Synthesis of 5-acetoxy-2(5H)-furanones through manganese(III)-promoted functionalization of arylacetylenes

Article abstract of DOI:10.1016/S0040-4020(00)00898-X

Reaction of phenylacetylenes 1a-e with manganese(III) triacetate in acetic acid/acetic anhydride at reflux gave the corresponding 5-acetoxy-5-phenyl-2(5H)-furanones 2a-e in good yield (40-86%). Furanones 2 were derived from further oxidation of the initia

Full text of DOI:10.1016/S0040-4020(00)00898-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9339±9342
Synthesis of 5-Acetoxy-2(5H)-Furanones through
Manganese(III)-Promoted Functionalization of Arylacetylenes
*
Pier Carlo Montevecchi and Maria Luisa Navacchia
Á
Dipartimento di Chimica Organica `A. Mangini', Universita di Bologna, Viale Risorgimento 4, I-40136 Bologna, Italy
Received 17 May 2000; revised 1 September 2000; accepted 21 September 2000
AbstractÐReaction of phenylacetylenes 1a±e with manganese(III) triacetate in acetic acid/acetic anhydride at re¯ux gave the correspond-
ing 5-acetoxy-5-phenyl-2(5H)-furanones 2a±e in good yield (40±86%). Furanones 2 were derived from further oxidation of the initially
formed 5-phenyl-2(3H)-furanones 4 which were in turn obtained through regioselective addition of carboxymethyl radicals to the alkyne 1
triple bond and subsequent oxidative cyclization of the resulting a-phenylvinyl radical 3. In contrast, the (trimethylsilyl)alkylacetylene 1f
gave the corresponding furanone 2f in only 25% yield, whereas alkylacetylenes 1g±h totally failed to give the corresponding furanones 2f±h,
probably due to the incapability of the a-alkyl vinyl radical intermediates 3g±h of undergoing oxidative cyclization. q 2000 Elsevier
Science Ltd. All rights reserved.
Several methods are reported in the literature concerning the
oxidative functionalization of the CC double bond.1 In
contrast, the oxidation of the CC triple bond has received
much lesser attention. The hitherto known methods are
mainly con®ned to the oxidative transformation of the CC
triple bond to diketones or carboxylic acids.1a Recently, we
have reported the DDQ-promoted oxidation of alkyl-
acetylenes, which occurs at the propargylic carbon leading
to Z-enynes in a stereoselective mode.2
oxidative addition to the alkyne triple bond has not been
explored yet, notwithstanding that it could lead to syntheti-
cally useful unsaturated g-lactones. Unsaturated g-lactones
(the so called `butenolides') are encountered frequently in a
large number of natural products, including ¯avour compo-
nents, insect sex pheromones and antibiotics.10 A large
variety of synthetic methods have been reported.11
Results and Discussion
In our interest in the chemistry of the CC triple bond3 we
have undertaken a study of the manganese(III) triacetate
promoted oxidation of alkynes.
For this work we used commercially available acetylenes
1a±h. Reactions were carried out by heating a 0.2 M solu-
tion of the appropriate alkyne 1a±h in a 1:1 acetic acid/
acetic anhydride mixture to re¯ux in the presence of
4 molar equivalents of Mn(III) triacetate. With anhydrous
Mn(III) triacetate all the reactions were completed in
20 min. Within this time the deep brown colour faded and
a white precipitate of Mn(II) acetate was formed. GC-MS
analysis showed the disappearance of starting alkyne 1.
Reactions carried out with the commercial dihydrate salt
required a longer time; the disappearance of starting alkyne
1 occurred in 4±5 h.
Manganese(III) triacetate is widely employed in organic
synthesis as oxidising reagent.4 Heiba et al.5 reported in
1974 that b-ketoethers, and related b-dicarbonyl com-
pounds, are oxidised to radicals at 25±708C in acetic acid.
In 1984, Corey and Kang6 reported the cyclization of b-keto
acids. Since these pioneering works, Mn(III)-based oxida-
tive free radical cyclizations and annulations have been
extensively investigated.1,7
Previously, the oxidative addition of acetic acid to alkenes
had been reported.8 Under these conditions Mn(III) tri-
acetate generates carboxymethyl radicals. These add to the
alkene double bond to give alkyl radicals which are further
oxidised to give saturated g-lactones. These oxidative addi-
tions have been extensively explored.9 In contrast, the
Phenylacetylenes 1a±c,e gave, after work up, the corre-
sponding crude 5-acetoxy-2(5H)-furanones 2a±c,e
(Scheme 1). Subsequent puri®cation on silica gel column
gave these products in good yields (78±86%). Similar
results were obtained for diphenylacetylene 1d, but the
corresponding furanone 2d was recovered, after ¯ash
chromatography, only in 40% yield.
Keywords: manganese triacetate; alkynes; radical addition; furanone;
g-butenolide.
* Corresponding author. Tel.: 139-51-6443623; fax: 139-51-6443654;
e-mail: montevec@ms.fci.unibo.it
The formation of 5-acetoxy-2-(5H)-furanones 2a±d can be
explained by the reaction mechanism shown in Scheme 2.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00898-X

9340
P. C. Montevecchi, M. L. Navacchia / Tetrahedron 56 (2000) 9339±9342
and elemental analysis. All these compounds gave a low
intensity molecular ion in the MS spectrum, with important
fragment ions at M1242, 105 and 43. The regiochemistry
of furanones 2a±d was attributed on the basis of the H
1
NMR spectrum analysis, which showed coupling between
the C(3)±H and C(4)±H hydrogen atoms in 2a and allylic
coupling between the C(3)±H hydrogen and the C(4)-alkyl
group. The regiochemistry of 2e was attributed on the basis
of n.O.e. experiments. Irradiation on the trimethylsilyl
group signal caused a 5% enhancement of the vinylic proton
signal.
Scheme 1. a: RˆPh, R0ˆH; b: RˆPh, R0ˆMe; c: RˆPh, R0ˆpropyl; d:
RˆR0ˆPh; e: RˆPh, R0ˆSiMe3; f: RˆSiMe3, R0ˆbutyl; g: RˆR0ˆpropyl;
h: Rˆoctyl; R0ˆH.
In contrast to 1a±e, (trimethylsilyl)hexyne 1f gave a
complex mixture of products, from which furanone 2f was
separated by column chromatography in 25% yield, together
with large amounts of polymeric compounds, which showed
peaks at m/z.600 in the mass spectrum and unresolved
Regioselective addition12 of carboxymethyl radicals to the
CC triple bond gives vinyl radicals 3a±d, which afford
2(3H)-furanones 4 through oxidative cyclization onto the
oxygen atom. In turn, furanones 4 undergo a further two-
electron oxidation to allyl cations 5, with formation of
furanones 2 through regioselective trapping by the acetoxy
counterion at the benzylic position. The overall reaction
leading to 2 from 1 is a 4 electron oxidation process, and
4 molar equivalents of Mn(III) triacetate are required. When
the reaction of 1a±d was carried out with less than 4 molar
equivalents of Mn(III), unreacted alkyne was found, and no
traces of the possible furanone 4 intermediate was detected.
This ®nding indicates that the oxidation of 4 to 2 is a fast
process.
1
bands in the aliphatic region in the H NMR spectrum.
On the other hand, alkylacetylenes 1g,h gave only
unidenti®ed, polymeric products which showed unresolved
1
peaks in the aliphatic region in the H NMR spectrum and
peaks at m/z.600 in the MS spectrum. GC-MS analysis of
the reaction mixtures did not indicate the formation of
furanones 4g,h or 2g,h.
We think that the formation of polymeric materials in the
case of alkynes 1f±h might be attributed to a side reaction
involving addition of radicals 3f±h to the starting alkyne
triple bond, which should occur in competition with the
oxidative cyclization onto the oxygen atom.
Furanone 2d has already been prepared in 12% yield by
Oishi and Kurosawa13 through Mn(III) triacetate oxidation
of a-acetoxystilbene. In this case it was also suggested that
furanone 4d was an intermediate derived from initial
carboxymethyl radical addition to the alkene double bond,
followed by oxidative cyclization of the ensuing alkyl
radical.
The complete failure of 1g,h to afford the desired furanones
2g,h should result from the incapability of the vinyl radical
intermediates 3g,h of undergoing the oxidative cyclization
onto the oxygen atom under the reaction conditions
employed.
Structural assignment to the hitherto unknown furanones
The different behaviour exhibited by vinyl radicals 3g,h, as
compared with radicals 3a±e, might result from the fact that
1
2a±c,e came from H and 13C NMR, IR and MS spectra
Scheme 2.

P. C. Montevecchi, M. L. Navacchia / Tetrahedron 56 (2000) 9339±9342
9341
1
radicals 3g,h, belonging to the class of the sp2-hybrizided,
bent a-alkyl-substituted vinyl radicals, have the unpaired
electron in a sp2 orbital,14 whereas radicals 3a±e, belonging
to the class of the sp-hybridized, linear a-aryl-substituted
vinyl radicals, have the unpaired electron in a p orbital.14,15
Thus, a-phenyl-substituted vinyl radicals 3a±e would be
expected to be more easily oxidised due to the lower
ionisation potential of the p orbital with respect to the sp2
one.
The residue was analysed by H NMR and then chromato-
graphed on a silica gel column.
From 1a. Elution with petroleum ether (bp 40±70)/ethyl
acetate 70:30 gave 5-acetoxy-5-phenyl-2(5H)-furanone 2a
as a pale yellow oil (340 mg, 1.55 mmol, 78%) [dH
(200 MHz, CDCl3) 2.15 (3H, s), 6.3 (1H, d, Jˆ5.3 Hz),
7.3±7.5 (5H, m), 7.75 (1H, d, Jˆ5.3 Hz; collapsing to sing-
let upon irradiation at d 6.3); dC (75.5 MHz, CDCl3) 22.05
(CH3), 106.8(C), 122.64(CH), 125.6(CH), 129.15 (CH),
130.4 (CH), 133.8 (C), 153.8 (CH),168.44 (C), 170.03
(C); m/z (rel. int.) 218 (M1, 1), 176 (100), 159 (55), 131
(35), 105 (65), 77 (50), 43 (70); nmax 1780 (CO, broad).
Found: C, 66.24; H, 4.63. C12H10O4 requires C, 66.05; H,
4.62; O, 29.33%].
Conclusions
In summary, we have shown that the Mn(III)-promoted
oxidative functionalization of acetylenes can lead to the
corresponding 5-acetoxyfuranones 2 trough initial carboxy-
methyl radical addition to the alkyne triple bond, followed
by oxidative cyclization of the ensuing vinyl radical 3. The
resulting furanones 4 give furanones 2 by further oxidation
and eventual capture of allyl cations 5 by the acetoxy
counterion. The key step of the entire process seems to be
the oxidative cyclization of intermediate vinyl radicals 3,
which is governed by the nature of the a-substituent.
From 1b. Elution with petroleum ether (bp 40±70)/ethyl
acetate 70:30 gave 3-methyl-5-acetoxy-5-phenyl-2(5H)-
furanone 2b as a pale yellow oil (400 mg, 1.72 mmol,
86%) [dH (200 MHz, CDCl3) 1.9 (3H, d, Jˆ1.8 Hz; collaps-
ing to singlet upon irradiation at d 5.9), 2.15 (3H, s), 5.9
(1H, q, Jˆ1.8 Hz), 7.3±7.5 (5H, m); dC (75.5 MHz, CDCl3)
13.1 (CH3), 22.2 (CH3), 106.8 (C), 117.7 (CH), 125.4 (CH),
129.1 (CH), 130.0 (CH), 135.1 (C), 167.2 (C), 168.2 (C),
170.5 (C); m/z (rel. int.) 232 (M1, 5), 190 (50), 173 (30), 158
(25), 127 (50), 105 (100), 85 (55), 77 (55), 43 (95); nmax
1780 (CO, broad). Found: C, 67.40; H, 5.20. C13H12O4
requires C, 67.23; H, 5.21; O, 27.56%]. Further elution
with ethyl acetate gave intractable tarry materials.
a-Phenylvinyl radicals 3a±e generally gave the correspond-
ing furanones 2a±e in good yields, (trimethylsilyl)alkyl-
acetylene 1f gave the furanone 2f in 25% yield only,
whereas no furanone 2g,h was detected with alkylacetylenes
1g,h.
From 1c. Elution with petroleum ether (bp 40±70)/ethyl
acetate 70:30 gave 3-propyl-5-acetoxy-5-phenyl-2(5H)-
furanone 2c as a pale yellow oil (430 mg, 1.65 mmol,
82%) [dH (200 MHz, CDCl3) 1.9 (3H, t, Jˆ7 Hz); 1.4±
1.65 (2H, m), 2.0 (1H, A part of an ABXY system,
JABˆ18, JAXˆ8.5, JAYˆ6 Hz; lines broadened by coupling
at d 5.9), 2.18 (3H, s), 2.2 (1H, B part of an ABXY system,
JABˆ18, JBXˆ9.5, JAYˆ6 Hz; lines broadened by coupling
at d 5.9), 5.9 (1H, t, Jˆ1.5 Hz), 7.3±7.5 (5H, m); dC
(75.5 MHz, CDCl3) 13.44 (CH3), 19.58 (CH2), 21.52
(CH3), 28.46 (CH2), 106.28 (C), 115.70 (CH), 124.78
(CH), 128.63 (CH), 129.44 (CH), 134.86 (C), 167.61 (C),
170.24 (C), 171.03 (C); m/z (rel. int.) 260 (M1, 5), 260 (M1,
5), 218 (40), 201 (25), 173 (20), 155 (35), 113 (100), 105
(80), 77 (40), 43 (60); nmax 1780 (CO, broad). Found: C,
69.40; H, 6.40. C15H16O4 requires C, 69.21; H, 6.20; O,
24.59.]. Further elution with ethyl acetate gave intractable
tarry materials.
The short reaction time, the easy work up and the high
yields make this reaction a useful method to synthesise
functionalizated 5-acetoxy-5-aryl-2(5H)-furanones.
Experimental
1H NMR spectra were recorded with a Varian Gemini 200
instrument using Me4Si as an internal standard. 13C NMR
were recorded with a Varian Gemini 300 instrument. Mass
spectra were recorded with a VG 7070E instrument using
electron impact ionisation. IR spectra were recorded in
CHCl3 solution with a Perkin±Elmer FTIR 1600 instrument.
GC-MS analyses were performed with a Carlo Erba QMD
1000 instrument. Elemental analyses were performed with a
Carlo Erba 1106 instrument. Anhydrous Mn(III) triacetate
was obtained by heating at 1008C under nitrogen
atmosphere the commercially available dihydrate salt for
more than 24 h. Alkynes 1a±h are commercially available.
From 1d. Elution with petroleum ether (bp 40±70)/ethyl
acetate 80:20 gave 5-acetoxy-3,5-diphenyl-2(5H)-furanone
1
2d (230 mg, 0.8 mmol, 40%); H NMR and MS spectra
Reaction of alkynes 1a±i with Mn(III) triacetate.
General procedure
were as reported in the literature;13 dC (75.5 MHz, CDCl3)
21.6 (CH3), 106.3 (C), 117.1 (CH), 126.0 (CH), 128.6 (CH),
129.4 (CH), 129.6 (CH), 130.5 (CH), 132.0 (CH), 136.3 (C),
163.7 (C), 168.1 (C), 169.8 (C). Further elution with ethyl
acetate gave intractable tarry materials.
Anhydrous Mn(III) triacetate (8 mmol, 2 g) was added to a
solution of the appropriate alkyne 1a±i (2 mmol) in a 1:1
acetic acid/acetic anhydride mixture (10 mL). The resulting
mixture was re¯uxed for ca. 20 min, until the brown colour
faded and a white precipitate of manganese(II) diacetate
was separated. The reaction mixture was cooled and
quenched with water (50 mL) and diethyl ether (50 mL).
The organic layer was separated, washed 5 times with
water and the organic solution concentrated under vacuum.
From 1e. Elution with petroleum ether (bp 40±70)/ethyl
acetate 70:30, 3-(trimethylsilyl)-5-acetoxy-5-phenyl-2(5H)-
furanone 2e as a pale yellow oil (485 mg, 1.67 mmol, 84%)
[dH (200 MHz, CDCl3) 20.05 (9H, s), 2.18 (3H, s), 6.3 (1H,
s), 7.3±7.5 (5H, m); dC (75.5 MHz, CDCl3) 21.4 (CH3),

9342
P. C. Montevecchi, M. L. Navacchia / Tetrahedron 56 (2000) 9339±9342
22.4 (CH3), 109.7 (C), 125.8 (CH), 129.3 (CH), 130.1 (CH),
130.35 (CH), 135.8 (C), 168.45 (C), 168.45 (C), 171.2 (C),
172.8 (C); m/z (rel. int.) 290 (M1, 1), 248 (10), 174 (25), 159
(100), 129 (10), 105 (15); nmax 1780 (CO, broad). Found: C,
62.22; H, 6.23. C15H18O4Si requires C, 62.04; H, 6.25; O,
22.04; Si, 9.67.]. Further elution with ethyl acetate gave
intractable tarry materials.
References
1. (a) Hudlicky M. Oxidations in Organic Chemistry; ACS
Monograph 186, 1990. (b) Comprehensive Organic Synthesis;
Pergamon: Oxford, UK, 1991; Vol. 7, Chapter 3.
2. Montevecchi, P. C.; Navacchia, M. L. J. Org. Chem. 1998, 63,
8035.
3. Montevecchi, P. C.; Navacchia, M. L. J. Org. Chem. 1997, 62,
5600; Montevecchi, P. C.; Navacchia, M. L. J. Org. Chem. 1998,
63, 537 and references cited therein.
From 1f. The residue (360 mg) was constituted by a
mixture of several products, as evidenced by the H NMR
1
spectrum. Column chromatography on silica gel column
separated, by gradual elution with petroleum ether (bp
40±70)/ethyl acetate: (1) a ca. 1:1 mixture (70 mg) of 2f
4. Snider, B. B. Chem Rev. 1996, 96, 339.
5. Heiba, E. I.; Dessau, R. M. J. Org. Chem. 1974, 39, 3456.
6. Corey, E. J.; Kang, M.-C. J. Am. Chem. Soc. 1984, 106, 5384.
7. Snider, B. B. In Transition Metals Organic Synthesis, Beller,
M., Bolm, C., Eds.; Wiley: Weinheim, 1998; Vol. 2, pp 439±446.
8. Heiba, E. I.; Dessau, R. M.; Koehl Jr., W. J. J. Am. Chem. Soc.
1968, 90, 5905.
1
and an unidenti®ed product. The H NMR spectrum, in
addition to peaks ascribable to 2f, showed peaks at d 0.18
(s), 0.82 (t, Jˆ7 Hz) and 2.08 (s); the GC-MS spectrum, in
addition to 2f, showed a chromatographic peak with m/z 239
(1), 212 (30), 169 (20), 73 (100), and 43 (70); (2) 3-butyl5-
acetoxy-5-(trimethylsilyl)-2(5H)-furanone 2f as a pale
yellow oil (110 mg, 0.4 mmol, 20%) [dH (200 MHz,
CDCl3) 0.20 (9H, s), 0.85 (3H, t, Jˆ7 Hz), 1.1±1.4 (4H,
m), 1.55±1.75 (1H, m), 2.0 (3H, s), 2.05±2.2 (1H, m),
6.22 (1H, s); dC (75.5 MHz, CDCl3) 21.72 (CH3), 13.90
(CH3), 21.7 (CH3), 22.4 (CH2), 24.3 (CH2), 37.1 (CH2),
11.6 (C), 131.9 (CH), 167.4 (C), 168.2 (C), 170.3 (C); m/z
(rel. int.) 270 (M1, 3), 228 (25), 185 (50), 75 (70), 73 (100),
43 (90); nmax 1780 (CO, broad). Found: C, 57.90; H, 8.23.
C13H22O4Si requires C, 57.75; H, 8.20; O, 23.67; Si,
10.39%]; and (3) a mixture of unidenti®able, polymeric
products (180 mg). MS spectrum of this fraction showed
9. Iqbal, J.; Bathia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519.
10. Dean, F. M. Naturally Occurring Oxygen Ring Compounds;
Butterworths: Washington, DC, 1963; pp 53±81.
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12. The radical addition to 1-arylcetylenes, including carbon-
centred radical addition (see: Montevecchi, P. C.; Navacchia, M.
L.; Spagnolo, P. Tetrahedron 1997, 53, 7929, and references cited
therein) occurs at the C(2) carbon atom in a regioselective mode,
leading to sp-hybridized linear vinyl radicals having the unpaired
electron in the p orbital (Ref. 15). For reviews on radical addition
to alkynes see ref. 14.
1
high weight peaks (m/z.600). H NMR spectrum showed
unresolved bands in the aliphatic region and no vinylic
protons.
13. Oishi, K.; Kurosawa, K. Bull. Chem. Soc. Jpn 1980, 53, 179.
14. Chatgilialoglu, C.; Ferreri, C. Radical addition involving CC
triple bonds. In The Chemistry of Triple-bonded Functional
Groups; Patai, S., Ed.; Wiley: New York, 1994; Suppl. C2, Vol.
2, Chapter 16; Curran, D. P. Radical addition reactions. In
Comprehensive Organic Synthesis; Pergamon: Oxford, UK,
1991; Vol. 4, Chapter 4.1.
From 1g and 1h. The reaction mixture consisted of a thick
oil (380 mg). MS spectrum showed high weight peaks
1
(m/z.600). H NMR spectrum showed unresolved bands
in the aliphatic region and no vinylic protons.
Acknowledgements
15. Korth, H.-G.; Lusztyk, J.; Ingold, K. U.; J. Chem. Soc., Perkin
Trans. 2 1990, 1997; Bennett, J. E.; Howard, J. A. Chem. Phys.
Lett. 1971, 9, 460.
Á
Work supported by the Ministero dell'Universita e della
Ricerca Scienti®ca e Tecnologica (MURST) (funds 60%
and 40%) and by University of Bologna (funds for selected
research topics A.A. 1997±99).