Synthesis of polycyclic coumarin derivatives by combined Claisen rearrangement, ring-closing metathesis, and Diels-Alder reaction

Article abstract of DOI:10.1246/cl.2006.376

A new route to several hitherto unknown linearly and angularly architectured polycyclic coumarin derivatives has been developed involving tandem applications of three atom economic processes viz. Claisen rearrangement, ring-closing enyne metathesis, and D

Full text of DOI:10.1246/cl.2006.376

376
Chemistry Letters Vol.35, No.4 (2006)
Synthesis of Polycyclic Coumarin Derivatives by Combined Claisen Rearrangement,
Ring-closing Metathesis, and Diels–Alder Reaction
Shital K. Chattopadhyay,ꢀ Titas Biswas, and Kaushik Neogi
Department of Chemistry, University of Kalyani, Kalyani-741235, West Bengal, India
(Received December 1, 2005; CL-051486; E-mail: skc@klyuniv.ernet.in)
A new route to several hitherto unknown linearly and
angularly architectured polycyclic coumarin derivatives has
been developed involving tandem applications of three atom
economic processes viz. Claisen rearrangement, ring-closing
enyne metathesis, and Diels–Alder reactions.
i
iii
18 h
66%
2 h
O
O
O
O
O
O
RO
O
O
79%
2, R = H
3, R = CH2-C=CH
1
ii
5
81%
Multiple bond metathesis reactions have emerged1 as an
elegant tool in organic synthesis for the creation of molecular
complexity. Of the two types viz. double–double bond and
double–triple bond metathesis, the latter version2 is relatively
new but is enjoying increasing attention with regard to further
transformations of the resulting conjugate dienes. These tandem
transformations have led to synthetic applications in the field of
polycycle construction and natural product synthesis.3
iii
i
3 h
12h
88%
O
O
RO
O
O
O
O
O
83%
9
6
7, R = H
8, R = CH2-C=CH
ii
89%
Various coumarin derivatives are known4 to display impor-
tant photophysical and biological activities and, for this and
other reasons, interest in the synthesis5 of derivatives of this
important ring system continues to increase. We have recently
described6 tandem applications of Claisen rearrangement and
ring-closing metathesis reactions as a route to several carbo- and
heterocyclic systems. Herein, we wish to report synthesis of
several 6,6,7,6,5- and 6,6,7,6,6,6-ring fused hitherto unknown
coumarin derivatives utilizing tandem applications of three
atom-economic processes viz. Claisen rearrangement, ring-
closing enyne metathesis, and Diels–Alder reaction.
O
RO
i
iii
O
0.5 h
O
76%
18 h
69%
O
O
O
O
O
10
11, R = H
12, R = CH2-C=CH
ii
13
83%
Scheme 1. Reagents and conditions; (i) diphenyl ether, reflux;
(ii) propargyl bromide, acetone, K2CO3, reflux, 12 h; (ii)
Grubbs’ catalyst (4, 5 mol %), benzene (0.008 M), reflux.
Thus, Claisen rearrangement of 7-allyloxy-4-methylcou-
marin (1) neatly provided the known7 8-allyl-7-hydroxy-4-meth-
ylcoumarin (2, Scheme 1) under our modified procedure. The
latter on alkylation with propargyl bromide under conventional
conditions provided the ether 3 in good yield. Ring-closing
metathesis of oxygen-tethered enynes leading to oxepin-deriva-
tives is less documented and proved to be erratic in other instan-
ces.8 Pleasingly, metathesis of the enyne derivative 3 with
Grubbs’ catalyst bis(tricyclohexylphosphine)benzylideneruthe-
nium(IV) dichloride9 (4) in refluxing benzene proceeded
smoothly to provide the diene 5 as single isolable product. Sim-
ilarly, Claisen rearrangement of 7-allyloxy-4,8-dimethylcou-
marin10 under modified conditions neatly provided the rear-
ranged phenol 7 which was alkylated with propargyl bromide
to provide the ether 8 in high yield. Ring-closing metathesis of
the resulting enyne proved to be even more facile, and the con-
jugated diene 9 was obtained as a colorless solid, mp 152 ꢁC, in a
gratifying yield of 88%. The same sequence of reactions on 6-
allyloxycoumarin11 (10) viz. Claisen rearrangement to the
phenol 11, etherification of the latter to the enyne 11 followed
by its RCM led to the diene 13 in an overall yield of 43.5% over
three steps.
the resulting cycloadduct 14 (Scheme 2) crystallized out of the
solution on cooling. It is interesting to note that the
cycloadduct was obtained as a single diastereomer and its stereo-
chemistry was assigned to be all cis based on precedence12 and
observed coupling constants of the appropriate protons in the
1H NMR spectrum. Similarly, reaction of the diene 5 with maleic
anhydride and naphthoquinone led exclusively to the cycload-
ducts 15 and 16, respectively.
The reaction of the diene 9 with all the three dienophiles
tried proceeded uneventfully to provide the cycloadducts 17–
19 in very good yield. On the other hand, the diene 13 reacted
sluggishly with either of N-phenylmaleimide and 1,4-naphtho-
quinone to provide modest yields of the cycloadducts 20 and
21, respectively. In some instances of application of ring-closing
enyne metathesis and Diels–Alder reaction, considerable im-
provement in yield has been observed when the reaction was car-
ried out in a one-pot manner without isolating the diene. Howev-
er, controlled experiment with each of the dienes 5, 9, and 13 and
N-phenylmaleimide revealed no significant improvement in
yield when the reactions were carried out in a one-pot manner.
In continuation of our earlier studies6 on sequential RCM-
aromatization protocol leading to carbocycles and heterocycles,
we further became interested to see whether the cycloadducts
with naphthaquinone (16, 19, and 21) could be aromatized lead-
We then focused our attention to the Diels–Alder reaction of
the resulting dienes 5, 9, and 13. Thus, when a solution of the di-
ene 5 and N-phenylmaleimide was refluxed in benzene for 30 h,
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.4 (2006)
377
2
3
For recent reviews on enyne metathesis, see: M. Mori, Top. Orga-
nomet. Chem. 1998, 1, 133; C. S. Poulsen, R. Madsen, Synthesis
2003, 1; S. T. Diver, A. J. Giessert, Chem. Rev. 2004, 104, 1317.
M. Mori, T. Kitamura, N. Sakakibara, Y. Sato, Org. Lett. 2000, 2,
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E. Brahmachary, T. Ganesh, Synlett 2000, 853; J. Renaud, C.-D.
Graph, L. Oberer, Angew. Chem., Int. Ed. 2000, 39, 3101; M.
Moreno-Manas, R. Pleixats, A. Santamaria, Synlett 2001, 1784;
N. Saito, Y. Sato, M. Mori, Org. Lett. 2002, 4, 803.
A. Murakami, G. Gao, M. Omura, M. Yano, C. Ito, H. Furukawa,
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5, 797; J. C. Gonzalez-Gomez, E. Uriarte, Synlett 2003, 2225;
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A. S. C. Chan, L.-Q. Gu, Org. Lett. 2004, 6, 4853; E. Sekino, T.
Kumamoto, T. Tanaka, T. Ikeda, T. Ishikawa, J. Org. Chem.
2004, 69, 2760.
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43, 7781; S. K. Chattopadhyay, B. K. Pal, S. Maity, Chem. Lett.
2003, 32, 1190; S. K. Chattopadhyay, R. De, S. Biswas, Synthesis
2005, 403; S. K. Chattopadhyay, K. Sarkar, S. Karmakar, Synlett
2005, 2083.
naphtho-
O
O
O
O
O
O
O
quinone
O
O
X
5
H
H
benzene
reflux,
36 h
benzene
reflux,
30 h
H
O
H
X
H
H
O
O
16, 83%
14, X = NPh, 66%
15, X = O, 69%
O
O
H
X
4
5
O
H
O
H
H
H
H
''
''
9
12 h
12 h
O
O
O
O
O
O
17, X = NPh, 72%
18, X = O, 76%
19, 77%
O
O
H
Ph
O
H
N
H
H
O
H
O
H
naphtho-
quinone
N
O
Ph
O
O
13
benzene
reflux,
36 h
benzene
reflux,
30 h
O
O
O
O
20, 41%
21, 36%
6
Scheme 2.
O
O
7
8
9
V. Satyanarayana, C. P. Rao, G. L. D. Krupadanam, G.
Srimannarayana, Synth. Commun. 1991, 21, 661.
K. Tonogaki, M. Mori, Tetrahedron Lett. 2002, 43, 2235; J. A.
Smulik, S. T. Diver, Org. Lett. 2000, 2, 2271.
O
Et3N
O
16
Silicagel
10h
O
22, 61%
P. Schwab, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1996,
118, 100.
10 K. D. Kaufman, J. Org. Chem. 1961, 26, 117.
Et3N
Silicagel
10 h
O
O
19
11 K. R. Shah, K. N. Trivedi, J. Indian Chem. Soc. 1975, 52, 436.
12 M. Mori, N. Sakakibara, A. Kinoshita, J. Org. Chem. 1998, 63,
6082; M. Rosillo, G. Dominguez, L. Casarrubios, U. Amador, J.
Perez-Castles, J. Org. Chem. 2004, 69, 2084; H.-Y. Lee, H. Y.
Kim, H. Tae, B. G. Kim, J. Lee, Org. Lett. 2003, 5, 3439.
13 All new compounds reported gave satisfactory spectroscopic and
analytical data. Data for 17: mp 296–298 ꢁC. ꢀmax: 328 nm. IR
(KBr, cmꢂ1): 1716, 1698, 1610, 1387, 1114. 1H NMR (CDCl3,
500 MHz) ꢁ 7.48–7.45 (2H, m), 7.41–7.38 (1H, m), 7.20–7.17
(3H, m), 6.18 (1H, app. t, J ¼ 3:4 Hz), 6.11 (1H, s), 5.19 (1H, d,
J ¼ 12:6 Hz), 4.52 (1H, d, J ¼ 12:6 Hz), 4.24 (1H, app. t, J ¼
14:8 Hz), 3.43 (1H, dd, J ¼ 8:9, 5.9 Hz), 3.40–3.37 (1H, m),
3.01 (1H, dd, J ¼ 15:0, 2.5 Hz), 2.92 (1H, dd, J ¼ 16:3, 6.8 Hz),
2.78 (1H, brd, J ¼ 12:8 Hz), 2.34 (3H, s), 2.23–2.18 (1H, m),
2.14 (3H, s). 13C NMR (CDCl3, 75 MHz) ꢁ 178.2 (s), 176.6 (s),
161.6 (s), 157.3 (s), 152.3 (s), 151.6 (s), 139.7 (s), 131.6 (s),
129.1 (d), 128.8 (d), 127.1 (d), 126.3 (d), 124.7 (d), 121.7 (s),
115.4 (s), 113.4 (s), 112.1 (d), 70.1 (t), 44.4 (d), 40.2 (d), 38.7
(t), 34.4 (d), 24.8 (t), 18.6 (q), 8.9 (q). Elemental analyses: Found:
C, 73.70; H, 5.46; N, 3.04%. Calcd for C27H23NO5: C, 73.46; H,
5.25; N, 3.17%. m=z (EI, 70 eV): 441 (100%), 268 (63%), 203
(81%). Data for 14: mp 218–220 ꢁC. ꢀmax: 326 nm. IR (KBr,
cmꢂ1): 1707, 1595, 1494, 1389, 1265. 1H NMR (CDCl3, 300
MHz) ꢁ 7.48–7.40 (4H, m), 7.35 (1H, d, J ¼ 8:5 Hz), 7.19 (1H,
d, J ¼ 7:8 Hz), 6.77 (1H, d, J ¼ 8:8 Hz), 6.15 (2H, brs), 5.25
(1H, d, J ¼ 12:5 Hz), 4.44 (1H, d, J ¼ 12:6 Hz), 3.94 (1H, d,
J ¼ 2:7 Hz), 3.91 (1H, s), 3.52 (1H, dd, J ¼ 8:9, 5.6 Hz), 3.38
(1H, t, J ¼ 8:3 Hz), 2.93–2.86 (2H, m), 2.39 (3H, s), 2.33–2.30
(1H, m). 13C NMR (CDCl3, 75 MHz) ꢁ 178.3 (s), 176.5 (s),
161.2 (s), 159.7 (s), 152.9 (s), 152.8 (s), 140.1 (s), 131.7 (s),
129.1 (d), 128.6 (d), 126.9 (d), 126.4 (d), 123.4 (d), 115.9 (s),
114.0 (s), 113.8 (s), 111.6 (d), 70.3 (t), 44.8 (d), 40.3 (d), 38.9
(d), 25.2 (t), 22.9 (t), 18.8 (q). Elemental analyses: Found: C,
73.19; H, 5.12; N, 3.41%. Calcd for C26H21NO5: C, 73.06; H,
4.95; N, 3.28%. m=z (EI, 70 eV): 427 (100%), 307 (22%), 254
(61%).
O
O
O
23, 68%
Scheme 3.
ing possibly to new coumarin–anthraquinone conjugate mole-
cules in view of the known importance of these two ring systems.
Thus, when a solution of the cycloadduct 16 in dichloromethane
was stirred with triethylamine in the presence of silica gel,
smooth oxidative aromatization took place to provide the corre-
sponding anthraquinone derivative 22 (Scheme 3) in good yield.
Similar aromatization/oxidation of the cycloadduct 19 provided
the conjugate molecule 23 in comparable yield.
In short, we have demonstrated that combined Claisen
rearrangement, ring-closing enyne metathesis, and Diels–Alder
reaction is an efficacious strategy for the preparation of several
hitherto unknown linearly and angularly architectured polycy-
clic complex coumarin derivatives. The advantage of the meth-
odology lies in its true atom-economic nature, operational
simplicity, predetermined mode of cyclization and high level
of stereocontroll. The prepared compounds13 may find biological
applications.
Financial assistance from DST, New Delhi (Grant No: SR/
OC-24/2002) is gratefully acknowledged. One of us (T.B.) is
also thankful to CSIR, New Delhi for a fellowship.
References and Notes
1
For recent reviews on olefin metathesis, see: T. M. Trnka, R. H.
Grubbs, Acc. Chem. Res. 2001, 34, 18; A. Furstner, Angew. Chem.,
Int. Ed. 2000, 39, 3012; A. Deiters, S. F. Martin, Chem. Rev. 2004,
104, 2199.
Published on the web (Advance View) March 11, 2006; DOI 10.1246/cl.2006.376