Application and details of photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones and related compounds

Article abstract of DOI:10.1016/j.tet.2008.01.084

As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7a-c) and related compounds 9a-c was accomplished to give 5,10-metha

Full text of DOI:10.1016/j.tet.2008.01.084

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3225e3231
www.elsevier.com/locate/tet
Application and details of photoinduced oxidative cyclization
of 5-(40,90-methanocycloundeca-20,40,60,80,100-pentaenylidene)-
pyrimidine-2,4,6(1,3,5H)-triones and related compounds
y
,z
*
Shin-ichi Naya , Yohei Yamaguchi, Makoto Nitta
Department of Chemistry, School of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Received 8 December 2007; received in revised form 17 January 2008; accepted 19 January 2008
Available online 30 January 2008
Abstract
As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(40,90-methanocycloundeca-20,40,60,80,100-
pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7aec) and related compounds 9aec was accomplished to give 5,10-methanocyclounde-
ca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates (8aecD$BF4L) and related compounds 2aecD$BF4L, respectively. In the
photoinduced oxidative cyclization, the molecular oxygen in air is used as oxidant and the reaction proceeds under mild conditions to give de-
sired products without byproducts, and thus, it is interesting from the viewpoint of the green chemistry. On the reactions of the mono-substituted
derivatives 7d,e and 9e,f, the selectivity of the photoinduced cyclizations were reversed as compared with those of the DDQ-promoted oxidative
cyclizations. By the NMR monitoring of the reactions of 7a and deuterated compound 7a-D2 under degassed conditions, the details of the
reaction pathway were clarified and rationalized on the basis of the MO calculation by the 6-31G* basis set of the MP2 levels as well.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Photoinduced oxidative cyclization; 5-(40,90-Methanocycloundeca-20,40,60,80,100-pentaenylidene)-pyrimidine-2,4,6(1,3,5H)-trione; Heptafulvene;
Furo[2,3-d]pyrimidine
1. Introduction
environment-friendly synthesis of furo[2,3-d]pyrimidine deriv-
atives (1) (Fig. 1) was also reported.10 As the investigation of the
compoundscontainingthefuro[2,3-d]pyrimidine-ringsystem,we
have previously reported the synthesis, properties, and reactivity
of cyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium
ions (2aecD$BFL4 ).11 Furthermore, as the model of flavin-type
reaction,12 their novel photoinduced autorecycling oxidizing
reactions toward some alcohols and amines were clarified.11,13
In this relation, the alternative synthesis of 2aecD$BF4L from
heptafulvene derivatives (9aec) (Scheme 1) was accomplished
by the novel oxidative cyclization using DDQ.14 While several
methodologiesforsynthesizingfuro[2,3-d]pyrimidinederivatives
have been developed due to their high potential and unique
characteristics,15 to our best knowledge, this is the first example
of synthesizing methodology starting from the pyrimidine
derivatives containing the heptafulvene-ring system.
Construction of the furan ring, which is found in many natu-
ral and biologically important molecules,1e3 has been the focus
of much research attention.4 Among these, the synthesis of
furo[2,3-d]pyrimidine systems as formal isoelectronic com-
pounds of purine is interesting in developing novel medicinal
and agrochemical agents namely antimalarials,5 antifolates,6
and antivirus,7 as well as potential radiation protection agents.8
Recently, some furo[2,3-d]pyrimidines were shown to be potent
VEGFR2 (vascular endothelial growth factor receptor 2) and
EGFR (epidermal growth factor receptor) inhibitors,9 and the
* Corresponding author. Tel.: þ81 3 5286 3236; fax: þ81 3 3208 2735.
E-mail address: nitta@waseda.jp (M. Nitta).
y
Present address: Harmful Materials Management Center, Kinki University,
Hzigashiosaka-shi, Osaka 577-8502, Japan.
Professor Emeritus of Waseda University.
On the other hand, heptafulvenes have intrigued chemists
for several decades, especially in the context of the concept
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.084

3226
S. Naya et al. / Tetrahedron 64 (2008) 3225e3231
to activate DDQ22 and under higher temperature and long re-
action time, the reaction of 5 with DDQ proceeded to afford
compound 6D$BFL4 , although the yield was still low (20%).
Thus, we accomplished the photoinduced oxidative cyclization
of 5 by the photoirradiation (RPR-100, 350 nm lamps) under
aerobic conditions in the presence of 42% aq HBF4 to result
in the formation of compound 6D$BF4L in quantitative yield.
In the photoinduced oxidative cyclization, the molecular oxy-
gen in air was used as oxidant, and thus, byproducts derived
from oxidant such as hydroquinone and heavy metal ions
were not generated. Furthermore, the reaction proceeded un-
der room temperature, and the hard reaction conditions were
not required. Consequently, the photoinduced oxidative cycli-
zation is environmentally-friendly synthetic method, and thus,
it is interesting from the viewpoint of the green chemistry. Fur-
thermore, in the synthesis of tropylium ions annulated with
two 2,4-dimethylfuro[2,3-d]pyrimidine-1,3(2,4H)-diones, we
have clarified that the photoinduced oxidative cyclization ex-
hibits a complete selectivity.23 In addition, we have carried
out the similar reaction on a large scale to obtain the desired
product at gram scale. Thus, the further application of the re-
action and its details are very attractive to explore the novel
methodology for synthesizing furan-ring systems. We have re-
cently reported that the DDQ-promoted oxidative cyclization
of 5-(40,90-methanocycloundeca-20,40,60,80,100-pentaenylide-
ne)pyrimidine-2,4,6(1,3,5H)-triones 7aec (Scheme 1), which
are vinylogous compounds of 9aec, afforded the compounds
8aecD$BFL4 .24 In the present study, photoinduced oxidative
cyclization of 7aec and related compounds 9aec was investi-
gated. In addition, the selectivity of the cyclization of mono-
substituted derivatives 7d,e and 9def was studied as well.
Furthermore, by the NMR monitoring of the reactions of 7a
and deuterated compound 7a-D2 under degassed conditions,
the details of the reaction were clarified and rationalized on
the basis of the MO calculation by the 6-31G* basis set of the
MP2 levels. We report herein the results in detail.
Figure 1. Furo[2,3-d]pyrimidine derivatives and heptafulvenes.
Scheme 1. Photoinduced oxidative cyclization of disubstituted compounds
7aec and 9aec.
2. Results and discussion
of aromaticity.16 The chemistry of the heptafulvenes derived
by insertion of more complex conjugated p-systems has also
been studied relative to the molecular design of organic
dyes, highly polarized compounds, and electron acceptors or
electron donors.17 Recently, the synthesis and photochemical
properties of vinylheptafulvene 3 have been studied to demon-
strate that compound 3 possesses a remarkable property of
multimode-switching arising from the ring-closure and
ring-opening process: a very fast photoreversible switch and
a thermal switch.18 While it is well known that the 10p-elec-
trocyclization of vinylheptafulvenes gives dihydroazulenes,19
there are few reports of the oxa 10p-electrocyclization using
carbonyl-moiety of heptafulvenes.20 Thus, the studies on the
properties and reactivity of carbonyl-substituted heptafulvenes
are interesting from the viewpoint of molecular function. In
this relation, we have recently reported that the oxidative cy-
clization of benzo-annulated derivative 5 afforded the corre-
sponding compound 6D$BFL4 .21 In the study, the reaction of
5 by using only DDQ did not proceed. By adding Sc(OTf)3
2.1. Application of photoinduced oxidative cyclization
In order to clarify the scope and limitation of photoinduced
oxidative cyclization, the reaction of 7aec24 and related com-
pounds 9aec14 was investigated (Scheme 1). The photoirra-
diation (RPR-100, 350 nm lamps) of 7aec was carried out
under aerobic condition in CH3CN and (CH2Cl)2 in the pres-
ence of 42% aq HBF4 (Table 1, runs 1e3). By irradiation for
2e3 h, the oxidative cyclization of 7aec proceeded more
smoothly to give 8aecD$BFL4 in good yields (94e100%) as
compared with the reaction of 5 (irradiation time: 36 h).21
Moreover, the reaction of related compounds 9aec was car-
ried out under similar conditions (Table 1, runs 4e6). Al-
though the reaction of compounds 9aec was relatively slow,
the oxidative cyclization was completed by photoirradiation
for 7e21 h to give 2aecD$BF4L quantitatively. The feature
shows that the oxidative cyclization of 11-membered ring pro-
ceeded more effectively as compared with that of 7-membered

S. Naya et al. / Tetrahedron 64 (2008) 3225e3231
3227
Table 1
Results for the photoinduced oxidative cyclization of disubstituted compounds
7aec and 9aec
Runa
Compound
Time/h
Product (yield/%)
1
2
3
4
5
6
a
7a (R¼Me)
7b (R¼Et)
7c (R¼Ph)
9a (R¼Me)
9b (R¼Et)
9c (R¼Ph)
2
2
8aD$BFL4 (94)
8bD$BFL4 (100)
8cD$BFL4 (97)
2aD$BFL4 (100)
2bD$BFL4 (100)
2cD$BFL4 (100)
3
7
5
21
A solution of 7aec or 9aec (0.1 mmol) and 42% aq HBF4 (0.4 mL) in
CH3CN (10 mL) and (CH2Cl)2 (10 mL) in a Pyrex tube was irradiated by
RPR-100, 350 nm lamps under aerobic conditions at room temperature.
ring. In addition, the reaction of 7c and 9c having phenyl-sub-
stituent required longer irradiation time, while the spectro-
scopic properties of 7c and 9c such as 1H and 13C NMR
spectra and UVevis spectra seemed similar to those of 7a,b
and 9a,b, respectively.14,24 The products 2aecD$BFL4 and
8aecD$BFL4 were confirmed by inspection of the spectro-
scopic data.14,24
Furthermore, the photoinduced oxidative cyclization of
mono-substituted derivatives 7d,e25 and 9def14 was also ac-
complished (Scheme 2). Since 7d,e and 9def have two kinds
of reactive carbonyl groups (eCONRe and eCONHe), these
reactions could afford two types of products. The fast reaction
of 7d,e proceeded to give possible mixtures of 8d,eD$BF4L
and 10d,eD$BFL4 , respectively, in good combined yields
(Table 2, runs 1 and 2). Similarly, the relatively slow reaction
of 9def gave mixtures of 2defD$BF4L and 11defD$BF4L,
respectively (Table 2, runs 3e5). On the reaction of phenyl-
substituted derivative 9f, longer irradiation time was also re-
quired (vide supra). The products 8d,eD$BF4L and
10d,fD$BFL4 as well as 2defD$BF4L and 11defD$BF4L
were confirmed by inspection of the spectroscopic data.14,25
The ratios of 8d,eD$BF4L and 10d,eD$BFL4 as well as 2de
Scheme 2. Photoinduced oxidative cyclization of mono-substituted
compounds 7d,e and 9def.
the photoinduced reaction of 9e,f showed a different selectiv-
ity, and compounds 11e,fD$BFL4 became major products
(Table 2, runs 4 and 5). Moreover, the reverse in the selectivity
between the reaction of 7d,e and 9e,f was also observed.
While the DDQ-promoted reaction proceeds via intramolecu-
lar radical addition on the radical cations generated by oxida-
tion of starting compounds,14,24 the photoinduced oxidative
cyclization would be initiated by the photoinduced electrocyc-
lization (vide infra). Moreover, in contrast to the planar 7-
membered ring of 9e,f, the 11-membered ring of 7d,e has
the bending structure.25 However, MO calculations of reac-
tants and possible intermediates such as 12 (Scheme 3) could
not rationalize the different selectivity, and thus, further inves-
tigations are required.
1
fD$BFL4 and 11defD$BFL4 were determined from H NMR
spectra of the mixtures. We have previously reported that the
DDQ-promoted oxidative cyclization of 7d,e and 9def also
affords similar mixtures.14,25 However, in the photoinduced
oxidative cyclization, the different selectivity was observed
as compared with the DDQ-promoted reaction. In the photoin-
duced reaction of 7d,e, compound 8d,eD$BF4L was obtained
as major product, while the DDQ-promoted reaction gave
10d,eD$BFL4 preferentially (Table 2, runs 1 and 2). Similarly,
2.2. Reaction pathway
In order to clarify the details of the reaction, 1H NMR mon-
itoring of reactions of 7a and 9a as well as 20,110-deuterated
Table 2
Results for the photoinduced oxidative cyclization of mono-substituted compounds 7d,e and 9def
Runa
Compound
Time/h
Product (yield/%)
Ratiob of 8þ/10þ or 2þ/11þ
Ratioc of 8þ/10þ or 2þ/11þ
1
2
3
4
5
a
7d (R¼Me)
7e (R¼Bu)
9d (R¼Me)
9e (R¼Bu)
9f (R¼Ph)
3
3
8dD$BFL4 (63), 10dD$BFL4 (37)
8eD$BFL4 (68), 10eD$BFL4 (32)
2dD$BFL4 (50), 11dD$BFL4 (50)
2eD$BFL4 (39), 11eD$BFL4 (61)
2fD$BFL4 (39), 11fD$BFL4 (61)
1.7:1
2.1:1
1:1
1:2.0
1:2.0
1:1
9
9
26
1:1.6
1:1.6
2.5:1
3.3:1
A solution of 7d,e or 9def (0.1 mmol) and 42% aq HBF4 (0.4 mL) in CH3CN (10 mL) and (CH2Cl)2 (10 mL) in a Pyrex tube was irradiated by RPR-100,
350 nm lamps under aerobic conditions at room temperature.
b
Photoinduced oxidative cyclization.
DDQ-promoted oxidative cyclization (Refs. 14 and 25).
c

3228
S. Naya et al. / Tetrahedron 64 (2008) 3225e3231
under degassed conditions afforded compound 2aD$BF4L di-
rectly, and thus, intermediates such as compound 14 were
not observed. Since the photoinduced oxa 10p-electrocycliza-
tion of 9a is relatively slow, the oxidation of intermediate 14
would proceed fast to give compound 2aD$BF4L. Under sim-
ilar conditions, irradiation of 7a-D2 afforded 13-D2 having two
deuterium atoms at C5- and C13endo-position, while the exo-
isomer 15-D2 and mono-deuterated compound 16-D were not
observed. We have previously clarified the bending structure
1
of the 11-membered ring of 7a on the basis of the H and
13C NMR spectra.24 On the MO calculation of two possible
structures 7a-syn and 7a-anti by the 6-31G* basis set of the
MP2 levels,29 the former structure is more stable by
10.486 kcal molꢀ1 than the latter structure (Fig. 2). Thus, the
photoinduced oxa 14p-electrocyclization of 7a and 7a-D2
would proceed from the structure 7a-syn and 7a-D2-syn, re-
spectively, to give intermediate 12 and 12-D2, the C13a-proton
and the C13a-deuterium of which are located at endo-position.
In compound 13-D2, the deuterium located at the C13endo-
position shows that suprafacial [1,11]-deuterium shift of 12-
D2 would proceed to give 13-D2 as a photochemically allowed
process.28,30 Furthermore, oxidation of 13-D2 gave mono-deu-
terated cation 8aD-D$BF4L, suggesting that the oxidative deu-
terium abstraction occurred at the C13endo-position of 13-D2
as similar to the oxidation by using DDQ.24 The feature would
be due to the higher reactivity of endo-position as compared
with that of exo-position in this ring system,24,25 however,
the details are unclear at this stage. It is well known that the
photoinduced oxidation of various olefins by using molecular
oxygen proceeds through a charge transfer (CT) complex. In
a reaction pathway proceeding through the CT complex, the
intermediate would be the radical cation as similar to
the DDQ-promoted reaction. Thus, the similar selectivity to
the DDQ-promoted reaction would be expected to be observed
on the reaction of the mono-substituted derivatives. However,
the selectivity of the photoinduced cyclizations was reversed
as compared with those of the DDQ-promoted oxidative cycli-
zations. Consequently, the present photoinduced oxidative
cyclization would consist of photoinduced oxa 14p-electro-
cyclization and suprafacial [1,11]-hydrogen shift and subse-
quent photoinduced oxidation by the molecular oxygen.
There is a possibility that the photoinduced oxidation proceeds
through CT complex, and thus, further investigations are
required. The compounds 7a-D2, 13, and 13-D2 as well as
Scheme 3. Reaction pathway for the photoinduced oxidative cyclization.
compound 7a-D2 prepared by the reaction of 7a with CD3OD
and D2O26 were carried out (Scheme 3). Under degassed con-
ditions in NMR tubes, solutions of 7a and 9a in CD3CN and
CDCl3 in the presence of 42% aq HBF4 were irradiated by
RPR-100, 350 nm lamps. Before irradiation, the addition of
1
42% aq HBF4 caused no change of the H NMR spectra of
7a and 9a. In addition, the visible region of the UVevis spec-
tra of 7a and 9a was not changed by adding 42% aq HBF4,
suggesting that the protonation would not occur under the
ground states. By irradiation for 2 h, compound 7a was con-
verted completely to compound 13. After additional irradia-
tion for 6 h, compound 8aD$BFL4 was generated by the
oxidation of 13 using the stray oxygen in the solvent. In the
independent reaction, the compound 13 prepared by NaBH4
reduction of 8aD$BF4L, was oxidized by photoirradiation un-
der aerobic conditions in the presence of 42% aq HBF4 to give
8aD$BFL4 quantitatively. Thus, the present photoinduced oxi-
dative cyclization of 7a would proceed as shown in Scheme 3.
The photoinduced oxa 14p-electrocyclization27 of 7a gives
intermediate 12, which would undergo [1,11]-hydrogen shift
to give 13 as similar to the photochemical [1,7]-hydrogen shift
of 1,3,5-cycloheptatriene.28 Under photoirradiation and aero-
bic conditions, oxidation of 13 in the presence of 42% aq
HBF4 affords 8aD$BF4L. In contrast, the irradiation of 9a
Figure 2. Two possible conformations of 7a and 7a-D2.

S. Naya et al. / Tetrahedron 64 (2008) 3225e3231
3229
8aD-D$BFL4 were confirmed by inspection of the spectro-
completed. The mixture was concentrated in vacuo, and the re-
sulting residue was dissolved in a mixture of acetic anhydride
(2 mL) and 42% aq HBF4 (0.4 mL) at 0 ꢁC, and stirred for 1 h.
To the resulting mixture was added Et2O (100 mL) and the
precipitate was collected by filtration to give a mixture of
8d,eD$BFL4 and 10d,eD$BFL4 or a mixture of 2defD$
BFL4 and 11defD$BFL4 (Table 2).
scopic data.24
3. Conclusion
A photoinduced oxidative cyclization of 7aec and related
compounds 9aec was accomplished to give 8aecD$BF4L
and 2aecD$BFL4 in almost quantitative yields, respectively.
The reactions of the mono-substituted derivatives 7d,e and
9def afforded mixtures of 8d,eD$BF4L and 10d,eD$BFL4
and mixtures of 2defD$BF4L and 11defD$BFL4 , respectively.
The selectivity of photoinduced cyclizations of 7d,e and 9e,f
was reversed as compared with that of DDQ-promoted oxida-
tive cyclization, respectively. On the basis of the NMR moni-
toring of reactions of 7a and deuterated compound 7a-D2
under degassed conditions, the details of the reaction pathway
were clarified and rationalized on the basis of the MO calcu-
lation by the 6-31G* basis set of the MP2 levels. In the pho-
toinduced oxidative cyclization, the molecular oxygen in air
is used as oxidant to give desired products without byproducts,
and thus, it is interesting from the viewpoint of the green
chemistry. Further studies concerning application of the photo-
induced oxidative cyclization are currently underway.
4.4. Preparation of deuterated derivative 7a-D2
To a solution of 7a (15 mg, 0.05 mmol) in CD3OD (5 mL)
and D2O (2 mL) was added a drop of TFA-D, and the mixture
was heated in a sealed tube at 130 ꢁC for 72 h. The resulting
mixture was poured into saturated aq NaHCO3, and extracted
with CH2Cl2. The combined organic layer was washed with
water, and dried over MgSO4. The solution was concentrated
in vacuo, and purified through column chromatography on
Al2O3 using hexaneeAcOEt (2:1) as the eluent to give product
7a-D2 (8 mg, 53%).
4.4.1. 20,110-Dideuterio-1,3-dimethyl-5-(40,90-
methanocycloundeca-20,40,60,80,100-
pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione (7a-D2)
1H NMR (500 MHz, DMSO-d6) d ꢀ0.38 (1H, d, J¼
11.0 Hz, HE), 1.79 (1H, d, J¼11.0 Hz, HZ), 3.18 (6H, s,
NMe), 6.86 (2H, br s, H-30, 100), 7.06 (4H, m, H-50, 80),
7.35 (2H, m, H-60, 70); IR (CHCl3) nmax 1655 cmꢀ1; MS
(FAB) m/z 311 (MþþH); HRMS calcd for C18H15D2N2O3:
311.1450 (MþH), found: 311.1326 (MþþH).
4. Experimental
4.1. General
IR spectra were recorded on a HORIBA FT-710 spectrometer.
Mass spectra and high-resolution mass spectra were run on JMS-
1
AUTOMASS 150 and JMS-SX102A spectrometers. H NMR
spectra were recorded on a JNM-lambda500 spectrometer, and
the chemical shifts are given relative to internal SiMe4 standard,
J values are given in hertz. Photoirradiation was carried out by
using RPR-100 fitted with 350 nm lamps though a Pyrex filter.
1
4.5. H NMR monitoring of the photoirradiation of 7a and
7a-D2
Under degassed conditions, a solution of compound 7a or
7a-D2 (3.1 mg, 0.01 mmol) in CD3CN (0.25 mL) and CDCl3
(0.25 mL) in the presence of 42% aq HBF4 (0.01 mL) was ir-
radiated by RPR-100, 350 nm lamps at room temperature in an
NMR tube. After 2 h, the NMR measurement confirmed the
formation of 13 or 13-D2. After additional irradiation for
6 h, oxidation of 13 or 13-D2 to 8aD$BF4L or 8a-DD$BFL4
was observed, respectively.
4.2. General procedure for the oxidative cyclization of 7aec
and 9aec
A solution of 7aec or 9aec (0.1 mmol) and 42% aq HBF4
(0.4 mL) in CH3CN (10 mL) and (CH2Cl)2 (10 mL) in a Pyrex
tube was irradiated by RPR-100, 350 nm lamps under aerobic
conditions at room temperature until the reaction was com-
pleted. The mixture was concentrated in vacuo, and the result-
ing residue was dissolved in a mixture of acetic anhydride
(2 mL) and 42% aq HBF4 (0.4 mL) at 0 ꢁC, and stirred for
1 h. To the resulting mixture was added Et2O (100 mL) and
the precipitate was collected by filtration to give compound
8aecD$BFL4 or 2aecD$BF4L (Table 1).
4.5.1. 5,13-Dideuterio-1,13-dihydro-7,12-methanocyclo-
undeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dione (13-D2)
1H NMR (500 MHz, CD3CNeCDCl3) d 1.62 (1H, d,
J¼11.0 Hz, HE), 3.20 (3H, s, N3Me), 3.35 (3H, s, N1Me),
4.02 (1H, br s, H-13exo), 4.15 (1H, d, J¼11.0 Hz, HZ), 6.06
(1H, m, H-8), 6.17 (1H, m, H-11), 6.30 (1H, br s, H-6),
6.53e6.63 (2H, m, H-9, 10); IR (KBr) nmax 1703, 1662,
1525, 1254 cmꢀ1; MS (FAB) m/z 310 (Mþ); HRMS calcd
for C18H14D2N2O3: 310.1310 (M), found: 310.1280 (Mþ).
4.3. General procedure for the oxidative cyclization of 7d,e
and 9def
4.5.2. 5-Deuterio-7,12-methanocycloundeca[4,5]furo[2,3-
d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborate
(8a-Dþ$BFꢀ4 )
A solution of 7d,e or 9def (0.1 mmol) and 42% aq HBF4
(0.4 mL) in CH3CN (10 mL) and (CH2Cl)2 (10 mL) in a Pyrex
tube was irradiated by RPR-100, 350 nm lamps under aerobic
conditions at room temperature until the reaction was
1H NMR (500 MHz, CD3CNeCDCl3) d ꢀ1.24 (1H, d,
J¼11.5 Hz, HE), ꢀ0.47 (1H, d, J¼11.5 Hz, HZ), 3.40 (3H, s,

3230
S. Naya et al. / Tetrahedron 64 (2008) 3225e3231
7. Janeba, Z.; Balzarini, J.; Andrei, G.; Snoeck, R.; De Clercq, E.; Robins,
M. J. J. Med. Chem. 2005, 48, 4690e4696.
N3Me), 3.72 (3H, s, N1Me), 8.32e8.62 (2H, m, H-9, 10), 8.50
(1H, d, J¼8.0 Hz, H-8), 8.57 (1H, d, J¼8.0 Hz, H-11), 9.15
(1H, br s, H-6), 9.72 (1H, s, H-13); IR (KBr) nmax 1726,
1673, 1646, 1574, 1084 cmꢀ1; MS (FAB) m/z 308 (MþꢀBF4);
HRMS calcd for C18H14DN2O3: 308.1170 (MꢀBF4), found:
308.1202 (MþꢀBF4).
8. Furukawa, S.; Takada, M.; Castle, H. N. J. Heterocycl. Chem. 1981, 18,
581e585.
´
9. Martin-Kohler, A.; Widmer, J.; Bold, G.; Meyer, T.; Sequin, U.; Traxler, P.
Helv. Chim. Acta 2004, 87, 956e975.
10. (a) Shaabani, A.; Teimouri, M. B.; Bijanzadeh, H. R. Tetrahedron Lett.
2002, 43, 9151e9154; (b) Teimouri, M. B.; Bazhrand, R. Bioorg. Med.
Chem. Lett. 2006, 16, 3697e3701.
1
4.6. H NMR monitoring of the photoirradiation of 9a
11. Naya, S.; Miyama, H.; Yasu, K.; Takayasu, T.; Nitta, M. Tetrahedron
2003, 59, 1811e1821.
Under degassed conditions, a solution of compound 9a
(2.4 mg, 0.01 mmol) in CD3CN (0.25 mL) and CDCl3
(0.25 mL) in the presence of 42% aq HBF4 (0.01 mL) was ir-
radiated by RPR-100, 350 nm lamps at room temperature in an
NMR tube. The NMR measurement was carried out at inter-
vals, however, intermediates such as compound 14 were not
observed, and compound 9a was transformed to 2aD$BF4L
gradually. After 24 h, the NMR measurement confirmed the
exclusive formation of 2aD$BF4L.
12. (a) Muller, F. Chemistry and Biochemistry of Flavoenzymes; Muller, F.,
Ed.; CRC: Boca Raton, 1991; Vol. 1, pp 1e71 and references cited
therein; (b) Yoneda, F.; Hirayama, R.; Yamashita, M. Chem. Lett. 1980,
1157e1160.
13. Naya, S.; Nitta, M. Tetrahedron 2004, 60, 9139e9148.
14. Naya, S.; Nitta, M. Tetrahedron 2003, 59, 3709e3718.
15. (a) Otter, B. A.; Saluja, S. S.; Fox, J. J. J. Org. Chem. 1972, 37, 2858e
2863; (b) Secrist, J. A.; Liu, P. S. J. Org. Chem. 1978, 43, 3937e3941;
(c) Kawahara, N.; Nakajima, T.; Itoh, T.; Ofura, H. Heterocycles 1984,
22, 2217e2220; (d) Kawahara, N.; Nakajima, T.; Itoh, T.; Ogura, H.
Chem. Pharm. Bull. 1985, 33, 4740e4748; (e) Figueroa-Villar, J. D.;
Carneiro, C. L.; Cruz, E. R. Heterocycles 1992, 34, 891e895; (f) Kobaya-
shi, K.; Tanaka, H.; Yoneda, K.; Morikawa, O.; Konishi, H. Synth.
Commun. 2000, 30, 4277e4291; (g) Rao, M. S.; Esho, N.; Sergeant, C.;
Dembinski, R. J. Org. Chem. 2003, 68, 6788e6790; (h) Kidwai, M.;
Rastogi, S.; Venkataramanan, R. Bull. Chem. Soc. Jpn. 2003, 76, 203e
204; (i) Nematollahi, D.; Goodarzi, H. J. Org. Chem. 2002, 67, 5036e
5039; (j) Qian, C.-.Y.; Nishino, H.; Kurosawa, K.; Korp, J. D. J. Org.
Chem. 1993, 58, 4448e4451; (k) Kajikawa, S.; Nishino, H.; Kurosawa,
K. Heterocycles 2001, 54, 171e183.
4.7. Photoinduced oxidation of 13
A solution of 13 (31 mg, 0.1 mmol) and 42% aq HBF4
(0.4 mL) in CH3CN (10 mL) and (CH2Cl)2 (10 mL) in a Pyrex
tube was irradiated by RPR-100, 350 nm lamps under aerobic
conditions at room temperature for 2 h. The mixture was con-
centrated in vacuo, and the resulting residue was dissolved in
a mixture of acetic anhydride (2 mL) and 42% aq HBF4
(0.4 mL) at 0 ꢁC, and stirred for 1 h. To the resulting mixture
was added Et2O (100 mL) and the precipitates were collected
by filtration to give compound 8aD$BF4L (39 mg, 100%).
16. (a) Ogliaruso, M. A.; Romanelli, M. G.; Becker, E. I. Chem. Rev. 1965,
65, 261e367; (b) Bertelli, D. J.; Andrews, T. G., Jr.; Crew, P. O. J. Am.
Chem. Soc. 1969, 91, 5286e5296; (c) Hollenstein, R.; Mooser, A.;
Neuenschwander, M.; von Philipsborn, W. Angew. Chem. 1974, 87,
595e596.
17. Takahashi, K. J. Synth. Org. Chem. Jpn. 1986, 806e818; Chem. Abstr.
1987, 107, 115439v and references cited therein.
18. Waele, V. D.; Schmidhammer, U.; Mrozek, T.; Daub, J.; Riedle, E. J. Am.
Chem. Soc. 2002, 124, 2438e2439.
Acknowledgements
Financial support from a Waseda University Grant for Spe-
cial Research Project and 21COE ‘Practical Nano-Chemistry’
from MEXT, Japan, is gratefully acknowledged. We thank the
Materials Characterization Central Laboratory, Waseda Uni-
versity, for technical assistance with the spectral data.
19. (a) Daub, J.; Knochel, T.; Mannschreck, A. Angew. Chem., Int. Ed. Engl.
¨
¨
1984, 23, 960e961; (b) Gorner, H.; Fischer, C.; Gierisch, S.; Daub, J.
J. Phys. Chem. 1993, 97, 4110e4117; (c) Gobbi, L.; Seiler, P.; Diederich,
F. Angew. Chem., Int. Ed. 1999, 38, 674e678; (d) Boggio-Pasqua, M.;
Bearpark, M. J.; Hunt, P. A.; Robb, M. A. J. Am. Chem. Soc. 2002,
124, 1456e1470; (e) Trieflinger, C.; Rohr, H.; Rurack, K.; Daub, J.
¨
Angew. Chem., Int. Ed. 2005, 44, 6943e6947.
References and notes
20. (a) Reichardt, C.; Yun, K. Y.; Massa, W.; Schmidt, R. E.; Exner, O.;
Wurthwein, E. U. Liebigs Ann. Chem. 1985, 1997e2011; (b) Reichardt,
¨
1. (a) Konig, B. Hetarenes and Related Ring Systems. Science of Synthesis;
C.; Yun, K. Y. Angew. Chem. 1982, 94, 69e70.
¨
Maas, G., Ed.; George Thieme: Stuttgart, 2001; Vol. 9, pp 183e285,
Category 2; (b) Dell, C. P. Hetarenes and Related Ring Systems. Science
of Synthesis; Thomas, E. J., Ed.; George Thieme: Stuttgart, 2000; Vol. 10,
pp 11e86, Category 2; (c) Hou, X. L.; Cheung, H. Y.; Hon, T. Y.; Kwan,
P. L.; Lo, T. H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998, 54, 1955e
2020.
21. Naya, S.; Tokunaka, T.; Nitta, M. J. Org. Chem. 2003, 68, 9317e9321.
22. Fukuzumi, S.; Ohkubo, K. Chem.dEur. J. 2000, 6, 4532e4535.
23. Naya, S.; Tokunaka, T.; Nitta, M. J. Org. Chem. 2004, 69, 4732e4740.
24. Naya, S.; Yamaguchi, Y.; Nitta, M. J. Org. Chem. 2003, 68, 9284e9291.
25. Naya, S.; Yamaguchi, Y.; Nitta, M. Tetrahedron 2005, 61, 7384e7391.
26. (a) Kimura, M.; Morita, M. Bull. Chem. Soc. Jpn. 1993, 66, 3120e3123;
(b) Hooley, R. J.; Rebek, J., Jr. J. Am. Chem. Soc. 2005, 127, 11904e
11905; (c) Mathias, L. J.; Colletti, R. F. Macromolecules 1988, 21,
858e860.
2. Mendez-Andino, J.; Paquette, L. A. Org. Lett. 2000, 2, 4095e4097 and
references therein.
3. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893e
930.
27. (a) Lukeman, M.; Wan, P. J. Am. Chem. Soc. 2003, 125, 1164e1165; (b)
Malerich, J. P.; Maimone, T. J.; Elliott, G. I.; Trauner, D. J. Am. Chem.
Soc. 2005, 127, 6276e6283.
4. (a) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 2001, 2491e2515; (b)
Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1999, 2849e2866.
5. Campaigne, E.; Ellis, R. L.; Bradford, M.; Ho, J. J. Med. Chem. 1969, 12,
339e342.
28. (a) Reid, P. J.; Wickham, S. D.; Mathies, R. A. J. Phys. Chem. 1992, 96,
5720e5724; (b) Reid, P. J.; Shreve, A. P.; Mathies, R. A. J. Phys. Chem.
1993, 97, 12691e12699; (c) Bornemann, C.; Klessinger, M. Org. Lett.
1999, 1, 1889e1891.
6. (a) Gangjee, A.; Devraj, R.; McGuire, J. J.; Kisliuk, R. L.; Queener, S. F.;
Barrews, L. R. J. Med. Chem. 1994, 37, 1169e1176; (b) Gangjee, A.;
Zeng, Y.; McGuire, J. J.; Kisliuk, R. L. J. Med. Chem. 2005, 48, 5329e
5336.
29. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;

S. Naya et al. / Tetrahedron 64 (2008) 3225e3231
3231
Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels,
A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.;
Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cio-
slowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe,
M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.;
Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision
A.11; Gaussian: Pittsburgh, PA, 2001.
30. Woodward, R. B.; Hoffmann, R. J. Am. Chem. Soc. 1965, 87, 2511e2513.