Palladium-catalyzed annulation of 2-substituted silylethynyloxybiaryls through δ-C-H activation

Article abstract of DOI:10.1246/cl.140725

The intramolecular hydroarylation of 2-(silylethynyloxy)-biphenyls takes place with the aid of a palladium catalyst to give 6-methylene-6H-d ibenzo[b,d]pyrans. The product can be transformed into 6,6-disubstituted dibenzopyrans via protodesilylation, foll

Full text of DOI:10.1246/cl.140725

Received: July 31, 2014 | Accepted: August 10, 2014 | Web Released: August 14, 2014
CL-140725
Palladium-catalyzed Annulation of 2-Substituted
Silylethynyloxybiaryls through δ-C-H Activation
Yasunori Minami,*1,2 Tomohiro Anami,3 and Tamejiro Hiyama*1,2
1Research and Development Initiative, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551
2ACT-C, JST, Chiyoda-ku, Tokyo 102-0076
3Department of Applied Chemistry, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551
(E-mail: yminami@kc.chuo-u.ac.jp, thiyama@kc.chuo-u.ac.jp)
The intramolecular hydroarylation of 2-(silylethynyloxy)-
biphenyls takes place with the aid of a palladium catalyst to give
6-methylene-6H-dibenzo[b,d]pyrans. The product can be trans-
formed into 6,6-disubstituted dibenzopyrans via protodesilyl-
ation, followed by 1,2-addition. 1,4-Bis[2-(triisopropylsilyl-
ethynyloxy)phenyl]benzene is shown to undergo a dual intra-
molecular insertion reaction leading to the formation of
pentacyclic condensed aromatics.
were futile to give cyclization products, thus showing that the
presence of bulky silyl substituents and the ethereal oxygen is
essential for this hydroarylation. Of note, the intramolecular
hydroarylation of 1a proceeded on a gram-scale to give 2a in
90% yield (1.28 g from 4.0 mmol of 1a).
Si
Pd(OAc)2 (5 mol%)
O
Si
H
PCy3 (5 mol%)
H
O
toluene (0.1 M)
90 °C
ð1Þ
1a (Si = Sii-Pr3)
2a, 88% (6 h)
90% (16 h, gram-scale)
Heteroatom-bridged condensed aromatics and heteroaro-
matics play key roles as biologically active agents and functional
materials.1 Typical examples are dibenzofurans,1b -pyrroles,1c
and -siloles.1d Moreover, two atom-bridged biaryls are also
attractive conjugated π-electron building blocks. For the synthe-
sis and functionalization of such compounds, an approach
involving C-H bond activation is ideal in view of efficient use
of natural resources and step economy.2,3 For example, 6H-
benzo[c]chromenes4,5 can be prepared by the metal-catalyzed
intramolecular aryl-aryl bond-forming reaction using C-H
bond-cleaving intramolecular cross-coupling.2c-2h,2j An econom-
ical approach for the synthesis of such cycles is an intra-
molecular insertion of unsaturated bonds into C-H bonds with
the aid of transition-metal catalysts.3 Along this line we have
disclosed that an O-alkynyl group is effective for site selective
C-H activation by palladium(0) complexes, which allows the
synthesis of various oxygen-containing heterocycles from al-
kynyl aryl ethers.6-8 Herein we report that an intramolecular
insertion of a silylethynyl group into a δ-aryl-C-H bond in 2-
(silylethynyloxy)biaryls proceeds in the presence of a palladium
catalyst to give 3-membered cyclic structures through novel
annulation. This system can be easily applied to the synthesis of
various oxygen-containing condensed cycles.
We first examined the intramolecular hydroarylation of
2-triisopropylsilylethynyloxybiphenyl (1a) in the presence
of Pd(OAc)2 (5 mol %) and tricyclohexylphosphine (PCy3,
5 mol %) in toluene (0.1 M of 1a) at 90 °C for 6 h and obtained
6-(Z)-triisopropylsilylmethylidene-6H-dibenzo[b,d]pyran (2a) in
88% isolated yield (eq 1).9 Apparently, the δ-aryl-C-H bond is
selectively cleaved to allow the ethyne moiety to insert between
the C-H bond. Other bulky silyl substituents on alkynyl carbon
were potent for the hydroarylation. tert-Butyldiphenylsilyl (1b)
and tert-butyldimethylsilyl (1c) groups were effective for this
transformation to give the corresponding dibenzopyran 2b and
2c in 89% and 37%10 yields, respectively. However, less bulky
silyl groups such as triethylsilyl and dimethylphenylsilyl or
carbonaceous substituents like C(OMe)(-CH2-)5 gave the
heterocycles in much lower or null yields. Substrates like 2-
Ph-C6H4-CH(OMe)C¸CTIPS and 2-Ph-C6H4-C(O)C¸CTIPS
1b (Si = Sit-BuPh2)
1c (Si = Sit-BuMe2)
2b, 89% (4 h)
2c, 37% (3 h)
We next examined the scope of the aromatic moiety in 1 and
summarize the results in Table 1. Phenyl (1d) and methyl (1e)
groups and fluorine (1f) on the aryl part did not hamper the
reaction to give the corresponding adducts 2d-2f in 88-91%
yield (Runs 1-3). Hydroarylation of 2-silylethynyloxy-4¤-meth-
ylbiphenyl (1g) and -4¤-fluorobiphenyl (1h) smoothly proceeded
to give both 8-substituted dibenzopyrans 2g and 2h in 92% yield
(Runs 4 and 5). 3¤-Substituted biphenyls 1i-1l have a regio-
chemical issue: two different C-H reaction sites (2¤ and 6¤) are
possible to form 2 and 2¤ substituted at C9 and C7 positions,
respectively. In fact, 1i and 1j having trifluoromethyl and methyl
groups gave 2i, 2¤i and 2j, 2¤j in 86% (63:37) and 86% (52:48)
yield, respectively (Runs 6 and 7). In these cases, the less-
hindered C-H bond participated preferentially in the reaction
probably due to steric hindrance. In contrast, substrates having
methoxy group 1k and fluorine 1l reacted at more-hindered C-H
bonds to give the corresponding products 2k and 2¤k (33:67) in
86% yield and 2l and 2¤l (7:93) in 87% yield, respectively (Runs
8 and 9). The observed selectivity may be attributed to the
preferred ligation of a fluorine and methoxy group to the
palladium center.11 The reaction of 1-[2-(triisopropylsilylethy-
nyloxy)phenyl]naphthalene (1m) took place smoothly to give
tetracycle 2m in 92% yield (Run 10). 2-(2-Thienyl)phenyl ether
1n gave thienobenzopyran 2n in 93% yield (Run 11). In the case
of 3-thienyl isomer 1o, the 2¤-C-H bond rather than the 4¤-C-H
in 1o was selectively activated to give 2o in 95% yield (Run 12).
With the protocol of the hydroarylation data in our hand,
double annulation was examined for the synthesis of poly-
condensed cycles. 2,2¤-Bis(alkynoxy)biphenyl 1p was heated in
the presence of Pd(OAc)2 and PCy3 to give the single insertion
product 3 in 38% yield without the formation of the double
hydroarylation product 4 (eq 2). The structure of 3 was
unambiguously determined by NMR spectra and X-ray crystal-
lographic analysis.12 As the isolated mono-cycloadduct 3 failed
to undergo the second hydroarylation and generated a complex
mixture, the conformational flexibility of 2-aryl groups appears
Chem. Lett. 2014, 43, 1791–1793 | doi:10.1246/cl.140725
© 2014 The Chemical Society of Japan | 1791

Table 1. Palladium-catalyzed hydroarylation of 1a
b. BuLi, CuCN
or
c. PhCCLi, CuCN
R
6
6
O
i-Pr3Si
O
Br
HBr in AcOH
Pd(OAc)2 (5 mol%)
2a
H
O
Sii-Pr3
PCy3 (5 mol%)
hexane, rt, 1 h
Et2O, -78°C, 2 h
H
O
a
toluene (0.1 M)
90 °C
R3
7a (R = Bu), 75% (2 steps)
7b (R = CCPh), 71% (2 steps)
R2
6, 89%
R2
R3
1
2
Run
1
Time/h
Product, yield/%b
Scheme 1. Synthetic application of 2. Reagents and conditions;
a) 2a (1.0 equiv), HBr in AcOH (2.5 equiv, ca. 5.1 M), hexane, rt, 1 h;
then b) BuLi (2.0 equiv), CuCN (2.0 equiv), Et2O, ¹78 °C, 2 h;
c) PhC¸CH (4.0 equiv), BuLi (4.0 equiv), CuCN (2.0 equiv), Et2O,
¹78 °C, 2 h.
i-Pr3Si
H
O
O
Sii-Pr3
4
2
H
R3
R3
8
R2
R2
1
2
3
4
5
1d (R2 = 4-Ph, R3 = H)
3
2d, 88
2e, 91
2f, 90
2g, 92
2h, 92
i-Pr3Si
For the synthetic transformation of 2, the introduction of
carbonaceous groups at the C6 position was tested (Scheme 1).
The treatment of 2a with hydrogen bromide in acetic acid gave
6-methyldibenzo[b,d]pyrylium bromide (6) via desilylation in
89% yield.6a The isolated 6 reacted with Li{Cu(CN)(Bu)} or
Li{Cu(R)(C¸CPh)} (R = CN or C¸CPh) reagent prepared
respectively from BuLi or PhC¸CLi and CuCN to form 6-
butylated and 6-phenylethynylated 6-methyldibenzopyrans 7a or
7b in 75% or 71% yield over 2 steps.
To get an insight into the C-H cleaving event, we carried out
deuterium-labeling experiments. The reaction of 1a-d5 in toluene
for 30 h provided 2a-d7, as assayed by 1H NMR, showing that the
original deuterium at the 2¤-position shifted to three positions:
6-methylidene, C1, and C4 (48%, 15%, and 40% D) (eq 4). The
reaction of 1a with 1 equivalent of acetic acid-d1 gave deuterated
2a-d4 containing 34% D at 6-methylidene, 17% D at C1, 43% D
at C4, and 12% D at C10 (eq 5).13,14 With higher equivalents of
acetic acid-d1, the deuterium contents were enhanced at every
position (see the Supporting Information). These facts clearly
demonstrate that the 2¤-C-H bond is cleaved probably via a
CMD pathway from both the alkynoxy- and twisted aryl-ligated
1e (R2 = 2-Me, R3 = H)
1f (R2 = 2-F, R3 = H)
1g (R2 = H, R3 = Me)
1h (R2 = H, R3 = F)
4
4
4
3
i-Pr3Si
H
H
O
O
R3
7
+
O
Sii-Pr3
H
6'
9
R3
3'
2'
R3
2
2’
6
7
8
9
1i (R3 = CF3)
1j (R3 = Me)
3
3
3
2
2i and 2′i, 86 (63:37)
2j and 2′j, 86 (52:48)
2k and 2′k, 86 (33:67)
2l and 2′l, 87 (7:93)
1k (R3 = MeO)
1l (R3 = F)
i-Pr3Si
O
Sii-Pr3
H
O
10
3
1m
2m, 92
i-Pr3Si
O
O
Sii-Pr3
H
O
11
12
2
2
complex i to give aryl-Pd complex iii (Figure 1).
S
1n
48% D
S
2n, 93
i-Pr3Si
40% D
i-Pr3Si
Pd(OAc)2 (5 mol%)
PCy3 (5 mol%)
H/D
O
Sii-Pr3
Sii-Pr3
H
6
D
H/D
O
O
S
4
toluene (0.1 M)
90 °C, 30 h
ð4Þ
ð5Þ
S
D4
1o
1
10
D3
>99% D
2o, 95
1a-d5
15% D
H/D
D
aUnless otherwise noted, a mixture of 1 (0.3 mmol), Pd(OAc)2
(0.015 mmol), PCy3 (0.015 mmol), and toluene (3.0 mL) was
heated at 90 °C. Isolated yield.
2a-d7, 95%
34% D
b
i-Pr3Si
43% D
Pd(OAc)2 (5 mol%)
PCy3 (5 mol%)
1a
H/D
6
H/D
O
essential for the cyclization.3k,3l In contrast, bis(silylethynyl-
oxy)terphenyl 1q underwent a double insertion smoothly to give
pentacycle 5 in 92% yield (eq 3). This result also suggests that
rotational flexibility of the aryl rings at the 2-position is the key
for successful intramolecular hydroarylation.
+
toluene (0.1 M)
4
AcOD (1 equiv)
90 °C, 6 h
1
10
H/D H/D
12% D
17% D
2a-d4, 92%
H
6
Si
Si
i-Pr3Si
O
Si
AcOH
O
i-Pr3Si
H
(AcO)LPd
H
O
O
Sii-Pr3
Pd(OAc)L
Pd(OAc)L
Pd(OAc)2 (5 mol%)
PCy3 (5 mol%)
H
O
O
Pd(OAc)L
OAc
O
+
ð2Þ
ð3Þ
AcOH
AcOH
H
toluene (0.1 M)
90 °C, 6 h
2'
iii
Ph
i-Pr3Si
O
ii
i
1p
i-Pr3Si
O
H
Sii-Pr3 4, 0%
Si
Si
3, 38%
i-Pr3Si
Pd(OAc)2 (10 mol%)
AcOH + L
H
O
O
H
O
Sii-Pr3
H
PCy3 (20 mol%)
L = PCy3
O
Pd(OAc)2L2
O
v
iv
toluene (0.1 M)
90 °C, 12 h
H
i-Pr3Si
O
Sii-Pr3
H
5, 92%
Figure 1. Possible pathway of C-H cleavage.
1q
1792 | Chem. Lett. 2014, 43, 1791–1793 | doi:10.1246/cl.140725
© 2014 The Chemical Society of Japan

Chem. Pharm. Bull. 1998, 46, 1683. b) L. Zhi, C. M. Tegley, B. Pio, J. P.
Edwards, T. K. Jones, K. B. Marschke, D. E. Mais, B. Risek, W. T.
Schrader, Bioorg. Med. Chem. Lett. 2003, 13, 2071. c) L. Zhi, C. M.
Tegley, B. Pio, J. P. Edwards, M. Motamedi, T. K. Jones, K. B.
Marschke, D. E. Mais, B. Risek, W. T. Schrader, J. Med. Chem. 2003,
46, 4104. d) B.-C. Hong, P. Kotame, C.-W. Tsai, J.-H. Liao, Org. Lett.
2010, 12, 776. e) L. P. T. Hong, J. M. White, C. D. Donner, Aust. J.
Chem. 2012, 65, 58. f) Organic Photochromic and Thermochromic
Compounds, ed. by J. C. Crano, R. J. Guglielmetti, Plenum Press, New
York, 1999. g) C.-G. Huang, K. A. Beverldge, P. Wan, J. Am. Chem.
Soc. 1991, 113, 7676. h) Y. Shi, P. Wan, Chem. Commun. 1997, 273.
Selected examples for the synthesis of 6H-benzo[c]chromenes, see:
a) J. P. Devlin, Can. J. Chem. 1975, 53, 343. b) C.-G. Huang, D. Shukla,
P. Wan, J. Org. Chem. 1991, 56, 5437. c) D. L. J. Clive, S. P. Fletcher,
D. Liu, J. Org. Chem. 2004, 69, 3282. d) B. Wang, M. Li, S. Xu, H.
Song, B. Wang, J. Org. Chem. 2006, 71, 8291. e) C.-L. Sun, H. Li,
D.-G. Yu, M. Yu, X. Zhou, X.-Y. Lu, K. Huang, S.-F. Zheng, B.-J. Li,
Z.-J. Shi, Nat. Chem. 2010, 2, 1044. f) S. Furuyama, H. Togo, Synlett
2010, 2325. g) L. Mahendar, J. Krishna, A. G. K. Reddy, B. V. Ramulu,
G. Satyanarayana, Org. Lett. 2012, 14, 628. h) E. Motti, N. Della Ca’, D.
Xu, A. Piersimoni, E. Bedogni, Z.-M. Zhou, M. Catellani, Org. Lett.
2012, 14, 5792. i) A. Ahmed, S. Dhara, J. K. Ray, Tetrahedron Lett.
2013, 54, 1673.
The following insertion of the C¸C bond into the 2¤-C-Pd bond
takes place to give a vinyl-Pd-OAc complex iv. The protonation
of iv by AcOH affords v with the regeneration of the acetoxy-
palladium complex. The 6-C-H bond is also cleaved to generate
complex ii via the CMD pathway reversibly maybe with the
assistance of the 2-phenyl group.15,16
The present study demonstrated that the palladium-cata-
lyzed hydroarylation of 2-alkynoxybiphenyls gives 6-methyl-
idene-6H-dibenzo[b,d]pyrans via arylic C-H activation. The
alkynoxy moiety and freely rotating aryl group at the 2-position
play key roles in this novel transformation. The synthesis of
other cyclic compounds utilized by the hydroarylation is now in
progress. Our efforts will also continue to elucidate the details of
the reaction mechanism.
5
This work has been supported financially by a Grant-in-Aids
for Scientific Research (S) (No. 21225005 to T.H.) and Young
Scientists (B) (No. 25870747 to Y.M.) from JSPS. Y.M. also
acknowledges Asahi Glass Foundation.
Supporting Information is available electronically on J-STAGE.
6
7
a) Y. Minami, Y. Shiraishi, K. Yamada, T. Hiyama, J. Am. Chem. Soc.
2012, 134, 6124. b) Y. Minami, K. Yamada, T. Hiyama, Angew. Chem.,
Int. Ed. 2013, 52, 10611. c) Y. Minami, M. Kanda, T. Hiyama, Chem.
Lett. 2014, 43, 181. d) Y. Minami, M. Kanda, T. Hiyama, Chem. Lett.
2014, 43, 1408.
References and Notes
1
For selected reviews, see: a) Comprehensive Heterocyclic Chemistry III,
ed. by A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor,
Elsevier Ltd., Oxford, 2008, Vol. 3, and previous editions of this series.
b) B. Voigt, L. Meijer, O. Lozach, C. Schächtele, F. Totzke, A.
Hilgeroth, Bioorg. Med. Chem. Lett. 2005, 15, 823. c) H.-J. Knölker, K.
R. Reddy, Chem. Rev. 2002, 102, 4303. d) J. Chen, Y. Cao, Macromol.
Rapid Commun. 2007, 28, 1714. e) Y. Yamamoto, Chem. Soc. Rev.
2014, 43, 1575.
For examples of C-C unsaturated bonds as a directing group, see: a) R.
Takeuchi, H. Yasue, J. Org. Chem. 1993, 58, 5386. b) K. Tanaka, G. C.
Fu, Org. Lett. 2002, 4, 933. c) M. Murakami, T. Itahashi, Y. Ito, J. Am.
Chem. Soc. 2002, 124, 13976. d) K. Takeishi, K. Sugishima, K. Sasaki,
K. Tanaka, Chem.®Eur. J. 2004, 10, 5681. e) reference 3k. f) M.
Tobisu, I. Hyodo, M. Onoe, N. Chatani, Chem. Commun. 2008, 6013.
g) reference 3l. h) P. Gandeepan, C.-H. Cheng, J. Am. Chem. Soc. 2012,
134, 5738. i) T. Xu, G. Dong, Angew. Chem., Int. Ed. 2012, 51, 7567.
j) T. Xu, H. M. Ko, N. A. Savage, G. Dong, J. Am. Chem. Soc. 2012,
134, 20005. k) P. Gandeepan, C.-H. Cheng, Org. Lett. 2013, 15, 2084.
l) E. Parker, N. Cramer, Organometallics 2014, 33, 780. m) T. Iitsuka,
K. Hirano, T. Satoh, M. Miura, Chem.®Eur. J. 2014, 20, 385.
n) reference 2j.
2
Selected examples of C-H bond-cleaving annulations, see: a) L. T.
Scott, P.-C. Cheng, M. M. Hashemi, M. S. Bratcher, D. T. Meyer, H. B.
Warren, J. Am. Chem. Soc. 1997, 119, 10963. b) H.-J. Knölker, A.
Braier, D. J. Bröcher, P. G. Jones, H. Piotrowski, Tetrahedron Lett. 1999,
40, 8075. c) L.-C. Campeau, M. Parisien, M. Leblanc, K. Fagnou, J. Am.
Chem. Soc. 2004, 126, 9186. d) L.-C. Campeau, M. Parisien, A. Jean, K.
Fagnou, J. Am. Chem. Soc. 2006, 128, 581. e) L.-C. Campeau, P.
Thansandote, K. Fagnou, Org. Lett. 2005, 7, 1857. f) D. S. Roman, Y.
Takahashi, A. B. Charette, Org. Lett. 2011, 13, 3242. g) C.-L. Sun, Y.-F.
Gu, W.-P. Huang, Z.-J. Shi, Chem. Commun. 2011, 47, 9813. h) E.
Campos-Gómez, P. J. Campos, H. F. González, M. A. Rodríguez,
Tetrahedron 2012, 68, 4292. i) J. Zhou, L.-Z. Huang, Y.-Q. Li, Z.-T. Du,
Tetrahedron Lett. 2012, 53, 7036. j) J. Zhao, N. Asao, Y. Yamamoto, T.
Jin, J. Am. Chem. Soc. 2014, 136, 9540.
8
9
For a review of alkynyl ethers, see: M. Shindo, Tetrahedron 2007, 63,
10.
In the absence of ligand, no reaction was occurred. [Pd(dba)2] or PdCl2
instead of Pd(OAc)2 did not proceed the reaction.
10 Homocycloadducts of 1c were generated mainly in 41% yield,
suggesting that bulky silyl groups avoid the dimeric forms of 1. For
the dimeric forms, see reference 6a.
3
For examples of trans-additions, see: a) A. Fürstner, V. Mamane, J. Org.
Chem. 2002, 67, 6264. b) A. Fürstner, V. Mamane, Chem. Commun.
2003, 2112. c) V. Mamane, P. Hannen, A. Fürstner, Chem.®Eur. J. 2004,
10, 4556. d) H.-C. Shen, J.-M. Tang, H.-K. Chang, C.-W. Yang, R.-S.
Liu, J. Org. Chem. 2005, 70, 10113. e) A. Fürstner, J. W. J. Kennedy,
Chem.®Eur. J. 2006, 12, 7398. f) K. Komeyama, R. Igawa, K. Takaki,
Chem. Commun. 2010, 46, 1748. g) T.-A. Chen, T.-J. Lee, M.-Y. Lin,
S. M. A. Sohel, E. W.-G. Diau, S.-F. Lush, R.-S. Liu, Chem.®Eur. J.
2010, 16, 1826. h) T. Matsuda, T. Moriya, T. Goya, M. Murakami,
Chem. Lett. 2011, 40, 40. i) J. Carreras, M. Patil, W. Thiel, M. Alcarazo,
J. Am. Chem. Soc. 2012, 134, 16753. j) M. Weimar, R. C. de Costa,
F.-H. Lee, M. J. Fuchter, Org. Lett. 2013, 15, 1706. For examples of cis-
additions, see: k) N. Chernyak, V. Gevorgyan, J. Am. Chem. Soc. 2008,
130, 5636. l) N. Chernyak, V. Gevorgyan, Adv. Synth. Catal. 2009, 351,
1101. m) N. Chernyak, S. I. Gorelsky, V. Gevorgyan, Angew. Chem., Int.
Ed. 2011, 50, 2342. For a example of 1,1-additions, see: n) W. Lim, Y.
H. Rhee, Eur. J. Org. Chem. 2013, 460.
11 J. L. Kiplinger, T. G. Richmond, C. E. Osterberg, Chem. Rev. 1994, 94,
373.
12 CCDC-1013075 (3) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via http://www.ccdc.cam.
ac.uk/data_request/cif.
13 Yu’s group reported Pd(OAc)-catalyzed ortho-deuteration of phenyl-
acetic acids and others in the presence of bases. See: S. Ma, G. Villa,
P. S. Thuy-Boun, A. Homs, J.-Q. Yu, Angew. Chem., Int. Ed. 2014, 53,
734.
14 Acetic acid did not show any catalytic activity for the present insertion
reaction. In addition, deuterium-exchange reaction of 1a did not occur at
all only in the presence of acetic acid-d1. See the Supporting Information
for detail.
15 No ortho-deuteration was observed under the treatment of phenyl
TIPSethynyl ethers with acetic acid-d1 in the presence of Pd(OAc)2 and
PCy3, suggesting that 6-C-H bond cleavage of 1a is assisted by 2-
phenyl group with remaining unexplored.
16 The mechanism of the cleavages of C-H bonds at C1 and C10 position
is discussed in the Supporting Information.
4
6H-Benzo[c]chromenes represent an important structural motif for
biologically-active and photochromic agents. See: a) K. Sawada, H.
Hirai, P. Golden, S. Okada, Y. Sawada, M. Hashimoto, H. Tanaka,
Chem. Lett. 2014, 43, 1791–1793 | doi:10.1246/cl.140725
© 2014 The Chemical Society of Japan | 1793