Synthesis of 2,5-dihydrobenzo[b]oxepins and 5,6-dihydro-2H-benzo[b]oxocines based on [3+3] cyclizations of 1,3-bis(silyl enol ethers)

Article abstract of DOI:10.1016/j.tet.2007.05.056

Functionalized 2,5-dihydrobenzo[b]oxepins and 5,6-dihydro-2H-benzo[b]oxocines were prepared based on a '[3+3] cyclization-olefin-metathesis' strategy.

Full text of DOI:10.1016/j.tet.2007.05.056

Tetrahedron 63 (2007) 8037–8045
Synthesis of 2,5-dihydrobenzo[b]oxepins and
5,6-dihydro-2H-benzo[b]oxocines based on [3D3]
cyclizations of 1,3-bis(silyl enol ethers)
Van Thi Hong Nguyen,a Esen Bellur,a Christine Fischera,b and Peter Langera,b,
*
aInstitut fu€r Chemie, Universita€t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
bLeibniz-Institut fu€r Katalyse e. V. an der Universita€t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Received 20 February 2007; revised 9 May 2007; accepted 16 May 2007
Available online 21 May 2007
Abstract—Functionalized 2,5-dihydrobenzo[b]oxepins and 5,6-dihydro-2H-benzo[b]oxocines were prepared based on a ‘[3+3] cyclization–
olefin-metathesis’ strategy.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
the synthesis of 2,5-dihydrobenzo[b]oxepins and 5,6-di-
hydro-2H-benzo[b]oxocines based on the combination of
formal [3+3] cyclizations11 of 1,3-bis(silyl enol ethers)12
with RCM. Herein, we report full details of these studies.
2,3,4,5-Tetrahydrobenzo[b]oxepins are present in a number
of natural products (e.g., heliannuols C and D1 or plumbagic
acid lactone).2 3,4,5,6-Tetrahydro-2H-benzo[b]oxocines
occur in heliannuols A and K,1,3 helianane4 and protosappa-
nine B.5 2,5-Dihydrobenzo[b]oxepins occur in heliannuol
B1 and in radulanins A, H and L.6 5,6-Dihydro-2H-benzo-
[b]oxocines are present in heliannuols G and H,4 specionine7
and sophoroside A.7 Benzene-fused oxygen heterocycles are
available by combination of the directed-ortho-metallation
(DoM) or arenes with ring-closing metathesis (RCM).8 A
number of benzo[b]oxepin and benzo[b]oxocine natural
products were prepared by RCM.9 Recently, we reported10
2. Results and discussion
The known 1,3-bis(silyl enol ethers) 1a,b are prepared
as reported (Scheme 1).13,14 The TiCl4 mediated [3+3]
Me3SiO OSiMe3
()
n
OEt
()
n
1a,b
i
OH
OMe OMe
EtO
O
3a,b
MeO
OMe
OH
2
HO
ii
O
Ph
OH
O
Heliannuol B
Radulanin A
()
n
()
n
iii
OH
O
O
6 (cat.)
HO
EtO
O
EtO
O
5a,b (n = 1, 2)
4a,b
O
O
PCy3
Ru CHPh
PCy3
Cl
Cl
Helianane
Heliannuol H
6
Keywords: Cyclizations; Heterocycles; Medium-sized rings; Ring-closing
metathesis; Silyl enol ethers.
* Corresponding author. Fax: +49 381 4986412; e-mail: peter.langer@
uni-rostock.de
Scheme 1. Synthesis of 5a,b: (i) TiCl4, CH2Cl2, ꢀ78/20 ꢁC; (ii)
H2C]CH–CH2Br (1.5 equiv), NaH (2.0 equiv), TBAI (2.0 equiv), THF,
0 ꢁC, 24 h, 0/20 ꢁC, 8–12 h; (iii) 6 (5 mol %), CH2Cl2 (1.5 equiv),
20 ꢁC, 6–8 h.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.056

8038
V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
Table 1. Products and yields
Table 2. Products and yields
1
3–5
n
3 (%)a
4 (%)a
5 (%)a
1
7
8–10
n
R1 R2
R3
8 (%)a 9 (%)a 10 (%)a
a
b
h
i
1
2
45
53
86
84
99
75
a
a
a
a
b
b
b
a
b
c
d
b
c
a
b
c
d
e
f
1
1
1
1
2
2
2
Me H
Me Me
Me
Me
Et
44
52
31
43
47
50
33
85
95
78
77
76
82
96
90
93
91
80
76
91
70
Et
Me
H
a
Yields of isolated products.
(CH2)2C6H4
Me Me
Me
Et
Et
Me
H
d
g
(CH2)2C6H4
cyclization of 1a and 1b with 1,1,3,3-tetramethoxypropane
(2) affords salicylates 3a and 3b, respectively (Scheme 1,
Table 1). Allylation of the hydroxy group affords the allylic
ethers 4a and 4b. Application of the Mitsunobu reaction for
O-allylation was not successful. Compounds 4a and 4b are
transformed into the desired 2,5-dihydrobenzo[b]oxepin 5a
and 5,6-dihydro-2H-benzo[b]oxocine 5b by RCM using
Grubbs’ I catalyst (6).15,16 Migration of the olefin function-
ality during RCM (to form cyclic enol ethers) is not
observed.17
a
Yields of isolated products.
The sodium hydride mediated reaction of 8a–g with allyl
bromide and homoallyl bromide affords the arylethers 9a–g,
which are transformed into the desired 2,5-dihydrobenzo-
[b]oxepins 10a–d and 5,6-dihydro-2H-benzo[b]oxocines
10e–g by RCM using Grubbs’ I catalyst (6) (Scheme 3,
Table 2).15,16 Migration of the olefin functionality during
RCM (to form cyclic enol ethers) is again not observed.17
The known silyl enol ethers 7a–d are prepared from pentane-
2,4-dione, 3-methylpentane-2,4-dione, heptane-3,5-dione
and 2-acetyltetralone.13,14 The TiCl4 mediated [3+3] cycli-
zation of 1,3-bis(silyl enol ethers) 1a,b with 7a–d affords
the salicylates 8a–g (Scheme 2, Table 2). Derivatives 8d
and 8g are formed with very good regioselectivity. The cycli-
zation proceeds by TiCl4 mediated isomerization of 7 by
shift of the silyl group (intermediate A), TiCl4 mediated at-
tack of carbon atom C-4 of 1a,b onto the carbon located next
to substituent R1 to give intermediate B (conjugate addition),
cyclization (intermediate C), and subsequent aromatiza-
tion.11,13 The yields of 8a–g are similar to those reported
for related [3+3] cyclizations11 and are not decreased by
the presence of the additional alkenyl moiety in the 1,3-bis-
(silyl enol ether).
R1
R1
R2
R3
R2
R3
()
()
n
n
i
OH
O
EtO
O
EtO
O
9a-g
8a-g
ii
R1
PCy3
Ru CHPh
R2
Cl
Cl
()
n
R3
EtO
PCy3
6
O
O
10a-g
Scheme 3. Synthesis of 10a–g: (i) H2C]CHCH2Br or H2C]CH(CH2)2Br
(1.5 equiv), NaH (2.0 equiv), TBAI (2.0 equiv), THF, 0/20 ꢁC, 8–12 h;
(ii) 6 (5 mol %), CH2Cl2 (1.5 equiv), 20 ꢁC, 6–8 h.
Me3SiO OSiMe3
()
n
In summary, we reported the synthesis of functionalized 2,5-
dihydrobenzo[b]oxepins and 5,6-dihydro-2H-benzo[b]oxo-
cines by combination of formal [3+3] cyclizations with the
ring-closing metathesis.
OEt
O
OH
1a,b
()
n
i
OEt
O
OSiMe3
R3
R1
R3
+
R1
R2
R2
7a-d
8a-g
3. Experimental section
3.1. General
O
O
Me3SiO
R1
O
()
n
OEt
R3
Bruker TO 250 (250 MHz), Bruker ARX 300 (300 MHz) or
Varian Inova 500 (500 MHz); d¼0.00 ppm for tetramethyl-
silane, d¼2.04 ppm for acetone-d6, d¼7.26 ppm for deutero-
chloroform (CDCl3). Characterization of the signal
fragmentations: s¼singlet, d¼doublet, dd¼doublet of dou-
blet, ddd¼doublet of a double doublet, t¼triplet, q¼quartet,
quint¼quintet, sixt¼sextet, sept¼septet, m¼multiplet,
br¼broadly. Spectra were evaluated according to first order
rule. Equipment: Bruker AM 250 (62.9 MHz), Bruker
ARX 300 (75 MHz) or Bruker Advance 600 (150 MHz);
d¼128.00 ppm for acetone-d6, d¼77.00 ppm for CDCl3.
The multiplicity of the carbon atoms was determined by
the DEPT 135 and APT (APT¼Attached Proton Test)
techniques and quoted as CH3, CH2, CH and C for primary,
secondary, tertiary and quaternary carbon atoms. Character-
ization of the signal fragmentations: quart¼quartet, the
R3
R1
R2
OTiCl3
R2
A
C
1a,b
_
(Me3Si)2O
TiCl4
_
Me3SiCl
O
Me3SiO
()
R1
OEt
n
R3
O
Me3SiO
R2 TiCl3
B
Scheme 2. Synthesis of 8a–g: (i) TiCl4 (1.0 equiv), CH2Cl2, ꢀ78/20 ꢁC.

V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
8039
multiplicity of the signals was determined by the DEPT re-
cording technology and/or the APT recording technology.
Mass spectroscopy: APPM MS40, Varian MAT CH 7,
MAT 731, Finnigan MAT 95 spectrometer (EI, 70 eV),
Finnigan LC-Q (ESI). High-resolution mass spectroscopy:
Finnigan MAT 95 or Varian MAT 311, Bruker FT CIR.
Infrared spectroscopy (IR): Bruker IFS 66 (FTIR), Nicolet
205 FTIR; KBr and/or KAP; abbreviations for signal
allocations: w¼weak, m¼middle, s¼strong, br¼broad.
UV–vis spectroscopy: Perkin–Elmer UV–vis/NIR Lambda
19, as solvent CH3CN was used. Elementary analyses: Mi-
croanalytical laboratory of the University of Greifswald
(Leco CHN CHNS-932). Melting points: Microheating
1,1,3,3-tetramethoxypropane (1.642 g, 10 mmol) and CH2Cl2
(25 mL), 3b was isolated by column chromatography (n-
hexane/EtOAc¼20:1) as a colourless oil (1.177 g, 53%).
1H NMR (CDCl3, 300 MHz): d¼1.41 (t, J¼7.2 Hz, 3H,
OCH2CH3), 2.38 (q, J¼7.8 Hz, 2H, CH2CH2CH]CH2),
2.75 (t, J¼7.8 Hz, 2H, CH2CH2CH]CH2), 4.43 (q,
J¼7.2 Hz, 2H, OCH2CH3), 4.95–5.07 (m, 2H, CH2]
CHCH2), 5.81–5.94 (m, 1H, CH2]CHCH2), 6.80 (t,
J¼7.8 Hz, 1H, Ar), 7.31 (dd, J¼7.3, 1.2 Hz, 1H, Ar),
7.72 (dd, J¼7.8, 1.8 Hz, 1H, Ar), 11.1 (s, 1H, OH).
13C NMR (CDCl3, 75 MHz): d¼14.2 (CH3), 26.2, 33.5,
61.4 (CH2), 112.1 (C), 114.5 (CH2), 119.2 (CH), 127.1
(C), 128.2, 134.4, 138.6 (CH), 159.2, 171.2 (C). IR
(KBr, cmꢀ1): n¼3100 (m, br), 2981 (m), 2937 (m), 1669
(s), 1612 (m), 1448 (m), 1400 (m), 1375 (m), 1316 (s),
1256 (s), 1194 (s), 1125 (m), 1027 (m), 913 (m), 763 (m).
MS (EI, 70 eV): m/z (%)¼220 (M+, 12), 179 (33),
134 (100), 106 (34), 91 (19), 77 (25). HRMS (EI, 70 eV)
calcd for C13H16O3 ([M+]): m/z¼220.10994, found:
m/z¼220.10953.
€
~
table HMK 67/1825 Kuestner (Buchi apparatus). Melting
points are uncorrected. Column chromatography: chromato-
graphic separation took place at Merck silica gel 60 (0.063–
0.200 mm, 70–230 mesh) as normal and/or at Macherey
silica gel 60 (0.040–0.063 mm, 200–400 mesh) as flash
chromatography. TLC: Merck DC finished foils, silica gel
60 F254 on aluminium foil and Macherey finished foils
AlugramÒ Sil G/UV254. Detection under UV light with
254 nm and/or 366 nm without dipping reagent, as well
as with anisic aldehyde sulfuric acid dip reagent (1 mL of
anisic aldehyde dissolved in 100 mL of a stock solution of
85% methanol, 14% acetic acid and 1% sulfuric acid).
3.2.3. Ethyl 3-allyl-2-hydroxy-4,6-dimethylbenzoate (8a).
Starting with 1a (1.257 g, 4.0 mmol), TiCl4 (0.760 g,
4.0 mmol) in 10 mL of CH2Cl2 and 7a (0.680 g,
4.0 mmol), 8a was isolated by column chromatography (n-
hexane/EtOAc¼20:1) as a colourless oil (0.338 g, 44%).
1H NMR (CDCl3, 300 MHz): d¼1.42 (t, J¼7.2 Hz, 3H,
OCH2CH3), 2.25 (s, 3H, CH3), 2.49 (s, 3H, CH3), 3.43 (m,
J¼1.5 Hz, 2H, CH2]CHCH2), 4.42 (q, J¼7.1 Hz, 2H,
OCH2CH3), 4.89–4.99 (m, J¼15.5, 10.4, 1.7 Hz, 2H,
CH2]CHCH2), 5.93 (m, J¼5.2, 1.5 Hz, 1H, CH2]
CHCH2), 6.55 (s, 1H, CH, Ar), 11.75 (s, 1H, OH). 13C
NMR (CDCl3, 75 MHz): d¼14.2, 19.6, 23.9 (CH3), 30.1,
61.4 (CH2), 109.8 (C), 114.4 (CH2), 123.8 (C), 124.7,
135.7 (CH), 138.5, 143.6, 160.8, 172.2 (C). IR (KBr,
cmꢀ1): ~n¼2979 (m), 2934 (m), 1654 (s), 1616 (m), 1449
(m), 1396 (s), 1268 (s), 1173 (s), 1031 (m), 847 (m). UV–
vis (CH3CN, nm): lmax (log 3)¼216.7 (4.41), 253.2 (3.98),
315.6 (3.57). MS (EI, 70 eV): m/z (%)¼234 (M+, 29), 188
(34), 173 (24), 160 (53), 145 (27), 114 (9), 91 (11), 28
(100). HRMS (EI, 70 eV) calcd for C14H18O3: m/z¼
234.1256 ([M+]), found: m/z¼234.1256ꢃ2 ppm.
3.2. General procedure for the synthesis of 3a,b and 8a–g
To a CH2Cl2 solution of 1a,b and 7a–d or 1,1,3,3-tetrameth-
oxypropane (2) was dropwise added TiCl4 at ꢀ78 ꢁC under
argon atmosphere. The solution was stirred at ꢀ78 ꢁC for
30 min andwassubsequentlyallowed towarmto20 ꢁCwithin
18 h. To the solution was added a saturated aqueous solution
of NaHCO3. The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (4ꢂ100 mL). The combined
organic layers were dried (Na2SO4), filtered and the filtrate
was concentrated in vacuo. The residue was purified by
column chromatography (silica gel, n-hexane/EtOAc).
3.2.1. Ethyl 3-allyl-2-hydroxybenzoate (3a). Starting with
1a (1.570 g, 5.0 mmol), TiCl4 (0.945 g, 5.0 mmol), 1,1,3,3-
tetramethoxypropane (0.821 g, 5.0 mmol) and CH2Cl2
(10 mL), 3a was isolated by column chromatography (n-
hexane/EtOAc¼20:1) as a colourless oil (0.464 g, 45%).
1H NMR (CDCl3, 300 MHz): d¼1.41 (t, J¼7.2 Hz, 3H,
OCH2CH3), 3.44 (d, J¼6.6 Hz, 2H, CH2]CHCH2), 4.42
(q, J¼7.1 Hz, 2H, OCH2CH3), 5.05–5.12 (m, 2H,
CH2]CHCH2), 5.95–6.08 (m, 1H, CH2]CHCH2), 6.82
(t, J¼7.8 Hz, 1H, Ar), 7.31 (dd, J¼6.0, 1.5 Hz, 1H, Ar),
7.75 (dd, J¼6.3, 1.7 Hz, 1H, Ar), 11.14 (s, 1H, OH). 13C
NMR (CDCl3, 75 MHz): d¼14.2 (CH3), 33.6, 61.4 (CH2),
112.2 (C), 115.8 (CH2), 118.6, 127.9 (CH), 128.5 (C),
135.6, 136.2 (CH), 159.6, 170.6 (C). IR (KBr, cmꢀ1):
~n¼3139 (m, br), 2983 (m), 1672 (s), 1614 (m), 1449 (s),
1303 (s), 1248 (s), 1150 (s), 1025 (s), 760 (s). UV–vis
(CH3CN, nm): lmax (log 3)¼209.3 (4.47), 242.4 (3.92),
309.7 (3.63). MS (EI, 70 eV): m/z (%)¼206 (M+, 38),
160 (43), 132 (100), 103 (34), 77 (41), 51 (16). Anal.
Calcd for C12H14O3: C 69.88, H 6.79; found: C 69.31,
H 7.04.
3.2.4. Ethyl 3-allyl-2-hydroxy-4,5,6-trimethylbenzoate
(8b). Starting with 1a (1.257 g, 4.0 mmol) and 7b (0.745 g,
4.0 mmol) in 10 mL of CH2Cl2 and TiCl4 (0.760 g,
4.0 mmol), 8b was isolated by column chromatography (n-
hexane/EtOAc¼30:1) as a colourless oil (0.520 g, 52%).
1H NMR (CDCl3, 300 MHz): d¼1.41 (t, J¼7.1 Hz, 3H,
OCH2CH3), 2.17 (s, 3H, CH3), 2.23 (s, 3H, CH3), 2.44 (s,
3H, CH3), 3.50 (m, J¼1.18 Hz, 2H, CH2]CHCH2), 4.43
(q, J¼7.1 Hz, 2H, OCH2CH3), 4.95 (m, J¼15.5, 11.5,
1.8 Hz, 2H, CH2]CHCH2), 5.98 (m, J¼5.5, 1.3 Hz, 1H,
CH2]CHCH2), 11.51 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼14.2, 16.1, 16.9, 19.2 (CH3), 30.5, 61.4
(CH2), 111.6 (C), 114.4 (CH2), 123.4, 127.2 (C), 135.6,
136.1 (CH), 142.3, 156.9, 172.0 (C). IR (KBr, cmꢀ1):
~n¼2981 (m), 2931 (m), 1654 (s), 1600 (m), 1456 (s), 1403
(s), 1374 (s), 1312 (s), 1260 (s), 1196 (s), 1045 (m), 1019
(m), 910 (m), 806 (m). UV–vis (CH3CN, nm): lmax (log 3)¼
217.1 (4.38), 256.1 (3.94), 320.9 (3.57). MS (EI, 70 eV): m/z
(%)¼248 (M+, 58), 202 (55), 187 (40), 174 (100), 159 (65),
91 (18), 28 (12). HRMS (ESI+) calcd for C15H20O3 [M++1]:
3.2.2. Ethyl 3-(but-3-enyl)-2-hydroxybenzoate (3b). Start-
ing with 1b (3.286 g, 10 mmol), TiCl4 (1.89 g, 10 mmol),

8040
V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
m/z¼249.14907; found: m/z¼249.14867. Anal. Calcd for
CH2]CHCH2), 10.74 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼14.2, 16.1, 16.9, 19.2 (CH3), 26.2, 33.3, 61.4
(CH2), 111.2 (C), 114.3 (CH2), 125.8, 127.1, 135.1 (C),
138.8 (CH), 141.6, 157.0, 172.1 (C). IR (KBr, cmꢀ1):
~n¼3075 (m), 2979 (s), 2932 (s), 1651 (s), 1599 (s), 1446
(s), 1403 (s), 1374 (s), 1312 (s), 1254 (s), 1196 (s), 1117
(m), 1045 (s), 1023 (m), 911 (m), 806 (m). UV–vis
(CH3CN, nm): lmax (log 3)¼217.2 (4.37), 256.6 (3.92),
321.4 (3.54). MS (EI, 70 eV): m/z (%)¼262 (M+, 16), 221
(24), 175 (100), 146 (8), 91 (15), 79 (16), 28 (30). HRMS
(ESI+) calcd for C16H22O3 [M++1]: m/z¼263.16472; found:
m/z¼263.16413.
C15H20O3: C 72.55, H 8.18; found: C 72.13, H 7.67.
3.2.5. Ethyl 3-allyl-4,6-diethyl-2-hydroxybenzoate (8c).
Starting with 1a (1.257 g, 4.0 mmol), 7c (0.800 g, 4.0 mmol)
in 10 mL of CH2Cl2 and TiCl4 (0.760 g, 4.0 mmol), 8c
was isolated by column chromatography (n-hexane/
1
EtOAc¼50:1) as a colourless oil (0.320 g, 31%). H NMR
(CDCl3, 300 MHz): d¼1.17 (t, J¼7.4 Hz, 6H, 2CH3CH2),
1.42 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.60 (q, J¼7.5 Hz, 2H,
CH3CH2), 2.92 (q, J¼7.4 Hz, 2H, CH3CH2), 3.44 (m,
J¼2.4, 1.7 Hz, 2H, CH2]CHCH2), 4.43 (q, J¼7.2 Hz,
2H, OCH2CH3), 4.99 (m, J¼10.0, 1.7 Hz, 2H, CH2]
CHCH2), 5.97 (m, J¼1.3 Hz, 1H, CH2]CHCH2), 6.59 (s,
1H, CH, Ar), 11.66 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼14.2, 15.1, 16.3 (CH3), 26.1, 29.7, 29.8, 61.1
(CH2), 109.1 (C), 114.4 (CH2), 121.8 (CH), 123.2 (C),
136.5 (CH), 145.0, 149.4, 160.8, 172.0 (C). IR (KBr,
cmꢀ1): ~n¼3078 (w), 2974 (m), 2879 (w), 1978 (w), 1654
(s), 1614 (m), 1401 (s), 1317 (m), 1266 (s), 1167 (m),
1019 (w), 909 (w), 865 (w). UV–vis (CH3CN, nm): lmax
(log 3)¼217.0 (4.44), 254.4 (4.02), 315.9 (3.63). MS (EI,
70 eV): m/z (%)¼263 (M++1, 6), 262 (M+, 52), 216 (100),
201 (51), 173 (99), 159 (67), 73 (36), 28 (94).
3.2.8. Ethyl 3-(but-3-enyl)-4,6-diethyl-2-hydroxybenz-
oate (8f). Starting with 1b (0.985 g, 3.0 mmol) and 7c
(0.600 g, 3.0 mmol) in 8 mL of CH2Cl2 and TiCl4
(0.569 g, 3.0 mmol), 8f was isolated by column chromato-
graphy (n-hexane/EtOAc¼50:1) as
a colourless oil
1
(0.415 g, 50%). H NMR (CDCl3, 300 MHz): d¼1.20 (t,
J¼7.4 Hz, 6H, 2CH3CH2), 1.42 (t, J¼7.1 Hz, 3H,
OCH2CH3), 2.28 (m, 2H, CH2]CHCH2CH2), 2.60 (q,
J¼7.5 Hz, 2H, CH3CH2), 2.73 (m, J¼6.5, 1.5 Hz, 2H,
CH2]CHCH2CH2), 2.91 (q, J¼7.4 Hz, 2H, CH3CH2),
4.43 (q, J¼7.1 Hz, 2H, OCH2CH3), 4.95–5.09 (m, J¼10.1,
15.4, 1.2 Hz, 2H, CH2]CHCH2CH2), 5.92 (m, J¼6.5,
3.4 Hz, 1H, CH2]CHCH2CH2), 6.57 (s, 1H, CH, Ar),
11.65 (s, 1H, OH). 13C NMR: d¼14.0, 15.2, 16.3 (CH3),
25.4, 26.3, 29.7, 33.5, 61.3 (CH2), 109.0 (C), 114.3 (CH2),
121.8 (CH), 125.6 (C), 138.9 (CH), 144.4, 148.9, 161.0,
172.0 (C). IR (KBr, cmꢀ1): ~n¼3077 (w), 2973 (s), 2936
(m), 1652 (s), 1614 (m), 1454 (w), 1399 (s), 1376 (m),
1318 (m), 1260 (s), 1171 (m), 1022 (w), 847 (w). UV–vis
(CH3CN, nm): lmax (log 3)¼217.1 (4.46), 254.9 (4.02),
316.4 (3.61). MS (EI, 70 eV): m/z (%)¼277 (M++1, 6),
276 (M+, 7), 235 (23), 189 (100), 91 (6), 79 (6), 32 (20),
28 (89). HRMS (ESI+) calcd for C17H24O3 [M++1]:
m/z¼277.18037; found: m/z¼277.18001. Anal. Calcd for
C17H24O3: C 73.88, H 8.75; found C 73.35, H 8.58.
3.2.6. Ethyl 2-allyl-9,10-dihydro-3-hydroxy-1-methyl-
phenanthrene-4-carboxylate (8d). Starting with 1a (1.89 g,
6.0 mmol), 7d (1.56 g, 6.0 mmol) in 15 mL of CH2Cl2 and
TiCl4 (1.14 g, 6.0 mmol), 8d was isolated by column chro-
matography (n-hexane/EtOAc¼30:1) as a colourless oil
1
(0.820 g, 43%). H NMR (CDCl3, 300 MHz): d¼1.00 (t,
J¼7.1 Hz, 3H, OCH2CH3), 2.28 (s, 3H, CH3), 2.65 (m,
J¼5.5, 1.2 Hz, 2H, CH2), 2.81 (m, J¼6.8 Hz, 2H, CH2),
3.55 (m, J¼2.5, 1.8 Hz, 2H, CH2]CHCH2), 4.16 (q,
J¼7.1 Hz, 2H, OCH2CH3), 4.96–5.04 (m, J¼6.0, 1.8 Hz,
2H, CH2]CHCH2), 5.96 (m, J¼5.8, 1.4 Hz, 1H,
CH2]CHCH2), 7.09–7.24 (m, 4H, Ar), 9.95 (s, 1H, OH).
13C NMR (CDCl3, 75 MHz): d¼13.4, 15.9 (CH3), 25.7,
29.2, 30.7, 61.2 (CH2), 109.1 (C), 114.8 (CH2), 123.8, 125.2
(C), 125.3 (CH), 126.8 (C), 126.9, 129.2 (CH), 130.5,
134.7, 135.6 (C), 135.7 (CH), 140.2, 156.3, 172.1 (C). IR
(KBr, cmꢀ1): ~n¼3217 (br, w), 3072 (m), 2980 (m), 2899
(m), 1661 (s), 1597 (m), 1442 (s), 1401 (s), 1375 (s), 1315
(s), 1255 (s), 1191 (s), 1123 (m), 1054 (m), 1018 (m), 911
(m), 785 (s). UV–vis (CH3CN, nm): lmax (log 3)¼203.9
(4.49), 231.9 (4.39), 279.9 (3.94), 340.9 (3.89). MS (EI,
70 eV): m/z (%)¼322 (M+, 2), 276 (3), 248 (5), 105 (8), 78
(8), 74 (29), 32 (23), 28 (100). HRMS (ESI+) calcd for
C21H22O3 [M++1]: m/z¼323.16472; found: 323.16442.
Anal. Calcd for C15H20O3: C 78.23, H 6.88; found: C 78.42,
H 7.60.
3.2.9. Ethyl 2-(but-3-enyl)-9,10-dihydro-3-hydroxy-1-
methylphenanthrene-4-carboxylate (8g). Starting with
1b (2.63 g, 8.0 mmol) and 7d (2.08 g, 8.0 mmol) in 20 mL
of CH2Cl2 and TiCl4 (1.52 g, 8.0 mmol), 8g was isolated
by column chromatography (n-hexane/EtOAc¼30:1) as
a colourless solid (0.874 g, 33%). 1H NMR (CDCl3,
300 MHz): d¼1.02 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.27 (m,
J¼2.5 Hz, 2H, CH2]CHCH2CH2), 2.29 (s, 3H, CH3),
2.65 (m, J¼5.7 Hz, 2H, CH2), 2.81 (m, J¼5.3 Hz, 2H,
CH2), 2.86 (m, J¼2.5 Hz, 2H, CH2]CHCH2), 4.16 (q,
J¼7.1 Hz, 2H, OCH2CH3), 4.98–5.12 (m, J¼10.2, 15.1,
1.8 Hz, 2H, CH2]CHCH2CH2), 5.95 (m, 1H, CH2]
CHCH2CH2), 7.09 (m, 1H, Ar), 7.14–7.25 (m, 3H, Ar),
9.93 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz): d¼13.4,
16.0 (CH3), 25.7, 26.3, 29.2, 33.2, 61.2 (CH2), 108.9 (C),
114.5 (CH2), 125.3, 126.8, 126.9 (CH), 127.7 (C), 129.2
(CH), 130.5, 134.3, 134.7, 137.6 (C), 138.6 (CH), 139.6,
3.2.7. Ethyl 3-(but-3-enyl)-2-hydroxy-4,5,6-trimethyl-
benzoate (8e). Starting with 1b (1.97 g, 6.0 mmol) and 7b
(1.12 g, 6.0 mmol) in 15 mL of CH2Cl2 and TiCl4 (1.14 g,
6.0 mmol), 8e was isolated by column chromatography (n-
hexane/EtOAc¼30:1) as a colourless oil (0.735 g, 47%).
1H NMR (CDCl3, 300 MHz): d¼1.41 (t, J¼7.1 Hz, 3H,
OCH2CH3), 2.16 (s, 3H, CH3), 2.19–2.26 (m, 2H,
CH2]CHCH2CH2), 2.27 (s, 3H, CH3), 2.43 (s, 3H, CH3),
2.80 (m, J¼6.9, 2.1 Hz, 2H, CH2]CHCH2CH2), 4.43 (q,
J¼7.1 Hz, 2H, OCH2CH3), 4.95–5.10 (m, J¼9.5, 17.1,
1.6 Hz, 2H, CH2]CHCH2CH2), 5.92 (m, J¼5.2 Hz, 1H,
1
156.5, 172.2 (C). H NMR (CDCl3, 500.13 MHz) d: 9.93
(s, 1H, OH), 7.24 (dd, J10,11¼7.3 Hz, J10,12¼1.6 Hz, 1H,
3
4
3
H-10), 7.20–7.13 (m, 2H, H-11,12), 7.08 (dd, J12,13
7.3 Hz, J11,13¼1.6 Hz, 1H, H-13), 5.96 (m, 1H, H-17),
¼
4
5.10 (dq, 3J17,18a¼17.0 Hz, 1H, H-18a), 5.00 (dq, 3J17,18b
¼
10.0 Hz, 1H, H-18b), 4.17 (q, 2H, CH2CH3), 2.86 (m, 2H,
H-15), 2.81 (m, 2H, H-8), 2.64 (m, 2H, H-7), 2.30 (s, 3H,

V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
8041
3
Me), 2.29 (m, 2H, H-16), 1.00 (t, 3H, JCH ;CH ¼ 7:3 Hz,
1.5 Hz, 1H, Ar), 7.32–7.38 (ddd, J¼7.5, 3.6, 1.8 Hz, 1H,
Ar), 7.64–7.71 (ddd, J¼7.5, 7.5, 1.8 Hz, 1H, Ar). 13C
NMR (CDCl3, 75 MHz): d¼14.2 (CH3), 26.4, 34.5, 61.2,
75.8, 114.6, 116.7 (CH2), 117.5 (C), 122.9 (CH), 125.2
(C), 128.9, 133.9, 134.6, 138.4 (CH), 155.7, 167.2 (C). IR
(KBr, cmꢀ1): ~n¼2928 (m), 1725 (s), 1644 (m), 1556 (w),
1456 (m), 1415 (m), 1288 (m), 1257 (s), 1145 (m), 1099
(w), 991 (m), 919 (m). MS (EI, 70 eV): m/z (%)¼260 (M+,
32), 219 (65), 203 (5), 174 (100), 148 (10), 103 (17), 87
(25), 76 (55). HRMS (EI, 70 eV) calcd for C16H20O3
([M+]): m/z¼260.14124; found: m/z¼260.14095.
2
3
CH2CH3). 13C NMR (CDCl3, 125.8 MHz) d: 172.2 (CO),
156.5 (C-3), 139.6 (C-5), 138.6 (C-17), 137.6 (C-9), 134.8
(C-14), 134.3 (C-1), 130.5 (C-6), 129.2 (C-13), 127.7 (C-
4), 126.9, 126.8 (C-10,11), 125.3 (C-12), 114.5 (C-18),
109.0 (C-2), 61.2 (CH2CH3), 33.2 (C-16), 29.2 (C-8), 26.3
(C-15), 25.7 (C-7), 16.0 (Me), 13.4 (CH2CH3). IR (KBr,
cmꢀ1): ~n¼3429 (br, m), 2981 (m), 2898 (m), 1660 (s),
1443 (m), 1398 (m), 1373 (m), 1315 (s), 1251 (s), 1197
(s), 1026 (m), 910 (w), 762 (m). UV–vis (CH3CN, nm):
lmax (log 3)¼203.1 (4.53), 231.8 (4.39), 280.2 (3.94),
341.2 (3.89). MS (EI, 70 eV): m/z (%)¼336 (M+, 8),
275 (5), 249 (24), 114 (9), 79 (8), 74 (18), 32 (24), 28
(100). HRMS (ESI+) calcd for C22H24O3 [M++1]: m/z¼
337.18037; found: m/z¼337.18044.
3.3.3. Ethyl 3-allyl-2-(allyloxy)-4,6-dimethylbenzoate
(9a). Starting with 8a (0.285 g, 1.22 mmol, 1.0 equiv) in
15 mL of THF, NaH (0.059 g, 2.44 mmol, 2.0 equiv),
n-Bu4NI (0.797 g, 2.44 mmol, 2.0 equiv) and allyl bromide
(0.220 g, 1.83 mmol, 1.5 equiv), 9a was isolated as a colour-
less oil (0.285 g, 85%). 1H NMR (CDCl3, 300 MHz):
d¼1.37 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.24 (s, 3H, CH3),
2.26 (s, 3H, CH3), 3.42 (m, J¼1.8 Hz, 2H,
CH2]CHCH2Ar), 4.37 (q, J¼7.1 Hz, 2H, OCH2CH3),
4.39 (m, J¼1.5 Hz, 2H, CH2]CHCH2O), 4.86–4.93 (m,
J¼15.3, 10.2, 1.8 Hz, 2H, CH2]CHCH2Ar), 5.34–5.41
(m, J¼10.4, 15.5, 1.6 Hz, 2H, CH2]CHCH2O), 5.88–5.93
(m, J¼5.4 Hz, 1H, CH2]CHCH2), 5.99–6.03 (s,
J¼5.3 Hz, 1H, CH2]CHCH2O), 6.80 (s, 2H, Ar). 13C
NMR (CDCl3, 75 MHz): d¼14.3, 19.0, 19.4 (CH3), 30.5,
61.1, 76.0, 115.2, 116.8 (CH2), 126.8 (C), 127.8 (CH),
128.9 (C), 133.9 (CH), 134.0 (C), 136.1 (CH), 140.1,
154.4, 168.6 (C). IR (KBr, cmꢀ1): ~n¼3081 (m), 2981 (s),
2928 (s), 2870 (m), 1726 (s), 1642 (m), 1609 (m), 1666
(m), 1453 (s), 1411 (s), 1297 (s), 1270 (s), 1150 (s), 1108
(s), 1067 (s), 1041 (s), 992 (s), 918 (s), 864 (m). UV–vis
(CH3CN, nm): lmax (log 3)¼202.9 (4.59), 276.4 (3.89).
MS (EI, 70 eV): m/z (%)¼275.5 (M++1, 11), 274.5 (M+,
62), 233 (24), 232 (26), 229 (36), 228 (17), 201 (12), 188
(19), 187 (100), 173 (20), 161 (34), 160 (36), 159 (31),
145 (18), 91 (16), 41 (20), 29 (11). Anal. Calcd for
C17H22O3: C 74.42, H 8.08; found: C 74.41, H 7.91.
3.3. General procedure for the synthesis of salicylates
4a,b and 9a–g
To a mixture of NaH and of n-Bu4NI was simultaneously
added a THF solution of 3a,b or 8a–g and of allyl bromide
or homoallyl bromide at 0 ꢁC under argon atmosphere.
The pale yellow coloured solution was stirred at 0 ꢁC and
was allowed to warm to 20 ꢁC within 8–12 h. The solvent
was removed in vacuo and the residue was purified by col-
umn chromatography (silica gel, n-hexane/EtOAc¼20:1).
3.3.1. Ethyl 3-allyl-2-(allyloxy)benzoate (4a). Starting
with 3a (0.300 g, 1.46 mmol) in 20 mL of THF, NaH
(0.077 g, 3.2 mmol), n-Bu4NI (1.182 g, 3.2 mmol) and allyl
bromide (0.440 g, 3.2 mmol), 4a was isolated as a yellow oil
(0.308 g, 86%). 1H NMR (CDCl3, 300 MHz): d¼1.39
(t, J¼7.2 Hz, 3H, OCH2CH3), 3.46 (d, J¼6.6 Hz,
2H, CH2]CHCH2), 4.37 (q, J¼7.2 Hz, 2H, OCH2CH3),
4.42–4.46 (m, 2H, CH2]CHCH2O), 4.81 (dt, J¼5.7,
1.4 Hz, 1H, CH2]CHCH2Ar), 5.03–5.10 (m, 1H, CH2]
CHCH2Ar), 5.27 (tquint, J¼10.5, 1.4 Hz, 1H, CH2]
CHCH2O), 5.35–5.45 (m, 1H, CH2]CHCH2O), 5.90–6.15
(m, 2H, 2ꢂCH2]CH), 7.11 (dt, J¼7.8, 1.5 Hz, 1H, Ar),
7.34–7.39 (ddd, J¼7.5, 3.6, 1.8 Hz, 1H, Ar), 7.66–7.72
(ddd, J¼7.5, 7.5, 1.8 Hz, 1H, Ar). 13C NMR (CDCl3,
75 MHz): d¼14.3 (CH3), 33.8, 65.8, 75.6, 116.3, 117.4
(CH2), 118.6 (C), 123.7 (CH), 125.4 (C), 129.7, 133.8,
134.5, 136.8 (CH), 157.1, 166.1 (C). IR (KBr, cmꢀ1):
~n¼2927 (m), 1724 (s), 1645 (w), 1452 (m), 1417 (m),
1290 (m), 1258 (s), 1219 (w), 1136 (s), 1099 (w), 992
(m), 922 (w). MS (EI, 70 eV): m/z (%)¼246 (M+, 1), 204
(64), 191 (22), 179 (41), 159 (91), 145 (30), 131 (100),
115 (31), 103 (58), 91 (22), 77 (44). HRMS (EI, 70 eV)
calcd for C15H18O3 ([M+]): m/z¼246.1250; found: m/z¼
246.1241.
3.3.4. Ethyl 3-allyl-2-(allyloxy)-4,5,6-trimethylbenzoate
(9b). Starting with 8b (0.179 g, 0.72 mmol, 1.0 equiv) in
10 mL of THF, NaH (0.035 g, 1.44 mmol, 2.0 equiv),
n-Bu4NI (0.471 g, 1.44 mmol, 2.0 equiv) and allyl bromide
(0.130 g, 1.08 mmol, 1.5 equiv), 9b was isolated as a colour-
less oil (0.195 g, 94%). 1H NMR (CDCl3, 300 MHz):
d¼1.37 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.16 (s, 3H, CH3),
2.17 (s, 3H, CH3), 2.19 (s, 3H, CH3), 3.46 (m, J¼1.9 Hz,
2H, CH2]CHCH2Ar), 4.33 (m, J¼1.4 Hz, 2H, CH2]
CHCH2O), 4.36 (q, J¼7.0 Hz, 2H, OCH2CH3), 4.85–5.04
(m, J¼15.4, 10.3, 1.8 Hz, 2H, CH2]CHCH2Ar), 5.18–
5.39 (m, J¼10.5, 15.5, 1.6 Hz, 2H, CH2]CHCH2O),
5.95–5.98 (m, 1H, CH2]CHCH2Ar), 5.99–6.04 (m, 1H,
CH2]CHCH2O). 13C NMR (CDCl3, 75 MHz): d¼14.2,
15.9, 16.4, 17.3 (CH3), 30.8, 61.2, 76.1, 115.2, 116.7
(CH2), 127.6, 128.8, 131.6, 131.8 (C), 133.9, 136.5 (CH),
138.4, 151.6, 169.3 (C). IR (KBr, cmꢀ1): ~n¼2982 (m),
2931 (m), 1728 (s), 1445 (m), 1418 (m), 1273 (s), 1189
(s), 1045 (s), 917 (m). UV–vis (CH3CN, nm): lmax
(log 3)¼202.9 (4.58), 279.4 (2.96). MS (EI, 70 eV): m/z
(%)¼289 (M++1, 10), 288 (M+, 59), 247 (27), 201 (100),
174 (34), 159 (23), 91 (19), 41 (23), 28 (4). Anal. Calcd
for C18H24O3: C 74.96, H 8.39; found: C 74.34, H 8.50.
3.3.2. Ethyl 2-(allyloxy)-3-(but-3-enyl)benzoate (4b).
Starting with 3b (0.500 g, 2.27 mmol) in 30 mL of THF,
NaH (0.120 g, 5.0 mmol), n-Bu4NI (1.847 g, 5.0 mmol)
and allyl bromide (0.605 g, 5.0 mmol), 4b was isolated as
1
a yellow oil (0.496 g, 84%). H NMR (CDCl3, 300 MHz):
d¼1.38 (t, J¼7.2 Hz, 3H, OCH2CH3), 2.25 (m, 2H,
CH2CH2CH]CH2), 2.72 (m, 2H, CH2CH2CH]CH2),
4.37 (q, J¼7.2 Hz, 2H, OCH2CH3), 4.44 (m, 2H,
CH2]CHCH2O), 4.95–5.10 (m, 2H, CH2]CHCH2CH2),
5.25–5.45 (m, 2H, CH2]CHCH2O), 5.80–6.12 (m, 2H,
CH2]CHCH2CH2, CH2]CHCH2O), 7.08 (dt, J¼7.8,

8042
V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
3.3.5. Ethyl 3-allyl-2-(allyloxy)-4,6-diethylbenzoate (9c).
Starting with 8c (0.200 g, 0.76 mmol, 1.0 equiv) in 10 mL
THF, NaH (0.036 g, 1.52 mmol, 2.0 equiv), n-Bu4NI
(0.497 g, 1.52 mmol, 2.0 equiv) and allyl bromide
(0.137 g, 1.14 mmol, 1.5 equiv), 9c was isolated as a colour-
less oil (0.180 g, 78%). 1H NMR (CDCl3, 300 MHz):
d¼1.20 (t, J¼7.5 Hz, 6H, 2CH3CH2), 1.36 (t, J¼7.2 Hz,
3H, OCH2CH3), 2.56–2.64 (q, J¼7.5 Hz, 4H, 2CH3CH2),
3.43 (m, J¼1.8 Hz, 2H, CH2]CHCH2Ar), 4.34 (q,
J¼7.1 Hz, 2H, OCH2CH3), 4.39 (m, 2H, CH2]CHCH2O),
4.87–4.99 (m, J¼11.6, 8.7, 1.8 Hz, 2H, CH2]CHCH2Ar),
5.18–5.41 (m, J¼8.9, 15.5, 1.5 Hz, 2H, CH2]CHCH2O),
5.89–6.06 (m, 2H, CH2]CHCH2Ar, CH2]CHCH2O),
6.86 (s, 1H, Ar). 13C NMR (CDCl3, 75 MHz): d¼14.2,
15.1, 15.5 (CH3), 25.5, 26.4, 29.9, 61.1, 75.9, 115.1, 116.6
(CH2), 124.4 (CH), 126.3, 128.3 (C), 133.9, 136.9 (CH),
140.3, 146.0, 154.2, 168.8 (C). IR (KBr, cmꢀ1): ~n¼2972
(m), 2934 (w), 1728 (s), 1641 (w), 1459 (w), 1414 (w),
1277 (m), 1149 (m), 1027 (w), 918 (w). UV–vis (CH3CN,
nm): lmax (log 3)¼203.4 (4.57). MS (EI, 70 eV): m/z
(%)¼302 (M+, 12), 261 (18), 215 (44), 173 (11), 41 (15),
32 (21), 28 (100). HRMS (EI, 70 eV) calcd for C19H26O3:
m/z¼302.18819; found: m/z¼302.18775.
2H, CH2]CHCH2O), 5.86–5.99 (m, J¼5.9 Hz, 1H,
CH2]CHCH2CH2), 6.00–6.06 (m, J¼5.2 Hz, 1H,
CH2]CHCH2O). 13C NMR (CDCl3, 75 MHz): d¼14.2,
15.9, 16.4, 17.2 (CH3), 26.5, 34.2, 61.1, 76.0, 114.5, 116.7
(CH2), 127.5, 131.1, 131.4, 131.8 (C), 133.9 (CH), 137.5
(C), 138.3 (CH), 151.5, 169.3 (C). IR (KBr, cmꢀ1):
~n¼2981 (m), 2932 (m), 1727 (s), 1449 (m), 1423 (m),
1279 (s), 1189 (s), 1046 (m). UV–vis (CH3CN, nm): lmax
(log 3)¼203.1 (4.50), 279.9 (2.79). MS (EI, 70 eV): m/z
(%)¼303 (M++1, 5), 302 (M+, 48), 261 (38), 215 (100),
189 (17), 175 (47), 146.5 (16), 91 (30), 41 (52), 28 (49).
HRMS (ESI+) calcd for C19H26O3 [M++1]: m/z¼
303.19602; found: m/z¼303.19603. Anal. Calcd for
C19H26O3: C 75.46, H 8.67; found: C 75.80, H 8.46.
3.3.8. Ethyl 2-(allyloxy)-3-(but-3-enyl)-4,6-diethylben-
zoate (9f). Starting with 8f (0.350 g, 1.28 mmol, 1.0 equiv)
in 20 mL of THF, NaH (0.061 g, 2.56 mmol, 2.0 equiv),
n-Bu4NI (0.836 g, 2.56 mmol, 2.0 equiv) and allyl bromide
(0.230 g, 1.91 mmol, 1.5 equiv), 9f was isolated as a colour-
less oil (0.330 g, 82%). 1H NMR (CDCl3, 300 MHz):
d¼1.23 (t, J¼7.1 Hz, 6H, 2CH3CH2), 1.37 (t, J¼7.1 Hz,
3H, OCH2CH3), 2.26 (m, 2H, CH2]CHCH2CH2), 2.54–
2.61 (q, J¼7.5 Hz, 4H, 2CH3CH2), 2.69 (m, 2H,
CH2]CHCH2CH2), 4.35 (q, J¼7.1 Hz, 2H, OCH2CH3),
4.42 (m, J¼1.5 Hz, 2H, CH2]CHCH2O), 4.96–5.20 (m,
J¼9.3, 15.3, 1.5 Hz, 2H, CH2]CHCH2CH2), 5.24–5.44
(m, J¼8.9, 15.5, 1.5 Hz, 2H, CH2]CHCH2O), 5.89–6.02
(m, 2H, CH2]CHCH2CH2, CH2]CHCH2O), 6.84 (s, 1H,
CH, Ar). 13C NMR (CDCl3, 75 MHz): d¼14.2, 15.5
(2CH3), 25.8 (2CH2), 26.3, 34.7, 61.1, 75.7, 114.5, 116.6
(CH2), 124.5 (CH), 126.2, 130.8 (C), 133.9, 138.5 (CH),
139.9, 145.3, 154.3, 168.8 (C). UV–vis (CH3CN, nm):
lmax (log 3)¼203.5 (4.61), 278.5 (3.06). IR (KBr, cmꢀ1):
~n¼2972 (m), 2935 (w), 1727 (s), 1458 (w), 1414 (w), 1282
(m), 1149 (m), 917 (m). MS (EI, 70 eV): m/z (%)¼316
(M+, 28), 275 (69), 229 (100), 189 (45), 105 (14), 91 (28),
70 (55), 41 (95), 28 (88). HRMS (ESI+) calcd for
C20H28O3 [M++1]: m/z¼317.21167; found: m/z¼
317.21222. Anal. Calcd for C20H28O3: C 75.91, H 8.92;
found: C 75.72, H 8.72.
3.3.6. Ethyl 2-allyl-3-(allyloxy)-9,10-dihydro-1-methyl-
phenanthrene-4-carboxylate (9d). Starting with 8d
(0.322 g, 1.00 mmol, 1.0 equiv) in 15 mL of THF, NaH
(0.048 g, 2.0 mmol, 2.0 equiv), n-Bu4NI (0.653 g,
2.00 mmol, 2.0 equiv) and allyl bromide (0.181 g,
1.5 mmol, 1.5 equiv), 9d was isolated as a slight yellow oil
1
(0.280 g, 77%). H NMR (CDCl3, 300 MHz): d¼1.23 (t,
J¼7.1 Hz, 3H, OCH2CH3), 2.26 (s, 3H, CH3), 2.73–2.78
(m, 4H, 2CH2), 3.54 (m, J¼1.9 Hz, 2H, CH2]CHCH2Ar),
4.29 (q, J¼7.2 Hz, 2H, OCH2CH3), 4.46 (m, J¼2.5,
1.5 Hz, 2H, CH2]CHCH2O), 4.91–5.09 (m, J¼22.3, 17.2,
8.5, 1.7 Hz, 2H, CH2]CHCH2Ar), 5.21–5.44 (m, J¼15.5,
8.8, 1.7 Hz, 2H, CH2]CHCH2O), 6.05 (m, 2H,
CH2]CHCH2Ar, CH2]CHCH2O), 7.18–7.23 (m, 3H,
Ar), 7.55 (s, 1H, Ar). 13C NMR (CDCl3, 75 MHz):
d¼13.9, 16.0 (CH3), 25.8, 29.1, 31.0, 61.4, 76.3, 115.6,
116.7 (CH2), 124.6 (C), 126.1, 126.4, 127.37, 127.40
(CH), 130.9, 131.7, 133.7, 133.9 (C), 134.3 (CH), 136.2
(C), 137.2 (CH), 138.5, 153.4, 169.6 (C). IR (KBr, cmꢀ1):
~n¼2979 (w), 2933 (w), 1725 (s), 1641 (w), 1408 (w), 1285
(w), 1189 (m), 1022 (w), 918 (w), 764 (w). UV–vis
(CH3CN, nm): lmax (log 3)¼210.7 (4.49), 268.7 (4.15),
295.3 (3.78), 303.8 (3.78). MS (EI, 70 eV): m/z (%)¼363
(M++1, 1), 362 (M+, 7), 275 (11), 248 (7), 215 (7), 32
(22), 28 (100). HRMS (EI, 70 eV) calcd for C24H26O3
([M+]): m/z¼362.18729; found: m/z¼362.18764.
3.3.9. Ethyl 3-(allyloxy)-2-(but-3-enyl)-9,10-dihydro-1-
methylphenanthrene-4-carboxylate (9g). Starting with
8g (0.336 g, 1.00 mmol, 1.0 equiv) in 15 mL of THF, NaH
(0.048 g, 2.00 mmol, 2.0 equiv), n-Bu4NI (0.653 g,
2.00 mmol, 2.0 equiv) and allyl bromide (0.181 g,
1.50 mmol, 1.5 equiv), 9g was isolated as a colourless
oil (0.362 g, 96%). 1H NMR (CDCl3, 300 MHz): d¼
1.24 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.27 (m, 2H,
CH2]CHCH2CH2), 2.31 (s, 3H, CH3), 2.70–2.83 (m, 6H,
CH2]CHCH2CH2, C6H4(CH2)2), 4.27 (q, J¼7.1 Hz, 2H,
OCH2CH3), 4.48 (m, 2H, CH2]CHCH2O), 4.99–5.08 (m,
J¼10.2, 15.4, 1.5 Hz, 2H, CH2]CHCH2CH2), 5.39–5.47
(m, J¼10.5, 15.5, 1.6 Hz, 2H, CH2]CHCH2O), 5.87–5.98
(m, J¼6.5 Hz, 1H, CH2]CHCH2CH2), 6.01–6.13 (m,
J¼5.3 Hz, 1H, CH2]CHCH2O), 7.17–7.51 (m, 3H, Ar),
7.52 (m, 1H, Ar). 13C NMR (CDCl3, 75 MHz): d¼13.9,
15.9 (CH3), 25.9, 26.8, 29.1, 34.1, 61.4, 76.3, 114.7, 116.8
(CH2), 124.6 (C), 126.1, 126.4, 127.32, 127.33 (CH),
131.4, 133.6, 133.7 (C), 133.9 (CH), 134.4, 136.3 (C),
138.2 (CH), 138.4, 153.3, 169.7 (C). IR (KBr, cmꢀ1):
~n¼3075 (m), 2978 (s), 2900 (s), 1724 (s), 1643 (m), 1557
3.3.7. Ethyl 3-(but-3-enyl)-2-(allyloxy)-4,5,6-trimethyl-
benzoate (9e). Starting with 8e (0.325 g, 1.31 mmol,
1.0 equiv) in 20 mL of THF, NaH (0.063 g, 2.62 mmol,
2.0 equiv), n-Bu4NI (0.855 g, 2.62 mmol, 2.0 equiv) and al-
lyl bromide (0.235 g, 1.95 mmol, 1.5 equiv), 9e was isolated
1
as a slight yellow oil (0.300 g, 76%). H NMR (CDCl3,
300 MHz): d¼1.37 (t, J¼7.1 Hz, 3H, OCH2CH3), 2.16 (s,
3H, CH3), 2.17–2.26 (m, 2H, CH2]CHCH2CH2), 2.22 (s,
3H, CH3), 2.24 (s, 3H, CH3), 2.74 (m J¼6.0, 1.5 Hz, 2H,
CH2]CHCH2CH2), 4.35–4.40 (m, 4H, OCH2CH3,
CH2]CHCH2O), 4.97–5.10 (m, J¼10.1, 17.1, 1.5 Hz, 2H,
CH2]CHCH2CH2), 5.19–5.43 (m, J¼10.5, 15.5, 1.7 Hz,

V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
8043
(m), 1444 (m), 1409 (m), 1286 (m), 1187 (m), 1109 (m),
1024 (m), 989 (m), 916 (m), 760 (m). UV–vis (CH3CN,
nm): lmax (log 3)¼210.1 (4.57), 268.2 (4.25), 304.8 (3.88).
MS (EI, 70 eV): m/z (%)¼377 (M++1, 26), 376 (M+, 100),
335 (92), 307 (32), 249 (53), 221 (27), 178 (39), 85 (25),
57 (26), 41 (62), 28 (80). HRMS (ESI+) calcd for
C25H28O3 [M++1]: m/z¼377.21167; found: m/z¼377.21185.
(CDCl3, 300 MHz): d¼1.38 (t, J¼7.1 Hz, 3H, OCH2CH3),
2.26 (s, 3H, CH3), 2.27 (s, 3H, CH3), 3.44 (m, J¼1.9 Hz,
2H, CH2), 4.39 (q, J¼7.1 Hz, 2H, OCH2CH3), 4.63 (m,
J¼1.5 Hz, 2H, CH2), 5.46 (m, J¼5.2, 1.4 Hz, 1H, CH),
5.83 (m, 1H, CH), 6.76 (s, 1H, Ar). 13C NMR (CDCl3,
75 MHz): d¼14.3, 18.9, 19.8 (CH3), 25.7, 60.9, 71.4
(CH2), 124.9 (CH), 126.1 (C), 127.5, 127.8 (CH), 133.5
(2C), 136.6, 152.2, 168.1 (C). IR (KBr, cmꢀ1): ~n¼3438
(w), 2979 (s), 2930 (s), 1726 (s), 1609 (s), 1456 (s), 1387
(m), 1293 (s), 1270 (s), 1223 (m), 1149 (s), 1091 (s), 1046
(s), 862 (m), 653 (w). UV–vis (CH3CN, nm): lmax
(log 3)¼205.8 (4.25), 263.1 (3.62), 301.8 (3.27). MS (EI,
70 eV): m/z (%)¼247 (M++1, 9), 246 (M+, 77), 201 (92),
200 (100), 199 (47), 183 (35), 173 (23), 172 (63), 171
(24), 157 (53), 129 (41), 128 (31), 114 (21), 45 (18), 31
(41). Anal. Calcd for C15H18O3: C 73.15, H 7.36; found: C
73.03, H 6.96.
3.4. General procedure for the synthesis of products 5a,b
and 10a–g
To a CH2Cl2 solution of 4a,b or 9a–g was added a CH2Cl2
solution of catalyst 6 under argon atmosphere. After stirring
for 6–8 h at 20 ꢁC under argon atmosphere, the solution was
exposed to air and concentrated in vacuo. The residue was
purified by column chromatography (silica gel, n-hexane/
EtOAc¼25:1). The product should be stored at ca. 0 ꢁC or
below.
3.4.4. Ethyl 6,7,8-trimethyl-2,5-dihydrobenzo[b]oxepin-
9-carboxylate (10b). Starting with 9b (0.140 g, 0.50 mmol,
3.4.1. Ethyl 2,5-dihydrobenzo[b]oxepin-9-carboxylate
(5a). Starting with 4a (0.123 g, 0.5 mmol) in 10 mL of
CH2Cl2 and 6 (0.021 g, 0.025 mmol), 5a was isolated as
a colourless oil (0.108 g, 99%). 1H NMR (CDCl3,
300 MHz): d¼1.39 (t, J¼7.2 Hz, 3H, OCH2CH3), 3.48 (m,
J¼3.0 Hz, 2H, CH2), 4.38 (q, J¼7.2 Hz, 2H, OCH2CH3),
4.69–4.72 (m, J¼2.4 Hz, 2H, CH2), 5.44–5.48 (m, 1H,
CH), 5.81–5.88 (m, 1H, CH), 7.03–7.08 (dt, J¼7.8,
1.8 Hz, 1H, Ar), 7.23–7.27 (m, 1H, Ar), 7.62–7.68 (ddd,
J¼6.9, 6.9, 1.8 Hz, 1H, Ar). 13C NMR (CDCl3, 75 MHz):
d¼14.1 (CH3), 31.2, 60.8, 70.9 (CH2), 118.1 (C), 123.5
(CH), 125.2 (C), 127.4, 128.9, 129.9, 132.0 (CH), 156.3
(C), 165.8 (CO). IR (KBr, cmꢀ1): ~n¼2932 (m), 1723 (s),
1465 (m), 1290 (s), 1216 (m), 1170 (w), 1137 (s), 1085
(m), 1056 (w), 1023 (w), 989 (w), 761 (w). MS (EI,
70 eV): m/z (%)¼218 (M+, 64), 189 (15), 173 (100), 145
(42), 91 (28), 75 (15). HRMS (EI, 70 eV) calcd for
C13H14O3 ([M+]): m/z¼218.09429; found: m/z¼218.09471.
1.0 equiv) in 10 mL of CH2Cl2 and 6 (0.021 mg,
0.025 mmol, 5 mol %, dissolved in 1 mL of CH2Cl2), 10b
was isolated as a colourless oil (0.121 g, 93%). H NMR
1
(CDCl3, 300 MHz): d¼1.38 (t, J¼7.2 Hz, 3H, OCH2CH3),
2.17 (s, 3H, CH3), 2.20 (s, 3H, CH3), 2.27 (s, 3H, CH3),
3.51 (m, J¼1.8 Hz, 2H, CH2), 4.40 (q, J¼7.1 Hz, 2H,
OCH2CH3), 4.61 (m, J¼2.4 Hz, 2H, CH2), 5.42 (m, J¼6.1,
1.2 Hz, 1H, CH), 5.82–5.89 (m, J¼2.3 Hz, 1H, CH). 13C
NMR (CDCl3, 75 MHz): d¼14.3, 16.2, 16.3, 17.3 (CH3),
26.0, 61.0, 71.6 (CH2), 125.3 (CH), 126.7 (C), 127.8 (CH),
131.1, 131.4, 133.9, 134.8, 152.2, 168.9 (C). IR (KBr,
cmꢀ1): ~n¼3451 (br, m), 2982 (s), 2932 (s), 1730 (s), 1673
(s), 1587 (s), 1453 (s), 1386 (m), 1309 (s), 1278 (s), 1189
(s), 1101 (s), 1043 (s), 735 (m). UV–vis (CH3CN, nm):
lmax (log 3)¼205.6 (4.25), 301.6 (3.43). MS (EI, 70 eV):
m/z (%)¼261 (M++1, 10), 260 (M+, 81), 215 (45), 214
(40), 186 (41), 171 (55), 143 (22), 129 (13), 128 (20), 45
(16), 32 (20), 31 (31), 28 (100). HRMS (ESI+) calcd for
C16H20O3 [M++1]: m/z¼261.14907; found: m/z¼261.14879.
3.4.2. Ethyl 5,6-dihydro-2H-benzo[b]oxocine-10-carb-
oxylate (5b). Starting with 4b (0.130 g, 0.5 mmol) in 10 mL
of CH2Cl2 and 6 (0.021 g, 0.025 mmol), 5b was isolated
as a colourless oil (0.087 g, 75%). 1H NMR (CDCl3,
300 MHz): d¼1.37 (t, J¼7.2 Hz, 3H, OCH2CH3), 2.68 (m,
2H, CH2), 2.93 (m, J¼6.2 Hz, 2H, CH2), 4.38 (q,
J¼7.2 Hz, 2H, OCH2CH3), 4.70 (m, 2H, CH2), 5.35–5.41
(m, J¼3.0, 1.2 Hz, 1H, CH), 5.71–5.78 (m, J¼3.0, 1.5 Hz,
1H, CH), 7.05 (dt, J¼7.8, 1.8 Hz, 1H, Ar), 7.23–7.27 (m,
1H, Ar), 7.65 (ddd, J¼6.9, 6.9, 1.8 Hz, 1H, Ar). 13C NMR
(CDCl3, 75 MHz): d¼14.3 (CH3), 28.0, 30.2, 61.2, 73.3
(CH2), 118.2 (C), 123.5 (CH), 125.2 (C), 127.3, 129.1,
131.8, 133.9 (CH), 157.1 (C), 166.3 (CO). IR (KBr,
cmꢀ1): ~n¼2982 (m), 2932 (m), 1725 (s), 1668 (w), 1452
(m), 1285 (s), 1216 (m), 1186 (m), 1142 (w), 1075 (m),
1023 (m), 763 (w). MS (EI, 70 eV): m/z (%)¼232 (M+,
52), 203 (5), 187 (100), 159 (42), 91 (35), 75 (12). HRMS
(EI, 70 eV) calcd for C14H16O3 ([M+]): m/z¼232.10994;
found: m/z¼232.11039.
3.4.5. Ethyl 6,8-diethyl-2,5-dihydrobenzo[b]oxepin-9-
carboxylate (10c). Starting with 9c (0.120 g, 0.397 mmol,
1.0 equiv) in 5 mL of CH2Cl2 and 6 (0.014 g, 0.017 mmol,
5 mol %, dissolved in 0.5 mL of CH2Cl2), 10c was isolated
as a colourless oil (0.099 g, 91%). 1H NMR (CDCl3,
300 MHz): d¼1.18 (t, J¼7.4 Hz, 3H, CH3CH2), 1.23
(t, J¼7.5 Hz, 3H, CH3CH2), 1.38 (t, J¼7.1 Hz, 3H,
OCH2CH3), 2.63 (m, J¼7.4 Hz, 4H, 2CH3CH2), 3.44 (m,
J¼2.0 Hz, 2H, CH2), 4.38 (q, J¼7.1 Hz, 2H, OCH2CH3),
4.63 (m, J¼2.3 Hz, 2H, CH2), 5.46 (m, J¼7.3, 1.4 Hz, 1H,
CH), 5.85 (m, J¼5.7 Hz, 1H, CH), 6.79 (s, 1H, Ar). 13C
NMR (CDCl3, 75 MHz): d¼14.3, 15.2, 15.6 (CH3), 25.5
(CH2), 26.3, 26.9 (CH3), 61.3, 71.5 (CH2), 124.7, 125.1,
127.9 (CH), 128.5, 133.2, 139.9, 142.9, 153.7, 168.7 (C).
IR (KBr, cmꢀ1): ~n¼2981 (m), 2930 (m), 1655 (s), 1600
(m), 1446 (m), 1403 (s), 1312 (s), 1260 (s), 1195 (s), 1116
(w), 1045 (m), 910 (w), 806 (w). UV–vis (CH3CN, nm):
lmax (log 3)¼204.4 (4.41), 299.8 (3.43). MS (EI, 70 eV):
m/z (%)¼274 (M+, 12), 259 (3), 229 (4), 213 (7), 186 (7),
171 (9), 128 (6), 32 (22), 28 (100).
3.4.3. Ethyl 8,6-dimethyl-2,5-dihydrobenzo[b]oxepin-9-
carboxylate (10a). Starting with 9a (0.260 g, 0.95 mmol,
1.0 equiv) in 18 mL of CH2Cl2 and
0.047 mmol, 5 mol %, dissolved in 2 mL of CH2Cl2), 10a
was isolated as a colourless oil (0.210 g, 99%). H NMR
6
(0.039 g,
3.4.6. Ethyl 5,6,8,11-tetrahydro-7-methylphenan-
thro[3,2-b]oxepin-13-carboxylate (10d). Starting with 9d
1

8044
V. T. H. Nguyen et al. / Tetrahedron 63 (2007) 8037–8045
(0.250 g, 0.688 mmol, 1.0 equiv) in 12 mL of CH2Cl2 and 6
(0.028 g, 0.034 mmol, 5 mol %, dissolved in 1 mL of
CH2Cl2), 10d was isolated as a colourless oil (0.185 g,
80%). H NMR (CDCl3, 300 MHz): d¼1.27 (t, J¼7.2 Hz,
HRMS (ESI+) calcd for C18H24O3 [M++1]: m/z¼
289.18037; found: m/z¼289.18049.
1
3.4.9. Ethyl 6,8,9,12-tetrahydro-7-methyl-5H-phenan-
thro[3,2-b]oxocine-14-carboxylate (10g). Starting with
9g (0.300 g, 0.797 mmol, 1.0 equiv) in 19 mL of CH2Cl2
and 6 (0.033 g, 0.0398 mmol, 5 mol %, dissolved in 1 mL
of CH2Cl2), 10g was isolated as a colourless oil (0.180 g,
3H, OCH2CH3), 2.31 (s, 3H, CH3), 2.72–2.80 (m, J¼4.1,
2.5 Hz, 4H, C6H4(CH2)2), 3.58 (m, J¼2.1 Hz, 2H, CH2),
4.34 (q, J¼7.1 Hz, 2H, OCH2CH3), 4.70 (m, J¼2.3 Hz,
2H, CH2), 5.49 (m, J¼11.3 Hz, 1H, CH), 5.90 (m, 1H,
CH), 7.18–7.24 (m, 3H, Ar), 7.53 (s, 1H, Ar). 13C NMR
(CDCl3, 75 MHz): d¼14.1, 15.9 (CH3), 26.0, 26.2, 29.2,
61.3, 71.9 (CH2), 123.8 (C), 125.0, 126.0 (CH), 126.2,
126.4 (C), 126.5, 127.3, 127.9, 128.0 (CH), 131.1, 133.5,
133.7, 138.3, 153.8, 169.3 (C). IR (KBr, cmꢀ1): ~n¼2977
(w), 2935 (w), 1722 (s), 1446 (w), 1280 (m), 1194 (s),
1071 (w), 1026 (w). UV–vis (CH3CN, nm): lmax
(log 3)¼209.4 (4.48), 269.2 (4.16), 303.2 (3.90). MS (EI,
70 eV): m/z (%)¼335 (M++1, 23), 334 (M+, 100), 320
(18), 319 (37), 289 (27), 260 (34), 245 (24), 202 (22), 29
(32). HRMS (ESI+) calcd for C22H22O3 [M++1]: m/z¼
335.16472; found: m/z¼335.16511.
1
65%). H NMR (CDCl3, 300 MHz): d¼1.23 (t, J¼7.2 Hz,
3H, OCH2CH3), 2.24 (s, 3H, CH3), 2.26 (m, 2H, CH2),
2.67–2.78 (m, 4H, C6H4(CH2)2), 3.00 (m, J¼1.3 Hz, 2H,
CH2), 4.30 (q, J¼7.1 Hz, 2H, OCH2CH3), 5.41 (m, J¼6.2,
1.3 Hz, 1H, CH), 5.75 (m, J¼5.7, 1.7 Hz, 1H, CH), 7.17–
7.25 (m, 3H, Ar), 7.54 (s, 1H, CH). 13C NMR (CDCl3,
75 MHz): d¼13.9, 15.7 (CH3), 26.0, 28.10, 28.14, 29.2,
61.3, 73.7 (CH2), 124.4 (C), 125.4, 126.1, 126.4, 127.25,
127.29, 131.2 (CH), 131.6, 132.8, 133.85, 133.98, 135.7,
138.4, 152.7 (C), 169.8 (CO). IR (KBr, cmꢀ1): ~n¼3432
(br, m), 2978 (w), 2890 (w), 1723 (s), 1450 (w), 1283 (m),
1188 (s), 1159 (w), 1023 (m). UV–vis (CH3CN, nm): lmax
(log 3)¼209.3 (4.50), 268.2 (4.18), 304.9 (3.84). MS (EI,
70 eV): m/z (%)¼348 (M+, 2), 125 (1), 40 (3), 32 (29), 28
(100). HRMS (ESI+) calcd for C25H28O3 ([M++1]): m/z¼
349.18037; found: m/z¼349.18032.
3.4.7. Ethyl 7,8,9-trimethyl-5,6-dihydro-2H-benzo[b]ox-
ocine-10-carboxylate (10e). Starting with 9e (0.243 g,
0.804 mmol, 1.0 equiv) in 16 mL of CH2Cl2 and 6
(0.035 g, 0.040 mmol, 5 mol %, dissolved in 1 mL of
CH2Cl2), 10e was isolated as a colourless oil (0.166 g,
1
76%). H NMR (CDCl3, 300 MHz): d¼1.37 (t, J¼7.1 Hz,
Acknowledgements
3H, OCH2CH3), 2.13 (s, 3H, CH3), 2.18 (s, 3H, CH3), 2.24
(s, 3H, CH3), 2.68 (m, J¼5.5, 1.2 Hz, 2H, CH2), 2.94 (m,
J¼6.2 Hz, 2H, CH2), 4.38 (q, J¼7.1 Hz, 2H, OCH2CH3),
4.71 (m, J¼1.3 Hz, 2H, CH2), 5.33–5.39 (m, J¼3.0,
1.3 Hz, 1H, CH), 5.69–5.76 (m, J¼3.0, 1.5 Hz, 1H, CH).
13C NMR (CDCl3, 75 MHz): d¼14.3, 16.0, 16.1, 17.3
(CH3), 28.0, 28.2, 61.1, 73.2 (CH2), 125.2 (CH), 127.5,
130.4, 131.2, 131.4 (C), 131.6 (CH), 136.9, 150.8, 169.5
(C). IR (KBr, cmꢀ1): ~n¼2981 (m), 2932 (m), 1727 (s),
1449 (m), 1423 (m), 1279 (s), 1189 (s), 1046 (m), 98 (m).
UV–vis (CH3CN, nm): lmax (log 3)¼203.1 (4.50), 279.9
(2.79). MS (EI, 70 eV): m/z (%)¼275 (M++1, 15), 274
(M+, 100), 229 (39), 187 (53), 175 (31), 146.5 (28), 91
(31), 28 (47). HRMS (ESI+) calcd for C17H22O3 [M++1]:
m/z¼275.16472; found: m/z¼275.16444.
Financial support by the state of Vietnam (MOET scholar-
ship for V.T.H.N.) and by the DAAD (scholarship for E.B.)
is gratefully acknowledged.
References and notes
1. Macias, F. A.; Molinillo, J. M. G.; Varela, R. M.; Torres, A.;
Fronczek, F. R. J. Org. Chem. 1994, 59, 8261.
2. Dinda, B.; Das, S. K.; Hajra, A. K.; Bhattacharya, A.; De, K.;
Chel, G.; Achari, B. Indian J. Chem., Sect. B 1999, 38, 577.
3. (a) Macias, F. A.; Varela, R. M.; Torres, A.; Molinillo, J. M. G.;
Fronczek,F. R. TetrahedronLett.1993, 34, 1999;(b)Takabatake,
K.; Nishi, I.; Shindo, M.; Shishido, K. J. Chem. Soc., Perkin
Trans. 1 2000, 1807; (c) Macias, F. A.; Varela, R. M.; Torres,
A.; Molinillo, J. M. G. J. Nat. Prod. 1999, 62, 1636.
3.4.8. Ethyl 7,9-diethyl-5,6-dihydro-2H-benzo[b]oxocine-
10-carboxylate (10f). Starting with 9f (0.265 g, 0.837 mmol,
1.0 equiv) in 16 mL of CH2Cl2 and 6 (0.035 g, 0.042 mmol,
5 mol %, dissolved in 1 mL of CH2Cl2), 10f was isolated as
a colourless oil (0.220 g, 91%). 1H NMR (CDCl3, 300 MHz):
d¼1.20 (t, J¼7.5 Hz, 6H, 2CH3CH2), 1.37 (t, J¼7.1 Hz, 3H,
OCH2CH3), 2.56 (q, J¼7.5 Hz, 4H, 2CH3CH2), 2.68 (m,
J¼7.0, 1.2 Hz, 2H, CH2), 2.92 (m, J¼6.3, 2.3 Hz, 2H,
CH2), 4.38 (q, J¼7.1 Hz, 2H, OCH2CH3), 4.70 (m,
J¼1.4 Hz, 2H, CH2), 5.37–5.43 (m, J¼3.0, 1.2 Hz, 1H,
CH), 5.73–5.77 (m, J¼1.6 Hz, 1H, CH), 6.82 (s, 1H, CH,
Ar). 13C NMR (CDCl3, 75 MHz): d¼14.3, 14.9, 15.5
(CH3), 26.2, 26.2, 27.0, 27.8, 60.9, 73.1 (CH2), 124.3,
125.5 (CH), 126.6, 129.9 (C), 131.9 (CH), 139.7, 144.8,
153.6, 168.9 (C). IR (KBr, cmꢀ1): ~n¼2968 (s), 2935 (s),
2875 (m), 1726 (s), 1606 (m), 1562 (m), 1454 (m), 1415
(m), 1282 (s), 1245 (s), 1148 (s), 1100 (s), 1072 (s), 877
(w), 707 (w). UV–vis (CH3CN, nm): lmax (log 3)¼203.7
(2.44), 277.5 (3.07). MS (EI, 70 eV): m/z (%)¼288 (M+,
4), 234 (18), 188 (18), 163 (5), 91 (6), 32 (24), 28 (100).
4. Crews, P.; Harrison, B. J. Org. Chem. 1997, 62, 2646.
5. (a) Nagai, M.; Nagumo, S. Chem. Pharm. Bull. 1987, 35, 3002;
(b) Oh, S. R.; Kim, D. S.; Lee, I. S.; Jung, K. Y.; Lee, J. J.; Lee,
H.-K. Planta Med. 1998, 64, 456.
6. (a)Asakawa, Y.;Toyota, M.;Takemoto, T. Phytochemistry1978,
17, 2005; (b) Asakawa, Y.; Takeda, R.; Toyota, M.; Tsunematsu,
T. Phytochemistry 1981, 20, 858; (c) Asakawa, Y.; Hashimoto,
T.; Takikawa, K.; Tori, M.; Ogawa, S. Phytochemistry 1991,
30, 235; (d) Yamaguchi, S.; Furihata, K.; Miyazawa, M.;
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