Photosensitized oxidation of furans. 20. A novel thermal rearrangement of suitably substituted alkoxyfuran endoperoxides via neighboring-group mechanism: Synthesis and reactivity of the first functionalized 2-oxetanyl hydroperoxides

Full text of DOI:10.1021/jo0102112

4732
J . Org. Chem. 2001, 66, 4732-4735
P h otosen sitized Oxid a tion of F u r a n s. 20.1 A
Novel Th er m a l Rea r r a n gem en t of Su ita bly
Su bstitu ted Alk oxyfu r a n En d op er oxid es
via Neigh bor in g-Gr ou p Mech a n ism :
Sch em e 1
Syn th esis a n d Rea ctivity of th e F ir st
F u n ction a lized 2-Oxeta n yl Hyd r op er oxid es
M. R. Iesce,*,† F. Cermola,† F. De Lorenzo,†
I. Orabona,‡ and M. L. Graziano†
Dipartimento di Chimica Organica e Biochimica and
Dipartimento di Chimica, Universita` degli Studi di Napoli
Federico II, Complesso Universitario Monte Sant’ Angelo,
via Cinthia, I-80126, Napoli, Italy
iesce@unina.it
Received February 26, 2001
In tr od u ction
Our recent studies on the dye-sensitized photooxygen-
ation of 2-alkoxyfurans 1 have strongly evidenced the
high synthetic potential of the related endoperoxides 2.
These compounds are thermally unstable and take dif-
ferent rearrangement pathways strictly depending on the
nature of the substituent at C5.2 In any case, the driving-
force of these conversions is the facile loosening of the
C1-O2 bond due to the presence of an ortho ester
function in a strained bicyclic structure.2 The rationale
of the mechanisms involved has provided the develop-
ment of selective synthetic procedures for a large variety
of organic compounds, from new peroxidic systems to
already known compounds but whose classical approach
is difficult or unsuccessful.2,3
Within the research work on synthesis and use of
organic peroxides,2,3 we have now examined the reaction
of singlet oxygen with the hydroxyalkyl-substituted
2-alkoxyfurans 1 purposely prepared to enlarge the
synthetic applicability of the related endoperoxides 2.
oxetanes 3b-f in very high yields. As expected due to
the presence of an additional stereogenic center, 3e and
3f were obtained as diastereomeric mixtures in ca. 1:1
and 2:1 molar ratios, respectively.5 For entry g, the only
reaction product was the Z-keto ester 4g,4 and evidence
for oxetane 3g was just obtained by carrying out the
oxygenation at -75 °C.6
Resu lts a n d Discu ssion
The structural assignments of hydroperoxy oxetanes
3 were based on the spectral data, in particular, on the
appearance in the 13C NMR spectra of signals in the
range of δ 80-115 for the saturated carbon atoms in the
heterocyclic ring and, in addition to the ester values, of
signals in the range of δ 160-165 due to the ring carbon
which is part of the exocyclic double bond. In the MS
spectra the molecular ions are not observed but all of
them displayed fragment ions at [M - 33]+ due to the
loss of the OOH radical.7 The structure of 3b, which was
solid and could be purified by recrystallization, was
additionally proven by X-ray diffraction.8
The methylene blue-sensitized oxygenation of 1a was
carried out at -20 °C in CH2Cl2. Unexpectedly, the
reaction product was the hydroperoxy oxetane 3a , in
addition to trace amounts of the Z-keto ester 4a (Scheme
1). The peroxidic nature of 3a was tested by treatment
with Et2S, which rapidly and quantitatively led to 4a .
The latter was isolated and fully characterized (see
below),4 while compound 3a decomposed on contact with
chromatographic adsorbents.
Similar behavior was also observed starting from the
2-methoxyfurans 1b-f which provided the corresponding
† Dipartimento di Chimica Organica e Biochimica.
‡ Dipartimento di Chimica.
(1) Part 19: Iesce, M. R.; Cermola, F.; Guitto, A.; Scarpati, R.;
Graziano, M. L. Synlett 1995, 1161.
(2) Scarpati, R.; Iesce, M. R.; Cermola, F.; Guitto, A. Synlett 1998,
17.
(3) See for example: Iesce, M. R.; Cermola, F.; Guitto, A. Synlett
1999, 417; Iesce, M. R.; Cermola, F.; Guitto, A. Giordano F. J . Chem.
Soc., Perkin Trans. 1 1998, 475; and references therein.
(4) Stereochemistry has been assigned on the basis of the upfield
value of the CO2Me protons (δ 3.46) in the 1H NMR due to the
anisotropy of the aromatic ring which lies at the same side.
(5) Stereochemistry not assigned.
(6) Control experiments showed that 3g does not convert into 4g
under oxygenation conditions (see Experimental Section).
(7) Other fragment ions were also observed mainly due to primary
and secondary fragmentations of oxetane system: Searles, S. In
Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Eds.; Pergamon Press: New York, 1984; Vol. 7, part 5, p 368.
(8) Crystal structure of compound 3b is available in Supporting
Information. Crystallographic data have been deposited with Cam-
bridge Crystallographic Data Center, 12 Union Road, Cambridge, CB2
1EZ, UK.
10.1021/jo0102112 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/02/2001

Notes
J . Org. Chem., Vol. 66, No. 13, 2001 4733
Sch em e 2
Sch em e 3
Oxetanes 3a -f were similarly obtained even when the
oxygenation was performed in methanol at -20 °C.
Usually, this solvent adds to furan endoperoxides afford-
ing the corresponding 2,5-dihydrofurans, and the reaction
represents one of the most significant trapping modes for
these unstable peroxidic species.2,9 Neverthless, no traces
of dihydrofurans were present in the reaction mixtures
from 1a -f while the exception was still observed for 1g
which led quantitatively to the corresponding 2,5-dihy-
drofuran 5g.
For entries a -f, the inability of methanol to trap the
related endoperoxides 2 suggests that compounds 3 are
formed by an intramolecular reaction faster than the
methanol addition. Indeed, the obtaining of 3 can be
explained considering that a neighboring-group mecha-
nism is operating in the thermal conversion of the
unstable corresponding endoperoxides 2.10 While the C1-
O2 bond is loosening,11 the hydroxy substituent, when
well oriented as in [B], gives an intramolecular nucleo-
philic attack to C4, as shown in Scheme 2.13
The different course for 2g can be explained by two
factors: i, the lower nucleophilicity of the secondary OH
(entry g) than that of the tertiary ones (entries a -f); ii,
the conformer [B] which is well oriented to the nucleo-
philic attack is sterically unfavored when R2 is a hydro-
gen. Thus, at -20 °C for 2g the interconversion of the
rotamers is slower than the thermal decomposition into
4g in CH2Cl2,14 or than the methanol trapping. The
formation of 3g, albeit in low yield, at -75 °C in CH2Cl2
confirms this hypothesis.
Indeed, treatment with an equimolecular amount of Et2S
quantitatively and stereoselectively led to the Z-keto
ester 4a , while acid-catalyzed hydrolysis gave, in fair
yield, the 5-hydroperoxyfuran-2(5H)-one 6a in addition
to 4a (Scheme 3).17 It is interesting to note that a similar
behavior has been previously observed for the methanol-
trapped products such as 2,5-dihydrofurans 5.18,19
Con clu sion
This work reports an easy one-pot method for the first
functionalized 2-oxetanyl hydroperoxides 3, starting from
the furans 1, via a novel thermal conversion of methoxy-
furan endoperoxides 2. As indicated by preliminary
investigations, compounds 3 can be used as starting
material both for the highly functionalized Z-keto esters
4, very usable intermediates in organic synthesis,18 and
for furanones 6, which belong to a class of compounds of
both biological and applicative interest.19
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. IR spec-
1
tra were recorded with chloroform as solvent. H and 13C NMR
spectra were run in CDCl3 at 400 and 100.6 MHz. Chemical
shifts are reported in ppm referenced to TMS. Elemental
analyses were obtained using a Carlo Erba EA 1108-Elemental
Analyzer. Low-resolution electron impact mass spectra were
obtained operating at 70 eV on a GCMS-QP5050A (Shimadzu).
The solvents used for the reactions were anhydrous. Methylene
blue (MB) (Fluka), ethylmagnesium bromide (1 M in tert-butyl
methyl ether, Aldrich), phenylmagnesium bromide (3 M in
diethyl ether, Aldrich), sodium borohydride (Aldrich), and diethyl
sulfide (Aldrich) were used without purification. Methyl 2-meth-
oxy-5-phenylfuran-4-carboxylate,20 methyl 2-methoxy-5-(4-bro-
mophenyl)furan-4-carboxylate,19 and 4-acetyl-2-methoxy-5-phe-
nylfuran20 used as starting compounds for 1 were prepared as
previously reported. Silica gel (0.063-0.2 mm Macherey-Nagel)
and light petroleum (bp 40-60 °C) were used for column
chromatography.
Compounds 3 are the first examples of functionalized
2-oxetanyl hydroperoxides16 and, as exemplified by de-
rivative 3a , exhibit interesting chemical properties.
(9) Gollnick, K.; Griesbeck, A. Tetrahedron 1985, 41, 2057.
(10) Although the neighboring-group participation is important
when a five- or six-membered intermediate is formed, the likelihood
of four-membered analogue is increased when there are alkyl groups
R or â to the neighboring-group: Advanced Organic Chemistry; March,
J ., Ed.; Wiley: New York, 1992; p 311.
(11) The presence of the OMe group is determinant. Indeed, control
experiments showed that in the oxygenation, in CH2Cl2, of the 2,5-
diphenylfuran substituted in â as 1a no trace of an oxetanyl hydrop-
eroxide as 3a was observed and, as reported for other diarylfurans,12
only the corresponding cis-1,2-dibenzoyloxirane was detected [Selected
1H NMR signals (CDCl3): δ 1.13 and 1.26 (2 × t, J ) 7.0 Hz, 6 H, 2 ×
CH3), 1.60-1.90 (m, 4 H, 2 × CH2), 4.78 (s, 1 H, CHepoxidic), 7.40-8.20
(m, 10 H, Ar)].
CAUTION: since organic peroxides are potentially hazardous
compounds, they must be handled with care. No particular
difficulties were experienced in handling any of the new perox-
ides reported in this work.
(12) Graziano, M. L.; Iesce, M. R.; Chiosi, S.; Scarpati, R. J . Chem
Soc., Perkin Trans. 1 1983, 2071.
(13) On the basis of the proposed mechanism, the diastereoselec-
tivity observed for entries f, g should be the same to the face-selectivity
in the endoperoxide formation step. If and how this selectivity is
influenced by the hydroxy group, it has not been investigeted.
(14) cis-1,4-Dicarbonyl compounds are generally formed in the
singlet oxygen oxygenation of furans via the corresponding endoper-
oxides.2,15
Substrates 1a-f were prepared by reactions of methyl 2-meth-
oxy-5-phenylfuran-4-carboxylate (for 1a ,b), methyl 2-methoxy-
5-(4-bromophenyl)furan-4-carboxylate (for 1c,d ), and 4-acetyl-
(17) The presence, in 3a , of keto ester 4a as the impurity has no
influence since the latter is a reaction product in both the cases.
(18) Iesce, M. R.; Cermola, F.; Piazza, A.; Scarpati, R.; Graziano,
M. L. Synthesis 1995, 439.
(15) Bloodworth, A. J .; Eggelte, H. J . In Singlet O2; Frimer, A. A.,
Ed.; CRC Press: Boca Raton, FL, 1985; Vol. II, p 166.
(16) Only the parent 2-oxetanyl hydroperoxide has been reported
whose data are not easily consultable: Rakhimova, T. F.; Litinskii, A.
O.; Nikishin, G. I.; Glukhovtsev, V. G. Khim. Khim. Teknol. 1986, 29,
38; Chem. Abstr. 1986, 105,133097v.
(19) Iesce, M. R.; Cermola, F.; Graziano, M. L.; Scarpati, R. Synthesis
1994, 944.
(20) Graziano, M. L.; Iesce, M. R.; Cimminiello, G.; Scarpati, R. J .
Chem. Soc., Perkin Trans. 1 1988, 1699.

4734 J . Org. Chem., Vol. 66, No. 13, 2001
Notes
2-methoxy-5-phenylfuran (for 1e, f) with EtMgBr or PhMgBr
according to standard protocols.21,22 A representative example
is here reported for 1a : to the stirred commercial solution of
EtMgBr (3 equiv, 3 mL) was added methyl 2-methoxy-5-
phenylfuran-4-carboxylate (1 mmol) in dry Et2O (3 mL) drop-
wise. After stirring for 5 h at room temperature, the mixture
was poured into water (3 mL) and slightly acidified with 2 N
HCl, the ether layer separated, and the aqueous layer extracted
with Et2O (3 × 3 mL). The combined organic solutions were dried
over MgSO4. Then the solvent was evaporated and the mixture
chromatographed on a short column of silica gel with light
petroleum/Et2O (8:2) to give 4-(1-eth yl-1-h yd r oxyp r op yl)-2-
m eth oxy-5-p h en ylfu r a n (1a ): yield 90%; oil; IR (CHCl3) 3600,
furans 1a -f (0.5 mmol), after the addition of the sensitizer
(4 × 10-3 mmol), was irradiated at -20 °C with a halogen lamp
(General Electric, 650 W). During irradiation, dry oxygen was
bubbled through the solution, which was kept at this temper-
ature. When each reaction was complete (3 h), the solvent was
removed under reduced pressure at room temperature and the
residue analyzed by 1H NMR. After removal of the solvent, for
entries a ,c-f each residue was taken up in dry Et2O, the
suspension filtered to remove Methylene Blue, and the filtrate
evaporated to give the hydroperoxy oxetanes 3a -f. All the
attempts to purify 3 chromatographically failed since they
decompose on contact with the adsorbents. Derivative 3b was
obtained pure by two subsequent recrystallizations with
CH2Cl2/n-hexane.
3460 cm-1 1H NMR (CDCl3) δ 0.89 (t, J ) 7.1 Hz, 6 H), 1.59
;
(brs, 1 H), 1.77 (q, J ) 7.1 Hz, 4 H), 3.84 (s, 3 H), 5.10 (s, 1 H),
7.20-7.70 (m, 5 H); 13C NMR (CDCl3) δ 8.1, 34.4, 57.6, 75.1,
81.5, 127.2, 127.4, 127.7, 128.8, 132.0, 139.5, 160.2. Anal. Calcd
for C16H20O3 (260.32): C, 73.82; H, 7.74. Found: C, 73.7; H, 7.8.
4-(Hyd r oxyd ip h en ylm et h yl)-2-m et h oxy-5-p h en ylfu r a n
Meth yl 2-(4,4-d ieth yl-2-h yd r op er oxy-2-p h en yl-3-oxeta -
n ylid en e)a ceta te (3a ): 88% yield (with a purity of 90%); oil;
IR (CHCl3) 3510, 3316, 1724 cm-1; 1H NMR (CDCl3) δ 0.88 and
1.00 (2 x t, J ) 7.3 Hz, 6 H), 1.58-2.20 (m, 4 H), 3.78 (s, 3 H),
5.89 (s, 1 H), 7.35-7.80 (m, 5 H), 9.68 (brs, 1 H); 13C NMR
(CDCl3) δ 7.4, 7.9, 28.0, 28.2, 52.1, 88.6, 112.1, 113.3, 127.1,
128.2, 129.6, 136.8, 162.7, 165.5; MS (EI) m/z 259 (M+ - 33),
227, 215, 105, 77, 57.
1
(1b): yield 88%; oil; IR (CHCl3) 3589 cm-1; H NMR (CDCl3) δ
3.05 (brs, 1 H), 3.78 (s, 3 H), 4.74 (s, 1 H); 7.20-7.50 (m, 15 H);
13C NMR (CDCl3) δ 57.7, 78.5, 84.8, 127.0, 127.3 (overlapping
doublets), 128.0 (overlapping doublets), 128.9, 131.1, 139.9,
146.7, 159,5. Anal. Calcd for C24H20O3 (356.40): C, 80.88; H, 5.66.
Found: C, 80.7; H, 5.6.
Meth yl 2-(2-h yd r op er oxy-2,4,4-tr ip h en yl-3-oxeta n ylid e-
n e)a ceta te (3b): 90% (with a purity of 90%) [57% isolated yield
by recrystallization]; mp 167-168 °C (dec); IR (CHCl3) 3500,
3318, 1720 cm-1; 1H NMR (CDCl3) δ 3.78 (s, 3 H), 6.20 (s, 1 H),
7.20-7.65 (m, 15 H), 9.46 (brs, 1 H); 13C NMR δ 52.1, 88.3,
113.2, 116.6, 126.1, 126.5, 127.3, 127.8, 127.9, 128.2, 128.6, 129.4,
135.5, 141.3, 142.5, 160.4, 165.2. Anal. Calcd for C24H20O5
(388.40): C, 74.21; H, 5.19. Found: C, 74.4; H, 5.3; MS (EI) m/z
355 (M+ - 33), 323, 295, 250, 206, 105, 77.
5-(4-Br om op h en yl)-4-(1-eth yl-1-h yd r oxyp r op yl)-2-m eth -
oxyfu r a n (1c): yield 92%; oil; IR (CHCl3) 3598 cm-1; 1H NMR
(CDCl3) δ 0.88 (t, J ) 7.1 Hz, 6 H), 1.65 (brs, 1 H), 1.75 (q, J )
7.1 Hz, 4 H), 3.86 (s, 3 H), 5.08 (s, 1 H), 7.40-7.65 (m, 4 H); 13
C
NMR (CDCl3) δ 8.0, 34.1, 57.5, 75.3, 81.8, 121.1, 128.2, 130.2,
130.8, 131.8, 138.6, 160.4. Anal. Calcd for C16H19O3Br (339.23):
C, 56.65; H, 5.65. Found: C, 56.7; H, 5.6.
Meth yl 2-[2-(4-br om op h en yl)-4,4-d ieth yl-2-h yd r op er oxy-
3-oxeta n ylid en e]a ceta te (3c): 92% yield (with a purity of
5-(4-Br om op h en yl)-4-(h yd r oxyd ip h en ylm eth yl)-2-m eth -
oxyfu r a n (1d ): yield 65%; mp 156-158 °C; IR (CHCl3) 3597
cm-1; 1H NMR (CDCl3) δ 2.89 (brs, 1 H); 3.79 (s, 3 H); 4.73 (s, 1
H), 7.20-7.50 (m, 14 H); 13C NMR (CDCl3) δ 57.7, 78.4, 85.0,
120.8, 127.2, 127.4, 127.8, 128.0, 128.6, 129.6, 129.9, 130.9, 146.3,
159.6. Anal. Calcd for C24H19O3Br (435.31): C, 66.21; H, 4.40.
Found: C, 66.1; H, 4.4.
4-(1-H yd r oxy-1-m et h y1p r op yl)-2-m et h oxy-5-p h en ylfu -
r a n (1e): yield 60%; oil; IR (CHCl3) 3597 cm-1; 1H NMR (CDCl3)
δ 0.89 (t, J ) 7.1 Hz, 3 H), 1.49 (s, 3 H), 1.60 (brs, 1 H), 1.81 (q,
J ) 7.1 Hz, 2 H), 3.87 (s, 3 H), 5.16 (s, 1 H), 7.30-7.70 (m, 5 H);
13C NMR (CDCl3) δ 8.4, 29.0, 35.6, 57.4, 72.2, 81.4, 127.1, 127.7,
128.7, 129.1, 131.9, 138.9, 160.0. Anal. Calcd for C15H18O3
(246.29): C, 73.14; H, 7.37. Found: C, 73.2; H, 7.3.
4-(1-H yd r oxy-1-p h e n yle t h yl)-2-m e t h oxy-5-p h e n ylfu -
r a n (1f): yield 90%; oil; IR (CHCl3) 3596 cm-1; 1H NMR (CDCl3)
δ 1.83 (s, 3 H), 2.40 (brs, 1 H), 3.90 (s, 3 H), 5.35 (s, 1 H), 7.10-
7.70 (m, 10 H); 13C NMR (CDCl3) δ 32.5, 57.7, 73.3, 82.7, 125.4,
127.0, 127.1, 127.4, 128.0, 128.2, 129.4, 131.3, 139.3, 147.8, 160.0.
Anal. Calcd for C19H18O3 (294.33): C, 77.53; H, 6.16. Found: C,
77.6; H, 6.1.
1
>90%); IR (CHCl3) 3509, 3309, 1729 cm-1; H NMR (CDCl3) δ
0.89 and 0.98 (2 × t, J ) 7.7 Hz, 6 H); 1.53-2.28 (m, 4 H); 3.77
(s, 3 H), 5.90 (s, 1 H), 7.40-7.65 (m, 4 H), 9.99 (brs, 1 H); 13C
NMR (CDCl3) δ 7.3, 7.4, 27.8, 28.2, 52.0, 89.1, 112.1, 113.6, 123.8,
129.0, 131.2, 135.7, 162.1, 164.9; MS (EI) m/z 337/339 (M+/M++2
- 33), 305/307, 183/185, 155/157, 57.
Meth yl 2-[2-(4-br om op h en yl)-2-h yd r op er oxy-4,4-d ip h e-
n yl-3-oxeta n ylid en e]a ceta te (3d ): 93% yield (with a purity
1
of >90%); IR (CHCl3) 3516, 3271, 1728 cm-1; H NMR (CDCl3)
δ 3.77 (s, 3 H), 6.18 (s, 1 H), 7.20-7.70 (m, 14 H), 9.40 (brs, 1
H); 13C NMR (CDCl3) δ 52.2, 88.6, 112.6, 116.8, 124.0, 126.0,
126.4, 128.0, 128.2, 128.3 (two overlapping d), 129.2, 131.0,
134.6, 141.1, 142.3, 160.0, 165.0; MS (EI) m/z 433/435 (M+/M++2
- 33), 401/403, 373/375, 183/185, 155/157, 105, 77.
Meth yl 2-(4-eth yl-2-h yd r op er oxy-4-m eth yl-2-p h en yl-3-
oxeta n ylid en e)a ceta te (3e) (mixture of diastereomers in ca.
1
1:1): 90% yield (with a purity of 90%); H NMR (CDCl3) δ 0.92
and 1.04 (2 × t, J ) 7.3 Hz, 6 H), 1.44 (s, 3 H), 1.55-2.20 (m)
and 1.60 (s) (together 7 H), 3.75 and 3.76 (2 × s, 6 H), 5.85 (s, 2
H), 7.25-7.80 (m, 10 H), 10.05 (brs, 1 H), 10.24 (brs, 1 H); 13C
NMR (CDCl3) δ 7.6, 8.0, 22.6, 23.0, 32.0, 32.2, 51.8 (two
overlapping q), 86.1, 86.5, 112.0, 112.4, 113.0, 113.5, 127.2 (two
overlapping d), 128.1(two overlapping d), 128.5, 129.4, 136.3,
136.6, 162.9, 163.4, 165.1 (two overlapping s); MS (EI) m/z 245
(M+ - 33), 213, 201, 105, 77, 43.
Furan 1g was prepared as follows: to the solution of 4-acetyl-
2-methoxy-5-phenylfuran (1 mmol) in MeOH (3 mL), cooled to
0 °C, was added NaBH4 (1 mmol) in portions. After warming up
to room temperature, the reaction mixture was stirred for 12 h.
Then the solution was concentrated and water (2.5 mL) was
added. The resulting mixture was extracted with CH2Cl2 (3 × 5
mL), the combined organic phases were dried, and, after
evaporation of the solvent, the residue was chromatographed
on silica gel (light petroleum/Et2O 3:2) to give 4-(1-h yd r oxy-
eth yl)-2-m eth oxy-5-p h en ylfu r a n (1g): yield 85%; oil;21 IR
Meth yl 2-(2-h yd r op er oxy-4-m eth yl-2,4-d ip h en yl-3-oxeta -
n ylid en e)a ceta te (3f) (mixture of diastereomers in ca. 2:1):
1
93% yield (with a purity >90%); H NMR (CDCl3) δ 1.84* (s, 3
H), 1.98 (s, 3 H), 3.73* (s, 3 H), 3.75 (s, 3 H), 6.08* (s, 1 H), 6.22
(s, 1 H), 7.15-7.85 (m, 20 H), 9.69* (brs, 1 H), 10.61 (brs, 1 H);
13C NMR (CDCl3) δ 27.9*, 28.3, 51.9 (two overlapping q), 85.5*,
86.2, 112.9*, 114.6*, 115.1, 115.3, 124.4 (two overlapping d),
126.9, 127.1, 127.6, 127.8, 128.2 (two overlapping d), 128.3,
128.6, 129.3, 129.6, 135.3, 136.4*, 142.0, 142.8*, 161.7, 162.4*,
164.7, 164.9* (* refers to the minor isomer). MS (EI) m/z 293
(M+ - 33), 261, 233, 105, 77, 43.
(CHCl3) 3600, 3320 cm-1 1H NMR (CDCl3) δ 1.53 (d, J ) 6.5
;
Hz, 3 H), 1.92 (brs, 1 H), 3.89 (s, 3 H), 5.11 (q, J ) 6.5 Hz, 1 H),
5.39 (s, 1 H), 7.20-7.60 (m, 5 H, C6H5); 13C NMR (CDCl3) δ 23.5,
57.6, 62.6, 79.7, 125.6, 126.7, 128.5, 130.6, 139.2, 160.9. Anal.
Calcd for C13H14O3 (218.24): C, 71.54; H, 6.47. Found: C, 71.4;
H, 6.5.
Similar results were obtained when the oxygenation of 1a -f
was carried as above using MeOH as solvent.
MB-Sen sitized P h otooxygen a tion of 2-Meth oxyfu r a n s
1a -f in CH2Cl2 a t -20 °C. Each solution (5 × 10-2 M) of the
MB-Sen sitized P h otooxygen a tion of 2-Meth oxyfu r a n 1g.
A solution of the furan 1g (0.5 mmol) in CH2Cl2, after the
addition of the sensitizer (4 × 10-3 mmol), was photooxygenated
at -20 °C as above. When the reaction was complete (3 h), the
solvent was removed under reduced pressure at room temper-
ature and the residue analyzed by 1H NMR showed the presence
(21) As previously reported for other 2-alkoxyfurans,22 compounds
1 are sensitive to air oxidation, particularly on silica gel, so that they
must be stored under N2.
(22) Wulff, W. D.; Gilbertson, S. R.; Springer, J . P. J . Am. Chem.
Soc. 1986, 108, 520.

Notes
J . Org. Chem., Vol. 66, No. 13, 2001 4735
of the only keto ester 4g which was purified by silica gel
chromatography with CHCl3 as eluent.
The residue, analyzed by 1H NMR, showed the presence of the
only keto ester 4a which was obtained in 90% yield by chroma-
tography on silica gel (light petroleum/ether 1:1).
Meth yl (Z)-3-ben zoyl-4-h yd r oxyp en t-2-en oa te (4g): 87%
yield; oil; IR (CHCl3) 3531, 3106, 1729, 1669 cm-1 1H NMR
;
Meth yl
(Z)-3-ben zoyl-4-eth yl-4-h yd r oxyh ex-2-en oa te
(4a ): mp 91-92 °C; IR (CHCl3) 3602, 1719, 1669, 1638 cm-1
;
(CDCl3) δ 1.32 (d, J ) 6.5 Hz, 3 H), 3.17 (brs, 1 H), 3.46 (s, 3H),
4.62 (dq, J ) 6.5,1.5 Hz, 1 H), 6.29 (d, J ) 1.5 Hz, 1 H), 7.40-
7.90 (m, 5 H); 13C NMR (CDCl3) δ 22.1, 51.6, 68.5, 117.4, 128.6,
128.9, 133.6, 135.6, 161.2, 165.5, 197.4. Anal. Calcd for C13H14O4
(234.24): C, 66.65; H, 6.02. Found: C, 66.7; H, 6.1.
1H NMR (CDCl3) δ 0.92 (t, J ) 7.2 Hz, 6 H), 1.68 (m, 4 H), 2.13
(brs, 1 H), 3.46 (s, 3 H), 6.17 (s, 1 H), 7.35-7.90 (m, 5 H); 13C
NMR (CDCl3) δ 7.5, 31.6, 51.5, 77.8, 118.8, 128.4 (two overlap-
ping d), 133.0, 136.7, 161.4, 165.3, 197.2. Anal. Calcd for
C16H20O4 (276.32): C, 69.54; H, 7.30. Found: C, 69.7; H, 7.4.
Acid Hyd r olysis of 3a . A solution (0.02 M) of 3a (0.5 mmol)
in acetone (25 mL) was treated with HCl (2 N, 0.2 mL) and kept
at room temperature. After 30 min acetone was removed, water
was added, and the mixture was extracted with CHCl3 (3 × 5
mL), dried (MgSO4), and evaporated. The residue, analyzed by
1H NMR, showed the presence of keto ester 4a and the
hydroperoxyfuranone 6a in 3:2 molar ratio, respectively. Chro-
matography on silica gel, eluting with CHCl3-EtOAc (100:0, 9:1),
gave successively the keto ester 4a (45%) and furanone 6a (38%).
4-(1-Eth yl-1-h yd r oxyp r op yl)-5-h yd r op er oxy-5-p h en ylfu -
r a n -2(5H)-on e (6a ): oil; IR (CHCl3) 3592, 3508, 3283, 1772
When the oxygenation was carried out at -75 °C, after
completion of the reaction (3 h), NMR analysis of the reaction
mixture performed either at this temperature or at room
temperature showed the presence of 3g (one isomer) and keto
ester 4g in ca. 1:8 molar ratio; this ratio did not change also
when the reaction mixture was kept for further 3 h under the
oxygenation conditions. Selected NMR data for 3g were deduced
by a careful analysis of the reaction mixture after the signals of
the keto ester 4g were subtracted. No spectroscopic evidence for
isomer of 3g was obtained likely due to its low concentration.
Met h yl 2-(2-h yd r op er oxy-4-m et h yl-2-p h en yl-3-oxet a -
n ylid en e)a ceta te (3g): Selected 1H NMR signals (CDCl3) δ 1.66
(d, J ) 6.3 Hz, 3 H), 3.80 (s, 3 H), 5.67 (dq, J ) 6.3, 1.8 Hz, 1 H),
5.90 (d, J ) 1.8 Hz, 1 H), 11.04 (brs, 1 H); selected 13C NMR
signals (CDCl3) δ 23.1, 51.7, 80.2, 110.7, 115.2, 159.0, 164.0.
When the reaction was carried out at -20 °C using methanol
as solvent, after completion of the reaction (3 h), NMR analysis
showed the presence of only dihydrofuran 5g as a diastereomeric
mixture in ca. 3:1 molar ratio. All attempts to isolate the
diastereomers chromatographically failed since both decompose
on contact with chromatographic adsorbents.
1
cm-1; H NMR (CDCl3) δ 0.54 (t, J ) 7.1 Hz, 3 H), 0.81 (t, J )
7.1 Hz, 3 H), 0.95-1.80 (m, 4 H), 2.65 (brs, 1 H), 5.95 (s, 1 H),
7.20-7.60 (m, 5 H), 10.90 (brs, 1 H); 13C NMR (CDCl3) δ 6.9,
7.6, 31.2, 31.8, 76.8, 113.4, 119.1, 126.4, 128.4, 129.8, 132.9,
170.7, 172.0. Anal. Calcd for C15H18O5 (278.29): C, 64.73; H, 6.52.
Found: C, 64.9; H, 6.6.
Ack n ow led gm en t. Financial Support from Murst
(PRIN 1999-2001) is gratefully acknowledged. NMR
spectra were run and crystallographic work was under-
taken at the Centro di Metodologie Chimico-Fisiche,
Universita` di Napoli Federico II. MS spectra were run
at the Laboratorio INCA (Interuniversity Consortium
Chemistry for the Environment) of Naples.
5-Hydr oper oxy-3-(1-h ydr oxyeth yl)-2,2-dim eth oxy-5-ph en -
yl-2,5-d ih yd r ofu r a n (5g) (mixture of diastereomers in ca. 3:1
1
molar ratio): 90% (with a purity of >90%); H NMR (CDCl3) δ
1.18* (d, J ) 6.8 Hz, 3 H), 1.40 (d, J ) 6.8 Hz, 3 H), 3.47, 3.48
and 3.49 (3 x s, 12 H), 4.11 (two overlapping q, J ) 6.8 Hz, 2 H),
6.05* and 6.08 (2 x s, 2 H), 7.30-7.60 (m, 10 H), 9.31 (brs, 1 H),
9.86* (brs, 1 H); 13C NMR (CDCl3) δ 21.4*, 21.8, 49.5 (two
overlapping q), 51.2 (two overlapping q), 61.6*, 63.3, 114.1,
114.8*, 122.0*, 122.1*, 122.6, 123.7, 126.1, 128.1, 128.4*, 128.7*,
136.4*, 136.7, 150.2*, 151.4, (* refers to the minor isomer).
Red u ction of 3a . A solution (0.05 M) of 3a (0.5 mmol) in
CH2Cl2 (10 mL) was treated with Et2S (54 mg, 0.6 mmol). After
30 min the solvent was removed together with the excess of Et2S.
Su p p or tin g In for m a tion Ava ila ble: Crystal structure
and tables of X-ray crystallographic data for compound 3b.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0102112