Lewis-acid-promoted arylation reaction: Synthesis of dihydrobenzofuran derivatives from aryltriazenes

Article abstract of DOI:10.1002/ejoc.201200902

A Lewis-acid-promoted approach to the synthesis of highly functionalized dihydrobenzofuran derivatives was developed. A diverse range of functional groups are tolerated in this type of reaction. The reaction mechanism investigation indicates that the highly reactive phenyl cation intermediate is probably involved in this process. The chirality of substrate is retained under the reaction conditions.

Full text of DOI:10.1002/ejoc.201200902

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FULL PAPER
DOI: 10.1002/ejoc.201200902
Lewis-Acid-Promoted Arylation Reaction: Synthesis of Dihydrobenzofuran
Derivatives from Aryltriazenes
Guoqing Zhao,[a] Binjie Wang,[a] Weijun Yang,[a] and Hongjun Ren*[a,b]
Keywords: Synthetic methods / Oxygen heterocycles / Carbocations / Lewis acids / Cyclization
A Lewis-acid-promoted approach to the synthesis of highly
functionalized dihydrobenzofuran derivatives was devel-
oped. A diverse range of functional groups are tolerated in
this type of reaction. The reaction mechanism investigation
indicates that the highly reactive phenyl cation intermediate
is probably involved in this process. The chirality of substrate
is retained under the reaction conditions.
catalyst was developed by Buchwald and Hartwig.[6] The
intramolecular Heck reaction,[7] which was used in the total
synthesis of galanthamine (1b),[8] is another good method
Introduction
Dihydrobenzofuran rings are common structural motifs
in many natural and pharmaceutical products, such as (–)-
serotobenine (1a, Scheme 1), (–)decursivine (1b),[1] galanth-
amine (1c),[2,8] and beraprost (1d),[3] most of which show
strong biological activity. Hence, effective methods for the
synthesis of dihydrobenzofurans have been developed over
the past decades (Scheme 2).[4] The transition-metal-cata-
lyzed synthesis of dihydrobenzofurans has proved to be a
robust method. The formation of C–O bonds[5] using Pd as
Scheme 1. Natural and pharmaceutical products containing a dihy-
drobenzofuran moiety.
[a] Department of Chemistry, Zhejiang University
Hangzhou 310027, P. R. China
Fax: +86-571-8795-1512
E-mail: renhj@zstu.edu.cn
[b] Department of Chemistry, Zhejiang Sci-Tech University
Hangzhou 310018, P. R. China
Scheme 2. Strategies for the synthesis of dihydrobenzofurans and
related compounds.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200902.
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G. Zhao, B. Wang, W. Yang, H. Ren
FULL PAPER
to synthesize dihydrobenzofuran cores. Intramolecular oxi- vents. When the reaction was carried out in dichlorometh-
dative cyclization of orthoallyl phenol,[9] intramolecular al- ane, the desired cyclization product (i.e., 3a) was formed in
kane arylation,[10] hydroxy-directed C–H activation/C–O the highest yield of 76%. The structure of 3a was confirmed
cyclization,[11] and carbenoid C–H insertion[12] also provide by X-ray analysis (Scheme 3).[17]
efficient methods to synthesize dihydrobenzofurans
(Scheme 2).
It is very important to find efficient ways to construct
heterocyclic compounds.[13] The direct nucleophilic substi-
tution of a phenyl cation is an efficient and straightforward
method for arylation, but the instability of phenyl cation[14]
limits its applicability. Recently, we have focused our inter-
est on the generation of reactive phenyl cations and their
application in the synthesis of heterocyclic compounds such
as unsymmetrical and highly functionalized carbazoles and
dibenzofurans.[15] In this paper, we describe a Lewis-acid-
promoted protocol for the synthesis of dihydrobenzofurans
from aryl triazenes.[16]
Scheme 3. Screening of different solvents for the cyclization reac-
tion of 2a, and X-ray crystal structure of 3a.
Results and Discussion
Initially, we treated triazene alcohol 2a with BF3·OEt2 in
Triazene alcohol derivatives were prepared from the cor-
different solvents (Scheme 3), and we found that the cycliza- responding iodoaryltriazenes. The iodoaryltriazenes were
tion reaction occurred in both polar and non-polar sol- transformed into the corresponding Grignard reagents
Scheme 4. Synthesis of triazene alcohols from iodoaryltriazenes by metal–halogen exchange. Isolated yields after flash chromatography
are shown.
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Lewis-Acid-Promoted Arylation
smoothly by metal–halogen exchange with iPrMgCl.[18] The corresponding dihydrobenzofurans. However, electron-
reaction of these Grignard reagents with epoxides[19] pro- withdrawing groups such as fluoro decreased the yield (to
vided the triazene alcohol derivatives in moderate to good 27% for 3p). Under these mild reaction conditions, the terti-
yields, and a variety of examples are shown in Scheme 4.
ary alcohols gave the desired dihydrobenzofurans success-
The generality of the BF3·OEt2-promoted cyclization is fully in 40–78% yields (3o, 3q, and 3r). Substrates 2r and
shown in Scheme 5. A variety of secondary alcohols were 2s bearing bromide on the aromatic ring afforded bromo-
cyclized to form the corresponding dihydrobenzofurans in dihydrobenzofurans 3r and 3s in 40 and 43% yields, respec-
moderate to good yields (3b–f, 3h–n, and 3s). Functional tively.
groups such as alkenyl (3j, 3k, and 3m), ester (3b–g, 3i, 3j,
This method could be extended to the synthesis of com-
3n–q, and 3t–v), cyano (3d), and azido (3e), were tolerated pounds containing sixmembered rings. Primary alcohol 2t
in this BF3·OEt2-promoted process. The secondary alcohols and secondary alcohols 2u and 2v all provided the desired
bearing αsubstituents such as chloride, cyano, N- 6Hdibenzo[b,d]pyran derivatives (i.e., 3t–v) in 44–57%
phthalimido, and even azido, afforded the corresponding yields (Scheme 6).
dihydrobenzofurans (i.e., 3c–e and 3i) in moderate to good
We next turned our attention to the cyclization of op-
yields. Steric hindrance near to the reaction center (as in tically active triazene alcohols to determine whether the op-
the formation of 3l–o) did not decrease the yields of the tical purity was retained under these reaction conditions. As
Scheme 5. Synthesis of functionalized dihydrobenzofurans. All reactions were carried out with triazene alcohol (0.5 mmol), BF3·OEt2
(1.0 mmol) in CH2Cl2 (20 mL) at 40 °C for 4 h, except for the synthesis of 3r, which was carried out for 24 h. Isolated yields after flash
chromatography are shown.
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G. Zhao, B. Wang, W. Yang, H. Ren
FULL PAPER
and then decompose to generate an aryl cation, which can
cyclize onto the hydroxy group.
Conclusions
In summary, we have developed a Lewis-acid-promoted
approach to the synthesis of highly functionalized dihydro-
benzofurans in moderate to good yields. These reactions
were carried out under mild reaction conditions with good
tolerance of a variety of functional groups. Mechanistic in-
Scheme 6. Synthesis of compounds containing sixmembered rings vestigations indicated that a highly reactive phenyl cation
from triazene alcohols.
intermediate is probably involved in the reaction. Further
investigations of the reaction mechanism and synthetic ap-
plications are underway.
shown in Scheme 7, the chirality of optically active triazene
alcohols (S)4a and (S)4b was retained during the course of
cyclization sequence.
Experimental Section
General Methods: THF was dried with sodium and distilled freshly
before use. CH2Cl2 was dried with CaH2 and distilled freshly before
use. DMF was dried with CaH2 and distilled under reduced pres-
sure. Other materials and solvents were purchased from commer-
cial suppliers and used without additional purification. NMR spec-
tra were recorded on Bruker Avance spectrometers operating for 1H
NMR at 400 or 500 MHz, and for 13C NMR at 100 or 125 MHz.
Chemical shifts were calibrated using residual CHCl3 (δ
=
7.26 ppm) for 1H NMR, and CDCl3 (δ = 77.0 ppm) for 13C NMR.
Mass spectroscopy data of the products were collected with an
HRMS-TOF instrument or a low-resolution MS instrument using
EI ionization. Infrared spectra were recorded with a Bruker ATR-
FTIR spectrometer. Melting points were measured with a WRS-
1A digital point apparatus.
Scheme 7. Cyclization of optically active triazene alcohols.
In this reaction, the initial interaction between the ter-
minal nitrogen atom of the triazene and the Lewis acid gen-
erates a complex, decomposes to form aryl cations and aryl
radicals.[20] In order to probe the reaction mechanism, a
radical-inhibition test was performed for the standard reac-
Typical Procedure for the Synthesis of Aryltriazenes: Aniline
(10 mmol, 1.0 equiv.) was dissolved in CH3CN (10 mL) at room
temperature, and then concentrated hydrochloric acid (4 mL,
50 mmol, 5.0 equiv.) was added. The resulting solution was stirred
and cooled to –10 °C. After 15 min, a solution of NaNO2
tion conditions. When radical scavengers, such as butylated (10.5 mmol, 1.05 equiv.) in cold water (10 mL) was added dropwise.
The resulting solution of the diazonium salt was stirred for 30 min
and then added to a solution of pyrrolidine (11.0 mmol, 1.1 equiv.)
and K2CO3 (25.0 mmol, 2.5 equiv.) in CH3CN/H2O (1:2, 30 mL),
which was previously cooled to –10 °C. The reaction mixture was
warmed to room temperature and stirred for 30 min. After comple-
tion of the reaction, as monitored by TLC, the reaction mixture
was extracted with ethyl acetate (3ϫ 15 mL). The organic extracts
were dried with Na2SO4, filtered, concentrated under reduced pres-
sure, and purified by silica gel chromatography (eluent: hexanes/
EtOAc, 50:1).
hydroxytoluene (BHT), 2,2,6,6-tetramethylpiperidinooxy
(TEMPO), or 1,1-diphenylethylene, were added to reac-
tions, the yields of the reactions were not affected
(Scheme 8). These results suggest that the reaction does not
go via aryl radical intermediates. The triazene may initially
form a diazonium salt in the presence of the Lewis acid,
General Procedure for the Preparation of Triazene Alcohol Deriva-
tives 2a–2c, 2f–2h, 2j, 2k and 2q–2s: In a dry and N2-flushed 50 mL
Schlenk tube, ethyl 3-iodo-4-(pyrrolidin-1-yldiazenyl)benzoate
(1.49 g, 4.0 mmol, 1.0 equiv.) was dissolved in dry THF (4.0 mL).
iPrMgCl (0.984 m in THF, 4.90 mL, 4.80 mmol, 1.2 equiv.) was
then added dropwise at –30 °C. After 3 h, a complete conversion
into the corresponding Grignard reagent was observed, as indi-
cated by TLC and GC analysis. A CuCN·2LiCl solution (1.0 m in
THF, 0.2 mL, 0.2 mmol, 0.05 equiv.) and 7-oxabicyclo[4.1.0]hept-
ane (628 mg, 6.4 mmol, 1.6 equiv.) were added slowly to the re-
sulting reaction mixture. Then the reaction mixture was slowly
warmed to room temperature and stirred for 4 h before the addition
of saturated aqueous NH4Cl solution. The resulting reaction was
Scheme 8. Reaction results in the presence of radical inhibitors.
4
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Lewis-Acid-Promoted Arylation
quenched by saturated aqueous NH4Cl solution (5 mL), extracted
with ethyl acetate (3ϫ 10 mL). The organic layers were dried with
Na2SO4, filtered, concentrated under reduced pressure and purified
by flash chromatography on silica gel (hexanes/EtOAc, 5:1) to af-
ford 2a (0.926 g, 67%) as a yellow solid.
CHOH), 4.35 (q, J = 7.2 Hz, 2 H, CH3CH2O), 4.18–4.27 (m, 1 H,
CHOH), 3.99 (t, J = 6.6 Hz, 2 H, CH2N), 3.55–3.76 (m, 2 H,
CH2N), 3.18–3.28 (m, 1 H), 3.03–3.13 (m, 1 H), 2.53 (dq, J = 16.3,
J = 5.7 Hz, 2 H, CH2CHOH), 1.98–2.17 (m, 4 H, 2 CH2CH2N),
1.38 (t, J = 7.2 Hz, 3 H, CH3CH2) ppm. 13C NMR (100 MHz,
CDCl3): δ = 166.3, 152.4, 132.8, 130.7, 129.5, 127.0, 117.8, 116.6,
69.2, 60.8, 51.9, 47.4, 38.8, 26.1, 23.8, 23.5, 14.3 ppm. IR (thin
Ethyl 3-(2-Hydroxycyclohexyl)-4-[(E)-pyrrolidin-1-yldiazenyl]benzo-
ate (2a): Yellow solid, m.p. 101–103 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.01 (s, 1 H, ArH), 7.86 (d, J = 8.0 Hz, 1 H, ArH),
7.42 (d, J = 8.0 Hz, 1 H, ArH), 4.36 (q, J = 6.8 Hz, 2 H,
CH3CH2O), 3.98 (br., 2 H, CH2N), 3.51–3.75 (m, 3 H, CH2N and
OH), 3.20–3.40 (m, 2 H, CHOH and ArCH), 2.18–2.20 (m, 1 H),
1.95–2.07 (m, 4 H, 2 CH2CH2N), 1.74–1.84 (m, 4 H, 2 CH2), 1.30–
1.44 (m, 6 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.8, 152.8,
137.2, 128.6, 128.4, 127.1, 116.5, 75.3, 60.7, 51.3, 47.0, 45.6, 36.4,
film): ν = 3671, 2980, 2902, 1684, 1400, 1251, 1054, 895 cm–1. MS
˜
(EI): m/z (%) = 330 (21) [M]+, 285 (16), 260 (20), 246 (8), 232 (3),
204 (6), 186 (100). HRMS (EI-TOF): calcd. for C17H22N4O3 [M]+
330.1692; found 330.1696.
Ethyl 3-(3-Azido-2-hydroxypropyl)-4-(pyrrolidin-1-yldiazenyl)benzo-
ate (2e): NaN3 (975 mg, 15 mmol, 3.0 equiv.) and KI (83 mg,
0.5 mmol, 0.1 equiv.) were added to a solution of triazene alcohol
2c (1.70 g, 5 mmol, 1.0 equiv.) in DMF (50 mL). The reaction mix-
ture was stirred vigorously at 160 °C for 60 h before it was allowed
to cool to room temperature. Water was added to the reaction mix-
ture, and the resulting mixture was extracted with ethyl acetate.
The organic extracts were washed with H2O and brine, dried with
Na2SO4, filtered, concentrated in vacuo. After flash chromatog-
raphy (eluent: hexanes/EtOAc, 5:1), pure product 2e (1.006 g, 58%)
was obtained as a yellow solid, m.p. 75–77 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.88 (dd, J = 8.4, J = 2.0 Hz, 1 H, ArH), 7.85 (d, J =
2.0 Hz, 1 H, ArH), 7.49 (d, J = 8.4 Hz, 1 H, ArH), 5.48 (d, J =
3.6 Hz, 1 H, CHOH), 4.35 (q, J = 7.2 Hz, 2 H, CH3CH2O), 4.04–
4.13 (m, 1 H, CHOH), 3.99 (t, J = 6.6 Hz, 2 H, CH2N), 3.55–3.74
(m, 2 H, CH2N), 3.32–3.36 (m, 1 H), 3.12–3.18 (m, 1 H), 2.97–3.01
(m, 1 H), 1.98–2.16 (m, 4 H, 2 CH2CH2N), 1.38 (t, J = 7.0 Hz, 3
H, CH3CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.4, 152.4,
132.9, 131.8, 129.1, 126.9, 116.5, 72.5, 60.8, 56.5, 51.8, 47.3, 37.4,
31.7, 26.3, 25.1, 23.9, 23.5, 14.4 ppm. IR (thin film): ν = 3664,
˜
2979, 2902, 1700, 1599, 1402, 1247, 1071 cm–1. MS (EI): m/z (%)
= 345 (3) [M]+, 300 (13), 272 (12), 261 (65), 218 (32), 201 (17), 179
(100). HRMS (EI-TOF): calcd. for C19H27N3O3 [M]+ 345.2052;
found 345.2054.
Ethyl 3-(2-Hydroxypropyl)-4-(pyrrolidin-1-yldiazenyl)benzoate (2b):
Yield 871 mg, 71%, red solid, m.p. 76–77 °C. Rf = 0.15 (hexanes/
1
EtOAc, 5:1). H NMR (400 MHz, CDCl3): δ = 7.84–7.88 (m, 2 H,
ArH), 7.48 (d, J = 8.4 Hz, 1 H, ArH), 4.76 (s, 1 H, OH), 4.35 (q,
J = 7.1 Hz, 2 H, CH3CH2O), 4.05–4.15 (m, 1 H, CHOH), 3.92–
4.02 (m, 2 H, CH2N), 3.56–3.72 (m, 2 H, CH2N), 2.98–3.03 (m, 2
H, ArCH2), 2.00–2.08 (m, 4 H, 2 CH2CH2N), 1.39 (t, J = 7.2 Hz,
3 H, CH3CH2), 1.22 (d, J = 6.0 Hz, 3 H, CH3CH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 166.6, 152.5, 133.12, 133.07, 128.8, 126.8,
116.4, 69.4, 60.7, 51.6, 47.2, 41.9, 23.9, 23.6, 23.5, 14.4 ppm. IR
(thin film): ν = 3671, 2978, 2902, 1686, 1398, 1255, 1053 cm–1. MS
˜
23.8, 23.5, 14.3 ppm. IR (thin film): ν = 3672, 2981, 2902, 2105,
˜
(EI): m/z (%) = 305 (6) [M]+, 260 (20), 235 (9), 221 (38), 179 (100).
HRMS (EI-TOF): calcd. for C16H23N3O3 [M]+ 305.1739; found
305.1747.
1705, 1395, 1253, 1056, 901 cm–1. MS (EI): m/z (%) = 346 (16)
[M]+, 304 (53), 290 (22), 276 (22), 262 (13), 206 (11), 192 (11), 174
(14), 164 (24), 147 (36), 119 (59), 103 (22), 91 (100). HRMS (EI-
TOF): calcd. for C16H22N6O3 [M]+ 346.1753; found 346.1755.
Ethyl
3-(3-Chloro-2-hydroxypropyl)-4-(pyrrolidin-1-yldiazenyl)-
benzoate (2c): Yield 2.904 g, 85%. yellow solid, m.p. 68–70 °C. Rf
= 0.15 (hexanes/EtOAc, 5:1). 1H NMR (500 MHz, CDCl3): δ =
7.90 (s, 1 H, ArH), 7.88 (dd, J = 8.0, J = 2.0 Hz, 1 H, ArH), 7.49
(d, J = 9.0 Hz, 1 H, ArH), 5.51 (d, J = 4.0 Hz, 1 H, CHOH), 4.35
(q, J = 7.0 Hz, 2 H, CH3CH2O), 4.08–4.15 (m, 1 H, CHOH), 3.99
(t, J = 6.5 Hz, 2 H, CH2N), 3.60–3.70 (m, 2 H, CH2N), 3.46–3.54
(m, 2 H, CH2Cl), 3.11–3.22 (m, 2 H, CH2CHOH), 2.00–2.14 (m, 4
H, 2 CH2CH2N), 1.39 (t, J = 7.3 Hz, 3 H, CH3CH2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 166.5, 152.5, 133.0, 131.4, 129.2,
127.0, 116.5, 72.9, 60.8, 51.8, 48.7, 47.3, 36.8, 23.8, 23.5, 14.3 ppm.
Ethyl 3-(2-Hydroxy-2-phenylethyl)-4-(pyrrolidin-1-yldiazenyl)benzo-
ate (2f): Yield 476 mg, 32%. yellow solid, m.p. 141–144 °C. Rf =
1
0.2 (hexanes/EtOAc, 5:1). H NMR (500 MHz, CDCl3): δ = 7.88
(dd, J = 8.5, J = 2.0 Hz, 1 H, ArH), 7.79 (d, J = 2.0 Hz, 1 H,
ArH), 7.52 (d, J = 8.5 Hz, 1 H, ArH), 7.41 (d, J = 7.5 Hz, 2 H,
ArH), 7.34 (t, J = 7.5 Hz, 2 H, ArH), 7.24 (d, J = 7.0 Hz, 1 H,
ArH), 5.38 (d, J = 3.0 Hz, 1 H, OH), 5.00–5.08 (m, 1 H, CHOH),
4.35 (q, J = 3.0 Hz, 2 H, CH3CH2), 3.98–4.05 (m, 2 H, CH2N),
3.71–3.81 (m, 2 H, CH2N), 3.26–3.35 (m, 1 H), 3.17 (dd, J = 14.0,
J = 2.5 Hz, 1 H), 2.03–2.20 (m, 4 H, 2 CH2CH2N), 1.38 (t, J =
7.0 Hz, 3 H, CH3CH2) ppm. 13C NMR (125 MHz, CDCl3): δ =
166.6, 152.6, 145.2, 133.0, 132.8, 129.0, 128.2, 127.0, 126.9, 125.6,
116.4, 76.0, 60.7, 51.8, 47.3, 43.0, 23.9, 23.6, 14.3 ppm. IR (thin
IR (thin film): ν = 3672, 2983, 2902, 1699, 1603, 1403, 1314, 1254,
˜
1071, 899, 734 cm–1. MS (EI): m/z (%) = 341 (2) [M, Cl37]+, 339
(5) [M, Cl35]+, 303 (7), 294 (8), 269 (8), 195 (25), 179 (100). HRMS
(EI-TOF): calcd. for C16H22ClN3O3 [M]+ 339.1350; found
339.1354.
film): ν = 3672, 2979, 2902, 1700, 1395, 1256, 1053 cm–1. MS (EI):
˜
m/z (%) = 367 (2) [M]+, 350 (2), 294 (22), 283 (100), 261 (42), 232
(54), 223 (62), 178 (91). HRMS (EI-TOF): calcd. for C21H25N3O3
[M]+ 367.1896; found 367.1900.
Ethyl
3-(3-Cyano-2-hydroxypropyl)-4-(pyrrolidin-1-yldiazenyl)-
benzoate (2d): NaCN (588 mg, 12 mmol, 2 equiv.) and KI (100 mg,
0.6 mmol, 0.1 equiv.) were added to a solution of triazene alcohol
2c (2.04 g, 6 mmol, 1.0 equiv.) in DMF (50 mL). The reaction mix-
ture was stirred vigorously at 105 °C for 2.5 h before it was allowed
to cool to room temperature. Water was added to the reaction mix-
ture, and the resulting mixture was extracted with ethyl acetate.
The organic extracts were washed with H2O and brine, dried with
Na2SO4, and concentrated in vacuo. After flash chromatography
(eluent: hexanes/EtOAc, 5:1), pure product 2d (1.657 g, 84%) was
Ethyl 3-(2-Hydroxy-1-phenylethyl)-4-(pyrrolidin-1-yldiazenyl)benzo-
ate (2g): Yield 233 mg, 16%. red solid, m.p. 106–109 °C. Rf = 0.15
1
(hexanes/EtOAc, 5:1). H NMR (500 MHz, CDCl3): δ = 7.94 (d, J
= 1.5 Hz, 1 H, ArH), 7.87 (dd, J = 8.3, J = 1.8 Hz, 1 H, ArH),
7.49 (d, J = 8.5 Hz, 1 H, ArH), 7.28 (d, J = 4.5 Hz, 4 H, ArH),
7.19 (br., 1 H, ArH), 4.98 (t, J = 7.0 Hz, 1 H, CH), 4.33 (q, J =
7.2 Hz, 2 H, CH3CH2O), 4.18–4.30 (m, 2 H, CH2OH), 3.93 (br., 2
H, CH2N), 3.59 (br., 2 H, CH2N), 2.76 (br., 1 H, OH), 2.03 (m, 4
H, 2 CH2CH2N), 1.37 (t, J = 7.3 Hz, 3 H, CH3CH2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 166.7, 152.3, 141.7, 135.6, 130.0,
1
obtained as a yellow solid, m.p. 111–114 °C. H NMR (400 MHz,
CDCl3): δ = 7.90 (dd, J = 8.8, J = 1.6 Hz, 1 H, ArH), 7.87 (s, 1 H,
ArH), 7.49 (d, J = 8.4 Hz, 1 H, ArH), 5.85 (d, J = 3.6 Hz, 1 H,
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G. Zhao, B. Wang, W. Yang, H. Ren
13C NMR (100 MHz, CDCl3): δ = 166.5, 152.5, 134.7, 133.0, 132.3,
FULL PAPER
128.7, 128.4, 128.3, 126.7, 126.2, 116.5, 66.1, 60.7, 51.2, 47.9, 46.9,
23.8, 23.4, 14.3 ppm. IR (thin film): ν = 3672, 2978, 2902, 1684, 128.8, 126.7, 116.9, 116.3, 73.8, 72.2, 71.6, 60.6, 51.5, 47.1, 36.6,
˜
1394, 1254, 1059 cm–1. MS (EI): m/z (%) = 367 (4) [M]+, 349 (21),
322 (15), 283 (12), 265 (25), 223 (46), 179 (92), 165 (100). HRMS
(EI-TOF): calcd. for C21H25N3O3 [M]+ 367.1896; found 367.1894.
23.8, 23.4, 14.3 ppm. IR (thin film): ν = 3671, 2980, 2902, 1708,
˜
1396, 1253, 1073 cm–1. MS (EI): m/z (%) = 361 (6) [M]+, 316 (30),
290 (38), 277 (38), 260 (12), 232 (5), 217 (21), 206 (99), 191 (26),
177 (54), 163 (22), 147 (100). HRMS (EI-TOF): calcd. for
C19H27N3O4 [M]+ 361.2002; found 361.2008.
trans-2-{5-Methyl-2-[(E)-pyrrolidin-1-yldiazenyl]phenyl}cyclohex-
anol (2h): Yield 634 mg, 55%. red oil. Rf = 0.2 (hexanes/EtOAc,
1
1-(Allyloxy)-3-[5-methyl-2-(pyrrolidin-1-yldiazenyl)phenyl]propan-2-
ol (2k): Yield 1.177 g, 97%. red oil. Rf = 0.2 (hexanes/EtOAc, 5:1).
1H NMR (400 MHz, CDCl3): δ = 7.32 (d, J = 8.8 Hz, 1 H, ArH),
7.00 (br., 2 H, ArH), 5.88–6.00 (m, 1 H, CH=), 5.27 (d, J =
17.2 Hz, 1 H), 5.23 (s, 1 H), 5.17 (d, J = 10.8 Hz, 1 H), 4.04–4.13
(m, 1 H), 4.01 (t, J = 4.8 Hz, 2 H), 3.50–3.95 (br., 4 H, 2
CH2CH2N), 3.40–3.47 (m, 1 H), 3.32–3.39 (m, 1 H), 2.98–3.05 (m,
2 H), 2.30 (s, 3 H, CH3), 1.98 (m, 4 H, 2 CH2CH2N) ppm. 13C
NMR (100 MHz, CDCl3): δ = 146.6, 134.9, 134.8, 132.4, 132.1,
127.9, 116.7, 116.4, 74.0, 72.1, 71.8, 36.8, 23.7, 20.8 ppm. IR (thin
5:1). H NMR (400 MHz, CDCl3): δ = 7.28 (s, 1 H, ArH), 7.12 (s,
1 H, ArH), 7.00 (d, J = 8.0 Hz, 1 H, ArH), 3.80 (br., 4 H, 2 CH2N),
3.62–3.69 (m, 2 H), 3.17–3.27 (m, 1 H), 2.34 (s, 3 H, CH3), 2.15–
2.20 (m, 1 H), 2.05 (br. s, 4 H), 1.70–1.85 (m, 4 H), 1.27–1.43 (m,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 146.9, 136.8, 135.2,
127.6, 127.4, 116.7, 75.5, 45.5, 36.4, 31.6, 26.3, 25.2, 23.7, 21.2 ppm.
IR (thin film): ν = 3671, 2979, 2903, 1404, 1252, 1055, 893 cm–1.
˜
MS (EI): m/z (%) = 287 (13) [M]+, 203 (80), 160 (28), 121 (100),
105 (47), 91 (36). HRMS (EI-TOF): calcd. for C17H25N3O [M]+
287.1998; found 287.1988.
film): ν = 3665, 2976, 2903, 1405, 1317, 1258, 1219, 1073, 819 cm–1.
˜
Ethyl 3-[3-(1,3-Dioxoisoindolin-2-yl)-2-hydroxypropyl]-4-(pyrrolidin-
1-yldiazenyl)benzoate (2i): KI (9.96 g, 60 mmol, 10 equiv.) was
added to a solution of triazene alcohol 2c (2.04 g, 6 mmol,
1.0 equiv.) in acetone (45 mL). The reaction mixture was stirred
vigorously at reflux for 72 h. The solvent was then removed in
vacuo, and the residue was dissolved in water and extracted with
ethyl acetate. The organic extracts were washed with aqueous
Na2S2O3 and brine, dried with MgSO4, and concentrated in vacuo.
Ethyl 3-(2-hydroxy-3-iodopropyl)-4-(pyrrolidin-1-yldiazenyl) benz-
oate (2.107 g, 81%) was obtained after flash column chromatog-
raphy (eluent: hexanes/EtOAc, 5:1).
MS (EI): m/z (%) = 303 (20) [M]+, 279 (23), 233 (23), 219 (53), 176
(24), 161 (94), 145 (55), 133 (71), 121 (90), 105 (100). HRMS (EI-
TOF): calcd. for C17H25N3O2 [M]+ 303.1947; found 303.1955.
1-{[3-Iodo-5-methyl-(1,1Ј-biphenyl)-2-yl]diazenyl}pyrrolidine (1l): A
dry and N2-flushed 50 mL Schlenk tube, equipped with a magnetic
stirrer and a septum was charged with [(2,6-diiodo-4-methylphenyl)
pyrrolidin-1-yl]diazene (3.024 g, 6.86 mmol, 1.0 equiv.) in dry THF
(6 mL). iPrMgCl (0.984 m in THF, 8.4 mL, 8.30 mmol, 1.2 equiv.)
was then added dropwise at –30 °C. After 2 h, complete conversion
to the corresponding Grignard reagent was observed, as indicated
by TLC. ZnBr2 (1.0 m in THF, 9.0 mL, 9 mmol, 1.3 equiv.) was
added. The reaction mixture was allowed to warm slowly to room
temperature over 0.5 h. Then iodobenzene (0.8 mL, 7.09 mmol,
1.03 equiv.) and Pd(PPh3)4 (162 mg, 0.14 mmol, 0.02 equiv.) were
added. The reaction mixture was stirred at room temperature for
12 h, before being quenched by H2O. The resulting mixture was
extracted with ethyl acetate. The organic layers were dried with
Na2SO4, and concentrated in vacuo. Purification by flash
chromatography on silica gel (hexanes/EtOAc, 50:1) gave 1l (1.62 g,
61%) as a yellow solid, m.p. 110–111 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.69 (s, 1 H, ArH), 7.21–7.30 (m, 5 H, ArH), 7.11 (s,
1 H, ArH), 3.54 (t, J = 6.0 Hz, 4 H, 2 CH2N), 2.33 (s, 3 H, CH3),
1.91 (br., 4 H, 2 CH2CH2N) ppm. 13C NMR (100 MHz, CDCl3):
δ = 147.7, 140.6, 138.6, 136.1, 135.1, 131.9, 129.9, 127.5, 126.1,
Potassium 1,3-dioxoisoindolin-2-ide (1.11 g, 6 mmol, 2.0 equiv.)
was added to a solution of ethyl 3-(2-hydroxy-3-iodopropyl)-4-(pyr-
rolidin-1-yldiazenyl)benzoate (1.293 g, 3 mmol, 1.0 equiv.) in dry
DMF (6 mL). The reaction mixture was stirred vigorously at
100 °C for 8 h. After cooling, water was added to the reaction mix-
ture, and the resulting mixture was extracted with ethyl acetate. The
organic layers were washed with H2O and brine, dried with
Na2SO4, filtered, and concentrated in vacuo. After flash
chromatography (eluent: hexanes/EtOAc, 5:1), pure product 2i
(1.309 g, 97%) was obtained as a yellow solid . m.p.137–139 °C. 1H
NMR (500 MHz, CDCl3): δ = 7.84–7.90 (m, 2 H, ArH), 7.79–7.84
(m, 2 H, ArH), 7.65–7.72 (m, 2 H, ArH), 7.48 (d, J = 9.0 Hz, 1 H,
ArH), 4.81 (d, J = 4.6 Hz, 1 H, CHOH), 4.33 (q, J = 7.3 Hz, 2 H,
CH2O), 4.25–4.29 (m,
1 H, CHOH), 3.90–4.02 (m, 2 H,
94.0, 23.8, 20.3 ppm. IR (thin film): ν = 2974, 2888, 1408, 1319,
˜
1254, 1221, 1054 cm–1. MS (EI): m/z (%) = 391 (15) [M]+, 321 (26),
293 (42), 180 (11), 166 (100). HRMS (EI-TOF): calcd. for
C17H18IN3 [M]+ 391.0545; found 391.0544.
CH2CH2N), 3.70–3.82 (m, 2 H, CH2N), 3.50–3.68 (m, 2 H,
CH2CH2N), 3.02–3.15 (m, 2 H, CH2), 1.95–2.10 (m, 4 H, 2
CH2CH2N), 1.37 (t, J = 7.0 Hz, 3 H, CH3CH2) ppm. 13C NMR
(125 MHz, CDCl3): δ = 168.5, 166.5, 152.5, 133.8, 132.9, 132.1,
131.7, 129.1, 126.8, 123.2, 116.3, 70.5, 60.7, 51.6, 47.2, 44.3, 38.0,
trans-2-{5-Methyl-2-[(E)-pyrrolidin-1-yldiazenyl]-(1,1Ј-biphenyl)-3-
yl}cyclohexanol (2l): Yield 634 mg, 44%. red oil. Rf = 0.2 (hexanes/
1
23.8, 23.5, 14.3 ppm. IR (thin film): ν = 3671, 2980, 2902, 1697,
˜
EtOAc, 5:1). H NMR (500 MHz, CDCl3): δ = 7.23–7.28 (m, 4 H,
1385, 1253, 1072, 875 cm–1. MS (EI): m/z (%) = 450 (2) [M]+, 405
(19), 377 (14), 366 (14), 352 (40), 321 (16), 306 (100), 290 (19), 262
(19), 232 (7), 206 (100), 190 (14), 179 (44), 160 (100). HRMS (EI-
TOF): calcd. for C24H26N4O5 [M]+ 450.1903; found 450.1901.
ArH), 7.17–7.20 (m, 1 H, ArH), 7.14 (d, J = 2.5 Hz, 1 H, ArH),
7.01 (d, J = 1.5 Hz, 1 H, ArH), 3.71 (br., 1 H, OH), 3.60–3.66 (m,
1 H), 3.40–3.49 (m, 4 H), 2.83–2.89 (m, 1 H), 2.36 (s, 3 H, CH3),
2.16–2.20 (m, 1 H), 1.88 (br., 4 H, 2 CH2CH2N), 1.72–1.86 (m, 3
H), 1.56–1.67 (m, 1 H), 1.21–1.43 (m, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 146.0, 141.5, 136.2, 134.88, 134.84, 130.2,
129.7, 127.3, 126.5, 125.7, 75.4, 48.7, 45.7, 36.4, 32.7, 29.6, 26.2,
Ethyl 3-[3-(Allyloxy)-2-hydroxypropyl]-4-(pyrrolidin-1-yldiazenyl)-
benzoate (2j): Yield 1.03 g, 71%. red solid, m.p. 67–70 °C. Rf = 0.2
1
(hexanes/EtOAc, 5:1). H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1
25.1, 23.7, 21.2 ppm. IR (thin film): ν = 3342, 2920, 2849, 1427,
˜
H, ArH), 7.85 (dd, J = 8.4, J = 2.0 Hz, 1 H, ArH), 7.46 (d, J =
8.4 Hz, 1 H, ArH), 5.86–5.98 (m, 1 H, CH=), 5.26 (dd, J = 17.2,
J = 1.6 Hz, 1 H), 5.15 (dd, J = 10.2, J = 1.8 Hz, 1 H), 4.84 (d, J
= 3.2 Hz, 1 H, CHOH), 4.33 (q, J = 7.2 Hz, 2 H, CH3CH2O), 4.04–
4.15 (m, 1 H, OH), 3.87–4.04 (m, 4 H), 3.53–3.71 (m, 2 H), 3.37–
1339, 1214, 1066, 701 cm–1. MS (EI): m/z (%) = 363 (2) [M]+, 307
(4), 293 (4), 279 (37), 264 (46), 249 (9), 235 (10), 221 (20), 209 (16),
197 (100). HRMS (EI-TOF): calcd. for C23H29N3O [M]+ 363.2311;
found 363.2316.
3.45 (m, 1 H), 3.29–3.37 (m, 1 H), 3.08 (d, J = 5.6 Hz, 2 H), 1.90– 1-[(2-Allyl-6-iodo-4-methylphenyl)diazenyl]pyrrolidine (1m): A dry
2.13 (m, 4 H, CH2CH2N), 1.37 (t, J = 7.2 Hz, 3 H, CH3CH2) ppm. and N2-flushed 50 mL Schlenk tube, equipped with a magnetic stir-
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
Lewis-Acid-Promoted Arylation
rer and a septum was charged with [(2,6-diiodo-4-methylphenyl)
pyrrolidin-1-yl]diazene (6.615 g, 15 mmol, 1.0 equiv.) in dry THF
(15 mL). iPrMgCl (0.984 m in THF, 18.3 mL, 18 mmol, 1.2 equiv.)
was then added dropwise at –30 °C. After 3 h, complete conversion
into the corresponding Grignard reagent was observed, as indi-
cated by TLC. CuCN·2LiCl (1.0 m in THF, 0.75 mL, 0.75 mmol,
0.05 equiv.) and allyl bromide (1.8 mL, 19.5 mmol, 1.3 equiv.) were
added slowly to the resulting reaction mixture. Then the reaction
mixture was allowed to warm slowly to room temperature, and
stirred for 2 h before the addition of saturated aqueous NH4Cl
solution. The resulting mixture was extracted with ethyl acetate.
The organic extracts were dried with Na2SO4 and concentrated un-
der reduced pressure. Purification by flash chromatography on sil-
ica gel (hexanes/EtOAc, 50:1) gave 1m (4.48 g, 84%) as a yellow
247 (100). HRMS (EI-TOF): calcd. for C14H20IN3O [M]+
373.0651; found 373.0653.
Ethyl 3Ј-(2-Hydroxypropyl)-5Ј-methyl-2Ј-(pyrrolidin-1-yldiazenyl)-
[1,1Ј-biphenyl]-4-carboxylate (2n): [4-(Ethoxycarbonyl)phenyl]bo-
ronic acid (640 mg, 3.3 mmol, 1.1 equiv.), Pd(PPh3)4 (87 mg,
0.075 mmol, 0.025 equiv.), Cs2CO3 (1.956 g, 6.0 mmol, 2 equiv.)
were added to a solution of iodotriazene alcohol 1n (1.16 g,
3.0 mmol, 1.0 equiv.) in dioxane (8 mL) and H2O (2 mL) in a
screw-cap vial. The vial was flushed with N2, sealed, and heated at
100 °C for 12 h while stirring. After cooling, the solution was di-
luted with ethyl acetate and washed with water. The combined or-
ganic extracts were washed with water and brine, and dried with
Na2SO4. After silica gel chromatography (eluent: hexanes/EtOAc,
1
5:1), pure product 2n (913 mg, 77%) was obtained as a red oil. H
1
liquid. H NMR (400 MHz, CDCl3): δ = 7.56 (s, 1 H, ArH), 6.97
NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.0 Hz, 2 H, ArH), 7.29
(d, J = 8.0 Hz, 2 H, ArH), 7.01 (s, 1 H, ArH), 7.03 (s, 1 H, ArH),
4.62 (s, 1 H, CHOH), 4.37 (q, J = 7.1 Hz, 2 H, CH2O), 4.10 (br.,
1 H, OH), 3.30–3.50 (m, 4 H, 2 CH2N), 2.75–2.90 (m, 2 H,
CH2CH), 2.34 (s, 3 H, CH3), 1.74–2.20 (m, 4 H, 2 CH2CH2N),
1.40 (t, J = 7.2 Hz, 3 H, CH3CH2), 1.25 (d, J = 6.4 Hz, 3 H,
CH3CH) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.7, 146.9,
145.6, 134.7, 133.7, 132.9, 131.7, 130.0, 129.9, 128.7, 127.6, 69.2,
(s, 1 H, ArH), 5.84–5.94 (m, 1 H, CH=), 5.00–5.04 (m, 2 H, CH2=),
3.81 (br., 4 H, 2 CH2N), 3.33 (d, J = 6.4 Hz, 2 H, CH2), 2.26 (s, 3
H, CH3), 2.05 (s, 4 H, 2 CH2CH2N) ppm. 13C NMR (100 MHz,
CDCl3): δ = 147.8, 137.4, 137.2, 135.9, 132.5, 130.9, 115.4, 93.3,
36.6, 23.7, 20.2 ppm. IR (thin film): ν = 3665, 2974, 2904, 1636,
˜
1596, 1417, 1321, 1257, 1216, 1054 cm–1. MS (EI): m/z (%) = 355
(5) [M]+, 285 (19), 130 (100). HRMS (EI-TOF): calcd. for
C17H18IN3 [M]+ 355.0545; found 355.0555.
60.8, 41.8, 23.7, 23.6, 20.8, 14.3 ppm. IR (thin film): ν = 3672,
˜
2974, 2903, 1711, 1606, 1414, 1268, 1073, 857 cm–1. MS (EI): m/z
(%) = 395 (17) [M]+, 350 (18), 325 (13), 311 (64), 296 (19), 279 (13),
269 (28), 251 (100). HRMS (EI-TOF): calcd. for C23H29N3O3
[M]+ 395.2209; found 395.2208.
trans-2-{3-Allyl-5-methyl-2-[(E)-pyrrolidin-1-yldiazenyl]phenyl} cy-
clohexanol (2m): Yield 993 mg, 76%, red oil. Rf = 0.2 (hexanes/
EtOAc, 5:1). 1H NMR (500 MHz, CDCl3): δ = 7.02 (s, 1 H, ArH),
6.88 (s, 1 H, ArH), 5.88–5.96 (m, 1 H, CH=), 4.97–5.03 (m, 2 H,
CH2=), 3.77 (br., 4 H, 2 CH2N), 3.57 (dt, J = 10.3, J = 4.3 Hz, 2
H), 3.33 (d, J = 5.2 Hz, 2 H), 2.75 (m, 1 H), 2.30 (s, 3 H, CH3),
2.15–2.18 (m, 1 H), 2.05 (t, J = 6.5 Hz, 4 H, 2 CH2CH2N), 1.70–
1.80 (m, 3 H), 1.52–1.59 (m, 1 H), 1.19–1.41 (m, 3 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 146.4, 138.0, 135.5, 134.8, 132.1,
128.7, 125.4, 114.9, 75.3, 36.6, 36.4, 32.8, 26.2, 25.1, 23.8,
Ethyl 3Ј-(2-Hydroxy-2-methylpropyl)-5Ј-methyl-2Ј-(pyrrolidin-1-yl-
diazenyl)[1,1Ј-biphenyl]-4-carboxylate (2o): Compound 2o was pre-
pared from 2,2-dimethyloxirane and [(2,6-diiodo-4-methylphenyl)-
pyrrolidin-1-yl]diazene according to the procedure for the prepara-
tion of 2n. Yield 954 mg, 78%, yellow solid, m.p. 84–86 °C. Rf =
1
0.2 (hexanes/EtOAc, 5:1). H NMR (400 MHz, CDCl3): δ = 7.93
(d, J = 8.0 Hz, 2 H, ArH), 7.25 (d, J = 8.0 Hz, 2 H, ArH), 6.98 (d,
J = 7.2 Hz, 2 H, ArH), 5.80 (s, 1 H, OH), 4.37 (q, J = 7.1 Hz, 2
H, CH3CH2O), 3.38 (br., 4 H, 2 CH2N), 2.89 (s, 2 H, CH2), 2.35
(s, 3 H, CH3), 1.60–2.00 (m, 4 H, 2 CH2CH2N), 1.40 (t, J = 7.2 Hz,
3 H, CH3CH2), 1.27 (s, 6 H, 2 CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 166.8, 147.2, 145.5, 134.5, 133.4, 132.8, 130.3, 129.8,
128.8, 127.4, 71.3, 60.8, 45.9, 30.3, 23.6, 20.9, 14.3 ppm. IR (thin
21.2 ppm. IR (thin film): ν = 3664, 2978, 2903, 1406, 1252, 1069,
˜
895 cm–1. MS (EI): m/z (%) = 327 (3) [M]+, 271 (3), 257 (6), 243
(40), 228 (6), 200 (16), 185 (18), 161 (100), 143 (35), 128 (26).
HRMS (EI-TOF): calcd. for C20H29N3O [M]+ 327.2311; found
327.2307.
1-[3-Iodo-5-methyl-2-(pyrrolidin-1-yldiazenyl)phenyl]propan-2-ol (1n):
A dry and N2-flushed 50 mL Schlenk tube, equipped with a mag-
netic stirrer and a septum was charged with [(2,6-diiodo-4-meth-
ylphenyl)pyrrolidin-1-yl]diazene (2.205 g, 5 mmol, 1.0 equiv.) in dry
THF (5 mL). iPrMgCl (1.15 m in THF, 4.8 mL, 5.5 mmol,
1.1 equiv.) was then added dropwise at –30 °C. After 2.5 h, com-
plete conversion into the corresponding Grignard reagent was ob-
served, as indicated by TLC and GC analysis. A CuCN·2LiCl solu-
tion (1.0 m in THF, 0.25 mL, 0.25 mmol, 0.05 equiv.) and 2-methyl-
oxirane (0.56 mL, 8 mmol, 1.6 equiv.) were added slowly to the re-
sulting reaction mixture. Then the reaction mixture was slowly al-
lowed to warm to room temperature, and stirred for 4 h before
the addition of saturated aqueous NH4Cl solution. The resulting
mixture was extracted with ethyl acetate. The organic extracts were
dried with Na2SO4 and concentrated under reduced pressure. After
silica gel chromatography (eluent: hexanes/EtOAc, 5:1), pure prod-
uct 1n (1.208 g, 62%) was obtained as a red solid, m.p. 65–67 °C.
film): ν = 3665, 2976, 1713, 1407, 1054 cm–1. MS (EI): m/z (%) =
˜
409 (29) [M]+, 392 (8), 293 (84), 265 (100), 197 (86). HRMS (EI-
TOF): calcd. for C24H31N3O3 [M]+ 409.2365; found 409.2362.
Ethyl 5Ј-Fluoro-3Ј-[(1R,2S)-2-hydroxycyclohexyl]-2Ј-[(E)-pyrrolidin-
1-yldiazenyl][1,1Ј-biphenyl]-4-carboxylate (2p): Triazene alcohol 2p
was prepared from [(2,6-dibromo-4-fluorophenyl)pyrrolidin-1-yl]-
diazene according to the procedure for the preparation of 2m. Yield
972 mg, 74%, brown solid, m.p. 117–119 °C. Rf = 0.3 (hexanes/
EtOAc, 3:1). 1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.0 Hz,
2 H, ArH), 7.31 (d, J = 8.4 Hz, 2 H, ArH), 7.07 (dd, J = 10.0, J =
2.4 Hz, 1 H, ArH), 6.90 (dd, J = 8.8, J = 2.4 Hz, 1 H, ArH), 4.38
(q, J = 7.2 Hz, 2 H, CH3CH2O), 3.55–3.70 (m, 2 H), 3.35–3.55 (m,
4 H), 2.91 (t, J = 10.2 Hz, 1 H), 2.18 (d, J = 12.0 Hz, 1 H), 1.65–
2.10 (m, 7 H), 1.53–1.56 (m, 1 H), 1.39 (t, J = 7.2 Hz, 3 H), 1.15–
1.47 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.6, 160.4
(d, JC,F = 242.0 Hz), 145.4, 144.6 (d, JC,F = 3.0 Hz), 139.3 (d, JC,F
1H NMR (400 MHz, CDCl3): δ = 7.57 (s, 1 H, ArH), 6.96 (s, 1 H, = 6.7 Hz), 135.5 (d, JC,F = 7.6 Hz), 129.9, 128.8, 128.2, 115.2 (d,
ArH), 3.63–4.03 (m, 5 H), 2.62–2.75 (m, 2 H), 2.25 (s, 3 H, CH3), JC,F = 23.0 Hz), 113.1 (d, JC,F = 22.1 Hz), 75.3, 60.9, 45.8, 36.5,
2.00–2.14 (m, 4 H, 2 CH2CH2N), 1.19 (d, J = 6.4 Hz, 3 H, CH3CH)
32.5, 26.0, 25.0, 23.6, 14.3 ppm. IR (thin film): ν = 3671, 2979,
˜
ppm. 13C NMR (100 MHz, CDCl3): δ = 147.8, 138.4, 136.2, 132.3,
2902, 1690, 1407, 1257, 1070, 863 cm–1. MS (EI): m/z (%) = 440
131.9, 92.6, 68.8, 50.9, 46.8, 46.7, 41.9, 23.7, 23.6, 20.2 ppm. IR (24) [M]+, 422 (2), 394 (4), 369 (12), 355 (54), 338 (7), 323 (3),
(thin film): ν = 3671, 2972, 2904, 1412, 1316, 1257, 1226,
312 (19), 295 (9), 273 (100), 257 (11). HRMS (EI-TOF): calcd. for
˜
1052 cm–1. MS (EI): m/z (%) = 374 (14) [M]+, 303 (26), 289 (34), C25H30FN3O3 [M]+ 439.2271; found 439.2265.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
G. Zhao, B. Wang, W. Yang, H. Ren
3-(2-Hydroxy-2-methylpropyl)-4-(pyrrolidin-1-yldiazenyl)- and OH), 3.80–3.96 (br., 2 H, CH2N), 3.28 (br., 2 H, CH2N), 1.93
FULL PAPER
Ethyl
benzoate (2q): Compound 2q was prepared from ethyl 3-iodo-4-
(pyrrolidin-1-yldiazenyl) benzoate by treatment with 2,2-dimeth-
yloxirane according to the procedure for the preparation of com-
pound 2a. Yield 804 mg, 63%, red solid, m.p. 79–80 °C. Rf = 0.2
(br., 4 H, 2 CH2CH2N), 1.37 (t, J = 7.2 Hz, 3 H, CH3CH2) ppm.
13C NMR (100 MHz, CDCl3): δ = 166.4, 152.6, 139.2, 138.9, 135.4,
132.2, 130.3, 129.8, 129.3, 127.9, 127.7, 126.8, 117.8, 64.6, 60.7,
51.6, 46.9, 23.6, 23.4, 14.3 ppm. IR (thin film): ν = 3671, 2979,
˜
1
(hexanes/EtOAc, 5:1). H NMR (400 MHz, CDCl3): δ = 7.86 (d, J
2902, 1696, 1397, 1233, 1052 cm–1. MS (EI): m/z (%) = 353 (6)
[M]+, 308 (22), 283 (9), 269 (31), 252 (56), 225 (17), 209 (100), 193
(10), 182 (72), 165 (100), 152 (62). HRMS (EI-TOF): calcd. for
C20H23N3O3 [M]+ 353.1739; found 353.1733.
= 8.4 Hz, 1 H, ArH), 7.80 (s, 1 H, ArH), 7.50 (d, J = 8.4 Hz, 1 H,
ArH), 5.70 (s, 1 H, OH), 4.36 (q, J = 7.2 Hz, 2 H, CH3CH2O),
3.99 (br., 2 H, CH2N), 3.63 (br., 2 H, CH2N), 3.04 (s, 2 H, CH2),
2.03–2.09 (m, 4 H, 2 CH2CH2N), 1.39 (t, J = 7.0 Hz, 3 H,
CH3CH2), 1.23 (s, 6 H, 2 CH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 166.7, 152.6, 134.1, 132.6, 128.8, 126.7, 116.5, 71.6, 60.7, 51.8,
Ethyl 2Ј-(1-Hydroxypropyl)-6-(pyrrolidin-1-yldiazenyl)[1,1Ј-biphen-
yl]-3-carboxylate (2u): Compound 2u was prepared from 1-(2-
bromophenyl)propan-1-ol by treatment with [5-(ethoxycarbonyl)-
2-(pyrrolidin-1-yldiazenyl)phenyl]boronic acid according to the
procedure for the synthesis of compound 2t. Yield 273 mg, 24%,
red oil. Rf = 0.2 (hexanes/EtOAc, 5:1). 1H NMR (400 MHz,
CDCl3): δ = 8.02 (d, J = 8.4 Hz, 1 H, ArH), 7.88 (s, 1 H, ArH),
7.54 (d, J = 8.0 Hz, 1 H, ArH), 7.38–7.47 (m, 2 H, ArH), 7.30 (t,
J = 7.6 Hz, 1 H, ArH), 7.11 (d, J = 7.2 Hz, 1 H, ArH), 4.65 (s, 1
H, OH), 4.45 (t, J = 7.2 Hz, 1 H, CHCH2), 4.36 (q, J = 6.9 Hz, 2
H, CH3CH2O), 3.87 (br., 2 H, CH2N), 3.27 (br., 2 H, CH2N), 1.91–
1.97 (m, 4 H, 2 CH2CH2N), 1.73–1.78 (m, 2 H, CH2CH3), 1.38 (t,
J = 7.0 Hz, 3 H, CH3CH2O), 0.82 (t, J = 7.4 Hz, 3 H, CH3CH2)
ppm. 13C NMR (100 MHz, CDCl3): δ = 166.5, 152.7, 141.8, 139.4,
135.7, 132.2, 130.2, 129.7, 128.0, 127.2, 126.9, 124.9, 117.8, 72.4,
47.3, 46.2, 30.1, 23.8, 23.5, 14.4 ppm. IR (thin film): ν = 3666,
˜
2973, 2903, 1702, 1600, 1399, 1314, 1258, 1072 cm–1. MS (EI): m/z
(%) = 319 (6) [M]+, 302 (3), 274 (10), 261 (32), 249 (13), 232 (30),
179 (100). HRMS (EI-TOF): calcd. for C17H25N3O3 [M]+
319.1896; found 319.1899.
1-[5-Bromo-2-(pyrrolidin-1-yldiazenyl)phenyl]-2-methylpropan-2-ol
(2r): Compound 2r was prepared from 1-[(4-bromo-2-iodophenyl)-
diazenyl]pyrrolidine by treatment with 2,2-dimethyloxirane accord-
ing to the procedure for the preparation of compound 2a. Yield
850 mg, 65%, yellow solid, m.p. 110–112 °C. Rf = 0.2 (hexanes/
1
EtOAc, 5:1). H NMR (400 MHz, CDCl3): δ = 7.20–7.40 (m, 3 H,
ArH), 5.70 (s, 1 H, OH), 3.94 (br., 2 H, CH2N), 3.58 (br., 2 H,
CH2N), 2.95 (s, 2 H, CH2), 2.04 (br., 4 H, 2 CH2CH2N), 1.22 (s, 6
H, 2 CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.0, 134.9,
134.8, 130.1, 118.3, 118.2, 71.5, 51.5, 47.1, 46.0, 30.1, 23.8,
60.8, 51.6, 46.8, 27.8, 23.6, 23.5, 14.3, 10.6 ppm. IR (thin film): ν
˜
= 3664, 2973, 2904, 1710, 1599, 1394, 1303, 1234, 1051 cm–1. MS
(EI): m/z (%) = 382 (8) [M + H]+, 364 (66), 268 (100), 252 (26).
HRMS (EI-TOF): calcd. for C22H27N3O3 [M]+ 381.2052; found
381.2050.
23.6 ppm. IR: ν = 3669, 2971, 1392, 1311, 1072 cm–1. MS (EI): m/z
˜
(%) = 327 (8) [M, Br81]+, 325 (8) [M, Br79]+, 267 (9), 257 (20), 199
(12), 187 (72), 171 (25), 130 (100). HRMS (EI-TOF): calcd. for
C14H20BrN3O [M]+ 325.0790; found 325.0797.
Ethyl
2Ј-(1-Hydroxy-2-methylpropyl)-6-(pyrrolidin-1-yldiazenyl)-
[1,1Ј-biphenyl]-3-carboxylate (2v): Compound 2v was prepared from
1-(2-bromophenyl)-2-methylpropan-1-ol by treatment with [5-
(1S,2R)-2-{5-Bromo-2-[(E)-pyrrolidin-1-yldiazenyl]phenyl}cyclohex-
anol (2s): Compound 2s was prepared from 1-[(4-bromo-2-iodo-
phenyl)diazenyl]pyrrolidine by treatment with 7-oxabicyclo[4.1.0]-
heptane according to the procedure of compound 2a. Yield 722 mg,
51%, brown solid, m.p. 110–112 °C. Rf = 0.2 (hexanes/EtOAc, 5:1).
1H NMR (400 MHz, CDCl3): δ = 7.43 (s, 1 H, ArH), 7.25–7.34
(m, 2 H, ArH), 3.55–4.05 (m, 5 H), 3.45 (br., 1 H), 3.20–3.30 (m,
1 H), 2.15–2.25 (m, 1 H), 2.00–2.14 (m, 4 H, 2 CH2CH2N), 1.75–
1.90 (m, 3 H), 1.60–1.70 (m, 1 H), 1.23–1.50 (m, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 148.1, 139.4, 129.74, 129.69, 119.0,
(ethoxycarbonyl)-2-(pyrrolidin-1-yldiazenyl)phenyl]boronic
acid
according to the procedure for the preparation of compound 2t.
Yield 371 mg, 31%, yellow solid, m.p. 63–65 °C. Rf = 0.2 (hexanes/
EtOAc, 5:1). 1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz,
1 H, ArH), 7.88 (s, 1 H, ArH), 7.52 (d, J = 8.0 Hz, 1 H, ArH),
7.36–7.46 (m, 2 H, ArH), 7.25–7.30 (m, 2 H, ArH), 7.10 (d, J =
6.8 Hz, 1 H, ArH), 4.36 (q, J = 7.1 Hz, 2 H, CH3CH2O), 4.06 (d,
J = 10.0 Hz, 1 H, CHOH), 3.86 (br., 2 H, CH2N), 3.25 (br., 2 H,
CH2N), 2.15–2.20 [m,
1 H, (CH3)2CH], 1.90 (br., 4 H, 2
CH2CH2N), 1.38 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.33 (d, J =
7.2 Hz, 1 H), 1.03 (d, J = 6.0 Hz, 3 H, CH3CH), 0.58 (d, J =
6.4 Hz, 3 H, CH3CH) ppm. 13C NMR (125 MHz, CDCl3): δ =
166.6, 152.7, 141.7, 139.5, 135.9, 132.0 (2 C), 130.0, 129.6, 128.0,
127.0, 125.4, 117.7, 60.8, 51.6, 46.8, 32.1, 23.6, 23.5, 23.4, 19.8,
118.4, 75.4, 45.4, 36.5, 31.6, 26.2, 25.1, 23.7 ppm. IR (thin film): ν
˜
= 3665, 2977, 1392, 1059 cm–1. MS (EI): m/z (%) = 353 (5) [M,
Br81]+, 351 (5) [M, Br79]+, 267 (41), 187 (100). HRMS (EI-TOF):
calcd. for C16H22BrN3O [M]+ 351.0946; found 351.0939.
19.3, 14.3 ppm. IR (thin film): ν = 3665, 2977, 2902, 1709, 1404,
˜
Ethyl 2Ј-(Hydroxymethyl)-6-(pyrrolidin-1-yldiazenyl)[1,1Ј-biphenyl]-
3-carboxylate (2t): [5-(ethoxycarbonyl)-2-(pyrrolidin-1-yldiazenyl)-
phenyl]boronic acid (961 mg, 3.3 mmol, 1.1 equiv.), Pd(PPh3)4
(87 mg, 0.075 mmol, 0.025 equiv.), and Cs2CO3 (1.956 g, 6.0 mmol,
2.0 equiv.) were added to a solution of (2-bromophenyl)methanol
(561 mg, 3.0 mmol, 1.0 equiv.) in dioxane (8 mL) and H2O (2 mL)
in a screw-cap vial. The vial was flushed with N2, sealed, and
heated at 100 °C for 12 h while stirring. After cooling, the solution
was diluted with ethyl acetate and washed with water. The com-
bined organic extracts were washed with water and brine, and dried
with Na2SO4. After filtration and evaporation, the residue was
purified by silica gel chromatography (eluent: hexanes/EtOAc, 5:1)
to give pure compound 2t (360 mg, 34%) as a yellow solid,
m.p.112–114 °C. 1H NMR (400 MHz, CDCl3): δ = 8.02 (dd, J =
8.4, J = 2.0 Hz, 1 H, ArH), 7.88 (d, J = 2.0 Hz, 1 H, ArH), 7.40–
7.51 (m, 2 H, ArH), 7.27–7.40 (m, 2 H, ArH), 7.15 (dd, J = 7.4, J
= 1.4 Hz, 1 H, ArH), 4.44–4.54 (m, 2 H), 4.27–4.40 (m, 3 H, CH2O
1232, 1054 cm–1. MS (EI): m/z (%) = 396 (2) [M + H]+, 352 (15)
[M – iPr]+, 322 (16), 311 (10), 277 (12), 268 (100), 262 (44), 251
(65), 225 (57), 183 (57). HRMS (EI-TOF): calcd. for C23H29N3O3
[M]+ 395.2209; found 395.2215.
General Procedure for the Synthesis of Compounds 3a–3v: BF3·OEt2
(0.13 mL, 1 mmol, 2.0 equiv.) was slowly added to a solution of
triazene alcohol 2a–2v (0.5 mmol, 1.0 equiv.) in CH2Cl2 (20 mL) at
room temperature, and stirring was continued at 40 °C for 4 h, be-
fore the reaction mixture was cooled and the reaction was
quenched by a 5% aqueous solution of NaHCO3. The resulting
mixture was extracted with CH2Cl2. The organic extracts were
dried with anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The residue was purified by flash column
chromatography on silica gel (eluent: hexanes/EtOAc, 50:1).
Ethyl 5a,6,7,8,9,9a-Hexahydrodibenzo[b,d]furan-2-carboxylate (3a):
Yield 94 mg, 76%, white solid, m.p. 63–64 °C. 1H NMR (400 MHz,
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
Lewis-Acid-Promoted Arylation
CDCl3): δ = 7.89 (d, J = 8.4 Hz, 1 H, ArH), 7.79 (s, 1 H, ArH),
6.83 (d, J = 8.8 Hz, 1 H, ArH), 4.33 (q, J = 7.2 Hz, 2 H,
CH3CH2O), 3.86–3.93 (m, 1 H, OCH), 2.75–2.85 (m, 1 H, CH),
2.31–2.40 (m, 2 H), 1.94–1.98 (m, 1 H), 1.77–1.88 (m, 2 H), 1.41–
1.46 (m, 3 H), 1.36 (t, J = 7.2 Hz, 3 H, CH3CH2O) ppm. 13C NMR
5 H, ArH), 6.88 (d, J = 9.0 Hz, 1 H, ArH), 5.84 (t, J = 8.8 Hz, 1
H, ArOCHPh), 4.35 (q, J = 7.2 Hz, 2 H, CH3CH2O), 3.65–3.70
(m, 1 H), 3.20–3.30 (m, 1 H), 1.38 (t, J = 7.0 Hz, 3 H, CH3CH2)
ppm. 13C NMR (125 MHz, CDCl3): δ = 166.4, 163.6, 141.2, 131.2,
128.7, 128.3, 126.9, 126.6, 125.7, 123.3, 109.0, 85.2, 60.6, 37.6,
(100 MHz, CDCl3): δ = 166.5, 164.1, 132.2, 130.7, 124.0, 123.1, 14.4 ppm. IR (thin film): ν = 2979, 2903, 1707, 1609, 1485, 1443,
˜
109.5, 91.4, 60.5, 48.0, 30.5, 26.9, 25.3, 24.4, 14.3 ppm. IR (thin 1394, 1261, 1165, 1077 cm–1. MS (EI): m/z (%) = 268 (100) [M]+,
film): ν = 2981, 2939, 2903, 1707, 1610, 1244, 1073, 1014 cm–1. MS 223 (63), 253 (4), 240 (7), 194 (17), 165 (30), 152 (16). HRMS (EI-
˜
(EI): m/z (%) = 246 (100) [M]+, 201 (50), 173 (35), 145 (31), 115 TOF): calcd. for C17H16O3 [M]+ 268.1099; found 268.1101.
(23), 67 (24). HRMS (EI-TOF): calcd. for C15H18O3 [M]+ 246.1256;
found 246.1258.
Ethyl 3-Phenyl-2,3-dihydrobenzofuran-5-carboxylate (3g): Yield
102 mg, 76%, yellow solid, m.p. 57–59 °C. 1H NMR (500 MHz,
Ethyl 2-Methyl-2,3-dihydrobenzofuran-5-carboxylate (3b): Yield
71 mg, 69%, pale yellow oil. 1H NMR (500 MHz, CDCl3): δ =
CDCl3): δ = 7.94 (d, J = 8.3 Hz, 1 H, ArH), 7.72 (s, 1 H, ArH),
7.32–7.35 (m, 2 H, ArH), 7.24–7.30 (m, 1 H, ArH), 7.17–7.22 (m,
7.85–7.88 (m, 2 H, ArH), 6.75 (d, J = 8.5 Hz, 1 H, ArH), 4.98– 2 H, ArH), 6.90 (d, J = 8.0 Hz, 1 H, ArH), 4.99 (t, J = 9.3 Hz, 1
5.03 (m, 1 H, CHCH3), 4.33 (q, J = 7.2 Hz, 2 H, CH3CH2O), 3.20– H, ArCH), 4.69 (t, J = 8.5 Hz, 1 H), 4.50–4.54 (m, 1 H), 4.23–4.33
3.40 (m, 1 H), 2.78–2.86 (m, 1 H), 1.48 (d, J = 6.0 Hz, 3 H,
(m, 2 H, CH3CH2O), 1.34 (t, J = 7.3 Hz, 3 H, CH3) ppm. 13C
CH3CH), 1.37 (t, J = 7.3 Hz, 3 H, CH3CH2) ppm. 13C NMR NMR (125 MHz, CDCl3): δ = 166.3, 164.1, 142.2, 131.4, 131.0,
(125 MHz, CDCl3): δ = 166.5, 163.5, 131.0, 127.3, 126.7, 122.8, 128.9, 127.7, 127.3, 127.1, 123.5, 109.3, 80.1, 60.6, 47.8, 14.3 ppm.
108.9, 80.8, 60.5, 36.4, 21.7, 14.4 ppm. IR (thin film): ν = 2978, IR (thin film): ν = 2979, 2902, 1707, 1603, 1458, 1395, 1248,
˜
˜
2904, 1707, 1610, 1485, 1443, 1384, 1265, 1167, 1081 cm–1. MS 1075 cm–1. MS (EI): m/z (%) = 268 (100) [M+], 253 (2), 239 (9),
(EI): m/z (%) = 206 (95) [M]+, 191 (12), 178 (44), 161 (100), 133 223 (66), 195 (20), 165 (28), 152 (15). HRMS (EI-TOF): calcd. for
(36), 77 (28). HRMS (EI-TOF): calcd. for C12H14O3 [M]+ 206.0943;
found 206.0948.
C17H16O3 [M]+ 268.1099; found 268.1100.
trans-8-Methyl-1,2,3,4,4a,9b-hexahydrodibenzo[b,d]furan (3h): Yield
Ethyl 2-(Chloromethyl)-2,3-dihydrobenzofuran-5-carboxylate (3c): 50 mg, 53%, white solid, m.p. 73–76 °C. 1H NMR (400 MHz,
Yield 42 mg, 35%, white solid, m.p. 41–43 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.86–7.92 (m, 2 H, ArH), 6.80 (d, J = 8.0 Hz, 1 H,
ArH), 5.04–5.12 (m, 1 H, CHCH2Cl), 4.33 (q, J = 7.2 Hz, 2 H,
CDCl3): δ = 6.90–6.95 (m, 2 H, ArH), 6.75 (d, J = 7.6 Hz, 1 H,
ArH), 3.83 (dt, J = 12.0, J = 3.6 Hz, 1 H, ArOCH), 2.70–2.82 (m,
1 H, ArCH), 2.32–2.36 (m, 2 H), 2.30 (s, 3 H, ArCH3), 1.94–1.99
CH3CH2O), 3.66–3.78 (m, 2 H, CH2Cl), 3.34–3.41 (m, 1 H), 3.12– (m, 1 H), 1.76–1.88 (m, 2 H), 1.34–1.47 (m, 3 H) ppm. 13C NMR
3.20 (m, 1 H), 1.37 (t, J = 7.3 Hz, 3 H, CH3CH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.0, 132.1, 130.0, 127.8, 123.1, 109.5,
(125 MHz, CDCl3): δ = 166.3, 163.0, 131.1, 126.7, 126.1, 123.5, 90.6, 48.6, 30.7, 27.2, 25.5, 24.5, 20.9 ppm. IR (thin film): ν = 2978,
˜
109.1, 82.4, 60.6, 45.9, 32.7, 14.3 ppm. IR (thin film): ν = 2980, 2904, 1452, 1400, 1228, 1055, 891, 812 cm–1. MS (EI): m/z (%) =
˜
2902, 1694, 1613, 1438, 1267, 1242, 1079, 767 cm–1. MS (EI): m/z
(%) = 242 (23) [M, Cl37]+, 240 (67) [M, Cl35]+, 225 (7), 212 (23),
195 (100), 191 (26). HRMS (EI-TOF): calcd. for C12H13ClO3
[M]+ 240.0553; found 240.0554.
188 (100) [M]+, 173 (31), 159 (42), 145 (76), 121 (45). HRMS (EI-
TOF): calcd. for C13H16O [M]+ 188.1201; found 188.1199.
Ethyl 2-[(1,3-Dioxoisoindolin-2-yl)methyl]-2,3-dihydrobenzofuran-5-
carboxylate (3i): Yield 125 mg, 71%, white solid, m.p. 118–120 °C.
1H NMR (500 MHz, CDCl3): δ = 7.85–7.90 (m, 4 H, ArH), 7.71–
7.76 (m, 2 H, ArH), 6.75 (d, J = 9.5 Hz, 1 H, ArH), 5.15–5.23 (m,
1 H, ArOCH), 4.31 (q, J = 7.3 Hz, 2 H, CH3CH2O), 4.03 (dd, J =
14.3, J = 7.8 Hz, 1 H), 3.83 (dd, J = 14.0, J = 5.0 Hz, 1 H), 3.36
(dd, J = 16.3, J = 9.3 Hz, 1 H), 3.04 (dd, J = 16.3, J = 6.3 Hz, 1
Ethyl 2-(Cyanomethyl)-2,3-dihydrobenzofuran-5-carboxylate (3d):
Yield 64 mg, 55%, pink solid, m.p. 58–61 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.86–7.92 (m, 2 H, ArH), 6.82 (d, J = 8.5 Hz, 1 H,
ArH), 5.05–5.15 (m, 1 H, CHCH2CN), 4.32 (q, J = 7.2 Hz, 2 H,
CH3CH2O), 3.45–3.51 (m, 1 H), 3.07 (dd, J = 16.3, J = 6.3 Hz, 1
H), 2.80 (d, J = 6.5 Hz, 2 H, CHCH2CN), 1.36 (t, J = 3.5 Hz, 3 H), 1.35 (t, J = 7.3 Hz, 3 H, CH3CH2) ppm. 13C NMR (125 MHz,
H, CH2CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.1, 162.2,
CDCl3): δ = 168.1, 166.3, 162.8, 134.1, 131.8, 131.2, 126.7, 126.1,
131.3, 126.8, 125.3, 123.9, 116.0, 109.4, 78.1, 60.7, 34.2, 24.3,
123.4, 109.4, 80.6, 60.5, 41.7, 32.5, 14.3 ppm. IR (thin film): ν =
˜
14.3 ppm. IR (thin film): ν = 2979, 2903, 2252, 1698, 1611, 1398,
2981, 2902, 1708, 1392, 1242, 1055, 838, 709 cm–1. MS (EI): m/z
(%) = 351 (70) [M]+, 306 (51), 277 (45), 259 (1), 204 (100), 191 (52).
HRMS (EI-TOF): calcd. for C21H17NO5 [M]+ 351.1107; found
351.1104.
˜
1267, 1071, 768 cm–1. MS (EI): m/z (%) = 231 (90) [M]+, 216 (11),
203 (30), 191 (8), 186 (100). HRMS (EI-TOF): calcd. for
C13H13NO3 [M]+ 231.0895; found 231.0889.
Ethyl 2-(Azidomethyl)-2,3-dihydrobenzofuran-5-carboxylate (3e):
Ethyl
2-[(Allyloxy)methyl]-2,3-dihydrobenzofuran-5-carboxylate
1
Yield 56 mg, 45%, red oil. 1H NMR (400 MHz, CDCl3): δ = 7.86–
(3j): Yield 85 mg, 65%, yellow oil. H NMR (500 MHz, CDCl3): δ
7.92 (m, 2 H, ArH), 6.82 (d, J = 8.0 Hz, 1 H, ArH), 4.95–5.08 (m, = 7.83–7.90 (m, 2 H, ArH), 6.78 (d, J = 8.5 Hz, 1 H, ArH), 5.84–
1 H, CHCH2N3), 4.33 (q, J = 7.2 Hz, 2 H, CH3CH2O), 3.52–3.60
(m, 1 H), 3.43–3.52 (m, 1 H), 3.30–3.40 (m, 1 H), 3.00–3.08 (m, 1
H), 1.37 (t, J = 7.2 Hz, 3 H, CH3CH2) ppm. 13C NMR (100 MHz,
CDCl3): δ = 166.0, 162.5, 130.9, 126.4, 125.9, 123.2, 108.9, 81.9,
5.93 (m, 1 H, CH=), 5.26 (d, J = 17.5 Hz, 1 H), 5.18 (d, J =
10.0 Hz, 1 H), 4.99–5.06 (m, 1 H, OCH), 4.31 (q, J = 7.0 Hz, 2 H,
CH3CH2O), 4.00–4.10 (m, 2 H), 3.58–3.69 (m, 2 H), 3.23–3.32 (m,
1 H), 2.98–3.06 (m, 1 H), 1.35 (t, J = 7.0 Hz, 3 H, CH3CH2) ppm.
13C NMR (125 MHz, CDCl3): δ = 166.4, 163.4, 134.2, 130.9, 126.7,
126.6, 122.9, 117.5, 109.0, 82.7, 72.4, 71.8, 60.5, 31.3, 14.3 ppm. IR
60.3, 54.0, 31.7, 14.0 ppm. IR (thin film): ν = 2981, 2099, 1705,
˜
1610, 1487, 1440, 1266, 1241, 1164, 1111, 1019, 767 cm–1. MS (EI):
m/z (%) = 247 (53) [M]+, 218 (5), 202 (39), 190 (100), 175 (20), 162 (thin film): ν = 2980, 2903, 1706, 1610, 1487, 1264, 1165, 1084,
˜
(45), 145 (73), 129 (7), 119 (60), 91 (100). HRMS (EI-TOF): calcd. 768 cm–1. MS (EI): m/z (%) = 262 (73) [M]+, 217 (39), 204 (100),
for C12H13N3O3 [M]+ 247.0957; found 247.0954.
191 (38), 175 (27). HRMS (EI-TOF): calcd. for C15H18O4 [M]+
262.1205; found 262.1201.
Ethyl 2-Phenyl-2,3-dihydrobenzofuran-5-carboxylate (3f): Yield
106 mg, 79%, pale yellow oil. 1H NMR (500 MHz, CDCl3): δ =
7.94 (d, J = 9.0 Hz, 1 H, ArH), 7.90 (s, 1 H, ArH), 7.30–7.45 (m, 38 mg, 37%, yellow oil. H NMR (400 MHz, CDCl3): δ = 6.98 (s,
2-[(Allyloxy)methyl]-5-methyl-2,3-dihydrobenzofuran (3k): Yield
1
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
G. Zhao, B. Wang, W. Yang, H. Ren
FULL PAPER
1 H, ArH), 6.91 (d, J = 8.0 Hz, 1 H, ArH), 6.71 (d, J = 8.0 Hz, 1
H, ArH), 5.86–6.00 (m, 1 H, CH=), 5.30 (dd, J = 17.0, J = 1.4 Hz,
1 H), 5.21 (d, J = 10.0 Hz, 1 H), 4.90–5.00 (m, 1 H, OCH), 4.02–
4.16 (m, 2 H), 3.56–3.72 (m, 2 H), 3.18–3.28 (m, 1 H), 2.90–3.02
(m, 1 H), 2.28 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 157.3, 134.5, 129.6, 128.2, 126.2, 125.5, 117.4, 109.0, 81.4, 72.4,
Ethyl 4-[(5aS,9aR)-2-Fluoro-5a,6,7,8,9,9a-hexahydrodibenzo[b,d]-
furan-4-]benzoate (3p): Yield 47 mg, 27%, white solid, m.p. 86–
89 °C. H NMR (500 MHz, CDCl3): δ = 8.10 (d, J = 8.5 Hz, 2 H,
ArH), 7.78 (d, J = 8.5 Hz, 2 H, ArH), 7.03 (dd, J = 10.5, J =
2.0 Hz, 1 H, ArH), 6.84 (dd, J = 6.0, J = 1.0 Hz, 1 H, ArH), 4.39
(q, J = 7.2 Hz, 2 H, CH3CH2O), 3.91 (m, 1 H, OCH), 2.83 (t, J =
1
72.1, 32.2, 20.7 ppm. IR (thin film): ν = 2978, 2903, 1489, 1451, 12.3 Hz, 1 H), 2.25–2.45 (m, 2 H), 1.75–2.05 (m, 3 H), 1.30–1.40
˜
1404, 1246, 1072, 922, 807 cm–1. MS (EI): m/z (%) = 204 (100)
(m, 3 H), 1.41 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR (125 MHz,
[M]+, 163 (13), 145 (100), 133 (100), 115 (22), 105 (100). HRMS CDCl3): δ = 166.4, 157.9 (d, JC,F = 238.1 Hz), 153.5, 140.7, 134.8
(EI-TOF): calcd. for C13H16O2 [M]+ 204.1150; found 204.1151.
(d, JC,F = 7.5 Hz), 129.7, 129.2, 128.2, 122.9 (d, JC,F = 8.1 Hz),
112.9 (d, JC,F = 23.1 Hz), 109.8 (d, JC,F = 25.5 Hz), 91.1, 60.9,
trans-8-Methyl-6-phenyl-1,2,3,4,4a,9b-hexahydrodibenzo[b,d]furan
(3l): Yield 71 mg, 54%, red oil. H NMR (500 MHz, CDCl3): δ =
7.72 (dd, J = 8.5, J = 1.5 Hz, 2 H, ArH), 7.43 (t, J = 7.8 Hz, 2 H,
ArH), 7.29–7.33 (m, 1 H, ArH), 7.12 (s, 1 H, ArH), 6.93 (s, 1 H,
ArH), 3.85–3.91 (m, 1 H, OCH), 2.80–2.85 (m, 1 H, ArCH), 2.37
48.6, 30.7, 27.0, 25.3, 24.4, 14.3 ppm. IR (thin film): ν = 2972,
˜
1
1707, 1608, 1387, 1267, 1100, 1075, 1021, 794, 778 cm–1. MS (EI):
m/z (%) = 340 (100) [M]+, 325 (4), 311 (9), 295 (15). HRMS (EI-
TOF): calcd. for C21H21FO3 [M]+ 340.1475; found 340.1479.
(s, 3 H, CH3), 2.31–2.36 (m, 2 H), 1.95–2.02 (m, 1 H), 1.80–1.92 Ethyl 2,2-Dimethyl-2,3-dihydrobenzofuran-5-carboxylate (3q): Yield
1
(m, 2 H), 1.37–1.50 (m, 3 H) ppm. 13C NMR (125 MHz, CDCl3): 86 mg, 78%, pink oil. H NMR (400 MHz, CDCl3): δ = 7.86 (d, J
δ = 155.4, 137.4, 133.0, 130.4, 128.4, 128.3, 127.8, 126.9, 123.5,
= 8.8 Hz, 1 H, ArH), 7.83 (s, 1 H, ArH), 6.72 (d, J = 8.4 Hz, 1 H,
ArH), 4.32 (q, J = 7.2 Hz, 2 H, CH3CH2O), 3.02 (s, 2 H, CH2),
1.48 (s, 6 H, 2 CH3), 1.36 (t, J = 7.2 Hz, 3 H, CH3CH2) ppm. 13C
122.2, 90.6, 48.6, 30.8, 27.3, 25.5, 24.6, 20.9 ppm. IR (thin film): ν
˜
= 2978, 2906, 1499, 1450, 1388, 1251, 1197, 1073 cm–1. MS (EI):
m/z (%) = 264 (100) [M]+, 249 (13), 235 (15), 221 (30), 197 (26). NMR (100 MHz, CDCl3): δ = 166.6, 162.8, 131.0, 127.4, 126.9,
HRMS (EI-TOF): calcd. for C19H20O [M]+ 264.1514; found
264.1519.
122.5, 109.1, 88.3, 60.5, 42.2, 28.1, 14.3 ppm. IR (thin film): ν =
˜
2975, 1708, 1611, 1486, 1386, 1269, 1094, 873, 768 cm–1. MS (EI):
m/z (%) = 220 (100) [M]+, 205 (62), 192 (26), 175 (100), 159 (11),
147 (70), 133 (82). HRMS (EI-TOF): calcd. for C13H16O3 [M]+
220.1099; found 220.1097.
trans-6-Allyl-8-methyl-1,2,3,4,4a,9b-hexahydrodibenzo[b,d]furan
(3m): Yield 59 mg, 52%, pale yellow oil. 1H NMR (400 MHz,
CDCl3): δ = 6.81 (s, 1 H, ArH), 6.78 (s, 1 H, ArH), 5.96–6.06 (m,
1 H, CH=), 5.05–5.13 (m, 2 H, CH2=), 3.78–3.84 (m, 1 H, OCH), 5-Bromo-2,2-dimethyl-2,3-dihydrobenzofuran (3r): Yield 46 mg,
1
3.35 (dd, J = 6.6, J = 1.4 Hz, 2 H, CH2CH=), 2.76 (t, J = 12.0 Hz, 40%, colorless oil. H NMR (400 MHz, CDCl3): δ = 7.23 (s, 1 H,
1 H), 2.30–2.36 (m, 2 H), 2.29 (s, 3 H, CH3), 1.95–1.98 (m, 1 H),
1.80–1.88 (m, 2 H), 1.35–1.46 (m, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 156.0, 136.6, 131.8, 130.0, 128.3, 121.7, 120.9, 115.5,
ArH), 7.19 (d, J = 8.8 Hz, 1 H, ArH), 6.60 (d, J = 8.4 Hz, 1 H,
ArH), 2.99 (s, 2 H, CH2), 1.46 (s, 6 H, 2 CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 158.0, 130.7, 129.6, 128.1, 111.6, 111.0,
90.4, 48.8, 33.7, 30.8, 27.3, 25.5, 24.6, 20.9 ppm. IR (thin film): ν
87.5, 42.7, 28.1 ppm. IR (thin film): ν = 2971, 2904, 1392, 1311,
˜
˜
= 2975, 2933, 1451, 1388, 1254, 1213, 1055, 858, 832 cm–1. MS
1266, 1227, 1072, 827 cm–1. MS (EI): m/z (%) = 228 (2) [M,
(EI): m/z (%) = 228 (100) [M]+, 213 (21), 199 (22), 185 (34), 161 Br81]+, 226 (2) [M, Br79]+, 211 (22), 185 (5), 147 (9), 132 (100).
(33). HRMS (EI-TOF): calcd. for C16H20O [M]+ 228.1514; found
228.1521.
HRMS (EI-TOF): calcd. for C10H11BrO [M]+ 225.9993; found
225.9993.
Ethyl 4-(2,5-Dimethyl-2,3-dihydrobenzofuran-7-yl)benzoate (3n): trans-8-Bromo-1,2,3,4,4a,9b-hexahydrodibenzo[b,d]furan (3s): Yield
Yield 86 mg, 58%, white solid, m.p. 47–50 °C. 1H NMR (400 MHz, 55 mg, 43%, white solid, m.p. 117–119 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.09 (d, J = 8.4 Hz, 2 H, ArH), 7.79 (d, J = 8.4 Hz, 2 CDCl3): δ = 7.21 (d, J = 7.2 Hz, 1 H, ArH), 7.20 (s, 1 H, ArH),
H, ArH), 7.12 (s, 1 H, ArH), 7.00 (s, 1 H, ArH), 4.90–5.05 (m, 1 6.71 (d, J = 8.8 Hz, 1 H, ArH), 3.86 (dt, J = 12.8, J = 3.7 Hz, 1
H, ArOCH), 4.39 (q, J = 7.2 Hz, 2 H, CH3CH2O), 3.33 (dd, J =
15.6, J = 8.8 Hz, 1 H), 2.84 (dd, J = 15.2, J = 7.6 Hz, 1 H), 2.34
(s, 3 H, CH3), 1.49 (d, J = 6.4 Hz, 3 H CH3CH), 1.41 (t, J = 7.0 Hz,
H, OCH), 2.79 (t, J = 12.0 Hz, 1 H, CH), 2.29–2.33 (m, 2 H), 1.95–
1.98 (m, 1 H), 1.75–1.88 (m, 2 H), 1.33–1.47 (m, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 159.3, 134.6, 130.3, 125.7, 112.8,
3 H, CH3CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.6, 111.5, 91.0, 48.7, 30.6, 27.0, 25.4, 24.4 ppm. IR (thin film): ν =
˜
154.9, 142.1, 130.0, 129.5, 128.6, 128.3, 128.1, 127.9, 125.6, 121.5,
2931, 2860, 1452, 1215, 1176, 1010, 816 cm–1. MS (EI): m/z (%) =
79.7, 60.8, 37.1, 21.8, 20.8, 14.3 ppm. IR (thin film): ν = 3671, 254 (54) [M, Br81]+, 252 (54) [M, Br79]+, 239 (10), 225 (13), 211
˜
2978, 2903, 1702, 1463, 1395, 1259, 1071 cm–1. MS (EI): m/z (%) (31), 198 (33), 145 (43), 132 (40), 115 (45), 77 (33), 67 (100). HRMS
= 296 (100) [M]+, 281 (3), 268 (7), 251 (19). HRMS (EI-TOF):
calcd. for C19H20O3 [M]+ 296.1412; found 296.1407.
(EI-TOF): calcd. for C12H13BrO [M]+ 252.0150; found 252.0145.
Ethyl 6H-Benzo[c]chromene-2-carboxylate (3t): Yield 62 mg, 48%,
Ethyl 4-(2,2,5-Trimethyl-2,3-dihydrobenzofuran-7-yl)benzoate (3o): pale yellow oil. 1H NMR (400 MHz, CDCl3): δ = 8.45 (d, J =
Yield 95 mg, 61%, yellow oil. 1H NMR (400 MHz, CDCl3): δ =
8.09 (d, J = 8.4 Hz, 2 H, ArH), 7.80 (d, J = 8.4 Hz, 2 H, ArH),
7.13 (s, 1 H, ArH), 6.98 (s, 1 H, ArH), 4.40 (q, J = 7.1 Hz, 2 H,
2.0 Hz, 1 H, ArH), 7.93 (dd, J = 8.4, J = 2.0 Hz, 1 H, ArH), 7.80
(d, J = 7.6 Hz, 1 H, ArH), 7.41 (t, J = 7.6 Hz, 1 H, ArH), 7.29 (t,
J = 7.6 Hz, 1 H, ArH), 7.15 (d, J = 8.0 Hz, 1 H, ArH), 7.00 (d, J
CH3CH2O), 3.03 (s, 2 H, CH2), 2.34 (s, 3 H, ArCH3), 1.50 (s, 6 H, = 8.8 Hz, 1 H, ArH), 5.18 (s, 2 H, CH2O), 4.29 (q, J = 6.9 Hz, 2
2 CH3), 1.41 (t, J = 7.0 Hz, 3 H, CH3CH2) ppm. 13C NMR H, CH3CH2O), 1.42 (t, J = 7.0 Hz, 3 H, CH3CH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 166.7, 154.4, 142.3, 129.6, 129.5, 128.45, (100 MHz, CDCl3): δ = 166.3, 158.5, 131.0, 130.7, 129.1, 128.7,
128.40, 128.0, 127.9, 125.7, 121.5, 86.7, 60.8, 42.8, 28.2, 20.8,
128.2, 125.2, 124.6, 124.3, 122.4, 122.2, 117.3, 68.6, 60.8, 14.4 ppm.
14.3 ppm. IR (thin film): ν = 2974, 1713, 1608, 1465, 1392, 1369,
IR (thin film): ν = 2979, 2903, 1709, 1610, 1449, 1239, 1102, 1029,
˜
˜
1269, 1100, 1022, 853 cm–1. MS (EI): m/z (%) = 310 (100) [M]+,
295 (31), 265 (31), 222 (22), 195 (25). HRMS (EI-TOF): calcd. for
C20H22O3 [M]+ 310.1569; found 310.1570.
770, 726 cm–1. MS (EI): m/z (%) = 254 (100) [M]+, 239 (2), 225
(46), 209 (55). HRMS (EI-TOF): calcd. for C16H14O3 [M]+
254.0943; found 254.0940.
10
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
Lewis-Acid-Promoted Arylation
H. Ila, H. P. Bell, Chem. Rev. 2004, 104, 3453–3516; f) G. Zeni,
Ethyl 6-Ethyl-6H-benzo[c]chromene-2-carboxylate (3u): Yield
81 mg, 57%, pale yellow oil. 1H NMR (400 MHz, CDCl3): δ = 8.45
(s, 1 H, ArH), 7.95 (d, J = 8.4 Hz, 1 H, ArH), 7.81 (d, J = 8.0 Hz,
1 H, ArH), 7.40 (t, J = 7.2 Hz, 1 H, ArH), 7.32 (t, J = 7.6 Hz, 1
H, ArH), 7.12 (d, J = 6.8 Hz, 1 H, ArH), 7.01 (d, J = 8.4 Hz, 1
H, ArH), 5.10–5.18 (m, 1 H, CHCH2), 4.40 (q, J = 6.8 Hz, 2 H,
CH3CH2O), 1.85–1.95 (m, 1 H), 1.70–1.80 (m, 1 H), 1.42 (t, J =
6.8 Hz, 3 H, CH3CH2O), 1.04 (t, J = 7.6 Hz, 3 H, CH3CH2) ppm.
13C NMR (100 MHz, CDCl3): δ = 166.4, 156.9, 134.2, 131.0, 128.3,
128.1, 128.0, 124.91, 124.87, 123.9, 122.4, 122.1, 117.8, 79.4, 60.8,
R. C. Larock, Chem. Rev. 2006, 106, 4644–4680.
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28.3, 14.4, 9.9 ppm. IR (thin film): ν = 2975, 1711, 1241 cm–1. MS
˜
(EI): m/z (%) = 282 (2) [M]+, 252 (100), 225 (50). HRMS (EI-TOF):
[7]
[8]
calcd. for C18H18O3 [M]+ 282.1256; found 282.1247.
Ethyl 6-Isopropyl-6H-benzo[c]chromene-2-carboxylate (3v): Yield
65 mg, 44%, pale yellow oil. 1H NMR (400 MHz, CDCl3): δ = 8.44
(d, J = 2.0 Hz, 1 H, ArH), 7.93 (dd, J = 8.4, J = 1.6 Hz, 1 H,
ArH), 7.81 (d, J = 8.0 Hz, 1 H, ArH), 7.40 (dt, J = 7.8, J = 1.1 Hz,
1 H, ArH), 7.30 (dt, J = 7.2, J = 0.8 Hz, 1 H, ArH), 7.10 (d, J =
7.2 Hz, 1 H, ArH), 7.00 (d, J = 8.4 Hz, 1 H, ArH), 4.85 (d, J =
7.6 Hz, 1 H, OCH), 4.39 (q, J = 7.1 Hz, 2 H, CH3CH2O), 1.96–
2.05 [m, 1 H, CH(CH3)2], 1.41 (t, J = 7.0 Hz, 3 H, CH3CH2O),
1.01 (d, J = 6.4 Hz, 3 H, CH3CH), 0.89 (d, J = 6.8 Hz, 3 H,
CH3CH) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.4, 157.2,
132.9, 131.0, 128.31, 128.27, 127.6, 126.3, 124.8, 123.7, 122.4,
122.2, 117.5, 83.6, 60.7, 32.6, 18.8, 18.3, 14.4 ppm. IR (thin film):
[9]
[10]
[11]
ν = 2972, 1711, 1609, 1494, 1448, 1367, 1241, 1103, 1002 cm–1. MS
˜
(EI): m/z (%) = 296 (7) [M]+, 253 (100), 225 (42), 180 (12), 152
(15). HRMS (EI-TOF): calcd. for C19H20O3 [M]+ 296.1412; found
296.1407.
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Supporting Information (see footnote on the first page of this arti-
cle): experimental procedures, characterization data, copies of 1H
and 13C NMR spectra for all products, and crystallographic infor-
mation file (CIF) for compound 3a.
Acknowledgments
We thank the financial support from the National Nature Science
Foundation of China (NSFC) (grant number 20902081) as well as
the Science Foundation of Zhejiang Sci-Tech University (grant
number 1206820-Y). We are grateful to Prof. Junliang Zhang for
assistance with HPLC analysis.
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Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
G. Zhao, B. Wang, W. Yang, H. Ren
FULL PAPER
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Received: July 8, 2012
Published Online: ᭿
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Job/Unit: O20902
/KAP1
Date: 25-09-12 16:15:10
Pages: 13
Lewis-Acid-Promoted Arylation
Oxygen Heterocycles
G. Zhao, B. Wang, W. Yang,
H. Ren* .......................................... 1–13
Lewis-Acid-Promoted Arylation Reaction:
Synthesis of Dihydrobenzofuran Deriva-
tives from Aryltriazenes
Highly functionalized dihydrobenzofuran
derivatives can be prepared from triazene
alcohols in the presence of a Lewis acid.
The cyclization of optically active triazene
alcohols is also discussed in this paper.
Keywords: Synthetic methods / Oxygen het-
erocycles / Carbocations / Lewis acids /
Cyclization
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