Novel synthesis, properties, and NAD+-NADH type redox ability of 1,3-dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium ions annulated with additional pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-dione and furan analogue, and their hydride adducts

Article abstract of DOI:10.1021/jo0514523

A convenient preparation of novel cations 11a,b⁺·BF ₄^- and 12a,b⁺·BF₄ ^-, which are derived from annulation of the 1,3-dimethylcyclohepta[4, 5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium ion with additional pyrrolo[2,3-d]pyrimidine-1,3(2,4ii)-dione and a furan analogue, was accomplished by a novel oxidative cyclization of 1,7-dihydro-7-[1′,3′-dimethyl- 2′,4′(1′,3′H)-dioxo-6′-(phenylamino) -pyrimidin-5′-yl]-1,3-dimethyl-10-phenylcyclohepta[4,5]pyrrolo[2,3-d] pyrimidine-2,4(1,3H)-dione 9 and its furan-analogue by using DDQ or photoirradiation under aerobic conditions. Structural characteristics of 11a,b⁺ and 12a,b⁺ were clarified on inspection of the UV-vis and NMR spectral data as well as X-ray crystal analyses. The stability of cations 11a,b⁺ and 12a,b⁺ is expressed by the pK _R+ values that were determined spectrophotometrically to be 10.7-12.6. The electrochemical reduction of 11a,b⁺·BF ₄ and 12a,b⁺·BF₄^- exhibited reduction potential at -0.93 to -1.00 (V vs Ag/AgNO₃). The first reduction potential of 11a⁺ was reversible due to steric hindrance of two phenyl groups. The photoinduced oxidation reaction of 11a,b ⁺·BF₄^- and 12a,b⁺· BF₄^- toward some amines under aerobic conditions was carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling numbers of 0.6-30.3. Furthermore, as an example of the NAD⁺-NADH models, the reduction of a pyruvate analogue and some carbonyl compounds with the hydride-adduct of 11a⁺-BF₄^- was accomplished for the first time to give the corresponding alcohol derivatives.

Full text of DOI:10.1021/jo0514523

Novel Synthesis, Properties, and NAD+-NADH Type Redox Ability
of 1,3-Dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-
2,4(1,3H)-dionylium Ions Annulated with Additional
Pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-dione and Furan Analogue, and
Their Hydride Adducts
Shin-ichi Naya, Junya Nishimura, and Makoto Nitta*
Department of Chemistry, School of Science and Engineering, Waseda University, Shinjuku-ku,
Tokyo 169-8555, Japan
nitta@waseda.jp
Received July 14, 2005
-
A convenient preparation of novel cations 11a,b+‚BF4 and 12a,b+‚BF4-, which are derived from
annulation of the 1,3-dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium ion with
additional pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-dione and a furan analogue, was accomplished by a
novel oxidative cyclization of 1,7-dihydro-7-[1′,3′-dimethyl-2′,4′(1′,3′H)-dioxo-6′-(phenylamino)-
pyrimidin-5′-yl]-1,3-dimethyl-10-phenylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dione 9
and its furan-analogue by using DDQ or photoirradiation under aerobic conditions. Structural
characteristics of 11a,b+ and 12a,b+ were clarified on inspection of the UV-vis and NMR spectral
data as well as X-ray crystal analyses. The stability of cations 11a,b+ and 12a,b+ is expressed by
the pKR+ values that were determined spectrophotometrically to be 10.7-12.6. The electrochemical
reduction of 11a,b+‚BF4 and 12a,b+‚BF4 exhibited reduction potential at -0.93 to -1.00 (V vs
Ag/AgNO3). The first reduction potential of 11a+ was reversible due to steric hindrance of two
phenyl groups. The photoinduced oxidation reaction of 11a,b+‚BF4- and 12a,b+‚BF4- toward some
amines under aerobic conditions was carried out to give the corresponding imines (isolated by
converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling numbers of 0.6-
30.3. Furthermore, as an example of the NAD+-NADH models, the reduction of a pyruvate analogue
-
-
and some carbonyl compounds with the hydride-adduct of 11a+‚BF4 was accomplished for the
-
first time to give the corresponding alcohol derivatives.
Introduction
N-substituent in the amide of 1-alkylated 1,4-dihydroni-
cotinamides, e.g., 1, can induce a modest to moderate
chirality transfer toward carbonyl compounds (Figure
1).12,13 Furthermore, Ohno and co-workers have improved
considerably a chirality transfer by the additional intro-
duction of methyl groups at the C2 and C4 in the NADH
model, e.g., compound 2.14 The new chiral center at the
Coenzyme NADH, a cofactor of L-lactate dehydroge-
nase, functions as an enantioselective agent that reduces
pyruvate to L-lactate during anaerobic glycolysis. During
several decades, efforts have been made to create model
compounds mimicking the activity of the NAD+-NADH
redox couple.1-11 The introduction of an optically active
(3) Murakami, Y.; Kikuchi, J.; Hisaeda, Y.; Hayashida, O. Chem.
Rev. 1996, 96, 721.
* To whom correspondence should be addressed. Tel: +81-(0)3-5286-
3236. Fax: +81-(0)3-3208-2735.
(1) Kanomata, N.; Nakata, T. J. Am. Chem. Soc. 2000, 122, 4563.
(2) Kanomata, N. J. Synth. Org. Chem. Jpn. 1999, 57, 512.
(4) Dupas, G.; Levacher, V.; Bourguignon, J.; Que´guiner, G. Het-
erocyles 1994, 39, 405.
(5) Burgess, V. A.; Davies, S. G.; Skerlj, R. T. Tetrahedron: Asynm-
metry 1991, 2, 299.
10.1021/jo0514523 CCC: $30.25 © 2005 American Chemical Society
Published on Web 11/03/2005
9780
J. Org. Chem. 2005, 70, 9780-9788

Novel NAD+-NADH Model
novel photoinduced autorecycling oxidizing reactions
toward some alcohols and amines.19 In these studies, it
-
was clarified that the pyrrole analogue 4c+‚BF4 has
higher stability (pKR+ ) 10.9, vide infra) when compared
with 4a,b+‚BF4 (4a+‚BF4 pKR+ ) ca. 6.0; 4b+‚BF4
-
-
-
pKR+ ) 5.1). The π-conjugation mode in polycyclic con-
jugated π-systems containing more than one (4n + 2)
conjugation loop is an important subject from both
theoretical and experimental viewpoints. Combination of
more than one π-system can endow the original π-system
with new properties. From this viewpoint, we have
recently reported the synthesis, properties, and oxidizing
ability of 5+‚BF4
and 6a,b+‚BF4
.
The properties
- 20
- 21
and reactivity of compound 5+‚BF4- indicated that much
perturbation occurs by the benzo-annulation onto 4a+‚
BF4-, and the pKR+ value of 5+‚BF4- is reduced to 4.7 as
compared with the parent cation 4a+‚BF4 (pKR+ ) ca.
-
6.0). The properties and reactivity of compounds 6a,b+‚
BF4- were also much perturbed by the annulation of the
furopyrimidine ring onto 4a+‚BF4-; however, the pKR+
FIGURE 1.
-
values of 6a,b+‚BF4 were larger to be 8.8 and 8.6,
C4 controls the mode of hydride transfer. Moreover, the
reduction of carbonyl compounds by using 1,5-dihydro-
5-deazaflavin 3 has been reported.15 As reported, most
of the NADH models are alternant aromatic compounds
consisting of six-membered rings. In contrast, however,
it has not been reported that nonalternant heteroaro-
matic compounds such as heteroazulenes have been used
for the NADH model reduction. In this context, we have
reported the synthesis, properties, and reactivity of 1,3-
dimethylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-
dionylium ion 4a+‚BF4- 16 and its thiophene and pyrrole
respectively. The higher stability of 6a,b+‚BF4 demon-
-
strates the stabilizing effect of additional annulation of
the furopyrimidine ring onto 4a+‚BF4-. Furthermore, the
cation 6a,b+‚BF4 was converted to the C12-hydride
-
adducts, which were used for the attempted reduction of
carbonyl compounds. However, the reduction did not
proceed and the starting materials were recovered. Since
the stability of cations 6a,b+‚BF4- was not so high, their
hydride adducts do not have enough lability toward
-
carbonyl compounds. The pyrrole analogues of 6a,b+‚BF4
analogues 4b+‚BF4
and 4c+‚BF4
,
as well as their
- 17
- 18
are expected to have higher stability as compared with
4a-c+‚BF4 and 6a,b+‚BF4-. Thus, the studies of the
-
-
pyrrole analogues of 6a,b+‚BF4-, such as 11a,b+‚BF4
(6) (a) Ohno, A.; Ikeuchi, M.; Kimura, T.; Oka, S. J. Am. Chem. Soc.
1979, 101, 7036. (b) Mikata, Y.; Hayashi, K.; Mizukami, K.; Matsumoto,
S.; Yano, S.; Yamazaki, N.; Ohno, A. Tetrahedron Lett. 2000, 41, 1035.
(c) de Kok, P. M. T.; Bastiaansen, L. A. M.; van Lier, P. M.; Vekemans,
J. A. J. M.; Buck, H. M. J. Org. Chem. 1989, 54, 1313. (d) Meyers, A.
I.; Oppenlaender, T. J. Am. Chem. Soc. 1986, 108, 1989. (e) Meyers,
A. I.; Brown, J. D. J. Am. Chem. Soc. 1987, 109, 3155.
(7) (a) Combret, Y.; Torche´, J. J.; Pie´, N.; Duflos, J.; Dupas, G.;
Bourguignon, J.; Que´guiner, G. Tetrahedron 1991, 47, 9369. (b)
Combret, Y.; Torche´, J. J.; Binay, P.; Dumpas, G.; Bourguignon, J.;
Que´guiner, G. Chem. Lett. 1991, 125. (c) Combret, Y.; Duflos, J.; Dupas,
G.; Bourguignon, J.; Que´guiner, G. Tetrahedron 1993, 49, 5237.
(8) (a) Burgess, V. A.; Davies, S. G.; Skerlj, R. T.; Whittaker, M.
Tetrahedron: Asymmetry 1992, 3, 871. (b) Burgess, V. A.; Davies, S.
G.; Skerlj, R. T. J. Chem. Soc, Chem. Commun. 1990, 1759.
(9) (a) Seki, M.; Baba, N.; Oda, J.; Inouye, Y. J. Am. Chem. Soc.
1981, 103, 4613. (b) Hoshide, F.; Ohi, S.; Baba, N.; Oda, J.; Inouye, Y.
Agric. Biol. Chem. 1982, 46, 2173. (c) Seki, M.; Baba, N.; Oda, J.;
Inouye, Y. J. Org. Chem. 1983, 48, 1370.
and 12a,b+‚BF4 (Scheme 2), seemed to be a very
-
interesting project from the viewpoint of exploration of
novel functions. In this study, we report the synthesis,
properties, and structural details of novel cations
11a,b+‚BF4 and 12a,b+‚BF4-, which are derived from
-
annulation of 4c+ with additional pyrrolo[2,3-d]pyrimi-
dine-1,3(2,4H)-dione and a furan analogue. The photo-
induced oxidizing reaction of 11a,b+‚BF4 and 12a,b+‚
-
BF4- toward some amines was studied as well. Further-
more, as an example of NAD+-NADH models, the reduc-
tion of a pyruvate analogue and some carbonyl com-
-
pounds with hydride-adduct 23a of 11a+‚BF4 was
investigated for the first time to give the corresponding
alcohol derivatives. We report here the results in detail.
(10) (a) de Vries, J. G.; Kellogg, R. M. J. Am. Chem. Soc. 1979, 101,
2759. (b) Jouin, P.; Troostwijk, C. B.; Kellogg, R. M. J. Am. Chem. Soc.
1981, 103, 2091.
(11) (a) Imanishi, T.; Hamano, Y.; Yoshikawa, H.; Iwata, C. J. Chem.
Soc., Chem. Commun. 1988, 473. (b) Obika, S.; Nishiyama, T.;
Tatematsu, S.; Miyashita, K.; Iwata, C.; Imanishi, T. Tetrahedron 1997,
53, 593. (c) Obika, S.; Nishiyama, T.; Tatematsu, S.; Miyashita, K.;
Imanishi, T. Chem. Lett. 1996, 853.
Results and Discussion
-
Synthesis. A strategy for the synthesis of 11a,b+‚BF4
and 12a,b+‚BF4 consists of the oxidative cyclization of
-
9 and 10 and subsequent anion exchange. The reaction
of 2-chlorotropone 7 with 2 molar equiv amounts of
6-phenylamino-1,3-dimethyluracil 8 in EtOH in the pres-
ence of ButNH2 at room temperature for 48 h gave 9 as
(12) Ohnishi, Y.; Kagami, M.; Ohno, A. J. Am. Chem. Soc. 1975,
97, 4766.
(13) Endo, T.; Hayashi, Y.; Okawara, M. Chem. Lett. 1977, 391.
(14) Ohno, A.; Kashiwagi, M.; Ishihara, Y.; Ushida, S.; Oka, S.
Tetrahedron 1986, 42, 961; Mikata, Y.; Mizukami, K.; Hayashi, K.;
Matsumoto, S.; Yano, S.; Yamazaki, N.; Ohno, A. J. Org. Chem. 2001,
66, 1590.
(15) (a) Yoneda, F.; Sakuma, Y.; Nitta, Y. Chem. Lett. 1978, 1177.
(b) Yoneda, F.; Kuroda, K.; Tanaka, K. Chem. Commun. 1984, 1194.
(16) (a) Naya, S.; Miyama, H.; Yasu, K.; Takayasu, T.; Nitta, M.
Tetrahedron 2003, 59, 1811-1821. (b) Naya, S.; Nitta, M. Tetrahedron
2003, 59, 3709-3718.
(17) Naya, S.; Miyama, H.; Yasu, K.; Takayasu, T.; Nitta, M.
Tetrahedron 2003, 59, 4929-4938.
(18) Naya, S.; Nitta, M. Tetrahedron 2003, 59, 7291-7299.
pale yellow solids in 75% yield (Scheme 1). Similarly to
the synthesis of 4a,b+‚BF4
,
the reaction would
- 16,17
proceed as follows: the reaction of 7 with 8 affords 4c+,
which undergoes a reaction with the second 8 to give 9.
(19) Naya, S.; Nitta, M. Tetrahedron 2004, 60, 9139-9148.
(20) Naya, S.; Tokunaka, T.; Nitta, M. J. Org. Chem. 2003, 68, 9317.
(21) Naya, S.; Tokunaka, T.; Nitta, M. J. Org. Chem. 2004, 69, 4732.
J. Org. Chem, Vol. 70, No. 24, 2005 9781

Naya et al.
SCHEME 1a
giving 17a,b via 15 in the less polar solvent would
proceed more quickly. Consequently, the selectivity of the
cyclization would depend on the stability of the interme-
diate 13+.
Molecular-orbital (MO) calculation of 15 was carried
out using the AM1 method (MOPAC97),22 and the coef-
ficients of the highest-occupied molecular orbital (HOMO)
and the lowest-unoccupied molecular orbital (LUMO) of
15 at the C6 and the C8 are depicted in Figure 2.
Regarding the coefficients of both HOMO and LUMO for
15, the value is larger for C8 than for C6, suggesting that
the reaction of the former position giving 17a occurs
preferentially over that of the latter position giving 17b.
Furthermore, by X-ray crystal analysis of 11a+‚BF4
-
a Reagents and conditions: (i) ButNH2, EtOH, rt, 48 h; (ii) NaH,
CH3CN, rt, 48 h.
(vide infra), the interaction between the contained solvent
(Et2O) and four phenyl groups of two closely located
molecules of 11a+ was observed in the solid state. Thus,
Furthermore, the reaction of 4a+‚BF4
with 6-pheny-
- 16
-
lamino-1,3-dimethyluracil 8 in CH3CN in the presence
of NaH at room temperature for 48 h gave 10 as pale
yellow solids in 89% yield. Compounds 9 and 10 were
sensitive to acidic conditions, and the reactions of 9 and
there may be possibility that the formation of 11a+‚BF4
as the major product would be attributable partially to
the solvent-mediated interaction between two phenyl
groups.
-
10 with 42% aqueous HBF4 in Ac2O gave 4a+‚BF4 and
On the other hand, the reactions of 10 with DDQ in
both CH2Cl2 and DMF, respectively, afforded mixtures
4c+‚BF4 in quantitative yields, respectively.
-
-
-
of 12a+‚BF4 and 12b+‚BF4 in a ratio of 1:1 in good
combined yields (runs 7 and 8). Although the MO
calculation of 16 showed a tendency similar to that of 15
(Figure 2), the cyclization of 14+ in both polar and less
polar solvents would proceed unselectively. The feature
seems to be attributable to the instability of 14+(cf. 4a+
pKR+ ) ca. 6.0; 4c+ pKR+ ) 10.9). The reaction of 10 with
an equivalent amount of DDQ in Ac2O at -16 °C for 1 h
and subsequent anion exchange reaction did not afford
The oxidative cyclization of 9 and 10 was carried out
-
to give 11a,b+‚BF4 and 12a,b+‚BF4-, respectively
(Scheme 2, Table 1). The reaction of 9 with 2.2 molar
equiv of DDQ in PhH at room temperature for 24 h and
subsequent anion exchange reaction by using aqueous
HBF4 in Ac2O afforded a mixture of 11a+‚BF4 and
-
11b+‚BF4 in a good combined yield (93%, run 1). The
-
ratio of 11a+‚BF4- and 11b+‚BF4- was determined to be
1
2:1 from the H NMR spectrum of the mixture. Separa-
tion of 11a+‚BF4 and 11b+‚BF4 was accomplished by
fractional recrystallization from CH3CN/AcOEt to give
pure samples of 11a+‚BF4- and 11b+‚BF4-. The reaction
of 9 by using PhH proceeded slowly, and thus a similar
reaction at room temperature for 1 h gave a mixture of
-
-
-
cation 14+‚BF4-, and a mixture of 12a+‚BF4 and
12b+‚BF4- was obtained in addition to 4a+‚BF4-, which
was generated by the reaction of unreacted 10 with HBF4.
The feature suggests the instability of 14+, which cyclizes
immediately after generation. Separation of 12a+‚BF4
-
11a+‚BF4-, 11b+‚BF4-, and tropylium cation 13+‚BF4
-
and 12b+‚BF4 was also accomplished by fractional
recrystallization from CH3CN/AcOEt to give pure samples
-
(run 2). Under elevated temperature, the reaction was
-
completed in 2 h to give a mixture of 11a+‚BF4 and
of 12a+‚BF4 and 12b+‚BF4
.
-
-
11b+‚BF4 in a ratio of 2.5:1 (run 3); however, the
-
Furthermore, the photoinduced oxidative cyclization of
9 and 10 in the presence of NH4BF4 in CH3CN gave
mixtures of 11a,b+‚BF4- and 12a,b+‚BF4-, respectively
(runs 6 and 9). The oxidative cyclization of 9 and 10
would proceed via a pathway similar to the reaction by
using DDQ as outlined in Scheme 2. On the other hand,
reaction of 9 with 1 molar equiv of DDQ in Ac2O at -16
°C for 1 h and the following anion exchange reaction
afforded cation 13+‚BF4 in a quantitative yield. Thus,
-
the oxidative cyclization of 9 would proceed via a pathway
as outlined in Scheme 2. The oxidation of 9 gives cation
13+, which undergoes deprotonation to give intermediate
15. The intermediate 15 undergoes cyclization reactions
to give two kinds of intermediates, 17a and 17b, the
hydrogen abstraction of which by another DDQ gives
cations, 11a+ and 11b+, respectively. Subsequent anion
exchange reaction with aqueous HBF4 solution results
photoirradiation of 13+‚BF4 under aerobic conditions
-
was monitored by NMR spectroscopy in CD3CN. After
irradiation for 16 h, 13+‚BF4- was completely converted
to 11a+‚BF4 as a single product. In addition, the
-
-
photoirraditation of the isolated cation 13+‚BF4 in the
presence of 42% aqueous HBF4 (0.2 mL) in CH3CN for
96 h afforded 11a+‚BF4- in quantitative yield. Thus, the
selective preparation of cation 11a+‚BF4-, which is useful
for the NAD+-NADH model reduction (vide infra), was
achieved.
-
in the formation of 11a+‚BF4 and 11b+‚BF4-. The
reaction of 9 in CH2Cl2, on the other hand, proceeded
more quickly and afforded a mixture of 11a+‚BF4 and
-
11b+‚BF4- in good combined yield (89%) in a ratio of 4:1
(run 4). In a similar reaction of 9 in DMF, a mixture of
11a+‚BF4- and 11b+‚BF4- was obtained in a ratio of 15:1
(run 5). The facts show that selectivity of cyclization of 9
would correlate with the polarity of the solvent as in the
order DMF > CH2Cl2 > PhH. Thus, decrease of the
solvent polarity would cause a lowering of selectivity. The
intermediate 13+ is less stabilized by the solvent having
smaller polarity, and thus the cyclization reaction of 13+
Properties. Compounds 9, 10, 11a,b+‚BF4-, 12a,b+‚
BF4-, and 13+‚BF4- were fully characterized on the basis
1
of H NMR, 13C NMR, IR, UV-vis, and mass spectral
data, as well as elemental analyses and X-ray analyses.
(22) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P.
J. Am. Chem. Soc. 1985, 107, 3902. Dewar, M. J. S.; Zoebisch, E. G.
THEOCHEM 1988, 180, 1.
9782 J. Org. Chem., Vol. 70, No. 24, 2005

Novel NAD+-NADH Model
TABLE 1. Results for Preparation of Cations 11a,b+‚BF4 and 12a,b+‚BF4
-
-
run compd
oxidant
solvent
time/ha
product (yield/%)
ration of 11a+:11b+ and 12a+:12b+
1
2
3
4
5
6
7
8
9
9
DDQ
DDQ
DDQ
DDQ
DDQ
PhH
24
1
11a+‚BF4- (62), 11b+‚BF4- (31)
2:1
1.8:1
2.5:1
4:1
15:1
2.3:1
1:1
9
PhH
11a+‚BF4- (39), 11b+‚BF4- (22), 13+‚BF4- (31)
11a+‚BF4- (71), 11b+‚BF4- (29)
11a+‚BF4- (71), 11b+‚BF4- (18)
11a+‚BF4- (93), 11b+‚BF4- (6)
11a+‚BF4- (70), 11b+‚BF4- (30)
12a+‚BF4- (45), 12b+‚BF4- (45)
12a+‚BF4- (49), 12b+‚BF4- (49)
12a+‚BF4- (47), 12b+‚BF4- (52)
9
PhH
2b
1
9
CH2Cl2
DMF
9
1
9
air, hν c CH3CN
3
10
10
10
DDQ
CH2Cl2
DMF
CH3CN
1
DDQ
1
1:1
0.9:1
air, hνc
3
a Unless otherwise specified, reaction was carried out at room temperature. b Reaction was carried out under reflux. c In the presence
of NH4BF4.
SCHEME 2a
FIGURE 2.
FIGURE 3. UV-vis spectra of 11a,b+‚BF4- and 12a,b+‚BF4
-
in CH3CN.
in acetonitrile are shown in Figure 3. The spectra of
11a,b+‚BF4- and 12a,b+‚BF4- are similar and the long-
est wavelengths absorption maxima (λmax) show similar
values (11a+ 461 nm; 11b+ 462 nm; 12a+ 465 nm; 12b+
467 nm). The λmax of 11a,b+ and 12a,b+ appear at longer
wavelength than that of 4c+ (414 nm),18 suggesting that
a Reagents and conditions: (i) (a) DDQ, conditions listed in
cations 11a,b+ and 12a,b+ have a more enlongated
Table 1 or hν, aerobic, NH4BF4, CH3CN, rt, 3 h; (b) 42% aq HBF4,
conjugation as compared with that of 4c+. In addition,
Ac2O, 0 °C, 1 h; (ii) (a) DDQ, Ac2O, -16 °C, 1 h; (b) 42% aq HBF4,
cations 12a,b+ having a furopyrimidine ring show the
Ac2O, -16 °C, 1 h; (iii) (a) hν, aerobic, 42% aq HBF4, CH3CN, rt,
peaks at ca. 390 nm. The fact seems to show that cations
12a,b+ retain a partial structural feature similar to
cation 4a+.
96 h; (b) 42% aq HBF4, Ac2O, 0 °C, 1 h.
-
The analytical data of 13+‚BF4 is not satisfactory
-
because of its instability under recrystallization; however,
Single crystals of 11a,b+‚BF4 were obtained by re-
correct HRMS was obtained. Mass spectra of 11a,b+‚BF4
crystallization from CH3CN/Et2O. Thus, X-ray crystal
analyses of 11a,b+‚BF4- were performed, and the ORTEP
drawings are shown in Figure 4.23 The counteranion
-
-
-
and 12a,b+‚BF4 exhibited the correct M+ - BF4 ion
peak, which is indicative of the cationic nature of the
compound. The characteristic absorption band for the
(BF4-) in 11a,b+‚BF4 and the solvent molecule (1/2
-
-
-
counterion BF4 was observed at 1084 cm-1 in the IR
Et2O) contained in 11a+‚BF4 are omitted for clarity. It
spectra. UV-vis spectra of 11a,b+‚BF4- and 12a,b+‚BF4
was interesting that the Et2O molecule contained in the
-
J. Org. Chem, Vol. 70, No. 24, 2005 9783

Naya et al.
FIGURE 4. ORTEP drawings of 11a,b+‚BF4 with thermal ellipsoid plot (50% probability). Selected bond lengths (Å) of 11a+‚
BF4-: N1-C2 1.402(4), N1-C9 1.372(5), N4-C7 1.401(5), N4-C11 1.368(5), C1-C2 1.389(5), C2-C3 1.433(5), C3-C4 1.404(5),
C4-C5 1.372(5), C5-C6 1.414(5), C6-C7 1.429(5), C1-C7 1.374(5), C3-C8 1.409(5), C8-C9 1.383(5), C6-C10 1.413(5), C10-
C11 1.375(3). Selected bond lengths (Å) of 11b+‚BF4-: N1-C2 1.405(3), N1-C9 1.366(3), N4-C7 1.401(3), N4-C11 1.382(3),
C1-C2 1.371(3), C2-C3 1.441(3), C3-C4 1.401(3), C4-C5 1.383(3), C5-C7 1.386(3), C6-C7 1.430(3), C1-C6 1.395(3), C3-C8
1.416(3), C8-C9 1.383(3), C6-C10 1.414(3), C10-C11 1.375(3).
-
single crystal is surrounded by four phenyl groups of two
closely located molecules of 11a+‚BF4-. The π-system of
11a,b+‚BF4 has a nearly planar structure. The planes
-
of the phenyl groups are twisted 72.6-87.8° against the
plane of the π-system. In both compounds 11a,b+‚BF4
,
-
the bond lengths of N1-C9 and N4-C11 are shorter than
those of N1-C2 and N4-C7, suggesting that the former
bonds have a larger bond order. Furthermore, in com-
pound 11a+‚BF4-, the bond length of C4-C5 is shorter
than those of C3-C4 and C5-C6. In compound 11b+‚
BF4-, the bond length of C1-C2 is shorter than that of
C1-C6. These facts suggest the existence of bond alter-
nation as shown in the canonical structures of 11a,b+-B
and 11a,b+-C (Figure 5). Concerning the two canonical
structures, 11b+-B and 11b+-C, the contribution of the
former structure would be larger than that of the latter
structure due to the stability of the closed pyrrole ring.
The difference between the contributions of 11b+-B and
11b+-C seems to cause the slight deformation of 11b+
from planarity. MO calculation of 11a,b+ was carried out
by using the 6-31G* basis set of the MP2 level24 and
demonstrated that the bond length alternations obtained
by the MO calculations are very similar to those obtained
by the X-ray analysis in the solid state.
FIGURE 5.
cally in buffer solutions prepared in 50% aqueous CH3-
CN and are summarized in Table 2, along with those of
the reference compounds 4a,c+.16,18 As expected, the pKR+
values of 11a+ (pKR+ ) 12.6) and 11b+ (pKR+ ) 12.6) are
larger than that of 4c+ (pKR+ ) 10.9).18 Similarly, the
pKR+ values of 12a+ (pKR+ ) 10.9) and 12b+ (pKR+ ) 10.7)
are also larger than that of 4a+ (pKR+ ) ca. 6.0).16 Thus,
the additional annulation of the pyrrolopyrimidine ring
onto the cations 4a,c+ stabilizes the cations quite ef-
fectively. The pKR+ values are similar for 11a+ and 11b+
as well as for 12a+ and 12b+; the difference in perturba-
tion originating from the annulating position of the
pyrrolopyrimidine ring is small.20,21,26,27
The affinity of the carbocation toward hydroxide ions
expressed by the pKR+ value is the most common criterion
of carbocation stability.25 The pKR+ values of cations
11a,b+ and 12a,b+ were determined spectrophotometri-
(23) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.;
Giacovazzo, C.; Guagliardi, A.; Polidori, G. J. Appl. Crystallogr. 1994,
27, 435.
(24) Gaussian 98, Revision A.11, Gaussian, Inc., Pittsburgh, PA,
2001.
(25) Freedman, H. H. Carbonium Ions; Olah, G. A., Schleyer, P.,
Eds.; Wiley-Insterscience, New York, 1973.
9784 J. Org. Chem., Vol. 70, No. 24, 2005

Novel NAD+-NADH Model
TABLE 2. λmax, pKR+ Values, and Reduction Potentialsa
of Cations 11a,b+ and 12a,b+,b and Reference Compounds
4a,c+
SCHEME 3a
compd
λmax
pKR+
reduction potential (E1red)
11a+
11b+
12a+
12b+
4a+ c
4c+ d
461
462
465
467
397
414
12.6
12.6
10.9
10.7
∼6.0
10.9
-0.95 (-0.93)e
-1.00
-0.77
-0.84
-0.58
-0.84
a V vs Ag/AgNO3; cathodic peak potential. b Salts 11a,b+‚BF4
-
and 12a,b+‚BF4- were used for the measurement. c Reference 16.
d Reference 18. e Reversible process.
The reduction potentials of 11a,b+ and 12a,b+ were
determined by cyclic voltammentry (CV) in CH3CN.
Except that of E1red of 11a+, the reduction waves were
irreversible under the conditions of the CV measure-
ments; thus, the peak potentials are summarized in Table
1, together with those of the reference compounds
4a,c+.16,18 Both E1red values of 11a,b+ and 12a,b+ are
more negative than those of 4c+ and 4a+, respectively.
The feature is similar to the nature of their pKR+ values.
The pKR+ values of 11a,b are similar; however, the E1red
of 11a+ is less negative than that of 11b+. Similarly, the
E1red of 12a+ is less negative than that of 12b+. The
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
ions such as 4a-c+.16-18 Cation 11a+ shows the reversible
reduction wave for the first time in the series of uracil-
annulated heteroazulenylium ions. The feature would be
due to the phenyl groups, which inhibit dimerization of
the radical species sterically.
a Reagents and conditions: (i) hν, aerobic, CH3CN, rt, 16 h.
TABLE 3. Autorecycling Oxidation of Some Amines by
11a,b+‚BF4 and 12a,b+‚BF4 under Photoirradiationa
-
-
run
compd
amine
yield/µmolb,c recycling no.d
-
1
2
3
4
5
6
7
8
9
11a+‚BF4- PhCH2NH2
11a+‚BF4- PhCH(Me)NH2
11a+‚BF4- hexylamine
11a+‚BF4- cyclohexylamine
11b+‚BF4- PhCH2NH2
11b+‚BF4- PhCH(Me)NH2
11b+‚BF4- hexylamine
11b+‚BF4- cyclohexylamine
12a+‚BF4- PhCH2NH2
138.1
151.4
17.5
24.5
96.9
87.7
25.7
32.8
140.2
129.4
2.9
37.8
79.4
0e
6.8
26.6
27.6
30.3
3.5
4.9
19.4
17.5
5.1
6.6
28.0
25.9
0.6
10 12a+‚BF4- PhCH(Me)NH2
11 12a+‚BF4- hexylamine
12 12a+‚BF4- cyclohexylamine
13 12b+‚BF4- PhCH2NH2
14 12b+‚BF4- PhCH(Me)NH2
15 12b+‚BF4- hexylamine
16 12b+‚BF4 cyclohexylamine
Autorecycling Oxidation of Amines. We have pre-
viously reported that compounds 4a-c+‚BF4 undergo
-
7.6
15.9
0.0
1.4
5.3
autorecycling oxidation toward some alcohols and amines
under photoirradiation.16-19 In this context, we found that
compounds 11a,b+‚BF4- and 12a,b+‚BF4- have oxidizing
ability toward benzylamine, 1-phenylethylamine, hexy-
lamine, and cyclohexylamine to give the corresponding
imines under aerobic and photoirradiation conditions
(Scheme 3). Imine R1R2CdNH is produced at first;
however, it reacts with another amine to result in the
formation of R1R2CdN-CHR1R2. Then the reaction mix-
ture was diluted with ether and filtered, and the filtrate
was treated with 2,4-dinitrophenylhydrazine in 6% HCl
to give 2,4-dinitrophenylhydrazone of the corresponding
carbonyl compound. The results are summarized in Table
3. Direct irradiation of the amines in the absence of
11a,b+‚BF4- and 12a,b+‚BF4- (named “blank”) gives the
corresponding carbonyl compounds in low to modest
yields. Thus, the yields are calculated by subtraction of
the “blank” yield from the yield of the carbonyl compound
-
a A CH3CN (16 mL) solution of compound 11a,b+‚BF4 or
12a,b+‚BF4 (5 µmol) and amines (2.5 mmol, 500 equiv) was
-
irradiated by RPR-100, 350 nm lamps under aerobic conditions
for 16 h. b Isolated by converting to the corresponding 2,4-
dinitrophenylhydrazone. c The yield is calculated by subtraction
of the blank yield from the total yield. d Recycling number of
-
11a,b+‚BF4- and 12a,b+‚BF4
.
e The blank yield was higher than
the yield in the presence of 12b+‚BF4
.
-
We propose that the present autorecycling oxidation
proceeds via electron transfer from amine to the excited
-
-
state of 11a,b+‚BF4 and 12a,b+‚BF4 as shown in
Scheme 3.19,28 The electron transfer from amine to the
excited state of 11a,b+‚BF4 and 12a,b+‚BF4 would
occur to produce radicals 11a,b• and 12a,b• and a cation
radical 19. On the other hand, there is an alternative
possibility that the photoinduced homolysis of the amine
adducts, which are generated by the reaction of 11a,b+‚
-
-
in the presence of 11a,b+‚BF4 and 12a,b+‚BF4-. The
-
recycling numbers are more than 1 (Table 3) and thus
autorecycling oxidation clearly proceeds; however, hexy-
lamine and 1-phenylethylamine were not oxidized ef-
BF4 and 12a,b+‚BF4 with amines, would afford radi-
cals 11a,b• and 12a,b• and cation radical 19 directly. An
electron transfer from radical species 11a,b• and 12a,b•
to molecular oxygen would give the superoxide anion
radical, 11a,b+, and 12a,b+; tropyl radical derivatives are
-
-
-
fectively by 12a+‚BF4 and 12b+‚BF4-, respectively
(Table 3, runs 11 and 14).
(26) Naya, S.; Warita, M.; Mitsumoto, Y.; Nitta, M. J. Org. Chem.
2004, 69, 9184.
(27) Yamane, K.; Yamamoto, H.; Nitta, M. J. Org. Chem. 2002, 67,
8114.
(28) Naya, S.; Iida, Y.; Nitta, M. Tetrahedron 2004, 60, 459.
J. Org. Chem, Vol. 70, No. 24, 2005 9785

Naya et al.
SCHEME 4a
SCHEME 5a
a Reagents and conditions: (i) NaBH4, CH3CN, rt, 1 h; (ii) (a)
DDQ, CH2Cl2, rt, 1 h; (b) 42% aq HBF4, Ac2O, 0 °C, 1 h.
known to be oxidized readily by molecular oxygen.29
Then, a proton transfer from cation radical 19 to the
superoxide anion radical would occur, followed by forma-
tion of the products 21 and H2O2. Compound 21 reacts
with excess amine to give imine 22.
Reducing Ability toward Some Carbonyl Com-
pounds. The hydride adduct 23a, obtained by reduction
-
of 11a+‚BF4 with NaBH4, achieved reduction of a
pyruvate analogue and some carbonyl compounds to
produce the corresponding alcohols in the presence of Mg-
-
(ClO4)2. Whereas the reduction of 4a-c+‚BF4 with
NaBH4 proceeded at the C5, C7, and C9 to give mixtures
of three regioisomers,16-18 the reduction of 11a,b+‚BF4
-
a Reagents and conditions: (i) Mg(ClO4)2, conditions listed in
Table 4.
-
and 12a,b+‚BF4 occurred at the C12 to give single
products containing two closed pyrrolopyrimidine rings
or pyrrolopyrimidine and furopyrimidine ring, 23a,b and
24a,b in good yields, respectively (Scheme 4). Upon
hydride abstraction with DDQ and subsequent anion
exchange reaction, compounds 23a,b and 24a,b regener-
reduction of 26 was almost completed to give 30 in 96%
yield (run 6). Furthermore, the reduction of dialkylated
ketone 27 by using 24a at 60 °C afforded 4-phenyl-2-
butanol 31 in modest yield (42%, run 7). At elevated
temperature (140 °C), the reduction of 27 proceeded
smoothly to give 31 in 81% yield (run 8). In addition,
compound 23a reduced an aromatic ketone 28 at 60 °C
to give 1-phenylethanol 32 in modest yield (38%, run 9);
however, the yields were not improved by the raising
temperature (runs 10 and 11). By using 3 molar equiv of
23a, reduction of 28 was almost completed to give 32 in
good yield (92%, run 12). Thus, spontaneous hydride
elimination seems to occur at elevated temperature. In
all reactions, cation 11a+ was recovered by converting
to 23a in good yield (76-91%). These facts show that 23a
could reduce activated ketone, aromatic aldehyde, aro-
matic ketone as well as aliphatic ketone. This is the first
example of the reduction of carbonyl compounds by
nonalternant heteroaromatic compounds (heteroazu-
lenes), which provides promising possibility for the
exploration of novel reduction systems.
-
-
ated 11a,b+‚BF4 and 12a,b+‚BF4 in 82-100% yields,
respectively. Thus, to investigate the reducing ability of
23a,b and 24a,b, reduction of the pyruvate analogue,
methyl benzoylformate, and some carbonyl compounds
was carried out in the presence of Mg(ClO4)2 (Scheme 5).
Although the reduction of methyl benzoylformate 25 by
using 23b and 24a,b did not proceed at even 60 °C (Table
4, runs 2-4), the reduction of 25 with 23a in CH2Cl2-
CH3CN (2/1) at room temperature for 20 h afforded
methyl mandelate 29 in quantitative yield (run 1). In
addition, generated cation 11a+ was recovered in 82%
yield by converting to 23a on treatment with NaBH4.
Thus, the NADH model reduction by using nonalternant
heteroaromatic compounds was accomplished for the first
time. The low reactivity of 24a,b would be attributable
to the lower stability of the corresponding cations
12a,b+‚BF4-. The stability of cation 11b+‚BF4- is similar
to that of 11a+‚BF4 (vide supra); however, only 23a
-
Conclusion
could reduce 25. The difference of the reactivity of 23a
and 24b is unclear at this stage. Furthermore, we found
that 23a has reducing ability toward benzaldehyde 26,
4-phenyl-2-butanone 27, and acetophenone 28 (runs
5-12). Yields are calculated by the ratios of alcohols and
carbonyl compounds obtained by the 1H NMR data of the
mixtures. The reduction of aromatic aldehyde 26 by using
23a at 60 °C afforded benzyl alcohol 30 in good yield
(89%, run 5). At elevated temperature (100 °C), the
-
A convenient preparation of novel cations 11a,b+‚BF4
and 12a,b+‚BF4-, which are derived from annulation of
4c+ with additional pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-
dione and a furan analogue, was accomplished by the
novel oxidative cyclization of 9 and 10 by using DDQ or
photoirradiation under aerobic conditions. Structural
characteristics of 11a,b+ and 12a,b+ were clarified on
inspection of the UV-vis and NMR spectral data as well
as X-ray crystal analyses. The stability of cations 11a,b+
and 12a,b+ is expressed by the pKR+ values, which were
determined spectrophotometrically to be 10.7-12.6. The
(29) (a) Jacobi, D.; Abraham, W.; Pischel, U.; Grubert, L.; Schnabel,
W. J. Chem. Soc., Perkin Trans. 2 1999, 1241-1248. (b) Jacobi, D.;
Abraham, W.; Pischel, U.; Grubert, L.; Sto¨sser, R.; Schnabel, W. J.
Chem. Soc., Perkin Trans. 2 1999, 1695-1702.
electrochemical reduction of 11a,b+‚BF4- and 12a,b+‚BF4
-
9786 J. Org. Chem., Vol. 70, No. 24, 2005

Novel NAD+-NADH Model
TABLE 4. Reduction of Carbonyl Compounds by 23a,b and 24a,b
run
hydride adduct
carbonyl compd
temp/°C
time
product (yield)
recovery of cations/%e
1
23a
23b
24a
24b
23a
23a
23a
23a
23a
23a
23a
23af
25
25
25
25
26
26
27
27
28
28
28
28
rta
20 h
67 h
96 h
96 h
7 d
29 (100%)
82
87
75
64
85
78
82
91
80
87
89
76
2
60b
60b
60b
60b
100c
60b
140c
60b
100c
140c
60b
25 (81%)
3
25 (88%)
25 (100%)
4
5
30 (89%), 26 (11%)d
30 (96%), 26 (4%)d
31 (42%), 27 (58%)d
31 (81%), 27 (19%)d
32 (38%), 28 (62%)d
32 (42%), 28 (58%)d
32 (44%), 28 (56%)d
32 (92%), 28 (8%)d
6
7 d
7
7 d
8
7 d
9
7 d
10
11
12
7 d
7 d
7 d
a CH2Cl2-CH3CN was used. b CHCl3-CH3CN was used. c (CH2Cl)2-CH3CN was used. d The yield was determined by 1H NMR spectrum
of the mixture. e Isolated by converting to 23a,b and 24a,b by treatment with NaBH4. f 3 molar equiv was used.
filtration to give a mixture of 11a+‚BF4- and 11b+‚BF4- or a
exhibited reduction potential at -0.93 to -1.00 (V vs
mixture of 12a+‚BF4 and 12b+‚BF4 (Table 1).
-
-
Ag/AgNO3). The photoinduced oxidation reaction of
Synthesis of 13+‚BF4-. To a stirred solution of 9 (54.8 mg,
0.1 mmol) in Ac2O (2 mL) at -16 °C was added DDQ (35 mg,
0.15 mmol) and the mixture was stirred at -16 °C for 1 h. To
the mixture was added 42% aqueous HBF4 (0.4 mL) at -16
°C and the mixture was stirred for 1 h. To the mixture was
added Et2O (50 mL) and the precipitate was collected by
11a,b+‚BF4 and 12a,b+‚BF4 toward some amines
under aerobic conditions was carried out to give the
corresponding imines with the recycling number of 0.6-
30.3. By using 23a, which is the hydride adduct of
11a+‚BF4-, the reduction of some carbonyl compounds
including a pyruvate analogue was accomplished; thus,
a novel NADH model system is designed. Further studies
including the mechanistic aspects and enantioselective
reduction of carbonyl compounds will be reported in due
course.
-
-
filtration and washed with Et2O to give 13+‚BF4 (63 mg,
-
100%).
1H NMR Monitoring of the Photoirradiation of 13+‚
BF4-. A solution of compound 13+‚BF4 (6.3 mg, 0.01 mmol)
-
in CD3CN (0.5 mL) was irradiated by RPR-100, 350 nm lamps
under aerobic conditions at room temperature in an NMR tube.
After 16 h, the NMR measurement confirmed the exclusive
formation of 11a+‚BF4
.
Experimental Section
-
Photoinduced Oxidative Cyclization of 13+‚BF4-. A
CH3CN (15 mL) solution of compound 13 +‚BF4- (31.7 mg, 0.05
mmol) in the presence of 42% aqueous HBF4 (0.2 mL) in a
Pyrex tube was irradiated by RPR-100, 350 nm lamps under
aerobic conditions for 96 h. After evaporation of CH3CN, the
residue was dissolved in a mixture of Ac2O (1 mL) and 42%
aqueous HBF4 (0.2 mL) at 0 °C, and the mixture was stirred
for another 1 h. To the mixture was added Et2O (50 mL) and
Preparation of 9. A solution of 2-chlorotropone 7 (70 mg,
0.5 mmol), 1,3-dimethyl-6-phenylaminopyrimidine-2,4(1,3H)-
dione 8 (231 mg, 1 mmol), and ButNH2 (91 mg, 1.3 mmol) in
EtOH (10 mL) was stirred at room temperature for 48 h. The
precipitate was collected by filtration and washed with EtOH
to give 9 (205 mg, 75%).
Preparation of 10. A solution of 4a+‚BF4 (660 mg, 2
-
mmol) and 8 (462 mg, 2 mmol) in CH3CN (25 mL) in the
presence of NaH (48 mg, 2 mmol) was stirred at room
temperature for 48 h. The precipitate was collected by filtration
and washed with EtOH to give 10 (839 mg, 89%).
Reaction of 9 and 10 with HBF4. To a stirred solution of
9 or 10 (1 mmol) in Ac2O (10 mL) was added 42% aqueous
HBF4 (2 mL) at 0 °C and the mixture was stirred for 1 h until
the reaction completed. To the mixture was added Et2O (200
mL) and the precipitate was collected by filtration and washed
the precipitate was collected by filtration to give 11a+‚BF4
-
(31.6 mg, 100%).
Determination of pKR+ Values of 11a,b+ and 12a,b+.
Buffer solutions of slightly different acidities were prepared
by mixing aqueous solutions of Na2B4O7 (0.025 M) and HCl
(0.1 M) (for pH 8.2-9.0), Na2B4O7 (0.025 M) and NaOH (0.1
M) (for 9.2-10.8), Na2HPO4 (0.05 M), and NaOH (0.1 M) (for
pH 11.0-12.0) and KCl (0.2M) and NaOH (0.1 M) (for pH
12.0-14.0) in various portions. For the preparation of sample
solutions, 1 mL portions of the stock solution, prepared by
with Et2O to give 4c+‚BF4 (397 mg, 98%) or 4a+‚BF4 (330
-
-
mg, 100%).
dissolving 6 mg of compound 11a,b+‚BF4 and 12a,b+‚BF4
-
-
Synthesis of 11a,b+‚BF4 and 12a,b+‚BF4 by Using
DDQ. To a stirred solution of 9 or 10 (1 mmol) in a solvent
(20 mL) was added DDQ (515 mg, 2.2 mmol) and the mixture
was stirred under conditions described in Table 1. After
evaporation of the solvent, the residue was dissolved in a
mixture of Ac2O (10 mL) and 42% aqueous HBF4 (2 mL) at 0
°C and the mixture was stirred for 1 h. To the mixture was
added Et2O (200 mL) and the precipitate was collected by
-
-
in CH3CN (20 mL), were diluted to 10 mL with the buffer
solution (8 mL) and CH3CN (1 mL). The UV-vis spectrum was
recorded for each cation 11a,b+‚BF4 and 12a,b+‚BF4 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 absor-
bance at the specific absorption wavelength (456 nm for
11a+‚BF4-; 458 nm for 11b+‚BF4-; 460 nm for 12a+‚BF4-; 462
-
-
filtration and washed with Et2O to give a mixture of 11a+‚BF4
-
nm for 12b+‚BF4-) of each cation 11a,b+‚BF4- and 12a,b+‚BF4
-
and 11b+‚BF4 or a mixture of 12a+‚BF4 and 12b+‚BF4
-
-
-
was plotted against pH to give a classical titration curve,
whose midpoint was taken as the pKR+ value.
(Table 1).
Synthesis of 11a,b+‚BF4- and 12a,b+‚BF4- by Photoir-
radiation. A solution of 9 or 10 (0.1 mmol) and NH4BF4 (0.1
mmol) in CH3CN (30 mL) in a Pyrex tube was irradiated by
RPR-100, 350 nm lamps under aerobic conditions for 3 h until
the reaction was completed. The mixture was concentrated in
vacuo, and the resulting residue was dissolved in a mixture
of acetic anhydride (10 mL) and 42% aqueous HBF4 (2 mL) at
0 °C. The mixture was stirred for 1 h. To the mixture was
added Et2O (100 mL) and the precipitate was collected by
Cyclic Voltammetry of Cations 11a,b+ and 12a,b+. The
reduction potential of 11a,b+ and 12a,b+ was determined by
means of CV-27 voltammetry controller (BAS Co). A three-
electrode cell was used, consisting of Pt working and counter
electrodes and a reference Ag/AgNO3 electrode. Nitrogen was
bubbled through a CH3CN solution (4 mL) of each cation
11a,b+‚BF4- and 12a,b+‚BF4- (0.5 mmol dm-3) and Bu4NClO4
(0.1 mol dm-3) to deaerate it. The measurements were made
J. Org. Chem, Vol. 70, No. 24, 2005 9787

Naya et al.
at a scan rate of 0.1 V s-1 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 potential was corrected with reference to this
standard. The cations 11a,b+‚BF4- and 12a,b+‚BF4- exhibited
reduction waves, and they are summarized in Table 2.
Reduction of Some Carbonyl Compound by Using
23a,b and 24a,b. To a solution of 23a,b and 24a,b (0.1 mmol)
and Mg(ClO4)2 (22 mg, 0.1 mmol) in CH3CN (5 mL) and CH2-
Cl2 (5 mL) or CHCl3 (5 mL) or (CH2Cl)2 (5 mL) was added 25-
28 (0.1 mmol), and the mixture was stirred under the
conditions indicated in Table 4. To the resulting mixture was
added AcOH (6 mg, 0.1 mmol), and concentrated in vacuo. The
resulting residue was dissolved in Et2O and the precipitated
solids were collected by filtration. The filtrate was concentrated
in vacuo to give a reduced alcohol derivative or a mixture of
carbonyl compound and alcohol derivative as summarized in
Table 4. On the other hand, the collected crystals containing
11a,b+‚ClO4- and 12a,b+‚ClO4- were dissolved in CH3CN and
reacted with NaBH4 (8 mg, 0.2 mmol), and stirred at room
temperature for 1 h. To the mixture was added saturated
aqueous NH4Cl solution, and the mixture was extracted with
CH2Cl2. The extract was dried over Na2SO4 and concentrated
in vacuo to recover 23a,b and 24a,b as summarized in Table
4.
General Procedure for Autorecycling Oxidation of
-
Amines in the Presence of 11a,b+‚BF4- and 12a,b+‚BF4
.
A CH3CN (16 mL) solution of compound 11a,b+‚BF4 (3.16
mg, 5 µmol) or 12a,b+‚BF4- (2.79 mg, 5 µmol) 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 with Et2O and
filtered. The 1H NMR spectra of the filtrates revealed the
formation of the corresponding imines. The filtrate was treated
with a saturated solution of 2,4-dinitrophenylhydrazine in 6%
HCl to give 2,4-dinitrophenylhydrazone of the corresponding
carbonyl compounds. The results are summarized in Table 3.
Reaction of 11a,b+‚BF4- and 12a,b+‚BF4- with NaBH4.
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A solution of 11a,b+‚BF4 and 12a,b+‚BF4 (0.1 mmol) and
NaBH4 (8 mg, 0.2 mmol) in CH3CN (15 mL) was stirred at
room temperature for 1 h. To the mixture was added saturated
aqueous NH4Cl solution, and the mixture was extracted with
CH2Cl2. The extract was dried over Na2SO4 and concentrated
in vacuo to give 23a,b and 24a,b (23a 53 mg, 97%; 23b 53
mg, 97%; 24a 37 mg, 64%; 24b 46 mg, 88%).
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Acknowledgment. Financial support from a Wase-
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,
elemental analyses, and X-ray analyses.
Oxidation of 23a,b and 24a,b. To a stirred solution of
23a,b and 22a4b (0.05 mmol) in CH2Cl2 (5 mL) was added
DDQ (25 mg, 0.11 mmol), and the mixture was stirred at room
temperature for 0.5 h. After evaporation of CH2Cl2, the residue
was dissolved in a mixture of Ac2O (1 mL) and 42% aqueous
HBF4 (0.2 mL) at 0 °C, and the mixture was stirred for another
1 h. To the mixture was added Et2O (20 mL) and the
precipitate was collected by filtration to give 11a,b+‚BF4- and
12a,b+‚BF4- (11a+‚BF4- 31 mg, 98%; 11b+‚BF4- 32 mg, 100%;
Supporting Information Available: Physical, analytical,
and spectroscopic data of 9, 10, 11a,b+‚BF4-, 12a,b+‚BF4
,
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13+‚BF4-, 23a,b, and 24a,b. 1H and 13C NMR spectra of 9,
10, 11a,b+‚BF4-, 12a,b+‚BF4-, 13+‚BF4-, 23a,b, and 24a,b.
Cyclic voltammogram of 11a,b+‚BF4-. CIF files. This material
is available free of charge via the Internet at http://pubs.acs.org.
12a+‚BF4 23 mg, 82%; 12b+‚BF4 27 mg, 96%).
JO0514523
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9788 J. Org. Chem., Vol. 70, No. 24, 2005