Synthesis of 2-naphthols via carbonylative stille coupling reaction of 2-bromobenzyl bromides with tributylallylstannane followed by the heck reaction

Article abstract of DOI:10.1021/jo201907t

A method for the synthesis of 2-naphthols 4 is described. The carbonylative Stille coupling reactions of 2-bromobenzyl bromides with tributylallylstannane to produce 2-bromobenzyl β,γ-unsaturated ketones 2 in satisfactory to excellent yields has been achieved. The isomerization of 2-bromobenzyl β,γ-unsaturated ketones 2 can readily occur under basic conditions to generate 2-bromobenzyl α,β-unsaturated ketones 3. The 2-bromobenzyl α,β-unsaturated ketones 3 can be transformed into 2-naphthols 4 via intramolecular Heck reaction in satisfactory to good yields (Figure presented).

Full text of DOI:10.1021/jo201907t

Article
pubs.acs.org/joc
Synthesis of 2-Naphthols via Carbonylative Stille Coupling Reaction
of 2-Bromobenzyl Bromides with Tributylallylstannane Followed by
the Heck Reaction
Yao Dai,† Xiujuan Feng,*,† Hesong Liu,*,‡ Hua Jiang,† and Ming Bao†
†State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China
‡Department of Dermatology & Venereology, The First Hospital of JiLin University, Changchun 130021, China
S
* Supporting Information
ABSTRACT: A method for the synthesis of 2-naphthols 4 is described.
The carbonylative Stille coupling reactions of 2-bromobenzyl bromides
with tributylallylstannane to produce 2-bromobenzyl β,γ-unsaturated
ketones 2 in satisfactory to excellent yields has been achieved. The
isomerization of 2-bromobenzyl β,γ-unsaturated ketones 2 can readily occur under basic conditions to generate 2-bromobenzyl
α,β-unsaturated ketones 3. The 2-bromobenzyl α,β-unsaturated ketones 3 can be transformed into 2-naphthols 4 via intra-
molecular Heck reaction in satisfactory to good yields.
Scheme 1. Synthesis of 2-Naphthols 4 Using 2-Bromobenzyl
Bromides, Tributylallylstannane, and CO as Starting
Materials
INTRODUCTION
■
The development of convenient and efficient methods for the
synthesis of 2-naphthols has attracted considerable attention.
2-Naphthols can be utilized as versatile and key synthetic inter-
mediates for the preparation of several natural products, bio-
active compounds, and chiral ligands.1 Over the past three decades,
two main methods have been developed for the preparation of
2-naphthols. One method involves intramolecular cyclization
reactions, such as electrophilic cyclization,2 cyclodehydration,3
oxidative cyclization,4 rhodium(II)-catalyzed cycloisomerization,5
photo- or thermal-promoted cyclization,6 and intramolecular
Aldol condensation7 and Dieckmann condensation.8 The other
method involves intermolecular cyclization reactions such as
palladium(II)-catalyzed annulation reactions.9 Although mono-
and polysubstituted-2-naphthols can be obtained using these
methods, the synthesis frequently suffers from drawbacks such
as multistep reactions, harsh reaction conditions, and special
starting materials.
the reaction conditions. The optimization included selecting the
most suitable palladium catalysts and solvents at 80 °C (Table 1).
Several palladium catalysts were tested in acetonitrile (MeCN)
under 0.3 MPa CO pressure. These catalysts include Pd(II) chloride
(PdCl2)/PPh3, Pd(II) acetate [Pd(OAc)2]/PPh3, Pd(II) acetylacet-
onate [Pd(acac)2]/PPh3, tris(dibenzylideneacetone)dipalladium(0)
[Pd2(dba)3]/PPh3, and tetrakis(triphenylphosphine)palladium(0)
[Pd(PPh3)4] (entries 1−5). Pd(PPh3)4 exhibited higher catalytic
activity than the others and gave the desired benzyl β,γ-unsaturated
ketone, 1-(2-bromophenyl)pent-4-en-2-one (2a), in 87% 1H NMR
yield (entry 5). The solvents were then screened using Pd(PPh3)4 as
the catalyst (entries 5−9). Both polar [MeCN, 1-methyl-2-
pyrrolidinone (NMP), dioxane, and tetrahydrofuran (THF)]
and nonpolar (toluene) solvents were examined, and MeCN
proved to be the best solvent (entry 5). The yield of 2a decreased
with decreased Pd(PPh3)4 loading (entry 10), lowered reaction
temperature (entry 11), and decreased CO pressure (entry 12).
In the course of our continuous research on the η3-benzyl-
palladium chemistry,10 we found that benzyl α,β-unsaturated
ketones 311 can be readily obtained from the isomerization
reaction of benzyl β,γ-unsaturated ketones 212 under basic
conditions. The ketones 2 are generated from the carbonyla-
tive Stille coupling reaction of 2-bromobenzyl bromides 1 with
tributylallylstannane. The ketones 3 can be transformed into
2-naphthols 4 via an intramolecular Heck reaction (Scheme 1).
In the present paper, we report a method of preparing 2-naph-
thols using simple and readily available starting materials, such
as 2-bromobenzyl bromides, tributylallylstannane, and carbon
monoxide (CO).
RESULTS AND DISCUSSION
■
Synthesis of Benzyl β,γ-Unsaturated Ketones 2. In our
initial studies, the reaction of 2-bromobenzyl bromide (1a),
tributylallylstannane, and CO was chosen as a model to optimize
Received: September 16, 2011
Published: November 10, 2011
© 2011 American Chemical Society
10068
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
transformed into α,β-unsaturated ketones 3 under basic con-
ditions. The carbonylative Stille coupling reactions of 1a−i with
tributylallylstannane were again performed to obtain 3 for the
synthesis of the 2-naphthols 4. The results are shown in Table 3.
After the reactions were completed, mixtures of the β,γ-
unsaturated ketones 2 and a small amount of 3 were obtained via
silica gel column chromatography. The isomerization of the 2
easily occurred when the resulting mixtures were passed through a
short basic alumina column to give 3. The cis- and trans-isomers
of 3 were then separated via silica gel column chromatography
using the appropriate eluents.
Synthesis of 2-Naphthols 4. In our initial studies, we
have chosen the reaction of a trans-isomer 3aE of the α,β-
unsaturated ketone 3a as a model to screen the reaction con-
ditions. The results are shown in Table 4. When the intra-
molecular Heck reaction of 3aE was performed in NMP at
120 °C for 3 h using various Pd sources and NaHCO3 as a base,
Pd(PPh3)4 was found to be the optimal catalyst (entries 1−5).
The desired 2-naphthol, 4-methylnaphthalen-2-ol (4a), was
obtained in 87% GC yield (entry 5). Evaluation of the bases
and solvents (entries 5−13) reveal NaHCO3 and NMP to be
the optimal. The use of the tertiary amines NEt3 and NnBu3 as
bases resulted in a reductive Heck reaction product 5, a by-
product, in the same (or almost the same) yield as that of 4a
(40% GC yield, entries 8 and 9).14 The yield of 4a decreased
with decreased Pd(PPh3)4 loading (5 mol %, entry 14) and lowered
reaction temperature (110 °C, entry 15).
Table 1. Optimization of Reaction Conditions for the
Carbonylative Stille Coupling Reaction of 2-Halogenbenzyl
Halides 1 with Tributylallylstannane
a
b
entry
catalyst
solvent
yield (%)
1
2
3
4
5
6
7
8
9
PdCl2/PPh3
Pd(OAc)2/PPh3
Pd(acac)2/PPh3
Pd2(dba)3/PPh3
Pd(PPh3)4
MeCN
MeCN
MeCN
MeCN
MeCN
NMP
85
80
81
84
87
15
81
83
60
79
80
81
Pd(PPh3)4
Pd(PPh3)4
dioxane
THF
Pd(PPh3)4
Pd(PPh3)4
toluene
MeCN
MeCN
MeCN
c
10
Pd(PPh3)4
d
11
Pd(PPh3)4
e
12
Pd(PPh3)4
a
Reaction conditions: 3 mmol each of 1a and tributylallylstannane,
2 mol % of Pd, and 8 mol % of PPh3 in 12 mL of solvent under
0.3 MPa CO pressure at 80 °C for 2 h; all reactions were performed in
b
a 75 mL autoclave. 1H NMR yield, mesitylene was used as an internal
c
d
standard. 1 mol % of Pd(PPh3)4 was used. The reaction was
e
performed at 70 °C. The reaction was performed under 0.2 MPa CO
pressure.
The intramolecular Heck reactions of the α,β-unsaturated
ketones 3 were performed under the optimized conditions, and
the results are summarized in Table 5. The reaction of 3aE was
completed within 3 h to afford the desired product 4a in 86%
yield (entry 1). The reactions of α,β-unsaturated ketones 3bE,
3cE, 3dE, and 3eE also proceeded smoothly to furnish the
corresponding 2-naphthols 4b−e in moderate to good yields
(63%−89%, entries 2−5). Low yields were observed from the
reactions of α,β-unsaturated ketones 3fE and 3gE, which bear
a F and Cl atom on the benzene ring, respectively (entries 6
and 7). The 2-naphthols 4f and 4g were obtained in 35% and
21% yields, respectively. Decomposition or no reaction was
observed when the starting materials 3hE and 3iE were treated
under the same conditions (entries 8 and 9). The 2-naphthol
4a was also obtained in good yield when the cis- isomer 3aZ of
3a was used (82%, entry 10).
The direct use of the β,γ-unsaturated ketone 2a and one-pot
reactions of 1a, tributylallylstannane, and CO were attempted
for preparation of the 2-naphthol 4a. The results are shown in
Scheme 2. As expected, the β,γ-unsaturated ketone 2a underwent
the desired reaction smoothly to provide the 2-naphthol 4a
in 85% yield (eq 1). The three successive one-pot reactions
(carbonylative Stille coupling, isomerization, and Heck reac-
tion) of 1a, tributylallylstannane, and CO led to the formation
of a mixture of 4a and (E)-3-(prop-1-en-1-yl)-1H-isochromen-
1-one (6), an isocoumarin derivative.15 Products 4a and 6 were
isolated in 29% and 18% yields, respectively (eq 2).
Therefore, the subsequent reactions of the 2-halogenbenzyl halides
1 with tributylallylstannane were performed in MeCN at 80 °C
under 0.3 MPa CO pressure in the presence of Pd(PPh3)4 as the
catalyst.
The carbonylative Stille coupling reactions of 2-halogen-
benzyl halides 1a−i with tributylallylstannane were performed
under the optimized conditions, and the results are summarized
in Table 2. The reactions of 2-bromobenzyl bromide (1a) and
1-bromo-2-(bromomethyl)naphthalene (1b), a polycyclic analogue
of 1a, with tributylallylstannane and CO smoothly proceeded to
furnish the corresponding β,γ-unsaturated ketones, 2a and 2b
in good yields (86% and 77%, respectively; entries 1 and 2).
Substrates 1c−e, which bear the electron-donating groups
methyl and methoxyl on the benzene ring, exhibited almost the
same reactivities as those of substrates 1a and 1b to give β,γ-
unsaturated ketones 2c−e in satisfactory yields (90%, 73%, and
68%, respectively; entries 3−5). Substrates 1f−h, bearing halogen
atoms F, Cl, and Br on the benzene ring, also smoothly under-
went the desired reactions to give products 2f−h in good yields
(84%, 76%, and 84%, respectively, entries 6−8). These results
indicate that the reaction yield was not affected by the electronic
property of the substituent linked to the benzene ring of the sub-
strate. As expected, the reaction of 2-chlorobenzyl chloride (1i)
gave β,γ-unsaturated ketone 2i in good yield (82%, entry 9).
Notably, the Cl and Br atoms linked to the aromatic ring were
maintained in the structures of the products 2 under the carbo-
nylative Stille coupling reaction conditions.13 Although the forma-
tion of α,β-unsaturated ketones 3 in all cases was detected via 1H
NMR analysis of the product mixture, 3 were not isolated because
the amount formed was considered too small.
Finally, tributylvinylstannane was employed instead of tribut-
ylallylstannane as a starting material for the three-component
coupling reaction. The results are shown in Scheme 3. As
expected, the carbonylative Stille coupling product 7 was ob-
tained in moderate yield (69%) under the same reaction con-
ditions. The yield of 7 was improved to 75% when the catalyst
loading was increased to 4 mol %. The desired product 2-
naphthol 8 was finally obtained in moderate yield (59%) under
the modified reaction conditions.
Transformation of β,γ-Unsaturated Ketones 2 into
α,β-Unsaturated Ketones 3. The β,γ-unsaturated ketones 2
obtained from the synthesis via carbonylative Stille coupling
reactions of benzyl halides with tributylallylstannane were very
stable under thermal and acidic conditions but can be easily
10069
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
a
Table 2. Carbonylative Stille Coupling Reactions of 2-Halogenbenzyl Halides 1 with Tributylallylstannane
a
A mixture of 2-halogenbenzyl halide 1a−i (3 mmol), tributylallylstannane (3 mmol), and Pd (PPh3)4 (2 mol %) in MeCN (12 mL) was stirred at
b
80 °C under 0.3 MPa CO pressure for the period indicated in the table; all reactions were performed in a 75 mL autoclave. Crude products were
purified via silica gel column chromatography.
CONCLUSION
EXPERIMENTAL SECTION
■
■
General Methods. All solvents were dried according to standard
literature procedures. All reagents were purchased from commercial
sources and used without further purification. 1-Bromo-2-(bromomethyl)-
benzene (1a) and 1-chloro-2-(chloromethyl) benzene (1i) are commercially
available. 1-Bromo-2-(bromomethyl)naphthalene (1b),16 1-bromo-2-
(bromomethyl)-4,5-dimethoxybenzene (1e),17 2-bromo-1-(bromo-
methyl)-4-fluorobenzene (1f),18 2-bromo-1-(bromomethyl)-4-chloro-
benzene (1g),19 and 2,4-dibromo-1-(bromomethyl)benzene (1h)20
were prepared following literature procedures. 1H and 13C NMR
In conclusion, we have developed a new, highly efficient proto-
col to synthesize 2-naphthols under very mild reaction conditions.
The present methodology utilizes simple and readily available
starting materials, namely, 2-bromobenzyl bromides, tributylallyl-
stannane, and CO, and generally affords products in good yields.
We have also developed a convenient and efficient method for the
preparation of the benzyl β,γ-unsaturated ketone and benzyl α,β-
unsaturated ketone intermediates.
10070
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
a
Table 3. Preparation of Benzyl α,β-Unsaturated Ketones 3
a
A mixture of 2-halogenbenzyl halide 1a−i (3 mmol), tributylallylstannane (3 mmol), and Pd (PPh3)4 (2 mol %) in MeCN (12 mL) was stirred at
b
80 °C under 0.3 MPa CO pressure for the period indicated in the table; all reactions were performed in a 75 mL autoclave. Crude products were
c
purified via silica gel column chromatography and a short basic alumina column. The ratio of the cis- to trans-isomers was determined via 1H NMR
analysis.
(proton decoupled) spectra were recorded in CDCl3 solvent on a 400
MHz NMR spectrometer. Chemical shifts (δ) were reported in parts
per million (ppm) with respect to TMS as an internal standard.
Coupling constants (J) are quoted in hertz (Hz). IR spectra were
recorded on FT-IR spectrometer. The high-resolution mass spectra
were recorded on a mass spectrometer equipped with a Z-spray
ionization source. Thin-layer chromatography (TLC) was performed
on SiO2 (silica gel 60 F254), and the spots were detected with UV light
10071
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
CDCl3) δ 7.36 (d, J = 8.5 Hz, 1H), 7.12 (d, J = 2.6 Hz, 1H), 6.84 (dd,
J = 8.5, 2.6 Hz, 1H), 4.60 (s, 2H), 3.80 (s, 3H).24
Table 4. Optimization of Reaction Conditions for the
Intramolecular Heck Reaction of 2-Bromobenzyl α,β-
a
Representative Procedure for the Preparation of Benzyl β,γ-
Unsaturated Ketones 2. Pd(PPh3)4 (69 mg, 0.06 mmol, 2 mol %),
1a (750 mg, 3 mmol), tributylallylstannane (993 mg, 3 mmol), and
MeCN (12 mL) were placed in a 75 mL autoclave with a magnetic stir
bar under a N2 atmosphere. The autoclave was purged with CO three
times, filled with CO to 0.3 MPa pressure, and heated to 80 °C for 2 h.
The autoclave was allowed to cool to room temperature and the
remaining CO was vented. The resultant mixture was evaporated in
vacuo to give the crude product, which was then purified via silica gel
chromatography (eluent: ethyl acetate/petroleum ether = 1:20) to
afford 2a as a light yellow oil.
Unsaturated Ketones 3
b
yield (%)
entry
Pd source
base
solvent
4a
81
5
c
c
c
c
c
1
PdCl2
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaOAc
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
MeCN
dioxane
DMF
toluene
NMP
NMP
ND
ND
ND
ND
ND
4
2
Pd(OAc)2
Pd(acac)2
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
81
55
78
87
67
3
1-(2-Bromophenyl)pent-4-en-2-one (2a): 617 mg, 86% yield, light
1
3
yellow oil; H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 1H),
4
7.33−7.10 (m, 3H), 5.95 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.20
(d, J = 9.5 Hz, 1H), 5.16 (dd, J = 17.1, 1.2 Hz, 1H), 3.89 (s, 2H), 3.27
(d, J = 7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 204.7, 134.6,
132.9, 131.8, 130.3, 128.9, 127.7, 125.0, 119.2, 49.5, 47.4; IR (neat)
3073, 3017, 2958, 2922, 1720, 1470, 1440, 1331, 1054, 1026, 920,
750 cm−1; HRMS (EI) calcd for C11H11BrO 237.9993 [M]+, found
238.0004.
5
6
c
7
K3PO4
ND
40
8
NEt3
NnBu3
45
40
40
12
79
trace
50
61
9
40
10
11
12
13
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
trace
1-(1-Bromonaphthalen-2-yl)pent-4-en-2-one (2b): 668 mg, 77%
c
ND
1
yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.4
c
ND
Hz, 1H), 7.81 (dd, J = 15.7, 8.2 Hz, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.52
(t, J = 7.4 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 5.97 (dt, J = 17.1, 6.7 Hz,
1H), 5.21 (d, J = 10.2 Hz, 1H), 5.16 (d, J = 17.2 Hz, 1H), 4.14 (s, 2H),
3.30 (d, J = 6.8 Hz, 2H); 13C NMR (101 MHz, CD3Cl) δ 204.3, 133.3,
132.6, 132.1, 130.2, 128.4, 127.9, 127.6, 127.3, 127.0, 126.2, 124.7,
118.8, 50.5, 47.1; IR (neat) 3053, 2908, 1718, 1501, 1410, 1329, 1055,
981, 921, 811, 755 cm−1; HRMS (ESI) calcd for C15H13ONaBr
311.0047 [M + Na]+, found 311.0050.
c
ND
d
c
14
ND
e
c
15
ND
a
Reaction conditions: 0.5 mmol of 3aE, 1.0 mmol of base, 10 mol %
of Pd, and 40 mol % of PPh3 [combined with PdCl2, Pd(OAc)2,
Pd(acac)2, or Pd2(dba)3] in 5 mL of solvent at 120 °C for 3 h; all
b
reactions were performed in a 25 mL Schlenk reactor. GC yield;
c
d
1-(2-Bromo-4-methylphenyl)pent-4-en-2-one (2c): 683 mg, 90%
1-naphthol was used as an internal standard. Not determined. 5 mol %
1
e
yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.40 (s, 1H),
of Pd(PPh3)4 was used. The reaction was performed at 110 °C.
7.09 (s, 2H), 5.95 (ddt, J = 17.1, 10.3, 7.0 Hz, 1H), 5.21−5.13 (m,
2H), 3.85 (s, 2H), 3.25 (d, J = 6.9 Hz, 2H), 2.32 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 204.3, 138.6, 132.9, 131.2, 130.2, 128.2, 124.4,
118.6, 48.8, 46.9, 20.4; IR (neat) 3078, 3004, 2979, 2919, 1720, 1683,
1636, 1598, 1392, 1038, 966, 923, 811, 705 cm−1; HRMS (ESI) calcd
for C12H13ONaBr 275.0047 [M + Na]+, found 275.0050.
or 1% aqueous KMnO4. Flash chromatography was also performed on
either SiO2 (silica gel 60, 200−300 mesh) or basic alumina (Al2O3 90,
100−200 mesh). Melting points were determined using a micro-
melting point apparatus and are uncorrected.
Preparation of 2-Bromo-1-(bromomethyl)-4-methylbenzene
(1c). To a solution of 2-bromo-4-methylbenzaldehyde21 (12.2 g,
61 mmol) in 200 mL of MeOH at 0 °C was added NaBH4 (2.7 g,
72 mmol) portionwise within 10 min. After the mixture was stirred for
10 min, an aqueous HCl (1 M) was added to quench the reaction and
neutralize the resulting solution. The solvents were removed under
vacuum, and the residue obtained was then extracted with dichloro-
methane (50 mL × 3). The combined organic layers were dried over
Na2SO4, and the solvent was removed under reduced pressure to give
a crude product, (2-bromo-4-methylphenyl)methanol, as an oil . This
oil was used without further purification in the next step. To a solution
of (2-bromo-4-methylphenyl)methanol in anhydrous Et2O (200 mL)
at 0 °C was added PBr3 (6.7 g, 22 mmol) dropwise, and the resulting
solution was stirred at room temperature for 3 h. The resultant mix-
ture was neutralized with an aqueous NaHCO3, and the product was
extracted with Et2O (100 mL × 2). The organic layers were dried over
Na2SO4, and the solvent was removed under vacuum. The crude prod-
uct was recrystallized from petroleum ether to give 1c (14.7 g, 91%) as
1-(2-Bromo-4-methoxyphenyl)pent-4-en-2-one (2d): 589 mg,
73% yield, light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.12
(dd, J = 7.5, 5.6 Hz, 2H), 6.84 (dd, J = 8.5, 2.6 Hz, 1H), 5.94 (ddt, J =
17.2, 10.2, 7.0 Hz, 1H), 5.20 (dd, J = 10.2, 1.3 Hz, 1H), 5.15 (dd, J =
17.1, 1.5 Hz, 1H), 3.82 (s, 2H), 3.79 (s, 3H), 3.25 (d, J = 7.0 Hz, 2H);
13C NMR (101 MHz, CDCl3) δ 204.8, 159.0, 131. 9, 130.3, 126.3,
124.9, 118.7, 117.8, 113.4, 55.3, 48.3, 46.9; IR (neat) 3079, 3006, 2942,
2905, 1716, 1605, 1440, 1245, 1029, 921, 863, 676 cm−1; HRMS (ESI)
calcd for C12H13O2NaBr 290.9997 [M + Na]+, found 291.0001.
1-(2-Bromo-4,5-dimethoxyphenyl)pent-4-en-2-one (2e): 610 mg,
68% yield, white solid; mp 65−66 °C; 1H NMR (400 MHz, CDCl3) δ
7.04 (s, 1H), 6.70 (s, 1H), 5.95 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.20
(dd, J = 10.2, 1.3 Hz, 1H), 5.16 (dd, J = 17.1, 1.5 Hz, 1H), 3.87 (s,
3H), 3.85 (s, 3H), 3.82 (s, 2H), 3.26 (d, J = 6.9 Hz, 2H); 13C NMR
(101 MHz, CDCl3) δ 204.8, 148.6, 148.3, 130.2, 126.1, 118.8, 115.3,
114.7, 113.9, 56.0, 55.9, 48.9, 46.9; IR (KBr) 3078, 3002, 2935, 2840,
1719, 1603, 1508, 1382, 1259, 1217, 1032, 921 cm−1; HRMS (ESI)
calcd for C13H15O3NaBr 321.0102 [M + Na]+, found 321.0094.
1-(2-Bromo-4-fluorophenyl)pent-4-en-2-one (2f): 648 mg, 84%
yield, light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.33 (dd, J = 8.2,
2.4 Hz, 1H), 7.18 (dd, J = 8.3, 6.1 Hz, 1H), 7.01 (td, J = 8.3, 2.4 Hz,
1H), 5.95 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.28−5.11 (m, 2H), 3.87
(s, 2H), 3.27 (d, J = 6.9 Hz, 2H); 13C NMR (101 MHz, CDCl3)
δ 204.2, 161.4 (d, JCF = 250.2 Hz), 132.5 (d, JCF = 8.3 Hz), 130.5 (d,
1
a colorless solid: mp 58−60 °C; H NMR (400 MHz, CDCl3) δ 7.40
(s, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H), 4.59 (s,
2H), 2.32 (s, 3H).22
Preparation of 2-Bromo-1-(bromomethyl)-4-methoxyben-
zene (1d). To a solution of 2-bromo-4-methoxy-1-methylbenzene23
(9.2 g, 46 mmol) in 150 mL of CCl4 were added N-bromosuccinimide
(NBS, 8.2 g, 46 mmol) and azobisisobutyronitrile (AIBN, 755 mg, 4.6
mmol). The reaction mixture was stirred under reflux for 12 h. After
being cooled to room temperature, the mixture was washed with
an aqueous sodium thiosulfate (NaS2O3, 5 wt %). The organic layer
was dried over Na2SO4, and the solvent was removed under vacuum.
The crude product was recrystallized from petroleum ether to give 1d
J
CF = 3.2 Hz), 130.2, 124.8 (d, JCF = 9.5 Hz), 119.9 (d, JCF = 24.5 Hz),
119.1, 114.7 (d, JCF = 21.0 Hz), 48.4, 47.3; IR (neat) 3084, 2919, 2840,
1719, 1600, 1488, 1231, 1055, 1032, 921 cm−1; HRMS (ESI) calcd for
C11H10OFNaBr 278.9797 [M + Na]+, found 278.9800.
1-(2-Bromo-4-chlorophenyl)pent-4-en-2-one (2g): 624 mg, 76%
1
1
(7.9 g, 62%) as a white solid: mp 54−56 °C; H NMR (400 MHz,
yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H),
10072
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
a
Table 5. Preparation of 2-Naphthols 4 via Intramolecular Heck Reaction of α,β-Unsaturated Ketones 3
a
A mixture of α,β-unsaturated ketone 3 (0.5 mmol), NaHCO3 (1.0 mmol), and Pd(PPh3)4 (10 mol %) in NMP (5 mL) was stirred at 120 °C under
b
c
a N2 atmosphere for the period indicated in the table. Crude products were purified via silica gel column chromatography. The starting material
3hE was decomposed. No reaction; the starting material 3iE was recovered.
d
7.27 (d, J = 7.4 Hz, 1H), 7.13 (d, J = 8.2 Hz, 1H), 5.95 (ddt, J = 17.2,
10.0, 7.0 Hz, 1H), 5.22 (d, J = 10.3 Hz, 1H), 5.18 (d, J = 17.2 Hz, 1H),
3.87 (s, 2H), 3.27 (d, J = 6.9 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ
203.8, 133.5, 133.1, 132.4, 132.2, 130.0, 127.7, 125.1, 119.1, 48.5, 47.3;
IR (neat) 3081, 2908, 2840, 1720, 1586, 1471, 1411, 1101, 1054, 1039,
921, 747 cm−1; HRMS (ESI) calcd for C11H10OClNaBr 294.9500
[M + Na]+, found 294.9504.
1-(2,4-Dibromophenyl)pent-4-en-2-one (2h): 801 mg, 84% yield,
1
light yellow oil; H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 1.7 Hz,
1H), 7.41 (dd, J = 8.2, 1.7 Hz, 1H), 7.08 (d, J = 8.2 Hz, 1H), 5.95 (ddt,
10073
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
7.13 (td, J = 7.8, 1.8 Hz, 1H), 6.99 (dq, J = 15.6, 6.9 Hz, 1H), 6.21 (dq,
Scheme 2. Direct Use of the β,γ-Unsaturated Ketone 2a and
One-Pot Reactions for Preparation of the 2-Naphthol 4a
J = 15.6, 1.5 Hz, 1H), 3.99 (s, 2H), 1.91 (dd, J = 6.9, 1.6 Hz, 3H); 13
C
NMR (101 MHz, CDCl3) δ 196.0, 143.7, 134.9, 132.8, 131.7, 131.0,
128.7, 127.6, 125.1, 47.5, 18.4; IR (neat) 3055, 2912, 1682, 1629,
1471, 1439, 1336, 1187, 1026, 968, 749 cm−1; HRMS (EI) calcd for
C11H11BrO 237.9993 [M]+, found 237.9985.
(Z)-1-(1-Bromonaphthalen-2-yl)pent-3-en-2-one (3bZ): 75 mg,
1
9% yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 8.31 (d,
J = 8.5 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H),
7.61−7.49 (m, 2H), 7.33 (d, J = 8.4 Hz, 1H), 6.29−6.19 (m, 2H), 4.16
(s, 2H), 2.13 (d, J = 5.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
197.5, 144.8, 133.8, 133.3, 132.7, 128.7, 128.24, 127.9, 127.7, 127.6,
127.0, 126.5, 125.2, 52.1, 16.2; IR (neat) 3053, 2922, 1716, 1692,
1619, 1501, 1433, 1074, 812, 759 cm−1; HRMS (EI) calcd for
C15H13BrO 288.0150 [M]+, found 288.0151.
(E)-1-(1-Bromonaphthalen-2-yl)pent-3-en-2-one (3bE): 679 mg,
78% yield, white solid; mp 76−78 °C; 1H NMR (400 MHz, CDCl3) δ
8.31 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.3 Hz,
1H), 7.59 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.4 Hz, 1H), 7.32 (d, J = 8.4
Hz, 1H), 7.02 (dq, J = 13.9, 6.8 Hz, 1H), 6.24 (dd, J = 15.4, 1.4 Hz,
1H), 4.24 (s, 2H), 1.90 (d, J = 6.8 Hz, 2H); 13C NMR (101 MHz,
CDCl3) δ 196.3, 144.0, 133.8, 133.2, 132.7, 131.1, 128.7, 128.3, 127.9,
127.7, 127.6, 126.5, 125.1, 49.1, 18.5; IR (KBr) 3052, 2911, 1676,
1630, 1501, 1438, 1325, 1189, 968, 808, 761 cm−1; HRMS (EI) calcd
for C15H13BrO 288.0150 [M]+, found 288.0149.
Scheme 3. Synthesis of 2-Naphthol 8 Using 2-Bromobenzyl
Bromide 1a, Tributylvinylstannane, and CO as Starting
Materials
(Z)-1-(2-Bromo-4-methylphenyl)pent-3-en-2-one (3cZ): 60 mg,
1
8% yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.41 (s,
1H), 7.12−7.07 (m, 2H), 6.28−6.19 (m, 2H), 3.86 (s, 2H), 2.32 (s,
3H), 2.12 (d, J = 5.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 197.7,
144.4, 138.8, 133.3, 131.8, 131.4, 128.5, 126.8, 124.8, 50.7, 20.7, 16.0;
IR (neat) 3025, 2920, 1693, 1620, 1492, 1435, 1317, 1074, 1040, 920,
870, 819, 743, 702 cm−1; HRMS (ESI) calcd for C12H13ONaBr
275.0047 [M + Na]+, found 275.0045.
J = 17.1, 10.2, 7.0 Hz, 1H), 5.22 (d, J = 10.2 Hz, 1H), 5.18 (d, J = 17.2
Hz, 1H), 3.85 (s, 2H), 3.27 (d, J = 6.9 Hz, 2H); 13C NMR (101 MHz,
CDCl3) δ 203.7, 134.9, 133.6, 132.8, 130.6, 130.0, 125.5, 121.3, 119.2,
48.6, 47.3; IR (neat) 3080, 2907, 1719, 1580, 1467, 1053, 1036, 920,
731 cm−1; HRMS (ESI) calcd for C11H10ONaBr2 338.8996 [M + Na]+,
found 338.8994.
1-(2-Chlorophenyl)pent-4-en-2-one (2i): 479 mg, 82% yield, light
yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.40−7.37 (m, 1H), 7.25−
7.19 (m, 3H), 5.95 (ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.20 (ddd, J =
10.3, 2.6, 1.2 Hz, 1H), 5.15 (ddd, J = 17.1, 2.9, 1.4 Hz, 1H), 3.87 (s,
2H), 3.26 (d, J = 7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 204.7,
134.4, 132.7, 131.8, 130.3, 129.6, 128.7, 127.0, 119.1, 47.3, 47.1; IR
(neat) 3076, 3020, 2981, 2909, 1720, 1638, 1474, 1444, 1330, 1053,
921, 752 cm−1; HRMS (EI) calcd for C11H11OCl 194.0498 [M]+,
found 194.0498.
Representative Procedure for the Preparation of Benzyl α,β-
Unsaturated Ketones 3. The carbonylative Stille coupling reaction
of 1a with tributylallylstannane [Pd(PPh3)4: 69 mg, 0.06 mmol, 2 mol %;
1a: 750 mg, 3 mmol; tributylallylstannane: 993 mg, 3 mmol; CO: 0.3
MPa; MeCN: 12 mL] was performed according to the procedure
described in the above section. When the reaction was completed, a
689 mg (96% yield) mixture of benzyl β,γ-unsaturated ketone 2a and a
small amount of benzyl α,β-unsaturated ketone 3a were obtained via
silica gel column chromatography (eluent: ethyl acetate/petroleum
ether =1:20). The resultant mixture in ethyl acetate (20 mL) was
passed through a short basic alumina column to give 3a in 95% yield
(681 mg) with a 12:88 Z/E ratio. The cis- and trans-isomers of 3a were
then separated via silica gel column chromatography using ethyl
acetate/petroleum ether (1:20) as an eluent.
(E)-1-(2-Bromo-4-methylphenyl)pent-3-en-2-one (3cE): 692 mg,
1
91% yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.40 (s,
1H), 7.11−6.93 (m, 3H), 6.20 (dd, J = 15.7, 1.6 Hz, 1H), 3.94 (s, 2H),
2.31 (s, 3H), 1.91 (dd, J = 6.9, 1.5 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 196.3, 143.6, 138.8, 133.2, 131.7, 131.3, 131.0, 128.4, 124.8,
47.1, 20.7, 18.4; IR (neat) 3034, 2969, 2914, 2868, 1681, 1632, 1492,
1441, 1332, 1187, 1073, 1041, 968, 867, 798, 674 cm−1; HRMS (ESI)
calcd for C12H13ONaBr 275.0047 [M + Na]+, found 275.0042.
(Z)-1-(2-Bromo-4-methoxyphenyl)pent-3-en-2-one (3dZ): 62 mg,
1
8% yield, white solid; mp 30−31 °C; H NMR (400 MHz, CDCl3) δ
7.14−7.10 (m, 2H), 6.84 (dd, J = 8.5, 2.6 Hz, 1H), 6.28−6.19 (m,
2H), 3.83 (s, 2H), 3.79 (s, 3H), 2.12 (d, J = 5.7 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 197.8, 159.2, 144.3, 132.0, 126.9, 126.8, 125.2,
118.1, 113.8, 55.5, 50.2, 16.0; IR (KBr) 3069, 3005, 2940, 2912, 2836,
1639, 1605, 1494, 1439, 1282, 1243, 1074, 1029, 920, 862, 840 cm−1
HRMS (EI) calcd for C12H13O2Br 268.0099 [M]+, found 268.0105.
;
(E)-1-(2-Bromo-4-methoxyphenyl)pent-3-en-2-one (3dE): 625
1
mg, 77%, white solid; mp 58−60 °C; H NMR (400 MHz, CDCl3)
δ 7.13−7.10 (m, 2H), 6.97 (dq, J = 13.7, 6.9 Hz, 1H), 6.83 (dd, J = 8.5,
2.5 Hz, 1H), 6.20 (dd, J = 15.7, 1.5 Hz, 1H), 3.91 (s, 2H), 3.79 (s,
3H), 1.90 (dd, J = 6.8, 1.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
196.4, 159.2, 143.5, 131.9, 130.9, 126.8, 125.2, 118.1, 113.7, 55.5, 46.6,
18.3; IR (KBr) 3006, 2941, 2910, 2836, 1686, 1631, 1605, 1495, 1440,
1243, 1185, 1028, 969, 864 cm−1; HRMS (EI) calcd for C12H13O2Br
268.0099 [M]+, found 268.0096.
(Z)-1-(2-Bromo-4,5-dimethoxyphenyl)pent-3-en-2-one (3eZ): 91
mg, 10% yield, white solid; mp 64−66 °C; 1H NMR (400 MHz,
CDCl3) δ 7.04 (s, 1H), 6.72 (s, 1H), 6.30−6.21 (m, 2H), 3.87 (s, 3H),
3.85 (s, 3H), 3.83 (s, 2H), 2.13 (d, J = 5.7 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 197.8, 148.6, 148. 5, 144.6, 126.8, 126.7, 115.5, 115.0,
113.9, 56.2, 56.0, 50.7, 16.0; IR (KBr) 3077, 3002, 2935, 2909, 2839,
1692, 1619, 1508, 1464, 1439, 1381, 1259, 1219, 1165, 1075, 1032,
967, 924, 852, 801 cm−1; HRMS (EI) calcd for C13H15O3Br 298.0205
[M]+, found 298.0211.
(Z)-1-(2-Bromophenyl)pent-3-en-2-one (3aZ): 82 mg, 11% yield,
1
light yellow oil; H NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 8.0, 0.8
Hz, 1H), 7.32−7.25 (m, 1H), 7.23 (dd, J = 7.6, 1.8 Hz, 1H), 7.13 (td,
J = 7.8, 1.9 Hz, 1H), 6.31−6.19 (m, 2H), 3.91 (s, 2H), 2.13 (d, J = 5.6
Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 197.3, 144.6, 135.0, 132.8,
131.7, 128.7, 127.6, 126.9, 125.1, 51.1, 16.1; IR (neat) 3058, 3025,
2910, 1696, 1618, 1470, 1439, 1074, 1026, 919, 742 cm−1; HRMS
(ESI) calcd for C11H11ONaBr 260.9891 [M + Na]+, found 260.9891.
(E)-1-(2-Bromophenyl)pent-3-en-2-one (3aE): 599 mg, 84% yield,
(E)-1-(2-Bromo-4,5-dimethoxyphenyl)pent-3-en-2-one (3eE): 609 mg,
68% yield, white solid; mp 62−64 °C; 1H NMR (400 MHz, CDCl3) δ
7.04−6.95 (m, 2H), 6.71 (s, 1H), 6.21 (dq, J = 15.6, 1.5 Hz, 1H), 3.91
1
light yellow oil; H NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 8.0, 1.0
Hz, 1H), 7.28 (dt, J = 7.3, 1.3 Hz, 1H), 7.22 (dd, J = 7.6, 1.8 Hz, 1H),
10074
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
(s, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 1.91 (dd, J = 6.9, 1.6 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ 196.3, 148.6, 148.4, 143.7, 130.8, 126.6,
115.4, 114.9, 113.9, 56.1, 56.0, 47.0, 18.3; IR (KBr) 2935, 2840, 1685,
1630, 1507, 1439, 1382, 1259, 1218, 1165, 1031, 969, 807 cm−1; HRMS
(EI) calcd for C13H15O3Br 298.0205 [M]+, found 298.0207.
1.6 Hz, 1H), 3.97 (s, 2H), 1.91 (dd, J = 6.9, 1.6 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 196.2, 143.9, 134.6, 133.2, 131.8, 131.1, 129.7,
128.7, 127.1, 45.1, 18.5; IR (neat) 3060, 2969, 2912, 1683, 1630, 1474,
1443, 1333, 1187, 1053, 968, 751 cm−1; HRMS (EI) calcd for C11H11OCl
194.0498 [M]+, found 194.0508.
(Z)-1-(2-Bromo-4-fluorophenyl)pent-3-en-2-one (3fZ): 80 mg,
10% yield, white solid; mp 58−60 °C; H NMR (400 MHz, CDCl3)
δ 7.33 (dd, J = 8.2, 2.6 Hz, 1H), 7.19 (dd, J = 8.5, 6.0 Hz, 1H), 7.01 (td,
J = 8.3, 2.6 Hz, 1H), 6.32−6.18 (m, 2H), 3.88 (s, 2H), 2.15−2.11 (m,
3H); 13C NMR (101 MHz, CDCl3) δ 196.97, 161.4 (d, JCF = 250.0 Hz),
144.7, 132.4 (d, JCF = 8.4 Hz), 131.0 (d, JCF = 3.6 Hz), 126.7, 125.0 (d,
Representative Procedure for the Preparation of 2-Naphthols
4. A mixture of Pd(PPh3)4 (58 mg, 0.05 mmol, 10 mol %), NaHCO3
(84 mg, 1.0 mmol, 2.0 equiv), 3aE (120 mg, 0.5 mmol), and NMP
(5 mL) was stirred at 120 °C under a N2 atmosphere. The reaction
progress was monitored via TLC. TLC analysis indicated that the reac-
tion was complete after the mixture was stirred for 3 h. The mixture
was then allowed to cool to room temperature. Water (20 mL) was
added to the resultant mixture, and the product was extracted with
ethyl acetate (10 mL × 3). The combined extracts were washed with
brine (10 mL × 2), dried over Na2SO4, and evaporated in vacuo. The
residue obtained was purified via silica gel chromatography (eluent:
ethyl acetate/petroleum ether = 1:10) to give 3a as a red solid.
4-Methylnaphthalen-2-ol (4a):.25 68 mg, 86% yield, red solid; mp
1
J
CF = 9.5 Hz), 120.0 (d, JCF = 24.4 Hz), 114.7 (d, JCF = 21.0 Hz), 50.1,
16.0; IR (KBr) 3069, 3027, 2956, 2923, 2871, 1696, 1621, 1600, 1488,
1299, 1074, 921, 884, 858 cm−1; HRMS (EI) calcd for C11H10BrFO
255.9899 [M]+, found 255.9907.
(E)-1-(2-Bromo-4-fluorophenyl)pent-3-en-2-one (3fE): 645 mg,
1
84%, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.32 (dd, J =
8.2, 2.6 Hz, 1H), 7.18 (dd, J = 8.5, 6.0 Hz, 1H), 7.03−6.94 (m, 2H),
6.21 (dd, J = 15.7, 1.6 Hz, 1H), 3.95 (s, 2H), 1.92 (dd, J = 6.9, 1.6 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 195.7, 161.4 (d, JCF = 249.9
Hz), 143.8, 132.4 (d, JCF = 8.4 Hz), 130.94, 130.89 (d, JCF = 3.7 Hz),
124.9 (d, JCF = 9.5 Hz), 119.9 (d, JCF = 24.4 Hz), 114.7 (d, JCF = 21.0
Hz), 46.5, 18.3; IR (neat) 3067, 3038, 2971, 2913, 2852, 1684, 1633,
1600, 1488, 1231, 969, 881, 859 cm−1; HRMS (EI) calcd for C11H10BrFO
255.9899 [M]+, found 255.9906.
1
72−74 °C; H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.3 Hz, 1H),
7.65 (d, J = 8.1 Hz, 1H), 7.41 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.5 Hz,
1H), 6.98−6.95 (m, 2H), 5.24 (s, 1H), 2.63 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 152.9, 136.9, 134.9, 128.3, 127.1, 126.3, 124.1, 123.5,
118.6, 107.8, 19.3; IR (KBr) 3369, 3066, 2920, 2859, 1622, 1602,
1512, 1462, 1349, 1282, 1233, 1172, 1133, 1000, 857, 769, 745 cm−1
HRMS (EI) calcd for C11H10O 158.0732 [M]+, found 158.0737.
;
4-Methylphenanthren-2-ol (4b): 66 mg, 63% yield, red solid; mp
126−128 °C; 1H NMR (400 MHz, CDCl3) δ 8.79 (d, J = 8.5 Hz, 1H),
7.88−7.85 (m, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.62−7.48 (m, 3H), 7.08
(dd, J = 28.3, 2.6 Hz, 2H), 3.07 (s, 3H); 13C NMR (101 MHz, CDCl3)
δ 152.9, 138.0, 135.5, 132.5, 131.8, 128.8, 127.9, 127.3, 126.7, 125.8,
125.0, 124.6, 120.8, 110.9, 27.4; IR (KBr) 3318, 3050, 2962, 2874,
1613, 1602, 1467, 1453, 1265, 1173, 993, 866, 856, 806, 744, 707
cm−1; HRMS (EI) calcd for C15H12O 208.0888 [M]+, found 208.0878.
4-Methylphenanthren-2-ol (4c): 74 mg, 86% yield, red oil; 1H
NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.57 (d, J = 8.3 Hz, 1H),
7.29−7.25 (m, 1H), 6.97−6.93 (m, 2H), 4.99 (s, 1H), 2.63 (s, 3H),
2.50 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 152.4, 136.0, 133.1,
132.8, 128.5, 128.4, 127.0, 123.3, 118.8, 107.8, 21.9, 19.4; IR (neat)
3373, 3048, 2920, 2858, 1634, 1612, 1512, 1440, 1395, 1287, 1139,
970, 854, 732 cm−1; HRMS (EI) calcd for C12H12O 172.0888 [M]+,
found 172.0881.
(Z)-1-(2-Bromo-4-chlorophenyl)pent-3-en-2-one (3gZ): 68 mg,
8% yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.59 (d,
1
J = 2.1 Hz, 1H), 7.27 (dd, J = 8.4, 1.9 Hz, 1H), 7.16 (d, J = 8.2 Hz, 1H),
6.32−6.20 (m, 2H), 3.88 (s, 2H), 2.13 (dd, J = 6.9, 1.3 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ 196.7, 145.1, 133.6, 132.4, 132.4, 127.8,
126.7, 125.4, 50.37, 16.11; IR (neat) 3026, 2912, 2852, 1694, 1621,
1471, 1435, 1314, 1074, 1038, 921, 866, 837, 817 cm−1; HRMS (ESI)
calcd for C11H10BrClNaO 294.9501 [M + Na]+, found 294.9502.
(E)-1-(2-Bromo-4-chlorophenyl)pent-3-en-2-one (3gE): 613 mg,
75% yield, white solid; mp 32−34 °C; 1H NMR (400 MHz, CDCl3) δ
7.59 (d, J = 2.1 Hz, 1H), 7.28−7.25 (m, 1H), 7.15 (d, J = 8.2 Hz, 1H),
6.99 (dq, J = 15.6, 6.9 Hz, 1H), 6.21 (dq, J = 15.7, 1.6 Hz, 1H), 3.96
(s, 2H), 1.93 (dd, J = 6.9, 1.7 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ 195.5, 144.1, 133.6, 133.5, 132.4, 130.93, 127.8, 125.3, 46.7, 18.4; IR
(KBr) 3036, 2912, 2852, 1691, 1674, 1632, 1588, 1471, 1440, 1378,
1327, 1187, 1039, 968, 864 cm−1; HRMS (ESI) calcd for C11H10BrClNaO
294.9501 [M + Na]+, found 294.9499.
6-Methoxy-4-methylnaphthalen-2-ol (4d): 84 mg, 89% yield, red
1
solid; mp 108−110 °C; H NMR (400 MHz, CDCl3) δ 7.58 (d, J =
(Z)-1-(2,4-Dibromophenyl)pent-3-en-2-one (3hZ): 69 mg, 7%
1
8.9 Hz, 1H), 7.17−7.11 (m, 2H), 6.96 (d, J = 6.3 Hz, 2H), 4.95 (s,
1H), 3.92 (s, 3H), 2.61 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
155.9, 151.5, 135.2, 130.1, 128.9, 128.6, 119.1, 118.4, 108.0, 103.3,
55.4, 19.5; IR (KBr) 3404, 2933, 2833, 1608, 1514, 1444, 1397, 1249,
1160, 1036, 851 cm−1; HRMS (EI) calcd for C12H12O2 188.0837
[M]+, found 188.0835.
yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.74 (d, J =
1.8 Hz, 1H), 7.41 (dd, J = 8.1, 1.8 Hz, 1H), 7.10 (d, J = 8.2 Hz, 1H),
6.30−6.20 (m, 2H), 3.87 (s, 2H), 2.13 (d, J = 6.6 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 196.5, 145.0, 135.1 134.1, 132.8, 130.7, 126.7,
125.7, 121.3, 50.4, 16.1; IR (neat) 3077, 3025, 2909, 1694, 1620, 1580,
1467, 1072, 1036, 921, 867, 832, 813 704 cm−1; HRMS (EI) calcd for
C11H10OBr2 315.9098 [M]+, found 315.9093.
(E)-1-(2,4-Dibromophenyl)pent-3-en-2-one (3hE): 799 mg, 84%
yield, white solid; mp 42−44 °C; 1H NMR (400 MHz, CDCl3) δ 7.73
(d, J = 1.8 Hz, 1H), 7.42−7.39 m, 1H), 7.09 (d, J = 8.2 Hz, 1H), 6.99
(dq, J = 13.7, 6.8 Hz, 1H), 6.20 (dd, J = 15.7, 1.4 Hz, 1H), 3.94 (s,
2H), 1.93 (dd, J = 6.9, 1.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
195.3, 144.0, 135.1, 134.0, 132.8, 130.9, 130.7, 125.6, 121.3, 46.8, 18.4;
IR (KBr) 3036, 2969, 2911, 1688, 1672, 1631, 1579, 1468, 1326, 1187,
1036, 968, 812 cm−1; HRMS (EI) calcd for C11H10OBr2 315.9098
[M]+, found 315.9091.
6,7-Dimethoxy-4-methylnaphthalen-2-ol (4e):.26 88 mg, 81%
1
yield, light red solid; mp 164−166 °C; H NMR (400 MHz, CDCl3) δ
7.13 (s, 1H), 6.98 (s, 1H), 6.92 (d, J = 2.3 Hz, 1H), 6.83 (d, J = 1.6 Hz,
1H), 4.80 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H), 2.60 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 152.1, 149.8, 147.5, 135.0, 130.6, 123.18, 116.5,
107.1, 105.9, 103.3, 55.82, 55.79, 19.6; IR (KBr) 3452, 3002, 2956, 2829,
1633, 1510, 1399, 1272, 1250, 1162, 1063, 862, 771 cm−1; HRMS (EI)
calcd for C13H14O3 218.0943 [M]+, found 218.0934.
6-Fluoro-4-methylnaphthalen-2-ol (4f): 31 mg, 35% yield, light
yellow solid; mp 86−88 °C; 1H NMR (400 MHz, CDCl3) δ 7.65 (dd,
J = 9.0, 5.8 Hz, 1H), 7.51 (d, J = 10.9 Hz, 1H), 7.22 (t, J = 8.7 Hz,
1H), 7.00 (d, J = 4.5 Hz, 2H), 4.93 (s, 1H), 2.61 (s, 3H); 13C NMR
(Z)-1-(2-Chlorophenyl)pent-3-en-2-one (3iZ): 61 mg, 10% yield,
1
light yellow oil; H NMR (400 MHz, CDCl3) δ 7.39 (dd, J = 6.6, 2.7
Hz, 1H), 7.23−7.20 (m, 3H), 6.29−6.20 (m, 2H), 3.89 (s, 2H), 2.12
(d, J = 5.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 197.3, 144.5,
134.5, 133.1, 131.7, 129.5, 128.5, 127.0, 126.8, 48.7 16.0; IR (neat)
3061, 3025, 2955, 2923, 2870, 1697, 1619, 1474, 1443, 1075, 1053,
920, 745 cm−1; HRMS (EI) calcd for C11H11OCl 194.0498 [M]+,
found 194.0510.
(101 MHz, CDCl3) δ 159.5 (d, JCF = 242.4 Hz), 152.4, 136.3 (d, JCF =
5.4 Hz), 131.8, 129.2 (d, JCF = 8.6 Hz), 128.9 (d, JCF = 8.1 Hz), 119.6,
116.5 (d, JCF = 25.1 Hz), 107.96 (d, JCF = 21.0 Hz), 107.95, 19.4; IR
(KBr) 3287, 2924, 2862, 1613, 1519, 1450, 1278, 1242, 1156, 852
cm−1; HRMS (EI) calcd for C11H9FO 176.0637 [M]+, found 176.0638.
6-Chloro-4-methylnaphthalen-2-ol (4g): 20 mg, 21% yield, yellow
1
(E)-1-(2-Chlorophenyl)pent-3-en-2-one (3iE): 494 mg, 85% yield,
solid; mp 90−92 °C; H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 1.6
1
light yellow oil; H NMR (400 MHz, CDCl3) δ 7.40−7.37 (m, 1H),
Hz, 1H), 7.60 (d, J = 8.7 Hz, 1H), 7.36 (dd, J = 8.7, 2.0 Hz, 1H), 6.98
7.23−7.21 (m, 3H), 6.98 (dq, J = 15.7, 6.9 Hz, 1H), 6.21 (dd, J = 15.7,
(s, 2H), 5.15 (s, 1H), 2.62 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
10075
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
153.3, 136.2, 133.3, 129.2, 129.0, 128.6, 127.2, 123.4, 119.7, 107.8,
19.4; IR (KBr) 3373, 2923, 2852, 1624, 1598, 1502, 1470, 1134, 1089,
889 cm−1; HRMS (EI) calcd for C11H9ClO 192.0342 [M]+, found
192.0339.
7.68 (d, J = 8.2 Hz, 1H), 7.45−7.40 (m, 1H), 7.35−7.30 (m, 1H), 7.15
(d, J = 2.3 Hz, 1H), 7.10 (dd, J = 8.8, 2.5 Hz, 1H), 5.06 (s, 1H).
ASSOCIATED CONTENT
4-Methyl-3,4-dihydronaphthalen-2(1H)-one (5):.27 32 mg, 40%
■
1
S
* Supporting Information
yield, light yellow oil; H NMR (400 MHz, CDCl3) δ 7.30−7.21 (m,
General information and copies of spectra for all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
3H), 7.13 (d, J = 7.2 Hz, 1H), 3.68−3.56 (m, 2H), 3.32−3.24 (m,
1H), 2.71 (dd, J = 16.6, 5.2 Hz, 1H), 2.34 (dd, J = 16.6, 7.5 Hz, 1H),
1.34 (d, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 210.4, 141.2,
132.8, 128.4, 127.0, 126.8, 126.0, 46.3, 44.6, 33.5, 20.1; IR (neat) 3023,
2961, 2874, 1718, 1489, 1458, 1236, 1107, 756 cm−1; HRMS (EI)
calcd for C11H12O 160.0888 [M]+, found 160.0883.
AUTHOR INFORMATION
■
Corresponding Author
*Email: (X.F.) fengxiujuan@dlut.edu.cn; (H.L.) liuhesong126@
126.com.
One-Pot Reactions of 1a, Tributylallylstannane, and CO. Pd-
(PPh3)4 (347 mg, 0.30 mmol, 10 mol %), 1a (750 mg, 3 mmol),
tributylallylstannane (993 mg, 3 mmol), NaHCO3 (504 mg, 6 mmol),
and NMP (30 mL) were placed in a 75 mL autoclave with a magnetic
stir bar under a N2 atmosphere. The autoclave was purged with CO
three times and then filled with CO to 0.3 MPa pressure. The auto-
clave was heated to 120 °C for 4 h. It was allowed to cool to room tem-
perature, and the remaining CO was vented. Water (20 mL) was added to
the resultant mixture, and the products were extracted with ethyl acetate
(10 mL × 3). The combined extracts were washed with brine (20 mL × 2)
and dried over Na2SO4. The solvent was removed in vacuo. The residue
obtained was purified via silica gel chromatography (eluent: ethyl acetate/
petroleum ether = 1:20) to give 4a (140 mg) and 6 (100 mg) in 29% and
18% yields, respectively.
ACKNOWLEDGMENTS
■
This work was funded by the National Natural Science Founda-
tion of China (Nos. 20972021 and 21073025) and the Specialized
Research Fund for the Doctoral Program of Higher Education
(No. 20090041110012).
REFERENCES
■
(1) For selected recent references, see: (a) Wang, H. Chirality 2010,
22, 827. (b) Gorth, F. C.; Rucker, M.; Eckhardt, M.; Bruckner, R. Eur.
̈
̈
(E)-3-(Prop-1-en-1-yl)-1H-isochromen-1-one (6): 100 mg, 18%
1
J. Org. Chem. 2000, 2605. (c) Krohn, K.; Zimmermann, G. J. Org.
Chem. 1998, 63, 4140. (d) Zhao, H.; Neamati, N.; Mazumder, A.;
Sunder, S.; Pommier, Y.; Burke, T. R. J. Med. Chem. 1997, 40, 1186.
(2) For selected examples of the electrophilic cyclization, see:
(a) Juteau, H.; Gareau, Y.; Lachance, H. Tetrahedron Lett. 2005, 46,
4547. (b) Zhang, X. X.; Sarkar, S.; Larock, R. C. J. Org. Chem. 2006,
71, 236.
yield, white solid; mp 89−90 °C; H NMR (400 MHz, CDCl3) δ
8.24 (d, J = 8.0 Hz, 1H), 7.65 (td, J = 7.9, 1.3 Hz, 1H), 7.42 (td, J =
8.0, 1.1 Hz, 1H), 7.36 (d, J = 7.9 Hz, 1H), 6.63 (dq, J = 13.8, 6.9 Hz,
1H), 6.24 (s, 1H), 6.05 (dd, J = 15.4, 1.7 Hz, 1H), 1.91 (dd, J = 6.9,
1.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 162.4, 152.7, 137.9,
134.8, 131.8, 129.8, 127.8, 125.7, 123.4, 120.8, 103.5, 18.5; IR (KBr)
3439, 3061, 2967, 2939, 2910, 1723, 1311, 1164, 1058, 959, 763 cm−1
HRMS (EI) calcd for C12H10O2 186.0681 [M]+, found 186.0675.
;
(3) For selected examples of the cyclodehydration, see: (a) Kel’in, A.
V.; Kozyrkov, Y. Y. Synthesis 1998, 729. (b) Daniewski, A. R.; Kiegiel,
J. J. Org. Chem. 1988, 53, 5535. (c) Teresa, J. D.; Mateos, A. F.;
Gonzalez, R. R. Tetrahedron Lett. 1982, 23, 3405.
(4) For selected examples of the oxidative cyclization, see: (a) Cooke,
H. A.; Zhang, J.; Griffin, M. A.; Nonaka, K.; Van Lanen, S. G.; Shen,
B.; Bruner, S. D. J. Am. Chem. Soc. 2007, 129, 7728. (b) Ji, N.; Rosen,
B. M.; Myers, A. G. Org. Lett. 2004, 6, 4551. (c) Citterio, A.; Pesce, L.;
Sebastiano, R.; Santi, R. Synthesis 1990, 142.
(5) For selected examples of the rhodium(II)-catalyzed cycloiso-
merization, see: (a) Collomb, D.; Chantegrel, B.; Deshayes, C. Tetra-
hedron 1996, 52, 10455. (b) Taylor, E. C.; Davies, H. M. L. Tetra-
hedron Lett. 1983, 24, 5453.
Synthesis of 2-Naphthol 8 Using 2-Bromobenzyl Bromide
1a, Tributylvinylstannane, and CO as Starting Materials. Pd-
(PPh3)4 (139 mg, 0.12 mmol, 4 mol %), 1a (750 mg, 3 mmol),
tributylvinylstannane (951 mg, 3 mmol), and MeCN (12 mL) were
placed in a 75 mL autoclave with a magnetic stir bar under a N2 atmo-
sphere. The autoclave was purged with CO three times, filled with CO
to 0.3 MPa pressure, and heated to 80 °C for 2 h. The autoclave was
allowed to cool to room temperature and the remaining CO was
vented. The resultant mixture was evaporated in vacuo to give the
crude product, which was then purified via silica gel chromatography
(eluent: ethyl acetate/petroleum ether = 1:20) to afford 7 as a light
yellow oil.
(6) For selected examples of photo- or thermal-promoted cyclization:
(a) Padwa, A.; Chiacchio, U.; Fairfax, D. J.; Kassir, J. M.; Litrico, A.;
Semones, M. A.; Xu, S. L. J. Org. Chem. 1993, 58, 6429. (b) Padwa, A.;
Austin, D. J.; Chiacchio, U.; Kassir, J. M.; Rescifina, A.; Xu, S. L.
Tetrahedron Lett. 1991, 32, 5923.
A mixture of Pd(OAc)2 (11 mg, 0.05 mmol, 10 mol %), TBAB
[tetra-n-butylammonium bromide, 322 mg, 0.1 mmol, 2 equiv], Et3N
(101 mg, 1.0 mmol, 2 equiv), 7 (113 mg, 0.5 mmol), and MeCN (10 mL)
was stirred at 70 °C under a N2 atmosphere. The reaction progress was
monitored via TLC. TLC analysis indicated that the reaction was
complete after the mixture was stirred for 2 h. The mixture was then
allowed to cool to room temperature. Water (20 mL) was added to the
resultant mixture, and the product was extracted with ethyl acetate (10
mL × 3). The combined extracts were washed with brine (10 mL × 2),
dried over Na2SO4, and evaporated in vacuo. The residue obtained was
purified via silica gel chromatography (eluent: ethyl acetate/petroleum
ether = 1:10) to give 8 as a light yellow solid.
(7) For selected examples of the aldol condensation, see: (a) Fernan
M. Synthesis 2009, 3051. (b) Martínez, A.; Fernandez, M.; Estevez, J. C.;
Estevez, R. J.; Castedo, L. Tetrahedron 2005, 61, 1353 and references
cited therein. (c) Martínez, A.; Fernandez, M.; Estevez, J. C.; Estevez, R.
J.; Castedo, L. Tetrahedron 2005, 61, 485.
́
dez,
́
́
́
́
́
́
(8) For selected examples of Dieckmann condensation, see: (a) Fei,
Z. B.; McDonald, F. E. Org. Lett. 2005, 7, 3617. (b) Martinez, A. D.;
Deville, J. P.; Stevens, J. L.; Behar, V. J. Org. Chem. 2004, 69, 991 and
references cited therein. (c) Deville, J. P.; Behar, V. Org. Lett. 2002, 4,
1403. (d) Terao, Y.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron
2000, 56, 1315. (e) Watanabe, M.; Date, M.; Furukawa, S. Chem.
Pharm. Bull. 1989, 37, 292.
1-(2-Bromophenyl)but-3-en-2-one (7): 506 mg, 75% yield, light
1
yellow oil; H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 1H),
7.29 (t, J = 7.4 Hz, 1H), 7.22 (dd, J = 7.5, 1.5 Hz, 1H), 7.15 (td,
J = 7.8, 1.7 Hz, 1H), 6.45 (dd, J = 17.6, 10.1 Hz, 1H), 6.36 (dd, J =
17.5, 1.3 Hz, 1H), 5.88 (dd, J = 10.1, 1.4 Hz, 1H), 4.06 (s, 2H); 13C
NMR (101 MHz, CDCl3) δ 196.4, 135.6, 134.5, 132.8, 131.8, 129.1,
128.8, 127.6, 125.0, 47.1; IR (neat) 3057, 3019, 2910, 1692, 1471,
1440, 1397, 1334, 1078, 1026, 986, 749 cm−1; HRMS (EI) calcd for
C10H9BrO 223.9837 [M]+, found 223.9826.
(9) Tsukamoto, H.; Kondo, Y. Org. Lett. 2007, 9, 4227.
(10) (a) Peng, B.; Feng, X. J.; Zhang, X.; Zhang, S.; Bao, M. J. Org.
Chem. 2010, 75, 2619. (b) Peng, B.; Feng, X. J.; Zhang, X.; Ji, L. Y.;
Bao, M. Tetrahedron 2010, 66, 6013. (c) Lu, S. R.; Xu, Z. W.; Bao, M.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2008, 47, 4366. (d) Bao, M.;
Nakamura, H.; Yamamoto, Y. J. Am. Chem. Soc. 2001, 123, 759.
Naphthalen-2-ol (8):.28 43 mg, 59% yield, light yellow solid; mp
100−102 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (t, J = 7.6 Hz, 2H),
10076
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077

The Journal of Organic Chemistry
Article
(11) For selected reviews, see: (a) Foster, C. E.; Mackie, P. R. Ketones:
α,β-Unsaturated Ketones. In Comprehensive Organic Functional Group
Transformations II; Katritzky, A. R., Taylor, R. J. K., Eds.; Elsevier:
Oxford, 2004; Vol. 3, pp 215−266. (b) Ebenezer, W. J.; Wight, P.
Ketones: α,β-Unsaturated Ketones. In Comprehensive Organic Functional
Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W.,
Eds.; Pergamon Press: Oxford, 1995; Vol. 3, pp 205−276.
(12) For selected examples of β,γ-unsaturated ketone synthesis, see:
(a) Randell-Sly, H. E.; Osborne, J. D.; Woodward, R. L.; Currie, G. S.;
Willis, M. C. Tetrahedron 2009, 65, 5110 and references cited therein.
(b) Wang, S. H.; Tu, Y. Q.; Wang, M. Tetrahedron Lett. 2006, 47, 8621
and references cited therein. (c) Liu, Y. J.; Zhang, Y. M. Tetrahedron
Lett. 2004, 45, 1295 and references cited therein.
(13) A similar selective reactivity was observed in the Heck reaction
of ortho bromoiodobenzenes: (a) Satyanarayana, G.; Maier, M. E. Org.
̀
Lett. 2008, 10, 2361. (b) Bruyere, D.; Gaignard, G.; Bouyssi, D.;
Balme, G.; Lancelin, J.-M. Tetrahedron Lett. 1997, 38, 827.
(14) Minatti, A.; Zheng, X. L.; Buchwald, S. L. J. Org. Chem. 2007, 72,
9253 and references cited therein.
(15) For an example of isocoumarin synthesis, see: Tadd, A. C.;
Fielding, M. R.; Willis, M. C. Chem. Commun. 2009, 6744.
(16) Carpino, L. A.; Lin, Y. Z. J. Org. Chem. 1990, 55, 247.
(17) Landais, Y.; Robin, J. P.; Lebrun, A. Tetrahedron 1991, 47, 3787.
(18) Musso, D. L.; Orr, G. F.; Cochran, F. R.; Kelley, J. L.; Selph, J.
L.; Rigdon, G. C.; Cooper, B. R.; Jones, M. L. J. Med. Chem. 2003, 46,
409.
(19) Campiani, G.; Butini, S.; Fattorusso, C.; Trotta, F.; Gemma, S.;
Catalanotti, B.; Nacci, V.; Fiorini, I.; Cagnotto, A.; Mereghetti, I.;
Mennini, T.; Minetti, P.; Di Cesare, M. A.; Stasi, M. A.; Di Serio, S.;
Ghirardi, O.; Tinti, O.; Carminati, P. J. Med. Chem. 2005, 48, 1705.
(20) Zhidkov, M. E.; Baranova, O. V.; Balaneva, N. N.; Fedorov, S.
N.; Radchenko, O. S.; Dubovitskii, S. V. Tetrahedron Lett. 2007, 48,
7998.
(21) Jolad, S. D.; Rajagopalan, S. Org. Synth. 1966, 46, 13.
(22) Chaumontet, M.; Piccardi, R.; Audic, N.; Hitce, J.; Peglion, J. L.;
Clot, E.; Baudoin, O. J. Am. Chem. Soc. 2008, 130, 15157.
(23) Wagner, P. J.; Wang, L. L. Org. Lett. 2006, 8, 645.
(24) Bower, J. F.; Szeto, P.; Gallagher, T. Org. Biomol. Chem. 2007, 5,
143.
(25) Baxter, G. J.; Brown, R. F. C. Aust. J. Chem. 1975, 28, 1551.
(26) Nagao, Y.; Lee, W. S.; Komaki, Y.; Sano, S.; Shiro, M. Chem.
Lett. 1994, 23, 597.
(27) Silveira, C. C.; Machado, A.; Braga, A. L.; Lenardao, E. J.
̃
Tetrahedron Lett. 2004, 45, 4077.
(28) Molander, G. A.; Cavalcanti, L. N. J. Org. Chem. 2010, 76, 623.
10077
dx.doi.org/10.1021/jo201907t | J. Org. Chem. 2011, 76, 10068−10077