Tandem carbon-carbon bond insertion and intramolecular aldol reaction of benzyne with aroylacetones: Novel formation of 4,4′-disubstituted 1,1′-binaphthols

Article abstract of DOI:10.1039/c2cc36128k

An efficient route to 4-aryl-2-naphthols from arynes and aroylacetones was developed by carbon-carbon bond insertion followed by an intramolecular aldol reaction and dehydration. Benzyne derived from 2-(trimethylsilyl)phenyl triflate reacted with benzoyla

Full text of DOI:10.1039/c2cc36128k

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COMMUNICATION
Tandem carbon–carbon bond insertion and intramolecular aldol reaction
of benzyne with aroylacetones: novel formation of 4,40-disubstituted
1,10-binaphtholsw
Kentaro Okuma,* Ryoichi Itoyama, Ayumi Sou, Noriyoshi Nagahora and Kosei Shioj
Received 23rd August 2012, Accepted 25th September 2012
DOI: 10.1039/c2cc36128k
An efficient route to 4-aryl-2-naphthols from arynes and aroyl-
acetones was developed by carbon–carbon bond insertion followed
by an intramolecular aldol reaction and dehydration. Benzyne
derived from 2-(trimethylsilyl)phenyl triflate reacted with benzoyl-
acetones in refluxing acetonitrile to give 4-aryl-2-naphthols and
3-aryl-1-naphthols.
Fluoride-induced aryne formation by using 2-(trimethylsilyl)-
phenyl triflate (1) has gathered much attention as a valuable
synthetic building tool.1 Naphthalene derivatives are ubiquitously
present in natural products, pharmaceuticals, and ligands for
transition-metal catalysts.2 In particular, binaphthyl compounds
are very important for enantioselective catalytic reactions.3
Although the synthesis of 1-naphthols through the reaction of
aryne with furans followed by acidic dehydration is a popular
method that emerged from the discovery of benzyne chemistry,4
2-naphthols are difficult to synthesize via benzyne intermediates.
4-Aryl-2-naphthols were previously synthesized by the intra-
molecular carbocyclization of alkynyl ketones,5 the Wittig
reaction of 2-benzoylphenylacetate,6 the cyclization of alkynone
with I2,7 and the Friedel–Crafts reaction of cyclopropanecarbonyl
chloride with benzene.8 All those methods, however, presented
some difficulties, such as the unavailability of starting materials
and/or the requirement of multi-step reactions. Thus, a more
convenient method for the synthesis of 4-substituted 2-naphthols
is required. A recently developed carbon–carbon insertion
reaction of arynes offers a new method for the synthesis of
ortho-selective aromatic compounds. For example, the reaction of
benzyne derived from triflate 1 with b-diketones, b-diketo esters,
or b-keto esters gave carbon–carbon insertion products.9,10 Other
carbon–heteroatom insertion reactions of arynes were reported as
well.11 Whereas the reaction of benzyne with acetylacetone (2a)
gave 1-(2-acetylphenyl)propane-2-one (3a),9 treatment of benzyne
with benzoylacetone (2b) in the presence of CuI catalyst resulted
in the formation of 1,3,3-triphenylbutane-1,3-dione.12 We have
Fig. 1 Proposed synthesis of 4-substituted 2-naphthols from arynes.
been interested in the difference in reactivity between those
two results. If the carbon–carbon bond insertion reaction of
arynes proceeds in b-diketones, the tandem intramolecular
aldol reaction followed by dehydration would provide a new
route to produce substituted 2-naphthols in a one-pot operation
(Fig. 1). Herein, we report the one-pot synthesis of 2-naphthols
from benzyne precursor 1 and CsF and its application to
4,40-biaryl-2,20-binaphthols.
We began our study by reacting diketone 2a or 2b with
benzyne generated from triflate 1 and CsF (Table 1). Treatment
of triflate 1 with CsF followed by the addition of acetylacetone 2
at rt for 3 h resulted in the formation of 1-(2-acetylphenyl)propan-
2-one 3a in 52% yield, the result of which was similar to that of
Yoshida et al. (entry 1).9 However, 3,4-dihydro-3-hydroxy-3-
methylnaphthalen-1(2H)-one (4a) was also isolated as the side
product (12%). Prolonging the reaction time produced a larger
amount of cyclized product 4a; the yield was increased to 25%
(entry 2). When excess amounts of 1 and CsF were used, 4a
was obtained in 40% yield (entry 3). Interestingly, when
benzoylacetone 2b was treated with triflate 1, not 1,2,2-triphenyl-
1,3-butanedione, the product reported by Yang et al.,12 but
1-(2-benzoylphenyl)propan-2-one (3b) was obtained in 60%
yield along with 3,4-dihydro-3-hydroxy-3-phenylnaphthalen-
1(2H)-one (4b) and 1,2-diphenylbutane-1,3-dione (7%). Since
the acetyl group attached to the aromatic group is more acidic
than a normal aliphatic acetyl group, the intramolecular aldol
reaction might proceed to give 4 even at room temperature.13
Thus, we then performed the reaction under refluxing conditions
to determine whether or not the intramolecular aldol reaction
Department of Chemistry, Faculty of Science, Fukuoka University,
Jonan-ku, Fukuoka 814-0180, Japan. E-mail: kokuma@fukuoka-u.ac.jp;
Fax: +81-92-865-6030; Tel: +81-92-871-6631
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and analytical data. CCDC 874289. For
ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c2cc36128k
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11145–11147 11145

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Table 1 Reaction of triflate 1 with b-diketones 2 in the presence of
CsF
Products
Yields (%)
3
4
Entry
1 (equiv.)
2
Time/h
1
2
3
4
5
1.2
1.2
2.2
1.2
2.2
2a
2a
2a
2b
2b
3.0
6.0
14.0
6.0
3a
3a
3a
3b
3b
52
4a
4a
4a
4b
4b
12
25
40
30
60
55
40
15a
12a
12.0
Scheme 2
a
A small amount of 1,2-diphenylbutane-1,3-dione was isolated.
Table 2 Reaction of triflate 1a with aroylacetones 2
and dehydration would proceed. The reaction of 1 with 2a and
CsF in refluxing acetonitrile proceeded with regioselectivity to
give 3-methyl-1-naphthol (5a) in 80% yield. Meanwhile, when 1
was treated with 2b and CsF in refluxing acetonitrile, a mixture
of 4-phenyl-2-naphthol (6b) and 3-phenyl-1-naphthol (5b) was
obtained in 58% and 15% yields, respectively (Scheme 1).
Thus, not only carbon–carbon insertion but also intramolecular
aldol cyclization and dehydration proceeded under refluxing
conditions (Scheme 2). This reaction has an interesting feature:
it proceeded regioselectively (4 : 1) and the intramolecular aldol
reaction proceeded even under these conditions.
Other substituted benzoylacetones 2 also reacted with triflate
1 and CsF to give the corresponding 3-substituted 1-naphthols
5 and 4-substituted 2-naphthols 6 in moderate to good yields
(Table 2).14
When electron-donating groups were substituted, moderate
amounts of 1-naphthols 5 were obtained (entries 1 and 2).
When electron-withdrawing groups were substituted at the
para position, 2-naphthols 6 were obtained in better yields
(entries 3–5). In particular, the nitro substituent afforded only
1-Naphthol
2-Naphthol
Yield (%)
Yield (%)
Entry
2
Time/h
1
2
3
4
5
6
7
2c
2d
2e
2f
2g
2h
2i
5
4
6
8
8
8
8
5c
5d
5e
5f
5g
5h
5i
39
6c
6d
6e
6f
6g
6h
6i
25
35
65
40
67
44
35
22
15
15
0
31
39
2-naphthol 6g (entry 5). By using 1-(1-naphthyl)butane-1,3-dione
(2h) and 1-(2-naphthyl)butane-1,3-dione (2i) as substrates,
the corresponding 3-naphthyl-1-naphthols and 4-naphthyl-2-
naphthols were obtained in moderate yields (entries 6 and 7).
Thus, naphthols 5 and 6 were synthesized in a one-pot operation
starting from easily available substituted benzoylacetones and
the benzyne precursor.
Scheme 1
c
11146 Chem. Commun., 2012, 48, 11145–11147
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J. Org. Chem., 2001, 66, 2358–2367; C. A. Mulrooney, X. Li,
E. S. DiVirgilio and M. C. Kozlowski, J. Am. Chem. Soc., 2003,
125, 6856–6857.
4 G. Wittig and L. Pohmer, Chem. Ber., 1956, 89, 1334–1351;
S. Akai, T. Ikawa, S. Takayanagi, Y. Morikawa, S. Mohri,
M. Tsubakiyama, M. Egi, Y. Wada and Y. Kita, Angew. Chem.,
Int. Ed., 2008, 47, 7673–7676.
5 T. Jin and Y. Yamamoto, Org. Lett., 2007, 9, 5259–5262.
6 J. H. Rupard, T. D. Paulis, A. Janowsky and H. E. Smith, J. Med.
Chem., 1989, 32, 2261–2268.
7 X. Zhangm, S. Sarkar and R. C. Larock, J. Org. Chem., 2006, 71,
236–243.
8 Y. Nishii and Y. Tanabe, Tetrahedron Lett., 1995, 36, 8803–8806.
9 H. Yoshida, M. Watanabe, J. Ohshita and A. Kunai, Chem.
Commun., 2005, 3292.
Scheme 3
Previously, 4-aryl-2-naphthols 6 were synthesized by the
AuCl3/AgOTf-catalyzed intramolecular cyclization of terminal
alkynyl benzophenone5 or the TiCl4 condensation of silyl enol
ether of a-diazoacetoacetate and ketones followed by rhodium
octanoate catalyzed annelation.15 However, those methods
required multistep synthesis of the starting materials. Although
the most straightforward synthesis of 4-phenyl-2-naphthol 6b
would be the Suzuki–Miyaura coupling of 4-bromo-2-naphthol,
the synthesis of 4-bromo-2-naphthol is relatively difficult,
requiring a three-step reaction from 1-naphthylamine.16 The
present method requires only a one-pot reaction starting from
commercially available triflate 1 and benzoylacetone. Thus, a
convenient synthesis of 1- and 2-naphthols was accomplished.
Binaphthols are well known for their synthetic ability due to
their chiral auxiliary and catalytic activity.17 Thus, many
substituted binaphthols were synthesized. In contrast, very
few 4,40-biaryl-1,10-binaphthols (7) were synthesized due to
the difficulty of synthesizing starting 4-aryl-2-naphthols.18 As
the regioselective synthesis of 4-substituted 2-naphthols was
achieved, we tried to perform the oxidative coupling of 4,40-
diaryl-1,10-binaphthols according to the method described by
Joseph et al.19 Treatment of 4-phenyl-2-naphthol with V2O5 in
refluxing dichloroethane resulted in the formation of 4,40-
diphenyl-1,10-binaphthol (7a) in 65% yield (Scheme 3).
10 U. K. Tamber and B. M. Stoltz, J. Am. Chem. Soc., 2005, 127, 5340.
11 For a review, see: H. Yoshida and J. Ohshita, Yuki Gosei
Kagaku Kyokaishi, 2011, 69, 877–888. For examples, see:
K. Z. Laczkowski, D. Garcia, D. Pena, A. Cobas, D. Peres and
E. Guitan, Org. Lett., 2011, 13, 960–963; Z. Liu and R. C. Larock,
J. Am. Chem. Soc., 2005, 127, 13112–13113; D. G. Pintori and
M. F. Greeney, Org. Lett., 2010, 12, 168–170; H. Yoshida, Y. Ito,
Y. Yoshioka, J. Ohshita and K. Takaki, Chem. Commun., 2011, 47,
8664–8666; H. Yoshida, T. Morishita and J. Ohshita, Chem. Lett.,
2010, 508–509; P. M. Tadross, S. C. Virgil and B. M. Stoltz, Org.
Lett., 2010, 12, 1612–1614; T. Zhang, X. Huang, J. Xian and
S. Sun, Tetrahedron Lett., 2009, 50, 1290–1294; H. Yoshida,
M. Watanabe, T. Morishita, J. Ohshita and A. Kunai, Chem.
Commun., 2007, 1505–1507; E. Yoshioka, S. Kohtani and
H. Miyabe, Org. Lett., 2010, 12, 1956–1957; E. Yoshioka,
S. Kotani and H. Miyabe, Angew. Chem., Int. Ed., 2011, 50,
6638–6642.
12 Y. Y. Yang, W.-G. Shou and Y.-G. Wang, Tetrahedron Lett.,
2007, 48, 8163–8165.
13 T. L. Amyes and J. P. Richard, J. Am. Chem. Soc., 1996, 118,
3129–3141. (pKa of acetophenone: 18.3; pKa of acetone: 19.3).
14 Synthesis of 6b: To a solution of benzoylacetone 2 (73 mg,
0.45 mmol) and CsF (228 mg, 1.5 mmol) in acetonitrile (7 mL)
was added triflate 1 (149 mg, 0.50 mmol). After refluxing for 5 h,
the reaction mixture was evaporated to give pale yellow oil, which
was chromatographed over silica gel by elution with hexane–
dichloromethane (1 : 1) to afford a mixture of 3-phenyl-1-naphthol
5b and 4-phenyl-2-naphthol 6b. The mixture was subjected to gel
permeation chromatography to give 1-naphthol 5b (15 mg,
0.07 mmol) and 2-naphthol 6b (57 mg, 0.26 mmol).
15 S. Karady, J. S. Amado, R. A. Reamer and L. M. Weinstock,
Tetrahedron Lett., 1996, 37, 8277–8280.
16 M. S. Newman, V. Sankaran and D. R. Olson, J. Am. Chem. Soc.,
1976, 98, 3237–3242.
17 For reviews, see: L. Pu, Acc. Chem. Res., 2012, 45, 150–163;
M. Shibasaki, M. Kanai, S. Matsunaga and N. Kumagai, Acc.
Chem. Res., 2009, 42, 1117–1127; S. Schenker, Z. A. Zamfir,
M. Freund and S. B. Tsogoeva, Eur. J. Org. Chem., 2011,
2209–2222; M. Hatano and K. Ishihara, Synthesis, 2010,
3785–3801; K. Maruoka, Chem. Rec., 2010, 10, 254–259;
H. Wang, Chirality, 2010, 22, 827–837.
The structure of 7a was determined by H and 13C NMR
1
analysis. In addition, the X-ray crystallographic analysis of 7a
was performed (Fig. S1, ESIw).20
In conclusion, the synthesis of 4-aryl-2-naphthols 6 from
easily available triflate 1 and aroylacetone 2 was accomplished in
a one-pot operation. Oxidation of 4-aryl-2-naphthols afforded
the corresponding binols 7 in moderate yields.
Notes and references
18 T. Hashimoto and K. Maruoka, Tetrahedron Lett., 2003, 44,
3313–3316. For the synthesis of 4,6,40,60-tetraphenyl-l,1-binols,
see: L.-Z. Gong, Q.-S. Hu and L. Pu, J. Org. Chem., 2001, 66,
2358–2367.
19 J. K. Joseph, S. L. Jain and B. Sain, Catal. Commun., 2006, 7,
184–186.
1 For reviews, see: C. Wentrup, Aust. J. Chem., 2010, 63, 979–986;
T. Kitamura, Aust. J. Chem., 2010, 63, 987–1001; H. Pellissier and
M. Santelli, Tetrahedron, 2003, 59, 701–730; H. Yoshida,
J. Ohshita and A. Kunai, Bull. Chem. Soc. Jpn., 2010, 83,
199–219; K. Okuma, Heterocycles, 2012, 85, 515–544.
2 For reviews, see: P. Kilian, F. Knight, R. Fergus and
J. D. Woollins, Chem.–Eur. J., 2011, 17, 2302–2328; S. Simon
and J. Petrasek, Plant Sci., 2011, 180, 454–460; Y. S. Cai,
Y. W. Guo and K. Krohn, Nat. Prod. Rep., 2010, 27, 1840–1870;
X. Qian, Y. Xiao, Y. Xu, X. Guo, J. Qian and W. Zhu, Chem.
Commun., 2010, 46, 6418–6436.
20 Compound 7a: yellow crystals, mp 145–146 1C; 1H NMR (CDCl3)
d = 5.21 (br, 2H, OH), 7.35 (m, 6H, Ar), 7.40 (m, 6H, Ar), 7.81 (m,
6H, Ar), 8.45 (d, 4H, J = 8.8 Hz, Ar). 13C NMR (CDCl3), d =
111.76, 119.13, 124.04, 125.04, 125.14, 126.27, 127.54, 128.23,
131.11, 134.16, 141.70, 146.80, 147.81 (Ar). Anal. calcd for
C32H22O2 + 2EtOH; C, 81.48; H, 6.46%. Found, C, 81.34; H,
6.65%.
3 For reviews, see: R. Irie and T. Katsuki, Chem. Rec., 2004, 4,
96–109For recent examples, see: L.-Z. Gong, Q.-S. Hu and L. Pu,
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11145–11147 11147