A generalised route for the synthesis of β-furyl-α,β-unsaturated aldehydes through Suzuki reactions

Article abstract of DOI:10.1016/j.tetlet.2008.01.010

A general method for the synthesis of β-(2-furyl)-α,β-unsaturated aldehydes is described using the Suzuki coupling reaction of furan-2-boronic acids and β-bromo-α,β-unsaturated aldehyde derivatives.

Full text of DOI:10.1016/j.tetlet.2008.01.010

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Tetrahedron Letters 49 (2008) 1461–1464
A generalised route for the synthesis of b-furyl-a,b-unsaturated
aldehydes through Suzuki reactions
Khokan Samanta, Gandhi Kumar Kar *, Achintya Kumar Sarkar *
Department of Chemistry, Presidency College, 86/1 College Street, Kolkata 700 073, India
Received 30 August 2007; revised 21 December 2007; accepted 3 January 2008
Available online 8 January 2008
Abstract
A general method for the synthesis of b-(2-furyl)-a,b-unsaturated aldehydes is described using the Suzuki coupling reaction of furan-
2-boronic acids and b-bromo-a,b-unsaturated aldehyde derivatives.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Suzuki reaction; b-(2-Furyl)-a,b-unsaturated aldehyde; Furan-2-boronic acid; b-Bromo-a,b-unsaturated aldehyde
A large number of substituted phenanthrenes, phenan-
thropyrans and their 9,10-dihydro derivatives (e.g., gymno-
pusin, erianthridin and coeloginin)1–9 have been isolated
from Himalayan orchids. Some of these compounds have
been reported to exhibit significant biological activities
(Fig. 1).
In our ongoing work towards the synthesis of such
phenanthrene derivatives we required b-furylacrolein deriv-
atives. These compounds are precursors for the synthesis of
substituted phenanthrenes via intramolecular Diels–Alder
reactions (Scheme 1).
In this connection, we have studied the Suzuki coupling
reaction8–10 of several b-bromoacroleins with furan-boro-
nic acids and we report here a high yielding general method
for the synthesis of b-(2-furyl)-a,b-unsaturated aldehydes
6–10 (Scheme 2).
The required bromoaldehydes11 1–5 were prepared via
modified Vilsmeier–Haack reactions from the correspond-
ing ketones and PBr3/DMF–CHCl3 following a standard
procedure.11 1-Bromo-6-methoxy-3,4-dihydronaphthalene-
2-aldehyde (3c) (1 mmol) on treatment with furan-2-boro-
nic acid A (1.15 mmol) and Et3N (3 mmol) in DMF (3–
4 mL) in the presence of Pd(PPh3)4 (1 mol %) as catalyst
under an argon atmosphere furnished 8e in 86% yield as
1
a yellow solid (entry 17). IR, H NMR and 13C spectra12
O
OH
OMe
of 8e were in good agreement with the assigned structure.
Following similar reactions, other furoacrolein derivatives
were prepared in 50–92% yields. The compounds were
characterized by spectroscopic (IR/NMR/MS) analysis.
The results are summarized in Table 1.
It is interesting to note that in the case of 3b, of the two
bromo substituents, the 1-bromo rather than the 7-bromo
took part in the Suzuki coupling reaction almost exclu-
sively (entries 15 and 16).The Suzuki coupling reaction of
4 with furan-2-boronic acid and 5-formylfuran-2-boronic
acid led to the formation of the fully aromatic compounds
9a and 9b, respectively (entries 19 and 20). At present we
are unable to explain this observation.
OMe
MeO
OMe
OMe
OH
MeO
OH
O
HO
HO
HO
OMe
Gymnopusin6-9
Erianthridin5
Coeloginin4
Fig. 1.
*
Corresponding authors. Tel.: +91 33 2241 3893.
E-mail addresses: gandhikar41@hotmail.com (G. K. Kar),
achintyasarkar@yahoo.co.in (A. K. Sarkar).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.010

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K. Samanta et al. / Tetrahedron Letters 49 (2008) 1461–1464
R3
R3
R2
R3
R2
R4
R5
R2
R4
Br
O
R5
+
R4
R1
R1
R1
(HO)2B
CHO
O
OR6
OR6
Scheme 1.
Br
O
R
Pd(PPh3)4, Et3N, DMF
+
°
100 C, Argon atm.
(HO)2B
O
R
CHO
CHO
5-9 h
R=H/CHO
6-10
A R = H
B R = CHO
1-5
Scheme 2.
Table 1
Entry
Bromoaldehyde
Boronic acid
Aa or Ba
Product
Time
(h)
Conversion
(%)
Isolated
yield (%)
Melting point
(°C)
Ph
Br
Ph
R2
O
CHO
CHO
6a-b
1
1
2
1
1
A
B
6a R2 = H
6b R2 = CHO
6
6
100
100
53
50
Viscous liquid
Viscous liquid
1
Br
R
( )
n
R1
)
(
n
R2
O
CHO
2a-e
CHO
7a-j
3
4
5
6
7
8
9
10
11
12
2a n = 1, R1 = H
2a
A
B
A
B
A
B
A
B
A
B
7a n = 1, R1 = H, R2 = H
7b n = 1, R1 = H, R2 = CHO
7c n = 2, R1 = H, R2 = H
7d n = 2, R1 = H, R2 = CHO
7e n = 2, R1 = Me, R2 = H
7f n = 2, R1 = Me, R2 = CHO
7g n = 2, R1 = tBu, R2 = H
7h n = 2, R1 = tBu, R2 = CHO
7i n = 4, R1 = H, R2 = H
5
6
7
6.5
6
7
6.5
7
6
6
100
100
95
100
100
100
90
90
100
100
75
70
71
62
54
50
67
60
78
70
55–57
101–102
42–43
58–60
Oil
Viscous liquid
50–52
Viscous liquid
Oil
2b n = 2, R1 = H
2b
2c n = 2, R1 = Me
2c
2d n = 2, R1 = tBu
2d
2e n = 4, R1 = H
2e
7j n = 4, R1 = H, R2 = CHO
Oil
X
X
Y
Y
Br
O
R2
CHO
3a-c
CHO
8a-f

K. Samanta et al. / Tetrahedron Letters 49 (2008) 1461–1464
1463
Table 1 (continued)
Entry
Bromoaldehyde
Boronic acid
Aa or Ba
Product
Time
(h)
Conversion
(%)
Isolated
yield (%)
Melting point
(°C)
13
14
15
16
17
18
3a X = H, Y = H
3a
A
B
A
B
A
B
8a X = H, Y = H, R2 = H
5.75
6
8
9
5.5
5.5
95
100
85
85
90
96
77
69
57
72
86
92
58–60
106–108
88–90
138–140
106–108
130
8b X = H, Y = H, R2 = CHO
8c X = Br, Y = H, R2 = H
8d X = Br, Y = H, R2 = CHO
8e X = H, Y = OMe, R2 = H
8f X = H, Y = OMe, R2 = CHO
3b X = Br, Y = H
3b
3c X = H, Y = OMe
3c
CHO
CHO
O
2
R
Br
4
9a-b
19
20
4
4
A
B
9a R2 = H
9b R2 = CHO
6
6
100
100
53
53
Semi-solid
115–117
Br
R2
O
CHO
CHO
5
10a-b
21
22
5
5
A
B
10a R2 = H
10b R2 = CHO
5.5
5.5
98
100
84
73
100
140
a
A = Furan-2-boronic acid, B = 5-formylfuran-2-boronic acid.
3. Majumder, P. L.; Sarkar, A. K. Indian J. Chem. 1982, 21B, 829 and
references cited therein.
4. Majumder, P. L.; Bandyopadhyay, D.; Joardar, S. J. Chem. Soc.,
Perkin Trans. 1 1982, 1131.
5. Majumder, P. L.; Joardar, M. Indian J. Chem. 1985, 24B, 1192.
6. Majumder, P. L.; Banerjee, S. Indian J. Chem. 1989, 28B, 1085.
7. Hughes, A. B.; Sargent, M. V. J. Chem. Soc., Perkin Trans. 1 1989,
1787.
Thus in conclusion, we have developed a general method
for the preparation of b-(2-furyl)-a,b-unsaturated alde-
hydes. We are utilising these compounds for the prepara-
tion of phenanthrene derivatives.
Acknowledgements
8. (a) Wang, X.; Snieckus, V. Tetrahedron Lett. 1991, 32, 4879; (b)
Snieckus, V. Pure Appl. Chem. 1994, 66, 2155.
We are thankful to CSIR for providing a JRF-NET
fellowship to K.S. CSIR funding [project no. 01(1976)/
05/EMR-II] to G.K.K. is also gratefully acknowledged.
9. Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic
Molecules, 2nd ed.; University Science Books, 1999.
10. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
11. (a) Coates, R. M.; Senter, P. D.; Baker, W. R. J. Org. Chem. 1982, 47,
3597; (b) Gilchrist, T. L.; Summersell, R. J. J. Chem. Soc., Perkin
Trans. 1 1988, 2595; (c) Kouichi, O.; Koji, M.; Tomomi, Y.; Fumiaki,
N.; Sakae, U. Organometallics 2000, 19, 5525.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2008.01.010.
12. Selected analytical data: Compound 7c: IR (KBr) 1645 cmÀ1 1H
,
NMR (400 MHz, CDCl3) d 1.56–1.62 (2H, m), 1.64–1.70 (2H, m),
2.31 (2H, t, J = 6), 2.51–2.54 (2H, m), 6.40 (1H, dd, J = 1.8, 3.2 Hz),
6.43 (1H, d, J = 3.2 Hz), 7.45 (1H, br s), 10.04 (1H, s) ppm. MS (ESI-
MS positive ion) m/z 177.09 [M+H]+,199.05 [M+Na]+.
Compound 8c: IR (KBr) 1669 cmÀ1 1H NMR (400 MHz, CDCl3) d
,
References and notes
2.64–2.68 (2H, m), 2.28 (2H, m), 6.60 (1H, t, J = 3.2 Hz), 6.63 (1H, d,
J = 3.2 Hz), 7.13 (1H, d, J = 8 Hz), 7.26 (1H, br s), 7.43 (1H, dd,
J = 1.6, 8 Hz), 7.65 (1H, d, J = 1.2 Hz), 9.87 (1H, s) ppm; HRMS
(ESI, 70 eV): m/z = 302.9966 [M++H] (calculated mass for
C15H12O2Br: 303.0022 [M++H]).
1. Majumder, P. L.; Datta, N.; Sarkar, A. K.; Chakraborti, J. J. Nat.
Prod. 1982, 45, 730 and references cited therein.
2. Majumder, P. L.; Sarkar, A. K.; Chakraborti, J. Phytochemistry 1982,
21, 2713 and references cited therein.

1464
K. Samanta et al. / Tetrahedron Letters 49 (2008) 1461–1464
Compound 8d: IR (KBr) 1656, 1677 cmÀ1
;
1H NMR (400 MHz,
CDCl3) d 20.7, 27.9, 55.3, 111.1, 111.8, 113.7, 115.1, 126.1, 129.9,
134.7, 141.1, 142.7, 143.9, 147.9, 161.2, 192.5 ppm; HRMS (ESI,
70 eV): m/z = 255.0893 [M++H] (calculated mass for C16H15O3:
255.1023 [M++H]).
CDCl3) d 2.68–2.71 (2H, m), 2.83 (2H, m), 6.79 (1H, d, J = 3.6 Hz),
7.13–7.16 (2H, m), 7.41–7.47 (2H, m), 9.75 (1H, s), 9.81 (1H, s) ppm;
13C NMR (100 MHz, CDCl3) d 20.6, 26.5, 116.8, 120.5, 121.0, 129.6,
130.1, 133.4, 134.3, 137.0, 139.7, 139.9, 152.4, 153.5, 177.7,
191.1 ppm; HRMS (ESI, 70 eV): m/z = 330.9926 [M++H] (calculated
mass for C16H12O3Br: 330.9972 [M++H]).
Compound 8f: IR (KBr) 1656, 1678 cmÀ1 1H NMR (400 MHz,
;
CDCl3) d 2.66–2.70 (2H, m), 2.84 (2H, m), 3.83 (3H, s), 6.71 (1H, dd,
J = 2.6, 8.6 Hz), 6.76 (1H, d, J = 3.5 Hz), 6.79 (1H, d, J = 2.6 Hz),
6.95 (1H, d, J = 8.6 Hz), 7.39 (1H, d, J = 3.5 Hz), 9.72 (1H, s), 9.76
(1H, s) ppm; MS (ESI-MS, positive ion) m/z: 283.12 [M+H]+, 305.08
[M+Na]+. HRMS (ESI, 70 eV): m/z = 305.0791 [M+Na]+ (calculated
mass for C17H14O4Na: 305.0790 [M+Na]+).
Compound 8e: IR (KBr) 1646 cmÀ1 1H NMR (400 MHz, CDCl3) d
;
2.63–2.67 (2H, m), 2.82 (2H, m), 3.83 (3H, s), 6.55–6.56 (1H, dd,
J = 1.9, 3.3 Hz), 6.59 (1H, d, J = 3.3 Hz), 6.71 (1H, dd, J = 2.6,
8.6 Hz), 6.77 (1H, br d, J = 2.5 Hz), 7.06 (1H, d, J = 8.6 Hz), 7.60
(1H, br d, J = 1.1 Hz), 9.82 (1H, s) ppm; 13C NMR (100 MHz,