7440-05-3)

dichloromethane (75-09-2)

lithium (7439-93-2)

magnesium sulfate (7487-88-9)

aluminum oxide (1344-28-1)

isopropylmagnesium bromide (920-39-8)

N,N-dimethylformamide (68-12-2)

hexane (110-54-3)

Cholest-4-en-3-one (601-57-0)

ethylamine (75-04-7)

triphenylphosphine (603-35-0)

tributylamine (102-82-9)

trifluoromethanesulfonic acid (1493-13-6)

Trifluoromethanesulfonic anhydride (358-23-6)

1,3-bis(diphenylphosphino)propane (6737-42-4)

deuterium (7782-39-0)

palladium acetate (3375-31-3)

titanium (7440-32-6)

phosphorus pentoxide (1314-56-3)

Cholesta-3,5-diene (747-90-0)

Cholesta-3,5-dien-3-yl trifluoromethanesulfonate (95667-40-6)

2,6-Di-tert-butyl-4-methylpyridine (38222-83-2)