Chelation-assisted electrocyclic reactions of 3-alkenyl-2,2′- bipyridines: An efficient method for the synthesis of 5,6-dihydro-1,10- phenanthroline and 1,10-phenanthroline derivatives

Article abstract of DOI:10.1039/b715442a

An efficient method for the synthesis of substituted 5,6-dihydro-1,10- phenanthrolines and 1,10-phenanthrolines has been developed by means of the chelation-assisted photochemical electrocyclic reactions of 3-alkenyl-2, 2′-bipyridines. The Royal Society o

Full text of DOI:10.1039/b715442a

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Chelation-assisted electrocyclic reactions of 3-alkenyl-2,29-bipyridines:
an efficient method for the synthesis of 5,6-dihydro-1,10-phenanthroline
and 1,10-phenanthroline derivatives{
Akihiko Takahashi, Yuko Hirose, Hiroyuki Kusama* and Nobuharu Iwasawa*
Received (in Cambridge, UK) 8th October 2007, Accepted 16th November 2007
First published as an Advance Article on the web 29th November 2007
DOI: 10.1039/b715442a
An efficient method for the synthesis of substituted 5,6-
dihydro-1,10-phenanthrolines and 1,10-phenanthrolines has
been developed by means of the chelation-assisted photo-
chemical electrocyclic reactions of 3-alkenyl-2,29-bipyridines.
1,10-Phenanthrolines are some of the most important, widely
used chelating ligands in coordination chemistry, and their metal
complexes have been used not only as catalysts in organic synthesis
but also as component molecules for functional materials and
building blocks in supramolecular chemistry.1 Various methodo-
logies for the synthesis of 1,10-phenanthrolines are known,
including the classical Skraup and Friedlander reactions, but
many of them are not necessarily useful for substrates bearing
labile functionalities, because these methods normally require
strongly acidic or basic conditions and high reaction tempera-
tures.2 Therefore, it remains desirable to develop efficient methods
for the preparation of variously substituted 1,10-phenanthroline
derivatives for the effective development of these research areas.
Photochemical electrocyclization of 6p-electron systems is highly
useful for the construction of fused aromatic systems. In fact,
this reaction is often applied to the synthesis of phenanthrene
derivatives by using stilbene or vinylbiphenyl derivatives as
substrates.3 However, to our knowledge, only one example
employing 1,2-bis(3-pyridyl)ethylene is known for the preparation
of 1,10-phenanthroline derivatives,4,5 and none is known for
the electrocyclic reactions of 3-alkenyl-2,29-bipyridines. In fact,
irradiation of a CH3CN solution of 5,59-bis(triethylsilyl)-3-alkenyl-
2,29-bipyridine 1a6 using a Xe or low-pressure Hg lamp through
a quartz tube at ambient temperature gave none of the desired
5,6-dihydro-1,10-phenanthroline 2a, even after 10 h, but most of
the starting material was recovered. This result is probably due to
the fact that the s-trans conformation of the bipyridine, which is
not suitable for electrocyclic reactions, is more stable than the s-cis
conformation. We then thought of the possibility of a chelation-
assisted electrocyclic reaction of 3-alkenyl-2,29-bipyridines based
on the following two expectations; (1) addition of a metal salt
would induce chelate formation with the bipyridine to fix the
conformation of the molecule suitably for cyclization (Scheme 1),
and (2) formation of a metal chelate would induce a significant
bathochromic shift of the absorption band,7 which would enable
Scheme 1 Chelation-controlled electrocyclic reaction.
the efficient photoexcitation of the substrate using a standard high
pressure Hg lamp without the necessity of using quartz apparatus.
Based on these considerations, the reaction was examined by
irradiating a de-gassed CH3CN solution of a mixture of the
bipyridine 1a and various kinds of metal salt using a Pyrex tube
(Table 1). Although the use of LiOTf was not so effective (Table 1,
entry 1), the reactions using Mg(OTf)2, ZnCl2 and Zn(OTf)2 were
completed in only 1 h to afford 5,6-dihydro-1,10-phenanthroline
2a in about 70% yield (Table 1, entries 3–5).8 Lanthanide triflates,
such as Yb(OTf)3 and Sc(OTf)3, were effective for this reaction but
Table 1 Screening of the reaction conditionsa
Entry
[M]
Solvent
Yield (%)
1
LiOTf
CuCl2
Mg(OTf)2
ZnCl2
Zn(OTf)2
Yb(OTf)3
Sc(OTf)3
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Et2O
15
40
72
72
67
56
62
26
24
49
41
44
2b
3
4
5
6
7
8
9
10
11
12
a
THF
CH2Cl2
DMF
MeOH
Tokyo Institute of Technology, Department of Chemistry, 2-12-1
O-okayama, Meguro-ku, Tokyo, Japan.
E-mail: niwasawa@chem.titech.ac.jp; hkusama@chem.titech.ac.jp
{ Electronic supplementary information (ESI) available: Experimental
section. See DOI: 10.1039/b715442a
1 equiv. of metal salt was added. Irradiation was carried out using
a 250 W super high pressure Hg lamp through a Pyrex tube in
de-gassed solvent. Aromatized 1,10-phenanthroline was obtained in
b
23% yield.
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Chem. Commun., 2008, 609–611 | 609

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substituted not only at the a-position but also at the b-position of
the alkenyl moiety were suitable for this electrocyclic reaction
to give the corresponding 5,6-dihydro-1,10-phenanthroline deriva-
tives in good yields. Silyl enol ether derivative 1e could be
employed as the substrate, giving an oxygen-functionalized
dihydrophenanthroline (Table 2, entry 4).
We next examined the synthesis of 1,10-phenanthroline deriva-
tives.10 The electrocyclic reaction of alkenyl carbonate 3a, which
was easily accessible from the corresponding ketone, also
proceeded smoothly to give 5,6-dihydrophenanthroline 4a. Next,
treatment of crude product 4a with DBU in CH2Cl2 induced the
elimination of MeOCOO2, giving the desired 1,10-phenanthroline
derivative 5a in good yield in 2 steps (Scheme 2).
Scheme 2 Synthesis of 1,10-phenanthroline derivatives.
gave 2a in slightly lower yields (Table 1, entries 6 and 7). The
addition of CuCl2 also promoted the desired reaction, albeit the
products contained a significant amount of the aromatized
product (Table 1, entry 2). Other solvents, such as Et2O, THF
and CH2Cl2, were also examined using Zn(OTf)2; however, 5,6-
dihydro-1,10-phenanthrolines 2a were obtained in low yield. This
was probably due to the low solubility of the zinc salt in these
solvents, and 3-alkenyl-2,29-bipyridine 1a was recovered (Table 1,
entries 8–10). The reactions in DMF and MeOH were slightly
sluggish and gave 2a in about 40% yield, along with unidentified
mixtures of by-products (Table 1, entries 11 and 12). It should be
noted that the absorption maximum of 1 : 1 mixtures of 1a
and Zn(OTf)2 or ZnCl2 in CH3CN were observed at ca. 320 nm,
which clearly shows that the expected bathochromic shift
actually occurred in the presence of metal salts, and that this
is the reason why the reaction proceeded using a high pressure
Hg lamp and Pyrex apparatus. These features would make the
reaction highly practical.
Reactions of some representative substrates are summarized in
Table 3. Thus, 3-alkenyl-2,29-bipyridines substituted with Me, Ph,
alkynyl and Br groups were converted into the corresponding
1,10-phenanthrolines 5 in good yield. Moreover, the electrocyclic
reaction of substrate 3b, which has a substituent at the b-position
of the alkenyl moiety, also proceeded in good yield to produce
Table 3 Reactions with various 3-alkenyl-2,29-bipyridines bearing a
methylcarbonate group on the alkenyl moietya
Yield
(%)
Entry
1
Starting material
Product
68
2
3
4
5
6
59
72
59
74
70
69
As the desired reaction was found to proceed as expected, we
next examined its generality by employing several 3-alkenyl-
2,29-bipyridine derivatives and zinc salts (Table 2).9 Substrates
Table 2 Reactions with various 3-alkenyl-2,29-bipyridinesa
Entry
1
Starting material
Product
Yield (%)
63
2
3
66
63
4b
66
7b
a
a
R = Et3Si. Conditions: 1 equiv. Zn(OTf)2, hn, CH3CN, 1 h, rt.
1 equiv. of ZnCl2 was used.
Conditions: 1 equiv. of Zn(OTf)2, hn, CH3CN, 1 h, rt; then DBU,
CH2Cl2, rt. Desilylation occurred upon treatment with DBU.
b
b
610 | Chem. Commun., 2008, 609–611
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Raton, FL, 2nd edn, 2004, pp. 33–1. For some recent studies on
photochemical electrocyclization of stilbenes or vinylbiphenyls, see: (d)
M. J. E. Hewlins and R. Salter, Synthesis, 2007, 2164; (e) S. Abbate,
C. Bazzini, T. Caronna, F. Fontana, C. Gambarotti, F. Gangemi,
G. Longhi, A. Mele, I. N. Sora and W. Panzeri, Tetrahedron, 2006, 62,
139; (f) M. C. Sajimon and F. D. Lewis, Photochem. Photobiol. Sci.,
2005, 4, 789; (g) F. D. Lewis, M. C. Sajimon, X. Zuo, M. Rubin and
V. Gevorgyan, J. Org. Chem., 2005, 70, 10447; (h) F. D. Lewis and
X. Zuo, Photochem. Photobiol. Sci., 2003, 2, 1059; (i) F. D. Lewis,
X. Zuo, V. Gevorgyan and M. Rubin, J. Am. Chem. Soc., 2002, 124,
13664.
4 H.-H. Perkampus and G. Kassebeer, Justus Liebigs Ann. Chem., 1966,
696, 1. This reaction gave a regioisomeric mixture of phenanthrolines,
and the yield of 1,10-phenanthroline was only 1%. For another related
example, see: S. C. Shim and S. K. Lee, Bull. Korean Chem. Soc., 1980,
1, 68.
5-methyl-1,10-phenanthroline 5b. In these reactions, the use of
ZnCl2 instead of Zn(OTf)2 gave the corresponding phenanthro-
lines in slightly lower yield.
In summary, we have developed an efficient method for the
synthesis of substituted 5,6-dihydro-1,10-phenanthrolines and
1,10-phenanthrolines via the chelation-assisted photochemical
electrocyclic reactions of 3-alkenyl-2,29-bipyridines. The formation
of zinc chelates controls the conformation of the substrate in a
desirable manner, and also induces a significant bathochromic shift
of the absorption band, which permits efficient excitation of the
substrate with a standard high pressure Hg lamp and Pyrex
apparatus. As chelation-controlled electrocyclization has scarcely
been employed in organic synthesis,11,12 the present method
offers new possibilities for the efficient synthesis of heterocycles via
pericyclic reactions.
5 G. I. Graf, D. Hastreiter, L. E. da Silva, R. A. Rebelo, A. G. Montalban
and A. McKillop, Tetrahedron, 2002, 58, 9095.
6 The absorption maximum of the substrate 1a in CH3CN (0.2 mM) was
observed at 283 nm.
This research was partly supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science, and Technology of Japan.
7 (a) M. Lepeltier, T. K.-M. Lee, K. K.-W. Lo, L. Toupet, H. Le Bozec
and V. Guerchais, Eur. J. Inorg. Chem., 2005, 110; (b) O. Maury,
L. Viau, K. Se´ne´chal, B. Corre, J.-P. Gue´gan, T. Renouard, I. Ledoux,
J. Zyss and H. Le Bozec, Chem.–Eur. J., 2004, 10, 4454; (c) K. Se´ne´chal,
O. Maury, H. Le Bozec, I. Ledoux and J. Zyss, J. Am. Chem. Soc.,
2002, 124, 4560. See also: (d) O. Maury and H. Le Bozec, Acc. Chem.
Res., 2005, 38, 691.
8 Thermal electrocyclization of 1a in the presence of Zn(OTf)2 at 180 uC
in PhCN did not proceed, and the starting material was recovered after
10 h.
9 Both Zn(OTf)2 and ZnCl2 gave almost the same result in every case.
10 We first examined the in situ-oxidation of dihydrophenanthroline 2 to
the corresponding 1,10-phenanthroline. However, photoirradiation of
the reaction mixture under an oxygen atmosphere resulted in a complex
mixture, and none of the desired compound was detected.
11 (a) D. A. Tocher, M. G. B. Drew, S. Nag, P. K. Pal and D. Datta,
Chem.–Eur. J., 2007, 13, 2230; (b) P. K. Pal, S. Chowdhury, M. G. B.
Drew and D. Datta, New J. Chem., 2000, 24, 931.
12 For metal template effects in other types of photochemical reaction, see:
(a) B. Grosch and T. Bach, in Chiral Photochemistry, ed. Y. Inoue and
V. Ramamurthy, Marcel Dekker, New York, 2004, ch. 8, pp. 315; (b)
M. Oelgemo¨ller, A. G. Griesbeck, J. Lex, A. Haeuseler, M. Schmittel,
M. Niki, D. Hesek and Y. Inoue, Org. Lett., 2001, 3, 1593; (c) H. Jiang,
H. Xu and J. Ye, J. Chem. Soc., Perkin Trans. 2, 2000, 925.
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Chem. Commun., 2008, 609–611 | 611