Direct access to highly substituted 1-naphthols through palladium-catalyzed oxidative annulation of benzoylacetates and internal Alkynes

Article abstract of DOI:10.1002/chem.201302740

One for the pot: 1-Naphthols, well-known structural design elements in medicinal chemistry, were readily prepared by means of a one-pot palladium-catalyzed oxidative annulation of readily available benzoylacetates to internal alkynes (see scheme). Copyright

Full text of DOI:10.1002/chem.201302740

DOI: 10.1002/chem.201302740
Direct Access to Highly Substituted 1-Naphthols through Palladium-
Catalyzed Oxidative Annulation of BenzoylACTHNUTRGNEUaGN cetates and Internal Alkynes
Shiyong Peng, Lei Wang, and Jian Wang*[a]
The synthesis of aromatic and heterocyclic molecules is a
ed much attention owing to their atom-economy, simple pro-
tocol, and environmentally benign features.[7] Although the
transition-metal-catalyzed oxidative annulations[8] through
topic of continued interest owing to the presence of these
skeletal motifs in countless natural products and synthetic
compounds that display important chemical, biological, and
medicinal properties.[1] 1-Naphthol and its highly substituted
derivatives fall into this category. For example, mollugin
(Figure 1a) and its analogues have shown antiviral activity
À
direct C H functionalization have proven to be a powerful
tool in the assembly of numerous structural motifs,[9] a de-
tailed survey of the literature reveals that the one-step syn-
thesis of highly substituted 1-naphthols from readily avail-
AHCTUNGTREGaNNNU ble starting materials has so far remained a major chal-
lenge. It is well known that a direct and efficient synthetic
method that utilizes simple and readily available starting
material would not only enable the construction of a new
class of scaffolds but would also facilitate the late-stage
structural modification of existing compounds. Very recently,
Younꢀs group reported a palladium-catalyzed method to
prepare 1-naphthols from alkenyl 1,3-dicarbonyl compounds
or aryl-substituted alkenyl b-keto esters (Scheme 1a).[10]
Figure 1. Important examples of substituted-1-naphthols.
against the hepatitis B virus.[2] Pentacycline (Figure 1b) dis-
plays a broad spectrum of antibacterial activity against both
Gram-positive and Gram-negative organisms.[3] Cercosporin,
phleichropme, and calphostins belong to a class of perylene-
quinone natural products (Figure 1c) and have been identi-
fied as potent protein kinase C inhibitors and photodynamic
cancer therapies.[4] Nigerone (Figure 1d) is a class of bis-
naphthopyrone natural products that exhibits antitumor and
antibacterial activities.[5]
Scheme 1. Challenges in the synthesis of 1-naphthols.
Despite some progress that has been made in constructing
the 1-naphthol scaffold,[6] these methods suffer from draw-
backs such as the use of high reaction temperature,[6e,f]
rarely used starting materials,[6e–g] multiple synthetic
steps,[6h–j] and limited substrate scope.[6k] Recently, transition-
Wang and co-workers independently reported an example
of rhodium-catalyzed cascade oxidative annulation reactions
of benzoylacetonitriles with alkynes, thereby affording sub-
stituted naphthopyrans through an in situ formed 1-naphthol
key intermediate (Scheme 1b).[11] As part of our continued
À
metal-catalyzed direct C H functionalizations have attract-
À
interest in transition-metal-mediated C C bond-forming
[a] S. Peng, L. Wang, Prof. Dr. J. Wang
Department of Chemistry
processes, we recently disclosed palladium-catalyzed oxida-
tive annulations of isatins and unactivated internal alkynes
to access the benzazepine scaffold.[12a] Herein, we report our
new results on a straightforward approach: palladium-cata-
lyzed oxidative annulation reactions of readily available
benzoylacetates with unactivated internal alkynes, which il-
National University of Singapore
3 Science Drive 3, Singapore 117543 (Singapore)
Fax: (+65)6516-1691
E-mail: chmwangj@nus.edu.sg
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302740.
13322
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Chem. Eur. J. 2013, 19, 13322 – 13327

COMMUNICATION
lustrated an efficient preparation of more substituted 1-
naphthols (Scheme 1c).
Our investigation began with the Pd-catalyzed oxidative
annulation of benzoylacetate 1a and diphenylacetylene 2a
to give the corresponding 1-naphthol 3aa (Table 1).[13] On
creased proportionally from 20 to 10%, a significant de-
crease in yield was observed (Table 1, entry 18; 50% versus
Table 1, entry 2; 22%). However, the use of 100% Pd-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ally, the use of an inert atmosphere (N2) was found to be es-
sential to avoid the side aerobic oxidation of alkynes.
Table 1. Optimization of the reaction conditions.[a]
With the optimized conditions in hand, our attention
turned to an evaluation of the scope and limitations of this
reaction (Tables 2 and 3). Given the great value of benzoyl-
AHCTUNGTREGaNNNU cetates, we used the simple diphenylacetylene 2a to exam-
Entry
Catalyst
Oxidant
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
AgOAc
CuOAc
CuCl2
Solvent
Yield [%][b]
ine the scope. To our delight, the optimized reaction condi-
tions allowed the oxidative annulations of benzoylacetates 1,
which contained a variety of functional groups, regardless of
electron-donating or electron-withdrawing properties, there-
by delivering the corresponding products in moderate to
high yields (Table 1; 45–90%). Notably, methoxy (3ca, 3oa),
trifluoromethyl (3da, 3ha, 3na), and bromo (3ga, 3ma)
were valuable functional groups amenable for further deco-
ration of the products. Excellent regioselectivity was ob-
served when 3-bromo-substituted b-keto ester (1g) was em-
ployed (only one regioisomer detected), thereby favoring
[c]
[d]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
–
G
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
anisole
1,4-dioxane
EtOH
–
Pd
[Pd
Pd(TFA)2
PdCl2
T
E
22
24
16
15
N
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
[d]
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
–
12
–
[d]
PhI
N
<5
–
–
–
–
–
–
–
[d]
oxones
K2S2O8
BQ[e]
[d]
[d]
[d]
Cu
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
A
[d]
À
U
activation of the less hindered C H bond (3ga). However,
[d]
U
3-fluoro- or 3-trifluoro-substituted benzoylacetates (1 f and
1h) led to limited regioselective control owing to both ortho
[d]
T
CH3CN
DMA[f]
DMSO
DMSO
DMSO
DMSO
T
<5
À
and para C H bond activation by means of strong electron-
C
50[g]
51[h]
76[i]
24[j]
drawing groups (F or CF3). It is noteworthy that the naph-
thalene ring and anthracene ring were well tolerated in sub-
strates, thereby leading to valuable p-conjugated aromatic
compounds (3pa and 3qa).
ACHTUNGTRENNUNG
Pd
Pd
N
ACHTUNGTRENNUNG
U
ACHTUNGTRENNUNG
[a] Reaction conditions: DMSO (2 mL), 1a (0.2 mmol, 1.0 equiv), 2a
(0.4 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), Cu(OAc)2 (2.0 equiv), 808C,
N
ACHTUNGTRENNUNG
Encouraged by these results, we next explored the scope
of internal alkynes 2 that could potentially react with 1a to
study the generality of the scheme for further synthetic ex-
ploitation. The reaction showed broad substrate tolerance
among internal alkynes. Electron-rich alkynes reacted to
give high reaction yields (Table 3, 3ab–ad, 3ah–ag; 75–
88%), whereas electron-deficient systems were slightly less
facile (Table 3, 3ae–ag, 3ao; 36–68%). Heteroaryl, ester-
containing, and aliphatic alkynes were all tolerated (3ap,
3aq, 3ar). When asymmetrical internal alkynes were em-
ployed, two regioisomers were usually both observed (3al–
aq; ratio of regioisomers was 1:1 to 4:1). In the event that
the internal alkyne (2r) was highly electron deficient, the
only regioisomer (3ar) was formed by following Markovni-
kovꢀs rule in the alkyne addition step.
To further understand the electronic effects of functional
groups, two comparative experiments were conducted
(Schemes 2 and 3). As outlined in Scheme 2, electron-rich
alkyne 2b generally proceeded slightly faster than its elec-
tron-deficient counterpart 2e (3ab/3ae 10:7). Similarly, elec-
tron-rich benzoylacetate 1j also exhibited a similar reactivi-
ty as well as electron-deficient benzoylacetate 1l when they
were treated with diphenylacetylene 2a (Scheme 3; 3ja/3la
5:4). These results suggested that the electronic effects of
functional groups from both benzoylacetates and internal al-
24 h, N2 (TFA=trifluoroacetic acid). [b] Isolated yield after purification
by column chromatography. [c] No catalyst. [d] No desired product.
[e] 1,4-Benzoquinone. [f] Dimethylacetamide. [g] Pd
Cu(OAc)2 (2.0 equiv), 808C. [h] Pd(OAc)2 (100 mol%), Cu
(2.0 equiv), 808C. [i] Pd(OAc)2 (20 mol%), Cu(OAc)2 (3.0 equiv), 808C.
[j] Pd(OAc)2 (20 mol%), Cu(OAc)2 (3.0 equiv), 1208C.
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
the basis of optimization experiments, the best results were
obtained using Pd(OAc)2 as catalyst with stoichiometric
amounts of Cu(OAc)2 as the oxidant in DMSO (Table 1,
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
entry 20). Under these conditions, the conversion was com-
plete within 24 h at 808C (Table 1, entry 20; 76% isolated
yield). No reaction was observed in the absence of palladi-
um catalyst (Table 1, entries 1–5). A variation of oxidants
(Table 1, entries 6–12) or solvents (Table 1, entries 13–18)
led to a significant decrease in chemical yield. The effects of
temperature are summarized in Table 1 (Table 1, entries 20
and 21), and a low yield was achieved at a high temperature
owing to the potential decomposition of starting materials
(Table 1, entry 21; 1208C, 24%). However, lowering the
temperature further also led to a slow reaction conversion
(see the details in the Supporting Information). Moreover,
production was highly sensitive to the loading of Pd
ACHTUNGERTN(NUNG OAc)2
and Cu(OAc)2 used. When the loading of Pd(OAc)2 was de-
A
ACHTUNGTRENNUNG
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J. Wang et al.
Table 2. Scope of b-keto esters.[a]
kynes might have limited ef-
fects on the chemoselectivity
of this reaction.
The versatility of this palla-
dium-catalyzed oxidative annu-
lation can be exploited in che-
moselective transformations to
access various frameworks
with high degrees of molecular
complexity. As outlined in
Equation (1), 3aa was readily
converted to the important Tf-
protected 1-naphthanol 4 by
the addition of 1.5 equivalents
of trifluoromethanesulfonic an-
hydride (Tf2O). Under condi-
tions of diphenyliodonium tri-
fluoromethanesulfonate
(Ph2IOTf) and potassium tert-
butoxide (KOtBu), 3aa was ex-
pectedly converted to a diaryl
ether 5 with a 95% yield in
2.0 h [Eq. (2)]. The reduction
of 3aa followed and intermedi-
ate 6 was generated and fur-
ther converted to a polycyclic
dihydropyran 7 in high yield
[Eq. (3)].
[a] Reaction conditions: DMSO (2 mL), 1a–q (0.2 mmol, 1.0 equiv), 2a (1.0 mmol, 5.0 equiv), PdACHTNUTRGNE(NUG OAc)2
(20 mol%), Cu
ACHTUNGTRENNUNG
troscopy. [c] Pd
N
N
ACHTUNGTRENNUNG
Scheme 2. Competition experiments of diphenylacetylenes.
Facile manipulation of intermediate 4 offers an additional
À
synthetic opportunity. For example, the OTf group in 4
could be replaced by an alkyne group to yield 8 in 93%
yield by means of [Pd
ACHTUNGTRENNUNG
pling (Scheme 4a). Pd
AHCTUNGTRENNUNG
tion of 4 led to the formation of 9 in 94% yield (Sche-
me 4b). When Tf-protected 1-naphthanol 4 was treated with
phenylboronic acid or isobutylboronic acid catalyzed by [Pd-
Scheme 3. Competition experiments of b-keto esters.
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Chem. Eur. J. 2013, 19, 13322 – 13327

Highly Substituted 1-Naphthols
Table 3. Scope of internal alkynes.[a]
COMMUNICATION
Scheme 4. Synthetic
transformations.
Reaction
conditions:
a) 4
(0.1 mmol), diphenylacetylene (0.3 mmol), [PdAHCUTNGTRE(NUNNG PPh3)2Cl2] (10 mol%),
CuBr (5 mol%), N,N-diisopropylethylamine (DIPEA; 0.3 mmol), DMF
(1 mL), 808C, 5 h, N2, 93%; b) 4 (0.1 mmol), ethyl acrylate (1.0 mmol),
Pd
94%; c) Compound
(10 mol%), triethylamine (TEA; 3.0 mmol), DMF (1 mL), 808C, 2 h, N2,
99%; d) 4 (0.1 mmol), 1-naphthylboronic acid (0.15 mmol), [Pd(PPh3)4]
ACHTUNGTRENNUNG
4
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
(10 mol%), K2CO3 (0.15 mmol), 4 ꢂ MS (50 mg), toluene (1 mL), 808C,
2 h, N2, 98%; e) 4 (0.1 mmol), phenylboronic acid (0.15 mmol), [Pd-
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
(10 mol%), K2CO3 (0.15 mmol), toluene (1 mL), 808C, 2 h, N2, 45%.
ble mechanism (Scheme 6). Formation of substituted 1-
naphthol 3aa presumably commences with the palladation
of benzoylacetate 1a to yield the palladium intermediate 15
(Scheme 6). The ensuing syn addition of intermediate 15 to
[a] Reaction conditions: DMSO (2.0 mL), 1a (0.2 mmol, 1.0 equiv), 2b–r
(1.0 mmol, 5.0 equiv), Pd
ACHTUNGTRENNUNG(OAc)2 (20 mol%), CuAHCUTNGTREN(NUGN OAc)2 (3.0 equiv), 808C, N2; the
ratio of regioisomers was determined by NMR spectroscopy.
ACHTUNGTRENNUNG(PPh3)4], Suzuki coupling reactions took place and afforded
aryl- or alkyl-functionalized products 12 and 13 (Sche-
me 4e,f). If formic acid was employed to react with Tf-pro-
tected 1-naphthanol 4, a reductive product 10 was obtained
in 99% yield (Scheme 4c). Gratifyingly, [PdACHTNUTRGNE(UNG PPh3)4]-pro-
moted Suzuki coupling allowed Tf-protected 1-naphthanol 4
to readily convert into binaphthyl product 11 (Scheme 4d),
which could potentially be used as a ligand in organometal-
lic and coordination chemistry, or as a functional material
due to its extended p-conjugated system. In addition to indi-
cating the potentially synthetic practicability, a Gram-scale
synthesis was examined under standard conditions and gave
3aa in 70% yield (Scheme 5; 1.24 g).
Scheme 6. Plausible mechanism.
À
On the basis of known transition-metal-catalyzed C H ac-
tivation/oxidative annulation reactions, we propose a plausi-
diphenylacetylene 2a generated the vinylpalladium inter-
mediate 16. Finally, intramolecular palladation of 16 led to
the formation of palladabenzocycloheptanone 17. The cata-
lytic cycle was completed by the liberation of the product
along with Pd0 through reductive elimination. To gain in-
sight into the mechanism, a significant kinetic isotope effect
was measured by using 1a and [D5]1r as substrates
(Scheme 7). A kinetic isotope effect (KIE) value of KH/
Scheme 5. Gram-scale synthesis of 3aa.
Chem. Eur. J. 2013, 19, 13322 – 13327
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J. Wang et al.
E. J. Sorensen, Classics in Total Synthesis, Wiley-VCH, Weinheim,
1995; c) K. C. Nicolaou, S. A. Snyder, Classics in Total Synthesis II,
Wiley-VCH, Weinheim, 2003; d) J. A. Joule, K. Mills, Heterocyclic
Chemistry, 4th ed., Blackwell, Oxford, 2000; e) T. Eicher, S. Haupt-
mann, The Chemistry of Heterocycles, Wiley-VCH, Weinheim, 2003;
f) A. R. Katrizky, A. F. Pozharskii, Handbook of Heterocyclic Chem-
istry, 2nd ed., Pergamon, Amsterdam, 2000.
[2] a) H. Itokawa, K. Mihara, K. Takeya, Chem. Pharm. Bull. 1983, 31,
2353; b) L.-K. Ho, M.-J. Don, H.-C. Chen, S.-F. Yeh, J.-M. Chen, J.
Nat. Prod. 1996, 59, 330; c) Y. Kawasaki, Y. Goda, K. Yoshishira,
Chem. Pharm. Bull. 1992, 40, 1504; d) M.-L. Chung, S.-J. Jou, T.-H.
Cheng, C.-N. Lin, J. Nat. Prod. 1994, 57, 313.
Scheme 7. Kinetic study.
[3] a) C.-X. Sun, D. K. Hunt, R. B. Ckark, D. Lofland, W. J. OꢀBrien, L.
Plamondon, X.-Y. Xiao, J. Med. Chem. 2011, 54, 3704; b) I. Chopra,
R. M. Hawkey, M. Hinton, J. Antimicrob. Chemother. 1992, 29, 245.
[4] a) U. Weiss, L. Merlini, G. Nasini, Prog. Chem. Org. Nat. Prod.
1987, 52, 1; b) G. Bringmann, C. Gꢃnther, M. Ochse, O. Schupp, S.
Tasler, Prog. Chem. Org. Nat. Prod. 2001, 82, 1; c) E. Kobayashi, K.
Ando, H. Nakano, T. Tamaoki, J. Antibiot. 1989, 42, 1470; d) J. W.
Lown, Can. J. Chem. 1997, 75, 99; e) B. J. Morgan, C. A. Mulrooney,
E. M. OꢀBrien, M. C. Kozlowski, J. Org. Chem. 2010, 75, 30.
[5] a) C. P. Gorst-Allman, P. S. Steyn, C. J. Rabie, J. Chem. Soc. Perkin
Trans. 1 1980, 2474; b) K. C. Ehrlich, A. J. DeLucca II, A. Ciegler,
Appl. Environ. Microbiol. 1984, 48, 1; c) K. Koyama, S. Natori, Y.
Iitaka, Chem. Pharm. Bull. 1987, 35, 4049; d) K. Koyama, K. Omi-
nato, S. Natori, T. Tashiro, T. Tsuruo, J. Pharmacobio-Dyn. 1988, 11,
630; e) P. Boutibonnes, Y. Auffray, C. Malherbe, W. Kogbo, C.
Marais, Mycopathologia 1984, 87, 43.
[6] a) G. Wittig, L. Pohmer, Chem. Ber. 1956, 89, 1334; b) D. G. Batt,
D. G. Jones, S. L. Greca, J. Org. Chem. 1991, 56, 6704; c) E. Wolth-
uis, B. Bossenbroek, G. DeWall, E. Geels, A. Leegwater, J. Org.
Chem. 1963, 28, 148; d) F.-Z. Peng, B.-M. Fan, Z.-H. Shao, X.-W. Pu,
P.-H. Li, H.-B. Zhang, Synthesis 2008, 19, 3043; e) H. Matsuzaka, Y.
Hiroe, M. Iwasaki, Y. Ishii, Y. Koyasu, M. Hidai, J. Org. Chem.
1988, 53, 3832; f) Y. Koyasu, H. Matsuzaka, Y. Hiroe, Y. Uchida, M.
Hidai, J. Chem. Soc. Chem. Commun. 1987, 575; g) T.-F. Yang, K.-Y.
Wang, H.-W. Li, Y.-C. Tseng, T.-C. Lien, Tetrahedron Lett. 2012, 53,
585; h) C. A. Mulrooney, X.-L. Li, E. S. DiVirgilio, M. C. Kozlowski,
J. Am. Chem. Soc. 2003, 125, 6856; i) N. J. P. Broom, P. G. Sammes,
J. Chem. Soc. Chem. Commun. 1978, 162; j) L.-Q. cui, Z.-L. Dong,
C. Zhang, Org. Lett. 2011, 13, 6488; k) Y. Tamura, A. Wada, M.
Sasho, Y. Kita, Tetrahedron Lett. 1981, 22, 4283.
KD =3.0 was obtained (see the Supporting Information),
À
thereby suggesting that the cleavage of the C H bond of the
phenyl ring was involved in the rate-determining step.[14]
In summary, we have developed an efficient synthesis of
highly substituted 1-naphthols. The method utilizes simple
and readily available benzoylacetates and unactivated inter-
nal alkynes, and employs a direct PdII-catalyzed oxidative
À
annulation procedure that involves C H activation. The re-
action proceeds under mild conditions and exhibits a broad
substrate scope with respect to the substituents. The signifi-
cance of the 1-naphthol scaffold as a structural element
should also render this method attractive for both synthetic
and medicinal chemistry. We expect this new method to
complement existing methods to access highly substituted 1-
naphthols, which are of great interest in different disciplines.
Experimental Section
General procedure: A solution of b-keto ester 1a (0.2 mmol, 1.0 equiv),
diphenyl actylene 2a (1.0 mmol, 5.0 equiv), Pd
ACHTUNGRTEN(NNUG OAc)2 (20 mol%), and
Cu(OAc)2 (3.0 equiv) in DMSO (2 mL) was stirred at 808C for 24 h
ACHTUNGTRENNUNG
(Table 2). The crude product was purified by column chromatography on
silica gel, eluted by hexane/EtOAc (20:1, then 8:1) to afford the desired
product 3aa as a yellow solid (54 mg, 76% yield). 1H NMR (500 MHz,
CDCl3): d=12.23 (s, 1H), 8.55 (d, J=8.0 Hz, 1H), 7.58–7.47 (m, 2H),
7.40 (d, J=8.0 Hz, 1H), 7.23–7.15 (m, 3H), 7.13–7.01 (m, 5H), 7.00–6.94
(m, 2H), 3.42 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=172.58,
160.47, 141.88, 138.84, 137.25, 135.73, 131.66, 131.41, 129.79, 127.64,
126.82, 126.47, 125.80, 125.76, 124.24, 124.00, 106.58, 77.41, 77.16, 76.91,
51.93 ppm; HRMS (ESI): m/z calcd for C24H17O3: 353.1183 [MÀH+];
found: 353.1170.
À
[7] For selected recent reviews on C H activation, see: a) J. Wencel-
Delord, T. Drçge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40, 4740;
b) J. Yamaguchi, A. D. Yamaguchi, K. Itami, Angew. Chem. 2012,
124, 9092; Angew. Chem. Int. Ed. 2012, 51, 8960; c) N. Kuhl, M. N.
Hopkinson, J. Wencel-Delord, F. Glorius, Angew. Chem. 2012, 124,
10382; Angew. Chem. Int. Ed. 2012, 51, 10236; d) C. Zhu, R. Wang,
J. R. Falck, Chem. Asian J. 2012, 7, 1502; e) M. C. White, Science
2012, 335, 807; f) K. M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu, Acc.
Chem. Res. 2012, 45, 788; g) T. Newhouse, P. S. Baran, Angew.
Chem. 2011, 123, 3422; Angew. Chem. Int. Ed. 2011, 50, 3362; h) L.
Ackermann, Chem. Rev. 2011, 111, 1315; i) L. McMurray, F. OꢀHara,
M. J. Gaunt, Chem. Soc. Rev. 2011, 40, 1885; j) C. S. Yeung, V. M.
Dong, Chem. Rev. 2011, 111, 1215; k) C.-L. Sun, B.-J. Li, Z.-J. Shi,
Chem. Rev. 2011, 111, 1293; l) S. H. Cho, J. Y. Kim, J. Kwak, S.
Chang, Chem. Soc. Rev. 2011, 40, 5068; m) T. W. Lyons, M. S. San-
ford, Chem. Rev. 2010, 110, 1147; n) R. Jazzar, J. Hitce, A. Renau-
dat, J. Sofack-Kreutzer, O. Baudoin, Chem. Eur. J. 2010, 16, 2654;
o) R. Giri, B.-F. Shi, K. M. Engle, N. Maugel, J.-Q. Yu, Chem. Soc.
Rev. 2009, 38, 3242; p) P. Thansandote, M. Lautens, Chem. Eur. J.
2009, 15, 5874; q) O. Daugulis, H.-Q. Do, D. Shabashov, Acc. Chem.
Res. 2009, 42, 1074; r) J. F. Hartwig, Chem. Soc. Rev. 2011, 40, 1992;
Acknowledgements
Financial support from the National University of Singapore and the Sin-
gapore Ministry of Education (academic research grant R14300480112
and R143000443112) are greatly appreciated.
À
Keywords: alkynes
naphthols · palladium
·
annulation
·
C H activation
·
À
s) Topics in Current Chemistry, Vol 292: C H Activation (Eds.: J.-Q.
Yu, Z.-J. Shi), Springer, Berlin, 2010; t) C. Liu, H. Zhang, W. Shi, A.
Lei, Chem. Rev. 2011, 111, 1780; u) W. Shi, C. Liu, A. Lei, Chem.
Soc. Rev. 2011, 40, 2761; v) J. Wencel-Delord, F. Glorius, Nat. Chem.
2013, 5, 369; w) S. R. Neufeldt, M. S. Sanford, Acc. Chem. Res. 2012,
[1] a) K. C. Nicolaou, T. Montagnon, Molecules that Changed the
World: A Brief History of the Art and Science of Synthesis and its
Impact on Society, Wiley-VCH, Weinheim, 2008; b) K. C. Nicolaou,
13326
www.chemeurj.org
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Chem. Eur. J. 2013, 19, 13322 – 13327

Highly Substituted 1-Naphthols
COMMUNICATION
45, 936; x) L. Ackermann, Acc. Chem. Res. 2013, DOI:10.1021/
ar3002798.
5196; Angew. Chem. Int. Ed. 2009, 48, 5094; c) I. V. Seregin, V. Ge-
vorgyan, Chem. Soc. Rev. 2007, 36, 1173; d) C. He, S. Guo, J. Ke, J.
Hao, H. Xu, H. Chen, A. Lei, J. Am. Chem. Soc. 2012, 134, 5766;
e) H. Zhang, R. Shi, P. Gan, C. Liu, A. Ding, Q. Wang, A. Lei,
Angew. Chem. 2012, 124, 5294; Angew. Chem. Int. Ed. 2012, 51,
5204.
À
[8] For selected references on metal-catalyzed C H activation cross-
coupling cyclization reactions with internal alkynes, see: a) N. Gui-
mond, C. Gouliaras, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6908;
b) S. Mochida, N. Umeda, K. Hirano, T. Satoh, M. Miura, Chem.
Lett. 2010, 39, 744; c) T. K. Hyster, T. Rovis, J. Am. Chem. Soc.
2010, 132, 10565; d) S. Rakshit, F. W. Patureau, F. Glorius, J. Am.
Chem. Soc. 2010, 132, 9585; e) C. Wang, S. Rakshit, F. Glorius, J.
Am. Chem. Soc. 2010, 132, 14006; f) N. Guimond, K. Fagnou, J. Am.
Chem. Soc. 2009, 131, 12050; g) D. R. Stuart, M. Bertrand-Laperle,
K. M. N. Burgess, K. Fagnou, J. Am. Chem. Soc. 2008, 130, 16474;
h) M. Yamashita, K. Hirano, T. Satoh, M. Miura, Org. Lett. 2009, 11,
2337; i) K. Morimoto, K. Hirano, T. Satoh, M. Miura, Org. Lett.
2010, 12, 2068; j) K. Ueura, T. Satoh, M. Miura, Org. Lett. 2007, 9,
1407; k) G. Song, D. Chen, C.-L. Pan, R. H. Crabtree, X. Li, J. Org.
Chem. 2010, 75, 7487; l) Y. Minami, Y. Shiraishi, K. Yamada, T.
Hiyama, J. Am. Chem. Soc. 2012, 134, 6124; m) Z.-Z. Shi, C. Zhang,
S. Li, D.-L. Pan, S.-T. Ding, Y.-X. Cui, N. Jiao, Angew. Chem. 2009,
121, 4642; Angew. Chem. Int. Ed. 2009, 48, 4572.
[10] S. W. Youn, B. S. Kim, A. R. Jagdale, J. Am. Chem. Soc. 2012, 134,
11308.
[11] X. Tan, B.-X. Liu, X.-Y. Li, B. Li, S.-S. Xu, H.-B. Song, B.-Q. Wang,
J. Am. Chem. Soc. 2012, 134, 16163.
[12] For examples of our groupꢀs recently developed palladium-catalyzed
À
C H activation with unactivated internal alkynes, see: a) L. Wang,
J. Y. Huang, S. Y. Peng, H. Liu, X.-F. Jiang, J. Wang, Angew. Chem.
2013, 125, 1812; Angew. Chem. Int. Ed. 2013, 52, 1768; b) L. Wang,
S. Y. Peng, J. Wang, Chem. Commun. 2011, 47, 5422.
[13] CCDC-919899 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. (The structure of compound 3la was determined by
X-ray crystal analysis.)
À
[9] For recent reviews on C H functionalization with applications to ar-
[14] a) E. M. Simmons, J. F. Hartwig, Angew. Chem. 2012, 124, 3120;
Angew. Chem. Int. Ed. 2012, 51, 3066; b) Y. Wei, L. Deb, N. Yoshi-
kai, J. Am. Chem. Soc. 2012, 134, 9098.
omatic and heterocyclic compound synthesis, see: a) D. A. Colby,
R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624; b) X.
Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem. 2009, 121,
Received: July 14, 2013
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