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DOI:10.15227/orgsyn.068.0138

Organic Syntheses, Coll. Vol. 8, p.126 (1993); Vol. 68, p.138 (1990).

PALLADIUM-CATALYZED REDUCTION OF VINYLTRIFLUOROMETHANESULFONATES TO ALKENES:
CHOLESTA-3,5-DIENE

Submitted by Sandro Cacchi1, Enrico Morera2, and Giorgio Ortar2.
Checked by Sean Kerwin, Christopher Schmid, and Clayton H. Heathcock.

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 2,6di-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 thedropping 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 ofdiethyl ether. The white pyridinium trifluoromethanesulfonate salt is filtered off and washed withadditional 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 fromhexane 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) ofcholesta-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 ofN,N-dimethylformamide. The mixture is gently flushed with nitrogen for 1–2 min. and capped with arubber septum. Formic acid, 99%, 0.73 mL (19.42 mmol), is added from a syringe dropwise and withswirling during 2–3 min. The resulting mixture is warmed in an oil bath at 60°C for 1 hr withcontinuous stirring under nitrogen. During this period the mixture becomes black. The contents of theflask are poured into 50 mL of 2 N hydrochloric acid and extracted with two 75-mL portions of ethylether. 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 chloridesolution, and are then dried over anhydrous magnesium sulfate. The drying agent is removed byfiltration, the ether is evaporated at reduced pressure, and the solid residue (3.92–4.16 g) is purified byopen-column chromatography on 100 g of basic aluminum oxide (Note 8) using hexane as eluent togive 3.12–3.22 g of nearly pure cholesta-3,5-diene, which is recrystallized from acetone to give a firstcrop (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 asecond 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 ashort column of silica gel by eluting with hexane. Alternatively, it may be prepared according to theprocedure 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 hrand distilled. It can also be prepared from trifluoromethanesulfonic acid (Fluka AG) according to theprocedure 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, 10CH3), 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, 13CH3), 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]3D (CHCl3, 1%) −115° (lit. [α]D −123°).

3. Discussion
The present preparation illustrates a general and convenient method for a two-step deoxygenation ofcarbonyl compounds to olefins.6 Related procedures comprise the basic decomposition of ptoluenesulfonylhydrazones,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 (orliquid ammonia),11 the reduction of enol phosphates by titanium metal under aprotic conditions,12 thereduction of thioketals by Raney nickel,13 and the reduction of vinyl sulfides by Raney nickel in thepresence of isopropylmagnesium bromide.14
Following our first report on the palladium-catalyzed reaction of vinyl triflates with olefins15 (Hecktype reaction), oxidative insertion of palladium(0) into the carbon–oxygen bond of easily available vinyland 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 andsilyloxycyclopropanes.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 beenpublished.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 ofalkenes 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 andfluoroalkanesulfonates39,42 to arenes.
Some selected examples of palladium-catalyzed reduction of vinyl and aryl triflates are summarizedin Table I.

TABLE IPALLADIUM-CATALYZED REDUCTION OF VINYL AND ARYL TRIFLATES
Substrate

Catalyst

Product% yield

Pd(OAc)2(PPh3)2

816

Pd(OAc)2(PPh3)2936

Pd(OAc)2(PPh3)2

856

Pd(OAc)2(PPh3)2

956

Pd(OAc)2(PPh3)2a876

Pd(OAc)2(PPh3)2a9543

Pd(OAc)2/dppfb

7938

Pd(OAc)2/dppfb

9438

Pd(OAc)2/dppfa

8738

Pd(OAc)2/dppf

8238

Pd(OAc)2(PPh3)2

9138

Pd(OAc)2(PPh3)2

9040

PdCl2(PPh3)2/dpppc

7641

DCOOD was used.
DPPF refers to 1, 1'-bis(diphenylphosphino)ferrocene.
cDPPP refers to 1,3-bis(diphenylphosphino)propane.
ab

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.

12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.

32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.

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.
Welch, S. C.; Walters, M. E. J. Org. Chem. 1978, 43, 2715.
Ben-Efraim, D. A.; Sondheimer, F. Tetrahedron 1969, 25, 2823; Fishman, J.; Torigoe, M.;
Guzig, H. J. Org. Chem. 1963, 28, 1443.
Trost, B. M.; Ornstein, P. L. Tetrahedron Lett. 1981, 22, 3463.
Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 25, 2271;
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.
Harnisch, W.; Morera, E.; Ortar, G. J. Org. Chem. 1985, 50, 1990;
Scott, W. J.; Pena, M. R.; Swärd, K.; Stoessel, S. J.; Stille, J. K. J. Org. Chem. 1985, 50, 2302;
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.
Cacchi, S.; Morera, E.; Ortar, G. Synthesis 1986, 320.
Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. R. J. Org. Chem.
1992, 57, 976.
Friess, B.; Cazes, B.; Gore, J. Tetrahedron Lett. 1988, 29, 4089.
Petrakis, S. K.; Nagabhushan, T. L. J. Am. Chem. Soc. 1987, 109, 2831; Holt, D. A.; Erb, J. M.
Tetrahedron Lett. 1989, 30, 5393.
Hinkle, R. J.; Stang, P. J.; Kowalski, M. H. J. Org. Chem. 1990, 55, 5033.
Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. J. Am. Chem. Soc. 1988, 110, 3296.
Piers, E.; Fleming, F. F. J. Chem. Soc., Chem. Commun. 1989, 756; Takagi, K.; Sakakibara, Y.
Chem. Lett. 1989, 1957.
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.
Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1991, 32, 6449.
Aoki, S.; Nakamura, E. Synlett. 1990, 741.
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.
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.
Oh-e, T.; Miyaura, N.; Suzuki, A. Synlett. 1990, 221.
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.
Hatanaka, Y.; Ebina, Y.; Hiyama, T. J. Am. Chem. Soc. 1991, 113, 7075.
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 andTheir Derivatives," Patai, S.; Rappoport, Z., Eds.: Wiley: New York, 1991, Chapter 21.
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.
Crisp, G. T.; Scott, W. J. Synthesis 1985, 335.
Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1986, 27, 5541;
Chen, Q.-Y.; He, Y.-B.; Yang, Z.-Y. J. Chem. Soc., Chem. Commun. 1986, 1452;
Peterson, G. A.; Kunng, F.-A.; McCallum, J. S.; Wulff, W. D. Tetrahedron Lett. 1987, 28, 1381.
Saa, J. M.; Dopico, M.; Martonell, G.; Garcia-Raso, A. J. Org. Chem. 1990, 55, 991.
Chen, Q.-Y.; He, Y.-B. Synthesis 1988, 896.
Dolle, R. E.; Schmidt, S. J.; Erhard, K. F.; Kruse, L. I. J. Am. Chem. Soc. 1989, 111, 278.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)p-toluenesulfonylhydrazones
vinyl triflates
silyloxycyclopropanes
σ-Vinyl palladium triflates
Pd(OAc)2(PPh3)2
Pd(OAc)2/dppf
PdCl2(PPh3)2/dppp
potassium carbonate (584-08-7)hydrochloric acid (7647-01-0)
ammonia (7664-41-7)
ether,
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)
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