Synthesis, properties, and NAD+-NADH-type redox ability of 14-substituted 1,3-dimethyl-5,10-methanocycloundeca[4,5]pyrrolo-[2,3-d] pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates and their hydride adducts

Article abstract of DOI:10.1021/jo052495m

A synthesis of 14-substituted 1,3-dimethyl-5,10-methanocycloundeca[4,5] pyirolo[2,3-d]pyrimidine-2,4-(1,3H)-dionylium tetrafluoroborates 11a,b ⁺·BF₄^- was accomplished by the methylation of 5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)- dione derivatives with MeI and following anion-exchange reaction by treatment with 42% aq HBF₄. Compound 11b⁺·BF₄ ^- was synthesized alternatively by the reaction of 1,6-methano[11]annulenylium tetrafluoroborate with 6-phenylamino-1,3- dimethyluracil and following oxidative cyclization reaction. Remarkable structural characteristics of 11a,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⁺ is expressed by the pK_R+ values which were determined spectrophotometrically as 9.8 and 9.7, which are smaller by 1.4 and 1.2 pH units than those of the corresponding seven-membered ring cations, respectively; however, the values are larger by 3.6 and 3.5 pH units than that of the parent 0,6-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 and the electron-donating ability of pyrrolopyrimidine. The electrochemical reduction of 11a,b⁺· BF₄^- exhibited reduction potential at -0.58 and -0.52 (V vs Ag/AgNO₃) upon cyclic voltammetry (CV). Reaction of 11a ⁺·BF₄^- with hydride afforded mixures of the C13- and C11-adducts in a ratio of 81:19. Reaction of 11b ⁺·BF₄^- with hydride afforded, on the other hand, the C13-adduct as a single product. In both cations, the methano-bridge seemed to control the nucleophilic attack to the C13 favorably with exo-selectivity. The photo-induced autorecycling oxidation reactions of 11a,b⁺·BF₄^- toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 1.1 to 32.2. Furthermore, as an example of the NAD ⁺-NADH models, the reduction of a pyruvate analogue and some carbonyl compounds with the hydride adducts of 11a,b⁺·BF ₄^- was accomplished for the first time to give the corresponding alcohol derivatives.

Full text of DOI:10.1021/jo052495m

Synthesis, Properties, and NAD+-NADH-Type Redox Ability of
14-Substituted 1,3-Dimethyl-5,10-methanocycloundeca[4,5]pyrrolo-
[2,3-d]pyrimidine-2,4(1,3H)-dionylium Tetrafluoroborates and Their
Hydride Adducts
Kazuhiro Igarashi, Yohei Yamaguchi, Yuhki Mitsumoto, Shin-ichi Naya, and Makoto Nitta*
Department of Chemistry, Faculty of Science and Engineering, Waseda UniVersity, Shinjuku-ku,
Tokyo 169-8555, Japan
nitta@waseda.jp
ReceiVed December 3, 2005
A synthesis of 14-substituted 1,3-dimethyl-5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4-
-
(1,3H)-dionylium tetrafluoroborates 11a,b+‚BF4 was accomplished by the methylation of 5,10-
methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dione derivatives with MeI and following
-
anion-exchange reaction by treatment with 42% aq HBF4. Compound 11b+‚BF4 was synthesized
alternatively by the reaction of 1,6-methano[11]annulenylium tetrafluoroborate with 6-phenylamino-1,3-
dimethyluracil and following oxidative cyclization reaction. Remarkable structural characteristics of 11a,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+ is expressed by the pKR+ values which were determined spectrophoto-
metrically as 9.8 and 9.7, which are smaller by 1.4 and 1.2 pH units than those of the corresponding
seven-membered ring cations, respectively; however, the values are larger by 3.6 and 3.5 pH units 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 and the electron-donating
ability of pyrrolopyrimidine. The electrochemical reduction of 11a,b+‚BF4- exhibited reduction potential
-
at -0.58 and -0.52 (V vs Ag/AgNO3) upon cyclic voltammetry (CV). Reaction of 11a+‚BF4 with
hydride afforded mixures of the C13- and C11-adducts in a ratio of 81:19. Reaction of 11b+‚BF4- with
hydride afforded, on the other hand, the C13-adduct as a single product. In both cations, the methano-
bridge seemed to control the nucleophilic attack to the C13 favorably with exo-selectivity. The photo-
induced autorecycling oxidation reactions of 11a,b+‚BF4- toward some amines under aerobic conditions
were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitro-
phenylhydrazones) with the recycling number of 1.1 to 32.2. Furthermore, as an example of the NAD+-
NADH models, the reduction of a pyruvate analogue and some carbonyl compounds with the hydride
adducts of 11a,b+‚BF4- was accomplished for the first time to give the corresponding alcohol derivatives.
Introduction
systems have been investigated extensively through synthetic
model systems and theoretical calculations.3 Among these
compounds, 5-deazaflavins have been studied extensively in
both enzymatic4 and model systems,5 in the hope of acquiring
mechanistic insight into flavin-catalyzed reactions. The reactivity
of 5-deazaflavins has been studied to be similar to that of
Flavins are known to play an important role as cofactors in
a wide variety of biological redox reactions.1,2 The flavin-redox
* Corresponding author. Tel: +81-(0)3-5286-3236. Fax: +81-(0)3-3208-
2735.
10.1021/jo052495m CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/07/2006
2690
J. Org. Chem. 2006, 71, 2690-2698

Reduction of Carbonyl Compounds by a Methano[11]annulenylium System
nicotinamide.6 Coenzyme NADH, a cofactor of L-lactate de-
hydrogenase, functions as an enantioselective agent that reduces
pyruvate to L-lactate during anaerobic glycolysis. During the
past several decades, efforts have been made to create model
compounds mimicking the activity of the NAD+-NADH redox
couple.7-17 The introduction of an optically active N-substituent
in the amide of 1-alkylated 1,4-dihydronicotinamides, e.g., 1,
can induce modest to moderate chirality transfer toward carbonyl
compounds (Figure 1).18,19 Furthermore, Ohno and co-workers
have improved considerably chirality transfer by the additional
introduction of methyl groups at C2 and C4 in the NADH
model, e.g., compound 2.20 The new chiral center at C4 controls
the mode of hydride transfer. Moreover, the reduction of
carbonyl compounds by using 1,5-dihydro-5-deazaflavin 3 has
been reported.21 On the basis of the above observations, we have
(1) Muller, F. Chemistry and Biochemistry of FlaVoenzymes; Muller, F.,
Eds.; CRC Press: Boca Raton, 1991; Vol. 1, p 1 and references therein.
FIGURE 1. NADH model compounds and 7- and 11-membered ring
cations.
(2) (a) Chiu, C. C.; Pan, K.; Jordan, F. J. Am. Chem. Soc. 1995, 117,
7027. (b) Kim, J.; Hoegy, S. E.; Mariano, P. S. J Am. Chem. Soc. 1995,
117, 100. (c) Murahashi, S.; Ono, S.; Imada, Y. Angew. Chem., Int. Ed.
2002, 41, 2366. (d) Bergstad, K.; Jonsson, S.; Ba¨chvall, J. J. Am. Chem.
Soc. 1999, 121, 10424. (e) Van Houten, K. A.; Kim, J.; Bogdan, M. A.;
Ferri, D. C.; Mariano, P. S. J. Am. Chem. Soc. 1998, 120, 5864. (f) Zheng,
Y.; Ornstein, R. L. J. Am. Chem. Soc. 1996, 118, 9402. (g) Breinlinger, E.
C.; Keenan, C. J.; Rotello, V. M. J. Am. Chem. Soc. 1998, 120, 8606. (h)
Hasford, J. J.; Rizzo, C. J. J. Am. Chem. Soc. 1998, 120, 2251. (i) Antony,
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1057.
(3) Yoneda, F.; Kokel, B. In Chemistry and Biochemistry of FlaVoen-
zymes; Muller, F., Ed.; CRC Press: Boca Raton, 1991; Vol. 1, p 121 and
references therein.
(4) Yoneda, F.; Hirayama, R.; Yamashita, M. Chem. Lett. 1980, 1157.
(5) Nitta, M.; Tajima, Y. Synthesis 2000, 651.
previously studied the synthesis, properties, and reactivity of
10-substituted 1,3-dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyri-
midine-2,4(1,3H)-dionylium ions 4a,b+‚BF4
and the furan
-22
analogue 4c+‚BF4- 23 In these studies, it was clarified that the
.
-
pyrrole analogues 4a,b +‚BF4- have higher stability (4a+‚BF4
:
pKR+ ) 11.2, 4b+‚BF4-: pKR+ ) 10.9) as compared with
4c+‚BF4 (pKR+ ) ca. 6.0). In addition, novel photoinduced
-
autorecycling oxidizing reactions of 4a-c+‚BF4- toward some
alcohols and amines have also been studied.24 Thus, structural
modifications of the uracil-annulated heteroazulenes such as 4a-
c+‚BF4 are an interesting project from the viewpoint of
-
(6) Walsh, C. Acc. Chem. Res. 1980, 13, 148.
(7) Kanomata, N.; Nakata, T. J. Am. Chem. Soc. 2000, 122, 4563.
(8) Kanomata, N. J. Synth. Org. Chem. Jpn. 1999, 57, 512.
(9) Murakami, Y.; Kikuchi, J.; Hisaeda, Y.; Hayashida, O. Chem. ReV.
1996, 96, 721.
(10) Dupas, G.; Levacher, V.; Bourguignon, J.; Que´guiner, G. Heterocyles
1994, 39, 405.
exploration of redox functions. Much of the motivation for
studying the properties of organic molecules stems from
manipulation of the primary chemical structure. One strategy
for raising or lowering the HOMO and LUMO levels includes
conjugation length control. 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. Combination of more
than one π-system can endow the original π-system with new
properties. From these viewpoints, we have recently reported
the synthesis, properties, and oxidizing ability of 5,10-
methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-di-
one derivatives 10a,b25 (Scheme 1, vide infra) and 1,3-dimethyl-
(11) Burgess, V. A.; Davies, S. G.; Skerlj, R. T. Tetrahedron: Asynm-
metry 1991, 2, 299.
(12) (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.
(13) (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.
(14) (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.
(15) (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.
(16) (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.
5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-
- 26
dionylium tetrafluoroborate 5+‚BF4
,
which is a vinylogous
compound of 4c+‚BF4-, to involve 1,6-methano[11]annulenylium
ion 7+ instead of tropylium ion 6+. The cation 7+, which is an
aromatic 10π-electron analogue of 6+, has higher thermody-
namic stability (pKR+ ) 6.2)27 as compared with 6+ (pKR+
)
3.9).28 Due to this property, the cation 5+‚BF4 was expected
-
to exhibit higher thermodynamic stability as compared with
(21) (a) Yoneda, F.; Sakuma, Y.; Nitta, Y. Chem. Lett. 1978, 1177. (b)
Yoneda, F.; Kuroda, K.; Tanaka, K. Chem. Commun. 1984, 1194.
(22) Naya, S.; Nitta, M. Tetrahedron 2003, 59, 7291.
(23) (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.
(17) (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.
(18) Ohnishi, Y.; Kagami, M.; Ohno, A. J. Am. Chem. Soc. 1975, 97,
4766.
(19) Endo, T.; Hayashi, Y. Okawara, M. Chem. Lett. 1977, 391.
(20) 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.
(24) Naya, S.; Nitta, M. Tetrahedron 2004, 60, 9139.
(25) Mitsumoto, Y.; Nitta, M. J. Org. Chem. 2004, 69, 1256.
(26) Naya, S.; Warita, M.; Mitsumoto, Y.; Nitta, M. J. Org. Chem. 2004,
69, 9184.
(27) (a) Grimme, W.; Hoffmann, H.; Vogel, E. Angew. Chem., Int. Ed.
Engl. 1965, 4, 354. (b) Vogel, E.; Feldmann, R.; Du¨wel, H. Tetrahedron
Lett. 1970, 1, 1941.
J. Org. Chem, Vol. 71, No. 7, 2006 2691

Igarashi et al.
SCHEME 1a
SCHEME 2a
a Reagents and conditions: (i) K2CO3, CH3CN, rt, 2 days; (ii) (a) DDQ,
CH3CN, rt, 1 h, (b) 42% aq HBF4, Ac2O, 0 °C, 30 min.
a Reagents and conditions: (i) AcOH, 60 °C, 25 h; (ii) AcOH, 80 °C,
54 h; (iii) (a) MeI, (CH2Cl)2, 100 °C, 5 days, (b) 42% aq HBF4, Ac2O, 0
°C, 30 min; (iv) (a) MeI, (CH2Cl)2, 100 °C, 2 days, (b) 42% aq HBF4,
Ac2O, 0 °C, 30 min.
FIGURE 2. UV-vis spectra of 11a,b+‚BF4 and 4a,b+‚BF4
.
-
-
4c+‚BF4-; however, it exhibited lower thermodynamic stability
(pKR+ ) 4.6). Furthermore, the reaction of 5+‚BF4- with NaBD4
shows that the methano-bridge controls the nucleophilic attacks
to occur with exo-selectivity at the C11 and C13 positions. Thus,
study of the methano-bridged compounds is an interesting
project from the viewpoint of exploration of novel chiral
auxiliaries. In this study, we report the synthesis, properties,
and structural details of 14-substituted 1,3-dimethyl-5,10-
methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-
dionylium tetrafluoroborates 11a,b+‚BF4-, which are derived
from annulation of 7+ with pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-
synthesized starting from 1,6-methano[11]annulenylium tet-
rafluoroborate 7+‚BF4- 27 (Scheme 2). The reaction of 7+‚BF4
-
with 6-phenylamino-1,3-dimethyluracil 12 in the presence of
K2CO3 furnished compound 13, which is unstable on TLC (SiO2
and Al2O3). Thus, without further purification, oxidative cy-
clization reaction of 13 with DDQ and following anion-exchange
reaction using 42% aq HBF4 in Ac2O at 0 °C was carried out
-
to give 11b+‚BF4 (81% yield based on 7+‚BF4-).
Properties of 11a,b+‚BF4-. Compounds 11a,b+‚BF4- were
fully characterized on the basis of the 1H NMR, 13C NMR, IR,
UV-vis, and mass spectral data as well as elemental analyses
dione. The photoinduced oxidizing reaction of 11a,b+‚BF4
-
-
and X-ray crystal analysis. The mass spectra of 11a,b+‚BF4
toward some amines was studied as well. Furthermore, as an
exploration of NAD+-NADH type redox functions, the reduc-
tion of a pyruvate analogue and some carbonyl compounds with
exhibited the correct M+ - BF4 ion peaks, which were
-
indicative of the cationic structures of these compounds. The
characteristic absorption bands for the counterion of BF4- were
observed at 1084 cm-1 in their IR spectra. The UV-vis spectra
the hydride-adducts of 11a,b+‚BF4 was studied for the first
-
time to give the corresponding alcohol derivatives.
of 11a,b+‚BF4 in CH3CN are similar, and they are shown in
-
- 22
Figure 2, together with those of 4a,b+‚BF4
.
The longest
Results and Discussion
wavelength absorption maxima (λmax) of 11a,b+‚BF4- exhibited
-
a red-shift by 114 nm as compared with those of 4a,b+‚BF4
respectively, due to the elongated π-conjugation.
,
Synthesis. We have previously reported a convenient prepa-
ration of 5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimi-
dine-2,4(1,3H)-dione derivatives 10a,b25 by the thermal reaction
of 11-chloro-3,8-methano[11]annulenone 8 with 6-aminouracil
derivatives 9a,b. In this work, 14-substituted 1,3-dimethyl-
5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4-
(1,3H)-dionylium tetrafluoroborates 11a,b+‚BF4- were prepared
from 10a,b. Methylation of 10a,b with MeI in (CH2Cl)2 under
reflux, and subsequent anion-exchange reaction consisting of
treatment with 42% aq HBF4 in Ac2O at 0 °C afforded desired
compounds 11a,b+‚BF4- in 98% and 100% yields, respectively
1
-
The H NMR spectra of 11a,b+‚BF4 are 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
1
analyzing H NMR and H-H COSY spectra. The chemical
shifts of bridge protons and selected coupling constants of
11a,b+‚BF4- are shown in Figure 3, together with those of the
reference compounds 10a,b.25 The large geminal coupling
constant of the methylene protons (JE,Z ) 12.2 Hz) supports
the absence of a norcaradiene structure for 11a,b+‚BF4
.
-
-
(Scheme 1). On the other hand, 11b+‚BF4 was alternatively
Furthermore, the bridge protons of 11a,b+‚BF4- appear at very
higher field (δ -0.54 to -1.44), and the peripheral protons
appear in lower field of the aromatic region (δ 8.06 to 10.29).
These features indicate that 11a,b+‚BF4- have a large diatropic
(28) 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.
2692 J. Org. Chem., Vol. 71, No. 7, 2006

Reduction of Carbonyl Compounds by a Methano[11]annulenylium System
10a are also summarized in Figure 4. The single crystals of
-
11a+‚BF4 and 10a are a racemic mixture, respectively, and
not a conglomerate, and thus, optical resolution through
recrystallization seems to be difficult. While the pyrrolopyri-
midine ring moiety of 10a has a nearly planar structure, small
deformation of the 11-membered ring from planarity is observed
(Figure 4, side view). On the contrary, owing to the steric
hindrance between two methyl groups, small deformation of
the pyrimidinedione ring moiety of 11a+ from planarity is
observed (Figure 4, side view), while 11-membered ring of 11a+
has a nearly planar structure. Moreover, the bond lengths of
the 11-membered ring of 11a+ are almost equal, exhibiting no
bond length alternation. In consideration of the results of X-ray
crystal analysis and NMR spectra, the canonical structures 11a+-
A, 11a+-B, and 11a+-C are important for 11a+ (Figure 5).
Furthermore, the bond length of the N1-C18 is shorter than
that of the N1-C10, suggesting that the contribution of 11a+-D
is less important.
The affinity of the carbocation toward hydroxide ions ex-
pressed by the pKR+ value is a common criterion of carbocation
stability.30 The pKR+ values of cations 11a,b+ were determined
spectrophotometrically in buffer solutions prepared in 50%
aqueous CH3CN and are summarized in Table 1, along with
those of the reference compounds 4a-c+,22,23 5+,26 6+,28 and
7+.27 The pKR+ values of 4a-c+are much larger than that of
6+, and they are in the order 4a+ > 4b+ > 4c+, indicating that
the electron-donating ability of pyrrolopyrimidine is larger than
that of furopyrimidine and destabilizing effect by double bond
fixation by annulation is not observed. On the other hand, the
pKR+ values of 11a,b+ were determined to be 9.8 and 9.7, which
are larger by 5.2 and 5.1 pH unit than that of 5+ (pKR+ ) 4.6),
respectively, reflecting large electron-donating ability of pyr-
rolopyrimidine as compared with that of furopyrimidine. The
cation 7+, which is an aromatic 10π-electron analogue of 6+,
has higher thermodynamic stability (pKR+ ) 6.2)27 than that of
6+ (pKR+ ) 3.9);28 however, the pKR+ values of 11a,b+ and
5+ are smaller by 1.4, 1.2, and 1.4 pH unit than those of 4a-
c+, respectively. Thus, the feature is rationalized on the basis
of large perturbation derived from the double bond fixation of
the parent cation 7+. Since the C7-C8 bond of 7+ has a small
bond order (small double bond character),31 the pyrrolopyrimi-
dine and furopyrimidine-annulation onto 7+ at this position
(introduction of a double bond) seems to cause larger perturba-
tion32 than the introduction of a double bond onto a fully
delocalized double bond of 6+. This electronic effect would act
as a considereble destabilizing effect of parent cation 7+ as
compared with that of 6+.
FIGURE 3. Chemical shifts of bridge protons and selected coupling
-
constants of 11a,b+‚BF4 and reference compounds 10a,b.
ring current.29 It is interesting that the signals of HZ of
11a,b+‚BF4 appear at higher field (δ -1.44 and -1.33,
-
respectively) as compared with those of HE (δ -0.61 and -0.54,
respectively). This tendency is similar to that of 10a. In addition,
the signals of the N1Me and the H13 of 11b+‚BF4 appeared
-
at higher field (δ 3.14 and 8.41, respectively) as compared with
those of 11a+‚BF4 (δ 3.96 and 8.99, respectively). This
-
-
tendency suggests that the N1Me and the H13 of 11b+‚BF4
are located at the shielding region of the phenyl group in the
pyrrole ring, and thus, the phenyl group would twist against
the plane of the π-system. The vicinal coupling constants of
the aromatic perimeter protons suggest that the C6-C7-C8-
C9 moiety exhibits small bond alternation in 11a+‚BF4 [J6,7
-
-
(9.1 Hz), J7,8 (9.9 Hz), J8,9 (8.4 Hz)] and 11b+‚BF4 [J6,7 (9.2
Hz), J7,8 (9.9 Hz), J8,9 (8.3 Hz)]. This feature is similar to that
of compound 10a. In contrast, it is noteworthy that the vicinal
coupling constants of the C11-C12-C13 moiety exhibits large
-
bond alternation in 11a+‚BF4 [J11,12 (9.7 Hz) < J12,13 (12.0
Hz)] and 11b+‚BF4- [J11,12 (9.7 Hz) < J12,13 (12.4 Hz)]. While
the C11-C12-C13 moiety in 10b shows a small bond
alternation, there is a large bond alternation at that of 10a. The
-
13C NMR spectral data for 11a+‚BF4 were fully assigned by
using the H-C COSY spectra (HMQC and HMBC). Concerning
the 11-membered ring, the signals of the C13 appeared at much
higher field (δc 128.6) as compared with those of the other
carbons. Moreover, the signals of the C11 appeared at much
lower field (δc 152.6) as compared with those of the other
carbons, suggesting that the positive charge may be localized
The reduction potentials of 11a,b+ were determined by cyclic
voltammentry (CV) in CH3CN. The reduction waves were
irreversible under the conditions of the CV measurements; the
peak potentials are summarized in Table 1, together with those
of the reference compounds 4a-c+,22,23 5+,26 6+,28 and 7+.27
The E1red of 11a,b+ are more positive by 0.29 and 0.32 V than
those of 4a,b+, respectively, suggesting the elongated π-con-
jugation of 11a,b+. Furthermore, the more negative E1red of
11a,b+ as compared with those of 5+, 6+, and 7+ would be
comparable with the higher pKR+ values of 11a,b+.22 The
irreversible nature is probably due to the formation of a radical
at this position. This tendency is observed similarly for
-
11b+‚BF4
.
-
A single crystal of 11a+‚BF4 was obtained by recrystalli-
zation from CH3CN/Et2O, and thus, X-ray crystal analysis was
carried out to clarify the structural details of 11a+‚BF4-. X-ray
crystal analysis of reference compound 10a was also carried
out. The ORTEP drawing of 11a+‚BF4- is shown in Figure 4,
together with that of 10a. The counteranion is omitted for clarity
in the ORTEP drawing, and selected bond lengths of 11a+ and
(30) Freedman, H. H. In Carbonium Ions; Olah, G. A., Schleyer, P.,
Eds.; Wiley-Insterscience: New York, 1973.
(31) Destro, R.; Simonetta, M. Acta Crystallogr. 1979, B35, 1846.
(32) Yamane, K.; Yamamoto, H.; Nitta, M. J. Org. Chem. 2002, 67,
8114.
(29) Vogel, E. Chem. Soc. Spec. Publ. 1967, 21, 113.
J. Org. Chem, Vol. 71, No. 7, 2006 2693

Igarashi et al.
FIGURE 4. ORTEP drawings of 11a+‚BF4 and 10a with thermal ellipsoid plot (50% probability). Selected bond lengths (Å) of 11a+‚BF4
:
-
-
N1-C10 1.408(4), N1-C18 1.355(4), N2-C18 1.363(4), C1-C2 1.392(4), C2-C3 1.408(5), C3-C4 1.395(5), C4-C5 1.392(5), C5-C6 1.387-
(5), C6-C7 1.398(5), C7-C8 1.394(5), C8-C9 1.402(5), C9-C10 1.398(4), C10-C11 1.457(4), C11-C13 1.408(4), C13-C18 1.393(4). Selected
bond lengths (Å) of 10a: N3-C15 1.37(3), N4-C15 1.36(2), N4-C11 1.37(3), C9-C14 1.40(3), C9-C15 1.40(2), C11-C14 1.47(2), C14-C21
1.42(3), C21-C17 1.37(2), C17-C16 1.42(3), C16-C12 1.39(3), C12-C10 1.39(2), C10-C8 1.42(3), C8-C19 1.38(2), C19-C22 1.38(3), C22-
C23 1.42(3), C23-C11 1.39(2).
SCHEME 3a
FIGURE 5. Resonance structure of 11a+.
TABLE 1. pKR+ Values and Reduction Potentialsa of Cations
11a,b+ b and Reference Compounds 4a-c+, 5+, 6+, and 7+
compd
pKR+
reduction potential (E1red)
11a+
11b+
4a+ c
4b+ c
4c+ d
5+ e
9.8
9.7
11.2
10.9
ca. 6.0
4.6
-0.58
-0.52
-0.87
-0.84
-0.58
-0.39
-0.51
-0.42e
6+f
3.9
6.2
7+ g
-
a V vs Ag/AgNO3; cathodic peak potential. b Salts 11a,b+‚BF4 were
used for the measurement. c Reference 22. d Reference 23. e Reference 26.
f Reference 28. g Reference 27.
a Reagents and conditions: (i) hV, aerobic, CH3CN, rt, 16 h.
filtrate was treated with 2,4-dinitrophenylhydrazine in 6% HCl
to give 2,4-dinitrophenylhydrazone of the corresponding car-
bonyl compound. Direct irradiation of the amines in the absence
of 11a,b+‚BF4- (named “blank”) gives the corresponding imines
in small amounts. Thus, the recycling number is calculated by
subtraction of the “blank” yield from the yield of the imine in
the presence of 11a,b+‚BF4-, and the results are summarized
species and its dimerization, as reported to be a typical property
of uracil-annulated heteroazulenylium ions 4a-c+ 22,23 and 5+.26
Autorecycling Oxidation of Some Amines. Compounds 4a-
c+‚BF4- act as a catalyst for oxidation of some alcohols under
-
photoirradiation.22,23 Moreover, compounds 10a,b and 5+‚BF4
have been reported to undergo autorecycling oxidation toward
some amines under photoirradiation.25,26 In this context, we
in Table 2, together with those of 4a,b+‚BF4
.
- 22 The recycling
-
studied the oxidizing ability of 11a,b+‚BF4 under similar
numbers of 11a,b+‚BF4 support the proceeding of autorecy-
-
conditions. Although 11a,b+‚BF4 did not show oxidizing
cling oxidation. The reactions with 11a,b+‚BF4 gave lower
-
-
-
ability toward alcohols, they have oxidizing ability toward
benzylamine, 1-phenylethylamine, hexylamine, and cyclohexyl-
amine to give the corresponding imines under aerobic and
photoirradiation conditions. In the amine oxidation, imine is
produced at first; however, it reacts with another amine to result
in the formation of another imine and NH3 (Scheme 3). Then
the reaction mixture was diluted with ether and filtered and the
recycling numbers as compared with those of 4a,b+‚BF4
,
respectively. As a representative, the postulated reaction path-
ways for the oxidation of benzylamine by 11a+‚BF4 are
-
depicted in Scheme 3. We propose that photoinduced homolytic
cleavage of the initially formed amine-adducts 14+ and/or 15+,
which is detected by UV-vis spectra as shown in Figure 6,
probably occurs to generate a radical 11a• and a radical cation
2694 J. Org. Chem., Vol. 71, No. 7, 2006

Reduction of Carbonyl Compounds by a Methano[11]annulenylium System
SCHEME 4a
TABLE 2. Autorecycling Oxidation of Some Amines by
11a,b+‚BF4 under Aerobic and Photoirradiation Conditionsa
-
entry
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
139.9
96.7
25.0
43.2
61.2
74.7
5.7
28.8
150.0
118.4
208.8
178.8
28.0
19.3
5.0
8.6
12.2
14.9
1.1
11b+‚BF4
cyclohexylamine
PhCH2NH2
5.8
-
4a+‚BF4-
30.0
23.7
41.8
35.7
10
11
12
4a+‚BF4-
4b+‚BF4-
4b+‚BF4
PhCH(Me)NH2
PhCH2NH2
PhCH(Me)NH2
a A CH3CN (16 mL) solution of compounds 11a,b+‚BF4- (5 µmol) and
amine (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 corre-
sponding 2,4-dinitrophenylhydrazone. c The yield is calculated by subtrac-
tion of the “blank” yield from the total yield. d Recycling number of
-
-
11a,b+‚BF4 and 4a,b+‚BF4
.
a Reagents and conditions: (i) NaBH4, CH3CN, rt, 30 min; (ii) (a) DDQ,
CH2Cl2, rt, 30 min, (b) 42% aq HBF4, Ac2O, 0 °C, 30 min.
and 21b would be ascribed to the stability of both the
cycloheptatriene moiety and the closed pyrrole ring. The feature
is similar to the reaction of 5+‚BF4- with NaBH4, in which the
ratio of the C13-adduct 19 was larger than that of the C11-
adduct 20.26 To clarify endo-exo selectivity, a reaction of
11a+‚BF4 with NaBD4 in CH3CN was carried out to give a
-
FIGURE 6. UV-vis spectra of 11a+‚BF4 with PhCH2NH2.
-
mixture of C13-adduct 21a-D, C11-adduct 22a-D, and 21a in
a ratio of 83:2:15 in quantitative yield. The ratio was determined
by the H NMR spectrum of the mixture. Since NaBD4 used
PhCH2NH2•+. In the presence of oxygen, an electron transfer
from 11a• to O2 may occur to give the radical ion pair
[PhCH2NH2•+O2•-] and 11a+. Then proton transfer from PhCH2-
1
for the reaction is of 96% deuterium content, the reaction of
11a+‚BF4 with the remaining hydride would give compound
-
•+
•-
NH2 to O2 may occur, followed by formation of products
H2O2 and PhCHdNH, which reacts with another amine to result
in the formation of PhCHdNCH2Ph and NH3.25,33 Alternatively,
the present autorecycling oxidation may proceed via an electron
transfer from benzylamine to excited cation 11a+ which would
21a. The structural assignments of 21a, 22a, 21a-D, and 22a-D
were based on the NMR and HRMS spectra. Compounds 21a-D
and 22a-D were determined to be the exo-adducts as shown in
1
Scheme 4 by the H NMR spectrum of the mixture of 21a-D,
22a-D, and 21a. Upon oxidative hydrogen abstraction with DDQ
and subsequent anion-exchange reaction, a mixture of 21a and
22a regenerated 11a+‚BF4- in quantitative yield. Upon similar
oxidation with DDQ and subsequent anion exchange reaction,
a mixture of 21a-D, 22a-D, and 21a (in a ratio of 83:2:15)
afforded a mixture of deuterated cations, 11a+-13D‚BF4-, 11a+-
11D‚BF4-, and 11a+‚BF4- in a ratio of 66:2:32 in quantitative
occur to produce a radical 11a• and PhCH2NH2•+ 25 Then, they
.
would follow the proposed reaction pathways shown above.
Reaction of 11a,b+•BF4 with NaBH4. While the reaction
-
-
of 4a,b+‚BF4 with NaBH4 proceeded at the C5, C7, and C9
positions to give mixtures of three regioisomers 16a-18a and
16b-18b in a ratio of 15:4:81 and 25:7:68, respectively
(Scheme 4),22 the reaction of 5+‚BF4 proceeded at the C13
-
1
yield (Scheme 5). The ratio was determined by the H NMR
and C11 positions to give a mixture of 19 and 20 in a ratio of
spectrum of the mixture. While the hydride adduct 21a
regenerated 11a+‚BF4-, the deuterated adducts 21a-D and
22a-D regenerated a mixture of deuterated cations, 11a+-13D‚
BF4-, 11a+-11D‚BF4-, and 11a+‚BF4-. Thus, 80% of hydrogen
and 20% of deuterium seems to be abstracted from 21a-D and
22a-D. The endo-exo selectivity including deuterium isotope
effect for the oxidation is obscure. On the other hand, in the
89:11.26 In contrast, a reaction of 11a+‚BF4 with NaBH4 in
-
CH3CN was carried out to afford hydride adducts 21a and 22a
in a ratio of 81:19, quantitative yield (Scheme 4). The ratio
1
was determined by the H NMR spectrum of the mixture. The
reaction of 11b+‚BF4- with NaBH4 in CH3CN was also carried
out to give only the C13-adduct 21b, and the C11-adduct 22b
was not obtained. There is well-known tendency for double bond
fixation in the methano[11]annulene system to favor a cyclo-
heptatriene moiety predominantly over a 1,6-dimethylenecy-
clohepta-2,4-diene moiety.34 Thus, the formation of 21a, 22a,
-
reaction of 21b with DDQ, a trace amount of 11b+‚BF4 was
obtained in addition to a substantial quantity of unidentified
(34) (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.
(33) Fukuzumi, S.; Kuroda, S. Res. Chem. Intermed. 1999, 25, 789.
J. Org. Chem, Vol. 71, No. 7, 2006 2695

Igarashi et al.
SCHEME 5a
FIGURE 8. Chemical shifts of bridge protons and selected coupling
constants of 21a.
a Reagents and conditions: (i) (a) DDQ, CH2Cl2, CH3CN, rt, 30 min;
(b) 42% aq HBF4, Ac2O, 0 °C, 30 min.
FIGURE 9. ORTEP drawing of 21a with thermal ellipsoid plot (50%
probability). Selected bond lengths (Å) of 21a: N1-C10 1.407(3), N1-
C14 1.359(3), N2-C14 1.377(3), C1-C2 1.369(3), C2-C3 1.428(3),
C3-C4 1.370(3), C4-C5 1.426(3), C5-C6 1.360(3), C6-C7 1.452-
(3), C7-C8 1.329(3), C8-C9 1.520(3), C9-C10 1.512(3), C10-C11
1.386(3), C11-C13 1.455(3), C13-C14 1.384(3).
To clarify the structural details of 21a, X-ray crystal analysis
was carried out and the ORTEP drawing of 21a is shown in
Figure 9. While the pyrropyrimidine ring moiety of 21a has a
nearly planar structure, large deformation of the bridged 11-
membered ring from planarity is observed (Figure 9, side views
1 and 2). It seems that the large deformation makes a distinction
between the upside and downside of planarity. Moreover, the
C9 of the 11-membered ring of 21a is closer to the bridged-
methylene group, and significant bond alternation is observed
in the 11-membered ring. Especially, the bond lengths of C5-
C6, C7-C8, and C9-C10 are shorter than those of C6-C7
and C8-C9, suggesting existence of the cycloheptatriene
structure for 21a. The oxidation potentials of 21a were
determined by cyclic voltammentry (CV) in CH3CN. Two
oxidation waves were irreversible under the conditions of the
CV measurements; the oxidation waves appeared at +0.56 and
+1.53.
FIGURE 7. UV-vis spectra of 21a with 11a+‚BF4
.
-
materials. In addition, photoirradiation of a mixture of 21a and
22a in CD3CN-CDCl3 solution containing 42% aq HBF4 in
an NMR tube under aerobic conditions for 4 h afforded serious
decomposition products, and a trace amount of 11a+‚BF4- was
detected. Thus, photoinduced oxidation reaction of 21a and 22a
to regenerate 11a+‚BF4 does not take place effectively.
-
Properties of Hydride Adduct 21a. Recrystallization of a
mixture 21a and 22a from CHCl3/Et2O gave a single crystal of
major product 21a, and thus, hydride adduct 21a was fully
characterized on the basis of the 1H NMR, 13C NMR, IR, UV-
vis, and mass spectral data as well as elemental analyses and
X-ray crystal analysis. The UV-vis spectra of 21a in CH3CN
are shown in Figure 7, together with that of 11a+‚BF4-. The
Reducing Ability toward Some Carbonyl Compounds. To
investigate the reducing ability of 21a,b and 22a, reduction of
the pyruvate analogue, ethyl benzoylformate, and some carbonyl
compounds was carried out in the presence of Mg(ClO4)2
(Scheme 6). The reaction conditions and the results are
summarized in Table 3. The yields were calculated by the ratios
of the reduced alcohols and carbonyl compounds obtained by
longest wavelength absorption maximum (λmax) of 21a exhibited
-
a blue-shift by 176 nm as compared with that of 11a+‚BF4
,
suggesting the contraction of π-conjugation in hydride adduct
21a (cf. 14+ and/or 15+). Unambiguous proton assignment was
1
made by analyzing H NMR and H-H COSY spectra. The
chemical shifts of bridge protons and selected coupling constants
of 21a are shown in Figure 8. The significant bond alternation
of the C6-C7-C8-C9 moiety [J6,7 (6.4 Hz), J7,8 (10.6 Hz),
J8,9 (5.6 Hz)] and the large geminal coupling constant of the
methylene protons (JE,Z ) 12.5 Hz) support the absence of a
norcaradiene structure for 21a. Furthermore, it is interesting that
the chemical shifts of the HZ of 21a appeared at lower field (δ
3.94) as compared with that of the HE (δ 0.83). The HZ of 21a
is located at a deshielding region of the cycloheptatriene moiety
and the pyrrole ring moiety. Consequently, the chemical shift
of the HZ appeared at such very low field.
1
the H NMR data of the mixtures. The hydride-adducts 21a
and 22a reduced ethyl benzoylformate 23 smoothly at rt for
1.5 h to produce ethyl mandelate 26 in quantitative yield (Table
3, entry 1). Generated cation 11a+ was recovered in 100% yield
by converting to a mixture of 21a and 22a on treatment with
NaBH4. The hydride-adduct 21b also reduced ethyl benzoyl-
formate 23 at 80 °C for 72 h to give 26 in 67% yield, and
generated cation 11b+ was recovered in 24% yield by converting
to 21b on treatment with NaBH4 (entry 2). The reduction of 23
by using hydride-adducts 21a and 22a proceeded more ef-
2696 J. Org. Chem., Vol. 71, No. 7, 2006

Reduction of Carbonyl Compounds by a Methano[11]annulenylium System
TABLE 3. Reduction of Some Carbonyl Compounds by Mixtures of 21a and 22a, and 21a-D and 22a-D, and Pure 21b
entry
hydride adduct
compd carbonyl
T (°C)
time (h)
product (yield, %)
recovery of cationsh (%)
1
2
3
4
5
6
21a, 22aa
21b
23
23
24
24
25
23
rtc
1.5
72
2
2
15
3
26 (100)
100
24
100
82
100
100
80d
rtc
26 (67), 23 (33)g
27 (88), 24 (12)g
27 (96), 24 (4)g
28 (99), 25 (1)g
26-D (96), 26 (4)g
21a, 22aa
21a, 22aa
21a, 22aa
21a-D, 22a-Db
60e
60e
rtf
a A mixture of 21a and 22a in a ratio of 81:19. b A mixture of 21a-D, 22a-D, and 21a in a ratio of 83:2:15. c CH2Cl2-CH3CN (2/1) was used. d (CH2Cl)2-
CH3CN (1/1) was used. e CHCl3-CH3CN (2/1) was used. f CH2Cl2-CH3CN (1/2) was used. g The yield was determined from the 1H NMR spectrum of the
mixture. h Isolated by converting to mixtures of 21a and 22a, 21a-D, 22a-D, and 21a, and pure 21b by treatment with NaBH4 or NaBD4.
SCHEME 6a
Summary
A synthesis of novel cations 11a,b+‚BF4-, which are cata-
condensed with pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-dione to-
ward 7+, was accomplished. Structural characteristics of 11a,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+ is expressed by the pKR+ values which were determined
spectrophotometrically as 9.8 and 9.7, respectively. The elec-
trochemical reduction of 11a,b+‚BF4 exhibited reduction
-
potential at -0.58 and -0.52 (V vs Ag/AgNO3). The photo-
induced oxidation reaction of 11a,b+‚BF4- toward some amines
under aerobic conditions was carried out to give the corre-
sponding imines with the recycling number of 1.1 to 32.2. While
-
the hydride reduction of 11a+‚BF4 afforded a mixture of the
C13-adduct 21a and the C11-adduct 22a, similar reaction of
11b+‚BF4 afforded only C13-adduct 21b. In both reactions,
-
the methano-bridge controls the hydride attack which occurs
preferentially with exo-selectivity. The reduction of some
carbonyl compounds including a pyruvate analogue was ac-
complished by using 21a and 22a; and thus, a novel NADH
model system is postulated. Further studies including the
mechanistic aspect and enantioselective reduction of carbonyl
compounds will be reported in due course.
a Reagents and conditions: (i) Mg(ClO4)2, in the dark, conditions listed
in Table 3.
ficiently as compared with that of 21b, and thus, 21a and 22a
were used for the further reactions. We found that 21a and 22a
have reducing ability toward 4-phenyl-2-butanone 24 and
acetophenone 25. The reduction of dialkylated ketone 24 by
using 21a and 22a at rt for 2 h afforded 4-phenyl-2-butanol 27
in good yield (88%, entry 3); however, the yield was not
improved by the prolonged reaction time. By raising temperature
(at 60 °C), the reduction of 24 proceeded smoothly to give 27
in 96% yield (entry 4). In addition, the hydride-adducts 21a
and 22a reduced aromatic ketone 25 at 60 °C for 15 h to give
1-phenylethanol 28 in good yield (99%, entry 5). These facts
show that 21a and 22a could reduce activated ketone, aliphatic
ketone as well as aromatic ketone. To clarify the exo or endo
selectivity of the hydride, which intervenes in the carbonyl
reduction, the reduction of 23 with deuterated adducts 21a-D
and 22a-D was carried out. The deuterated adducts 21a-D and
22a-D (containing 21a) reduced 23 at rt to give the correspond-
ing deuterated alcohol 26-D and 26 in 96% and 4% yields,
respectively (entry 6). Thus, the deuteride located at the exo-
position of 21a-D and 22a-D was mainly used to reduce 23,
suggesting that the methano-bridge controls the reaction. This
feature is very interesting in considering the DDQ-oxidation
reaction of a mixture of 21a-D, 22a-D, and 21a (vide supra);
the deuteride located at the exo-position of 21a-D and 22a-D
mainly used for reduction of 23 and deuterated alcohol 26-D
was obtained as the major product. Thus, the reduction of
carbonyl compounds using 21a and 22a would proceed via
hydride transfer process. This is the first example of the
reduction of carbonyl compounds by a methano[11]annulenylium
system, and provides promising possibility for the exploration
of chiral reduction systems.
Experimental Section
Preparation of 11a+‚BF4- by Methylation of 10a. A solution
of 10a (91.5 mg, 0.30 mmol) and MeI (6 mL) in (CH2Cl)2 (15
mL) was heated in a sealed tube at 100 °C for 48 h. Then, more
MeI (6 mL) was added to the solution, and it was heated at 100 °C
for further 48 h. Finally, more MeI (3 mL) was added to the solution
and it was heated at 100 °C for 3 h. After evaporation of the solvent,
the residue was dissolved in a mixture of Ac2O (10 mL), CH3CN
(4 mL), and 42% aq. HBF4 (2 mL) at 0 °C, and the mixture was
stirred for 30 min. To the mixture was added Et2O (200 mL) and
the precipitates were collected by filtration and washed with Et2O
to give 11a+‚BF4 (122 mg, 100%). Dark red crystals (120 mg,
-
98%) were obtained on recrystallization by slow evaporation of
the solvents from CH3CN/Et2O.
Preparation of 11b+‚BF4- by Methylation of 10b. A solution
of 10b (24.2 mg, 0.066 mmol) and MeI (1.3 mL) in (CH2Cl)2 (3.3
mL) was heated in a sealed tube at 100 °C for 29 h. Then, more
MeI (1.3 mL) was added to the solution and it was heated at 100
°C for further 19 h. After evaporation of the solvent, the residue
was dissolved in a mixture of Ac2O (3 mL) and 42% aq. HBF4
(0.6 mL) at 0 °C, and the mixture was stirred for 30 min. To the
mixture was added Et2O (100 mL) and the precipitates were
-
collected by filtration and washed with Et2O to give 11b+‚BF4
(30.9 mg, 100%).
Preparation of 11b+‚BF4- Starting from 7+. A mixture of 12
(46.2 mg, 0.20 mmol) and K2CO3 (278 mg, 2.0 mmol) in CH3CN
(3 mL) was stirred at rt for 1 h. To the mixture was added a solution
-
of 7+‚BF4 (48.4 mg, 0.20 mmol) in CH3CN (2 mL) dropwise,
J. Org. Chem, Vol. 71, No. 7, 2006 2697

Igarashi et al.
and the mixture was stirred at rt for 48 h to give 13. After
evaporation of the solvent, the residue was neutralized with saturated
aqueous NH4Cl and extracted with CH2Cl2, and the extract was
dried over Na2SO4. After evaporation of the solvent, to the residue
dissolved in CH3CN (5 mL) was added DDQ (90.8 mg, 0.40 mmol),
and the mixture was stirred at rt for 1 h. After evaporation of the
solvent, the residue was dissolved in a mixture of Ac2O (5 mL)
and 42% aq. HBF4 (1 mL) at 0 °C and stirred for 30 min. To the
mixture was added Et2O (200 mL) and the precipitates were
(100 mL) and the precipitate was collected by filtration to give
-
11a+‚BF4 (10 mg, 98%).
Oxidation of 21a-D and 22a-D. To a stirred solution of a
mixture of 21a-D, 22a-D, and 21a (in a ratio of 83:2:15, 8.1 mg,
0.025 mmol) in CH2Cl2 (3 mL) and CH3CN (3 mL) was added
DDQ (12 mg, 0.053 mmol), and the mixture was stirred at rt for
30 min. After evaporation of CH2Cl2, the residue was dissolved in
a mixture of CH3CN (1 mL), Ac2O (2 mL), and 42% aq HBF4 (0.4
mL) at 0 °C, and the mixture was stirred for another 30 min. To
the mixture was added Et2O (100 mL), and the precipitate was
collected by filtration to give a mixture of deuterated cations, 11a+-
-
collected by filtration and washed with Et2O to give 11b+‚BF4
(75.9 mg, 81%).
Determination of pKR+ Value of 11a,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), and
Na2HPO4 (0.05 M) and NaOH (0.1 M) (for pH 11.0-12.0) in
various portions. For the preparation of sample solutions, 1 mL
portions of the stock solution, prepared by dissolving 16 mg of
13D‚BF4-, 11a+-11D‚BF4-, and 11a+‚BF4 in a ratio of 66:2:32
-
(10.2 mg, 100%). The ratio was assessed by measurement of the
integrated signals of the 1H NMR spectrum of the H13 at δ ) 8.99
-
-
ppm (d) for a mixture of 11a+-11D‚BF4 and 11a+‚BF4 and the
-
H11 at δ ) 8.94 ppm (d) for a mixture of 11a+-13D‚BF4 and
11a+‚BF4- and the H6 at δ ) 10.23 ppm (d) for a mixture of 11a+-
13D‚BF4-, 11a+-11D‚BF4-, and 11a+‚BF4-. See the Supporting
Information (S29-S30).
compound 11a,b+‚BF4 in CH3CN (50 mL), were diluted to 10
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Cyclic Voltammetry of Cations 11a,b+ and Hydride Adduct
21a. The reduction potential of 11a,b+ and 22 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
mL with the buffer solution (8 mL) and CH3CN (1 mL). The UV-
vis spectrum was recorded for cation 11a,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 absorbance at the specific absorption
wavelength (531 nm for 11a+‚BF4-; 527 nm for 11b+‚BF4-) of
-
bubbled through a CH3CN solution (4 mL) of cation 11a,b+‚BF4
-
cation 11a,b+‚BF4 was plotted against pH to give a classical
(0.5 mM) and 21a (0.5 mM) and Bu4NClO4 (0.1 M) to deaerate it.
The measurements were made 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 cation 11a,b+‚BF4- exhibited reduction waves,
respectively, and they are summarized in Table 2.
titration curve, whose midpoint was taken as the pKR+ value.
General Procedure for Autorecycling Oxidation of Amines
in the Presence of 11a,b+‚BF4-. A CH3CN (16 mL) solution of
-
compound 11a,b+‚BF4 (11a+‚BF4-: 2.034 mg, 5 µmol, 11b+‚
BF4-: 2.344 mg, 5 µmol) and amines (2.5 mmol, 500 eq.) 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
1
and diluted with Et2O and filtered. The H NMR spectra of the
Reduction of Some Carbonyl Compounds by Using 21a and
22a, 21a-D and 22a-D, and 21b. To a solution of mixtures 21a
and 22a, 21a-D, 22a-D, and 21a, and pure 21b (0.1 mmol) and
Mg(ClO4)2 (22 mg, 0.1 mmol) in CH3CN (5 mL) and CH2Cl2 (10
mL) or CHCl3 (10 mL) or (CH2Cl)2 (5 mL) in a sealed tube was
added 23, 24, and 25 (0.1 mmol), and the mixture was stirred in
the dark under the conditions indicated in Table 3. To the resulting
mixture was added AcOH (6 mg, 0.1 mmol) and the mixture
concentrated in vacuo. The residue was dissolved in Et2O, and the
precipitated crystals 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 sum-
marized in Table 3. On the other hand, the collected crystals
filtrates revealed the formation of the corresponding imines. The
filtrate was treated with saturated solution of 2,4-dinitrophenylhy-
drazine in 6% HCl to give 2,4-dinitrophenylhydrazone of the
corresponding carbonyl compounds. The results are summarized
in Table 2.
Reaction of 11a,b+‚BF4- with NaBH4. A solution of 11a,b+‚BF4-
(11a+‚BF4-: 10.2 mg, 0.025 mmol; 11b+‚BF4-: 31.3 mg, 0.067
mmol) and NaBH4 (2.6 equiv) in CH3CN (5 mL) was stirred at rt
for 30 min. To the mixture was added saturated aqueous NH4Cl
solution, and the mixture was extracted with CH2Cl2. The CH2Cl2
extract was dried over Na2SO4 and concentrated in vacuo to give
21a and 22a in a ratio of 81:19 (8.0 mg, 100%) and 21b (25.7 mg,
100%). The ratio of 21a and 22a was assessed by measurement of
the integrated signals of the 1H NMR spectrum of the H12 at δ )
4.38 ppm (ddd) for 21a and the H12 at δ ) 4.48 ppm (ddd) for
22a. See the Supporting Information (S23-S25).
-
containing 11a,b+‚ClO4 were dissolved in CH3CN and reacted
with NaBH4 (10 mg, 0.26 mmol) or NaBD4 (11 mg, 0.26 mmol),
and stirred at rt for 30 min. To the mixture was added saturated
aqueous NH4Cl solution, and the mixture was extracted with CH2-
Cl2. The extract was dried over Na2SO4 and concentrated in vacuo
to recover mixtures 21a and 22a, 21a-D, 22a-D, and 21a, and pure
21b as summarized in Table 3.
-
Reaction of 11a+‚BF4- with NaBD4. A solution of 11a+‚BF4
(10.2 mg, 0.025 mmol) and NaBD4 (2.7 mg, 0.065 mmol) in CH3-
CN (5 mL) was stirred at rt for 30 min. To the mixture was added
saturated aqueous NH4Cl solution, and the mixture was extracted
with CH2Cl2. The CH2Cl2 extract was dried over Na2SO4 and
concentrated in vacuo to give a mixture of 21a-D, 22a-D, and 21a
in a ratio of 83:2:15 (8.1 mg, 100%). The ratio was assessed by
measurement of the integrated signals of the 1H NMR spectrum of
the H6 at δ ) 8.12 ppm (d) for 21a-D and the H6 at δ ) 8.18 ppm
(d) for 22a-D and the H12 at δ ) 4.41 ppm (ddd) for 21a. See the
Supporting Information (S26-S28).
Acknowledgment. Financial support from a Waseda Uni-
versity Grant for Special Research Project and 21COE “Practical
Nano-chemistry” from MEXT, Japan, is gratefully acknowl-
edged. We thank the Materials Characterization Central Labora-
tory, Waseda University, for technical assistance with the
spectral data, elemental analyses, and X-ray analyses.
Oxidation of 21a and 22a. To a stirred solution of 21a and 22a
(in a ratio of 81:19, 8.0 mg, 0.025 mmol) in a mixture of CH2Cl2
(3 mL) and CH3CN (3 mL) was added DDQ (24.0 mg, 0.11 mmol),
and the mixture was stirred at rt for 30 min. After evaporation of
CH2Cl2, the residue was dissolved in a mixture of CH3CN (1 mL),
Ac2O (2 mL), and 42% aq HBF4 (0.4 mL) at 0 °C, and the mixture
was stirred for another 30 min. To the mixture was added Et2O
Supporting Information Available: Physical, analytical, and
spectroscopic data of 11a,b+‚BF4-, 21a,b, 21a-D, and 11a+-13D‚
BF4-. H and 13C NMR spectra of 11a,b+‚BF4 and 21a,b. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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JO052495M
2698 J. Org. Chem., Vol. 71, No. 7, 2006