PhI(OAc)2-Promoted Rearrangement of the Hydroxyl Group: Ring Expansion of 4-Hydroxy-2-cyclobutenone to 2(5H)-Furanone in Comparison with Ring Cleavage of the α-Hydroxycycloalkanone to the ω-Formyl Ester

Article abstract of DOI:10.1021/jo990704v

Reaction of 4-hydroxy-2-cyclobutenones with PhI(OAc)₂ in 1,2-dichloroethane at reflux temperature gave rise to 5-acetoxy-2(5H)-furanones as a rearranged product, formation of which is explained by ring cleavage of the once formed hypervalent iodine intermediate and following recyclization of the resulting acyl cation with a carbonyl oxygen. Likewise, 5-methoxy-2(5H)-furanones were obtained in better yields by using methanol as both a solvent and a nucleophile. Extension of this reaction to simple 2-hydroxycycloalkanones resulted in ring cleavage to methyl ω-formylalkanoates under milder conditions. In this case, the mechanism is explained by known glycol cleavage with PhI-(OAc)₂.

Full text of DOI:10.1021/jo990704v

J . Org. Chem. 1999, 64, 8995-9000
8995
P h I(OAc)2-P r om oted Rea r r a n gem en t of th e Hyd r oxyl Gr ou p : Rin g
Exp a n sion of 4-Hyd r oxy-2-cyclobu ten on e to 2(5H)-F u r a n on e in
Com p a r ison w ith Rin g Clea va ge of th e r-Hyd r oxycycloa lk a n on e to
th e ω-F or m yl Ester
Masatomi Ohno*
Department of Materials Science and Engineering, Toyota Technological Institute,
2-12-1 Hisakata, Tempaku, Nagoya 468-8511, J apan
Isamu Oguri and Shoji Eguchi
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University,
Chikusa, Nagoya 464-8603, J apan
Received April 27, 1999
Reaction of 4-hydroxy-2-cyclobutenones with PhI(OAc)2 in 1,2-dichloroethane at reflux temperature
gave rise to 5-acetoxy-2(5H)-furanones as a rearranged product, formation of which is explained
by ring cleavage of the once formed hypervalent iodine intermediate and following recyclization of
the resulting acyl cation with a carbonyl oxygen. Likewise, 5-methoxy-2(5H)-furanones were obtained
in better yields by using methanol as both a solvent and a nucleophile. Extension of this reaction
to simple 2-hydroxycycloalkanones resulted in ring cleavage to methyl ω-formylalkanoates under
milder conditions. In this case, the mechanism is explained by known glycol cleavage with PhI-
(OAc)2.
Sch em e 1
Squaric acid (1) has been exploited as a useful C-4
synthon in organic syntheses,1 which are realized mainly
with 4-hydroxy-2-cyclobutenone derivatives 3 obtained
recombination between carbonyl and ketene ends was
estimated by the calculations,6 and such a unique process
is in fact utilized for a new annulation method by
Pattenden.7 Similar ring transformation was achieved by
the trigger of carbocation and carbene (carbenoid) inter-
mediates generated from diazo-functionalized 4-hydroxy-
2-cyclobutenones; the cationic route produced both
2-ylidenefuranone 7 and 4-cyclopentene-1,3-diones 8 but
the carbenoid route directed predominant formation of
8 via a metallacyclic intermediate.8
We have now envisaged an additional reaction involv-
ing an electron-deficient oxygen center for the above type
of ring transformation. To this end, an effective leaving
group is necessary on an oxygen atom and desirable to
be introduced on a hydroxyl group with ease. A hyper-
valent iodine reagent seems to satisfy these require-
ments. Facile displacement on hypervalent iodine with
nucleophiles and super-leaving ability of newly formed
hypervalent iodine intermediate have been highlighted
recently.9 On an amino group, Hofmann rearrangement
is known to be effected by such propensity (Scheme 3).10
On the other hand, none of rearrangements on a
hydroxyl group have yet been reported; because of
from 1.2 While tandem electrocyclic ring-opening and
-closure reactions have been demonstrated to be effective
for the ring transformation of 3 to poly-substituted six-
membered carbo- and heterocycles 4 (Scheme 1),1,3 an-
other reaction induced by a reactive intermediate is also
considered to be alternative and useful for ring expansion
to five-membered ring systems.4 Ring strain of 3 can be
relieved by the trigger of a reactive intermediate, and
the opened structure of this intermediate is ready for
recyclization with an unsaturated end. This sequence was
first realized in the radical-mediated reaction to give
2(5H)-furanones 5 via an oxy-centered radical and 4-cy-
clopentene-1,3-dione 6 via an carbon-centered radical
(Scheme 2).5 In the former case, unusual nonradical
(1) (a) Schmidt, A. H. Synthesis 1980, 961. (b) Liebeskind, L. S.
Tetrahedron 1989, 45, 3053. (c) Moore, H. W.; Yerxa, B. R. Chemtracts.
Org. Chem. 1992, 5, 273.
(2) (a) Kraus, J . L. Tetrahedron Lett. 1985, 26, 1867. (b) Reed, M.
W.; Polart, D. J .; Perri, S. T.; Foland, L. D.; Moore, H. W. J . Org. Chem.
1988, 53, 2477. (c) Liebeskind, L. S.; Fengl, R. W.; Wirtz, K. R.; Shawe,
T. T. J . Org. Chem. 1988, 53, 2482.
(3) For recent examples, see: (a) Sun, L.; Liebeskind, L. S. Tetra-
hedron Lett. 1997, 38, 3663. (b) Onofrey, T. J .; Gomez, D.; Winters,
M.; Moore, H. W. J . Org. Chem. 1997, 62, 5658. (c) Liu, F.; Liebeskind,
L. S. J . Org. Chem. 1998, 63, 2835. (d) Heileman, M. J .; Moore, H. W.
Tetrahedron Lett. 1998, 39, 3643.
(4) Ohno, M.; Yamamoto, Y.; Eguchi, S. Synlett 1998, 1167.
(5) Yamamoto, Y.; Ohno, M.; Eguchi, S. J . Am. Chem. Soc. 1995,
117, 9653.
(6) Yamamoto, Y.; Ohno, M.; Eguchi, S. J . Org. Chem. 1996, 61, 9264
(7) Boeck, B. D.; Herbert, N.; Pattenden, G. Tetrahedron Lett. 1998,
39, 6971.
(8) Ohno, M.; Noda, M.; Yamamoto, Y.; Eguchi, S. J . Org. Chem.
1999, 64, 707. For synthesis of dimethylgloiosiphone by a cationic
rearrangement, see: Paquette, L. A.; Sturino, C. F.; Dousso, P. J . Am.
Chem. Soc. 1996, 118, 9456.
10.1021/jo990704v CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/19/1999

8996 J . Org. Chem., Vol. 64, No. 25, 1999
Ohno et al.
Ta ble 1
Sch em e 2
entry compd
R
solventa time/temp. product [yield (%)]
1
2
3
4
5
6
7
8
9
9a
9a
9a
9a
9b
9c
9c
9d
9e
Me
Me
Me
Me
Bu
Ph
DM
DM
DE
T
DE
DE
DE
3 days/rt
2 days/reflux 10a [34]
10a [30]
6 h/reflux
6 h/reflux
6 h/reflux
6 h/reflux
6 h/reflux
6 h/reflux
6 h/reflux
10a [64]
10a [24]
10b [65]
10c [60]/12 [18]b
10c [84]
Ph/msc
CHdCH2 DE
2-furyl DE
10d /11 [43]d
11e [34]
a
b
DM: CH2Cl2. DE: ClCH2CH2Cl. T: Toluene. The compound
12 was a byproduct as a result of AcOH-catalyzed rearrangement.
c The reaction was carried out in the presence of 4A molecular
d
sieves (ms). The ratio of 10d /11 was determined to be 1/2 by
relative 1H NMR peak area.
reaction between them was examined by using 4-methyl-
substituted cyclobutenone 9a . Thus, 9a was treated with
a slight excess of PhI(OAc)2 in dichloromethane at room
temperature under exclusion of moisture. The reaction
took place quite slowly as judged by TLC analysis, and
the product was obtained in 30% yield by chromato-
graphic separation after stirring for 3 days. The structure
was determined to be 5-acetoxy-3,4-diethoxy-5-methyl-
2-(5H)-furanone (10a ) by direct comparison with an
authentic sample obtained by our previous method.5 As
the expected rearrangement was effected by the action
of PhI(OAc)2 on the hydroxyl group of cyclobutenone, we
next tried to improve the yield; reflux in dichloromethane
for 2 days slightly raised the yield to 34% and better yield
of 64% was obtained by reflux in 1,2-dichloroethane
within 6 h. Oppositely, the yield decreased to 24% at
higher temperature such as refluxing in toluene. We then
carried out the reaction of other cyclobutenones 9b-e
under refluxing conditions in 1,2-dichloroethane, and
comparative results were obtained (Table 1). In the
phenyl-substituted case (entry 6), 18% yield of a byprod-
uct, 4-ethoxy-3-phenyl-3-cycobutene-1,2-dione (12, Rd
Ph), was isolated as a result of acid-catalyzed rearrange-
ment.2b,c This was suppressed by addition of molecular
sieves to trap the formed acetic acid, and the yield was
increased to 84% (entry 7). The vinyl-substituted 9d gave
5-vinylfuranone 4d and (Z)-5-ethylidenefuranone 11 with
a ratio of 1:2 (1H NMR measurement).
Scheme 4 illustrates a plausible mechanism for the
formation of 2(5H)-furanones 10 by the PhI(OAc)2-
promoted rearrangement of 4-hydroxy-2-cyclobutenones
9. First, nucleophilic displacement on a hypervalent
iodine with hydroxyl group of 9 generates another
hypervalent iodine intermediate 13, which involves an
electron-deficient oxygen center susceptible to eliminative
ring opening to an acyl cation intermediate 14.11 Such a
ring-opening aptitude has been observed in radical-,
cation-, and carbene-triggered ring expansion of 4-hy-
droxy-2-cyclobutenones.4 Second, recyclization of this acyl
cation 14 with an carbonyl oxygen is a facile process to
Sch em e 3
similarity to Pb(OAc)4, the major applications of this
reagent fall into alcohol (phenol) oxidation and glycol
cleavage.9a Nevertheless, the exceeding ability as a
leaving group is expected to assist a rearrangement on
the hydroxyl group if it were cooperative with some
structural factor such as ring strain. This is the case for
4-hydroxy-2-cyclobutenones. We report here the first
example of PhI(OAc)2-promoted rearrangement of these
compounds and comparison with simple 2-hydroxycy-
cloalkanones.
Resu lts a n d Discu ssion
The starting 4-hydroxy-2-cyclobutenones 9 were pre-
pared from diethyl squarate (2) according to the estab-
lished procedure.5 PhI(OAc)2 is the reagent of choice for
the purpose because it is one of the most popular and
accessible hypervalent iodine compounds. Typically, the
(9) (a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: San Diego, 1997. (b) Kitamura, T.; Fujiwara, Y. Org.
Prep. Proc. Int. 1997, 29, 459. (c) Moriarty, R. M.; Vaid, R. K. Synthesis
1990, 431. (d) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990,
365. (e) Ochiai, M.; Nagao, Y. J . Synth. Org. Chem. J pn. 1986, 44,
660.
(10) Moriarty, R. M.; Khosrowshahi, J . S.; Awasthi, A. K.; Penmasta,
R. Synth. Commun. 1988, 18, 1179. For other rearrangements, see (a)
Ramsden, C. A.; Rose, H. L. J . Chem. Soc., Perkin Trans. 1 1997, 2319.
(b) Wipf, P.; Venkatraman, S. J . Org. Chem. 1996, 61, 8004. (c) De
Mico, A.; Roberto, M.; Piancatelli, G. Gazz. Chim. Ital. 1995, 125, 325.

PhI(OAc)2-Promoted Rearrangement of the Hydroxyl Group
J . Org. Chem., Vol. 64, No. 25, 1999 8997
Sch em e 4
Sch em e 5
give a furanone cation 15, which is trapped with an
acetate anion to give the final product 10 (and 11).12
Then, the above reaction was carried out in methanol
at reflux temperature. This solvent was used to avoid an
acid-catalyzed side reaction to give cyclobutenedione
(acetic acid should preferentially interact with a hydroxyl
group of largely existing solvent rather than of a reac-
tant) and to work as a nucleophile. A typical reaction is
again with 9a . Thus, the treatment under the same
conditions as above except using methanol as a solvent
for 2 h gave the expected rearrangement product, 3,4-
diethoxy-5-methoxy-5-methyl-2(5H)-furanone (16a ), in
79% yield. According to this procedure, other cyclobuten-
ones 9b-h were transformed to 5-methoxy-2(5H)-fura-
nones 16b-h (Scheme 5). Compared with the reaction
conducted in 1,2-dichloroethane, yields are better in
general and no byproduct 12 was obtained in the case of
phenyl-substituted 9c. Further, the vinyl-substituted 9d
gave a mixture of 5-vinylfuranone 16d and (Z)-5-eth-
ylidenefuranone 1713 with a ratio of 2:1 (reversal of entry
8 in Table 1), and the furyl-substituted 9e produced
5-[2(5H)-furylidene]furanone 1813 in 28% yield with a 1:1
E/Z ratio as an inseparable mixture together with 5-(2-
furyl)furanone 16e in 57% yield. Carbonyl- and alkynyl-
substituted furanones 16f-h were also obtained by this
method. The structures of these products were confirmed
by analogy with 5-acetoxyfuranones 10. For example, 16a
was characterized on the basis of spectral patterns
similar to 10a as follows; IR showed absorptions at 1771
and 1681 cm-1 (enone), and 1H NMR and 13C NMR
indicated reasonable signals at δ 1.61 (methyl) and 3.23
(methoxy) and at δ 23.1 (CH3), 50.8 (OCH3), 102.2 (C-5),
and 167.5 (C-2), respectively, and MS involved the
required M+ peaks at m/z 216. The ylidenefuranone
structure of 18 could be deduced even as a mixture;
(11) While the similar reaction was effected by both PhI(OAc)2 and
Pb(OAc)4, the mechanistic difference between them lies in the fate of
the initially formed intermediate ROIPh (OAc) and ROPb(OAc)3 (R )
2-oxo-3,4-diethoxy-3-cyclobutenyl). The latter case was proposed to
generate an oxy radical species from the above intermediate because
of the intrinsic nature of alkoxylead(IV) and the resemblance of
reactivity to the related hypoiodite (ref 5). The former case of
hypervalent iodine is likely to involve an oxy cation-like species (or
else an electron-deficient oxygen center), based on super-leaving ability
of this group. As an extreme, phenyliodinium(III) reagents have
recently been proposed to effect phenolic oxidation with the interven-
tion of phenoxenium ions as intermediates (Ku¨rti, L.; Herczegh, P.;
Visy, J .; Simonyi, M.; Antus, S.; Pelter, A. J . Chem. Soc., Perkin Trans.
1 1999, 379). The independent reaction course of ROIPh(OAc) from
that of ROPb(OAc)3 may be reflected in somewhat different product
distributions (e.g., entries 3, 5, and 8 in Table 1). At the ring expansion
step, stepwise (via acyl cation 14) and concerted (via 1,2-acyl shift)
processes are conceivable. Nevertheless, the former type of process was
favored in the related R-carbocation-induced ring expansion reaction
of cyclobutenones and cyclobutanones (ref 8 and its footnotes 5f and
12) and is believed to participate also in the present reaction. The
similar ring expansion route might be realized by using Me2SO/(COCl)2
(in this case Me2S is a leaving group); however, the reaction of 9a
resulted in the formation of 4-ethoxy-3-methyl-2-cyclobutene-1,2-dione
(12, R ) Me), indicating PhI(OAc)2 to be a useful reagent with a high
leaving ability for the aimed rearrangement.
1
chemical shifts observed in both H and 13C NMR spectra
were compatible with fully conjugated and thermody-
namically more stable 5-methoxy-2(5H)-furylidene rather
than deconjugated 3-methoxy-2(3H)-furylidene as a C-5
substituent (see Experimental Section).14
While methanol was employed as an external nucleo-
phile in the above reaction, intramolecular version may
be attained by locating a hydroxyl group within the same
molecule. Thus, 9i was prepared from 2 and benzyl
alcohol/BuLi-TMEDA15 and allowed to react with PhI-
(OAc)2. In this case, however, the reaction proceeded at
room temperature, and the expected spiro compound 21
to be formed according to Scheme 4 was not obtained.
The spectral data of the product were consistent with the
eight-membered lactone 20 rather than the furanone 21,
since a chiral carbon (such as C-5 of 21) was absent and
another carbonyl bond appeared instead of an ether bond;
methylene protons of ethoxy groups were no longer
diastereotopic as judged by simple quartet in 1H NMR,
and two carbonyl groups were indicated by absorptions
at 1738 and 1685 cm-1 in IR and signals at δ 166.3 and
(12) Liberated acetic acid seemed to play no significant role in the
rearrangement, since intentional removal of the acid caused the better
yield of the rearranged product (entry 7 in Table 1); thus, a glycol
cleavage pathway as depicted below is not likely.
(13) Predominant formation of the (Z)-isomer 17 from 9e was
suggested by analogy with the reaction of 9e to 11. In the case of 18,
no selectivity was observed because of no stereochemical difference
between (Z)- and (E)-isomers. PM3 calculations indicated that 17 was
more stable than the corresponding E-isomer by 4.1 kcal/mol but
energy difference was only 0.5 kcal/mol between (Z)- and (E)-18.
(14) Coupling constants of 2(5H)-furylidene (J 3,4 ) 5.8-6.0 Hz and
J 4,5 ) 1.0-1.2 Hz) were nicely correlated with those of 2,5-dihydrofu-
ran: Lozach, R.; Braillon, B. J . Magn. Reson. 1973, 12, 244.
(15) Meyer, N.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1978, 7,
521.

8998 J . Org. Chem., Vol. 64, No. 25, 1999
Ohno et al.
Sch em e 6
Sch em e 8
known to react with PhI(OAc)2 as its enolate form to give
a â-lactone.18 In the same manner employed for cy-
clobutenones 9, four- to seven-membered cycloalkanones
27a -d were treated with PhI(OAc)2 in methanol, and the
reaction was found to occur smoothly at room tempera-
ture. After chromatographic separation, the products
were obtained in moderate to good yields and identified
as methyl ω-formylalkanoate 28a -d by spectral com-
parison with authentic samples.19 In addition, the reac-
tion with benzoin (29) gave fragmented methyl benzoate
and benzaldehyde in nearly quantitative yield and 27%
yield (GLC), respectively. On the other hand, the reaction
of 27c in 1,2-dichloroethane was found to be suppressed,
and the related R-hydroxy ester (e.g., methyl lactate)
difficult to acetalize did not show any reactivity under
the same conditions as employed for R-hydroxy ketones.
These results imply the significancy of hemiacetal forma-
tion and agree with the glycol cleavage mechanism as
shown in Scheme 8.20 From a synthetic viewpoint, PhI-
(OAc)2 is known to be used in a way similar to Pb(OAc)4,
and this is also the case for bond-scission of R-ketols.21
In summary, the ring expansion reaction of 4-hydroxy-
2-cyclobutenones 9 was promoted by PhI(OAc)2 to give
2(5H)-furanones 10 and 16 (and, in some cases, 2-ylidene-
furanones 11, 17, and 18), providing the first example
for the rearrangement initiated by action of a hypervalent
iodine reagent on a hydroxyl group. The formation of
furanone products can be explained by tandem elimina-
tive ring opening to an acyl cation and its recyclization
with an carbonyl oxygen, and the first key-step resulted
from the high leaving ability of a hypervalent iodine
intermediate consonant with ring strain relief of a
cyclobutenone. Such a mechanism was operative in 1,2-
dichloroethane (as a solvent) and presumably also in
methanol (as both a solvent and a nucleophile). On the
other hand, an intramolecular version of the latter
reaction favored a glycol cleavage route, and this route
also participated with simple 2-hydroxycycloalkanones
27. Apart from the mechanism, PhI(OAc)2 is useful for
Sch em e 7
195.5 in 13C NMR. Mechanistically, the lactone formation
was elucidated by intramolecular hemiacetalization and
ring cleavage of the formed glycol 19 with PhI(OAc)2
leading to a different product (Scheme 6).
As the glycol cleavage route was revealed to participate
with the above intramolecular reaction, this might be also
the case for the intermolecular reaction with methanol
as shown in Scheme 7 (i.e., 9 f 22 f 23 f 16).
Nevertheless, the reactivity, which was reflected in the
foregoing reaction temperature (reflux conditions), seemed
to be fit for the acyl cation route via 14 rather than the
glycol cleavage route via 22 (cf., the reaction of 9a in 1,2-
dichloroethane vs those of 27a and 9i as described above
and below). Furthermore, the formation of an intermedi-
ate compound [for example, methyl (Z)-4-oxo-2,3-di-
ethoxy-2-pentenoate (23, R ) Me) from 9a ] was not found
throughout the reaction. Although 23 might cyclize to 16
with the aid of acetic acid, the following reaction is not
an exact but rather a suggestive reference. An olefinic
compound 24 with the cis relationship of acetyl and
alkoxycarbonyl groups, which was reported to lactonize
to 25 under p-TsOH-catalyzed conditions,16 underwent
only Michael addition to give 26 under refluxing condi-
tions in methanol with acetic acid. These facts inclined
us to suppose that the intermolecular reaction is different
from the intramolecular one and still obeys the same
(17) In this case the opened acyl cation 14 might be trapped with a
solvent to give 23, but this possibility could be subdued by preferential
cyclization of this cation with a proximate carbonyl end in the cis-
olefinic configuration
(18) Turuta, A. M.; Kamernitsky, A. V.; Fadeeva, T. M.; Zhulin, A.
V. Synthesis 1985, 1129.
(19) (a) Taylor, W. G. J . Org. Chem. 1981, 46, 4290. (b) Doleschall,
G.; Toth, G. Tetrahedron 1979, 36, 1649. (c) Claus, R. E.; Schreiber, S.
L. Org. Synth. 1986, 64, 150. (d) Finke, R. G.; Sorrell, T. N. Org. Synth.
1980, 59, 102.
(20) If the ring expansion mechanism was operative also for 27a , a
butyrolactone might be produced. However, this is not the case, and
the difference in reactivity between cyclobutenone such as 9a and
cyclobutanone such as 27a seems to be attributed to ring strain relief
of the four-membered rings and stabilization of the opened acyl cations
by conjugation, both of which are influenced by double vs single bond
nature adjacent to the carbonyl group. These are apparently advanta-
geous for 9a to undergo ring-opening.
17
mechanism as shown in Scheme 4.
Then, the above reaction was extended to simple
2-hydroxycycloalkanones, because it is interesting to
examine and compare with the hypervalent iodine chem-
istry of R-ketols. Until now, this class of compound is only
(16) Levison, B. S.; Miller, D. B.; Salomon, R. G. Tetrahedron Lett.
1984, 25, 4633.
(21) (a) Hazen, J . R. J . Org. Chem. 1970, 35, 973. (b) Crimmins, M.
T.; J ung, D. K.; Gray, J . L. J . Am. Chem. Soc. 1993, 115, 3146.

PhI(OAc)2-Promoted Rearrangement of the Hydroxyl Group
J . Org. Chem., Vol. 64, No. 25, 1999 8999
68.5, 101.2, 120.1, 122.0, 132.7, 155.0, 167.6; MS (EI) m/z
(relative intensity) 228 (M+, 76), 197 (38), 169 (32), 156 (49),
127 (100). Anal. Calcd for C11H16O5: C, 57.88; H, 7.07. Found:
C, 57.92; H, 7.05.
bond-scission of R-ketol as is Pb(OAc)4 and preferable to
that of the latter toxic reagent.
Exp er im en ta l Section
3,4-Die t h oxy-5-(2-m e t h oxye t h ylid e n e )-2(5H )-fu r a -
n on e (17). This was eluted as the second fraction and further
Gen er a l Rem a r k s. 1H and 13C NMR spectra were obtained
in CDCl3 or DMSO-d6 solution with SiMe4 as an internal
standard. 1,2-Dichloroethane was dried over CaCl2, distilled,
and kept over 4 Å molecular sieves, while THF was dried over
Na/Ph2CO and distilled before use. Methanol was dried over
3 Å molecular sieves. Flash chromatography was carried out
using a Fuji-Davison BW-300 with hexane (H) and ethyl
acetate (A) as an eluent. Squaric acid was provided by Kyowa
Hakko Kogyo Co., Ltd. Preparation of the squaric acid deriva-
tives 9a -h has been reported previously.5
Rep r esen ta tive P r oced u r e for th e Syn th esis of 10a -
e. To a solution of 9a (49 mg, 0.26 mmol) in 1,2-dichloroethane
(3 mL) was added PhI(OAc)2 (90 mg, 0.28 mmol) under
exclusion of moisture, and the solution was stirred at reflux
temperature for 6 h. After cooling, the solvent was removed
under vacuum, and the residue was chromatographed on a
silica gel column (H/A 10/1) to give 5-acetoxy-2(5H)-cyclobuten-
one 10a (40 mg, 64%). The other cyclobutenones 10b-e were
obtained in the same manner except elution with H/A 15/1
for 9b and 20/1 for 9c in yields shown in Table 1. For phenyl-
substituted 9c, the reaction was also carried out in the
presence of powdered 4 Å molecular sieves (300 mg) with the
yield increased to 84%. All of the products were identical with
those obtained by our previous method.5
purified as above: oil; IR (neat) 1777, 1687, 1655 cm-1 1H
;
NMR (CDCl3) δ 1.33 (3 H, t, J ) 7.0 Hz), 1.39 (3 H, t, J ) 7.0
Hz), 3.35 (3 H, s), 4.19 (2 H, d, J ) 7.0 Hz), 4.23 (2 H, q, J )
7.0 Hz), 4.94 (2 H, q, J ) 7.0 Hz), 5.45 (1 H, t, J ) 7.0 Hz); 13
C
NMR (CDCl3) δ 15.3, 15.4, 58.5, 65.7, 68.0, 68.6, 105.1, 123.8,
143.8, 148.4, 165; MS (EI) m/z (relative intensity) 228 (M+,
100), 197 (17), 169 (21), 156 (49). Anal. Calcd for C11H16O5:
C, 57.88; H, 7.07. Found: C, 57.94; H, 7.04.
3,4-Dieth oxy-5-(2-fu r yl)-5-m eth oxy-2(5H)-fu r an on e (16e).
This was eluted as the first fraction (H/A 10/1): oil; IR (neat)
1778, 1688 cm-1; 1H NMR (CDCl3) δ 1.34 (3 H, t, J ) 7.0 Hz),
1.36 (3 H, t, J ) 7.0 Hz), 3.40 (3 H, s), 4.21 and 4.27 (each 1
H, dq, J ) 7.0, 9.8 Hz), 4.47 and 4.54 (each 1 H, dq, J ) 7.0,
10.4 Hz), 6.40 (1 H, dd, J ) 1.8, 3.4 Hz), 6.59 (1 H, dd, J )
1.0, 3.4 Hz), 7.44 (1 H, dd, J ) 1.0, 1.8 Hz); 13C NMR (CDCl3)
δ 15.2, 15.3, 51.6, 68.4, 68.5, 99.0, 110.2, 110.8, 122.6, 143.9,
148.3, 153.6, 167.2; MS (EI) m/z (relative intensity) 268 (M+,
49), 237 (16), 195 (21), 167 (15), 111 (20), 95 (100). Anal. Calcd
for C13H16O6: C, 58.20; H, 6.01. Found: C, 58.19; H, 6.04.
3,4-Dieth oxy-5-[5-m eth oxy-2(5H)-fu r yliden e]-2(5H)-fu r a-
n on e (18). This was eluted as the second fraction and obtained
as an inseparable 1:1 E/ Z-mixture (oil). Attempted further
separation of these stereoisomers on thin-layer chromatogra-
phy caused gradual decomposition. Therefore the following
spectral data were analyzed as a mixture form; IR (neat) 1750,
1680, 1632 cm-1; 1H NMR (CDCl3) δ 1.33 and 1.34 (each 1/2 ×
3 H, t, J ) 7.0 Hz), 1.42 and 1.44 (each 1/2 × 3 H, t, J ) 7.0
Hz), 3.50 and 3.52 (each 1/2 × 3 H, s), 4.21 and 4.23 (each 1/2
× 2 H, q, J ) 7.0 Hz), 4.54 and 4.55 (each 1/2 × 2 H, q, J )
7.0 Hz), 6.15 and 6.25 (each 1/2 × 1 H, dd, J ) 1.2, 1.5 Hz and
1.0, 1.5 Hz, respectively), 6.27 and 6.29 (each 1/2 × 1 H, dd, J
) 1.5, 5.8 Hz and 1.5, 6.0 Hz, respectively), 6.89 and 6.94 (each
1/2 × 1 H, dd, J ) 1.0, 5.8 Hz and 1.2, 6.0 Hz, respectively);
13C NMR (CDCl3) δ 15.4 (overlapped 2C), 55.4 and 55.8, 68.2
and 68.4, 68.6 and 68.7, 110.7 and 112.1, 122.2 and 122.8,
123.9 and 124.1, 126.3 and 126.7, 132.3 and 133.4, 143.3 and
147.2, 150.4 and 150.7, 164.6 and 165.0; MS (EI) m/z (relative
intensity) 268 (M+, 100), 237 (50), 180 (46). Anal. Calcd for
Rep r esen ta tive P r oced u r e for th e Syn th esis of 16a -
h . To a solution of 6a (123 mg, 0.66 mmol) in methanol (3 mL)
was added PhI(OAc)2 (218 mg, 0.68 mmol) at room tempera-
ture under exclusion of moisture, and the solution was stirred
at reflux temperature for 2 h. The same workup and purifica-
tion as above gave 5-methoxy-2(5H)-cyclobutenone 16a (79 mg,
79%). The yields for 16b-h are summarized in Scheme 5.
3,4-Dieth oxy-5-m eth oxy-5-m eth yl-2(5H)-fu r an on e (16a):
Elution with (H/A 10/1); oil; IR (neat) 1771, 1687 cm-1 1H
;
NMR (CDCl3) δ 1.32 (3 H, t, J ) 7.0 Hz), 1.41 (3 H, t, J ) 7.0
Hz), 1.61 (3 H, s), 3.23 (3 H, s), 4.15 and 4.22 (each 1 H, dq, J
) 7.0, 9.6 Hz), 4.52 (2 H, q, J ) 7.0 Hz); 13C NMR (CDCl3) δ
15.30, 15.33, 23.1, 50.8, 68.1, 68.5, 102.2, 122.0, 155.2, 167.5;
MS (EI) m/z (relative intensity) 216 (M+, 86), 185 (31), 157
(47), 143 (100). Anal. Calcd for C10H16O5: C, 55.54; H, 7.46.
Found: C, 55.59; H, 7.45.
C
13H16O6: C, 58.20; H, 6.01. Found: C, 58.27; H, 6.06.
3,4-Diet h oxy-5-m et h oxy-5-p h en a cyl-2(5H )-fu r a n on e
5-Bu tyl-3,4-d ieth oxy-5-m eth oxy-2(5H)-fu r a n on e (16b):
(16f): Elution with (H/A 10/1); oil; IR (neat) 1779, 1693 cm-1
;
Elution with (H/A 12/1); oil; IR (neat) 1771, 1688 cm-1 1H
;
1H NMR (CDCl3) δ 1.33 (3 H, t, J ) 7.0 Hz), 1.36 (3 H, t, J )
7.0 Hz), 3.26 (3 H, s), 3.42 and 3.74 (each 1 H, d, J ) 15.6 Hz),
4.14 and 4.50 (each 1 H, dq, J ) 7.0, 9.8 Hz), 4.39 and 4.55
(each 1 H, dq, J ) 7.0, 10.2 Hz), 7.42-7.62 (3 H, m), 7.91-
7.97 (2 H, m); 13C NMR (CDCl3) δ 15.3 (2C), 43.2, 50.2, 68.2,
68.5, 101.6, 123.7, 128.8 (2C), 129.0 (2C), 133.8, 137.4, 153.0,
167.2, 194.7; MS (EI) m/z (relative intensity) 320 (M+, 28), 201
(15), 105 (100). Anal. Calcd for C17H20O6: C, 63.74; H, 6.29.
Found: C, 63.82; H, 6.30.
NMR (CDCl3) δ 0.89 (3 H, t, J ) 6.9 Hz), 1.32 (3 H, t, J ) 7.0
Hz), 1.41 (3 H, t, J ) 7.0 Hz), 1.23-1.39 (4 H, m), 1.76-1.97
(2 H, m), 3.23 (3 H, s), 4.16 and 4.22 (each 1 H, dq, J ) 7.0,
9.6 Hz), 4.51 (2 H, q, J ) 7.0 Hz); 13C NMR (CDCl3) δ 13.9,
15.3, 15.4, 22.5, 24.8, 35.6, 50.59, 68.0, 68.6, 104.2, 122.7, 154.4,
167.8; MS (EI) m/z (relative intensity) 258 (M+, 32), 227 (11),
201 (100). Anal. Calcd for C13H22O5: C, 60.44; H, 8.59. Found:
C, 60.51; H, 8.55.
3,4-Dieth oxy-5-m eth oxy-5-ph en yl-2(5H)-fu r an on e (16c):
Elution with (H/A 10/1); oil; IR (neat) 1773, 1684 cm-1 1H
;
5-(Ben zyloxycar bon ylm eth yl)-3,4-Dieth oxy-5-m eth oxy-
2(5H)-fu r a n on e (16 g): Elution with (H/A 10/1); oil; IR (neat)
NMR (CDCl3) δ 1.30 (3 H, t, J ) 7.0 Hz), 1.32 (3 H, t, J ) 7.0
Hz), 3.39 (3 H, s), 4.17 and 4.25 (each 1 H, dq, J ) 7.0, 9.6
Hz), 4.40 and 4.50 (each 1 H, dq, J ) 7.0, 10.2 Hz), 7.35-7.42
(3 H, m), 7.51-7.59 (2 H, m); 13C NMR (CDCl3) δ 15.1, 15.4,
51.6, 68.3, 68.6, 102.5, 122.0, 126.5 (2C), 128.7 (2C), 129.8,
136.1, 155.8, 167.9; MS (EI) m/z (relative intensity) 278 (M+,
97), 247 (26), 205 (21), 105 (100). Anal. Calcd for C15H18O5:
C, 64.73; H, 6.52. Found: C, 64.72; H, 6.55.
1
1779, 1743, 1692 cm-1; H NMR (CDCl3) δ 1.29 (3 H, t, J )
7.0 Hz), 1.35 (3 H, t, J ) 7.0 Hz), 2.97 and 3.07 (each 1 H, d,
J ) 15.2), 3.23 (3 H, s), 4.04 and 4.19 (each 1 H, dq, J ) 7.0,
9.8 Hz), 4.41 and 4.54 (each 1 H, dq, J ) 7.0, 10.3 Hz), 5.11 (2
H, s), 7.35 (5 H, s); 13C NMR (CDCl3) δ 15.3, 15.4, 40.7, 50.4,
67.0, 68.2, 68.5, 101.0, 123.5, 128.8 (3C), 129.0 (2C), 135.8,
152.7, 167.1, 167.7; MS (EI) m/z (relative intensity) 350 (M+,
20), 319 (1), 201 (7), 91 (100). Anal. Calcd for C18H22O7: C,
61.70; H, 6.33. Found: C, 61.70; H, 6.36.
5-Eth en yl-3,4-dieth oxy-5-m eth oxy-2(5H)-fu r an on e (16d).
This was eluted as the first fraction (H/A 10/1). The analytical
sample was obtained by further purification on preparative
3,4-Dieth oxy-5-m eth oxy-5-(p h en yleth yn yl)-2(5H)-fu r a -
n on e (16h ): Elution with (H/A 15/1); oil; IR (neat) 2234, 1780,
TLC (CHCl3) as an oil; IR (neat) 1772, 1685 cm-1 1H NMR
;
1
(CDCl3) δ 1.32 (3 H, t, J ) 7.0 Hz), 1.39 (3 H, t, J ) 7.0 Hz),
3.33 (3 H, s), 4.16 and 4.22 (each 1 H, dq, J ) 7.0, 9.6 Hz),
4.45 and 4.48 (each 1 H, dq, J ) 7.0, 9.8 Hz), 5.42 (1 H, dd, J
) 1.2, 10.4 Hz), 5.66 (1 H, dd, J ) 1.2, 17.2 Hz), 5.89 (1 H, dd,
J ) 10.4, 17.2 Hz); 13C NMR (CDCl3) δ 15.2, 15.3, 51.3, 68.3,
1691 cm-1; H NMR (CDCl3) δ 1.34 (3 H, t, J ) 7.0 Hz), 1.44
(3 H, t, J ) 7.0 Hz), 3.63 (3 H, s), 4.22 (2 H, q, J ) 7.0 Hz),
4.55 (2 H, q, J ) 7.0 Hz), 7.30-7.55 (5 H, m); 13C NMR (CDCl3)
δ 15.2, 15.4, 53.5, 68.5, 68.6, 80.4, 88.0, 95.7, 121.1, 122.0, 128.8
(2C), 130.0, 132.5 (2C), 154.1, 166.8; MS (EI) m/z (relative

9000 J . Org. Chem., Vol. 64, No. 25, 1999
Ohno et al.
intensity) 302 (M+, 17), 229 (30), 129 (100). Anal. Calcd for
7.0 Hz), 5.42 (2 H, s), 7.12-7.45 (4 H, m); 13C NMR (CDCl3) δ
15.4, 15.6, 66.9, 68.4, 68.9, 125.8, 126.9, 128.8, 130.4, 135.4,
136.6, 139.3, 154.8, 166.3, 195.5; MS (EI) m/z (relative
intensity) 276 (M+, 17), 203 (12), 174 (28), 135 (21), 118 (100).
Anal. Calcd for C15H16O5: C, 65.21; H, 5.84. Found: C, 65.20;
H, 5.85.
Attem p ted AcOH-Ca ta lyzed Rea ction of Eth yl 2-Ac-
eton ylid en em a lon a te (24). A solution of 2422 (64 mg, 0.3
mmol) in methanol (2 mL) including acetic acid (36 mg, 0.6
mmol) was refluxed for 2 h. The solvent and acetic acid were
removed under vacuum to give almost pure ethyl 2-(1-
methoxyacetonyl)malonate (26) as an oil (76 mg, 98%); IR
(neat) 1735 cm-1; 1H NMR (CDCl3) δ 1.28 (3 H, t, J ) 7.2 Hz),
1.29 (3 H, t, J ) 7.2 Hz), 2.31 (3 H, s), 3.51 (3 H, s), 3.93 (1 H,
d, J ) 6.8 Hz), 4.18 (1 H, dq, J ) 11.0, 7.2 Hz), 4.24 (1 H, dq,
J ) 11.0, 7.2 Hz), 4.25 (2 H, q, J ) 7.2 Hz) 13C NMR (CDCl3)
δ 14.0 (2C), 26.9, 54.4, 59.8, 62.0 (2C), 84.4, 167.2, 167.4, 208.5;
MS (CI) m/z (relative intensity) 247 (M+ + 1, 89), 215 (100),
169 (69). Anal. Calcd for C11H18O6: C, 53.65; H, 7.37. Found:
C, 53.70; H, 7.35.
Rep r esen ta tive P r oced u r e for th e Syn th esis of m eth yl
ω-for m yla lk a n oa te 28: To a solution of cyclohexanone 27c
(55 mg, 0.5 mmol) in methanol (2.5 mL) was added PhI(OAc)2
(161 mg, 0.5 mmol) under exclusion of moisture, and the
mixture was stirred at room temperature for 3 h. After
evaporation of the solvent, the residue was chromatographed
(H/A 3/1) to give methyl 6-oxohexanoate (28c) (64 mg, 88%).
The other reactions were carried out for periods of 1.5 h (27a ),
2 h (27b), and 12 h (27d ). The isolated yields were summarized
in Scheme 8. The reaction of benzoin (29) was carried out with
1.5 equiv of PhI(OAc)2 for 24 h, and the yield was estimated
with GLC (see text).
C
17H18O5: C, 67.54; H, 6.00. Found: C, 67.59; H, 5.98.
P r ep a r a tion of 3,4-Dieth oxy-4-h yd r oxy-4-[(2-h yd r oxy-
m eth yl)p h en yl)]-2-cyclobu ten on e (9i). To a solution of
benzyl alcohol (324 mg, 3 mmol) and tetramethylethylenedi-
amine (697 mg, 6 mmol) in pentane (12 mL) was added n-BuLi
(1.6 M hexane solution, 7.14 mL, 12 mmol) gradually at room
temperature under a nitrogen atmosphere, and the mixture
was refluxed for 11 h and diluted with THF (12 mL). To this
solution was added a solution of 2 (510 mg, 3 mmol) in THF
(6 mL) at -78 °C, and the mixture was stirred for 1 h. Then
1 N HCl (6 mL) was added at this temperature, and subse-
quently the solution was basified with sat. NaHCO3. The
product was extracted repeatedly with ether, while a separat-
ing funnel was cooled by adding ice. The extracts were
combined, washed with brine, and dried over Na2SO4. After
evaporation of the solvent, the residue was chromatographed
on a silica gel column (H/A 2/1) to give 9i (94 mg, 10%) as an
1
oil: IR (neat) 3335, 1769, 1622 cm-1; H NMR (DMSO-d6) δ
1.23 (3 H, t, J ) 7.0 Hz), 1.37 (3 H, J ) 7.0 Hz), 4.17 and 4.23
(each 1 H, dq, J ) 7.0, 10.4 Hz), 4.42 and 4.51 (each 1 H, dq,
J ) 7.0, 10.2 Hz), 4.88 (2 H, br s), 5.11 (1 H, br s), 6.61 (1 H,
s), 7.15-7.58 (5 H, m); 13C NMR (DMSO-d6) δ 15.0, 15.4, 61.3,
66.4, 69.5, 88.7, 126.0, 126.7, 127.8, 128.2, 132.4, 135.8, 142.4,
167.9, 186.0; MS (EI) m/z (relative intensity) 260 (M+ - 18,
16), 203 (65), 169 (21), 133 (40), 118 (100). Anal. Calcd for
C
15H18O5: C, 64.73; H, 6.52. Found: C, 64.81; H, 6.49.
Rea ction of 9i w ith P h I(OAc)2. To a solution of 9i (73
mg, 0.26 mmol) in methanol (3 mL) was added PhI(OAc)2 (85
mg, 0.26 mmol) under exclusion of moisture, and the solution
was stirred at room temperature for 1.5 h. After evaporation
of the solvent, the residue was chromatographed on a silica
gel column (H/A 10/1) to give 5,6-benzo-2,3-diethoxy-4-oxo-2-
hepten-7-olide (20) as an oil (50 mg, 70%); IR (neat) 1738, 1685,
J O990704V
1
1602 cm-1; H NMR (CDCl3) δ 1.33 (3 H, t, J ) 7.0 Hz), 1.41
(3 H, J ) 7.0 Hz), 4.02 (2 H, q, J ) 7.0 Hz), 4.25 (2 H, q, J )
(22) Ouall, M. S.; Vaulter, M.; Carrie, R. Synthesis 1977, 626.