Ring expansion of diazo-functionalized 4-hydroxycyclobutenone: Catalytic ring opening and recyclization to 2(5H)-furanone/cyclopentenedione and thermal 4π-8π electrocyclic ring opening-closure to diazepinedione

Article abstract of DOI:10.1021/jo980523d

The acid-catalyzed and Rh-catalyzed (also photolyzed) decomposition of 4-hydroxycyclobutenones with a diazo group at C-4 gave 2(5H)-furanone and/or cyclopentene-1,3-dione via an α-carbocation intermediate and a carbenoid (carbene) intermediate, respectively. Thermal rearrangement of some of these compounds led to the formation of diazepinediones without the extrusion of nitrogen through tandem 4π electrocyclic ring opening and 8π electrocyclic ring closure processes.

Full text of DOI:10.1021/jo980523d

J . Org. Chem. 1999, 64, 707-712
707
Rin g Exp a n sion of Dia zo-F u n ction a lized 4-Hyd r oxycyclobu ten on e:
Ca ta lytic Rin g Op en in g a n d Recycliza tion to 2(5H)-F u r a n on e/
Cyclop en ten ed ion e a n d Th er m a l 4π-8π Electr ocyclic Rin g
Op en in g-Closu r e to Dia zep in ed ion e
Masatomi Ohno,* Masashi Noda, Yoshihiko Yamamoto, and Shoji Eguchi*
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University,
Chikusa, Nagoya 464-8603, J apan
Received March 19, 1998
The acid-catalyzed and Rh-catalyzed (also photolyzed) decomposition of 4-hydroxycyclobutenones
with a diazo group at C-4 gave 2(5H)-furanone and/or cyclopentene-1,3-dione via an R-carbocation
intermediate and a carbenoid (carbene) intermediate, respectively. Thermal rearrangement of some
of these compounds led to the formation of diazepinediones without the extrusion of nitrogen through
tandem 4π electrocyclic ring opening and 8π electrocyclic ring closure processes.
Sch em e 1
Squaric acid (1) continues to attract attention in
organic synthesis as a useful C4-synthon with a four-
membered ring strain to drive reactions.1 Synthesis using
1 starts with the nucleophilic addition of a functional
group to cyclobutenedione (2 f 3), and the resulting
4-hydroxycyclobutenones 3 are subjected to various ring-
transformation reactions (e.g., Scheme 1). Most of these
reactions involve tandem electrocyclic rearrangements.
The relief of ring strain by 4π ring opening to vinylketene
is an initial step,2 and this is followed by 6π ring closure
with the participation of an unsaturated addend, to give
polysubstituted six-membered cyclic compounds (4 f 5).3
Paquette and co-workers recently developed an 8π ring
closure process for the bisadduct of vinylic carbanions to
polyquinanes, which raises new possibilities for the
synthetic application of 1.4 Alternative ring transforma-
tions rely on a 1,2-acyl shift induced by reactive inter-
mediates5 or transition metal catalysts.6 These reactions
give rise to five-membered rings including 4-cyclopen-
tene-1,3-diones and 2(5H)-furanones. Cationic rearrange-
(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. (d) Ohno, M.; Yamamoto, Y.; Eguchi, S. J .
Synth. Org. Chem., J pn. 1997, 55, 785.
(2) For a theoretical study, see (a) Niwayama, S.; Kallel, E. A.; Sheu,
C.; Houk, K. N. J . Org. Chem. 1996, 61, 2517. (b) Niwayama, S.; Kallel,
E. A.; Spellmeyer, D. C.; Sheu, C.; Houk, K. N. J . Org. Chem. 1996,
61, 2813.
(3) For recent examples, see: (a) Sun. L.; Liebeskind, L. S. J . Org.
Chem. 1995, 60, 8194. (b) Xiong, Y.; Xia, H.; Moore, H. W. J . Org.
Chem. 1995, 60, 6460. (c) Xiong, Y.; Moore, H. W. J . Org. Chem. 1996,
61, 9168. (d) Tomooka, C. S.; Liu, H.; Moore, H. W. J . Org. Chem. 1996,
61, 6009. (e) Sun, L.; Liebeskind, L. S. Tetrahedron Lett. 1997, 38, 3663.
(f) Onofrey, T. J .; Gomez, D.; Winters, M.; Moore, H. W. J . Org. Chem.
1997, 62, 5658.
ment has been used to synthesize dimethylgloiosiphone
A using such a cyclopentenedione as a key intermediate.5d
In our laboratory, the Lewis acid-catalyzed reaction of
alkynylsilanes with cyclobutenedione monoacetal 6 ob-
tained from 1 was found to involve a new 1,2-silyl shift
on the triple bond to generate an R-vinyl cation, which
induced ring-expansion to 2-alkylidene-4-cyclopentene-
1,3-dione (7 f 8).5f The oxy-radical generated by the
action of Pb(OAc)4 induced â-scission, which was followed
by 5-endo-trig cyclization to 2(5H)-furanones (9 f 10).5c
Regarding the above ring transformations, we have
been interested in 4-hydroxycyclobutenones functional-
ized with a diazo group at the C-4 side chain. This
functionality can serve as a carbene and carbocation
source and as an unsaturated moiety. The starting diazo-
functionalized 4-hydroxycyclobutenones 12a -e were pre-
pared by adding lithium enolates of diazoacetates and a
(4) Paquette, L. A.; Kuo, L. H.; Doyon, J . J . Am. Chem. Soc. 1997,
119, 3038 and refs cited therein.
(5) (a) Sun. L.; Liebeskind, L. S. J . Org. Chem. 1994, 59, 6856. (b)
Yamamoto, Y.; Ohno, M.; Eguchi, S. Tetrahedron Lett. 1995, 31, 5539.
(c) Yamamoto, Y.; Ohno, M.; Eguchi, S. J . Am. Chem. Soc. 1995, 117,
9653. (d) Paquette, L. A.; Sturino, C. F.; Dousso, P. J . Am. Chem. Soc.
1996, 118, 9456. (e) Yamamoto, Y.; Ohno, M.; Eguchi, S. J . Org. Chem.
1996, 61, 9246. (f) Yamamoto, Y.; Noda, M.; Ohno, M.; Eguchi, S. J .
Org. Chem. 1997, 62, 1292.
(6) (a) Liebeskind, L. S.; Chidambaram, R. J . Am. Chem. Soc. 1987,
109, 5025. (b) Liebeskind, L. S.; Mitchell, D.; Foster, B. S. J . Am. Chem.
Soc. 1987, 109, 7908. (c) Mitchell, D.; Liebeskind, L. S. J . Am. Chem.
Soc. 1990, 112, 291. (d) Zora, M.; Herndon, J . W. J . Org. Chem. 1994,
59, 699. (e) Liebeskind, L. S.; Bombrun, A. J . Org. Chem. 1994, 59,
1149.
10.1021/jo980523d CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/14/1999

708 J . Org. Chem., Vol. 64, No. 3, 1999
Ohno et al.
Ta ble 1. Ca ta lyzed a n d P h otolyzed Rea ction of
Dia zo-F u n ction a lized Cyclobu ten on es 12a -c
Sch em e 2
catalysta
[amount]
temp,b
°C
product [yield (%)]
(E/Z ratio)c
Sch em e 3
entry compd
1
2
12a
12a
12a
12a
12a
12a
12a
12b
12b
12b
12c
12c
12c
BF3
[1.2 equiv]
TiCl4
[1.2 equiv]
SnCl
[1.2 equiv]
TFA
[1.2 equiv]
TMSOTf
[20 mol %]
Rh2(OAc)4
[2.5 mol %]
hν
0
13d [9],
14a [27]
(E/Z ) 73/27)
0
13d [18]
13d [2]
3
0
4
0
13d [50], 14a [23]
(E/Z ) 58/42)
13d [42], 14a [36]
(E/Z ) 73/27)
13d [77], 14a [6]
(E/Z ) 0/100)
13d [45], 14a [14]
5
rt
0
6
diazoketone at -78 °C to cyclobutenedione 11, which was
derived from 1 (Scheme 2).7
7
rt
0
(E/Z ) 75/25)
14b [51]
(E/Z ) 50/50)
14b [58]
First, the catalyzed decomposition of the three diazo
compounds 12a -c was examined. Padwa and co-workers
recently reported the prototypical reaction of related
diazo-functionalized hydroxycyclobutanes with BF3‚OEt2
as a catalyst.8 In this case, ring expansion to a five-
membered ring was explained by a 1,2-methylene shift
via a vinyl cation intermediate (Scheme 3).
8
TFA
[1.2 equiv]
TMSOTf
[20 mol %]
Rh2(OAc)4
[2.5 mol %]
TFA
[1.2 equiv]
TMSOTf
[20 mol %]
Rh2(OAc)4
[2.5 mol %]
9
rt
0
(E/Z ) 75/25)
10
11
12
13
13b [69]/13d [17]
0
13c [83]
Thus, R-diazo-R-cyclobutenyl acetate 12a was allowed
to react with this catalyst, and the expected decomposi-
tion took place smoothly at 0 °C within 30 min (Table 1,
entry 1). After workup and chromatographic separation,
three products were obtained, albeit in low yields. One
of them was believed to be 1,2-acyl-shifted 4-cyclopen-
tene-1,3-dione 13d based on spectroscopic examination.
The MS molecular ion peak at m/z 154 reflected the loss
rt
0
13c [50], 14c [47]
(E/Z ) 64/36)
13c [70]
a
b
Solvent CH2Cl2. Reaction time: 30 min except for entry 7
(19 h). c The ratio was obtained by 1H NMR measurement.
to deduce the stereochemistry of analogous products
obtained from 12b,c. Other Lewis acids such as TiCl4 and
SnCl4 resulted in negligible yields of 13d (entries 2 and
3). On the other hand, trifluoroacetic acid (TFA) catalyzed
ring expansion with much better yields [13d : 50%, 14a :
23% (E/Z ) 58/42)] under the same reaction conditions
(entry 4); similar results were obtained in the case of
trimethylsilyl triflate (TMSOTf) (entry 5). Carbene-type
rearrangement was achieved by catalysis with Rh2(OAc)4
and by photolysis (entries 6 and 7). While these “lyses”
may proceed via different mechanisms, the same products
were obtained in the selective formation of the cyclopen-
tenedione (13d : 77%, 14a : 6% for Rh-catalysis; 13d :
45%, 14a : 14% for photolysis).
Among the reaction conditions examined above, the
catalytic reactions using TFA, TMSOTf, and Rh2(OAc)4
were fruitful and therefore selected for diazo-ester 12b
and diazo-ketone 12c. In the same manner, correspond-
ing products 13b,c and 14b,c were obtained in compa-
rable yields, as shown in entries 8-13, and were char-
acterized by analogy with 13d and 14a . The TFA-
catalyzed reaction selectively gave the furanone 14b from
12b and the cyclopentenedione 13c from 12c. The cyclo-
pentenedione structure of 13b from the ethyl ester 12b
was very susceptible to fragmentation, as seen in the tert-
butyl ester 13a , and thus Rh-catalyzed decomposition
was accompanied by the minor formation of 13d .
1
of N2, CO2, and CH2CMe2 from the molecule. H NMR
(only ethoxy, methyl, and methylene signals at δ 1.40 and
4.69, 1.94, and 2.91, respectively) and 13C NMR (ring
carbon signals at δ 42.2, 137.4, 166.7, 196.0, and 197.2
with required signals due to substituents) were compat-
ible with the assigned structure. Ring expansion took
place with concomitant fragmentation of the primarily
formed tert-butyl ester 13a , which could be due to the
leaving ability of the attached cyclopenetenedione moiety.
The other two products were determined to be geo-
metrical isomers of 5-[(tert-butoxycarbonyl)methylene]-
2(5H)-furanone 14a (E/Z ) 73/27) by comparison with
the authentic (E)- and (Z)-isomers (31/69) which were
obtained by our established procedure using Pb(OAc)4
oxidation (i.e., via an intermediate such as 9).5c In this
case, the stereochemistry could be determined based on
the relative 1H NMR chemical shift due to an exo-
methylene proton, which was observed at a lower region
in E (δ 5.85) than in Z (δ 5.54).5c,9 This tendency was used
(7) Squarate 2 was not suitable since the nucleophilic addition did
not occur at -78 °C. Furthermore, R-diazo carbonyl compounds were
used since derivatives of diazoalkane such as (trimethylsilyl)diazo-
methane were too unstable [decomposition during workup gave only
12% of the cyclopentenedione (13: R ) TMS) as a product].
(8) Pellicciari, R.; Natalini, B.; Sadeghpour, B. M.; Marinozzi, M.;
Snyder, J . P.; Williamson, B. L.; Kuethe, J . T.; Padwa, A. J . Am. Chem.
Soc. 1996, 118, 1. References are listed for some reactions of R-diazo
â-hydroxy carbonyl compounds.
The relative yields of cyclopentenedione to furanone
(13/14) shown in Table 1 seem to reflect a kinetic product
ratio, except for the less significant reactions in entries
(9) Begley, M. L.; Gedge, D. R.; Pattenden, G. J . Chem. Soc., Chem.
Commun. 1978, 60.

Ring Expansion of Diazo-Functionalized 4-Hydroxycyclobutenone
J . Org. Chem., Vol. 64, No. 3, 1999 709
Sch em e 4
bination of the acyl cation with an enol end) was reported
to be likely.12 These sequential reaction paths are con-
sistent with the formation of both products from the
catalytic and photolytic reactions as described above.
Thus, protonation (silylation) or coordination of BF3 on
the diazo group produces a diazonium salt 15, which then
eliminates nitrogen to generate a carbocation R to the
cyclobutenone ring. Interaction of the Rh catalyst with
this group forms a Rh-carbene complex 17, which has a
positive center because of the polar nature of the metal-
carbon double bond.13 The carbene generated under
photolytic conditions can be considered an electropositive
intermediate.14 Therefore, these intermediates with an
electron-deficient center, while formed by different pro-
cesses, induce ring-opening to give stable conjugated acyl
cations 16. In the subsequent recyclization step, these
cations have two opportunities to form a new bond with
both oxygen and carbon sites of the opposite enol end,
giving 13 and 14, respectively. In contrast, all of the Rh-
catalyzed reactions produced the cyclopentenedione se-
lectively. Since the Rh-carbenoid is known to undergo
cation-like rearrangement,15 17 can also follow the
similar type of ring-opening to give a zwitterionic inter-
mediate 18. While simple recyclization of 18 might lead
to the formation of 13, we prefer the involvement of a
metallacyclic intermediate 20 formed either from the
direct recombination of an acyl cation with a Rh center
or from the 6π electrocyclization of a conjugated vi-
nylketene 19. Subsequent reductive elimination may be
responsible for the observed selectivity.16 It is difficult
to completely explain the selectivity observed in TFA- and
TMSOTf-catalyzed reactions; e.g., TFA selectively pro-
duces the furanone in 12b, the cyclopentenedione in 12c,
and both in 12a , whereas TMSOTf tends to enhance
furanone formation. Nevertheless, the preference for an
enol form in the ring-opened 1,3-dicarbonyl intermediate
16 might be due to C-C bond formation rather than C-O
bond formation. On the other hand, a bulky silyl group
may play a role in TMSOTf catalysis, thus retarding the
formation of the former bond. Finally, we consider the
stereochemistry of the furanone products. While the oxy-
radical-mediated reaction predominantly gave the ther-
modynamically favored (Z)-isomer (3 f 10b),5c content
1-3. Control experiments indicated that 13 and 14 were
not interconvertible under these conditions10 (the pos-
sibility of the conversion 13a to 14a can be excluded
because of concomitant fragmentation). The observed
difference in the product ratio may be explained by the
nature of the catalysts and the enolizability of the
intermediates involved (vide infra). The E/Z ratio of the
furanones 14 varied slightly depending on the reaction
conditions, although (E)-isomers were generally predomi-
nant (E/Z ∼ 7/3).11
The mechanism of the ring expansion to two types of
five-membered rings is illustrated in Scheme 4. Regard-
less of the catalysts used, these rearrangements can be
explained by considering the participation of an electron-
deficient carbon center, which is generated by the action
of the catalysts or by photoexcitation and triggers the
ring expansion of cyclobutenone. Padwa’s related rear-
rangement of 2-diazo-(1-hydroxycyclobutyl)acetate has
been suggested to proceed via (1) complexation of the
alcohol functionality with a BF3 catalyst to generate
cyclobutylidene diazonium salt, (2) loss of nitrogen to
produce a linear vinyl cation, and (3) a 1,2-methylene
shift to a cyclopentenyl cation (see Scheme 3).8 However,
this mechanism is not consistent with our experimental
findings, since the furanone, one of the ring-expansion
products, should originate from the ring-opened struc-
ture. Our previous ring-expansion reaction induced by
an R-vinyl cation (i.e., 7 f 8) proceeded via the formation
of ring-opened acyl cation and recombination with an
allenyl end.5f In the analogous TFA-catalyzed rearrange-
ment of succinoin derivatives, a similar process (recom-
of (E)-isomer was increased in the present reaction.17
A
hydrogen-bonded structure such as 21 might contribute
in part to this inverse trend at the recyclization step.
The thermal reaction of diazo-functionalized cyclobuten-
ones 12 is a new type of ring transformation based on 1.
In contrast to the above decomposition reactions, the
(12) Shimada, J .; Hashimoto, K.; Kim, B. H.; Nakamura, E.;
Kuwajima, I. J . Am. Chem. Soc. 1984, 106, 1759.
(13) Ohno, M.; Itoh, M.; Umeda, M.; Furuta, R.; Kondo, K.; Eguchi,
S. J . Am. Chem. Soc. 1996, 118, 7075. See ref 6d for the case of
chromium carbene complexes.
(14) The rearrangement of cyclobutylcarbene to cyclopentene has
been reported: Paskovich, D. H.; Kwok, P. W. N. Tetrahedron Lett.
1967, 2227. For a general discussion on 1,2-rearrangement of carbene,
see Nickon, A. Acc. Chem. Res. 1993, 26, 84, and refs cited therein.
(15) For example, we have previously observed adamantylmethyl-
homoadamantyl rearrangement (which is typical in the cationic
version) in the reaction of adamantyldiazoacetate with Rh2(OAc)4; see
ref 13.
(16) Zwitterionic intermediates have often been proposed in the Rh-
promoted carbene rearrangement, in which a metallacycle is postulated
as a plausible intermediate: (a) Padwa, A.; Austin, D. J . Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1797. (b) Mu¨ller, P.; Pautex, N.; Doyle, A. P.;
Bagheri, V. Helv. Chim. Acta 1990, 73, 1233.
(10) Base-promoted conversion of 5-acylidene-2(5H)-furanone to
2-acyl-4-cyclopentene-1,3-dione has been reported: Gedge, D. R.;
Pattenden, G. J . Chem. Soc., Chem. Commun. 1978, 880.
(11) Control experiments suggested that the acid-catalyzed condi-
tions had little effect on the geometrical isomerization of formed
furanones 14.
(17) In an exception, the (Z)-isomer was a minor product in the Rh-
catalysis of 12a (entry 6), probably because of coordination with a Rh
center.

710 J . Org. Chem., Vol. 64, No. 3, 1999
Ohno et al.
Sch em e 5
opening-closure as a new type of ring transformation
in squaric acid chemistry.19
Exp er im en ta l Section
Gen er a l Rem a r k s. 1H and 13C NMR spectra were obtained
in CDCl3 solution with SiMe4 as an internal standard. CH2-
Cl2 was dried over CaCl2, distilled, and kept over 4 Å molecular
sieves, while THF was dried over Na/Ph2CO and distilled
before use. Aromatic solvents were dried over Na. 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. Prepara-
tion of the squaric acid derivatives 11a -c has been reported
previously.3c,20
Rep r esen ta tive P r oced u r e for th e Syn th esis of 12a -
e. To a solution of 11a (1117 mg, 7.97 mmol) and tert-butyl
diazoacetate (2266 mg, 15.94 mmol) in THF (40 mL) was added
LDA [prepared from diisopropylamine (1937 mg, 19.14 mmol)
and BuLi (11.86 mL of 1.6 M hexane solution, 19.14 mmol)
and cooled at -10 °C] at -78 °C under a nitrogen atmosphere,
and the solution was stirred for 1 h at this temperature. After
the solution was mixed with 1 N HCl (10 mL) and diluted with
brine, the product was extracted with ether (50 mL × 3).
Extracts were washed with brine, dried over Na2SO4, and
evaporated to dryness. The residue was chromatographed to
give the diazocyclobutenone 12a (868 mg, 47%).
In the same manner, 12d and 12e were obtained in yields
of 41% and 46% from 11b and 11c, respectively. Furthermore,
12b and 12c were obtained in yields of 41% and 30% from
11a with ethyl diazoacetate and benzoyldiazomethane, respec-
tively, except that the reaction was for 2 h at -78 °C and
quenching was with aq NH4Cl for 12b and acetic acid for 12c.
ter t-Bu tyl 2-(2-eth oxy-1-h yd r oxy-3-m eth yl-4-oxo-2-cy-
clobu ten yl)-2-d ia zoa ceta te (12a ): Elution with (H/A 3/1);
products were obtained as structural isomers in moderate
yields, when 12a -c were heated to reflux in xylene for
30 min. This isomerism was revealed by an MS analysis,
which showed molecular ion peaks with the same mass
numbers (m/z 254 and 286) as those of starting 12b and
12c, respectively, and was also supported by an elemental
analysis. The presence of an amino group was indicated
by IR absorption at around 3200 cm-1. The 1H NMR
spectra contained a broad singlet due to a NH group (δ
9.39-9.73), and all of the 13C NMR signals due to skeletal
carbons appeared in the sp2 region. These data allowed
us to assign the products as diazepinediones 24a -c,
which is consistent with the mechanism described below.
Although photolysis facilitated the decomposition of a
diazo group, it remained intact during thermolysis to lead
to a diazovinylketene intermediate 22 via 4π electrocyclic
ring-opening. The resulting conjugated system 22 could
recyclize via 8π electrocyclic ring closure (1,7-dipolar
cyclization) to 23, which was followed by prototropy to
the diazepinedione 24 (Scheme 5). 8π Electrocyclization
is a useful method for the synthesis of 1,2-diazepine.18
The reaction of 12c was accompanied by the formation
of 13c via the aforementioned carbene route; similarly,
12d gave both 13e and 22d . Phenyl-substituted 12e
resulted in the formation of only 13f. Since the 2-sub-
stituent on 12 influences the 4π electrocyclic ring-opening
less significantly,2 the relative instability of the diazo
group led to the carbene route.
1
oil; IR (neat) 2103, 1761, 1694, 1616 cm-1; H NMR δ 1.46 (3
H, t, J ) 7.0 Hz), 1.47 (9 H, s), 1.72 (3 H, s), 4.41 and 4.51
(each 1 H, dq, J ) 9.9, 7.0 Hz), 5.15 (1 H, br s); 13C NMR δ
6.8, 15.2, 28.4 (3C), 31.3, 69.2, 82.9, 85.9, 125.2, 165.5, 181.9,
189.9; MS (EI) m/z (relative intensity), 199 (M - 83, 14), 152
(87), 83 (100). Anal. Calcd for C13H18N2O5: C, 55.31; H, 6.43;
N, 9.22. Found: C, 55.86; H, 6.10; N, 9.42.
Eth yl 2-(2-eth oxy-1-h yd r oxy-3-m eth yl-4-oxo-2-cyclobu -
ten yl)-2-d ia zoa ceta te (12b): Elution with (H/A 5/1); crystal,
mp 81-83 °C; IR (KBr) 2103, 1763, 1696, 1615 cm-1; 1H NMR
δ 1.26 (3 H, t, J ) 7.2 Hz), 1.46 (3 H, t, J ) 7.0 Hz), 1.72 (3 H,
s), 4.21 (2 H, q, J ) 7.0 Hz), 4.42 and 4.52 (each 1 H, dq, J )
9.8, 7.0 Hz), 5.51 (1 H, br s); 13C NMR δ 6.7, 14.4, 15.1, 58.2,
61.2, 69.2, 85.3, 125.1, 165.4, 182.3, 190.7; MS (EI) m/z
(relative intensity), 226 (M - 28, 5), 152 (51), 83 (100). Anal.
Calcd for C11H14N2O5: C, 51.97; H, 5.55; N, 11.02. Found: C,
52.13; H, 5.57; N, 10.84.
4-(1-Dia zo-2-oxo-2-p h en yleth yl)-3-eth oxy-4-h yd r oxy-2-
m eth yl-2-cyclobu ten on e (12c): Elution with (H/A 3/1); oil;
1
IR (neat) 2091, 1763, 1615, 708 cm-1; H NMR δ 1.48 (3 H, t,
J ) 7.0 Hz), 1.79 (3 H, s), 4.45 and 4.56 (each 1 H, dq, J ) 9.8,
7.0 Hz), 5.77 (1 H, br s), 7.40-7.65 (5 H, m); 13C NMR δ 6.9,
15.1, 67.8, 69.4, 86.6, 125.5, 127.6 (2C), 129.1 (2C), 132.5, 137.3,
181.8, 189.5, 189.6; MS (EI) m/z (relative intensity), 258 (M -
28, 38), 105 (100). Anal. Calcd for C15H14N2O4: C, 62.93; H,
4.93; N, 9.79. Found: C, 62.78; H, 5.00; N, 9.71
In summary, diazo-functionalized 4-hydroxycyclobuten-
ones 12 derived from 1 underwent ring-expansion to
cyclopentenedione/2(5H)-furanone 13/14 through a se-
quential ring-opening and recombination process, trig-
gered by an electron-deficient carbon center generated
upon catalysis and photolysis. The thermal reaction of
12 gave a new seven-membered heterocyclic ring system,
diazepinedione 22, via tandem 4π-8π electrocyclic ring
ter t-Bu t yl 2-(3-b u t yl-2-et h oxy-1-h yd r oxy-4-oxo-2-cy-
clobu ten yl)-2-d ia zoa ceta te (12d ): Elution with (H/A 5/1);
1
oil; IR (neat) 2101, 1755, 1694, 1609 cm-1; H NMR δ 0.90 (3
H, t, J ) 7.2 Hz), 1.23-1.60 (4 H, m), 1.45 (3 H, t, J ) 7.0 Hz),
1.47 (9 H, s), 2.11 (2 H, t, J ) 7.4 Hz), 4.38 and 4.51 (each 1
H, dq, J ) 9.9, 7.0 Hz), 5.40 (1 H, br s); 13C NMR δ 13.7, 15.2,
(19) For a previous ring transformation based on 1 to a seven-
membered ring, see: Huffman, M. A.; Liebeskind, L. S. J . Am. Chem.
Soc. 1993, 115, 4895.
(20) For the synthesis of these types of compounds from 1, see (a)
Reed, M. W.; Polart, D. J .; Perri, S. T.; Foland, L. D.; Moore, H. W. J .
Org. Chem. 1988, 53, 2477. (b) Liebeskind, L. S.; Fengl, R. W.; Wirtz,
K. R.; Shawe, T. T. J . Org. Chem. 1988, 53, 2482.
(18) (a) Sharp, J . T. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: Oxford, 1984;
Vol. 7, pp 595-604. (b) For an example of 6π electrocyclization of
diazoketene, see Tomioka, H.; Okuno, A.; Sugiyama, T.; Murata, S. J .
Org. Chem. 1995, 60, 2344.

Ring Expansion of Diazo-Functionalized 4-Hydroxycyclobutenone
J . Org. Chem., Vol. 64, No. 3, 1999 711
22.1, 22.6, 28.4 (3C), 31.3, 69.0, 83.0, 85.9, 130.1, 165.5, 181.8,
189.6; MS (EI) m/z (relative intensity), 240 (M - 84, 34), 151
(100). Anal. Calcd for C16H24N2O5: C, 59.24; H, 7.46; N, 8.64.
Found: C, 59.43; H, 7.45; N, 8.46.
ter t-Bu tyl 2-(2-eth oxy-1-h yd r oxy-3-p h en yl-4-oxo-2-cy-
clobu ten yl)-2-d ia zoa ceta te (12e): Elution with (H/A 10/1);
(neat) 1715, 1699, 1624 cm-1; 1H NMR δ 1.40 (3 H, t, J ) 7.0
Hz), 1.98 (3 H, s), 4.67 (2 H, q, J ) 7.0 Hz), 7.43-7.99 (5 H,
m), 13.7 (1 H, br s); 13C NMR δ 6.5, 15.8, 68.1, 123.9, 128.3
(2C), 129.9 (2C), 130.2, 132.9, 163.8, 171.8, 185.4, 196.9, 201.0;
MS (EI) m/z (relative intensity), 258 (M+, 71), 105 (100). Anal.
Calcd for C15H14O4: C, 69.76; H, 5.46. Found: C, 69.88; H,
5.34.
crystal, mp 127-129 °C; IR (KBr) 2105, 1742, 1692, 1622 cm-1
;
1H NMR δ 1.39 (9 H, s), 1.55 (3 H, t, J ) 7.2 Hz), 4.52 and
4.70 (each 1 H, dq, J ) 9.8, 7.0 Hz), 5.73 (1 H, br s), 7.25-
7.73 (5 H, m); 13C NMR δ 15.2, 28.4 (3C), 31.2, 69.0, 70.0, 83.0,
86.6, 126.3, 127.6 (2C), 128.7, 128.6, 128.7, 128.8 (2C), 165.5,
180.9, 187.9; MS (EI) m/z (relative intensity), 316 (M - 28,
34), 242 (52), 214 (100). Anal. Calcd for C18H20N2O5: C, 62.78;
H, 5.85; N, 8.13. Found: C, 62.89; H, 6.02; N, 7.85.
(E)-5-(Ben zoylm eth ylid en e)-4-eth oxy-3-m eth yl-2(5H)-
fu r a n on e ((E)-14c): Elution with H/A 6/1; crystal as the third
fraction, mp 118-120 °C; IR (KBr) 1784, 1682, 1645, 1622
1
cm-1; H NMR δ 1.49 (3 H, t, J ) 7.0 Hz), 2.11 (3 H, s), 4.53
(2 H, q, J ) 7.0 Hz), 6.50 (1 H, s); 7.44-7.99 (5 H, m); 13C
NMR δ 9.0, 15.4, 68.1, 99.5, 101.9, 129.0 (4C), 133.6, 138.4,
151.9, 161.9, 170.4, 189.1; MS (EI) m/z (relative intensity), 258
(M+, 10), 105 (100). Anal. Calcd for C15H11O4: C, 69.76; H, 5.46.
Found: C, 69.79; H, 5.43.
Rep r esen ta tive P r oced u r e for th e Ca ta lyzed Decom -
p osition of 12a -c. To a solution of 12a (116 mg, 0.41 mmol)
in CH2Cl2 (2 mL) was added a catalyst in the amount and at
the temperature shown in Table 1 under a nitrogen atmo-
sphere, and stirring was continued for 30 min. The solution
was then mixed with 10% aq NaHCO3 (5 mL), and the products
were extracted with ether (10 mL × 3). The combined extracts
were washed with brine, dried over Na2SO4, and evaporated
to dryness. The residue was chromatographed to give the
cyclopentenedione and/or furanone. The yields are summarized
in Table 1.
(Z)-5-(Ben zoylm eth ylid en e)-4-eth oxy-3-m eth yl-2(5H)-
fu r a n on e ((Z)-14c): Elution with H/A 6/1; crystal as the
second fraction, mp 120-122 °C; IR (KBr) 1792, 1669, 1653,
1
1636 cm-1; H NMR δ 0.91 (3 H, t, J ) 7.0 Hz), 2.03 (3 H, s),
4.18 (2 H, q, J ) 7.0 Hz), 6.34 (1 H, s); 7.44-8.00 (5 H, m); 13
C
NMR δ 8.9, 14.4, 68.1, 103.3, 107.4, 129.0 (2C), 129.5 (2C),
134.0, 138.0, 148.7, 161.1, 170.4, 191.6; MS (EI) m/z (relative
intensity), 258 (M+, 7), 105 (100). Anal. Calcd for C15H11O4:
C, 69.76; H, 5.46. Found: C, 69.78; H, 5.44.
4-Eth oxy-5-m eth yl-4-cyclop en ten e-1,3-d ion e (13d ): Elu-
tion with H/A 10/1; oil as the first fraction; IR (neat) 1755,
P h otolysis of 12a . A solution of 12a (200 mg, 0.708 mmol)
in CH2Cl2 (5 mL) was irradiated with a 100-W high-pressure
Hg lamp with a Pyrex glass filter for 19 h at ambient
temperature under a nitrogen atmosphere. After evaporation
of the solvent, the products were separated by the method that
was used for the catalyzed reaction (see Table 1 for the yields).
1
1696, 1622 cm-1; H NMR δ 1.40 (3 H, t, J ) 7.0 Hz), 1.94 (3
H, t, J ) 1.0 Hz), 2.91 (2 H, q, J ) 1.0 Hz), 4.69 (2 H, q, J )
7.0 Hz); 13C NMR δ 7.2, 15.9, 42.2, 68.1, 137.4, 166.7, 196.0,
197.2; MS (EI) m/z (relative intensity), 154 (M+, 52), 83 (100).
Anal. Calcd for C8H10O3: C, 62.33; H, 6.54. Found: C, 62.45;
H, 6.42.
In d ep en d en t Syn th esis of (E)- a n d (Z)-F u r a n on e 14a .
To a solution of 11a (237 mg, 1.69 mmol) in THF (12 mL) was
added a THF solution (3 mL) of lithium enolate of tert-butyl
acetate [prepared from this ester (236 mg, 2.03 mmol) and LDA
(diisopropylamine + 1.6 M hexane solution of BuLi, each 2.03
mmol), -10 °C, 30 min] at -78 °C under a nitrogen atmo-
sphere, and stirring was continued for 30 min. After the
solution was mixed with 5% aq NH4Cl (10 mL), the products
were extracted with ether (10 mL × 3). The extracts were
combined, washed with brine, dried over Na2SO4, and evapo-
rated to dryness. The residue was chromatographed (H/A 3/1)
to give tert-butyl 2-ethoxy-1-hydroxy-3-methyl-4-oxo-2-cy-
clobutenylacetate (248 mg, 57%): crystal, mp 80-83 °C; IR
(neat) 1748, 1723, 1603 cm-1; 1H NMR δ 1.45 (3 H, t, J ) 7.0
Hz), 1.48 (9 H, s), 1.74 (3 H, s), 2.69 and 2.77 (each 1 H, d, J
) 15.4 Hz), 4.40 and 4.50 (2 H, dq, J ) 9.8, 7.0 Hz), 4.68 (1 H,
br s); 13C NMR δ 7.0, 15.1, 28.1 (3C), 38.3, 68.9, 82.7, 88.3,
122.2, 171.3, 181.8, 191.1; MS (EI) m/z (relative intensity), 200
(M+ - 57, 70), 155 (100). Anal. Calcd for C13H20O5: C, 60.92;
H, 7.86. Found: C, 60.97; H, 7.81.
The above cyclobutenylacetate (197 mg, 0.77 mmol) was
dissolved in benzene (5 mL) and added to a solution of Pb-
(OAc)4 (682 mg, 1.54 mmol) in benzene (5 mL) at room
temperature under a nitrogen atmosphere, and stirring was
continued for 30 min. The reaction mixture was then treated
with water (10 mL) and the precipitates were removed by
filtration. The products were extracted with ether (15 mL ×
3), and the extracts were washed with brine, dried over Na2-
SO4, and evaporated to dryness. The residue was chromato-
graphed (H/A 10/1) to give (E)-14a (15 mg, 8% as the first
fraction) and (Z)-14a (36 mg, 18% as the second fraction)
together with 5-acetoxy-5-[(tert-butoxycarbonyl)methyl]-4-
ethoxy-3-methyl-2(5H)-furanone (145 mg, 60% as the third
fraction).
(E)-5-[(ter t-Bu toxyca r bon yl)m eth ylid en e]-4-eth oxy-3-
m eth yl-2(5H)-fu r a n on e ((E)-14a ): Elution with H/A 10/1; oil
as the second fraction; IR (neat) 1780, 1726, 1638 cm-1 1H
;
NMR δ 1.41 (3 H, t, J ) 7.0 Hz), 1.51 (9 H, s), 2.07 (3 H, s),
4.45 (2 H, q, J ) 7.0 Hz), 5.85 (1 H, s); 13C NMR δ 9.1, 15.3,
28.2 (3C), 68.3, 82.3, 103.4, 103.9, 149.4, 161.3, 163.5, 170.3;
MS (EI) m/z (relative intensity), 254 (M+, 2), 199 (77), 181
(100). Anal. Calcd for C13H18O5: C, 61.40; H, 7.13. Found: C,
61.35; H, 7.18.
(Z)-5-[(ter t-Bu toxyca r bon yl)m eth ylid en e]-4-eth oxy-3-
m eth yl-2(5H)-fu r a n on e ((Z)-14a ): Elution with H/A 10/1;
crystal as the third fraction, mp 108-111 °C; IR (KBr) 1782,
1
1717, 1680, 1647 cm-1; H NMR δ 1.42 (3 H, t, J ) 7.0 Hz),
1.51 (9 H, s), 2.08 (3 H, s), 4.46 (2 H, q, J ) 7.0 Hz), 5.54 (1 H,
s); 13C NMR δ 8.9, 15.3, 28.2 (3C), 67.9, 81.7, 97.4, 101.6, 152.3,
161.8, 163.4, 170.2; MS (EI) m/z (relative intensity), 254 (M+,
2), 199 (76), 181 (100). Anal. Calcd for C13H18O5: C, 61.40; H,
7.13. Found: C, 61.45; H, 7.08.
Eth yl 3-eth oxy-4-m eth yl-2,5-d ioxo-3-cyclop en ten eca r -
boxyla te (13b): Elution with H/A 10/1, oil as the first fraction;
IR (neat) 1759, 1723, 1696, 1622 cm-1; 1H NMR δ 1.28 (3 H, t,
J ) 7.2 Hz), 1.41 (3 H, t, J ) 7.0 Hz), 1.98 (3 H, t, J ) 0.8 Hz),
3.83 (1 H, q, J ) 0.8 Hz), 4.23 (2 H, q, J ) 7.2 Hz), 4.74 (2 H,
q, J ) 7.0 Hz); 13C NMR δ 7.5, 14.0, 15.8, 58.2, 62.6, 68.6, 138.7,
165.0, 167.6, 190.8, 191.8; MS (EI) m/z (relative intensity), 226
(M+, 24), 198 (100). Anal. Calcd for C11H14O5: C, 58.35; H, 6.24.
Found: C, 58.28; H, 6.31.
(E)- an d (Z)-5-[(Eth oxycar bon yl)m eth yliden e]-4-eth oxy-
3-m eth yl-2(5H)-fu r a n on e ((E)- a n d (Z)-14b). These com-
pounds were obtained as an inseparable mixture on elution
with H/A 10/1; oil as the second fraction; IR (neat) 1780, 1726,
1
1638 cm-1; H NMR (chemical shifts due to the Z-isomer are
indicated in brackets) δ 1.32 [1.32] (3 H, t, J ) 7.0 Hz), 1.41
[1.43] (3 H, t, J ) 7.0 Hz), 1.51 (9 H, s), 2.08 [2.09] (3 H, s),
4.23 [4.26] (2 H, q, J ) 7.0 Hz), 4.45 [4.48] (2 H, q, J ) 7.0
Hz), 5.89 [5.61] (1 H, s); 13C NMR δ 9.0 [8.9], 14.1 [14.3], 15.1
[15.2], 61.4 [61.0], 68.3 [68.0], 101.7 [95.6], 104.2 [101.8], 150.4
[152.9], 161.1 [161.7], 164.6 [164.1], 170.0 [170.1]; MS (EI) m/z
(relative intensity), 226 (M+, 12), 198 (95), 83 (100). Anal. Calcd
for C11H14O5: C, 58.35; H, 6.24. Found: C, 58.37; H, 6.22.
2-Ben zoyl-4-et h oxy-5-m et h yl-4-cyclop en t en e-1,3-d i-
on e (13c): Elution with H/A 6/1; oil as the first fraction; IR
Rep r esen ta tive P r oced u r e for th e Th er m a l Rin g Ex-
p a n sion of 12a -e. A solution of 12a (70 mg, 0.25 mmol) in
p-xylene (10 mL) was heated to reflux for 2 h under a nitrogen
atmosphere. After evaporation of the solvent, the residue was
chromatographed (H/A 10/1) to give the diazepinedione 22a
(39 mg, 56%).
Compounds 12b-e were treated similarly, and the products
were separated. The yields are shown in Scheme 4; the
cyclopentenediones 13d ,e have been reported previously.5c

712 J . Org. Chem., Vol. 64, No. 3, 1999
Ohno et al.
of 13c by chromatography; IR (neat) 3277, 1665, 1630 cm-1
ter t-Bu tyl 5-eth oxy-6-m eth yl-4,7-d ioxo-1,2(1H)-d ia ze-
p in e-3-ca r boxyla te (24a ): crystal, mp 99-103 °C; IR (KBr)
;
1H NMR δ 1.40 (3 H, t, J ) 7.0 Hz), 2.21 (3 H, s), 4.27 (2 H, q,
J ) 7.0 Hz), 7.45-7.98 (5 H, m), 9.50 (1 H, br s); 13C NMR δ
14.1, 15.5, 68.5, 126.6, 128.9 (2C), 130.5 (2C), 134.4, 135.7,
145.1, 161.1, 166.8, 181.3, 191.5; MS (EI) m/z (relative
intensity), 286 (M+, 3), 105 (100). Anal. Calcd for C15H14N2O4:
C, 62.93; H, 4.93; N, 9.79. Found: C, 63.10; H, 4.99; N, 9.56.
1
3187, 1715, 1698, 1644 cm-1; H NMR δ 1.37 (3 H, t, J ) 7.0
Hz), 1.55 (9 H, s), 2.16 (3 H, s), 4.22 (2 H, q, J ) 7.0 Hz), 9.39
(1 H, br s); 13C NMR δ 13.7, 15.5, 28.0 (3C), 67.9, 84.5, 125.1,
141.2, 160.7, 161.9, 166.8, 180.1; MS (EI) m/z (relative
intensity), 226 (M+ - 56, 29), 152 (52), 83 (100). Anal. Calcd
for C13H18N2O5: C, 55.31; H, 6.43; N, 9.92. Found: C, 55.45;
H, 6.43; N, 9.78.
ter t-Bu tyl 6-bu tyl-5-eth oxy-4,7-dioxo-1,2(1H)-diazepin e-
3-ca r boxyla te (24d ): crystal as the second fraction after the
first fraction of 13d by chromatography, mp 81-83 °C; IR
Eth yl 5-eth oxy-6-m eth yl-4,7-d ioxo-1,2(1H)-d ia zep in e-
3-ca r boxyla te (24b): crystal, mp 96-98 °C; IR (KBr) 3183,
1
(KBr) 3239, 1726, 1682, 1657 cm-1; H NMR δ 0.94 (3 H, t, J
1
1723, 1680, 1645 cm-1; H NMR δ 1.37 (3 H, t, J ) 7.2 Hz),
) 7.0 Hz), 1.35-1.51 (4 H, m), 1.36 (3 H, t, J ) 7.0 Hz), 1.56
(9 H, s), 2.64 (2 H, q, J ) 7.4 Hz), 4.19 (2 H, q, J ) 7.0 Hz),
9.55 (1 H, br s); 13C NMR δ 14.0, 15.5, 23.0, 27.5, 28.1 (3C),
30.4, 67.9, 84.5, 129.2, 141.0, 160.7, 162.0, 166.8, 180.6; MS
(EI) m/z (relative intensity), 324 (M+, 7), 195 (100), 151 (85).
Anal. Calcd for C16H24N2O5: C, 59.24; H, 7.46; N, 8.64.
Found: C, 59.33; H, 7.51; N, 8.50.
1.38 (3 H, t, J ) 7.0 Hz), 2.17 (3 H, s), 4.24 (2 H, q, J ) 7.0
Hz), 4.40 (2 H, q, J ) 7.0 Hz), 9.70 (1 H, br s); 13C NMR δ
13.8, 14.1, 15.4, 62.9, 68.1, 125.2, 139.6, 160.7, 162.9, 166.8,
179.6; MS (EI) m/z (relative intensity), 254 (M+, 12), 152 (41),
83 (100). Anal. Calcd for C13H18N2O5: C, 55.31; H, 6.43; N,
9.92. Found: C, 55.45; H, 6.43; N, 9.78.
3-Ben zoyl-5-eth oxy-6-m eth yl-1,2(1H)-d ia zep in e-4,7-d i-
on e (24c): paste as the second fraction after the first fraction
J O980523D