New synthesis, properties, and oxidizing ability of 1,3-dimethyl-5,10- methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-dionylium tetrafluoroborate

Article abstract of DOI:10.1021/jo048575s

A novel synthesis of 1,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d] pyrimidin-2,4(1,3H)-dionylium tetrafluoroborate (10⁺·BF ₄^-) was accomplished by the reaction of 3,8-methano[11]-annulenone with dimethylbarbituric acid and following acidic cyclization, albeit in low yield. Remarkable structural characteristics were suggested on inspection of the spectral data and MO calculation, and it was clarified that the positive charge is largely localized at the C11. The pK _R+ value of cation 10⁺ was determined spectrophotometrically to be 4.6, which is much smaller by 4.1 pH unit than that of 1,3-dimethyl-7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)- dionylium tetrafluoroborate (pK_R+ = 8.7). This value is also smaller by 1.6 pH unit than that of the parent 1,6-methano[11]annulenylium ion (pK _R+ = 6.2). The feature is rationalized on the basis of the perturbation derived from the bond fixation of the parent cation. The electrochemical reduction of 10⁺ exhibited less negative reduction potential at -0.39 (V vs Ag/AgNO₃) upon cyclic voltammetry (CV). In a search for reactivity, reactions of 10⁺ with some nucleophiles, hydride and diethylamine, were carried out to give mixtures of C11- and C13-adducts. In both reactions, the methano-bridge controls the nucleophilic attacks to the C13 to favor exo selectivity. The photoinduced autorecycling oxidation reactions of 10⁺·BF₄^- toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) in 719-3286% yield (recycling number of 10⁺·BF ₄^-: 7.2-32.9).

Full text of DOI:10.1021/jo048575s

New Synthesis, Properties, and Oxidizing Ability of
1
,3-Dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-
2
,4(1,3H)-dionylium Tetrafluoroborate
Shin-ichi Naya, Masato Warita, Yuhki Mitsumoto, and Makoto Nitta*
Department of Chemistry, School of Science and Engineering, Waseda University, Shinjuku-ku,
Tokyo 169-8555, Japan
nitta@waseda.jp
Received August 16, 2004
A novel synthesis of 1,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-
+
-
4
dionylium tetrafluoroborate (10 ‚BF ) was accomplished by the reaction of 3,8-methano[11]-
annulenone with dimethylbarbituric acid and following acidic cyclization, albeit in low yield.
Remarkable structural characteristics were suggested on inspection of the spectral data and MO
calculation, and it was clarified that the positive charge is largely localized at the C11. The pKR+
+
value of cation 10 was determined spectrophotometrically to be 4.6, which is much smaller by 4.1
pH unit than that of 1,3-dimethyl-7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-
dionylium tetrafluoroborate (pKR+ ) 8.7). This value is also smaller by 1.6 pH unit than that of the
parent 1,6-methano[11]annulenylium ion (pKR+ ) 6.2). The feature is rationalized on the basis of
the perturbation derived from the bond fixation of the parent cation. The electrochemical reduction
+
of 10 exhibited less negative reduction potential at -0.39 (V vs Ag/AgNO
3
) upon cyclic voltammetry
+
(
CV). In a search for reactivity, reactions of 10 with some nucleophiles, hydride and diethylamine,
were carried out to give mixtures of C11- and C13-adducts. In both reactions, the methano-bridge
controls the nucleophilic attacks to the C13 to favor exo selectivity. The photoinduced autorecycling
+
-
oxidation reactions of 10 ‚BF
4
toward some amines under aerobic conditions were carried out to
give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhy-
drazones) in 719-3286% yield (recycling number of 10 ‚BF
+
-
4
: 7.2-32.9).
Introduction
Flavins are known to play an important role as
cofactors in a wide variety of biological redox reactions.1
The flavin-redox systems have been investigated exten-
sively through synthetic model systems and theoretical
,2
3
calculations. Among these compounds, 5-deazaflavins 1a
(
Figure 1) have been studied extensively in both enzy-
matic and model systems,5 in the hope of providing
4
mechanistic insight into flavin-catalyzed reactions. In
*
Address correspondence to this author. Phone: +81-(0)3-5286-
3
236. Fax: +81-(0)3-3208-2735.
(
1) Muller, F. Chemistry and Biochemistry of Flavoenzymes; Muller,
F., Ed.; CRC Press: Boca Raton, FL, 1991; Vol. 1, pp 1-71 and
references therein.
(
2) Hamilton, G. A. Progress in Bioorganic Chemistry; Kaiser, E.
T., Kezdy, F. J., Eds.; Wiley: New York, 1971; Vol. 1, p 83.
(3) (a) Chiu, C. C.; Pan, K.; Jordan, F. J. Am. Chem. Soc. 1995, 117,
FIGURE 1.
7
1
027-7028. (b) Kim, J.; Hoegy, S. E.; Mariano, P. S. J Am. Chem. Soc.
995, 117, 100-105. (c) Murahashi, S.; Ono, S.; Imada, Y. Angew.
this context, 5-deaza-10-oxaflavin 1b (2H-chromeno[2,3-
d]pyrimidin-2,4(3H)-dione), in which the nitrogen atom
is replaced by an oxygen, has also been synthesized and
found to possess a strong ability to oxidize alcohols to
the corresponding carbonyl compounds. On the basis of
the above observations, we have previously studied
Chem., Int. Ed. 2002, 41, 2366-2368. (d) Bergstad, K.; Jonsson, S.;
B a¨ chvall, J. J. Am. Chem. Soc. 1999, 121, 10424-10425. (e) Van
Houten, K. A.; Kim, J.; Bogdan, M. A.; Ferri, D. C.; Mariano, P. S. J.
Am. Chem. Soc. 1998, 120, 5864-5872. (f) Zheng, Y.; Ornstein, R. L.
J. Am. Chem. Soc. 1996, 118, 9402-9408. (g) Breinlinger, E. C.;
Keenan, C. J.; Rotello, V. M. J. Am. Chem. Soc. 1998, 120, 8606-8609.
6
(
h) Hasford, J. J.; Rizzo, C. J. J. Am. Chem. Soc. 1998, 120, 2251-
255. (i) Antony, J.; Medvedev, D. M.; Stuchebrukhov, A. A. J. Am.
Chem. Soc. 2000, 122, 1057-1065.
2
(
4) (a) Walsh, C. Acc. Chem. Res. 1986, 19, 216-221 and references
(5) Yoneda, F.; Kokel, B. Chemistry and Biochemistry of Flavoen-
zymes; Muller, F., Ed.; CRC Press: Boca Raton, FL, 1991; Vol. 1, pp
121-169 and references therein.
therein. (b) Yoneda, F.; Tanaka, K. Med. Res. Rev. 1987, 4, 477-506
and references therein.
10.1021/jo048575s CCC: $27.50 © 2004 American Chemical Society
9184
J. Org. Chem. 2004, 69, 9184-9190
Published on Web 11/10/2004

Novel Synthesis of Tetrafluoroborates
SCHEME 1a
TABLE 1. Results for the Reactions of 12 with 13
+
+
run
base
time/h
yield/%
ratio of 10 /4
1
2
3
4
Et3N
48
48
72
48
6
83:17
90:10
90:10
100:0
(TMS)2NH
(TMS)2NK
NaH
trace
trace
8
+
)
6.2)14 as compared with 5 (pKR+ ) 3.9).15 Due to this
+
-
property, cation 4 ‚BF
4
exhibited higher thermodynamic
stability (pKR+ ) 8.7). Furthermore, the reactions of
+
-
4
‚BF
4
4
with NaBD and diethylamine exhibit that the
methano-bridge controls the nucleophilic attacks to occur
with endo selectivity. Thus, study of the methano-bridged
compounds is an interesting project from the viewpoint
of exploration of novel chiral auxiliaries.
Furthermore, the π-conjugation mode in polycyclic
conjugated π-systems containing more than one (4n +
2
) conjugation loop is an important subject from both
theoretical and experimental viewpoints. We have re-
cently reported that perturbations derived from benzo-
annulation onto the cyclohepta[a]azulenylium ion are
highly dependent on the annulating positions.16 From this
viewpoint, the 1,6-methano[11]annulenylium ion annu-
lated with the furopyrimidine on a different position from
a
Reagents and conditions: (i) base, DMF, rt, 5 min; (ii) 35 °C,
+
-
that of 4 ‚BF
investigated the synthesis, properties, and reactivity of
,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]py-
4
seemed to be interesting. Thus, we have
4
8 or 72 h; (iii) 42% aq HBF4, Ac2O, 0 °C, 1 h.
1
convenient preparations of 10-substituted 3-methyl-
cyclohepta[4,5]pyrro[2,3-d]pyrimidin-2,4(3H)-diones 2a
and 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidin-2,4(3H)-
dione 2b, which are the structural isomers of 1a and
b, respectively, and their oxidation reactions toward
some alcohols to the corresponding carbonyl compounds.
In this relation, the synthesis, properties, and reactivity
+
-
4
rimidin-2,4(1,3H)-dionylium tetrafluoroborate (10 ‚BF ,
7
Scheme 1) for the first time. Its structural characteristics
are deduced based on the spectral data, pKR+, redox
potentials, and MO calculation. The photoinduced au-
torecycling oxidation of amines to give the corresponding
imines is studied as well. We report here the results in
detail.
8
1
+
- 9,10
of 3a ‚BF
4
,
and its sulfur and nitrogen analogues 3b-
+
- 11,12
d ‚BF
4
as well as their novel photoinduced auto-
Results and Discussion
recycling oxidation reactions toward some alcohols also
have been studied. Thus, structural modifications of the
uracil-annulated heteroazulenes such as 3a-d ‚BF
an interesting project from the viewpoint of exploration
of novel functions. Much of the motivation for studying
the properties of organic molecules stems from manipula-
tion of the primary chemical structure. One strategy for
raising or lowering the HOMO and LUMO levels includes
conjugation length control. On the basis of this concept,
we have recently reported the synthesis of 1,3-dimethyl-
Synthesis. A strategy for the preparation of 1,3-
dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimi-
+
-
4
are
+
-
din-2,4(1,3H)-dionylium tetrafluoroborate (10 ‚BF
4
) con-
1
7
sisted of the reaction of 3,8-methano[11]annulenone (12)
with dimethylbarbituric acid (13) and following acidic
cyclization. The reaction of 12 with 14, which is generated
3
by the reaction of 13 with Et N, proceeded at the C2 and
C11 to give a mixture of 15 and 16, as in the synthetic
reaction of 17 and 18 (Figure 3).18 Compounds 15 and
1
6 are unstable on TLC (SiO
2 2 3
and Al O ), and thus,
7
(
,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4-
1,3H)-dionylium tetrafluoroborate (4 ‚BF
which is a vinylogous compound of 3a, to involve 1,6-
+
-
13
without further isolation and purification, cyclization was
4
, Scheme 1),
+
-
carried out by using 42% aq HBF
4 ‚BF , respectively (Scheme 1, Table 1 run 1). Under
2 2
similar conditions, (TMS) NH- and (TMS) NK-induced
4
to give 10 ‚BF
4
and
+
-
+
methano[11]annulenylium ion 6 instead of tropylium ion
4
+
+
5
. The cation 6 , which is an aromatic 10π-electron
+
reactions of 12 and 13 afforded trace amounts of mixtures
analogue of 5 , has higher thermodynamic stability (pKR+
+
-
+
-
of 10 ‚BF
4
and 4 ‚BF
4
(Table 1, runs 2 and 3). In
contrast, the NaH-induced reaction of 12 with 13 afforded
(
6) Yoneda, F.; Hirayama, R.; Yamashita, M. Chem. Lett. 1980,
1
6
157-1160.
(
(
7) Nitta, M.; Tajima, Y. Synthesis 2000, 651-654.
(14) (a) Grimme, W.; Hoffmann, H.; Vogel, E. Angew. Chem., Int.
Ed. Engl. 1965, 4, 354. (b) Vogel, E.; Feldmann, R.; D u¨ wel, H.
Tetrahedron Lett. 1970, 1, 1941.
(15) Okamoto, K.; Takeuchi, K.; Komatsu, K.; Kubota, Y.; Ohara,
R.; Arima, M.; Takahashi, K.; Waki Y.; Shirai, S. Tetrahedron 1983,
39, 4011 and references therein.
(16) Yamane, K.; Yamamoto, H.; Nitta, M. J. Org. Chem. 2002, 67,
8114-8122.
(17) Vogel, E. 23rd Int. Congr. Pure Appl. Chem. 1971, 1, 275.
(18) Kanomata, N.; Kamae, K.; Iino, Y.; Nitta, M. J. Org. Chem.
1992, 57, 5313-5318.
8) Takayasu, T.; Mizuta, Y.; Nitta, M. Heterocycles 2001, 54, 601-
06.
(
(
9) Naya, S.; Nitta, M. Tetrahedron 2003, 59, 3709-3718.
10) Naya, S.; Miyama, H.; Yasu, K.; Takayasu, T.; Nitta, M.
Tetrahedron 2003, 59, 1811-1821.
(
11) Naya, S.; Miyama, H.; Yasu, K.; Takayasu, T.; Nitta, M.
Tetrahedron 2003, 59, 4929-4938.
(
(
12) Naya, S.; Nitta, M. Tetrahedron 2003, 59, 7291-7299.
13) Naya, S.; Yamaguchi, Y.; Nitta, M. J. Org. Chem. 2003, 68,
9
284-9291.
J. Org. Chem, Vol. 69, No. 26, 2004 9185

Naya et al.
TABLE 2. 3+C NMR Data and Calculated Charge
1
Density of 10
position
δc
charge
position
δc
charge
C2
C4
C4a
C4b
C5
C6
C7
C8
C9
150.6
164.9
101.1
151.7
129.4
139.0
141.7
139.6
141.3
1.106
0.944
-0.275
0.061
0.027
0.157
0.070
0.061
0.100
C10
140.0
157.2
130.7
129.3
153.7
158.4
31.4
0.049
0.121
0.058
0.052
0.343
0.895
0.392
0.379
0.044
C11
C12
C13
C13a
C14a
N1Me
N3Me
CH2
29.6
31.3
the methylene protons (JE,Z ) 12.4 Hz) supports the
+
-
absence of a norcaradiene structure for 10 ‚BF
4
. The
+
-
bridge protons of 10 ‚BF
4
appear at very high field (δ
-
0.53 and -1.33), and the peripheral protons appear in
+
FIGURE 2. UV-vis spectra of 10 and reference compounds
the aromatic region (δ 8.43 to 10.11), suggesting a large
+
+
3
3
a and 4 in CH CN.
diatropic ring current.19 The vicinal coupling constants
+
-
of protons of the aromatic perimeter of 10 ‚BF
4
suggest
that the C6-C7-C8-C9 moiety exhibits small bond
alternation [J6,7 (8.6 Hz), J7,8 (10.0 Hz), J8,9 (8.6 Hz)]. This
+
-
feature is similarly observed for compound 4 ‚BF
4
. In
contrast, it is noteworthy that the C11-C12-C13 moiety
+
-
of 10 ‚BF
4
exhibits large bond alternation [J11,12 (9.7 Hz)
<
J
12,13 (12.5 Hz)]. While the vicinal coupling constants
+
-
in the cycloheptatriene moiety of 4 ‚BF
4
and 18 are
similar, a large difference in the vicinal coupling con-
+
-
13
stants in 10 ‚BF
4
and 17 was observed. The C NMR
+
-
spectral data for 10 ‚BF
4
were fully assigned by using
the H-C Cosy spectra (HMQC and HMBC) as sum-
marized in Table 2. Concerning the 11-membered ring,
the chemical shift of the C13 carbon appeared at much
+
-,
higher field (δ
carbons. In addition, the C11 carbon appeared at much
lower field (δ 157.2) as compared with those of other
c
129.3) as compared with those of other
FIGURE 3. Coupling constants (J, in Hz) of 10 ‚BF
4
+
-
4
4
‚BF , 17, and 18.
c
+
-
carbons of the 11-membered ring, suggesting that the
positive charge is localized largely at the C11-position.
a single product 15, which is converted to 10 ‚BF
4
upon
treatment with 42% aq HBF in Ac O (Table 1, run 4).
Unfortunately, the yields are poor, and thus, details of
these reactions cannot be discussed at this stage.
is known and com-
was fully characterized on the basis of
the H NMR, C NMR, IR, UV-vis, and mass spectral
data, as well as elemental analysis. The mass spectrum
4
2
+
-
Unfortunately, a single crystal of 10 ‚BF
4
was not
obtained by recrystallization from various solvents; how-
+
-
13
ever, we have reported that the structural details of 3b-
Properties. Compound 4 ‚BF
4
+
+
+
-
d and 4 obtained by MO calculation show good agree-
pound 10 ‚BF
4
9,11-13
1
13
ment with those obtained by X-ray crystal analyses.
+
Thus, MO calculation of 10 was carried out by the
6-31G* basis set of the MP2 levels,20 and the results are
also summarized in Table 2. The calculated charge
density of the C11 (+0.121) is relatively large, which
accords with the feature of the C NMR spectrum. Thus,
the canonical structures 10 -B and 10 -C would be
important for 10 (Figure 4). Furthermore, the calculated
+
-
+
-
of 10 ‚BF
4
exhibited the correct M - BF
4
ion peak,
which is indicative of the cationic structure of the
compound. The characteristic absorption band for the
13
-
-1
counterion of BF
4
was observed at 1084 cm in the IR
+
+
+
-
spectrum. The UV-vis spectrum of 10 ‚BF
4
3
in CH CN
+
+
-
is shown in Figure 2, together with those of 3a ‚BF
4
+
-
bond length of C14a-O14 (1.349 Å) is shorter than that
of C13a-O14 (1.395 Å), suggesting that a contribution
and 4 ‚BF
4
. The longest wavelength absorption maxi-
+
-
mum (λmax) of 10 ‚BF
compared with that of 3a ‚BF
π-conjugation. In addition, a red-shift (14 nm) of λmax of
4
shows a red-shift by 110 nm as
+
+
-
of 10 -D is less important.
4
, suggesting the elongated
+
-
+
-
(19) Vogel, E. Chem. Soc. Spec. Publ. 1967, 21, 113.
1
0 ‚BF
4
from that of 4 ‚BF
4
shows a larger perturba-
tion due to the annulating position of the furopyrimidine
(
20) 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.; 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.; Cioslowski, 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, Inc.: Pittsburgh,
PA, 2001.
1
+
-
ring. The H NMR spectrum of 10 ‚BF
4
is noteworthy,
since the chemical shifts of bridged-annulene systems are
quite useful in determining such structural properties as
diatropicity and bond alternation. Unambiguous proton
assignment was made by analyzing 1H NMR, H-H
COSY, and NOE spectra and selected coupling constants
+
-
of the peripheral protons of 10 ‚BF
4
are shown in Figure
+
-
3
4
together with those of the reference compounds 4 ‚BF ,
1
8
18
1
7, and 18. The large geminal coupling constant of
9186 J. Org. Chem., Vol. 69, No. 26, 2004

Novel Synthesis of Tetrafluoroborates
SCHEME 2a
FIGURE 4.
TABLE 3. pKR+ Values and Reduction Potentials of
+
+
+
+
+
a
Cations 10 and Reference Compounds 3a , 4 , 5 , and 6
4 3
Reagents and conditions: (i) NaBH , CH CN, rt, 1 h; (ii) (a)
DDQ, CH2Cl2, rt, 1 h, (b) 42% aq HBF4, Ac2O, 0 °C, 1 h; (iii) hv,
aerobic, 42% aq HBF4, CH3CN-CH2Cl2, rt, 24 h.
reduction potential
b
compd
pKR+
(E1red)
+
a
1
3
4
5
6
0
4.6
ca. 6.0
8.7
-0.39
-0.58
-0.43
-0.51g
-0.42
4+
. Due to this larger perturbation, the λmax of 10 would
+
+
c
a
+
+
d
e
f
show a red-shift from that of 4 (vide supra). In the cation
+
+
+
3.9
10 , this destabilizing effect is larger than the stabilizing
6.2
effect derived from the electron-donating ability of furo-
+
a
+
-
b
pyrimidine, and thus the cation 10 would exhibit a
Salts 10 ‚BF4 are used for the measurement. V vs Ag/
AgNO3; cathodic peak potential. Reference 10. d Reference 13.
c
+
smaller pKR+ value as compared with that of 6 .
e
Reference 15. Reference 14. g This work.
f
+
The reduction potential of 10 was determined by cyclic
voltammentry (CV) in CH CN. The reduction wave was
3
irreversible under the conditions of the CV measure-
ments; the peak potential is summarized in Table 3,
The affinity of the carbocation toward hydroxide ions
expressed by the pKR+ value is the most common criterion
of carbocation stability. The pKR+ values of cation 10
were determined spectrophotometrically in buffer solu-
tions prepared in 50% aqueous CH CN and are sum-
marized in Table 3, along with those of the reference
21
+
9
+ 13
together with those of the reference compounds 3a, 4 ,
+
15
+ 14
+
5 , and 6 . The E1 of 10 is less negative by 0.19 V
red
+
3
than that of 3a , suggesting the elongated π-conjugation
+
-
+
of 10 ‚BF . Furthermore, the less negative E1 of 10
4
red
+
9
+ 13 + 15
+ 14
+
compounds 3a , 4 , 5 , and 6 . The pKR+ value of
by 0.04 V as compared with that of 4 would be
+
+ 12,23
1
0
was determined to be 4.6, which is smaller by 4.1
comparable to the lower pKR+ value of 10 .
The
+
pH unit than that of 4 (pKR+ ) 8.7). In the reference
irreversible nature is probably due to the formation of a
radical species and its dimerization, as reported to be a
typical property of uracil-annulated heteroazulenylium
+
+
compounds 3a and 4 , the annulation of the electron-
donating furopyrimidine ring stabilizes the parent cations
+
+
+ 10-12
+ 13
5
1
6
and 6 , respectively. In contrast, the pKR+ value of
ions 3a-d
and 4 .
0+ is smaller by 1.6 pH unit than that of 6 (pKR+
+
)
+
-
Reactivity. The reactions of 10 ‚BF4 with some
nucleophiles were investigated. While the reaction of
+
.2), and thus, on the cation 10 , the annulation of the
+
+
-
furopyrimidine ring destabilizes the parent cation 6 . The
3a ‚BF4 with NaBH proceeded at C5, C7, and C9 to
4
+
+
fact is quite different from those of 3a and 4 . The
give a mixture of three regioisomers 19-21 (19:20:21 29:
12:59),10 the reaction of 4 ‚BF proceeded at the C13 to
+
-
feature is rationalized on the basis of the perturbation
4
+
13
derived from the bond fixation of the parent cation 6 .
afford a single product 22. On the other hand, the
+
-
We have recently clarified that perturbations derived
from benzo-annulation onto the cyclohepta[a]azulenylium
ion are highly dependent on the annulating positions.16
While the benzo-annulation on the double bond having
a large bond order of the parent cation causes smaller
perturbation, the benzo-annulation on the double bond
having a small bond order significantly perturbs both the
original π-system and the annulating benzene ring.
reaction of 10 ‚BF4 with NaBH proceeded at C11 and
4
C13 to give a mixture of 23 and 24 (in a ratio of 11:89)
in quantitative yield (Scheme 2). There is a well-known
tendency for double bond fixation in the methano[11]-
annulene system to favor a cycloheptatriene moiety
predominantly over a 1,6-dimethylenecyclohepta-2,4-
diene moiety.24 Thus, the formation of 23 and 24 would
be ascribed to the stability of both the cycloheptatriene
moiety and the closed furan ring. The formation of the
C13-adduct predominates over the C11-adduct, although
the positive charge is localized at C11 mainly (vide
+
Regarding cation 6 , the X-ray crystal analysis has
revealed that the bond length of C7-C8 (1.416 Å) is
longer than that of C8-C9 (1.375 Å).22 Thus, the annu-
+
+
-
lation of the furopyrimidine ring onto 6 at C7-C8 giving
supra). The feature is similar to the reaction of 3a ‚BF
4
+
1
0 would cause a larger perturbation than the annula-
4
with NaBH , in which the ratio of C9-adduct 21 was
+
tion of the furopyrimidine ring onto 6 at C8-C9 giving
(
23) Naya, S.; Nitta, M. J. Chem. Soc., Perkin Trans. 2 2000, 2427-
(
21) Freedman, H. H. Carbonium Ions; Olah, G. A., Schleyer, P.,
Eds.; Wiley-Insterscience: New York, 1973.
22) Destro, R.; Simonetta, M. Acta Crystallogr. 1979, B35, 1846-
852.
2435.
(24) (a) Paquette, L. A.; Berk, H. C.; Ley, S. V. J. Org. Chem. 1975,
40, 902 and references therein. (b) Reisdorff, J.; Vogel, E. Angew.
Chem., Int. Ed. Engl. 1972, 11, 218.
(
1
J. Org. Chem, Vol. 69, No. 26, 2004 9187

Naya et al.
TABLE 4. Autorecycling Oxidation of Some Amines by 10 ‚BF4 under Photoirradiationa
+
-
entry
compd
amine
imine
yieldb,c/%
recycling no.d
+
-
-
-
-
-
1
2
3
4
5
6
7
8
10 ‚BF4
PhCH2NH2
PhCH(Me)NH2
hexylamine
cyclohexylamine
PhCH2NH2
PhCH2NH2
PhCHdNCH2Ph
2238
1733
3286
719
8161
3007
3947
2267
22.4
17.3
32.9
7.2
81.6
30.1
39.5
22.7
+
10 ‚BF4
PhMeCdNCHMePh
N-hexylhexanal imine
N-cyclohexylcyclohexanone imine
PhCHdNCH2Ph
+
10 ‚BF4
+
10 ‚BF4
+
3a ‚BF4
+
-
4 ‚BF4
PhCHdNCH2Ph
PhMeCdNCHMePh
PhMeCdNCHMePh
+
-
3a ‚BF4
PhCH(Me)NH2
PhCH(Me)NH2
+
-
4 ‚BF4
a
b
CH3CN solution was irradiated by RPR-100, 350-nm lamps under aerobic conditions. Isolated by converting to the corresponding
c
+
-
+
-
+
-
carbonyl compounds and then to 2,4-dinitrophenylhydrazones. Based on 10 ‚BF4 , 3a ‚BF4 , and 4 ‚BF4 used; the yield is calculated
+
-
+
-
+
- d
by subtraction of the “blank” yield from the total yield of imine in the presence of 10 ‚BF4 , 3a ‚BF4 , and 4 ‚BF4 . Recycling number
+
-
+
-
+
-
of 10 ‚BF4 , 3a ‚BF4 , and 4 ‚BF4 .
larger than those of C5- and C7-adducts, 19 and 20.10
SCHEME 3a
Recrystallization of a mixture of 23 and 24 from CH
3
CN
gave a pure sample of major product 24. To clarify the
+
-
endo-exo selectivity, a reaction of 10 ‚BF
was carried out in an NMR tube to give a mixture of C11-
adduct 23-d and C13-adduct 24-d and 24. Since NaBD
used for the reaction is of 96% deuterium content, the
4 4
with NaBD
4
+
-
reaction of 10 ‚BF
4
with the remaining hydride would
give also compound 24. The ratio of 23-d, 24-d, and 24
1
was determined to be 16:76:10 by the H NMR spectrum
of the mixture. The structural assignment of 23, 24, 23-
d, and 24-d was based on the NMR, IR, and mass spectral
data. Furthermore, compounds 23-d and 24-d were
determined to be the exo adduct by the H-H COSY and
NOE spectra. Upon hydride abstraction with DDQ and
subsequent anion exchange reaction, a mixture of com-
+
-
pounds 23 and 24 regenerated 10 ‚BF
yield. Furthermore, photoirradiation of a mixture of
compounds 23 and 24 in CH CN and (CH Cl) solution
under aerobic conditions
mainly in addition to uniden-
4
in quantitative
3
2
2
containing 42% aquaous HBF
4
+
-
for 24 h afforded 10 ‚BF
4
tified materials.
The reaction of 3a ‚BF
+
-
4
with diethylamine has been
shown to give a C9a-adduct, which underwent ring-
10
opening reaction to give 25 (Scheme 3). In contrast, the
+
-
diethylamine addition of 4 ‚BF
4
occurred at low tem-
perature (-65 °C) to give C13-adduct 26, which isomer-
13
a
ized to 27 (Scheme 3) at higher temperature (>-35 °C).
Reagents and conditions: (i) Et2NH, CH3CN, rt, 1 h; (ii) 42%
+
-
aq HBF4, Ac2O, 0 °C, 1 h; (iii) CH3CN, reflux, 24 h.
In the reaction of 10 ‚BF
of 28a,b and 29 was obtained in quantitative yield. Since
the products were unstable on SiO and Al , isomers
4
with diethylamine, a mixture
1
0-12
photoirradiation.
Moreover, compounds 2a and
have also been reported to undergo autorecycling
oxidation toward some amines under photoirradia-
2
2 3
O
+
-
4
‚BF
4
2
8a,b and 29 could not be separated. Thus, the structural
1
assignment of 28a,b and 29 was based on the H NMR,
tion.1
3,25
In this context, we examined the oxidation of
some amines by using 10 ‚BF . We found that com-
have an oxidizing ability toward ben-
1
IR, and HRMS spectra. The H NMR spectra of 28a,b
+
-
and 29 are unequivocally assigned by using the H-H
COSY and NOE spectra, and the ratio of 28a,b and 29
4
+
-
pounds 10 ‚BF
4
1
zylamine, 1-phenylethylamine, hexylamine, and cyclo-
hexylamine to give the corresponding imines under
aerobic and photoirradiation conditions. The results are
summarized in Table 4, together with the results ob-
was determined to be 22:14:64 by the H NMR spectrum
of the mixture; exo adduct 28a predominates slightly. On
the other hand, the addition reaction at the C13 pro-
ceeded selectively to give only exo adduct 29. This exo
+
-
+
-
tained by using reference compounds 3a ‚BF and
selectivity is similar to the reaction of 10 ‚BF
4
with
4
+
-
+
-
4
‚BF
as compared with those of 3a ‚BF
irradiation of the amines in the absence of 10 ‚BF
4
. The reactions with 10 ‚BF
4
gave lower yields
NaBD (vide supra). The results show the feasibility of
4
+
-
+
-
4
4
and 4 ‚BF . Direct
the methano[11]annulene system for the exploration of
+
-
a novel chiral auxiliary. Unlike in the case of 26,13
4
(
named “blank”) gives the corresponding imines in small
heating of 28a,b and 29 in CH
isomerization, such as a reaction giving 30. Upon treat-
ment with aq HBF in Ac O, a mixture of compounds
8a,b and 29 regenerated 10 ‚BF
Autorecycling Oxidation. Compounds 3a-d ‚BF
act as a catalyst for oxidation of some alcohols under
3
CN did not undergo any
amounts. Thus, the yield in Table 4 is calculated by
subtraction of the “blank” yield from the yield of the imine
4
2
+
-
+
-
in the presence of 10 ‚BF . Imines are obtained in more
2
4
in good yield.
4
+
-
4
(25) Naya, S.; Iida, Y.; Nitta, M. Tetrahedron 2004, 60, 459-467.
9188 J. Org. Chem., Vol. 69, No. 26, 2004

Novel Synthesis of Tetrafluoroborates
added saturated 3% HCl, and the mixture was extracted with
AcOEt. The extract was dried over Na SO and concentrated
in vacuo. The residue was dissolved in a mixture of Ac O (10
mL) and 42% HBF (2 mL) at 0 °C, and the mixture was stirred
for another 1 h. To the mixture was added Et O (50 mL) and
the precipitates were collected by filtration to give 4 ‚BF
2
4
2
4
2
+
-
4
and/
. The results are summarized in Table 1 (run 1,
3.6 mg, 6%; run 4, 31.5 mg, 8%).
Determination of pKR+ Value of Cation 10 . Buffer
+
-
or 10 ‚BF
4
2
+
solutions of slightly different acidities were prepared by mixing
aqueous solutions of potassium hydrogen phthalate (0.1M) and
HCl (0.1 M) (for pH 2.2-4.0), potassium hydrogen phthalate
(
2 4
0.1M) and NaOH (0.1 M) (for pH 4.1-5.9), and KH PO (0.1M)
and NaOH (0.1 M) (for pH 6.0-8.0) in various portions. For
the preparation of sample solutions, 1 mL portions of the stock
+
-
solution, prepared by dissolving 4 mg of compound 10 ‚BF
4
in CH
solution (8 mL) and CH
3
CN (20 mL), were diluted to 10 mL with the buffer
CN (1 mL). The UV-vis spectrum was
FIGURE 5. Time dependency of autorecycling oxidation of
3
+
-
+
benzylamine by using 10 ‚BF
4
.
recorded for cation 10 in 20 different buffer solutions.
Immediately after recording the spectrum, the pH of each
solution was determined on a pH meter calibrated with
standard buffers. The observed absorbance at the specific
than 100% yield [based on compound 10 ‚BF
4
-] under
+
photoirradiation, and thus, autorecycling oxidation clearly
proceeds. To clarify the time dependency of the oxidizing
+
absorption wavelength (500 nm) of cation 10 was plotted
1
against pH to give a classical titration curve, whose midpoint
reaction, H NMR monitoring of the photooxidation
+
-
was taken as the pKR+ value.
reaction of 10 ‚BF
4
toward benzylamine was carried out.
+
Cyclic Voltammetry of 10 . The reduction potential of
By using mesitylene as an internal standard, the yield
of imine is recorded by using the H NMR spectra at
+
-
1
0 ‚BF
4
was determined by means of CV-27 voltammetry
1
controller (BAS Co). A three-electrode cell was used, consisting
selected intervals. The results are summarized in Figure
of Pt working and counter electrodes and a reference Ag/
5
. The yield of benzaldimine was increased linearly as
AgNO electrode. Nitrogen was bubbled through an acetoni-
3
+
-
-3
the irradiation time was prolonged to 48 h, suggesting
that 10 ‚BF
trile solution (4 mL) of 10 ‚BF
4
(0.5 mmol dm ) and
+
-
Bu NClO (0.1 mol dm-3) to deaerate it. The measurements
4
would be stable under these conditions.
4 4
-
1
were made at a scan rate of 0.1 V s and the voltammograms
were recorded on a WX-1000-UM-019 (Graphtec Co) X-Y
recorder. Immediately after the measurements, ferrocene (0.1
mmol) (E1/2 ) +0.083) was added as the internal standard,
and the observed peak potentials were corrected with reference
Attempted detection of the intermediate such as reduced
compounds 23 and 24 in the oxidation reaction of amines
is unsuccessful at this stage. We propose that the present
autorecycling oxidation proceeds via electron transfer
+
- 10,25
from amines to the excited cation 10 ‚BF
4
;
however,
to this standard. Compound 10
reduction wave, which is summarized in Table 3.
+
‚BF
4
exhibited an irreversible
-
further studies will be required to clarify the detailed
mechanistic aspect.
+
-
+
-
Reaction of 10 ‚BF
19.7 mg, 0.05 mmol) and NaBH
CN (3 mL) was stirred at room temperature for 1 h. To the
mixture was added saturated aqueous NH Cl solution, and the
mixture was extracted with CH Cl . The extract was dried over
4
with NaBH
4 4
. A solution of 10 ‚BF
(
4
(8 mg, 0.20 mmol) in CH
3
-
Summary
4
Novel synthesis of 1,3-dimethyl-5,10-methanocyclo-
2
2
2 4
Na SO and concentrated in vacuo to give a mixture of 23 and
24 (15.5 mg, 100%).
undeca[4,5]furo[2,3-d]pyrimidin- 2,4(1,3H)-dionylium tet-
+
-
4
rafluoroborate (10 ‚BF ) was accomplished albeit in low
1
+
-
H NMR Monitoring of the Reaction of 10 ‚BF
4
with
yield. The structural characteristics were clarified by the
inspection of the spectral data and the MO calculation.
+
-
NaBD
mmol) in CD
4
. To a solution of compound 10 ‚BF
4
(3.9 mg, 0.01
4
(2.1 mg, 0.05
3
CN (0.5 mL) was added NaBD
+
-
The physical properties of 10 ‚BF
4
were studied by
mmol) at room temperature in an NMR tube. After 1 h, the
NMR measurement was carried out.
Oxidation of a Mixture of 23 and 24. To a stirred solution
2 2
of 23 and 24 (15.4 mg, 0.05 mmol) in CH Cl (2 mL) was added
measurement of the UV-vis spectra, the pKR+ values,
and the reduction potentials. Reactions of 10 ‚BF
+
-
4
with
hydride and diethylamine afforded mixures of C11- and
C13-adducts. In both reactions, the methano-bridge
controls the nucleophilic attacks to the C13 to prefer exo
selectivity. The results show that the methano[11]-
annulene system shows promise for the novel chiral
auxiliary. The photoinduced oxidation reactions of
DDQ (17.6 mg, 0.075 mmol), and the mixture was stirred at
room temperature for 1 h. After evaporation of the CH Cl
the residue was dissolved in a mixture of Ac O (2 mL) and
2% HBF (0.4 mL) at 0 °C, and the mixture was stirred for
2
2
,
2
4
4
2
another 1 h. To the mixture was added Et O (10 mL) and the
+
-
precipitates were collected by filtration to give 10 ‚BF
4
(20
+
-
1
0 ‚BF
were carried out to give the corresponding imines in 719-
286% yields (7.2-32.9 cycles).
4
toward some amines under aerobic conditions
mg, 100%).
Oxidation of a Mixture of 23 and 24 by Photoirradia-
3
tion. A solution of a mixture of 23 and 24 (16.7 mg, 0.054
mmol) and 42% aq HBF
2
4 3 2
(0.1 mL) in CH CN (1 mL) and CH -
Cl
(2 mL) in a Pyrex tube was irradiated by RPR-100, 350-
Experimental Section
nm lamps under aerobic conditions for 24 h until the reaction
was complete. The mixture was concentrated in vacuo, and
the resulting residue was dissolved in a mixture of acetic
Preparation of 1,3-Dimethyl-5,10-methanocycloundeca-
[
4,5]furo[2,3-d]pyrimidin- 2,4(1,3H)-dionylium Tetrafluo-
+
-
roborate (10 ‚BF
4
). A solution of dimethylbarbituric acid
anhydride (2 mL) and 42% aq HBF
4
(0.4 mL) at 0 °C. The
1
3 (780 mg, 5 mmol) and base (4 mmol) in DMF (2 mL) was
mixture was stirred for 1 h. To the mixture was added Et O
2
stirred at room temperature for 5 min. To the solution was
(20 mL) and the precipitate was collected by filtration to give
+
-
added 12 (204 mg, 1 mmol) and the mixture was stirred at 35
10 ‚BF
4
mainly in addition to unidentified materials (13.5
°
C for the period indicated in Table 1. To the mixture was
mg).
J. Org. Chem, Vol. 69, No. 26, 2004 9189

Naya et al.
+
-
+
-
Reaction of 10 ‚BF
4
with Diethylamine. To a solution
compound 10 ‚BF
4
(0.197 mg, 0.0005 mmol), benzylamine
+
-
of 10 ‚BF
4
(19.7 mg, 0.05 mmol) in CH CN (2 mL) was added
diethylamine (11 mg, 0.15 mmol), and the mixture was stirred
at room temperature for 1 h. To the mixture was added
3
(18.73 mg, 0.175 mmol), and mesitylene (internal standard;
3.6 mg, 0.03 mmol) in an NMR tube was irradiated by RPR-
100, 350-nm lamps under aerobic conditions. The NMR
measurement was carried out at intervals, and the yield of
benzaldimine calculated by the ratio of the H signal of
benzaldimine and mesitylene was plotted against them (Figure
saturated aqueous NH
extracted with CH Cl
4
Cl solution, and the mixture was
SO and
. The extract was dried over Na
2
4
1
2
2
concentrated in vacuo to give a mixture of 28a,b and 29 (19.0
mg, 100%).
5).
4
Reaction of a Mixture of 28a,b and 29 with HBF . To a
solution of a mixture of 28a,b and 29 (19.0 mg, 0.05 mmol) in
Ac O (2 mL) was added 42% aq HBF (0.4 mL) at 0 °C. The
Acknowledgment. Financial support from a Wase-
2
4
mixture was stirred for 1 h. To the mixture was added Et
2
O
da University Grant for Special Research Project and
21COE “Practical Nano-chemistry” from MEXT, Japan,
is gratefully acknowledged. We thank the Materials
Characterization Central Laboratory, Waseda Univer-
sity, for technical assistance with the spectral data and
elemental analyses.
(
1
10 mL) and the precipitate was collected by filtration to give
+
-
0 ‚BF
4
(20 mg, 100%).
General Procedure for Autorecycling Oxidation of
+
-
Amines in the Presence of 10 ‚BF
4
. A CH
3
CN (16 mL)
+
-
solution of compound 10 ‚BF
4
(1.97 mg, 0.005 mmol) and
amines (2.5 mmol, 500 equiv) in a Pyrex tube was irradiated
by RPR-100, 350-nm lamps under aerobic conditions for 16 h.
The reaction mixture was concentrated in vacuo and diluted
Supporting Information Available: Physical, analytical,
with Et
2
O and filtered. The filtrate was treated with a
+
-
4
and spectroscopic data for 10 ‚BF , 23, 24, 23-d, 24-d, 28a,b,
saturated solution of 2,4-dinitrophenylhydrazine in 6% HCl
to give 2,4-dinitrophenylhydrazone. The results are sum-
marized in Table 4.
1
13
+
-
4
and 29 and H and C NMR spectra of 10 ‚BF , 23, 24, 23-
d, 24-d, 28a,b, and 29. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
H NMR Monitoring of the Photooxidation of Benzyl-
amine by Using 10 ‚BF
+
-
4
. A CD
3
CN (0.5 mL) solution of
JO048575S
9190 J. Org. Chem., Vol. 69, No. 26, 2004