New Synthetic Methods for Seven- and Eight-Membered Cyclic Ethers Based on the Ring-Expansion Reactions of Hydroxy or Lithioxy Methoxyallenylisochroman Derivatives

Article abstract of DOI:10.1055/s-2004-815440

The Pd(0)-catalyzed ring-expansion reactions of hydroxy methoxyallenyl-4,4-dialkylisochroman derivatives in the presence of P(o-tolyl)₃ proceeded smoothly via hydropalladation to give 3-benzoxepan-1-one derivatives in high yields. Treatment of

Full text of DOI:10.1055/s-2004-815440

LETTER
481
New Synthetic Methods for Seven- and Eight-Membered Cyclic Ethers Based
on the Ring-Expansion Reactions of Hydroxy or Lithioxy Methoxyallenyliso-
chroman Derivatives
New
S
ynthetic Me
o
thods for Se
s
E
h
ight-Membe
i
red Cy
m
clic
E
thers itsu Nagao,*a Satoru Tanaka,a Kazuhiko Hayashi,a Shigeki Sano,a Motoo Shirob
a
Faculty of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Fax +81(88)6339503; E-mail: ynagao@ph.tokushima-u.ac.jp
b
Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima-shi, Tokyo 196-8666, Japan
Received 24 December 2003
4a–e were subjected to cyclization with TiCl4 in CH2Cl2
to give 4,4-dialkylisochromans 5a–e.7 Oxidation of 5a–e
with KMnO4 and CuSO4·5H2O in CH2Cl2 afforded the
corresponding d-lactones 6a–e in 62–91% overall yields
Abstract: The Pd(0)-catalyzed ring-expansion reactions of hy-
droxy methoxyallenyl-4,4-dialkylisochroman derivatives in the
presence of P(o-tolyl)3 proceeded smoothly via hydropalladation to
give 3-benzoxepan-1-one derivatives in high yields. Treatment of
isochroman-1-one derivatives with lithio methoxyallene followed from compound 1.8
by quenching the reaction with water furnished 3-benzoxocan-6-
one derivatives in good yields.
R
R
R
R
OH
i)
ii)
Key words: allenes, cyclic ether, palladium, hydropalladation, ring
expansion
iii)
CO2Et
CO2Et
3a–e
2a–e
1
O
R
R
Oxygen-containing medium-sized heterocycles are im-
portant structural units commonly found within the frame-
work of a variety of natural and synthetic biologically
active compounds.1 Specifically, six- to nine-membered
cyclic ethers often appear in marine natural products such
as brevetoxin and ciguatoxin.2,3 Hence, many efficient
synthetic methods have been reported for cyclic ethers.4
In a series of studies on cyclization, ring-expansion, and
cascade reactions utilizing allenylic molecular structure
characteristics, recent efforts in our laboratory have fo-
cused on base-mediated and Pd(0)-catalyzed ring-expan-
sion reactions of various hydroxy allenyl cyclic
compounds.5 In the previous ring-expansion reactions of
the cyclic ethers reported by our group, we carried out the
synthesis of six- or seven-membered cyclic ethers from
five-membered cyclic ethers (5→6 and 5→7) have been
performed.5d,f Here, we describe Pd(0)-catalyzed one-
atom ring-expansion reactions (6→7) of hydroxy meth-
oxyallenylisochroman derivatives toward 3-benzoxepan-
1-one derivatives via hydropalladation, as well as two-
atom ring-expansion reactions (6→8) of lithioxy meth-
oxyallenylisochroman derivatives.
OMEM
6a 62%
6b 83%
6c 71%
6d 69%
6e 91%
O
O
iv)
v)
R
R
R
R
4a–e
5a–e
6a–e
a R = Me; b R = Et; c R =n-Pr; d R = Bz; e R = –(CH2)4–
Scheme 1 Reagents and conditions: i) NaH (3.0 mol equiv), R-X
(3.0 mol equiv), THF, r.t.; ii) LiAIH4 (1.3 mol equiv), THF, reflux; iii)
MEMCI (1.2 mol equiv), DIPEA (1.2 mol equiv), CH2Cl2, r.t.; iv)
TiCl4 (1.19 mol equiv), CH2Cl2, 0 °C; v) KMnO4 (7.96 mol equiv),
CuSO4·5H2O (5.04 mol equiv), CH2Cl2, r.t.
Hydroxy methoxyallenyl-4,4-dialkylisochroman deriva-
tives 7a–c, precursors for the ring-expansion reaction,
were obtained in 69–98% yields by treatment of 6a–c
with 1.2 mol equivalents of lithio methoxyallene9 in
THF at –30 °C for 1 hour, as shown in Scheme 2.10 How-
ever, similar treatment of 6d,e with lithio methoxyallene
resulted in the decomposition of the starting compound.
The structures of 7a–c were determined by their charac-
teristic spectroscopic data [1H NMR (400 MHz, CDCl3):
d = 3.42–3.48 (s, 3 H, OMe), 3.42–3.50 (s, 1 H, OH),
The 4,4-dialkyl-isochroman-1-one derivatives 6a–e were 5.60–5.52 (d, 1 H, J = 8.3 Hz, allene H), and 5.55–5.66
readily accessible from ethyl phenylacetate (1) through (d, 1 H, J = 8.3 Hz, allene H). IR (KBr or neat): 3420–
the reaction pathway represented in Scheme 1. Namely, 3470 (OH), 1956–1957 (allenyl) cm–1; high resolution
dialkylation of 1 with five types of alkyl halides in the MS (M+)].10
presence of NaH in THF followed by the reduction of the
The desirable ring-expansion (6→7) reactions com-
resulting a,a-dialkyl esters 2a–e with LiAlH4 gave the
menced with the Pd(0)-promoted conditions which we
corresponding alcohols 3a–e.6 After protection of the hy-
first used successfully for the conversion of five-mem-
droxy group of 3a–e with the MEM group, the products
bered phthalans to six-membered isochromanones via hy-
dropalladation.5f Namely, the compounds 7a–c were
refluxed with 5 mol% of Pd(PPh3)4 and 10 mol% of P(o-
tolyl)3 in THF for 3–12 hours. The desired one-atom ring-
expansion reactions proceeded smoothly to afford 3-benz-
SYNLETT 2004, No. 3, pp 0481–0484
Advanced online publication: 06.02.2004
DOI: 10.1055/s-2004-815440; Art ID: U29303ST
© Georg Thieme Verlag Stuttgart · New York
1
8.
0
2.
2
0
0
4

482
Y. Nagao et al.
LETTER
MeO
HO
O
7a 98%
7b 87%
7c 69%
i)
O
O
7d
7e
–
–
R
R
R
R
6a–e
7a–e
a R = Me; b R = Et; c R =n-Pr; d R = Bz; e R = –(CH2)4–
Scheme 2 Reagents and conditions: i) methoxyallene (2.0 mol
equiv), n-BuLi (1.2 mol equiv), THF, –30 °C.
Figure 1 Computer-generated drawing from the X-ray coordinates
of 8a and 10b.
Subsequently, we undertook the development of a general
method for the ring-expansion reaction involving the
conversion of six-membered cyclic ethers into eight-
membered cyclic ethers based on nucleophillic methoxy-
allenylation to the d-lactone carbonyl followed by the
water-quenched ring-opening of lithioxy methoxyallenyl-
isochromans and then endo-mode cyclization, as shown in
Scheme 4.5d Isochroman-1-one derivatives 9a–e8,7c,13
were allowed to react with 1.2 mol equivalents of lithio
methoxyallene at –30 °C in THF for 0.5–1.0 hours, and
then each reaction was quenched by the addition of water
to furnish the corresponding 3-benzoxocan-6-one deriva-
tives 10a–e in 53–75% yields.14 The structures of 10a–e
were determined by their characteristic spectroscopic data
[1H NMR (400 MHz, CDCl3) d = 2.11–2.12 (s, 3 H, CMe),
2.92–2.98 (t, 2 H, J = 5.6–5.9 Hz, C1-H), 3.72–3.73 (s, 3
H, OMe), 3.99–4.03 (t, 2 H, J = 5.6–5.9 Hz, C2-H). IR
(KBr or neat): 1613–1620 (a,b-unsaturated ketone) cm–1;
high resolution MS (M+)] and elemental analyses,14 or by
X-ray crystallographic analysis of 10b, as shown in
Figure 1.15
oxepan-1-one derivatives 8a–c in 79–97% yields, as
shown in Scheme 3.11 The structures of 8a–c were expli-
citly determined by their characteristic spectroscopic data
[1H NMR (400 MHz, CDCl3): d = 3.34–3.36 (s, 3 H,
OMe), 5.35–5.37 (dd, 1 H, J = 1.5–1.6, 10.3–10.5 Hz, ole-
fin H), 5.48–5.53 (dd, J = 1.5–1.6, 17.3 Hz, olefin H), and
5.61–5.65 (dd, 1 H, J = 10.3–10.5, 17.2–17.3 Hz, olefin
H). IR (KBr or neat): 1700–1711 (ketone) cm–1; high res-
olution MS (M+)] and elemental analyses,11 or by X-ray
crystallographic analysis of 8a, as shown in Figure 1.12
Thus, we have achieved the first facile ring-expansion re-
action of six-membered cyclic ethers to seven-membered
cyclic ethers via hydropalladation.
MeO
Pd
O
MeO
HO
Me
O
O
O
H
O
i)
O
8a 79%
Pd(0)
8b 97%
8c 94%
R
R
R
R
R
R
8a–c
7a–c
Although we had previously encountered one example of
such a ring-expansion reaction (5→7) in the reaction of a
non-substituted phthalide with lithio methoxyallene,5d we
have now established a new general synthetic method for
the eight-membered cyclic ethers.
a R = Me; b R = Et; c R =n-Pr
Scheme 3 Reagents and conditions: i) Pd(PPh3)4 (5 mol%), P(o-to-
lyl)3 (10 mol%), THF, reflux.
OH2
Me
Li
Me
Li
O
O
O
O
O
R1
R2
R1
R2
R1
R2
i)
ii)
O
O
O
9a–e
OMe
O
O
O
10a 75%
10b 68%
10c 53%
10d 69%
10e 73%
R1
R2
R1
Me
MeO
O-
R2
10a–e
a R1 = R2 = H; b R1 = Me, R2 = H; c R1 = H, R2 = Me; d R1 = OMe, R2 = H; e R1 = R2 = OMe
Scheme 4 Reagents and conditions: i) methoxyallene (2.0 mol equiv), n-BuLi (1.2 mol equiv), THF, –30 °C; ii) H2O.
Synlett 2004, No. 3, 481–484 © Thieme Stuttgart · New York

LETTER
New Synthetic Methods for Seven- and Eight-Membered Cyclic Ethers
was quenched with H2O and extracted with Et2O. The
483
Acknowledgment
organic layer was washed with brine, dried over MgSO4, and
filtered. The filtrate was evaporated in vacuo to afford a
crude product, which was purified by column chromato-
graphy on silica gel with n-hexane–EtOAc (3:1) to give 1-
hydroxy-1-methoxyallenyl-4,4-dimethylisochroman (7a;
483.2 mg, 98%) as a pale yellow oil.
This work was supported in part by a Grant-in-Aid for Scientific
Research on Priority Areas (A)(2)(No. 13029085) from the Mini-
stry of Education, Culture, Science, Sports, and Technology, Japan.
References
Compound 7a: pale yellow oil. IR (neat): 3428, 1956 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.26 (s, 3 H), 1.33 (s, 3 H),
3.42 (s, 1 H), 3.47 (s, 3 H), 3.61 (d, J = 11.0 Hz, 1 H), 4.04
(d, J = 11.0 Hz, 1 H), 5.60 (d, J = 8.3 Hz, 1 H), 5.66 (d,
J = 8.3 Hz, 1 H), 7.17–7.36 (m, 4 H). 13C NMR (75 MHz,
CDCl3): d = 24.5, 28.2, 33.4, 56.8, 70.8, 94.3, 96.1, 124.4,
125.7, 127.4, 128.5, 133.7, 137.2, 144.1, 197.1. HRMS-EI
calcd for C15H18O3: MW 246.1256. Found: m/z = 246.1254
(M+). Compound 7b: pale yellow oil. IR (neat): 3470, 1956
cm–1. 1H NMR (400 MHz, CDCl3): d = 0.77 (t, J = 7.7 Hz, 3
H), 0.81 (t, J = 7.7 Hz, 3 H), 1.62–1.82 (m, 4 H), 3.48 (s, 3
H), 3.50 (s, 1 H), 3.76 (d, J = 11.2 Hz, 1 H), 4.11 (d, J = 11.2
Hz, 1 H), 5.52 (d, J = 8.3 Hz, 1 H), 5.55 (d, J = 8.3 Hz, 1 H),
7.16–7.31 (m, 3 H), 7.36–7.39 (m, 1 H). 13C NMR (75 MHz,
CDCl3): d = 8.6, 8.7, 28.5, 31.3, 39.4, 56.9, 66.5, 94.0, 96.3,
125.5, 125.6, 127.6, 128.0, 135.2, 136.7, 141.2, 197.4.
HRMS-EI calcd for C17H22O3: MW 274.1569. Found: m/z =
274.1569 (M+). Compound 7c: white powder. IR (KBr):
3420, 1957 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.83 (t,
J = 7.3 Hz, 3 H), 0.86 (t, J = 7.3 Hz, 3 H), 1.06–1.29 (m, 4
H), 1.59–1.73 (m, 4 H), 3.48 (s, 3 H), 3.49 (s, 1 H), 3.76 (d,
J = 11.5 Hz, 1 H), 4.10 (d, J = 11.5 Hz, 1 H), 5.52 (d, J = 8.3
Hz, 1 H), 5.55 (d, J = 8.3 Hz, 1 H), 7.15–7.30 (m, 3 H), 7.35–
7.37 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = 14.9, 15.0,
17.3, 17.4, 39.2, 39.4, 41.7, 57.0, 67.4, 94.1, 96.3, 125.4,
125.5, 127.6, 128.0, 134.7, 136.6, 141.9, 197.3. HRMS-EI
calcd for C19H26O3: MW 302.1882. Found: m/z = 302.1888
(M+).
(1) (a) Katrizky, A. R.; Ress, C. W.; Scriven, E. F. V. In
Comprehensive Heterocyclic Chemistry II; Pergamon Press:
Oxford UK, 1996. (b) Lecount, D. J. Progress in
Heterocyclic Chemistry 1998, 10, 320.
(2) (a) Shimizu, Y.; Chou, H. N.; Bando, H.; Van Duyne, G.;
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M.; Tempesta, M. S.; Golik, J.; Zagorski, M. G.; Lee, M. S.;
Nakanishi, K.; Iwashita, T.; Gross, M. L.; Tomer, K. B. J.
Am. Chem. Soc. 1987, 109, 1144.
(3) Murata, M.; Legrand, A. M.; Ishibashi, Y.; Yasumoto, T. J.
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Tetrahedron Lett. 1993, 34, 4385. (e) Robinson, R. A.;
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B.; Moser, W. H.; Hegedus, L. S. J. Org. Chem. 1998, 63,
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2002, 480. (f) Nagao, Y.; Ueki, A.; Asano, K.; Tanaka, S.;
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(10) Typical Experimental Procedure for the Synthesis of
Hydroxy Methoxyallenyl-4,4-dialkylisochromans 7a–c:
A solution of methoxyallene (280.4 mg, 4.0 mmol) in dry
THF (4.0 mL) was treated with 1.58 M n-BuLi in n-hexane
(1.52 mL, 2.4 mmol) under an argon atmosphere at –30 °C.
The solution was stirred for 30 min, and then the solution
was added to a THF (2.0 mL) solution of 4,4-dimethyl-
isochroman-1-one (6a; 352.4 mg, 2.0 mmol) at –30 °C.
After being stirred at –30 °C for 1 h, the reaction mixture
(11) Typical Procedure for the Ring-Expansion Reaction of
Hydroxy Methoxyallenyl-4,4-dialkylisochromans 7a–c:
A mixture of 1-hydroxy-1-methoxyallenyl-4,4-dimethyl-
isochroman (7a; 173.1 mg, 0.703 mmol), Pd(PPh3)4 (40.6
mg, 5.0 mol%), P(o-tolyl)3 (21.4 mg, 10.0 mol%) in THF
(7.0 mL) was refluxed under an argon atmosphere for 3 h.
The reaction mixture was evaporated in vacuo to afford a
solid residue, which was purified by column chromato-
graphy on silica gel with n-hexane–EtOAc (3:1) to give 5,5-
dimethyl-2-methoxy-2-vinyl-3-benzoxepan-1-one (8a;
137.4 mg, 79%) as colorless prisms.
Compound 8a: colorless prisms; mp 78.5–79.5 °C (n-
hexane–EtOAc). IR (KBr): 1711 cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.14 (s, 3 H), 1.60 (s, 3 H), 3.36 (s, 3 H), 3.69
(d, J = 13.2 Hz, 1 H), 4.03 (d, J = 13.2 Hz, 1 H), 5.37 (dd,
J = 1.6, 10.3 Hz, 1 H), 5.53 (dd, J = 1.6, 17.3 Hz, 1 H), 5.65
(dd, J = 10.3, 17.3 Hz, 1 H), 7.21–7.25 (m, 1 H), 7.41–7.50
(m, 3 H). HRMS-EI calcd for C15H18O3: MW 246.1256.
Found: m/z = 246.1258 (M+). Anal. Calcd for C15H18O3: C,
73.15; H, 7.37. Found: C, 73.03; H, 7.38. Compound 8b:
colorless oil. IR (neat): 1700 cm–1. 1H NMR (400 MHz,
CDCl3): d = 0.46 (t, J = 7.5 Hz, 3 H), 1.07 (t, J = 7.5 Hz, 3
H) 1.44–1.58 (m, 2 H), 1.76–1.89 (m, 1 H), 2.13–2.23 (m, 1
H), 3.35 (s, 3 H), 3.86 (d, J = 13.7 Hz, 1 H), 4.10 (d, J = 13.7
Hz, 1 H), 5.35 (dd, J = 1.5, 10.5 Hz, 1 H), 5.48 (dd, J = 1.5,
17.3 Hz, 1 H), 5.62 (dd, J = 10.5, 17.3 Hz, 1 H), 7.22–7.26
(m, 1 H), 7.24 (d, J = 7.8 Hz, 1 H), 7.42 (dd, J = 1.5, 7.7 Hz,
1 H), 7.46–7.50 (m, 1 H). HRMS-EI calcd for C17H22O3:
MW 274.1569. Found: m/z = 274.1558 (M+). Anal. Calcd for
C17H22O3: C, 74.42; H, 8.08. Found: C, 74.17; H, 8.08.
Compound 8c: colorless oil. IR (neat): 1701 cm–1. 1H NMR
(400 MHz, CDCl3): d = 0.54–0.73 (m, 4 H), 0.92–1.04 (m, 4
Synlett 2004, No. 3, 481–484 © Thieme Stuttgart · New York

484
Y. Nagao et al.
LETTER
Anal. Calcd for C13H14O3: C, 71.54; H, 6.47. Found: C,
H), 1.33–1.50 (m, 3 H), 1.63–1.78 (m, 3 H), 3.34 (s, 3 H),
3.87 (d, J = 13.7 Hz, 1 H), 4.11 (d, J = 13.7 Hz, 1 H), 5.35
(dd, J = 1.5, 10.5 Hz, 1 H), 5.48 (dd, J = 1.5, 17.3 Hz, 1 H),
5.61 (dd, J = 10.5, 17.3 Hz, 1 H), 7.21–7.24 (m, 1 H), 7.36
(d, J = 7.8 Hz, 1 H), 7.40 (dd, J = 1.5, 7.8 Hz, 1 H), 7.46–
7.50 (m, 1 H). HRMS-EI calcd for C19H26O3: MW 302.1882.
Found: m/z = 302.1888 (M+). Anal. Calcd for C19H26O3: C,
75.46; H, 8.67. Found: C, 75.21; H, 8.71.
71.32; H, 6.43. Compound 10b: colorless needles; mp 72.5–
73.5 °C (CHCl3–n-hexane–Et2O). IR (KBr): 1620, 1601
cm–1. 1H NMR (400 MHz, CDCl3): d = 2.11 (s, 3 H), 2.36 (s,
3 H), 2.94 (t, J = 5.9 Hz, 2 H), 3.72 (s, 3 H), 4.00 (t, J = 5.9
Hz, 2 H), 7.05 (d, J = 7.8 Hz, 1 H), 7.23–7.26 (m, 1 H), 7.56
(d, J = 0.7 Hz, 1 H). HRMS-EI calcd for C14H16O3: MW
232.1100. Found: m/z = 232.1104 (M+). Anal. Calcd for
C14H16O3: C, 72.39; H, 6.94. Found: C, 72.13; H, 6.96.
Compound 10c: colorless prisms; mp 56.0–56.5 °C (n-
hexane–Et2O). IR (KBr): 1617, 1608 cm–1. 1H NMR (400
MHz, CDCl3): d = 2.11 (s, 3 H), 2.37 (s, 3 H), 2.95 (t, J = 5.7
Hz, 2 H), 3.72 (s, 3 H), 4.01 (t, J = 5.7 Hz, 2 H), 6.97 (s, 1
H), 7.15 (d, J = 8.1 Hz, 1 H), 7.69 (d, J = 8.1 Hz, 1 H);
HRMS-EI calcd for C14H16O3: MW 232.1100. Found: m/z =
232.1092 (M+). Anal. Calcd for C14H16O3: C, 72.39; H, 6.94.
Found: C, 72.17; H, 6.98. Compound 10d: colorless plates;
mp 81.0 °C (n-hexane–EtOAc). IR (KBr): 1613, 1600 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.12 (s, 3 H), 2.92 (t,
J = 5.6 Hz, 2 H), 3.72 (s, 3 H), 3.83 (s, 3 H), 3.99 (t, J = 5.6
Hz, 2 H), 7.00 (dd, J = 2.0, 8.3 Hz, 1 H), 7.07 (d, J = 8.3 Hz,
1 H), 7.30 (d, J = 2.0 Hz, 1 H). HRMS-EI calcd for
(12) X-ray data for 8a: C15H18O3, MW = 246.31, colorless block,
orthorhombic, space group Aba2 (#41), a = 22.4114 Å,
b = 7.929(2) Å, c = 14.737 (4) Å, V = 2618 (1) Å3, Z = 8,
R = 0.181, Rw = 0.181. The structure factors are available
from the author upon request.
(13) (a) Bhide, B. H.; Shah, K. K. Indian J. Chem., Sect. B 1980,
19, 9. (b) Lamaty, G.; Moreau, C.; Mouloungui, Z. Can. J.
Chem. 1983, 61, 2643. (c) Isobe, K.; Takeda, N.; Mohri, K.;
Tsuda, Y. Chem. Pharm. Bull. 1989, 37, 3390.
(14) Typical Experimental Procedure for the Ring-Expansion
Reaction of Isochroman-1-ones 9a–e: A solution of
methoxyallene (140.2 mg, 2.0 mmol) in dry THF (2.0 mL)
was treated with 1.58 M n-BuLi in n-hexane (0.76 mL, 1.2
mmol) under an argon atmosphere at –30 °C with stirring for
30 min. Then the solution was added to a THF (1.0 mL)
solution of 7-methoxy-isochroman-1-one (9d; 178.2 mg, 1.0
mmol) at –30 °C. After being stirred at –30 °C for 1 h, the
reaction mixture was quenched with H2O and extracted with
Et2O. The organic layer was washed with brine, dried over
MgSO4, and filtered. The filtrate was evaporated in vacuo to
afford a crude product, which was purified by column
chromatography on silica gel with n-hexane–EtOAc (3:1) to
give 5,8-dimethoxy-4-methyl-1,2-dihydro-3-benzoxocin-6-
one (10d; 166.6 mg, 69%) as colorless plates.
C14H16O4: MW 248.1049. Found: m/z = 248.1049 (M+).
Anal. Calcd for C14H16O4: C, 67.73; H, 6.50. Found: C,
67.76; H, 6.52. Compound 10e: colorless needless; mp
147.0–147.5 °C (n-hexane–EtOAc); IR (KBr) 1617, 1596
cm–1; 1H NMR (400 MHz, CDCl3) d = 2.11 (s, 3 H), 2.97 (t,
J = 5.7 Hz, 2 H), 3.72 (s, 3 H), 3.92 (s, 3 H), 3.94 (s, 3 H),
4.03 (t, J = 5.7 Hz, 2 H), 6.62 (s, 1 H), 7.44 (s, 1 H). HRMS-
EI calcd for C15H18O5 MW 278.1154, found m/z 278.1172
(M+). Anal. Calcd for C15H18O5: C, 64.47; H, 6.52. Found: C,
64.74; H, 6.58.
Compound 10a: colorless oil. IR (neat): 1619, 1596 cm–1. 1H
NMR (400 MHz, CDCl3): d = 2.12 (s, 3 H), 2.98 (t, J = 5.7
Hz, 2 H), 3.73 (s, 3 H), 4.02 (t, J = 5.7 Hz, 2 H), 7.16 (d,
J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.44 (d, J = 7.6
Hz, 1 H), 7.74 (d, J = 7.6 Hz, 1 H). HRMS-EI calcd for
C13H14O3: MW 218.0943. Found: m/z = 218.0957 (M+).
(15) X-ray data for 10b: C14H16O3, MW = 232.28, colorless
needle, monoclinic, space group P21/c (#14), a = 10.223(3)
Å, b = 8.743(2) Å, c = 14.193(3) Å, V = 1237.9(5) Å3,
b = 102.64(1)o, Z = 4, R = 0.087, Rw = 0.131. The structure
factors are available from the author upon request.
Synlett 2004, No. 3, 481–484 © Thieme Stuttgart · New York