Competing regiodirecting effects of ester and aryl groups in [3+3] cyclocondensations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes: Regioselective synthesis of 3-hydroxyphthalates and 2-hydroxyterephthalates

Article abstract of DOI:10.1002/ejoc.200901373

3-Hydroxy-5-methylphthalates are prepared by regioselective chelation-controlled cyclization of 1,3-bis(silyloxy)-1,3butadienes with 4-silyloxy-2-oxo-3-butenoates derived, from acetylpyruvates. The employment of silylated benzoylpyruvates instead of acetylpyruvates results in a regioselectivity change and the formation, of 6-aryl-2-hyd:roxyterephthalates. The cyclization of l,3-bis(silyloxy)-l,3-butadienes with 4ethoxy-2-oxo-3- butenoates, readily available by condensation of enol ethers with methyl 2-chloro-2-oxoacetate, provides a convenient approach to 2-hydroxyterephthalates and 3-hydroxyphthalates depending on the substitution pattern of the diene.

Full text of DOI:10.1002/ejoc.200901373

FULL PAPER
DOI: 10.1002/ejoc.200901373
Competing Regiodirecting Effects of Ester and Aryl Groups in [3+3]
Cyclocondensations of 1,3-Bis(trimethylsilyloxy)-1,3-butadienes: Regioselective
Synthesis of 3-Hydroxyphthalates and 2-Hydroxyterephthalates
Mohanad Shkoor,[a] Olumide Fatunsin,[a] Abdolmajid Riahi,[a,b] Mathias Lubbe,[a]
Stefanie Reim,[a] Muhammad Sher,[a,b,c] Alexander Villinger,[a] Christine Fischer,[b] and
Peter Langer*[a,b]
Keywords: Arenes / Cyclization / Regioselectivity / Silicon / Enols
3-Hydroxy-5-methylphthalates are prepared by regioselec-
tive chelation-controlled cyclization of 1,3-bis(silyloxy)-1,3-
butadienes with 4-silyloxy-2-oxo-3-butenoates derived from
acetylpyruvates. The employment of silylated benzoylpyr-
uvates instead of acetylpyruvates results in a regioselectivity
change and the formation of 6-aryl-2-hydroxyterephthalates.
The cyclization of 1,3-bis(silyloxy)-1,3-butadienes with 4-
ethoxy-2-oxo-3-butenoates, readily available by condensa-
tion of enol ethers with methyl 2-chloro-2-oxoacetate, pro-
vides a convenient approach to 2-hydroxyterephthalates and
3-hydroxyphthalates depending on the substitution pattern
of the diene.
tions of 1,3-bis(silyloxy)-1,3-butadienes[8] with 3-silyloxy-2-
en-1-ones. This strategy has been widely applied in recent
years.[9] However, its scope is mainly limited to 3-silyloxy-
2-en-1-ones derived from symmetrical 1,3-diketones. Al-
though a few exceptions have been reported,[7] cyclizations
of 3-silyloxy-2-en-1-ones derived from unsymmetrical 1,3-
diketones often proceed with low regioselectivity.
Introduction
Highly functionalized benzene derivatives, such as hy-
droxylated benzoates and benzodioates, are of considerable
interest as lead structures and synthetic building blocks in
medicinal and agricultural chemistry.[1,2] Classical syntheses
of such compounds are based on electrophilic substitution
and oxidation reactions. Despite their great utility, electro-
philic substitutions have several drawbacks (e.g., low re-
gioselectivity and low reactivity of electron-poor sub-
strates). Oxidations of toluene derivatives to benzoic acid
derivatives often require drastic conditions. Transition-
metal-catalyzed cross-coupling reactions of functionalized
benzene derivatives proceed under relatively mild condi-
tions.[3] However, the synthesis of the required starting ma-
terials, highly functionalized or sterically encumbered ben-
zene derivatives, can be a difficult task.
Functionalized benzene derivatives have been prepared
also by application of a “building block” strategy. Examples
include base-mediated cyclizations of acetone-1,3-dicarbox-
ylates,[4] condensations of 1,3-dicarbonyl dianions with car-
boxylic acid derivatives and subsequent intramolecular al-
dol reactions of the polyketides thus formed[5] and [4+2]
cycloadditions.[6] Chan and Brownbridge were the first to
report[7] the synthesis of salicylates by formal [3+3] cycliza-
Recently, we reported[10] preliminary results related to
the synthesis of 3-hydroxy-5-methylphthalates based on re-
gioselective chelation-controlled[11,12] cyclizations of 1,3-
bis(silyloxy)-1,3-butadienes with 4-silyloxy-2-oxo-3-but-
enoates derived from acetylpyruvates. Herein, we report a
full account related to the scope. During our studies we
found that the employment of benzoylpyruvates instead of
acetylpyruvates results in a complete regioselectivity change
and the formation of 6-aryl-2-hydroxyterephthalates. In ad-
dition, we report what are, to the best of our knowledge,
the first cyclizations of 1,3-bis(silyloxy)-1,3-butadienes with
methyl 4-ethoxy-2-oxo-3-butenoates, which are readily
available by condensation of enol ethers with methyl 2-
chloro-2-oxoacetate. These reactions provide a convenient
approach to C5-unsubstituted 3-hydroxyphthalates.
Results and Discussion
[a] Institut für Chemie der Universität Rostock,
Albert-Einstein-Straße 3a, 18059 Rostock, Germany
Fax: +49-381-498-6411
4-Silyloxy-2-oxo-3-butenoates 2a,b were prepared by sil-
ylation of acetylpyruvates 1a,b (Scheme 1).
The TiCl4-mediated formal [3+3] cyclization of 4-silyl-
oxy-2-oxo-3-butenoate 2a with 1,3-bis(silyloxy)-1,3-butadi-
ene 3a (Chan’s diene), prepared in two steps from methyl
acetoacetate,[7] afforded 3-hydroxy-5-methylphthalate 4a
E-mail: peter.langer@uni-rostock.de
[b] Leibniz Institut für Katalyse e.V. an der Universität Rostock,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany
[c] Department of Chemistry, Allama Iqbal Open University,
Islamabad, Pakistan
3732
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3732–3742

Competing Regiodirecting Effects in [3+3] Cyclocondensations
regioselectivity (Scheme 3). The moderate yields can be ex-
plained by practical problems during the chromatographic
purification (Table 1). The formation of the other re-
gioisomer, a 2-hydroxy-6-methylterphthalate, was not ob-
served.
Scheme 1. Synthesis of silyl enol ethers 2a,b; the products were iso-
lated as mixtures of E/Z isomers.
with very good regioselectivity. The best yield was obtained
when the reaction was carried out in a highly concentrated
solution (Scheme 2).
Scheme 3. Synthesis of 4a–i. Reagents and conditions: (i) TiCl4
(1.1 equiv.), CH2Cl2, –78 to 20 °C.
Table 1. Synthesis of 4a–i.
% Yield of
2
3,4
R1
R2
R3
4[a]
a
a
a
b
a
b
b
b
b
a
b
c
d
e
f
g
h
i
Me
Me
Me
Et
Me
Et
Et
Et
Et
H
Me
Et
nHex
OMe
Me
Et
Et
Me
Me
Et
Me
Me
Me
43
32
42
37
45
40
39
42
42
OPh
4-(MeO)C6H4
nNon
nDec
[a] Yield of isolated products.
The reaction of 2a with dienes 5a and 5b, prepared from
acetylacetone and benzoylacetone, afforded products 6a
and 6b, respectively (Scheme 4). Treatment of 6b with con-
centrated sulfuric acid gave functionalized anthraquinone
7, which also confirms the constitution of 6b.
Scheme 2. Possible mechanism of the formation of 4a.
The formation of 4a can be explained by reaction of 2a
with TiCl4 to give intermediate A. The attack of the ter-
minal carbon atom of 3a onto A results in the formation of
intermediate B. The elimination of 1,1,1,3,3,3-hexamethyl-
disiloxane (intermediate C) and subsequent cyclization
gives intermediate D. The elimination of titanium hydroxide
and aromatization resulted in the formation of product 4a.
The regioselectivity might be explained by TiCl4-mediated
migration of the TMS group of 2a and formation of inter-
mediate A, which allows chelation of TiCl4 by the neigh-
bouring oxygen atoms. The reaction of 1,3-bis(silyloxy)-1,3-
butadienes with 3-silyloxy-2-en-1-ones usually proceeds by
attack of the terminal carbon atom of the diene onto the
double bond of the 3-silyloxy-2-en-1-one (conjugate ad-
dition).[7–9] The π-donating effect of the silyloxy group in-
creases the electron density (and thus decreases the electro-
philicity) of the carbonyl group of the enone moiety. There-
fore, conjugate addition is observed.
Scheme 4. Synthesis of 6a,b and 7. Reagents and conditions: (i)
TiCl4 (1.1 equiv.), CH2Cl2, –78 to 20 °C; (ii) conc. sulfuric acid,
1 h.
The structures of products 4 and 6 were established by
The TiCl4-mediated cyclization of 4-silyloxy-2-oxo-3- NOESY experiments. For 6a, NOE interactions are ob-
butenoates 2a,b with 1,3-bis(silyloxy)-1,3-butadienes 3a–i, served between proton H-4 and the protons of the OH
available from the corresponding β-keto esters,[13,14] af- group and of the methyl group located at carbon C-5. In
forded 3-hydroxy-5-methylphthalates 4a–i with very good addition, NOE interactions are observed between H-6 and
Eur. J. Org. Chem. 2010, 3732–3742
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3733

P. Langer et al.
FULL PAPER
the methyl group located at C-5 and between H-6 and the with those reported for 10a[16] and for its phthalate re-
methyl group of the ester (Scheme 5). Likewise, characteris- gioisomer in the literature.[17] The structures of
tic NOE effects are observed for 6b, 4c and 4e.
terephthalates 10f and 10i were unambiguously proved by
the fact that two singlets (instead of two doublets) were
observed for the aromatic protons. The phthalate regioiso-
mers of 10f[18] and 10i[19] are known, and their spectro-
scopic data are, as expected, different from terephthalates
10f and 10i. The structure of 10j was proved by NOESY
experiments (Scheme 8). Similar to 10j, 3-hydroxyphthal-
ates 10b–e,g,h show a singlet at approx. 7.10 ppm, which
can be assigned to proton H-5 located in the meta position
to the ester group. In contrast, the signals of the protons
located in the ortho position to an ester group are generally
shifted more downfield. The spectroscopic data of 10g are
identical with those reported in the literature.[20]
Scheme 5. Characteristic NOESY effects of compounds 4c,e and
6a,b.
The reaction of enol ethers 8a–c with methyl 2-chloro-2-
oxoacetate (7) afforded, following a known procedure,[15]
4-ethoxy-2-oxo-3-butenoates 9a–c (Scheme 6, Table 2). The
synthesis of derivative 9a has been previously reported.[15]
Scheme 7. Synthesis of 10a–j.
Table 3. Synthesis of 10a–j.
Scheme 6. Synthesis of 9a–c. Reagents and conditions: (i) 8a–c
(2.0 equiv.), 7 (1.0 equiv.), 0 °C, 2–4 h; the products were isolated
as mixtures of E/Z isomers.
3
9
10
R1
R2
R3
% Yield of 10[a]
a
j
c
k
l
a
j
m
a
j
a
a
a
a
a
b
b
b
c
a
b
c
d
e
f
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
H
Me
Et
nBu
n-Oct
H
Me
n-Pent
H
H
H
H
H
H
Me
Me
Me
Et
Et
40
42
45
43
45
45
45
48
47
48
Table 2. Synthesis of 9a–c.
8,9
R
% Yield of 9[a]
a
b
c
H
Me
Et
82
97
95
g
h
i
[a] Yield of isolated products.
The TiCl4-mediated cyclization of 1,3-bis(silyloxy)-1,3-
butadiene 3a with 4-ethoxy-2-oxo-3-butenoate 9a gave C5-
unsubstituted 3-hydroxyterephthalate 10a (Scheme 7,
Table 3). The product was formed with very good regiose-
lectivity. The formation of the other regioisomer was not
observed. The reaction proceeds by attack of the terminal
carbon atom of the diene to the carbonyl group and subse-
quent cyclization. The regioselectivity can be explained by
the high electrophilicity of the carbonyl group located next
to the ester group. Likewise, the cyclization of 3a with en-
ones 9b and 9c afforded terephthalates 10f and 10i, respec-
tively. In contrast, the reaction of 9a–c with dienes 3c,j–m,
c
j
Me
[a] Yield of isolated products.
Scheme 8. Characteristic NOESY effects of compound 10j.
The silylation of benzoylpyruvates 11a–d[21] afforded 3-
containing a substituent located at carbon atom C-4, gave silyloxy-2-en-1-ones 12a–d (Scheme 9). The TiCl4-mediated
3-hydroxyphthalates 10b–e,g,h,j instead of the regioisomeric cyclization of 12a–d with 1,3-bis(trimethylsilyloxy)-1,3-
2-hydroxyterephthalates. The change in the regioselectivity butadienes
3a,d,j,k,n,o
afforded
6-aryl-2-hydroxy-
might be explained by steric reasons (interaction of substit- terephthalates 13a–n (Scheme 10, Table 4). Interestingly, the
uent R2 with the ester group of the enone). The structure reaction proceeded with different regioselectivity as com-
of terephthalate 10a was proved by comparison of the data pared to the reaction of dienes 3 with acetylpyruvate-de-
3734
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3732–3742

Competing Regiodirecting Effects in [3+3] Cyclocondensations
rived 3-silyloxy-2-en-1-ones 2a,b. The aryl group of 13a–n
The structures of terephthalates 13 were confirmed by
is located in the ortho position to the ester group, whereas spectroscopic methods (NOESY experiments). The signals
the methyl group of 4a–i is located in the para position to (1H NMR) of the methyl group of the CO2Me moiety of
the ester group. Chan and Brownbridge reported[7] that the terephthalates 13 (δ = 3.36–3.47 ppm) are generally shifted
reaction of 3a with 4-phenyl-4-(trimethylsilyloxy)but-3-en- upfield by ca. 0.4 ppm relative to the corresponding signals
2-one, prepared from benzoylacetone, afforded methyl 6- of phthalates 4 and 10 (δ = 3.79–3.94 ppm). This can be
phenyl-4-methylsalicylate (whose phenyl group is located explained by the fact that the CO2Me groups of terphthal-
ortho to the ester group). This result was explained by ates 13 are located in the anisotropic cone of the neighbour-
TiCl4-mediated isomerization of the TMS group of 4- ing aryl group (Scheme 11). The structures of 13h and 13m
phenyl-4-(trimethylsilyloxy)but-3-en-2-one to give 1-phenyl- were independently confirmed by X-ray crystal structure
3-(trimethylsilyloxy)but-2-en-1-one (or its titanium com- analyses (Figures 1 and 2).[22]
plex) and subsequent conjugate addition of the terminal
carbon atom of 3a onto the enone. This might be explained
by an energetically favourable interaction of TiIV with the
neighbouring phenyl group. The regioselective formation of
13a–n shows that this effect successfully competes with the
chelation discussed above for the synthesis of products 4.
The tendency of the aryl group to be located in the ortho
position to the ester group is obviously higher than the ten-
dency of the pyruvate-derived ester group to be located in
the ortho position to the diene-derived ester group.
Scheme 11. Location of the CO2Me group in the anisotropic cone
of the neighbouring aryl group of 13a–n.
Scheme 9. Synthesis of silyl enol ethers 12a–d.
Figure 1. Crystal structure of 13h.
Scheme 10. Synthesis of 13a–n. Reagents and conditions: (i) TiCl4
(1.1 equiv.), CH2Cl2, –78 to 20 °C.
Table 4. Synthesis of 13a–n.
3
11,12 13
R1
R2
% Yield of 13[a] δ(OMe)[b]
a
j
n
k
a
j
n
j
n
a
j
a
a
a
a
b
b
b
c
a
b
c
d
e
f
g
h
i
j
k
l
m
n
H
Me
Et
nBu
H
Me
Et
Me
Et
H
Me
Et
nHex
nHept
H
H
H
43
49
50
46
44
46
46
66
67
53
55
59
50
50
3.43
3.36
3.41
3.41
3.46
3.45
3.45
3.39
3.45
3.43
3.47
3.47
3.36
3.47
H
Me
Me
Me
NO2
NO2
Br
Br
Br
Br
Br
c
d
d
d
d
d
n
d
o
[a] Yield of isolated products. [b] Chemical shift [ppm] (1H NMR,
CDCl3) of the CO2Me group.
Figure 2. Crystal structure of 13m.
Eur. J. Org. Chem. 2010, 3732–3742
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3735

P. Langer et al.
FULL PAPER
(w), 1731 (m), 1652 (w), 1615 (s), 1456 (w), 1439 (w), 1388 (w),
1370 (w), 1321 (m), 1301 (m), 1273 (m), 1207 (s), 1146 (m), 1108
(m), 1083 (s), 1021 (m), 965 (m), 898 (m), 871 (m), 798 (w), 777
(w), 732 (m), 706 (m), 648 (w), 547 (w) cm–1. GC–MS (EI, 70 eV):
m/z (%) = 186 (4) [M]+, 127 (100), 99 (90), 83 (4), 69 (4), 53 (7), 43
(10), 29 (6). HRMS (ESI): calcd. for C9H15O4 [M + H]+ 187.09649;
found 187.09595.
Conclusions
In conclusion, we have reported the synthesis of 3-hy-
droxy-5-methylphthalates by regioselective chelation-con-
trolled cyclization of 1,3-bis(silyloxy)-1,3-butadienes with 4-
silyloxy-2-oxo-3-butenoates derived from acetylpyruvates.
The employment of silylated benzoylpyruvates instead of
acetylpyruvates results in a change in the regioselectivity
and the formation of 6-aryl-2-hydroxyterphthalates. The re-
giodirecting effect of the aryl group is stronger than that
of the pyruvate-derived ester group. The cyclization of 1,3-
bis(silyloxy)-1,3-butadienes with 4-ethoxy-2-oxo-3-but-
enoates, readily available by condensation of enol ethers
with methyl 2-chloro-2-oxoacetate, provides a convenient
approach to 3-hydroxyphthalates and 2-hydroxy-
terephthalates depending on the substitution pattern of the
diene.
Synthesis of Benzoylpyruvates 11a-d: Products 11a–d were prepared
as previously reported.[21] The spectroscopic data of 11d have not
been previously reported: 1H NMR (300 MHz, CDCl3): δ = 1.34
(t, 3J = 7.1 Hz, 3 H, OCH2CH3), 4.33 (q, 3J = 7.3 Hz, 2 H,
OCH2CH3), 6.96 (s, 1 H, CH), 7.55–7.60 (m, 2 H, CHAr), 7.77–
7.81 (m, 2 H, CHAr), 15.10 (s, 1 H, OH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.1 (CH3), 62.7 (OCH2), 97.7 (CH), 129.0 (CAr),
129.3 (2 CHAr), 132.3 (2 CHAr), 133.7 (CAr), 162.0 (COH), 170.2,
189.5 (CO) ppm. IR (neat): ν = 3414 (w), 3107 (w), 2982 (w), 2935
˜
(w), 2910 (w), 2868 (w), 1718 (m), 1585 (m), 1478 (m), 1446 (w),
1392 (m), 1365 (m), 1300 (m), 1260 (s), 1247 (s), 1175 (m), 1132
(m), 1104 (m), 1070 (m), 1004 (m), 933 (m), 910 (m), 857 (m), 809
(m), 764 (m), 679 (m), 626 (m), 537 (m) cm–1. GC–MS (EI, 70 eV):
m/z (%) = 300 (4) [M+, 81Br], 298 (4) [M+, 79Br], 227 (98), 225
(100), 183 (33), 155 (12), 118 (9), 89 (11), 75 (10), 69 (42). HRMS
(EI): calcd. for C12H11O4Br [M+, 81Br] 299.98148; found
299.981660. HRMS (EI): calcd. for C12H11O4Br [M+, 79Br]
297.98352; found 297.983698.
Experimental Section
General Comments: All solvents were dried by standard methods,
and all reactions were carried out under an inert atmosphere. 1H
and 13C NMR spectra were recorded with Bruker AM 250,
ARX 300, and ARX 500 spectrometers. Mass spectrometric data
(MS) were obtained by electron ionization (EI, 70 eV), chemical
ionization (CI, isobutane) or electrospray ionization (ESI). For pre-
parative-scale chromatography silica gel 60 (0.063–0.200 mm, 70–
230 mesh) was used.
General Procedure for the Synthesis of 4a–i, 6a,b, 10a–j and 13a–n:
To a CH2Cl2 solution (2 mL/1 mmol of enone) of enones 2, 9 or
12 was added diene 3 or 5 (1.1 mmol) and, subsequently, TiCl4
(1.1 mmol) at –78 °C. The temperature of the solution was warmed
to 20 °C over 14 h with stirring. To the solution was added hydro-
chloric acid (10%, 20 mL) and the organic and aqueous layers were
separated. The latter was extracted with CH2Cl2 (3ϫ20 mL). The
combined organic layer was dried (Na2SO4) and filtered, and the
filtrate was concentrated in vacuo. The residue was purified by
chromatography (silica gel, heptanes/EtOAc) to give the product.
General Procedure for the Synthesis of Alkyl 4-Ethoxy-2-oxo-3-but-
butenoates 9a-c: To alkyl vinyl ether 8a–c (2.0 equiv.) was dropwise
added, over 20 min, methyl chlorooxoacetate (1.0 equiv.) under an
atmosphere of argon at 0 °C. The mixture was stirred at 0 °C for
3 h. The temperature was warmed to 20 °C over 15 h with stirring.
The mixture was distilled in vacuo to give 9a–c. The synthesis of
9a has been previously reported.[15]
Dimethyl 3-Hydroxy-5-methylphthalate (4a): Starting with 2a
(0.433 g, 2.0 mmol) and 3a (0.573 g, 2.2 mmol), 4a was isolated as
Methyl 4-Ethoxy-3-methyl-2-oxobut-3-butenoate (9b): Starting with
8b (11.75 mL, 106.1 mmol) and methyl chlorooxoacetate (4.89 mL,
53.1 mmol), the product was collected after drying under vacuum
as a reddish oil (8.86 g, 97%). 1H NMR (250 MHz, CDCl3): δ =
a
brownish solid (0.193 g, 43%). M.p. 88–91 °C. 1H NMR
(250 MHz, CDCl3): δ = 2.33 (s, 3 H, PhCH3), 3.86 (s, 3 H, OCH3),
3.89 (s, 3 H, OCH3), 6.74–6.75 (m, 1 H, CHAr), 6.86–6.87 (m, 1 H,
CHAr), 10.62 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ =
21.6 (CH3), 52.5, 52.7 (OCH3), 107.2 (CAr), 119.7, 120.2 (CHAr),
135.3, 146.2 (CAr), 161.3 (COH), 169.3, 169.6 (CO) ppm. IR (Nu-
3
1.33 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.70 (s, 3 H, CH3), 3.81 (s,
3
3 H, OCH3), 4.14 (q, J = 7.1 Hz, 2 H, OCH2CH3), 7.54 (s, 1 H,
CHOlf) ppm. 13C NMR (75 MHz, CDCl3): δ = 7.4, 15.2 (CH3),
jol): ν = 3163 (w), 1725 (s), 1686 (s), 1618 (w), 1574 (w), 1339 (s),
˜
52.4 (OCH3), 71.3 (OCH2), 114.7 (C), 164.6 (CO), 165.7 (CHOlf),
185.6 (CO) ppm. IR (neat): ν = 2985 (w), 2956 (w), 2903 (w), 2254
1303 (m), 1270 (s), 1201 (s), 1160 (s), 1096 (m), 1035 (m) cm–1. MS
(EI, 70 eV): m/z (%) = 224 (18) [M]+, 192 (38), 134 (100). HRMS
(EI, 70 eV): calcd. for C11H12O5 [M]+ 224.0679; found 224.0676.
˜
(w), 2254 (w), 1731 (m), 1617 (s), 1476 (w), 1437 (w), 1388 (w),
1369 (w), 1330 (w), 1210 (s), 1146 (m), 1108 (m), 1049 (m), 1025
(m), 971 (m), 910 (m), 845 (w), 824 (w), 779 (w), 726 (s), 647 (w)
cm–1. GC–MS (EI, 70 eV): m/z (%) = 172 (3) [M]+, 144 (1), 113
(82), 85 (100), 83 (5), 55 (5), 39 (4), 29 (20). HRMS (EI): calcd. for
C8H12O4 [M]+ 172.07301; found 172.073090
2-Ethyl 1-Methyl 3-Hydroxy-4,5-dimethylphthalate (4b): Starting
with 2b (0.461 g, 2.0 mmol) and 3b (0.635 g, 2.2 mmol), 4b was
isolated as a reddish viscous oil (0.161 g, 32%). 1H NMR
(250 MHz, CDCl3): δ = 1.27 (t, 3J = 7.6 Hz, 3 H, OCH2CH3), 2.26
(s, 3 H, PhCH3), 2.39 (s, 3 H, PhCH3), 3.85 (s, 3 H, OCH3), 4.24
Methyl 3-(Ethoxymethylene)-2-oxopentanoate (9c): Starting with 8c
(13.64 mL, 106.1 mmol) and methyl chlorooxoacetate (4.89 mL,
53.1 mmol), the product was collected after drying under vacuum
as a reddish oil (9.38 g, 95%). 1H NMR (250 MHz, CDCl3): δ =
3
(q, J = 7.4 Hz, 2 H, OCH2CH3), 6.94 (s, 1 H, CHAr), 11.54 (s, 1
H, OH) ppm. 13C NMR (62 MHz, CDCl3): δ = 11.5, 13.4, 21.6
(CH3), 51.3 (OCH3), 60.2 (OCH2), 112.4 (CAr), 121.4 (CHAr),
0.91 (t, 3J = 7.6 Hz, 3 H, CH2CH3), 1.31 (t, 3J = 7.1 Hz, 3 H, 124.0, 134.7, 136.7 (CAr), 160.3 (COH), 166.7, 171.2 (CO) ppm. IR
OCH2CH3), 2.24 (q, 3J = 7.5 Hz, 2 H, CH2CH3), 3.79 (s, 3 H,
(neat): ν = 1660 (s), 1619 (m), 1452 (s), 1343 (s), 1219 (m), 1136
˜
OCH3), 4.12 (q, 3J = 7.5 Hz, 2 H, OCH2CH3), 7.46 (s, 1 H, CHOlf
)
(s), 966 (m), 882 (m), 694 (m) cm–1. MS (EI, 70 eV): m/z (%) = 252
(55) [M]+, 220 (100), 207 (37), 192 (87), 175 (13), 164 (82), 147 (17),
119 (15), 91 (25), 77 (11), 65 (18). HRMS (EI): calcd. for C13H16O5
252.10056; found 252.09998.
ppm. 13C NMR (75 MHz, CDCl3): δ = 12.6, 15.0 (CH3), 16.0
(CH2), 52.3 (OCH3), 71.1 (OCH2), 120.7 (C), 164.5 (CO), 165.7
(CHOlf), 185.3 (CO) ppm. IR (neat): ν = 2970 (w), 2937 (w), 2878
˜
3736
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3732–3742

Competing Regiodirecting Effects in [3+3] Cyclocondensations
2-Ethyl 1-Methyl 4-Ethyl-3-hydroxy-5-methylphthalate (4c): Start-
ing with 2a (0.433 g, 2.0 mmol) and 3c (0.666 g, 2.2 mmol), 4c was
(s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.6, 19.0
(CH3), 51.4, 54.2 (OCH3), 60.1 (OCH2), 112.5 (CAr), 113.1 (2
CHAr), 121.2 (CHAr), 127.0, 129.1 (CAr), 129.4 (2 CHAr), 129.8,
isolated as
a
slightly yellow oil (0.225 g, 42%). 1H NMR
(500.13 MHz, CDCl3): δ = 1.09 (t, 3J = 7.6 Hz, 3 H, CH2CH3), 136.2, 157.6 (CAr), 159.2 (COH), 170.4, 170.9 (CO) ppm. IR (neat):
3
1.34 (t, J = 7.3 Hz, 3 H, OCH2CH3), 2.31 (s, 3 H, PhCH3), 2.69 ν = 3034 (w), 2953 (w), 2931 (w), 2871 (w), 2836 (w), 1720 (w),
˜
3
(q, J = 7.6 Hz, 2 H, PhCH2CH3), 3.84 (s, 3 H, OCH3), 4.34 (q, 3J 1661 (w), 1608 (m), 1510 (m), 1438 (w), 1392 (w), 1368 (w), 1299
= 7.3 Hz, 2 H, OCH2CH3), 6.74 (s, 1 H, CHAr) 10.03 (s, 1 H, OH)
(w), 1243 (s), 1193 (w), 1174 (m), 1156 (m), 1109 (w), 1078 (w),
ppm. 13C NMR (125.8 MHz, CDCl3): δ = 12.8, 13.9 (CH3), 19.4 1031 (m), 969 (w), 902 (w), 831 (m), 788 (w), 689 (w), 643 (w), 597
(PhCH3), 19.5 (PhCH2), 52.3 (OCH3), 61.9 (OCH2), 107.2 (CAr),
120.7 (CHAr), 132.3, 133.2, 143.1 (CAr), 159.4 (COH), 169.6, 169.8
(CO) ppm. MS (EI, 70 eV): m/z (%) = 266 (23) [M]+, 220 (100),
205 (28), 188 (17), 162 (57), 134 (30). HRMS (EI): calcd. for
C14H18O5 [M]+ 266.1145; found 266.1149.
(w), 578 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 344 (53) [M]+,
313 (21), 312 (100), 283 (18), 256 (13), 239 (8), 211 (6), 197 (5), 149
(7), 135 (10), 121 (12), 73 (12). HRMS (EI): calcd. for C19H20O6
[M]+ 344.125; found 349.071546.
1-Ethyl 2-Methyl 3-Hydroxy-5-methyl-4-nonylphthalate (4h): Start-
ing with 2b (0.461 g, 2.0 mmol) and 3h (0.851 g, 2.2 mmol), 4h was
isolated as a yellowish oil (0.306 g, 42%). 1H NMR (250 MHz,
1-Ethyl 2-Methyl 4-Hexyl-3-hydroxy-5-methylphthalate (4d): Start-
ing with 2b (0.461 g, 2.0 mmol) and 3d (0.758 g, 2.2 mmol), 4d was
isolated as a reddish viscous oil (0.238 g, 37%). 1H NMR
3
CDCl3): δ = 0.81 (t, J = 6.3 Hz, 3 H, CH3), 1.16–1.19 (m, 14 H,
3
(250 MHz, CDCl3): δ = 0.81 (br. t, J = 7.1 Hz, 3 H, CH3), 1.02–
7CH2), 1.32 (t, 3J = 6.7 Hz, 3 H, OCH2CH3), 2.44 (s, 3 H, PhCH3),
3
3
3
1.25 (m, 8 H, CH2), 1.31 (t, J = 7.6 Hz, 3 H, OCH2CH3), 2.24 (s, 2.53 (t, J = 7.5 Hz, 2 H, CH2), 3.83 (s, 3 H, OCH3), 4.29 (q, J =
3 H, PhCH3), 2.58 (t, 3J = 7.4 Hz, 2 H, PhCH2), 3.81 (s, 3 H, 7.5 Hz, 2 H, OCH2CH3), 6.12 (s, 1 H, CHAr), 11.84 (s, 1 H, OH)
OCH3), 4.25 (q, 3J = 7.2 Hz, 2 H, OCH2CH3), 6.69 (s, 1 H, CHAr), ppm. 13C NMR (75 MHz, CDCl3): δ = 13.0, 13.1, 21.6 (CH3), 22.7,
10.84 (s, 1 H, OH) ppm. 13C NMR (62 MHz, CDCl3): δ = 15.2,
15.4 (CH3), 23.7 (CH2), 25.1 (CH3), 28.3, 30.3, 30.1, 32.7 (CH2),
34.4 (OCH3), 64.4 (OCH2CH3), 114.8 (CAr), 123.7 (CHAr), 130.8,
137.1, 139.1 (CAr), 162.4 (COH), 168.4, 173.4 (CO) ppm. MS (EI,
25.9, 28.5, 29.0, 29.3, 29.6, 30.8, 31.8 (CH2), 50.7 (OCH3), 60.3
(OCH2), 112.9 (CAr), 121.4 (CHAr), 128.6, 134.8, 144.3, (CAr),
159.9 (COH), 165.0, 171.4 (CO) ppm. IR (neat): ν = 3336 (w), 3107
˜
(w), 2953 (w), 2919 (m), 2848 (w), 1725 (w), 1660 (w), 1612 (m),
70 eV): m/z (%) = 322 (20) [M]+, 290 (7), 261 (11), 233 (5), 220 1493 (w), 1462 (m), 1415 (m), 1284 (m), 1259 (m), 1201 (m), 1225
(100), 206 (32), 192 (32), 174 (8), 161 (6), 148 (7), 119 (8), 91 (6), 69 (m), 1089 (m), 1014 (m), 977 (m), 840 (w), 795 (s), 754 (m), 722
(7). HRMS (EI): calcd. for C18H26O5 322.17747; found 322.17730.
(w), 682 (w), 622 (w), 551 (w) cm–1. GC–MS (EI, 70 eV): m/z (%)
= 364 (22) [M]+, 260 (19), 259 (100), 192 (12), 191 (34). HRMS
(EI): calcd. for C21H32O5 [M]+ 364.22443; found 364.224257.
Dimethyl 3-Hydroxy-4-methoxy-5-methylphthalate (4e): Starting
with 2a (0.433 g, 2.0 mmol) and 3e (0.639 g, 2.2 mmol), 4e was iso-
lated as a colourless oil (0.229 g, 45%). 1H NMR (500.13 MHz,
CDCl3): δ = 2.28 (s, 3 H, CH3), 3.84 (s, 3 H, OCH3), 3.86 (s, 3 H,
1-Ethyl 2-Methyl 4-Decyl-3-hydroxy-5-methylphthalate (4i): Start-
ing with 2b (0.461 g, 2.0 mmol) and 3i (0.882 g, 2.2 mmol), 4i was
OCH3), 3.89 (s, 3 H, OCH3), 6.83 (s, 1 H, CHAr), 10.36 (s, 1 H, isolated as a yellowish oil (0.318 g, 42%). 1H NMR (250 MHz,
OH) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 16.2 (CH3), 52.6,
CDCl3): δ = 0.80 (t, J = 6.7 Hz, 3 H, CH3), 1.16–1.19 (m, 16 H,
3
52.8, 60.2 (OCH3), 110.2 (CAr), 121.4 (CHAr), 129.3, 137.3, 148.2 8CH2), 1.32 (t, 3J = 6.2 Hz, 3 H, OCH2CH3), 2.44 (s, 3 H, PhCH3),
3
3
(CAr), 154.1 (COH), 169.1, 169.4 (CO) ppm. IR (neat): ν = 3410 2.76 (t, J = 7.2 Hz, 2 H, PhCH2), 3.89 (s, 3 H, OCH3), 4.29 (q, J
˜
(m), 2999 (m), 2954 (s), 2846 (w), 1734 (s), 1674 (s), 1611 (m), 1575 = 6.2 Hz, 2 H, OCH2CH3), 6.94 (s, 1 H, CHAr), 11.54 (s, 1 H, OH)
(m) cm–1. MS (EI, 70 eV): m/z (%) = 254 (71) [M]+, 223 (70), 222
(100), 207 (37), 194 (64), 163 (71), 136 (48). C12H14O6 (254.24):
calcd. C 56.69, H 5.55; found C 56.76, H 5.59.
ppm. 13C NMR (75 MHz, CDCl3): δ = 13.0, 13.2, 21.6 (CH3), 22.8,
25.9, 26.2, 28.2, 28.4, 28.5, 29.0, 30.8, 31.8 (CH2), 51.3 (OCH3),
60.2 (OCH2), 112.6 (CAr), 121.4 (CHAr), 128.6, 134.7, 136.8 (CAr),
160.2 (COH), 166.9, 171.2 (CO) ppm. IR (neat): ν = 2953 (w), 2922
˜
Diethyl 3-Hydroxy-5-methyl-4-phenoxyphthalate (4f): Starting with
2b (0.461 g, 2.0 mmol) and 3f (0.807 g, 2.2 mmol), 4f was isolated
as a reddish viscous oil (0.275 g, 40%). 1H NMR (250 MHz,
CDCl3): δ = 0.91 (t, 3J = 7.2 Hz, 3 H, OCH2CH3), 1.27 (t, 3J =
7.5 Hz, 3 H, OCH2CH3), 2.42 (s, 3 H, PhCH3), 4.01 (q, 3J = 7.6 Hz,
(s), 2852 (m), 1724 (m), 1662 (m), 1624 (w), 1561 (w), 1445 (m),
1395 (m), 1367 (m), 1298 (m), 1229 (s), 1193 (m), 1148 (m), 1104
(m), 1058 (m), 1011 (m), 843 (m), 800 (m), 780 (m), 721 (w), 602
(w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 378 (21) [M]+, 274 (20),
273 (100), 192 (12), 191 (32). HRMS (EI): calcd. for C22H34O5
[M]+ 378.24008; found 378.239759.
3
2 H, OCH2CH3), 4.28 (q, J = 7.4 Hz, 2 H, OCH2CH3), 6.66 (m,1
H, CHAr), 6.67–6.83 (m, 2 H, 2 CHAr), 7.04 (m, 1 H, CHAr), 7.07–
7.08 (m, 2 H, CHAr), 11.16 (s, 1 H, OH) ppm. 13C NMR (62 MHz,
Methyl 2-Acetyl-3-hydroxy-5-methylbenzoate (6a): Starting with 2a
CDCl3): δ = 13.7, 14.1, 23.6 (CH3), 61.4, 62.3 (CH2), 114.8 (2 (0.433 g, 2.0 mmol) and 5a (0.538 g, 2.2 mmol), 6a was isolated as
CHAr), 116.4 (CAr), 121.7, 122.2 (CHAr), 129.3 (CHAr), 129.8,
yellow solid (0.142 g, 34%). M.p. 88–89 °C. 1H NMR
132.1, 137.1, 140.0 (CAr), 156.3 (COH), 158.4 (CAr), 165.1, 170.8 (250.13 MHz): δ = 2.32 (s, 3 H, PhCH3), 2.46 (s, 3 H, COCH3),
a
(CO) ppm. IR (neat): ν = 2980 (w), 1727 (m), 1661 (m), 1489 (m),
3.82 (s, 3 H, OCH3), 6.97 (br. s, 1 H, CHAr), 7.16 (br. s, 1 H, CHAr),
9.50 (s, 1 H, OH) ppm. 13C NMR (125.8 MHz): δ = 21.1 (CH3),
31.2 (COCH3), 52.6 (OCH3), 121.3, 122.3, 127.9, 131.1, 142.0
˜
1412 (m), 1371 (m), 1296 (m), 1236 (s), 1016 (s), 747 (m), 687 (m)
cm–1. GC–MS (EI, 70 eV): m/z (%) = 372 (2) [M]+, 344 (63), 298
(38), 269 (8), 253 (20), 226 (100), 197 (13), 177 (5), 148 (6), 121 (6), (CAr), 155.9 (COH), 167.9, 203.0 (CO) ppm. MS (EI, 70 eV): m/z
105 (48).
(%) = 208 (60) [M]+, 193 (100), 177 (54), 161 (28), 148 (18), 133
(15), 77 (15). C11H12O4 (208.21): calcd. C 63.45, H 5.81; found C
63.12, H 5.90.
4-Ethyl 3-Methyl 2-Hydroxy-4Ј-methoxy-6-methylbiphenyl-3,4-di-
carboxylate (4g): Starting with 2b (0.461 g, 2.0 mmol) and 3g
(0.842 g, 2.2 mmol), 4g was isolated as a yellowish oil (0.268 g,
Methyl 2-Benzoyl-3-hydroxy-5-methylbenzoate (6b): Starting with
2a (0.433 g, 2.0 mmol) and 5b (0.674 g, 2.2 mmol), 6b was isolated
1
3
39%). HNMR (250 MHz, CDCl3): δ = 1.27 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 2.51 (s, 3 H, PhCH3), 3.76 (s, 3 H, PhOCH3), 3.91 (s, as a yellow solid (0.222 g, 41%). M.p. 158–159 °C. 1H NMR
3
3 H, OCH3), 3.99 (q, J = 6.2 Hz, 2 H, OCH2CH3), 6.76 (s, 1 H,
(500.13 MHz, CDCl3): δ = 2.40 (s, 3 H, PhCH3), 3.16 (s, 3 H,
CHAr), 6.85–6.88 (m, 2 H, CHAr), 7.10–7.12 (m, 2 H, CHAr), 11.43 OCH3), 7.03–7.09 (br. m, 1 H, CHAr), 7.18–7.20 (br. d, 4J = 1.5 Hz,
Eur. J. Org. Chem. 2010, 3732–3742
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3737

P. Langer et al.
FULL PAPER
1
3
1 H, CHAr), 7.42–7.46 (m, 2 H, CHAr), 7.51–7.63 (m, 3 H, CHAr), oil (0.171 g, 43%). H NMR (300 MHz, CDCl3): δ = 0.86 (t, J =
9.78 (s, 1 H, OH) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 21.6
6.8 Hz, 3 H, CH3), 1.30–1.32 (m, 2 H, CH2), 1.46–1.48 (m, 2 H,
3
(PhCH3), 51.9 (OCH3), 117.8 (C-2), 121.7 (C-4), 122.5 (C-6), 128.4 CH2), 2.83 (t, J = 7.7 Hz, 2 H, PhCH2), 3.83 (s, 3 H, OCH3), 3.89
(o-Ph), 128.5 (m-Ph), 132.6 (p-Ph), 133.9 (C-1), 139.6 (i-Ph), 144.9 (s, 3 H, OCH3), 7.11 (d, 3J = 8.2 Hz, 1 H, CHAr), 7.64 (d, 3J =
(C-5), 159.6 (COH), 167.7 (OCO), 199.0 (CO) ppm. IR (Nujol): ν 8.0 Hz, 1 H, CHAr), 11.08 (s, 1 H, OH) ppm. 13C NMR (75 MHz,
˜
= 3182 (m), 3083 (w), 1715 (m), 1645 (s), 1614 (m), 1581 (m) cm–1. CDCl3): δ = 12.9 (CH3), 22.0, 29.3, 30.9 (CH2), 51.2, 51.5 (OCH3),
MS (EI, 70 eV): m/z (%) = 270 (27) [M]+, 237 (100), 193 (39), 105
(20), 77 (27). C16H14O4 (270.28): calcd. C 70.84, H 5.57; found C
70.53, H 5.22.
112.5 (CAr), 118.1, 125.7 (CHAr), 131.3 (CAr), 136.2 (CAr), 159.2
(COH), 166.7, 169.5 (CO) ppm. IR (neat): ν = 3152 (w), 2954 (m),
˜
2924 (m), 2854 (m), 1727 (m), 1677 (m), 1616 (w), 1572 (w), 1440
(m), 1366 (w), 1335 (m), 1296 (m), 1252 (s), 1199 (m), 1149 (s),
1093 (s), 1025 (m), 958 (w), 841 (m), 806 (m), 758 (s), 722 (m), 659
(w), 578 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 266 (60) [M]+,
235 (33), 233 (12), 224 (17), 223 (36), 207 (41), 206 (56), 205 (23),
192 (24), 191 (100), 176 (12), 175 (81), 174 (23), 173 (11), 164 (52),
145 (11), 133 (20), 131 (10), 105 (13), 104 (12), 77 (15). HRMS
(EI): calcd. for C14H18O5 [M]+ 266.11488; found 266.114803.
Dimethyl 2-Hydroxyterephthalate (10a): Starting with 9a (0.237 g,
1.5 mmol) and 3a (0.429 g, 1.65 mmol), 10a was isolated after
chromatography (silica gel, n-heptane/EtOAc) as a white solid
1
(0.127 g, 40%). M.p. 85–87 °C. H NMR (300 MHz, CDCl3): δ =
3
3.85 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 7.45 (dd, J = 8.1 Hz,
4J = 1.6 Hz,1 H, CHAr), 7.56–7.57 (m, 1 H, CHAr), 7.83 (d, J =
3
8.4 Hz, 1 H, CHAr), 10.67 (s, 1 H, OH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 51.4, 51.6 (OCH3), 114.6 (CAr), 117.9, 118.6, 129.0
(CHAr), 135.4 (CAr), 160.3 (COH), 164.9, 168.9 (CO) ppm. IR
Dimethyl 3-Hydroxy-4-octylphthalate (10e): Starting with 9a
(0.237 g, 1.5 mmol) and 3l (0.614 g, 1.65 mmol), 10e was isolated
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
(neat): ν = 3115 (w), 3079 (w), 2959 (w), 2916 (m), 2848 (m), 1725
˜
1
3
(m), 1678 (s), 1579 (m), 1504 (m), 1435 (m), 1393 (w), 1343 (m),
1297 (s), 1209 (s), 1104 (s), 980 (m), 953 (m), 923 (m), 845 (w), 823
(m), 795 (m), 750 (s), 706 (m), 690 (s), 570 (m), 564 (m) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 210 (42) [M]+, 178 (100), 147 (10), 120
(10), 119 (63), 63 (12). HRMS (EI): calcd. for C10H10O5 [M]+
210.05227; found 210.052499.
oil (0.217 g, 45%). H NMR (300 MHz, CDCl3): δ = 0.82 (t, J =
6.9 Hz, 3 H, CH3), 1.30–1.37 (m, 10 H, 5CH2), 1.48–1.54 (m, 2 H,
3
CH2), 2.81 (t, J = 7.8 Hz, 2 H, PhCH2), 3.83 (s, 3 H, OCH3), 3.89
(s, 3 H, OCH3), 7.11 (d, 3J = 8.2 Hz, 1 H, CHAr), 7.64 (d, 3J =
8.5 Hz, 1 H, CHAr), 11.08 (s, 1 H, OH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 13.0 (CH3), 21.6, 26.2, 28.2, 28.3, 28.6, 30.8, 30.8
(CH2), 51.2, 51.6 (OCH3), 112.5 (CAr), 118.3, 125.7 (CHAr), 131.3,
Dimethyl 3-Hydroxy-4-methylphthalate (10b): Starting with 9a
(0.237 g, 1.5 mmol) and 3j (0.453 g, 1.65 mmol), 10b was isolated
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
136.2 (CAr), 159.2 (COH), 166.6, 169.6 (CO) ppm. IR (neat): ν =
˜
2953 (m), 2922 (s), 2853 (m), 1727 (m), 1678 (m), 1619 (w), 1441
(m), 1376 (w), 1336 (w), 1291 (m), 1254 (m), 1229 (s), 1193 (m),
1148 (m), 1101 (m), 1026 (m), 841 (m), 803 (m), 759 (m), 721 (m),
660 (w), 578 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 322 (53)
[M]+, 291 (27), 289 (16), 264 (16), 263 (85), 247 (22), 232 (17), 231
(97), 224 (28), 223 (45), 205 (27), 192 (41), 191 (100), 178 (14), 177
(14), 173 (12), 165 (10), 164 (42), 160 (10), 133 (16), 105 (10), 77
(10), 41 (12). HRMS (EI): calcd. for C18H26O5 [M]+ 322.17748;
found 322.177861.
1
solid (0.141 g, 42%). M.p. 76–78 °C. HNMR (300 MHz, CDCl3):
δ = 2.37 (s, 3 H, PhCH3), 3.83 (s, 3 H, OCH3), 3.98 (s, 3 H, OCH3),
7.17 (d, 3J = 7.6 Hz, 1 H, CHAr), 7.64 (d, 3J = 8.3 Hz, 1 H, CHAr),
11.11 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 11.45
(CH3), 51.2, 51.5 (OCH3), 112.4 (CAr), 118.3, 125.6 (CHAr), 126.9,
136.2 (CAr), 159.3 (COH), 166.4, 169.9 (CO) ppm. IR (neat): ν =
˜
3152 (w), 2954 (w), 2924 (m), 2852 (w), 1724 (m), 1674 (m), 1616
(w), 1573 (w), 1439 (m), 1380 (w), 1327 (m), 1285 (m), 1249 (s),
1191 (m), 1148 (s), 1098 (m), 1050 (s), 1006 (m), 966 (w), 910 (w),
869 (w), 821 (w), 803 (m), 755 (s), 728 (m), 644 (w), 578 (w) cm–1.
GC–MS (EI, 70 eV): m/z (%) = 224 (40) [M]+, 193 (29), 192 (47),
165 (10), 164 (100), 133 (13), 105 (14), 77 (12), 51 (10). HRMS
(EI): calcd. for C11H12O5 [M]+ 224.06792; found 224.068299.
Dimethyl 2-Hydroxy-5-methylterephthalate (10f): Starting with 9b
(0.258 g, 1.5 mmol) and 3a (0.429 g, 1.65 mmol), 10f was isolated
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
1
oil (0.150 g, 45%). H NMR (300 MHz, CDCl3): δ = 2.41 (s, 3 H,
PhCH3), 3.83 (s, 3 H, OCH3), 3.98 (s, 3 H, OCH3), 7.41 (s, 1 H,
CHAr), 7.62 (s,1 H, CHAr), 10.37 (s, 1 H, OH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 19.3 (CH3), 51.1, 51.5 (OCH3), 113.7 (CAr),
118.4 (CHAr), 128.5 (CAr), 131.2 (CHAr), 139.3 (CAr), 157.0 (COH),
2-Ethyl 1-Methyl 4-Ethyl-3-hydroxyphthalate (10c): Starting with
9a (0.237 g, 1.5 mmol) and 3c (0.499 g, 1.65 mmol), 10c was iso-
lated after chromatography (silica gel, n-heptane/EtOAc) as a yel-
lowish oil (0.170 g, 45%). 1HNMR (300 MHz, CDCl3): δ = 0.78 (t,
166.0, 168.9 (CO) ppm. IR (neat): ν = 3112 (w), 2956 (w), 2922
˜
3J = 7.5 Hz, 3 H, CH2CH3), 1.18 (t, J = 7.2 Hz, 3 H, OCH2CH3),
3
(m), 2852 (w), 1723 (m), 1682 (m), 1619 (w), 1572 (w), 1388 (w),
1435 (m), 1387 (w), 1368 (w), 1287 (m), 1249 (m), 1205 (m), 1192
(m), 1102 (s), 1046 (m), 1016 (m), 958 (m), 910 (w), 888 (w), 849
(w), 784 (s), 740 (m), 676 (m), 603 (w), 578 (w) cm–1. GC–MS (EI,
70 eV): m/z (%) = 224 (46) [M]+, 193 (39), 192 (100), 133 (24), 132
(32), 77 (10), 51 (9). HRMS (EI): calcd. for C11H12O5 [M]+
224.06792; found 224.067938.
3
2.84 (q, J = 8.4 Hz, 2 H, PhCH2), 3.84 (s, 3 H, OCH3), 4.33 (q,
3J = 7.8 Hz, 2 H, OCH2CH3), 7.11 (d, 3J = 8.4 Hz, 1 H, CHAr),
7.65 (d, 3J = 8.0 Hz, 1 H, CHAr), 11.18 (s, 1 H, OH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 13.0, 13.1 (CH3), 19.3 (CH2), 51.2
(OCH3), 60.7 (OCH2), 112.8 (CAr), 118.1, 125.7 (CHAr), 132.4
(CAr), 135.9 (CAr), 159.2 (COH), 166.7, 169.2 (CO) ppm. IR (neat):
ν = 3133 (w), 2956 (w), 2923 (m), 2853 (w), 1727 (m), 1673 (m),
˜
Dimethyl 3-Hydroxy-4,6-dimethylphthalate (10g): Starting with 9b
(0.258 g, 1.5 mmol) and 3j (0.453 g, 1.65 mmol), 10g was isolated
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
1615 (w), 1572 (w), 1461 (m), 1398 (w), 1372 (m), 1330 (m), 1291
(s), 1267 (m), 1240 (s), 1222 (m), 1148 (s), 1077 (s), 1018 (m), 952
(w), 864 (w), 806 (m), 757 (s), 732 (m), 644 (w), 577 (w) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 252 (30) [M]+, 221 (11), 207 (10), 206
(10), 191 (11), 179 (12), 178 (100), 146 (28), 91 (11). HRMS (EI):
calcd. for C13H16O5 [M]+ 252.09923; found 252.098543.
1
oil (0.160 g, 45%). H NMR (300 MHz, CDCl3): δ = 2.11 (s, 3 H,
PhCH3), 2.14 (s, 3 H, PhCH3), 3.85 (s, 3 H, OCH3), 3.87 (s, 3 H,
OCH3), 7.46 (s, 1 H, CHAr), 10.86 (s, 1 H, OH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 11.6, 17.6 (CH3), 51.1, 51.4 (OCH3), 110.8
(CAr), 122.6, 123.1 (CAr), 127.1 (CHAr), 139.6 (CAr), 157.0 (COH),
Dimethyl 4-Butyl-3-hydroxyphthalate (10d): Starting with 9a
(0.237 g, 1.5 mmol) and 3k (0.522 g, 1.65 mmol), 10d was isolated 168.4, 169.5 (CO) ppm. IR (neat): ν = 2953 (m), 2922 (s), 2852 (m),
˜
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
1735 (m), 1677 (m), 1618 (w), 1440 (m), 1378 (w), 1343 (m), 1283
3738
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3732–3742

Competing Regiodirecting Effects in [3+3] Cyclocondensations
(m), 1259 (m), 1233 (s), 1204 (m), 1146 (s), 1094 (m), 1052 (m), CDCl3): δ = 14.33 (CH3), 52.19 (OCH3), 60.38 (OCH2) 115.51
1020 (m), 840 (w), 795 (s), 755 (m), 722 (m), 610 (w), 563 (w) cm–1. (CAr), 117.67, 122.90, 127.16 (CHAr), 127.75 (2 CHAr), 128.13 (2
GC–MS (EI, 70 eV): m/z (%) = 238 (45) [M]+, 207 (38), 206 (65), CHAr), 134.76, 141.93, 145.00 (CAr), 160.96 (COH), 165.38, 170.82
179 (12), 178 (100), 147 (12), 91 (11). HRMS (EI): calcd. for
(CO) ppm. IR (KBr): ν = 3065 (w), 3026 (w), 2959 (w), 2904 (w),
˜
C12H14O5 [M]+ 238.08358; found 238.0833769.
1713 (s), 1671 (s), 1611 (m), 1567 (m), 1497 (w), 1433 (m), 1410
(m), 1367 (m), 1341 (m), 1321 (m), 1307 (w), 1264 (m), 1238 (s),
1201 (s), 1155 (m), 1139 (m), 1113 (m), 1081 (m), 1025 (m), 982
(m), 948 (m), 922 (w), 892 (m), 870 (w), 828 (m), 806 (m), 766 (s),
699 (s), 666 (m), 648 (m), 621 (m), 607 (m), 563 (m) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 300 (28) [M]+, 269 (20), 268 (100), 196 (12),
195 (14), 168 (10), 139 (20). HRMS (EI): calcd. for C17H16O5
[M]+ 300.09923; found 300.099353.
Dimethyl 3-Hydroxy-6-methyl-4-pentylphthalate (10h): Starting
with 9b (0.258 g, 1.5 mmol) and 3m (0.546 g, 1.65 mmol), 10h was
isolated after chromatography (silica gel, n-heptane/EtOAc) as a
yellowish oil (0.203 g, 46%). 1H NMR (300 MHz, CDCl3): δ = 0.82
3
(t, J = 6.6 Hz, 3 H, CH3), 1.23–1.29 (m, 4 H, 2 CH2), 1.47–1.57
(m, 2 H, CH2), 2.12 (s, 3 H, PhCH3), 2.54 (t, 3J = 7.7 Hz, 2 H,
PhCH2), 3.81 (s, 3 H, OCH3), 3.83 (s, 3 H, OCH3), 7.08 (s, 1 H,
CHAr), 10.92 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ =
13.0, 17.4 (CH3), 21.6, 27.7, 28.8, 30.6 (CH2), 50.8, 51.9 (OCH3),
107.8, 124.1, 130.9, 131.8 (CAr), 136.2 (CHAr), 157.1 (COH), 168.8,
5-Ethyl 2-Methyl 3-Hydroxy-4-methylbiphenyl-2,5-dicarboxylate
(13b): Starting with 12a (0.439 g, 1.5 mmol) and 3j (0.453 g,
1.65 mmol), 13b was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a yellowish oil (0.231 g, 49%). 1H NMR
168.9 (CO) ppm. IR (neat): ν = 2954 (w), 2928 (w), 2859 (w), 1735
˜
3
(m), 1672 (m), 1610 (w), 1587 (w), 1433 (s), 1342 (m), 1253 (s),
1207 (s), 1179 (m), 1160 (m), 1097 (w), 1049 (m), 992 (w), 962 (w),
898 (w), 869 (w), 846 (w), 801 (m), 744 (m), 650 (w), 529 (w) cm–1.
GC–MS (EI, 70 eV): m/z (%) = 294 (24) [M]+, 263 (20), 247 (19),
219 (31), 206 (100), 148 (8), 91 (5). HRMS (ESI): calcd. for
C16H23O5 [M + H]+ 295.154; found 295.1532.
(300 MHz, CDCl3): δ = 1.24 (t, J = 7.5 Hz, 3 H, CH3), 2.35 (s, 3
H, PhCH3), 3.36 (s, 3 H, OCH3), 4.24 (q, 3J = 7.4 Hz, 2 H, OCH2),
7.06 (s, 1 H, CHAr), 7.11–7.18 (m, 2 H, CHAr), 7.21–7.27 (m, 3 H,
CHAr), 10.82 (s, 1 H, OH) ppm. 13C NMR (62.5 MHz, CDCl3): δ
= 12.71, 14.34 (CH3), 51.96 (OCH3), 60.37 (OCH2) 113.34 (CAr),
122.36 (CHAr), 126.75 (CAr), 126.95 (CHAr), 127.78 (2 CHAr),
128.13 (2 CHAr), 135.43, 141.49, 142.28 (CAr), 159.98 (COH),
Dimethyl 5-Ethyl-2-hydroxyterephthalate (10i): Starting with 9c
(0.279 g, 1.5 mmol) and 3a (0.429 g, 1.65 mmol), 10i was isolated
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
167.47, 171.51 (CO) ppm. IR (KBr): ν = 3025 (w), 2952 (w), 2929
˜
(w), 2871 (w), 1723 (s), 1665 (s), 1600 (w), 1561 (w), 1499 (w), 1437
(m), 1394 (m), 1380 (m), 1367 (m), 1341 (m), 1298 (m), 1261 (s),
1230 (s), 1194 (s), 1158 (s), 1138 (m), 1095 (s), 1049 (s), 1003 (m),
967 (m), 937 (m), 843 (m), 810 (m), 800 (m), 785 (m), 759 (m), 699
(s), 628 (w), 613 (m), 581 (w) cm–1. GC–MS (EI, 70 eV): m/z (%)
= 315 (11), 314 (53) [M]+, 283 (21), 282 (100), 281 (13), 269 (23),
254 (13), 253 (57), 226 (19), 210 (15), 209 (24), 197 (16), 182 (17),
181 (23), 153 (17), 152 (32), 151 (10). HRMS (EI): calcd. for
C18H18O5 [M]+ 314.11488; found 314.114942.
1
3
oil (0.168 g, 47%). H NMR (300 MHz, CDCl3): δ = 1.13 (t, J =
3
7.2 Hz, 3 H, CH3), 2.79 (q, J = 8.4 Hz, 2 H, PhCH2), 3.83 (s, 3
H, OCH3), 3.90 (s, 3 H, OCH3), 7.34 (s, 1 H, CHAr), 7.65 (s, 1 H,
CHAr), 10.39 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ =
14.8 (CH3), 25.6 (CH2), 51.1, 51.5 (OCH3), 113.7 (CAr), 118.3,
129.9 (CHAr), 134.4, 135.2 (CAr), 157.9 (COH), 168.8, 168.9 (CO)
ppm. IR (neat): ν = 3205 (w), 2957 (w), 2929 (w), 2872 (w), 1729
˜
(m), 1682 (m), 1636 (w), 1572 (w), 1487 (m), 1439 (m), 1375 (w),
1319 (w), 1281 (m), 1203 (s), 1103 (s), 1066 (m), 961 (m), 908 (w),
844 (w), 794 (m), 759 (m), 697 (m), 647 (w), 622 (w) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 238 (45) [M]+, 223 (9), 206 (100), 191 (56),
174 (11), 146 (27), 133 (8), 119 (7), 91 (11), 65 (6). HRMS (EI):
calcd. for C12H14O5 [M]+ 238.08358; found 238.083603.
5-Ethyl 2-Methyl 4-Ethyl-3-hydroxybiphenyl-2,5-dicarboxylate
(13c): Starting with 12a (0.439 g, 1.5 mmol) and 3n (0.476 g,
1.65 mmol), 13c was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a pale-yellowish oil (0.246 g, 50%). 1H NMR
3
3
(300 MHz, CDCl3): δ = 1.17 (t, J = 7.3 Hz, 3 H, CH3), 1.30 (t, J
3
= 7.3 Hz, 3 H, CH3), 2.88 (q, J = 7.3 Hz, 2 H, PhCH2), 3.41 (s, 3
H, OCH3), 4.29 (q, J = 7.2 Hz, 2 H, OCH2), 7.07 (s, 1 H, CHAr),
Dimethyl 6-Ethyl-3-hydroxy-4-methylphthalate (10j): Starting with
9c (0.279 g, 1.5 mmol) and 3j (0.453 g, 1.65 mmol), 10j was isolated
after chromatography (silica gel, n-heptane/EtOAc) as a yellowish
3
7.13–7.17 (m, 2 H, CHAr), 7.22–7.31 (m, 3 H, CHAr), 10.81 (s, 1
H, OH) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 13.06, 13.20
(CH3), 19.45 (PhCH2), 50.90 (OCH3), 60.31 (OCH2) 112.50 (CAr),
121.49, 125.94 (CHAr), 126.70 (2 CHAr), 127.14 (2 CHAr), 131.29,
134.30, 140.69, 141.22 (CAr), 159.13 (COH), 166.83, 170.47 (CO)
1
3
oil (0.181 g, 48%). H NMR (300 MHz, CDCl3): δ = 1.10 (t, J =
3
7.5 Hz, 3 H, CH3), 2.19 (s, 3 H, CH3), 2.40 (q, J = 7.7 Hz, 2 H,
PhCH2), 3.81 (s, 3 H, OCH3), 3.83 (s, 3 H, OCH3), 7.13 (s, 1 H,
CHAr), 10.98 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ =
14.8, 14.9 (CH3), 24.9 (CH2), 51.2, 51.8 (OCH3), 107.1, 127.6,
130.3, 130.4 (CAr), 135.7 (CHAr), 157.3 (COH), 168.6, 168.9 (CO)
ppm. IR (KBr): ν = 3025 (w), 2953 (w), 2934 (w), 2874 (w), 1723
˜
(s), 1665 (s), 1600 (w), 1558 (w), 1495 (w), 1437 (m), 1390 (m), 1367
(m), 1346 (m), 1283 (m), 1247 (s), 1222 (s), 1193 (s), 1157 (s), 1138
(m), 1076 (s), 1028 (m), 1007 (m), 966 (m), 947 (m), 887 (w), 844
(m), 815 (m), 800 (m), 785 (m), 759 (m), 699 (s), 627 (w), 581 (w)
cm–1. GC–MS (EI, 70 eV): m/z (%) = 329 (21), 328 (100) [M]+, 297
(22), 296 (94), 295 (22), 283 (35), 268 (39), 276 (67), 253 (19), 251
(11), 249 (23), 240 (11), 225 (19), 224 (35), 223 (28), 221 (13), 197
(49), 196 (42), 195 (25), 194 (10), 167 (10), 166 (14), 165 (51), 153
(12), 152 (34), 151 (11), 139 (14), 129 (11), 115 (12). HRMS (EI):
calcd. for C19H20O5 [M]+ 328.13053; found 328.130470.
ppm. IR (neat): ν = 3116 (w), 2953 (w), 2875 (w), 1732 (s), 1672
˜
(s), 1612 (w), 1588 (w), 1431 (m), 1378 (m), 1351 (m), 1277 (s),
1255 (m), 1204 (s), 1177 (s), 1160 (s), 1046 (m), 988 (m), 895 (m),
867 (w), 805 (m), 789 (m), 734 (m), 639 (m), 563 (m) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 252 (30) [M]+, 220 (100), 205 (16), 188
(18), 162 (40), 134 (27), 103 (10), 91 (8), 77 (13). HRMS (EI): calcd.
for C13H16O5 [M]+ 252.09923; found 252.099036.
5-Ethyl 2-Methyl 3-Hydroxybiphenyl-2,5-dicarboxylate (13a): Start-
ing with 12a (0.439 g, 1.5 mmol) and 3a (0.429 g, 1.65 mmol), 13a
was isolated after chromatography (silica gel, n-heptane/EtOAc) as
5-Ethyl 2-Methyl 4-Butyl-3-hydroxybiphenyl-2,5-dicarboxylate
(13d): Starting with 12a (0.439 g, 1.5 mmol) and 3k (0.522 g,
1
a pale-yellowish oil (0.194 g, 43%). H NMR (300 MHz, CDCl3):
3
δ = 1.31 (t, J = 7.5 Hz, 3 H, CH3), 3.43 (s, 3 H, OCH3), 4.31 (q, 1.65 mmol), 13d was isolated after chromatography (silica gel, n-
3J = 7.1 Hz, 2 H, OCH2), 7.14–7.18 (m, 2 H, CHAr), 7.26–7.33 (m,
3 H, CHAr), 7.39 (d, 4J = 1.7 Hz, 1 H, CHAr), 7.57 (d, 4J = 1.8 Hz, (300 MHz, CDCl3): δ = 1.24 (t, J = 7.7 Hz, 3 H, CH3), 1.30 (t, J
1 H, CHAr), 10.41 (s, 1 H, OH) ppm. 13C NMR (62.5 MHz,
= 7.8 Hz, 3 H, CH3), 1.35–1.40 (m, 2 H, CH2), 1.49–1.57 (m, 2 H,
heptane/EtOAc) as a yellowish oil (0.245 g, 46%). 1H NMR
3
3
Eur. J. Org. Chem. 2010, 3732–3742
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3739

P. Langer et al.
CH2), 2.87 (q, 3J = 7.5 Hz, 2 H, PhCH2), 3.41 (s, 3 H, OCH3), 4.28 (t, 3J = 7.5 Hz, 3 H, CH3), 2.32 (s, 3 H, PhCH3), 2.87 (q, 3J =
FULL PAPER
3
3
(q, J = 7.2 Hz, 2 H, OCH2), 7.07 (s, 1 H, CHAr), 7.13–7.17 (m, 2
H, CHAr), 7.24–7.30 (m, 3 H, CHAr), 10.81 (s, 1 H, OH) ppm. 13C H, OCH2), 7.01–7.11 (m, 5 H, 5CHAr), 10.72 (s, 1 H, OH) ppm.
NMR (62.5 MHz, CDCl3): δ = 13.02, 13.24 (CH3), 22.10, 28.67,
13C NMR (62.5 MHz, CDCl3): δ = 13.10, 13.22 (CH3), 19.55
7.6 Hz, 2 H, PhCH2), 3.45 (s, 3 H, OCH3), 4.29 (q, J = 7.2 Hz, 2
30.93 (CH2) 50.91 (OCH3), 60.53 (OCH2) 112.55 (CAr), 121.40, (CH2), 20.17 (CH3), 50.95 (OCH3), 60.37 (OCH2) 112.64 (CAr),
125.93 (CHAr), 126.74 (2 CHAr), 127.14 (2 CHAr), 130.20, 134.46, 121.50 (CHAr), 127.00 (2 CHAr), 127.42 (2 CHAr), 131.04, 134.33,
140.66, 141.28 (CAr), 158.75 (COH), 166.61, 170.42 (CO) ppm. IR 135.63, 138.23, 140.71 (CAr), 158.56 (COH), 166.67, 170.58 (CO)
(KBr): ν = 3058 (w), 3026 (w), 2954 (m), 2925 (m), 2856 (m), 1724 ppm. IR (KBr): ν = 3023 (w), 2971 (w), 2933 (w), 2874 (w), 1723
˜
˜
(s), 1666 (s), 1600 (m), 1555 (w), 1438 (m), 1391 (m), 1367 (m),
(s), 1664 (s), 1604 (m), 1555 (w), 1517 (w), 1437 (m), 1389 (m),
1345 (m), 1316 (m), 1290 (m), 1262 (s), 1232 (s), 1194 (s), 1156 (s), 1367 (m), 1344 (m), 1312 (w), 1282 (m), 1247 (s), 1222 (s), 1193 (s),
1138 (m), 1092 (s), 1030 (m), 1007 (m), 964 (m), 921 (w), 911 (w),
887 (w), 846 (m), 814 (w), 760 (m), 699 (s), 653 (w), 631 (w), 583
(w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 356 (38) [M]+, 296 (13),
254 (10), 253 (41), 252 (20), 251 (100), 225 (10), 224 (17), 209 (13),
1156 (s), 1137 (m), 1111 (w), 1075 (s), 1030 (m), 1007 (m), 967 (w),
949 (m), 908 (w), 888 (w), 846 (w), 823 (m), 784 (m), 723 (w), 709
(w), 670 (w), 654 (w), 627 (w), 598 (w), 567 (w) cm–1. GC–MS (EI,
70 eV): m/z (%) = 343 (22), 342 (98) [M]+, 311 (23), 310 (100), 309
152 (14). HRMS (EI): calcd. for C21H24O5 [M]+ 356.16183; found (16), 297 (31), 295 (30), 282 (25), 281 (49), 267 (38), 265 (10), 263
356.162654.
(26), 254 (13), 239 (14), 238 (28), 237 (32), 235 (10), 211 (33), 210
(37), 209 (18), 179 (10), 178 (12), 166 (16), 165 (38), 153 (10), 152
(14). HRMS (EI): calcd. for C20H22O5 [M]+ 342.14618; found
342.146471.
5-Ethyl 2-Methyl 3-Hydroxy-4Ј-methylbiphenyl-2,5-dicarboxylate
(13e): Starting with 12b (0.460 g, 1.5 mmol) and 3a (0.429 g,
1.65 mmol), 13e was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a yellowish oil (0.207 g, 44%). 1H NMR
5-Ethyl 2-Methyl 3-Hydroxy-4-methyl-4Ј-nitrobiphenyl-2,5-dicarb-
oxylate (13h): Starting with 12c (0.506 g, 1.5 mmol) and 3j (0.453 g,
1.65 mmol), 13h was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a pale-yellowish solid (0.356 g, 66%). M.p. 123–
3
(300 MHz, CDCl3): δ = 1.30 (t, J = 7.2 Hz, 3 H, CH3), 2.33 (s, 3
H, PhCH3), 3.46 (s, 3 H, OCH3), 4.30 (q, 3J = 7.2 Hz, 2 H, OCH2),
7.04–7.08 (m, 2 H, CHAr), 7.09–7.13 (m, 2 H, CHAr), 7.39 (d, 4J =
1
3
4
125. H NMR (300 MHz, CDCl3): δ = 1.27 (t, J = 7.3 Hz, 3 H,
CH3), 2.37 (s, 3 H, CH3), 3.39 (s, 3 H, OCH3), 4.25 (q, 3J = 7.4 Hz,
2 H, OCH2), 6.99 (s, 1 H, CHAr), 7.24–7.28 (m, 2 H, CHAr), 8.09–
8.13 (m, 2 H, CHAr), 11.13 (s, 1 H, OH) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 11.48, 12.85 (CH3), 50.83 (OCH3), 60.18
1.6 Hz, 1 H, CHAr), 7.55 (d, J = 1.7 Hz, 1 H, CHAr), 10.31 (s, 1
H, OH) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 13.26, 20.10
(CH3), 51.12 (OCH3), 60.31 (OCH2) 114.68 (CAr), 116.37, 122.02
(CHAr), 126.92 (2 CHAr), 127.50 (2 CHAr), 133.73, 136.00, 138.00,
144.07 (CAr), 159.84 (COH), 164.48, 169.92 (CO) ppm. IR (KBr):
(OCH2) 110.90 (CAr), 120.52 (CHAr), 121.58 (2 CHAr), 127.12 (CAr
)
ν = 3305 (w), 2952 (w), 2870 (w), 1720 (s), 1669 (s), 1610 (w), 1567
˜
127.71 (2 CHAr), 134.37, 137.57, 145.50, 147.74 (CAr), 159.35
(m), 1515 (w), 1492 (w), 1437 (m), 1402 (m), 1369 (m), 1343 (m),
1314 (m), 1236 (s), 1198 (s), 1112 (s), 1079 (m), 1022 (s), 976 (m),
949 (m), 892 (m), 863 (w), 831 (m), 806 (m), 770 (s), 726 (m), 707
(m), 649 (w), 625 (m), 614 (m), 583 (m), 558 (w) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 314 (37) [M]+, 283 (24), 282 (100), 254 (10),
210 (12), 209 (10), 153 (14), 152 (10). HRMS (EI): calcd. for
C18H18O5 [M]+ 314.11488; found 314.114722.
(COH), 165.62, 169.25 (CO) ppm. IR (KBr): ν = 3115 (w), 3053
˜
(w), 2988 (w), 2954 (m), 2906 (w), 2849 (w), 1730 (s), 1671 (s), 1594
(m), 1567 (w), 1513 (m), 1471 (w), 1435 (m), 1393 (m), 1377 (m),
1366 (m), 1342 (s), 1312 (m), 1194 (s), 1166 (s), 1137 (m), 1105 (m),
1050 (m), 1002 (s), 936 (m), 898 (w), 840 (s), 809 (s), 789 (s), 747
(s), 701 (s), 656 (w), 617 (w), 586 (m), 559 (m) cm–1. GC–MS (EI,
70 eV): m/z (%) = 395 (44) [M]+, 328 (21), 327 (100), 314 (18), 299
(11), 298 (38), 271 (18), 255 (17), 254 (9), 253 (10), 242 (22), 227
(13), 226 (15), 152 (17), 151 (12), 139 (10). HRMS (EI): calcd. for
C18H17O7N [M]+ 359.09995; found 359.100038.
5-Ethyl 2-Methyl 3-Hydroxy-4,4Ј-dimethylbiphenyl-2,5-dicarboxyl-
ate (13f): Starting with 12b (0.460 g, 1.5 mmol) and 3j (0.453 g,
1.65 mmol), 13f was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a pale-yellowish oil (0.227 g, 46%). 1H NMR
(300 MHz, CDCl3): δ = 1.29 (t, J = 7.2 Hz, 3 H, CH3), 2.32 (s, 3
H, PhCH3), 2.40 (s, 3 H, PhCH3), 3.45 (s, 3 H, OCH3), 4.29 (q, J
= 7.1 Hz, 2 H, OCH2), 7.02–7.06 (m, 2 H, CHAr), 7.08–7.11 (m, 3
H, CHAr), 10.79 (s, 1 H, OH) ppm. 13C NMR (62.5 MHz, CDCl3):
δ = 12.68, 14.24, 21.20 (CH3), 51.96 (OCH3), 61.32 (OCH2) 113.47
(CAr), 122.51 (CHAr), 126.42 (CAr), 128.04 (2 CHAr), 128.43 (2
CHAr), 135.39, 136.63, 139.23, 141.50 (CAr), 159.77 (COH), 167.47,
5-Ethyl 2-Methyl 4-Ethyl-3-hydroxy-4Ј-nitrobiphenyl-2,5-dicarb-
oxylate (13i): Starting with 12c (0.506 g, 1.5 mmol) and 3n (0.476 g,
1.65 mmol), 13i was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a yellowish solid (0.375 g, 67%). M.p. 90–92 °C.
3
3
3
1H NMR (250 MHz, CDCl3): δ = 1.19 (t, J = 7.7 Hz, 3 H, CH3),
1.31 (t, 3J = 7.7 Hz, 3 H, CH3), 2.90 (q, 3J = 7.2 Hz, 2 H, PhCH2),
3
3.45 (s, 3 H, OCH3), 4.31 (q, J = 7.2 Hz, 2 H, OCH2), 7.00 (s, 1
H, CHAr), 7.28–7.34 (m, 2 H, CHAr), 8.14–8.20 (m, 2 H, CHAr),
11.12 (s, 1 H, OH) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 12.95,
13.19 (CH3), 19.65 (CH2), 51.34 (OCH3), 60.70 (OCH2) 111.80
(CAr), 121.16 (CHAr), 122.12 (2 CHAr), 128.36 (2 CHAr), 133.16,
134.60, 138.44, 146.11, 148.27 (CAr), 159.79 (COH), 166.27, 169.63
171.75 (CO) ppm. IR (KBr): ν = 2951 (w), 2924 (w), 2854 (w),
˜
1723 (s), 1664 (s), 1606 (w), 1561 (w), 1517 (w), 1436 (m), 1392
(m), 1367 (m), 1340 (m), 1312 (w), 1297 (w), 1261 (s), 1229 (s),
1194 (s), 1157 (s), 1137 (s), 1111 (m), 1048 (s), 1003 (m), 932 (w),
888 (w), 847 (m), 821 (m), 809 (m), 782 (m), 723 (m), 624 (w), 600
(w), 545 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 329 (12), 328
(56) [M]+, 297 (21), 296 (100), 283 (21), 281 (10), 268 (10), 267 (49),
253 (39), 240 (11), 224 (10), 223 (27), 196 (13), 195 (14), 165 (18),
152 (18). HRMS (EI): calcd. for C19H20O5 [M]+ 328.13053; found
328.130451.
(CO) ppm. IR (KBr): ν = 3071 (w), 3049 (w), 2963 (m), 2930 (m),
˜
2871 (m), 2852 (m), 2450 (w), 2357 (w), 2123 (w), 2123 (w), 1935
(w), 1804 (w), 1730 (s), 1669 (s), 1594 (m), 1562 (m), 1504 (s), 1446
(m), 1412 (m), 1390 (m), 1345 (s), 1315 (m), 1290 (m), 1257 (s),
1227 (s), 1195 (s), 1153 (s), 1135 (s), 1106 (s), 1074 (s), 1062 (s),
1027 (m), 1008 (m), 970 (m), 944 (s), 897 (m), 852 (s), 913 (m), 776
(s), 749 (s), 702 (s), 672 (m), 644 (w), 622 (m), 588 (m), 573 (m)
cm–1. GC–MS (EI, 70 eV): m/z (%) = 374 (22), 373 (100) [M]+, 342
(20), 341 (84), 328 (38), 314 (14), 313 (74), 312 (57), 298 (16), 296
(13), 295 (10), 285 (10), 270 (23), 269 (60), 268 (13), 267 (12), 243
(10), 242 (68), 241 (38), 240 (22), 239 (13), 223 (12), 222 (14), 221
5-Ethyl 2-Methyl 4-Ethyl-3-hydroxy-4Ј-methylbiphenyl-2,5-dicarb-
oxylate (13g): Starting with 12b (0.460 g, 1.5 mmol) and 3n
(0.476 g, 1.65 mmol), 13g was isolated after chromatography (silica
gel, n-heptane/EtOAc) as a pale-yellowish oil (0.236 g, 46%). 1H
NMR (250 MHz, CDCl3): δ = 1.15 (t, 3J = 7.6 Hz, 3 H, CH3), 1.30
3740
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3732–3742

Competing Regiodirecting Effects in [3+3] Cyclocondensations
(51), 220 (10), 194 (11), 193 (10), 166 (10), 165 (42), 164 (13), 163
(12), 152 (15), 151 (10), 139 (15). HRMS (EI): calcd. for
C19H19O7N [M]+ 373.11560; found 373.115597.
5-Ethyl 2-Methyl 4Ј-Bromo-4-hexyl-3-hydroxybiphenyl-2,5-dicarb-
oxylate (13m): Starting with 12d (0.557 g, 1.5 mmol) and 3d
(0.569 g, 1.65 mmol), 13m was isolated after chromatography (silica
1
gel, n-heptane/EtOAc) as a brownish oil (0.347 g, 50%). H NMR
5-Ethyl 2-Methyl 4Ј-Bromo-3-hydroxybiphenyl-2,5-dicarboxylate
(13j): Starting with 12d (0.557 g, 1.5 mmol) and 3a (0.429 g,
1.65 mmol), 13j was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a pale-brownish oil (0.301 g, 53%). 1H NMR
(300 MHz, CDCl3): δ = 0.67–0.75 (m, 6 H, 2 CH3), 1.16–1.20 (m,
3
6 H, 3 CH2), 1.40–1.46 (m, 2 H, CH2), 2.74 (t, J = 7.7 Hz, 2 H,
CH2), 3.36 (s, 3 H, OCH3), 4.19 (q, 3J = 7.1 Hz, 2 H, OCH2), 6.90–
6.94 (m, 3 H, CHAr), 7.29–7.34 (m, 2 H, CHAr), 10.83 (s, 1 H, OH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 15.3, 15.5 (CH3), 23.9, 28.2,
31.0, 32.8, 32.9, (CH2), 53.3 (OCH3), 62.6 (OCH2), 114.2, 122.3
(CAr), 123.4 (CHAr), 131.0 (2 CHAr), 132.0 (2 CHAr), 133.0, 136.8,
141.5, 142.4 (CAr), 161.3 (COH), 168.7, 172.4 (CO) ppm. IR (neat):
3
(300 MHz, CDCl3): δ = 1.26 (t, J = 7.0 Hz, 3 H, CH3), 3.43 (s, 3
3
H, OCH3), 4.25 (q, J = 7.1 Hz, 2 H, OCH2), 6.97–7.01 (m, 2 H,
CHAr), 7.28 (d, 4J = 1.7 Hz, 1 H, CHAr), 7.36–7.41 (m, 2 H, CHAr),
7.54 (d, 4J = 1.8 Hz, 1 H, CHAr), 10.47 (s, 1 H, OH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 14.2 (CH3), 52.2 (OCH3), 61.6
(OCH2), 115.1 (CAr), 118.2 (CHAr), 121.4 (CAr), 122.7 (CHAr),
129.8 (2 CHAr), 130.9 (2 CHAr), 135.0, 140.9, 143.6, (CAr), 161.3
ν = 2953 (w), 2926 (m), 2855 (w), 1934 (w), 1725 (m), 1667 (m),
˜
1605 (w), 1566 (w), 1554 (w), 1492 (w), 1437 (m), 1388 (m), 1368
(m), 1347 (m), 1313 (w), 1248 (m), 1231 (m), 1195 (m), 1155 (m),
1099 (m), 1071 (m), 1010 (m), 953 (m), 920 (w), 843 (m), 785 (m),
720 (m), 673 (w), 663 (w), 628 (w), 588 (w) cm–1. GC–MS (EI,
70 eV): m/z (%) = 462 (42) [M+, 79Br], 419 (10), 357 (100), 331 (42),
302 (13), 278 (17), 253 (26), 196 (19), 152 (17). HRMS (EI): calcd.
for C23H27O5Br [M+, 79Br] 462.10364; found 462.104001.
(COH), 165.2, 170.5 (CO) ppm. IR (neat): ν = 3064 (w), 2980 (w),
˜
2953 (w), 2905 (w), 2872 (w), 2852 (w), 1721 (m), 1672 (m), 1611
(m), 1571 (m), 1493 (m), 1439 (m), 1392 (m), 1345 (m), 1238 (s),
1200 (s), 1114 (s), 1069 (m), 1023 (m), 1010 (m), 948 (m), 881 (m),
835 (m), 807 (m), 770 (m), 681 (m), 622 (m), 574 (m) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 378 (28) [M+, 79Br], 349 (18), 348 (100),
276 (7), 194 (16), 139 (14). HRMS (EI, 70 eV): calcd. for
C17H15O5Br [M+, 79Br] 378.00974; found 378.009529.
5-Ethyl 2-Methyl 4Ј-Bromo-4-heptyl-3-hydroxybiphenyl-2,5-dicarb-
oxylate (13n): Starting with 12d (0.557 g, 1.5 mmol) and 3o
(0.592 g, 1.65 mmol), 13n was isolated after chromatography (silica
5-Ethyl 2-Methyl 4Ј-Bromo-3-hydroxy-4-methylbiphenyl-2,5-dicarb-
oxylate (13k): Starting with 12d (0.557 g, 1.5 mmol) and 3j (0.453 g,
1.65 mmol), 13k was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a pale-brownish oil (0.323 g, 55%). 1H NMR
1
gel, n-heptane/EtOAc) as a brownish oil (0.357 g, 50%). H NMR
(300 MHz, CDCl3): δ = 0.78–0.83 (m, 6 H, 2 CH3), 1.28–1.33 (m,
3
8 H, 4 CH2), 1.35–1.39 (m, 2 H, CH2), 2.84 (t, J = 7.4 Hz, 2 H,
3
(300 MHz, CDCl3): δ = 1.30 (t, J = 7.2 Hz, 3 H, CH3), 2.40 (s, 3
CH2), 3.47 (s, 3 H, OCH3), 4.29 (q, 3J = 7.1 Hz, 2 H, OCH2), 7.00–
7.04 (m, 3 H, CHAr), 7.40–7.44 (m, 2 H, CHAr), 10.93 (s, 1 H, OH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 13.1, 13.2 (CH3), 21.6, 26.3,
28.1, 28.7, 30.3, 30.8 (CH2), 51.7 (OCH3), 60.4 (OCH2), 112.0,
120.1 (CAr), 121.2 (CHAr), 128.8 (2 CHAr), 129.8 (2 CHAr), 130.7,
134.6, 139.3, 140.2 (CAr), 159.1 (COH), 166.7, 170.2 (CO) ppm. IR
H, PhCH3), 3.47 (s, 3 H, OCH3), 4.30 (q, 3J = 7.2 Hz, 2 H, OCH2),
7.00–7.05 (m, 3 H, CHAr), 7.40–7.44 (m, 2 H, CHAr), 10.99 (s, 1
H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 11.7, 13.2 (CH3),
51.1 (OCH3), 60.4 (OCH2), 111.9, 120.1 (CAr), 121.2 (CHAr), 126.3
(CAr), 128.8 (2 CHAr), 129.8 (2 CHAr), 134.6, 139.2, 140.2 (CAr),
159.3 (COH), 166.3, 170.2 (CO) ppm. IR (neat): ν = 3046 (w), 2979
˜
(neat): ν = 2972 (w), 2954 (w), 2935 (w), 2875 (w), 2854 (w), 1723
˜
(w), 2952 (w), 2904 (w), 2873 (w), 1722 (m), 1665 (m), 1607 (m),
1567 (w), 1492 (w), 1437 (m), 1390 (m), 1367 (m), 1342 (m), 1305
(m), 1261 (s), 1230 (s), 1194 (s), 1157 (s), 1137 (m), 1071 (m), 1048
(s), 1009 (s), 933 (m), 918 (m), 889 (w), 828 (m), 782 (m), 742 (m),
724 (m), 665 (m), 618 (w), 588 (m), 557 (w) cm–1. GC–MS (EI,
70 eV): m/z (%) = 392 (47) [M+, 79Br], 360 (100), 333 (30), 304 (15),
253 (55), 196 (12), 180 (9), 152 (38), 139 (10), 104 (8), 76 (11).
HRMS (EI): calcd. for C18H17O5Br [M+, 79Br] 392.02539; found
392.025473.
(m), 1665 (m), 1605 (m), 1567 (w), 1490 (w), 1437 (m), 1387 (m),
1368 (m), 1347 (m), 1309 (m), 1282 (m), 1248 (s), 1222 (s), 1194
(m), 1158 (s), 1075 (s), 1029 (m), 1009 (m), 967 (m), 948 (m), 890
(w), 830 (m), 784 (m), 734 (m), 721 (m), 665 (m), 620 (w), 587 (m),
560 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 476 (30) [M+, 79Br],
416 (7), 373 (100), 333 (30), 292 (18), 253 (17), 196 (11), 152 (9).
HRMS (EI): calcd. for C24H29O5Br [M+, 79Br] 476.11929; found
476.119450.
5-Ethyl 2-Methyl 4Ј-Bromo-4-ethyl-3-hydroxybiphenyl-2,5-dicarb-
oxylate (13l): Starting with 12d (0.557 g, 1.5 mmol) and 3n (0.476 g,
1.65 mmol), 13l was isolated after chromatography (silica gel, n-
heptane/EtOAc) as a pale-brownish oil (0.359 g, 59%). 1H NMR
1-Hydroxy-3-methylanthraquinone (7): A mixture of 6b (0.102 g,
0.38 mmol) and concentrated sulfuric acid (4 mL) was stirred at
20 °C for 1 h. The solution was poured into ice water, and the mix-
ture was extracted with diethyl ether. The combined organic layer
was dried (Na2SO4) and filtered, and the filtrate was concentrated
in vacuo. The residue was purified by chromatography (silica gel,
heptanes/EtOAc, 20:1) to give 7 as a yellow solid (0.076 gm, 84%).
3
3
(300 MHz, CDCl3): δ = 1.18 (t, J = 7.5 Hz, 3 H, CH3), 1.31 (t, J
3
= 7.2 Hz, 3 H, CH3), 2.88 (q, J = 7.4 Hz, 2 H, PhCH2), 3.47 (s, 3
3
H, OCH3), 4.30 (q, J = 7.2 Hz, 2 H, OCH2), 7.01–7.05 (m, 3 H,
CHAr), 7.40–7.44 (m, 2 H, CHAr), 10.94 (s, 1 H, OH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 13.0, 13.2 (CH3), 19.6 (CH2), 51.1
(OCH3), 60.4 (OCH2), 112.1, 120.1 (CAr), 121.2 (CHAr), 128.8 (2
CHAr), 129.8 (2 CHAr), 131.8, 134.5, 139.4, 140.2 (CAr), 159.0
1
M.p. 234–237 °C. H NMR (250 MHz, CD3OD): δ = 2.39 (s, 3 H,
PhCH3), 6.95 (br. s, 1 H, OH), 7.39–7.42 (m, 2 H, CHAr), 7.45 (m,
3
3
1 H, CH), 7.54 (t, J = 7.3 Hz, 1 H, CH), 7.74 (d, J = 7.3 Hz, 2
H, CH) ppm. 13C NMR (75 MHz, CD3OD): δ = 21.7 (CH3), 122.0,
123.5, 129.8, 130.4 (CH), 132.1 (C), 134.3 (CH), 139.8, 142.2 (C),
156.5 (COH), 169.3 (C=O) ppm. MS (EI, 70 eV): m/z (%) = 238
(57) [M]+, 237 (100), 179 (36).
(COH), 166.4, 170.2 (CO) ppm. IR (neat): ν = 2972 (w), 2954 (w),
˜
2935 (w), 2875 (w), 2854 (w), 1723 (m), 1665 (m), 1605 (m), 1567
(w), 1490 (w), 1437 (m), 1387 (m), 1368 (m), 1347 (m), 1309 (m),
1282 (m), 1248 (s), 1222 (s), 1194 (m), 1158 (s), 1075 (s), 1029 (m),
1009 (m), 967 (m), 948 (m), 890 (w), 830 (m), 784 (m), 734 (m),
721 (m), 665 (m), 620 (w), 587 (m), 560 (w) cm–1. GC–MS (EI,
70 eV): m/z (%) = 406 (92) [M+, 79Br], 376 (98), 348 (32), 331 (16),
302 (34), 275 (50), 249 (17), 221 (89), 194 (21), 165 (72), 152 (24),
128 (7), 82 (11). HRMS (EI): calcd. for C19H19O5Br [M+, 79Br]
406.04104; found 406.041136.
Acknowledgments
Financial support by the State of Mecklenburg-Vorpommern
(scholarship to M. S.) is gratefully acknowledged.
Eur. J. Org. Chem. 2010, 3732–3742
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3741

P. Langer et al.
FULL PAPER
[8] For a review of 1,3-bis(silyloxy)-1,3-butadienes, see: P. Langer,
Synthesis 2002, 441.
[9] Review of [3+3] cyclocondensations: H. Feist, P. Langer, Syn-
thesis 2007, 327.
[1] W. Steglich, B. Fugmann, S. Lang-Fugmann (Eds.), Römpp
Lexikon Naturstoffe, Thieme, Stuttgart, 1997.
[2] a) S. Cabiddu, C. Fattuoni, C. Floris, G. Gelli, S. Melis, F.
Sotgiu, Tetrahedron 1990, 46, 861; b) R. Fusco, F. Sannicolo,
J. Org. Chem. 1981, 46, 83; c) J. T. Pinhey, P. T. Xuan, Aust. J.
Chem. 1988, 41, 69; d) W. A. Bonner, J. I. De Graw, Tetrahe-
dron 1962, 18, 1295; e) H. O. House, C. B. Hudson, J. Org.
Chem. 1970, 35, 647; f) S. Horii, H. Fukase, E. Mizuta, K.
Hatano, K. Mizuno, Chem. Pharm. Bull. 1980, 28, 3601; g)
A. J. Birch, J. Wright, Aust. J. Chem. 1969, 22, 2635; h) K. A.
Parker, D. M. Spero, K. A. Koziski, J. Org. Chem. 1987, 52,
183; i) R. K. Hill, R. M. Carlson, J. Org. Chem. 1965, 30, 2414;
j) K. C. Nicolaou, C. F. Claiborne, K. Paulvannan, M. H. D.
Postema, R. K. Guy, Chem. Eur. J. 1997, 3, 399; k) T. Ziegler,
M. Layh, F. Effenberger, Chem. Ber. 1987, 120, 1347; l) J. A.
Elix, D. O. Chester, K. L. Gaul, J. L. Parker, J. H. Wardlaw,
Aust. J. Chem. 1989, 42, 1191; m) J. A. Elix, C. E. Barclay, J. H.
Wardlaw, A. W. Archer, S.-h. Yu, G. Kantvilas, Aust. J. Chem.
1999, 52, 837.
[10] S. Reim, M. Lubbe, P. Langer, Tetrahedron Lett. 2006, 47, 6751.
[11] For reviews of chelation control in Lewis acid mediated reac-
tions, see: a) H. Yamamoto, Lewis Acid Chemistry: A Practical
Approach, Oxford University Press, Oxford, 1999; b) R.
Mahrwald, Chem. Rev. 1999, 99, 1095; c) M. Santelli, J. M.
Pons, Lewis Acids and Selectivity in Organic Synthesis, CRC
Press, Boca Raton, 1996; d) S. Shambayati, S. L. Schreiber in
Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Flem-
ing), Pergamon, Oxford, 1991, vol. 1, pp. 283–324.
[12] Chelation control has been reported for the [4+3] annulation
reaction of benzyloxy-substituted 1,4-dicarbonyl compounds
with bis(silyl enol ethers): a) G. A. Molander, P. R. Eastwood,
J. Org. Chem. 1996, 61, 1910; recently, we reported chelation
control in the [3+3] annulation of alkoxy-substituted 1,1-di-
acylcyclopropanes: b) J. Hefner, P. Langer, Tetrahedron Lett.
2008, 49, 4470; for chelation control in cyclizations of 3-acyl-
4-ethoxy-2-oxo-3-butenoates, see: c) A. Riahi, M. Shkoor, O.
Fatunsin, R. Ahmad Khera, C. Fischer, P. Langer, Org. Biomol.
Chem. 2009, 7, 4248.
[3] A. de Meijere, F. Diederich (Eds.), Metal-Catalyzed Cross-Cou-
pling Reactions, Wiley-VCH, Weinheim, 2004.
[4] a) V. Prelog, J. Würsch, K. Königsbacher, Helv. Chim. Acta
1951, 34, 258; b) M. Beringer, I. Kuntz, J. Am. Chem. Soc.
1951, 73, 364; c) S. H. Bertz, G. Dabbagh, Angew. Chem. 1982,
94, 317; Angew. Chem. Int. Ed. Engl. 1982, 21, 306; for intra-
molecular reactions of unsymmetrical derivatives, see: d) M.
Yamaguchi, K. Hasebe, T. Minabi, Tetrahedron Lett. 1986, 27,
2401; for the cyclization of a 1,3-dicarbonyl dianion with 3-
(N,N-dimethylamino)-2-ethylacroleine, see: e) D. H. R. Barton,
G. Dressaire, B. J. Willis, A. G. M. Barrett, M. Pfeffer, J. Chem.
Soc. Perkin Trans. 1 1982, 665.
[5] For a review, see: a) T. M. Harris, C. M. Harris, Tetrahedron
1977, 33, 2159; b) T. P. Murray, T. M. Harris, J. Am. Chem.
Soc. 1972, 94, 8253; c) C. M. Harris, J. S. Roberson, T. M. Har-
ris, J. Am. Chem. Soc. 1976, 98, 5380; d) T. M. Harris, J. V.
[13]
G. A. Molander, K. O. Cameron, J. Am. Chem. Soc. 1993, 115,
830.
[14]
[15]
V. T. H. Nguyen, E. Bellur, B. Appel, Synthesis 2006, 2865.
L. F. Tietze, H. Meier, E. Voß, Synthesis 1988, 274.
[16] K. Fujimoto, Y. Tokuda, M. Hirofumi, Y. Matsubara, T. Mi-
zuno, I. Nishiguchi, Tetrahedron 1996, 52, 3889.
[17] T. Ziegler, M. Layh, F. Effenberger, Chem. Ber. 1987, 120, 1347.
[18] a) A. G. Schultz, S. A. Hardinger, J. Org. Chem. 1991, 56, 1105;
b) A. Allen, P. Marquand, R. Burton, K. Villeneuve, W. Tam,
J. Org. Chem. 2007, 72, 7849.
[19] A. Moreno, M. V. Goìmez, E. Vaìzquez, A. de la Hoz, A.
Diìaz-Ortiz, P. Prieto, J. A. Mayoral, E. Pires, Synlett 2004,
1259.
Hay, J. Am. Chem. Soc. 1977, 99, 1631; e) J. S. Hubbard, T. M. [20] a) P. Vogel, B. Willham, H. Prinzbach, Helv. Chim. Acta 1969,
Harris, Tetrahedron Lett. 1978, 47, 4601; f) R. M. Sandifer,
A. K. Bhattacharya, T. M. Harris, J. Org. Chem. 1981, 46,
2260; g) S. G. Gilbreath, C. M. Harris, T. M. Harris, J. Am.
Chem. Soc. 1988, 110, 6172.
52, 593; b) M. S. Newman, H. M. Chung, J. Org. Chem. 1974,
39, 1036.
[21] A. K. Roy, S. Batra, Synthesis 2003, 2325.
[22] CCDC-764172 (for 13m) and -764173 (for 13h) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Received: November 26, 2009
[6] a) I. Hussain, M. A. Yawer, B. Appel, M. Sher, A. Mahal, A.
Villinger, P. Langer, Tetrahedron 2008, 64, 8003; b) M. Sher, H.
Reinke, P. Langer, Tetrahedron 2007, 63, 4080.
[7] T.-H. Chan, P. Brownbridge, J. Am. Chem. Soc. 1980, 102,
3534.
Published Online: May 12, 2010
3742
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3732–3742