An efficient and convenient Cu(OAc)2/air mediated oxidative coupling of azoles via C-H activation

Article abstract of DOI:10.1039/b919396k

An efficient and convenient approach to construct C-C bonds at the 2-position of azoles via Cu(OAc)₂/air mediated oxidative homo- and cross-coupling reaction was reported. The corresponding products were obtained in good to excellent yield.

Full text of DOI:10.1039/b919396k

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
An efficient and convenient Cu(OAc)2/air mediated oxidative coupling of
azoles via C–H activation†
Yan Li, Jun Jin, Weixing Qian* and Weiliang Bao*
Received 17th September 2009, Accepted 28th October 2009
First published as an Advance Article on the web 9th November 2009
DOI: 10.1039/b919396k
An efficient and convenient approach to construct C–C bonds
at the 2-position of azoles via Cu(OAc)2/air mediated oxida-
tive homo- and cross-coupling reaction was reported. The
corresponding products were obtained in good to excellent
yield.
In experiments searching for the best reaction condi-
tions, we initially examined the oxidative homo-coupling of
N-methylbenzimidazole with 1.2 equiv. Cu(OAc)2 and 2 mL xylene
under N2 atmosphere at 140 ◦C. 12 h later, the desired product was
obtained in 85% yield (Table 1, entry 7). The reaction proceeded
successfully with mild oxidant. The result of the reaction decreased
obviously when DDQ, 1,4-benzoquinone, PhI(OAc)2 were used as
the oxidant (Table 1, entries 6, 8 and 9). When the reaction was
carried out under air using 20 mol% Cu(OAc)2 as the catalyst, a
better result was obtained (Table 1, entry 1). Using pure oxygen
instead of air, the yield was almost the same (Table 1, entry
14). Other metal catalysts were also screened. However, the yield
declined to 42% when CuCl was used (Table 1, entry 11) and no
product was formed when CuSO4 and FeCl3 catalyzed the reaction
(Table 1, entries 10 and 12). Among the solvents investigated,
xylene was clearly the best choice (Table 1, entries 1–5). As for the
influence of Cu(OAc)2 dosage, it was found that decreasing the
amount of Cu(OAc)2 resulted in reduced yield (Table 1, entry 15).
No product was obtained in the absence of Cu(OAc)2 (Table 1,
entry 16). Cu(OAc)2 could be recovered and recycled. However,
the yield slightly declined as the number of times the catalyst was
recycled increased (Table 1, entry 17 and 18). The yield fell to 70%
when the reaction temperature was set to 125 ◦C (Table 1, entry 13).
Therefore, the optimized conditions were N-methylbenzimidazole
(0.5 mmol)/Cu(OAc)2 (20 mol%)/xylene (2 mL) at 140 ◦C.
The formation of carbon–carbon bonds is one of the most useful
and fundamental reactions since it represents a key step in the
synthesis of complex molecules.1 In particular, construction of
C–C bonds at the 2-position of azoles is important for the syn-
thesis of many pharmaceutically relevant compounds.2 The most
developed methods for C–C bond formation at the 2-position of
azoles involve transition-metal-catalyzed cross-coupling reactions
between prefunctionalized azoles (usually including organozinc
reagents, organotin reagents) and R–X (R = Ar, alkyl; X = I, Br,
Cl, OTf)3,4 or 2-halo azoles and R–M (R = Ar, alkyl; M = SnR3,
B(OR)2).5–7 Quite often, these functionalized starting materials
are either expensive or have to be prepared in several steps.8 In
recent years, research activities have focused on generating these
C–C bonds by transition-metal catalyzed direct C–H activation
because of its conciseness and “atom economy” 9 and a number
of excellent results have been obtained.8,10 However, for most of
these methods, expensive metal catalysts are inevitable. As a more
challenging subject, oxidative intermolecular C–C bond formation
using two C–H bonds of azoles has been rarely reported.
More recently, replacing these expensive metal catalysts with
more abundant and less expensive ones to execute similar C–
H activation reactions has attracted great interest.11 Daugulis12
and You13 both found that CuI could catalyze the arylation of
heterocycle C–H bonds. Miura recently discovered an arylation of
azoles with aryl bromides catalyzed by nickel.14 A similar nickel
catalyzed coupling of heteroarenes with aryl halides/triflates has
been uncovered by Itami and co-workers.15 Cu(II) catalysts have
also found increasing applications in the oxidative coupling of
two C–H bonds.16,17 With the emergence of the concept of “green
chemistry”,18 air as an environmentally benign, mild and facile
terminal oxidant is attracting more and more attention. A Cu(II)-
catalyzed air oxidative functionalization of aryl C–H bonds has
been achieved by Yu.19 Li used palladium and air to synthesize
(E)-3-(isobenzofuran-3(1H)-ylidene)-indolin-2-ones.20 Herein, we
report an efficient and convenient Cu(OAc)2 mediated oxidative
homo- and cross-coupling reaction of azoles via C–H activation
using air as the terminal oxidant.
With the optimized conditions in hand, various substrates
were subjected to this coupling reaction. The method could be
successfully applied to the oxidative homo-coupling reactions of
various azoles (imidazoles, benzimidazoles, thiazoles, oxadiazoles
and benoxazoles) (Table 2). Benzimidazoles bearing different
substituents including alkyl and aryl groups at the 1-position could
all give the product in good to excellent yield (Table 2, entries 1–3).
As for imidazoles, the yields were slightly reduced (Table 2, entries
4–6). No distinct electronic effect was observed. Other azoles
such as thiazoles, benzoxazoles and oxadiazoles could all react
smoothly and give the corresponding products in good yield
(Table 2, entries 7–11). No methyl oxidation was found in our
catalytic systems. And our protocol was regioselective: all the
dimerizations of these azole derivatives occurred at 2-position.
Encouraged by the above results, we further investigated
the cross-coupling reaction between two different azoles
(Table 3). To our delight, the corresponding cross-coupling
products were formed in moderate yield. The coupling of
N-methylbenzimidazole with N-benzylbenzimidazole gave 56%
cross-coupling products (Table 3, entry 1). For the coupling
of N-benzylbenzimidazole with N-phenylbenzimidazole, cross-
coupling products were obtained in more than 50% yield no
matter whether the ratio of 1 to 2 was 2 : 1 or 1 : 2 (Table 3,
Department of Chemistry, Xixi Campus, Zhejiang University, Hangzhou,
310028, P. R. China. E-mail: wlbao@css.zju.edu.cn; Fax: +86 571
88273814; Tel: +86 571 88273814
† Electronic supplementary information (ESI) available: Experimental
details and NMR spectra of products. See DOI: 10.1039/b919396k
326 | Org. Biomol. Chem., 2010, 8, 326–330
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Table 1 Screening of reaction conditionsa
Table 2 Formation of bisazolea
Entry
1
Substrate
Product
Yield (%)b
90
Entry Solvent Oxidant
Cat.
T/◦C Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
xylene air
toluene air
PhNO2 air
Cu(OAc)2 140
Cu(OAc)2 110
Cu(OAc)2 140
Cu(OAc)2 140
Cu(OAc)2 140
Cu(OAc)2 140
90
53
0
<5
64
<5c
85d
15c
23c
0
42
trace
70
90
86e
0
2
91
NMP
DMF
air
air
xylene DDQ
xylene Cu(OAc)2
xylene 1,4-benzoquinone
xylene PhI(OAc)2
xylene air
xylene air
xylene air
xylene air
xylene O2
xylene air
xylene air
—
140
Cu(OAc)2 140
Cu(OAc)2 140
CuSO4
CuCl
FeCl3
140
140
140
3
88
Cu(OAc)2 125
Cu(OAc)2 140
Cu(OAc)2 140
—
140
f
xylene air
xylene air
Cu(OAc)2 140
Cu(OAc)2 140
87
83
g
a 0.5 mmol of N-methylbenzimidazole, 20 mol% of catalyst, 2 mL solvent,
12 h. b Isolated yield. c 1.2 equiv. oxidant and under N2 atmosphere.
d 1.2 equiv. Cu(OAc)2 and under N2 atmosphere. e 15 mol% of Cu(OAc)2.
f Cu(OAc)2 was recycled once. g Cu(OAc)2 was recycled twice.
4
5
80
83
entries 2 and 3). When benzoxazole reacted with N-methylimida-
zole, the cross-coupling product was formed in 45% yield. While
N-benzylimidazole with 4,5-dimethylthiazole, the yield was 49%.
Though the cross-coupling yields were moderate, the method
provided a concise and convenient procedure to construct these
cross bisazoles.
The exact mechanism of the Cu(OAc)2 catalyzed air oxidative
coupling of azoles is not clear at the moment. According to
the literature21 and the observation in our reactions, a possible
mechanism was proposed (Scheme 1). The reaction started from
O2CuII(OAc)2, which was formed by the combination of Cu(OAc)2
and molecule oxygen. An electron transfer from O to Cu to
give ∑OOCuI(OAc)2.Then ∑OOCuI(OAc)2 abstracted the hydrogen
6
81
7
8
79
79
86
84
75
9
10
11
a 0.5 mmol of substrate, 20 mol% of Cu(OAc)2, 2 mL xylene, 140 ◦C, 12 h.
b Isolated yield.
Scheme 1 Possible mechanism.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 326–330 | 327
©

View Article Online
Table 3 Cross-coupling of two different benzimidazolesa
General procedures
General procedure for the formation of homo-coupling product.
A dry Schlenk tube was charged with the N-methylbenzimidazole
(0.5 mmol, 0.066 g) and Cu(OAc)2 (20 mol%, 0.0182 g) in
2 mL xylene. Then the Schlenk tube was sealed and the reaction
mixture was heated to 140 ◦C for 12 h. Purification was done
by column chromatography on silica gel (200–300 mesh) with
dichloromethane and ethyl acetate (5 : 1) as the eluent to give the
pure product (0.058 g, 90%).
Yield (%)
Entry
1
X
Substrate 2
3b
4c
5b
N–CH3 (1a)
56(3a) 31(4a)
54(3b) 22(4b)
52(3b) 28(4c)
19(5a)
Formation of cross-coupling product. A dry Schlenk tube
was charged with N-methylbenzimidazole (0.5 mmol, 0.066 g),
N-benzylbenzimidazole (0.25 mmol, 0.052 g) and Cu(OAc)2
(20 mol%, 0.0182 g) in 2 mL xylene. Then the Schlenk tube was
sealed and the reaction mixture was heated to 140 ◦C for 12 h.
Purification was done by column chromatography on silica gel
(200–300 mesh) with dichloromethane and ethyl acetate (10 : 1) as
the eluent to give the pure product 3a (0.048 g, 56%).
2
3
4
N–CH2Ph (1b)
N–Ph (1c)
N–CH3 (1a)
O (1d)
32(5b)
23(5a)
31(5c)
1,◦1¢-Dimethyl-1H,1¢H-2,2¢-bibenzo[d]imidazole22. M.p.: 208–
209 C, 1H NMR (400 MHz, CDCl3/TMS): d 4.33 (s, 6H), 7.36 (t,
J = 7.4 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.49 (d, J = 7.6 Hz, 2H),
7.88 (d, J = 7.6 Hz, 2H), 13C NMR (100 MHz, CDCl3/TMS):
32.4, 110.0, 120.3, 122.8, 123.9, 136.2, 142.5, 143.2.
1,◦1¢-Diphenyl-1H,1¢H-2,2¢-bibenzo[d]imidazole23. M.p.: 189–
199 C, 1H NMR (400 MHz, CDCl3/TMS): d 6.85 (d, J = 7.6 Hz,
4H), 7.19–7.31 (m, 10H), 7.36 (t, J = 7.4 Hz, 2H), 7.92 (d, J =
8.4 Hz, 2H), 13C NMR (100 MHz, CDCl3/TMS): 110.5, 120.9,
123.2, 124.3, 125.4, 127.7, 129.3, 135.1, 135.2, 142.9, 143.0.
66(3c)
44(4a)
1,◦1¢-Dibenzyl-1H,1¢H-2,2¢-bibenzo[d]imidazole24. M.p.: 215–
216 C, 1H NMR (400 MHz, CDCl3/TMS): d 6.22 (s, 4H), 7.00–
7.01 (m, 4H), 7.11–7.14 (m, 6H), 7.27–7.32 (m, 4H), 7.36–7.38 (m,
2H), 7.83–7.85 (m, 2H), 13C NMR (100 MHz, CDCl3/TMS): 48.5,
110.8, 120.4, 122.9, 124.1, 126.8, 127.4, 128.6, 135.5, 136.8, 142.6,
142.8.
5
6
45(3d) 25(4d)
25(5d)
35(5c)
49(3e)
24(4e)
1,1¢-Dimethyl-1H,1¢H-2,2¢-biimidazole25. M.p.: 105–106 ◦C,
1H NMR (400 MHz, CDCl3/TMS): d 4.03 (s, 6H), 6.95 (d, J =
0.4 Hz, 2H), 7.10 (d, J = 0.4 Hz, 2H), 13C NMR (100 MHz,
CDCl3/TMS): 35.2, 122.5, 127.7, 138.5.
a 0.5 mmol of 1, 0.25 mmol of 2, 20 mol% of Cu(OAc)2, 2 mL xylene,
140 ◦C, 12 h. b Isolated yield and based on 2. c Isolated yield and based
on 1
1,1¢-Dibenzyl-1H,1¢H-2,2¢-biimidazole26. M.p.: 148–149 ◦C,
1H NMR (400 MHz, CDCl3/TMS): d 5.69 (s, 4H), 6.92 (d, J =
1.2 Hz, 2H), 7.01–7.04 (m, 4H), 7.12 (d, J = 1.2 Hz, 2H), 7.22–7.24
(m, 6H), 13C NMR (100 MHz, CDCl3/TMS): 50.7, 121.4, 127.4,
127.5, 128.3, 128.6, 137.2, 138.2.
atom at the 2-position of azole and bisazole and H2O were
produced.
In conclusion, we have developed an efficient and convenient
air oxidative coupling reaction of azoles. It provides a new and
regioselective approach to construct C–C bonds at the 2-position
of azoles.
1,1¢-Dimethyl-4,4¢,5,5¢-tetraphenyl-1H,1¢H-2,2¢-biimidazole.
M.p.: 258–259 ◦C 1H NMR (400 MHz, CDCl3/TMS): d 3.94 (s,
6H), 7.13–7.16 (m, 2H), 7.19–7.23 (m, 4H), 7.41–7.43 (m, 4H),
7.47–7.55 (m, 10H), 13C NMR (100 MHz, CDCl3/TMS): 33.6,
126.3, 126.6, 128.1, 128.7, 129.0, 130.7, 130.9, 134.4, 137.2, 138.2.
Anal. Calc. for C32H26N4: C, 82.38; H, 5.62; N, 12.01. Found: C,
82.41; H, 5.65; N, 11.96%
Experimental
1H and 13C NMR spectra were recorded in CDCl3 on Bruker
AMX-400 MHz instrument with TMS as internal standard.
Coupling constants are reported in Hertz (Hz). MS was obtained
using EI ionization. Melting points were uncorrected.
◦
1
4,4¢-Dimethyl-2,2¢-bithiazole27. M.p.: 136–137 C, H NMR
(400 MHz, CDCl3/TMS): d 2.50 (s, 6H), 6.95 (s, 2H), 13C NMR
(100 MHz, CDCl3/TMS): 17.1, 115.3, 154.0, 160.7.
328 | Org. Biomol. Chem., 2010, 8, 326–330
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
4,4¢,5,5¢-Tetramethyl-2,2¢-bithiazole28. M.p.: 174–175 ◦C, 1H
NMR (400 MHz, CDCl3/TMS): d 2.36 (s, 6H), 2.38 (s, 6H), 13
Acknowledgements
C
This work was financially supported by the Specialized Research
Fund for the Doctoral Program of Higher Education of China
(20060335036).
NMR (100 MHz, CDCl3/TMS): 11.5, 14.7, 128.1, 149.5, 157.0.
2,2¢-Bibenzo[d]oxazole29. M.p.: 258–259 ◦C, 1H NMR
(400 MHz, CDCl3/TMS): d 7.45–7.54 (m, 4H), 7.71 (d, J = 8.8 Hz,
2H), 7.92 (d, J = 8.0 Hz, 2H), 13C NMR (100 MHz, CDCl3/TMS):
111.4, 121.4, 125.7, 127.4, 141.1, 150.9, 151.8.
Notes and references
1 (a) Modern Carbonyl Olefination, (Ed.: T. Takeda), Wiley-VCH,
Weinheim, 2004; (b) Handbook of Metathesis, (Ed.: R. H. Grubbs),
Wiley-VCH, Weinheim, 1993, Vols. 1–3.
◦
1
5,5¢-Dimethyl-2,2¢-bibenzo[d]oxazole30. M.p.: 217–218 C, H
NMR (400 MHz, CDCl3/TMS): d 2.51 (s, 6H), 7.30 (d, J = 8.4 Hz,
2H), 7.56 (d, J = 8.4 Hz, 2H), 7.67 (s, 2H), 13C NMR (100 MHz,
CDCl3/TMS): 21.4, 110.7, 121.0, 128.6, 135.7, 141.3, 149.1, 151.9.
2 D. J. Hlasta and C. A. Zificsak, Tetrahedron, 2004, 60, 8991–9016.
3 Negishi reaction see: (a) B. A. Anderson and N. K. Harn, Synthesis,
1996, 583–585; (b) B. A. Anderson, L. M. Becke, R. N. Booher,
M. E. Flaugh, N. K. Harn, T. J. Kress, D. L. Varie and J. P. Wepsiec,
J. Org. Chem., 1997, 62, 8634–8639; (c) M. R. Reeder, H. E. Gleaves,
S. A. Hoover, R. J. Imbordino and J. J. Pangborn, Org. Process Res.
Dev., 2003, 7, 696–699; (d) E. Crowe, F. Hossner and M. J. Hughes,
Tetrahedron, 1995, 51, 8889–8900; (e) A. S. B. Prasad, T. M. Stevenson,
J. R. Citineni, V. Nyzam and P. Knochel, Tetrahedron, 1997, 53, 7237–
7254; (f) T. Bach and S. Heuser, Tetrahedron Lett., 2000, 41, 1707–1710.
4 Stille reaction see: (a) S. Sahli, B. Stump, T. Welti, W. B. Schweizer
and R. Diederich, Helv. Chim. Acta, 2005, 88, 707–730; (b) D. J.
Brauer, K. W. Kottsieper, C. Liek, O. Stelzer, H. Waffenschmidt and P.
Wasserscheid, J. Organomet. Chem., 2001, 630, 177–184; (c) I. Collins,
J. L. Castro and L. J. Street, Tetrahedron Lett., 2000, 41, 781–784;
(d) O. Krebs and R. J. K. Taylor, Org. Lett., 2005, 7, 1063–1066; (e) G.
Kennedy and A. D. Perboni, Tetrahedron Lett., 1996, 37, 7611–7614;
(f) R. Wittenberg, J. Srogl, M. Egi and L. S. Liebeskind, Org. Lett.,
2003, 5, 3033–3035.
5 Suzuki–Miyaura reaction see: (a) Y. Gong and W. He, Org. Lett., 2002,
4, 3803–3805; (b) S. Grivas and S. Lindstro¨m, J. Heterocycl. Chem.,
1995, 32, 467–471; (c) J. Ezquerra and C. Lamas, Tetrahedron, 1997, 53,
12755–12764; (d) S.-H. Lee, K. Yoshida, H. Matsushita, B. Clapham,
G. Koch, J. Zimmermann and K. D. Janda, J. Org. Chem., 2004, 69,
8829–8835; (e) B. B. Wang and P. J. Smith, Tetrahedron Lett., 2003, 44,
8967–8969; (f) K. J. Hodgetts and M. T. Kershaw, Org. Lett., 2002, 4,
1363–1365; (g) K. J. Hodgetts and M. T. Kershaw, Org. Lett., 2003, 5,
2911–2914; (h) N. Zou, J.-F. Liu and B. Jiang, J. Comb. Chem., 2003,
5, 754–755; (i) G. A. Molander and B. Biolatto, J. Org. Chem., 2003,
68, 4302–4314; (j) V. J. Majo, J. Prabhakaran, J. J. Mann and J. S. D.
Kumar, Tetrahedron Lett., 2003, 44, 8535–8537; (k) J. J. Hangeland,
A. M. Doweyko, T. Dejneka, T. J. Friends, P. Devasthale, K. Mellstro¨m,
J. Sandberg, M. Grynfarb, J. S. Sack, H. Einspahr, M. Fa¨rnegardh, B.
Husman, J. Ljunggren, K. Koehler, C. Sheppard, J. Malm and D. E.
Ryono, Bioorg. Med. Chem. Lett., 2004, 14, 3549–3553; (l) R. Pereira,
C. Gaudon, B. Iglesias, P. Germain, H. Gronemeyer and A. R. de Lera,
Bioorg. Med. Chem. Lett., 2006, 16, 49–54.
5,5¢-Diphenyl-2,2¢-bi(1,3,4-oxadiazole)31. M.p.: 269–270 ◦C,
1H NMR (400 MHz, CDCl3/TMS): d 7.57–7.66 (m, 6H), 8.24
(d, J = 7.6 Hz, 4H), 13C NMR (100 MHz, CDCl3/TMS): 122.5,
127.7, 129.3, 132.9, 153.0, 166.3.
1-Benzyl-1¢-methyl-1H,1¢H-2,2¢-bibenzo[d]imidazole. M.p.:
◦
1
176-177 C, H NMR (400 MHz, CDCl3/TMS): d 4.30 (s, 3H),
6.23 (s, 2H), 7.15–7.21 (m, 5H), 7.29–7.34 (m, 3H), 7.36–7.40 (m,
2H), 7.46 (d, J = 8.0 Hz, 1H). 7.82 (d, J = 8.4 Hz, 1H), 7.87–7.89
(m, 1H), 13C NMR (100 MHz, CDCl3/TMS): 32.4, 48.7, 110.0,
110.9, 120.3, 120.4, 122.8, 122.9, 123.9, 124.1, 127.0, 127.4, 128.6,
135.6, 136.1, 137.0, 142.4, 142.7, 143.0, 143.1. Anal. Calc. for
C22H18N4: C, 78.08; H, 5.36; N, 16.56. Found: C, 78.03; H, 5.38;
N, 16.64%
1-Benzyl-1¢-phenyl-1H,1¢H-2,2¢-bibenzo[d]imidazole. M.p.:
◦
1
186–187 C, H NMR (400 MHz, CDCl3/TMS): d 6.02 (s, 2H),
7.04–7.06 (m, 2H), 7.16–7.20 (m, 5H), 7.21–7.26 (m, 2H), 7.28–
7.36 (m, 3H), 7.38–7.41 (m, 4H), 7.63 (d, J = 7.6 Hz, 1H), 7.92
(d, J = 7.6 Hz, 1H), 13C NMR (100 MHz, CDCl3/TMS): 48.2,
110.5, 111.0, 120.4, 120.8, 122.6, 123.3, 123.9, 124.4, 126.9, 127.2,
127.6, 128.3, 128.6, 129.2, 135.3, 136.4, 136.5, 136.8, 142.5, 142.6,
142.7, 143.0. Anal. Calc. for C27H20N4: C, 80.98; H, 5.03; N, 13.99.
Found: C, 80.90; H, 5.15; N, 14.02%
2-(1-Benzyl-1H-imidazol-2-yl)-1-methyl-1H-benzo[d]imidazole.
M.p.: 89–90 ◦C, 1H NMR (400 MHz, CDCl3/TMS): 4.17 (s,
3H), 5.93 (s, 2H), 7.04 (s, 1H), 7.19–7.35 (m, 8H), 7.40 (d, J =
8.0 Hz, 1H), 7.78 (d, J = 7.2 Hz, 1H), 13C NMR (100 MHz,
CDCl3/TMS): 32.1, 51.3, 109.7, 119.9, 122.4, 122.5, 123.2, 127.7,
127.8, 128.7, 128.9, 135.9, 137.2, 137.9, 142.4, 143.6. EI-MS:
m/z = 288.
6 Stille reaction see: I. Castellote, J. J. Vaquero, J. Fernandez-Gadea and
J. Alvarez-Builla, J. Org. Chem., 2004, 69, 8668–8675.
7 Sonogashira reaction see: (a) W. M. David, D. Kumar and S. M.
Kerwin, Bioorg. Med. Chem. Lett., 2000, 10, 2509–2512; (b) A. K.
Nadipuram, W. M. David, D. Kumar and S. M. Kerwin, Org. Lett.,
2002, 4, 4543–4546; (c) J. Schlegel and G. Maas, Synthesis, 1999, 100–
106; (d) S. M. Kerwin and A. Nadipuram, Synlett, 2004, 1404–1408;
(e) N. F. Langille, L. A. Dakin and J. S. Panek, Org. Lett., 2002, 4, 2485–
2488; (f) N. D. P. Cosford, L. Tehrani, J. Roppe, E. Schweiger, N. D.
Smith, J. Anderson, L. Bristow, J. Brodkin, X. Jiang, I. Mc-Donald,
S. Rao, M. Washburn and M. A. Varney, J. Med. Chem., 2003, 46,
204–206; (g) H. Siebeneicher and S. Doye, Eur. J. Org. Chem., 2002,
1213–1220; (h) R. U. Braun and T. J. J. Mu¨ller, Tetrahedron, 2004, 60,
9463–9469.
8 H. A. Chiong and O. Daugulis, Org. Lett., 2007, 9, 1449–1451.
9 (a) B. M. Trost, Acc. Chem. Res., 2002, 35, 695–705; (b) B. M. Trost,
Angew. Chem., 1995, 107, 285–307; B. M. Trost, Angew. Chem., Int. Ed.
Engl., 1995, 34, 259–281; (c) B. M. Trost, Science, 1991, 254, 1471–1477.
10 (a) S. Havez, M. Begtrup, P. Vedsø, K. Andersen and T. Ruhland,
Synthesis, 2001, 909–913; (b) Y. Kondo, T. Komine and T. Sakamoto,
Org. Lett., 2000, 2, 3111–3113; (c) D. Sames, B. Sezen, B. S. Lane,
WO 2004 069394 [Chem. Abstr. 141:207208]; (d) C. Hoarau, A. D. de
Kerdaniel, F. N. Bracq, P. Grandclaudon, A. Couture and F. Marsais,
Tetrahedron Lett., 2005, 46, 8573–8577; (e) F. Lopez-Calahorra, M.
Martinez-Rubio, D. Velasco, E. Brillas and L. Julia, Tetrahedron,
2-◦(1-Methyl-1H-imidazol-2-yl)benzo[d]oxazole. M.p.: 140–
141 C, 1H NMR (400 MHz, CDCl3/TMS): 4.23 (s, 3H), 7.12 (s,
1H), 7.26 (s, 1H), 7.35–7.40 (m, 2H), 7.61–7.63 (m, 1H), 7.75–7.77
(m, 1H), 13C NMR (100 MHz, CDCl3/TMS): 35.6, 111.0, 120.0,
124.7, 125.2, 125.6, 130.1, 135.6, 141.5, 149.8, 154.8. EI-MS:
m/z = 199.
2-(1◦-Benzyl-1H -imidazol-2-yl)-4,5-dimethylthiazole. M.p.:
91–92 C, 1H NMR (400 MHz, CDCl3/TMS): 2.32 (s, 3H), 2.36
(s, 3H), 5.83 (s, 2H), 6.92 (s, 1H), 7.08 (s, 1H), 7.23 (d, J = 7.6 Hz,
2H), 7.26–7.32 (m, 3H), 13C NMR (100 MHz, CDCl3/TMS): 11.1,
14.8, 50.7, 122.3, 127.1, 127.72, 127.73, 128.6, 129.2, 137.1, 140.7,
148.8, 154.8. EI-MS: m/z = 269.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 326–330 | 329
©

View Article Online
2004, 60, 285–289; (f) L. T. Kian, G. B. Robert and A. E. Jonathan,
J. Am. Chem. Soc., 2002, 124, 13964–13965; (g) L. T. Kian, G. B.
Robert and A. E. Jonathan, J. Am. Chem. Soc., 2001, 123, 2685–2686;
(h) S. Sahnoun, S. Messaoudi, J.-F. Peyrat, J.-D. Brion and M. Alami,
Tetrahedron Lett., 2008, 49, 7279–7283; (i) J. C. Lewis, J. Y. Wu, R. G.
Bergman and J. A. Ellman, Angew. Chem., Int. Ed., 2006, 45, 1589–
1591; (j) B. Sezen and D. Sames, J. Am. Chem. Soc., 2003, 125, 5274–
5275.
Chem., Int. Ed., 2008, 47, 1932–1934; (g) S. Ueda and H. Nagasawa,
Angew. Chem., Int. Ed., 2008, 47, 6411–6413.
18 N. Winterton, Green Chem., 2001, 3, G73.
19 D. H. Wang, M. Wasa, R. Giri and J. Q. Yu, J. Am. Chem. Soc., 2008,
130, 7190–7191.
20 P. Peng, B. X. Tang, S.-F. Pi, Y. Liang and J.-H. Li, J. Org. Chem., 2009,
74, 3569–3572.
21 J. Mao, N. Li, H. Li and X. Hu, J. Mol. Catal. A: Chem., 2006, 258,
11 P. L. Holland, K. R. Rodgers and W. B. Tolman, Angew. Chem., Int.
178–184.
Ed., 1999, 38, 1139–1142.
22 C. Holtgrewe, C. Diedrich, T. Pape, S. Grimme and F. E. Hahn,
Eur. J. Org. Chem., 2006, 3116–3124.
23 I. S. Kashparov and A. F. Pozharskii, Khim. Geterotsikl. Soedin, 1971,
7, 124.
24 B. Cetinkaya, E. Cetinkaya, J. A. Chamizo, P. B. Hitchcock, H. A.
Jasim, H. Kucukbay and M. F. Lappert, J. Chem. Soc., Perkin Trans.
1, 1998, 2047.
25 S. B. Park and H. Alper, Org. Lett., 2003, 5, 3209.
26 B. Flavio, B. Alfredo, R. P. Bianca and B. Bruna, J. Organomet. Chem.,
1989, 375, 147.
27 P. R. Stephane, R. V. Jean-Bernard and L. Roger, Tetrahedron Lett.,
1996, 37, 5889.
28 R. Mostaghim and Y. A. Beni, Indian J. Chem., Sect. B., 2001, 40, 498.
29 E. Tauer and K. H. Grellmann, J. Org. Chem., 1981, 46, 4252.
30 Y. M. Zhou, X. P. Xia and Z. H. Gao, Gaodeng Xuexiao Huaxue
Xuebao, 1991, 12, 189.
12 H.-Q. Do and O. Daugulis, J. Am. Chem. Soc., 2007, 129, 12404–
12405.
13 D. Zhao, W. Wang, F. Yang, J. Lan, L. Yang, G. Gao and J. You, Angew.
Chem., Int. Ed., 2009, 48, 3296–3300.
14 H. Hachiya, K. Hirano, T. Satoh and M. Miura, Org. Lett., 2009, 11,
1737–1740.
15 J. Canivet, J. Yamaguchi, I. Ban and K. Itami, Org. Lett., 2009, 11,
1733–1736.
16 X. Chen, G. Dobereiner, X.-S. Hao, R. Giri, N. Maugel and J.-Q. Yu,
Tetrahedron, 2009, 65, 3085–3089.
17 (a) J. Hassan, M. Se´vignon, C. Gozzi, E. Schulz and M. Lemaire, Chem.
Rev., 2002, 102, 1359–1470; (b) J. M. Richter, B. W. Whitefield, T. J.
Maimone, D. W. Lin, M. P. Castroviejo and P. S. Baran, J. Am. Chem.
Soc., 2007, 129, 12857–12869; (c) P. S. Baran and J. M. Richter, J. Am.
Chem. Soc., 2004, 126, 7450–7451; (d) Z. Li and C.-J. Li, J. Am. Chem.
Soc., 2006, 128, 56–57; (e) L. Menini and E. V. Gusevskaya, Chem.
Commun., 2006, 209–211; (f) G. Brasche and S. L. Buchwald, Angew.
31 L. I. Vereshchagin, A. V. Petrov, V. N. Kizhnyaev, F. A. Pokatilov and
A. I. Smirnov, Russ. J. Org. Chem., 2006, 42, 1049.
330 | Org. Biomol. Chem., 2010, 8, 326–330
This journal is
The Royal Society of Chemistry 2010
©