A facile route to polysubstituted naphthalenes and benzofluorenols via scandium triflate- and triflic acid-catalyzed benzannulation of 2-(2-alkynylarylidene)-1,3-dicarbonyl compounds

Article abstract of DOI:10.1002/adsc.201000286

This paper describes an efficient scandium triflate- and triflic acid-catalyzed benzannulation of 2-(2-alkynylarylidene)-1,3-dicarbonyl compounds to afford polysubstituted naphthalenes and benzo[a]fluorenols. The product selectivity could be tuned by subtle choice of the catalyst. An unprecedented process between alkynes and ketones is also explored.

Full text of DOI:10.1002/adsc.201000286

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DOI: 10.1002/adsc.201000286
A Facile Route to Polysubstituted Naphthalenes and
Benzofluorenols via Scandium Triflate- and Triflic Acid-
Catalyzed Benzannulation of 2-(2-Alkynylarylidene)-
1,3-Dicarbonyl Compounds
Lu Liu,a Lai Wei,a and Junliang Zhanga,b,*
a
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal
University, 3663 North Zhongshan Road, Shanghai 200062, Peopleꢀs Republic of China
Fax : (+86)-021-6223-5039; e-mail: jlzhang@chem.ecnu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, Shanghai 200032, Peopleꢀs Republic of China
Received: April 13, 2010; Published online: July 28, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000286.
Abstract: This paper describes an efficient scandi-
um triflate- and triflic acid-catalyzed benzannula-
tion of 2-(2-alkynylarylidene)-1,3-dicarbonyl com-
pounds to afford polysubstituted naphthalenes and
benzo[a]fluorenols. The product selectivity could be
tuned by subtle choice of the catalyst. An unprece-
dented process between alkynes and ketones is also
explored.
Keywords: benzannulation; benzofluorenols; naph-
thalenes; scandium triflate; triflic acid
Scheme 1. Previous work (a) and our projected strategy (b)
to synthesize naphthalene skeleton.
of 2-(2-alkynylarylidene)-1,3-dicarbonyl compounds,
which provides a facile route to highly substituted
Polysubstituted aromatics and polycyclic aromatics, naphthalenes and benzo[a]fluorenols.
such as the benzene, naphthalene and benzofluorene
Recently, cyclizations between alkynes and carbon-
scaffolds, are important subunits in many natural yl groups were found to be an efficient strategy for
products, pharmaceuticals, materials and organic carbocyclization.[6,7] Inspired by these results, we en-
building blocks in organic synthesis.[1,2] Thus, the de- visaged that the naphthalene skeleton 2 might be
velopment of efficient and general methods for the built-up from the precursor 1 via this discipline. Pre-
construction of these aromatics has received much at- cursor 1 could be easily prepared from readily avail-
tention in past years.[3] Within this context, benzannu- able o-alkynylbenzaldehydes and 1,3-dicarbonyl com-
lation is truly fascinating because of its good efficien- pounds [Scheme 1(b)].
cy and atom-economy. Recently, a variety of benzan-
We initiated our study with the benzannulation of
nulation strategies involving Lewis acid- and transi- 3-[2-(2-phenylethynyl)benzylidene]pentane-2,4-dione
tion metal-catalyzed transformations, iodocyclization, 1a upon treatment with various Lewis acids and
and thermal cyclization have been explored.[4] For ex- Brønsted acids (Table 1). Y
ACTHNUTRGNEN(UG OTf)3 and YbACHTUNGTNER(NUGN OTf)3 are
ample, Yamamoto and co-workers had developed a not effective at all (entries 1 and 2). To our delight,
variety of transition metal-catalyzed benzannulations the reaction carried out in 1,2-dichloroethane (DCE)
of readily avaible o-alkynylbenzaldehydes with al- at 508C could give the desired naphthalene 2a in 96%
kynes or enols leading to polysubstituted naphtha- isolated yield under the catalysis of 5 mol% Sc
ACHTUNGTRENNUNG(OTf)3
lenes [Scheme 1(a)].[5] Herein, we wish to report a (entry 5). The reaction can occur even at room tem-
novel ScACHTUNGTRENNUNG(OTf)3- and HOTf-catalyzed benzannulation perature to afford 2a in 90% yield after 48 h
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Adv. Synth. Catal. 2010, 352, 1920 – 1924

A Facile Route to Polysubstituted Naphthalenes and Benzofluorenols
Table 1. Screening of conditions for the formation of 2a.
(entry 6). Finally, HOTf was found to be the most ef-
ficient catalyst for this transformation to give the
product in 98% yield in 5 min (entry 7). Other tested
solvents and Brønsted acids such as HNTf2 and HOTs
failed to improve the yields (entries 8–11).
With the optimal conditions in hand, various substi-
tuted substrates 1b–1j were examined to study the re-
action scope (Table 2). Several points are noteworthy.
Firstly, when the substituents on the alkynes (R1) are
aromatic groups, excellent yields of the products are
obtained under the catalysis of HOTf (conditions B,
entries 1–3). However, only 22% yield of the 2e can
be obtained under these conditions for R1 is 1-cyclo-
hexenyl (entry 4). In contrast, much better yield
(80%) can be achieved under conditions A (entry 5).
Secondly, ester and ketone groups are compatible for
this transformation (R3). The reactions of both E and
Z isomers of 1h proceed smoothly to afford the corre-
sponding product in almost same yields (entries 8 and
9), indicating that both E and Z isomers can probably
interconvert each other or through a same intermedi-
ate under the reaction conditions. Thirdly, the sub-
stituents on phenyl (R4) probably play some role on
the reaction rate rather than the yield (entries 6 and
Entry Conditions[a]
Time
96 h
Yield
[%][b]
1
2
3
4
5
6
5 mol% Y
5 mol% Yb
5 mol% Sc(OTf)3, toluene, 708C
5 mol% In(OTf)3, DCE, 508C
(OTf)3, DCE, 508C
(OTf)3, DCE, r.t.
G
N.R.
N.R.
81
1 h
7 h
50min 96
96
48 h
90
98
83
13
63
N.R.
7
8
9
10
11
5 mol% HOTf, DCM, r.t.
5 mol% HNTf2, DCM, r.t.
5 mol% HOTs, DCM, reflux
5 mol% HOTf, MeOH, r.t.
5 mol% HOTf, THF, reflux
5min
5 min
48 h
20 h
24 h
[a]
[b]
Reaction conditions: 0.3 mmol of 1a in 3 mL of solvent.
Isolated yield (N.R. means no reaction).
Table 2. Synthesis of naphthalenes.
Entry Substrate
Cond.[a] Product
Yield [%][b]
1
2
3
4
5
1b R1 =1-naphthyl
B/5 min
B/5 min
B/5 min
2b R1 =1-naphthyl
2c R1 =4-MeOC6H4
2d R1 =4-MeC6H4
91
90
89
1c R1 =4-MeOC6H4
1d R1 =4-MeC6H4
1e R1 =1-cyclohexenyl B/16 h
2e R1 =1-cyclohexenyl 22
1e R1 =1-cyclohexenyl A/5 min
2e R1 =1-cyclohexenyl 80
1f R4 =4, 5-dimethoxy B/36 h
2f R4 =4, 5-dimethoxy
94
6
7
1g R4 =5-F
B/24 h
2g R4 =5-F
82
8
9
(E)-1h
(Z)-1h
B/16 h
B/16 h
2h
2h
94
96
10
11
(E)-1i
(Z)-1i
B/3 h
B/1 h
2i
2i
91
96
12
13
1j
1j
B/2 h
A/11 h
2j
2j
64
93
[a]
[b]
Conditions A: substrate (0.1M) in DCE, 5 mol% of Sc
HOTf, room temperature.
Yield of isolated product.
ACHTUNGRTEN(NNUG OTf)3, 508C; conditions B: substrate (0.1M) in DCM, 5 mol% of
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Lu Liu et al.
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Table 3. Selective synthesis of naphthalenes and benzo[a]fluorenols.
Entry
Substrate 1
Conditions[a]
Yield [%][b]
2/3
R1/R3/R4
1
2
3
4
5
6
7
8
1k Ph/Ph/H
A, 808C, 2.5 h
B, 18 h
A, 908C, 10 h
B, 10 h
A, 908C, 10 h
B, 12 h
A, 908C, 2 h
B, 18 h
2k (88)/3k (5)
2k (33)/3k (59)
2l (87)/3l (0)
2l (15)/3l (61)
2m (88)/3m (0)
2m (34)/3m (37)
2n (82)/3n (6)
2n (25)/3n (71)
1l 1-C10H7/Ph/H
1m Ph/OC2H5/H
1n Ph/Ph/5-F
[a]
Conditions A: substrate (0.1M) in toluene, 5 mol% of Sc
HOTf, room temperature.
Yield of isolated product.
ACHTUGNTNERN(UNG OTf)3; conditions B: substrate (0.1M) in CH2Cl2, 5 mol% of
[b]
7). The strong interaction between proton and the
To our surprise, when the substituent (R1) on the
oxygen atom of MeO (entry 6) may slow down the re- alkyne of 1 is an alkyl group (1o), the reactions pro-
action. Fourthly and gratifyingly, the phenyl ring can duces an unexpected product 2o’ as the major product
be replaced by an alkenyl (1j) group and the corre- along with the normal naphthalene 2o under both
sponding substituted benzene 2j is isolated in 64% conditions (Scheme 2). Substrate 1p bearing MeO on
yield under the catalysis of HOTf (conditions B). A the phenyl gives a similar result. The structure of 2p’
better yield (93%) can be obtained under the catalysis was further confirmed by single crystal X-ray diffrac-
of Sc
Sc(OTf)3 are complementary to each other for this
transformation.
ACHTUNGTRENNUNG
(OTf)3 (conditions A), indicating that HOTf and tion analysis.[8]
G
In order to gain insight into this transformation, the
substrate 4 with two different ketones were prepared
Interestingly, when R2 (1k–1n) is a phenyl group, and subjected to the reaction conditions (Scheme 3).
instead of an alkyl group (Table 3), the reactions in Under the catalysis of ScACTHNUTRGNEUNG(OTf)3, 4a was obtained as
the presence of HOTf (conditions B) produce the cor- the major product in 66% yield along with 29% yield
responding naphthalenes 2k–2n as minor products of 4b. However, in the presence of HOTf, the reaction
and benzo[a]fluorenols 3k–3n as the major products. afforded not only naphthalenes 4a (41%) and 4b
In contrast, naphthalenes 2k–2n remain the predomi- (4%), but also a 50% yield of benzo[a]fluorenol 4c.
nant or single product under the catalysis of ScACHTUNTRGNEUNG(OTf)3 These results were consistent with that of Table 3 and
in toluene (conditions A), indicating that the product further indicated that the E and Z isomers can be in-
selectivity can be tuned by subtle choice of the cata- terconvertible under the acid conditions.
lyst.
Scheme 2. Transformations of 1o–p.
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A Facile Route to Polysubstituted Naphthalenes and Benzofluorenols
Scheme 3. Transformations of compound 4.
Scheme 4. A proposed mechanism for the acid-catalyzed carbocyclizations.
A plausible mechanism accounting for the products undergoes an acid-catalyzed intramolecular Friedel–
is depicted (Scheme 4). At first, the carbonyl group of Crafts reaction. In order to check this reaction path-
1 is activated by a Brønsted acid or Lewis acid,[9] and way, one control experiment was carried out by sub-
alkyne attacks the activated carbonyl group to pro- jecting 2k to conditions A [Eq. (1)]. Product 3k is
duce alkenyl cation B. Then the alkenyl cation B can indeed formed but in only 16% yield after 36 h, indi-
react with the nucleophilic OM(H) to form the oxete cating that 3 is generated most probably through the
C, which in turn produces naphthalene 2 via retro- intermediate B–D–E pathway. When R1 is butyl,
[2+2] cycloaddition. When R2 is phenyl, the inter- beside the above pathway, intermediate B would un-
mediate B undergoes Friedel–Crafts cyclization to dergo an unprecedented process to generate allene F
produce benzo[a]fluorene skeleton intermediate D by the elimination of a proton, followed by elimina-
containing allylic alcohol moiety, which isomerizes tion of an MOH with the help of proton to give two
into benzo[a]fluorenols 3 via carbocations intermedi- interconvertibles G and H. Compound 2o’ is finally
ate E. Benzo[a]fluorenols 3 may come from 2 which produced through further elimination of a proton.
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Lu Liu et al.
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[2] a) X. Xu, Z. Shang, R. Li, Z. Cai, X. Zhao, Phys. Chem.
Chem. Phys. 2009, 11, 8560; b) P. E. Georghiou, Z. Li,
M. Ashram, S. Chowdhury, S. Mizyed, A. H. Tran, H.
Al-Saraierh, D. O. Miller, Synlett 2005, 879; c) M. Med-
arde, A. B. S. Maya, C. Pꢂrez-Melero, J. Enzyme Inhib.
Med. Chem. 2004, 19, 521; d) G. Sello, F. Orsini, Mini-
Rev. Org. Chem. 2004, 1, 77; e) M. N. Bochkarev, Chem.
Rev. 2002, 102, 2089; f) J. D. Hoefelmeyer, M. Schulte,
M. Tschinkl, F. P. Gabbaꢃ, Coord. Chem. Rev. 2002, 235,
93.
[3] For some recent selected reviews on the synthesis of
naphthalenes and their derivatives, see: a) C. B. de Kon-
ing, A. L. Rousseau, W. A. L. van Otterlo, Tetrahedron
2003, 59, 7; b) M. Brasholz, S. Sçrgel, C. Azap, H.-U.
Reißig, Eur. J. Org. Chem. 2007, 3801; c) K. Tsubaki,
Org. Biomol. Chem. 2007, 5, 2179; d) I. A. Maretina,
Russ. J. Gen. Chem. 2008, 78, 223; for some recent se-
lected examples on the synthesis of benzofluorenes scaf-
fold, see: e) J. Zhao, D. Yue, M. A. Campo, R. C.
Larock, J. Am. Chem. Soc. 2007, 129, 5288; f) Y.-B.
Zhao, B. Mariampillai, D. A. Candito, B. Laleu, M. Li,
M. Lautens, Angew. Chem. 2009, 121, 1881; Angew.
Chem. Int. Ed. 2009, 48, 1849; g) S. A. Shahzad, T.
Wirth, Angew. Chem. 2009, 121, 2626; Angew. Chem.
Int. Ed. 2009, 48, 2588; h) R. S. Laufer, G. I. Dmitrienko,
J. Am. Chem. Soc. 2002, 124, 1854.
In conclusion, we have developed a novel, efficient
and general route to polysubstituted naphthalenes
and benzo[a]fluorenols via ScACHTNUTRGNEUNG(OTf)3- and HOTf-cata-
lyzed benzannulation of 2-(2-alkynylarylidene)-1,3-di-
carbonyl compounds. For those substrates with R3 as
a phenyl group, the product selectivity can be tuned
by subtle choice of the catalyst. An unprecedented
process between alkynes and ketones was also ex-
plored, which may be useful for future synthesis
design. Further investigations on the scope, mechanis-
tic details, synthetic applications of this transforma-
tion are ongoing in this laboratory.
Experimental Section
Typical Procedure
[4] For some selected recent reviews, see: a) S. Kotha, S.
Misra, S. Halder, Tetrahedron 2008, 64, 10775; b) S.
Saito, Y. Yamamoto, Chem. Rev. 2000, 100, 2901;
c) K. H. Dçtz, P. Tomuschat, Chem. Soc. Rev. 1999, 28,
187; d) M. Lautens, W. Klute, W. Tam, Chem. Rev. 1996,
96, 49; e) B. M. Trost, Science 1991, 254, 1471.
[5] For selected reviews, see: a) V. Gevorgyan, Y. Yamamo-
to, J. Organomet. Chem. J. Orgnomet. Chem. 1999, 576,
232; b) Y. Yamamoto, J. Org. Chem. 2007, 72, 7817. For
selected examples, see, c) N. Asao, K. Takahashi, S. Lee,
T. Kasahara, Y. Yamamoto, J. Am. Chem. Soc. 2002,
124, 12650; d) N. Asao, T. Nogami, S. Lee, Y. Yamamo-
to, J. Am. Chem. Soc. 2003, 125, 10921; e) N. Asao, H.
Aikawa, Y. Yamamoto, J. Am. Chem. Soc. 2004, 126,
7458.
To a solution of HOTf (0.015 mmol, 2.3 mg, 1.4 mL) in
CH2Cl2 (3 mL) was added 1a (0.3 mmol, 86.4 mg) at room
temperature. After being stirred for 5 min, 1a was consumed
completely as was determined by TLC analysis. After re-
moval of solvent under reduced pressure, the residue was
purified by column chromatography on silica gel (Rf =0.25,
hexanes: EtOAc=6:1) to give the desired product 2a as a
white solid; yield: 84.7 mg (98%); mp 75–778C (hexane/
CH2Cl2); 1H NMR (300 MHz, CDCl3): d=8.26 (s, 1H),
7.90–7.96 (m, 1H), 7.80–7.86 (m, 2H), 7.56–7.62 (m, 1H),
7.41–7.52 (m, 5H), 2.73 (s, 3H), 2.41 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=201.63, 199.81, 138.14, 137.05, 136.91,
134.01, 131.52, 130.63, 130.47, 130.28, 129.56, 128.86, 128.72,
126.32, 124.73, 29.88, 18.15; MS (70 eV): m/z (%)=288
(100) [M+]; HR-MS (EI): m/z=288.1153, calcd. for
C20H16O2 [M+]: 288.1150
[6] L. Liu, J. Zhang, Angew. Chem. 2009, 121, 6209; Angew.
Chem. Int. Ed. 2009, 48, 6093.
[7] For some selected recent examples, see: a) J. U. Rhee,
M. J. Krische, Org. Lett. 2005, 7, 2493; b) T. Jin, Y. Ya-
mamoto, Org. Lett. 2007, 9, 5259; c) T. Jin, Y. Yamamo-
to, Org. Lett. 2008, 10, 3137; d) T. Jin, F. Yang, C. Liu, Y.
Yamamoto, Chem. Commun. 2009, 3533; e) C. Gon-
zꢄlez-Rodrꢅguez, L. Escalante, J. A. Varela, L. Castedo,
C. Saꢄ, Org. Lett. 2009, 11, 1531.
[8] CCDC 772729 (2p’) and CCDC 772730 (4) contain the
supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
Acknowledgements
We are grateful to the National Natural Foundation of China
(Nos. 20702015, and 20972054) and the Doctoral Fund of the
Ministry of Education of China (No. 20090076110007) for fi-
nancial support. This work was also sponsored by 973 Pro-
gram (2009CB825300).
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
References
[9] a) G. S. Viswanathan, M. Wang, C.-J. Li, Angew. Chem.
Int. Ed. 2002, 41, 2139; b) G. W. Kabalka, Y. Ju, Z. Wu,
J. Org. Chem. 2003, 68, 7915; c) A. Saito, J. Kasai, Y.
Odaira, H. Fukaya, Y. Hanzawa, J. Org. Chem. 2009, 74,
5644; d) R. Balamurugan, V. Gudla, Org. Lett. 2009, 11,
3116.
[1] For a monograph on the chemistry of naphthalenes and
their derivatives, see: R. T. Mason, M. Talukder, C. R.
Kates, in: Kirk-Othmer Encyclopedia of Chemical Tech-
nology, 4st edn., Vol. 16, (Ed.: R. E. Kirk), Wiley, New
York, 1995, pp 963–1017.
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Adv. Synth. Catal. 2010, 352, 1920 – 1924