Cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes - A new approach to diverse CF3-substituted fluorenes, dibenzofurans, 9,10-dihydrophenanthrenes and 6H-benzo[c]chromenes

Article abstract of DOI:10.1016/j.tet.2012.01.101

Trifluoromethyl-substituted fluorenes, dibenzofurans, 9,10- dihydrophenanthrenes and 6H-benzo[c]chromenes were prepared by formal [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes. The reactions proceeded with very good regioselectivity. The

Full text of DOI:10.1016/j.tet.2012.01.101

Tetrahedron 68 (2012) 3654e3668
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
[3þ3] Cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienesda new approach
to diverse CF3-substituted fluorenes, dibenzofurans, 9,10-dihydrophenanthrenes
and 6H-benzo[c]chromenes
a
a
,
,c,
Stefan Buttner , Nazken K. Kelzhanova b, Zharylkasyn A. Abilov b, Alexander Villinger a, Peter Langer a
*
€
a
€
€
Institut fur Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Al-Farabi Kazakh National University, Al-Farabi Ave. 71, 050040 Almaty, Kazakhstan
c
€
€
Leibniz-Institut fur Katalyse e. V. an der Universitat Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Trifluoromethyl-substituted fluorenes, dibenzofurans, 9,10-dihydrophenanthrenes and 6H-benzo[c]
chromenes were prepared by formal [3þ3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes. The
reactions proceeded with very good regioselectivity. The product distribution depends on the type of 1,3-
dielectrophile employed and can be explained by electronic reasons.
Received 24 November 2011
Received in revised form 27 January 2012
Accepted 31 January 2012
Available online 21 February 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Arenes
Cyclizations
Organofluorine compounds
Silyl enol ethers
1. Introduction
years, we have reported the regioselective synthesis of various
trifluoromethyl- and perfluoroalkyl-substituted phenol derivatives
The trifluromethyl group is of great importance in organic and
medicinal chemistry because CF3-substituted molecules are
chemically and metabolically stable.1e4 In contrast, undesired
enzymatic oxidations often occur in case of CH3 groups and CeH
bonds of arenes. Due to their metabolic stability and lipophilicity,
the bioavailability of CF3-substituted carba- and heterocycles is
generally high. Besides medicinal chemistry, the trifluromethyl
group also plays an important role for the development of catalysts
soluble in fluorophilic solvent systems5 and for the development of
new organocatalysts.6 Trifluoromethyl-substituted ring systems are
synthetically available by reaction of aryl halides with tri-
fluoromethylcopper7 and by conversion of CX3 into CF3 groups.8 An
interesting alternative is based on cyclization reactions of fluori-
nated building blocks.9 The cyclization of CF3-substituted enones
with hydrazones, amidines and enamines has been reported to give
CF3-substituted pyrazoles, pyrimidines and pyridines.10,11 However,
the synthesis of phenol derivatives using this approach is essen-
tially restricted to one example, i.e., 2-acetyl-5-(trifluoromethyl)
phenol, which was prepared from acetylacetone.12 In fact, it has
based on formal [3þ3] cyclocondensation of 1,3-bis(silyloxy)-1,3-
butadienes with various fluorinated 1,3-dielectrophiles.13 This
strategy has been successfully applied to the synthesis of 5-methyl-
3-(trifluoromethyl)phenols,14 5-aryl-3-(trifluoromethyl)phenols,15
5-hetaryl-3-(trifluoromethyl)phenols,16 5-alkyl-3-(perfluoroalkyl)
phenols, 5-aryl-3-(perfluoroalkyl)-phenols17 and 5-unsubstituted
3-(trifluoromethyl)phenols.18 Herein, we report, for the first time,
the application of our methodology to the synthesis of various
pharmacologically relevant CF3-substituted polycyclic ring systems,
including fluorenes, dibenzofurans, dihydrophenanthrenes and 6H-
benzo[c]chromenes. Interesting observations related to the regio-
selectivity are reported. The selectivity depends on the type of
dielectrophile employed and can be rationalized by consideration
of the electron distribution in the molecules. The starting materials,
1,3-bis(silyloxy)-1,3-butadienes, were prepared by known
procedures.19,20
2. Results and discussion
2.1. Fluorenes
been demonstrated that b
-ketoesters cannot be used.12 In recent
Parent fluorene has been isolated from coal tar and is used for
the technical synthesis of fluorenone. Substituted fluorene
* Corresponding author. Fax: þ49 381 4986412; e-mail address: peter.langer@
uni-rostock.de (P. Langer).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.101

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3655
derivatives are present in various pharmaceuticals and pesticides21
Fluorenes are important structural motifs of anti-cancer agents22
and also occur in natural products, such as (9R)-4-methoxy-9H-
fluorene-2,5-9-triol, which has been isolated from the orchidea
Dendrobium chrysotoxum Lindl (Fig. 1).23 The fluorene core struc-
ture also plays an important role in organic light emitting devices
(OLED).24 Fluorenes are synthetically available by functionalization
of parent fluorene25 and by intramolecular FriedeleCrafts acylation
and subsequent reduction.26
(HMBC, NOESY) (Fig. 2). A diagnostic NOE is observed between the
methyl group attached to one benzene moiety of the fluorene and
the ortho hydrogen of the other benzene moiety. The structure of
5h was independently confirmed by X-ray crystal structure analysis
(Fig. 3). The molecule is flat. The carbonyl group is in plane with the
phenyl moiety and an intramolecular hydrogen bond is observed
with the hydroxyl group. In all reactions, only one regioisomer
could be isolated. Analysis of the crude product mixture (before
chromatographic purification) by TLC revealed that no significant
amounts of the other regioisomer were formed. An exception is the
formation of 5h where the opposite regioisomer 5g was isolated as
a by-product in 24% yield. The synthesis of CF3-substituted fluo-
renes has, to the best of our knowledge, not been reported so far.
OH
HO
O
OH
R2
OCH3
OH
R3
CF3
Me3SiO OSiMe3
R2
R3
R1
4a-f
(9R)-4-Methoxy-
5a-p
i
9H-fluoren-2,5,9-triol
Me3SiO
O
O
OH
R2
CF3
Fig. 1. A naturally occuring fluorene derivative.
CF3
+
R3
The sodium methylate-mediated reaction of indan-1-ones 1aec
with ethyl trifluoroacetate afforded the 2-trifluoroacetyl-indan-1-
ones 2aec in good yields (Scheme 1, Table 1). The silylation of
2aec gave silyl enol ethers 3aec.
R1
3a-c
R1
Scheme 2. Synthesis of fluorenes 5aep. (i) TiCl4, CH2Cl2, ꢁ78 to 20 ꢀC, 16 h.
O
O
O
Table 2
Synthesis of 5aep
i
CF3
3
4
5
R1
R2
R3
% (5)a
R1
R1
a
a
a
a
a
a
b
b
b
b
c
a
b
c
d
e
f
a
b
c
d
a
b
c
a
b
c
d
e
f
h
j
k
l
H
H
H
H
H
H
Br
Br
Br
Br
OCH3
OCH3
OCH3
OCH3
H
OCH3
OCH3
OCH3
OCH3
OCH3
CH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
43
48
46
54
67
39
41b
62
50
60
69
50
37
43
2a-c
CH3
C2H5
C3H7
OCH3
H
1a-c
O
Me3SiO
H
CH3
C2H5
C3H7
H
CH3
C2H5
C3H7
CF3
R1
m
n
o
p
3a-c
c
c
c
Scheme 1. Synthesis of 3aec. (i) Na, CH3OH, F3CCO2Et, 0e20 ꢀC, 16 h; (ii) NEt3
(1.0 equiv), TMSOTf (0.95 equiv), (C2H5)2O, 20 ꢀC, 72 h.
d
a
Yields of isolated products.
The opposite regioisomer 5g was isolated as a by-product in 24% yield.
b
Table 1
Synthesis of 3aec
2.2. Dibenzofurans
2,3
R1
% (2)a
% (3)a
a
b
c
H
Br
OCH3
56
68
66
84
86
92
Substituted dibenzofurans occur as natural products. For ex-
ample, 2-chloro-3,7-dihydroxy-1,9-dimethyldibenzofuran was iso-
lated from the lychen Lecanora cinereocarnea and cytotoxic
kehokorin A was isolated from the fungi Trichia favoginea var. per-
similis. Usninic acid, which can be regarded as a dibenzofuran de-
rivative, possesses antibiotic, antiviral, antileukaemic and anti-
inflammatory activity.27 Classic syntheses of benzofurans rely on
the reaction of 4-bromophenols with arylhalides28 and on CuCl2-
mediated reactions of phenols.29
a
Yields of isolated products.
The TiCl4-mediated formal [3þ3] cyclization of 4aef with 3aec
afforded the CF3-substituted fluorenes 5aep in 37e69% yield
(Scheme 2, Table 2). The reaction proceeded by regioselective at-
tack of the terminal carbon atom of the diene to the carbon atom
attached to the silyloxy group and subsequent cyclization by attack
of the central carbon atom of the diene to the keto group. The
structure of product 5b was confirmed by 2D NMR experiments
The sodium methylate-mediated reaction of 3-coumaranone
(1d) with ethyl trifluoroacetate afforded 2d (Scheme 3). The sily-
lation of 2d gave silyl enol ether 3d.

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3656
methyl group attached to the aromatic ring and the aromatic car-
bon atom located next to the trifluoromethyl group. The structure
could also be confirmed by inspection of the 13C NMR spectra. In
case of 5q, the aromatic CH carbon atom appears as a quartet, due
to its coupling with the trifluoromethyl group located in ortho
position. This coupling would not be expected for the opposite
regioisomer where the CH carbon is located para to the CF3 group.
In case of 5ret, a splitting to a quartet is observed for the 13C NMR
signals of the sp3 hybridized carbon atoms located next to the ar-
Fig. 2. Diagnostic NOESY interaction of 5b.
Fig. 3. Ortep plot of 5h (50% probability level).
O
OH
O
O
O
R1
O
R2
CF3
i
CF3
Me3SiO OSiMe3
R1
O
O
R2
O
2d
1d
4a-d
i
OH
Me3SiO
O
Me3SiO
O
R1
CF3
R2
CF3
CF3
+
O
O
3d
O
5q-t
3d
Scheme 3. Synthesis of 3d. (i) Na, CH3OH, F3CCO2Et, 0e20 ꢀC, 16 h; (ii) NEt3
(1.0 equiv), TMSOTf (0.95 equiv), (C2H5)2O, 20 ꢀC, 72 h.
Scheme 4. Synthesis of fluorenes 5qet; (i) TiCl4, CH2Cl2, ꢁ78 to 20 ꢀC, 16 h.
The TiCl4-mediated formal [3þ3] cyclization of 4aed with 3d
afforded the CF3-substituted fluorenes 5qet in 31e51% yield
(Scheme 4, Table 3). The reactions proceeded with very good
regioselectivity by attack of the terminal carbon atom of the diene
to the carbon atom attached to the silyloxy group and subsequent
cyclization via the central carbon atom of the diene and the keto
group. The other regioisomer could not be detected in the crude
product mixture by TLC or 1H NMR.
For compounds 5r and 5s, 2D NMR experiments were carried
out to confirm the regioselectivity of cyclization (Fig. 4). Diagnostic
1H,1H-NOESY correlations were observed between the methoxy
group and the aromatic hydrogen atom of 5r. The 1H,13C-HMBC
spectrum of 5r revealed a coupling between the protons of the
Table 3
Synthesis of 5qet
4
5
R1
R2
% (5)a
a
b
c
q
r
s
t
H
OCH3
OCH3
OCH3
OCH3
44
48
31
51
CH3
C2H5
C3H7
d
a
Yields of isolated products.
omatic ring. This splitting can be again explained by coupling of the
alkyl group with the neighbouring CF3 group. The structure of 5t
was independently confirmed by X-ray crystal structure analysis

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3657
O
more electrophilic
O
H3CO
H
H3CO
OH
OH
_
Me3SiO
O
O
Me3SiO
O
+
CH3
CF3
CH3
CF3
CF3
CF3
O
O
3a
1H,1H-NOESY-
correlations of 5r
1H,13C-HMBC-
correlations of 5r
Me3SiO
Me3SiO
O
_
Fig. 4. Diagnostic NOESY and HMBC interactions of 5r.
CF3
CF3
O
(Fig. 5). The molecule is, as expected, flat. The carbonyl group is in
plane with the phenyl moiety and an intramolecular hydrogen
bond is observed with the hydroxyl group.
The regioselectivity of the formation of fluorenes 5aep is op-
posite to the regioselectivity of the formation of dibenzofurans
5qet. This striking difference might be explained by the different
+
O
3d
more electrophilic
Scheme 5. Possible explanation of the different regioselectivities of the cyclization
reactions of 1,3-bis(silyloxy)-1,3-butadienes 4 with 3a and 3d.
Fig. 5. Ortep plot of 5t (50% probability level).
electronic nature of the 3-silyloxy-2-en-1-one systems of 3aec and
3d. In case of 3aec, the carbon atom attached to the silyloxy group
is more electrophilic than the carbonyl group. In case of 3d, the
electrophilicity of the carbon attached to the silyloxy group is de-
dihydrophenanthrenes byTiCl4-mediated [3þ3]-cyclocondensation
reactions.34
2-Trifluoroacetyltetralone (2e) was prepared from tetralone
(1e). The silylation of 2e gave silyl enol ether 3e (Scheme 6). The
cyclization of 3e with diene 4a afforded a separable mixture of 9,10-
dihydrophenanthrene 5v (32%) and its regioisomer 5u (16%). Sim-
ilar to the formation of fluorenes 3aep, the major product 5v was
formed by attack of the terminal carbon atom of the diene to the
carbon atom attached to the silyloxy group. The synthesis of CF3-
substituted 9,10-dihydrophenanthrenes has, to the best of our
knowledge, not yet been reported.
The structure of 5v was independently confirmed by X-ray
crystal structure analysis (Fig. 7). The molecular structure clearly
shows that the biaryl system is twisted out of plane. The carbonyl
group is twisted with regard to the phenyl moiety, due to steric
reasons. In the 13C NMR spectrum of 5v, the aromatic quaternary
creased by the p-donating effect of the oxygen atom (Scheme 5).
2.3. 9,10-Dihydrophenanthrenes
The 9,10-dihydrophenanthrene core structure is present in var-
ious natural products. Examples include the sinensoles AeH isolated
from Spiranthes sinensis30 and the stemanthrenes AeC isolated from
Stemona cf. pierrei (Fig. 6).31 9,10-Dihydrophenanthrenes are avail-
able by palladium- and nickel-catalyzed [2þ2þ2]-cycloadditions of
alkenes with arynes.32 Dihydrophenanthrenes have been prepared
by nickel-catalyzed cross-coupling of iodo-substituted phenyl-
ethanols with iodo-xylenes.33 We have reported the synthesis of

€
3658
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
H3CO
HO
OCH3
HO
OH
CH3
HO
H3CO
H3C
SinensolG
Stemanthren A
CH3
Fig. 6. Naturally occuring 9,10-dihydrophenanthrenes.
O
O
O
i
CF3
1e
2e
ii
O
OH
Me3SiO
O
MeO
CF3
CF3
3e
iii
5u (16%)
OH O
Me3SiO OSiMe3
+
OMe
OMe
4a
CF3
5v (32%)
Scheme 6. Synthesis of 5u and 5v. (i) Na, CH3OH, F3CCO2Et, 0e20 ꢀC, 16 h; (ii) NEt3 (1.0 equiv), TMSOTf (0.95 equiv), (C2H5)2O, 20 ꢀC, 72 h; (iii) TiCl4, CH2Cl2, ꢁ78 to 20 ꢀC, 16 h.
carbon atom attached to the ester group is splitted to a quartet, due
to its coupling with the CF3 group located in ortho position. In case
of 5u, the aromatic CH carbon appears as a quartet, due to coupling
with the neighbouring CF3 group.
(48%) was isolated along with the regioisomeric by-product 5w (18%).
The regioselectivity can be explained by the fact that the heterocyclic
oxygen atom is not directly connected to the double bond of the silyl
enol ether moiety and thus exerts no electronic influence on the
carbon atom attached to the silyloxy group. Therefore, the same
regioselectivity is observed as in the case of fluorenes 5aep.
2.4. Benzo[c]chromenes
The structure of 5y was confirmed by 2D NMR experiments.
A NOE interaction was observed between the ethyl group and the
neighbouring aromatic proton (Fig. 9). The structures of 5w and 5x
were established based on the analysis of the coupling pattern of
the 13C NMR signals. In case of 5x, the aromatic quaternary carbon
atom attached to the ester group is splitted to a quartet, due to its
coupling with the CF3 group located in ortho position. In case of 5w,
the aromatic CH carbon appears as a quartet, due to coupling with
the neighbouring CF3 group. The structure of 5x was independently
confirmed by X-ray crystal structure analysis (Fig. 10). The two aryl
groups of the molecule are slightly twisted out of plane. The
Benzo[c]chromenes are very rare in nature.
D
1-Tetrahydrocan-
nabinol, a tetrahydro-benzo[c]chromene, represents a pharmaco-
logically relevant natural product (Fig. 8).21
Our synthesis of benzo[c]chromenes started with chroman-4-
one (1f), which was transformed to 2-trifluoroacetylchroman-4-
one (2f). The silylation of 2f gave 3f (Scheme 7).
The cyclization of 3f with dienes 4a,c,d afforded the benzo[c]
chromenes 5wez (Scheme 8, Table 4). In case of products 5y and 5z,
only one regioisomer was isolated. The opposite regioisomer could
not be detected in the crude product mixture. In contrast, product 5x

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3659
Fig. 7. Ortep plot of 5v (50% probability level).
and 5m, dibenzofuran 5q and benzo[c]chromenes 5y,z were
transformed into their triflates 6aee (Scheme 9, Table 5). The
SuzukieMiyaura reaction of 6aee with arylboronic acids afforded
the aryl-substituted products 7aeg in good yields.
CH3
OH
H
O
O
O
i
CF3
H
nH11C5
O
CH3
O
O
2f
CH3
1f
Fig. 8. Structure of
D
1-tetrahydrocannabinol.
ii
Me3SiO
O
carbonyl group is twisted with regard to the plane of the phenyl
moiety, due to steric reasons.
CF3
2.5. SuzukieMiyaura cross-coupling reactions
O
3f
To broaden the diversity of the products, we studied whether
the phenolic hydroxyl group could be replaced by aryl groups by
Suzuki reactions of the corresponding aryl triflates. Fluorenes 5a
Scheme 7. Synthesis of 3f. (i) Na, CH3OH, F3CCO2Et, 0e20 ꢀC, 16 h; (ii) NEt3 (1.0 equiv),
TMSOTf (0.95 equiv), (C2H5)2O, 20 ꢀC, 72 h.

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3660
Me3SiO OSiMe3
OH
Y
OTf
Y
O
R2
R3
R3
OH
R2
i
R2
R1
R2
R1
4a,c,d
i
CF3
CF3
+
R1
X
R1
X
CF3
Me3SiO
O
5a,m,q,y,z
6a-e
O
5w-z
Ar
CF3
ii
R2
R3
CF3
O
3f
Scheme 8. Synthesis of 5wez. (i) TiCl4, CH2Cl2, ꢁ78 to 20 ꢀC, 16 h.
Y
R1
X
7a-g
Table 4
Synthesis of 5wez
Scheme 9. SuzukieMiyaura cross-coupling reactions. (i) 1) Pyridine, CH2Cl2, ꢁ78 ꢀC,
10 min; 2) Tf2O, ꢁ78/0 ꢀC, 4 h; (ii) ArB(OH)2, K3PO4, Pd(PPh3)4, dioxane, 90 ꢀC, 5 h.
4
5
X
R1
R2
R3
% (5)a
a
c
d
x
y
z
O
O
O
H
H
H
H
C2H5
C3H7
OCH3
OCH3
OCH3
48b
53
51
Table 5
a
SuzukieMiyaura cross-coupling reactions
Yields of isolated products.
The opposite regioisomer 5w was formed as a by-product in 18% yield.
b
5
6
7
X
Y
R1
R2
R3
Ar
% (6)a % (7)a
a
m
a
b
a
b
c
d
e
f
CH2
CH2
CH2
O
O
CH2
CH2
d
d
d
d
d
O
H
H
H
H
CO2CH3 C6H5
CO2CH3 4-MeC6H4 98
CO2CH3 4-ClC6H4
95
68
85
71
90
99
95
59
OCH3
OCH3
H
H
H
CH3 OH O
q
c
CO2CH3
CO2CH3
C2H5
C3H7
H
H
C6H5
4-MeC6H4
92
H2C
OCH3
H
y
z
d
e
CO2CH3 4-MeC6H4 98
CO2CH3 C6H5 95
g
O
H
a
Yields of isolated products.
CF3
O
Fig. 9. Diagnostic NOESY interactions of 5y.
Fig. 10. Ortep plot of 5x (50% probability level).

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3661
79
3. Conclusions
C H
11 6
BrF3O2 (Mþ): 305.94978, found 305.94986; calcd for
C11H681BrF3O2 (Mþ): 307.94773, found 307.94826.
Trifluoromethyl-substituted fluorenes, dibenzofurans, 9,10-
dihydrophenanthrenes and 6H-benzo[c]chromenes were pre-
pared by formal [3þ3] cyclizations of 1,3-bis(silyloxy)-1,3-
butadienes. The reactions proceeded with very good regiose-
lectivity. The product distribution depends on the type of 1,3-
dielectrophile employed. In case of the synthesis of fluorenes,
9,10-dihydrophenanthrenes and benzo[c]chromenes, the cycliza-
tions proceed by attack of the terminal carbon of the diene to the
carbon attached to the silyloxy group. In contrast, the carbonyl
group is attacked first during the formation of dibenzofurans. This
4.2.2. 5-Methoxy-2-(2,2,2-trifluoroacetyl)-1-indanone (2c). Starting
with 5-methoxy-1-indanone 1c (5.00 g, 30.8 mmol), ethyl tri-
fluoroacetate (4.380 g, 30.8 mmol), sodium (0.850 g, 37.0 mmol)
and methanol (12.5 mL), product 2c was isolated as a colourless
solid (5.278 g, 66%); mp¼107e108 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼3.76 (s, 2H, CH2), 3.91 (s, 3H, CH3), 6.95e7.03 (m, 2H, ArH),
7.78 (dd, 3J¼7.5 Hz, 4J¼1.7 Hz, 1H, ArH); 19F NMR (282 MHz,
CDCl3):
d
¼ꢁ71.9 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼29.7 (q,
4J¼2.2 Hz, CH2), 55.8 (OCH3), 109.7 (CH), 110.3 (C), 115.9 (CH),
118.9 (q, 1J¼277.9 Hz, CF3), 124.4 (CH), 129.5 (C), 152.4 (C), 156.9
(q, 2J¼37.3 Hz, CCF3), 165.8 (C), 194.9 (CO); IR (ATR, cmꢁ1):
~
change of the selectivity can be explained by the p-donating effect
of the oxygen atom. The hydroxyl group of the products could be
replaced by aryl groups by Suzuki reactions of the aryl triflates. The
methodology reported herein provides a convenient and regiose-
lective approach to various CF3-substituted polycyclic ring sys-
tems, which are not readily available by other methods. The
products reported herein are of potential pharmacological rele-
vance, due to their structural similarity to drugs and natural
products.
n
¼3063 (w), 3018 (w), 2954 (w), 2908 (w), 2851 (w), 1684 (m),
1614 (m), 1578 (m), 1520 (w), 1486 (m), 1471 (m), 1453 (w), 1445
(w), 1425 (m), 1385 (w), 1334 (m), 1262 (m), 1208 (m), 1180 (m),
1161 (m), 1135 (s), 1107 (m), 1029 (m); MS (EI, 70 eV): m/z (%)¼
258 (Mþ, 80), 189 (100), 174 (8), 161 (69), 146 (13), 118 (22);
HRMS (EI, 70 eV): calcd for C12H9F3O3 (Mþ): 258.04983, found
258.04998.
4.2.3. 2-(2,2,2-Trifluoroacetyl)-3-coumaranone (2d). Starting with
3-coumaranone 1d (5.000 g, 37.3 mmol), ethyl trifluoroacetate
(5.296 g, 37.3 mmol), sodium (1.028 g, 44.7 mmol) and methanol
(15.1 mL), product 2d was isolated as a red solid (3.186 g, 37%);
4. Experimental section
4.1. General
mp¼121e122 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼7.36 (ddd,
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR
spectra, the deuterated solvents indicated were used. Mass spec-
trometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, isobutane) or electrospray ioniza-
tion (ESI). For preparative scale chromatography, silica gel 60
(0.063e0.200 mm, 70e230 mesh) was used. Crystallographic de-
tails are given in Ref. 35.
3J¼8.0 Hz, 3J¼7.2 Hz, 3J¼0.9 Hz, 1H, ArH), 7.51 (d, 3J¼8.6 Hz, 1H,
ArH), 7.66 (ddd, 3J¼8.5 Hz, 3J¼7.2 Hz, 3J¼1.3 Hz, 1H, ArH), 7.83 (d,
3J¼8.0 Hz, 1H, ArH), 8.71 (s, 1H, OH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ75.0 (CF3); 13C NMR (75 MHz, CDCl3):
¼113.3 (CH), 116.0 (q,
d
1J¼286.4 Hz, CF3), 118.8 (C), 121.8 (CH), 124.0 (CH), 131.9 (C), 132.9
(CH), 156.0 (C), 159.5 (C), 172.2 (q, 2J¼38.8 Hz, CCF3); IR (ATR, cmꢁ1):
~
n
¼3338 (w), 1666 (m), 1652 (m), 1614 (m), 1594 (m), 1553 (m), 1539
(m), 1504 (m), 1485 (w), 1480 (w), 1455 (m), 1435 (w), 1415 (w),
1392 (w), 1384 (w), 1372 (w), 1331 (w), 1294 (w), 1251 (m), 1229
(m), 1207 (m), 1189 (m), 1169 (m), 1134 (m), 1107 (m), 1009 (m), 993
(m); MS (EI, 70 eV): m/z (%)¼230 (Mþ, 74), 189 (4), 161 (100), 105
(26), 77 (15); HRMS (ESI, TOF/MS): calcd for C10H4F3O3 ((MꢁH)ꢁ):
229.01180, found 229.01198.
4.2. General procedure for the synthesis of diketones 2aef
Sodium (1.2 equiv) was reacted with methanol (10.0 equiv) at
0 ꢀC. To this freshly prepared sodium methylate suspension ethyl
trifluoroacetate (1.0 equiv) has been added under stirring at 0 ꢀC
and stirring was continued for 30 min followed by addition of ke-
tone 1aef (1.0 equiv). The reaction mixture was stirred for addi-
tional 14 h and then was worked up with hydrochloric acid (10%,
50 mL). The organic layer was separated and extracted with
diethylether (3ꢂ40 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-
heptane/EtOAc 20:1).
4.3. General procedure for the synthesis of silyl enol ethers
3aef
To a stirred diethyl ether solution (2 mL per 1.0 mmol of 2) of
2aef (1.0 equiv) were added triethylamine (1.0 equiv) and TMSOTf
(0.95 equiv) at 0 ꢀC under an argon atmosphere. The solution was
stirred for 30 min at 0 ꢀC. The temperature of the reaction mixture
was allowed to rise to 20 ꢀC and the stirring was continued for 3
days. A liquid salt layer separated at the bottom of the flask. The
upper layer (ether solution containing the product) was transferred
to a dry flask by syringe under an argon atmosphere. Diethyl ether
(1.5 mL per 1.0 mmol of 2) was added to the liquid salt layer, the
mixture was stirred for 2 min and the layers were allowed to sep-
arate in the period of 2 h. The ether solutions were combined and
concentrated in vacuo to give silyl enol ethers 3aef, which were not
further purified and, due to their unstable nature, were immedi-
ately used for the synthesis of phenols 5 (without detailed spec-
troscopic characterization).
4.2.1. 5-Bromo-2-(2,2,2-trifluoroacetyl)-1-indanone (2b). Starting
with 5-bromo-1-indanone 1b (5.00 g, 23.7 mmol), ethyl tri-
fluoroacetate (3.366 g, 23.7 mmol), sodium (0.654 g, 28.4 mmol)
and methanol (9.6 mL), product 2b was isolated as a grey solid
(4.958 g, 68%); mp¼100e106 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼3.81 (s, 2H, CH2), 7.62 (d, 3J¼8.2 Hz, 1H, ArH), 7.68e7.75 (m, 2H,
ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ72.8 (CF3); 13C NMR (75 MHz,
CDCl3):
d
¼30.0 (q, 4J¼2.2 Hz, CH2), 109.3 (C), 118.2 (q, 1J¼280.1 Hz,
CF3), 124.7 (CH), 129.3 (CH), 129.8 (C), 131.6 (CH), 135.0 (C), 149.8 (C),
163.5 (q, 2J¼37.4 Hz, CCF3), 191.4 (CO); IR (ATR, cmꢁ1):
n
¼1689 (m),
4.3.1. General procedure for the synthesis of products 5aez. To
a CH2Cl2 solution (4 mL) of 1,3-bis-silyl enol ether 4 (2.20 mmol)
and 4-(silyloxy)alk-3-en-2-one 3 (2.00 mmol) was added TiCl4
(2.20 mmol) at ꢁ78 ꢀC under argon atmosphere. The temperature
of the reaction mixture was allowed to rise to 20 ꢀC during 14 h
and, subsequently, hydrochloric acid (10%, 10 mL) was added. The
~
1633 (m), 1598 (m), 1574 (w), 1538 (w), 1519 (w), 1504 (w), 1484
(w), 1469 (w), 1416 (w), 1386 (w), 1310 (m), 1261 (m), 1187 (m), 1171
(m), 1151 (m), 1132 (m), 1111 (m), 1056 (m), 1040 (w), 1008 (m); MS
(EI, 70 eV): m/z (%)¼308 (81Br, Mþ, 66), 306 (79Br, Mþ, 65), 239 (85),
237 (100), 211 (60), 209 (58), 102 (50); HRMS (EI, 70 eV): calcd for

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3662
organic layer was separated and extracted with CH2Cl2
(3ꢂ15 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-heptane/
EtOAc 20:1).
(100), 284 (23), 276 (69), 207 (31); HRMS (EI, 70 eV): calcd for
18H15F3O3 (Mþ): 336.09678, found 336.09615.
C
4.3.5. Methyl
3-hydroxy-4-n-propyl-1-(trifluoromethyl)-9H-fluo-
rene-2-carboxylate (5d). Starting with silyl enol ether 3a (0.501 g,
1.67 mmol), 1,3-bis-silyl enol ether 4d (0.666 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (3 mL), product 5d was iso-
lated as a pale yellow solid (0.317 g, 54%); mp¼102e103 ꢀC; 1H
4.3.2. Methyl 3-hydroxy-1-(trifluoromethyl)-9H-fluorene-2-
carboxylate (5a). Starting with silyl enol ether 3a (0.622 g,
2.07 mmol), 1,3-bis-silyl enol ether 4a (0.573 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5a was iso-
lated as a colourless solid (0.272 g, 43%); mp¼77e78 ꢀC; 1H NMR
NMR (250 MHz, CDCl3):
d
¼1.13 (t, 3J¼7.3 Hz, 3H, CH2CH3),
1.65e1.82 (m, 2H, CH2CH3), 3.10e3.21 (m, 2H, ArCH2CH2), 3.98 (s,
3H, OCH3), 4.06e4.11 (m, 2H, CH2), 7.35e7.47 (m, 2H, ArH),
7.55e7.60 (m, 1H, ArH), 7.90e7.96 (m, 1H, ArH), 9.71 (s, 1H, OH);
(250 MHz, CDCl3):
d
¼3.99 (s, 3H, OCH3), 4.05 (q, J¼2.5 Hz, 2H, CH2),
19F NMR (235 MHz, CDCl3):
CDCl3):
d
¼ꢁ55.9 (CF3); 13C NMR (63 MHz,
7.35e7.45 (m, 2H, ArH), 7.49e7.56 (m, 2H, ArH), 7.72e7.80 (m, 1H,
ArH), 9.72 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
¼ꢁ56.2 (CF3);
d
d
¼12.3 (ArCH3), 21.5 (CH2), 27.9 (CH2), 37.0 (q, J¼4.0 Hz,
13C NMR (75 MHz, CDCl3):
d¼37.2 (q, J¼4.1 Hz, CH2), 52.9 (OCH3),
ArCH2Ar), 52.9 (OCH3), 110.1 (q, J¼2.3 Hz, C), 123.0 (q, 2J¼32.7 Hz,
CCF3), 124.0 (CH), 124.3 (q, 1J¼274.4 Hz, CF3), 124.8 (CH), 127.1 (CH),
128.2 (CH), 130.1 (C), 133.8 (q, J¼2.4 Hz, C), 139.5 (C), 145.0 (C),
~
110.8 (q, 3J¼2.3 Hz, C), 111.7 (CH), 121.0 (CH), 124.0 (q, 1J¼274.8 Hz,
CF3), 124.9 (CH), 126.2 (q, 2J¼32.7 Hz, CCF3), 127.2 (CH), 129.2 (CH),
133.6 (q, J¼2.4 Hz, C), 138.6 (C), 144.5 (q, J¼1.7 Hz, C), 148.2 (C),
~
145.4 (C), 156.9 (COH), 170.7 (CO); IR (ATR, cmꢁ1):
n
¼3420 (w),
159.5 (COH), 170.0 (CO); IR (ATR, cmꢁ1):
n
¼3534 (m), 3424 (w),
3076 (w), 3022 (w), 2968 (w), 2957 (w), 2935 (w), 2918 (w), 2875
(w), 2792 (w), 1707 (m), 1602 (w), 1574 (w), 1464 (w), 1452 (w),
1436 (m), 1409 (m), 1399 (m), 1371 (m), 1331 (m), 1310 (m), 1288
(m), 1252 (m), 1217 (m), 1191 (m), 1158 (m), 1129 (m), 1109 (s),
1036 (m), 1012 (m); MS (EI, 70 eV): m/z (%)¼350 (Mþ, 68), 318
(100), 290 (73), 270 (26), 183 (17); HRMS (EI, 70 eV): calcd for
C19H17F3O3 (Mþ): 350.11243, found 350.11156. Anal. Calcd for
C19H17F3O3 (350.33): C, 65.14; H, 4.89. Found: C, 64.75; H, 4.70.
3048 (w), 2960 (w), 2795 (w), 2726 (w), 2660 (w), 1705 (m), 1684
(m), 1651 (m), 1644 (m), 1616 (m), 1478 (m), 1440 (m), 1407 (m),
1315 (m), 1293 (m), 1264 (m), 1231 (m), 1206 (m), 1185 (m), 1157
(m), 1102 (s), 1021 (m); MS (EI, 70 eV): m/z (%)¼308 (Mþ, 54), 276
(100), 219 (18), 207 (68); HRMS (EI, 70 eV): calcd for C16H11F3O3
(Mþ): 308.06548, found 308.06486.
4.3.3. Methyl 3-hydroxy-4-methyl-1-(trifluoromethyl)-9H-fluorene-
2-carboxylate (5b). Starting with silyl enol ether 3a (0.598 g,
1.99 mmol), 1,3-bis-silyl enol ether 4b (0.604 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5b was iso-
lated as a pale yellow solid (0.309 g, 48%); mp¼100e102 ꢀC; 1H
4.3.6. Methyl
3-hydroxy-4-methoxy-1-(trifluoromethyl)-9H-fluo-
rene-2-carboxylate (5e). Starting with silyl enol ether 3a (0.590 g,
1.96 mmol), 1,3-bis-silyl enol ether 4e (0.639 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5e was
isolated as a pale yellow solid (0.446 g, 67%); mp¼124e125 ꢀC;
NMR (250 MHz, CDCl3):
d¼2.68 (s, 3H, ArCH3), 3.98 (s, 3H, OCH3),
4.05e4.11 (m, 2H, CH2), 7.38e7.45 (m, 2H, ArH), 7.52e7.61 (m, 1H,
1H NMR (250 MHz, CDCl3):
d
¼3.99 (s, 3H, OCH3), 4.05e4.10 (m,
ArH), 8.00e8.07 (m, 1H, ArH), 9.83 (s, 1H, OH); 19F NMR (235 MHz,
¼ꢁ55.9 (CF3); 13C NMR (125 MHz, CDCl3):
¼12.5 (ArCH3),
d
5H, ArOCH3, CH2), 7.34e7.48 (m, 2H, ArH), 7.48e7.58 (m, 1H,
CDCl3):
d
ArH), 8.11e8.20 (m, 1H, ArH), 8.89 (s, 1H, OH); 19F NMR
37.0 (q, J¼3.7 Hz, CH2), 52.9 (OCH3), 109.9 (C), 122.9 (q, 2J¼32.5 Hz,
CCF3), 124.3 (CH), 124.3 (q, 1J¼274.3 Hz, CF3), 124.7 (CH), 125.0 (C),
126.9 (CH), 128.2 (CH), 133.4 (C), 140.1 (C), 144.9 (C), 145.8 (C), 160.0
~
(235 MHz, CDCl3):
d
¼ꢁ56.2 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼37.4 (q, J¼3.6 Hz, CH2), 53.0 (OCH3), 60.3 (ArOCH3), 113.7 (q,
J¼2.4 Hz, C), 120.7 (q, 2J¼32.8 Hz, CCF3), 124.0 (q, 1J¼273.9 Hz,
CF3), 124.3 (CH), 124.5 (CH), 127.3 (CH), 128.4 (CH), 134.6 (q,
3J¼2.3 Hz, C), 137.8 (C), 138.3 (C), 143.8 (q, 3J¼1.4 Hz, C), 151.0
~
(COH), 170.7 (CO); IR (ATR, cmꢁ1):
n
¼3109 (w), 3034 (w), 3013 (w),
2955 (w), 2923 (w), 2853 (w), 1738 (w), 1667 (m), 1592 (w), 1440
(m), 1384 (m), 1366 (m), 1334 (m), 1313 (m), 1291 (m), 1251 (m),
1220 (m), 1206 (m), 1194 (m), 1162 (m), 1153 (m), 1113 (s), 1027 (m),
1003 (m); MS (EI, 70 eV): m/z (%)¼322 (Mþ, 55), 290 (67), 270 (100),
165 (23); HRMS (EI, 70 eV): calcd for C17H13F3O3 (Mþ): 322.08113,
found 322.08067. Anal. Calcd for C17H13F3O3 (322.28): C, 63.36; H,
4.07. Found: C, 62.83; H, 4.14.
(COH), 169.2 (CO); IR (ATR, cmꢁ1):
n
¼3305 (w), 3054 (w), 3007
(w), 2946 (w), 2905 (w), 2837 (w), 1711 (m), 1607 (m), 1591 (m),
1487 (m), 1449 (m), 1419 (m), 1403 (m), 1392 (m), 1326 (m), 1302
(m), 1286 (m), 1222 (m), 1204 (m), 1183 (m), 1163 (m), 1134 (m),
1098 (m), 1065 (m), 1024 (m); MS (EI, 70 eV): m/z (%)¼338 (Mþ,
71), 306 (100), 278 (70), 249 (26), 207 (44), 181 (37); HRMS (EI,
70 eV): calcd for C17H13F3O4 (Mþ): 338.07604, found 338.07545.
Anal. Calcd for C17H13F3O4 (338.28): C, 60.36; H, 3.87. Found: C,
59.97; H, 4.02.
4.3.4. Methyl 4-ethyl-3-hydroxy-1-(trifluoromethyl)-9H-fluorene-2-
carboxylate (5c). Starting with silyl enol ether 3a (0.600 g,
2.00 mmol), 1,3-bis-silyl enol ether 4c (0.635 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5c was iso-
lated as a pale yellow solid (0.309 g, 46%); mp¼112e114 ꢀC; 1H
4.3.7. 3-Hydroxy-2-(methylcarbonyl)-1-(trifluoromethyl)-9H-fluo-
rene (5f). Starting with silyl enol ether 3a (0.594 g, 1.98 mmol), 1,3-
bis-silyl enol ether 4f (0.538 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol) in CH2Cl2 (4 mL), product 5f was isolated as a grey solid
NMR (250 MHz, CDCl3):
d
¼1.33 (t, 3J¼7.5 Hz, 3H, CH2CH3), 3.23 (q,
3J¼7.5 Hz, 2H, CH2CH3), 3.98 (s, 3H, OCH3), 4.07e4.12 (m, 2H, CH2),
7.36e7.48 (m, 2H, ArH), 7.55e7.61 (m, 1H, ArH), 7.97e8.03 (m, 1H,
(0.225 g, 39%); mp¼167e169 ꢀC; 1H NMR (250 MHz, CDCl3):
¼2.61
d
ArH), 9.73 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
d
¼ꢁ55.9 (CF3);
13C NMR (75 MHz, CDCl3):
d
¼12.5 (ArCH2CH3), 19.4 (ArCH2CH3),
(s, 3H, COCH3), 3.85 (s, 3H, OCH3), 7.31e7.49 (m, 4H, ArH), 7.64e7.75
(m, 1H, ArH), 8.43 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
d
¼ꢁ55.4
37.0 (q, J¼4.0 Hz, CH2), 52.9 (OCH3), 110.1 (q, J¼2.2 Hz, C), 123.1 (q,
2J¼32.4 Hz, CCF3), 124.1 (CH), 124.3 (q, 1J¼274.3 Hz, CF3), 124.8 (CH),
127.2 (CH), 128.2 (CH), 131.4 (C), 133.8 (q, J¼2.2 Hz, C), 139.4 (C),
~
(CF3); 13C NMR (75 MHz, CDCl3):
d
¼32.1 (q, J¼4.1 Hz, CH2), 36.3
(COCH3), 111.9 (C), 120.6 (CH), 123.1 (q, 3J¼2.4 Hz, C), 124.1 (q,
2J¼32.2 Hz, CCF3), 124.2 (q, 1J¼272.1 Hz, CF3), 124.9 (CH), 127.1 (CH),
129.6 (CH),133.4 (q, 3J¼2.5 Hz, C),138.7 (C),144.1 (C),146.5 (C),154.7
~
145.0 (C), 145.2 (C), 156.8 (COH), 170.7 (CO); IR (ATR, cmꢁ1):
n
¼3432
(w), 3082 (w), 3024 (w), 2959 (w), 2935 (w), 2915 (w), 2873 (w),
2785 (w),1712 (m),1604 (w),1574 (w),1483 (w),1462 (w),1451 (w),
1436 (m), 1410 (m), 1397 (m), 1366 (m), 1327 (m), 1309 (m), 1293
(m), 1267 (m), 1218 (m), 1192 (m), 1160 (m), 1129 (m), 1107 (s), 1055
(m), 1037 (m), 1022 (m); MS (EI, 70 eV): m/z (%)¼336 (Mþ, 69), 304
(COH), 205.8 (CO); IR (ATR, cmꢁ1):
n
¼3233 (w), 3063 (w), 2926 (w),
2789 (w), 2713 (w),1682 (m),1614 (m),1514 (w),1477 (m),1456 (w),
1435(m),1403 (m),1355(m),1324(m),1294 (m),1285 (m),1256 (m),
1212 (m),1182 (m),1152 (m),1112 (m),1081 (m); MS (EI, 70 eV): m/z

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3663
(%)¼292 (Mþ, 41), 277 (100), 229 (14), 201 (17); HRMS (EI, 70 eV):
1278 (m), 1245 (m), 1217 (m), 1199 (m), 1155 (m), 1135 (m), 1112 (s),
1068 (m), 1025 (m), 1005 (m); MS (EI, 70 eV): m/z (%)¼402 (81Br,
Mþ, 59), 400 (79Br, Mþ, 61), 370 (98), 368 (96), 350 (97), 348 (100),
calcd for C16H11F3O2 (Mþ): 292.07057, found 292.07067.
4.3.8. Methyl 7-bromo-3-hydroxy-1-(trifluoromethyl)-9H-fluorene-
4-carboxylate (5g). Starting with silyl enol ether 3b (0.567 g,
1.50 mmol), 1,3-bis-silyl enol ether 4a (0.430 g, 1.65 mmol) and
TiCl4 (0.18 mL,1.65 mmol) in CH2Cl2 (3 mL), product 5g was isolated
as a pale orange solid (0.137 g, 24%); mp¼140e142 ꢀC; 1H NMR
289 (32), 269 (28), 233 (39); HRMS (EI, 70 eV): calcd for
79
C17
C17
H
12
81
H
12
BrF3O3 (Mþ): 399.99164, found 399.99150; calcd for
BrF3O3 (Mþ): 401.98960, found 401.98959. Anal. Calcd for
C17H12BrF3O3 (401.18): C, 50.90; H, 3.01. Found: C, 50.64; H, 2.82.
(300 MHz, CDCl3):
d
¼3.96 (s, 2H, CH2), 4.10 (s, 3H, OCH3), 7.25 (s,
4.3.11. Methyl 7-bromo-4-ethyl-3-hydroxy-1-(trifluoromethyl)-9H-
fluorene-2-carboxylate (5k). Starting with silyl enol ether 3b
(0.562 g, 1.48 mmol), 1,3-bis-silyl enol ether 4c (0.476 g, 1.65 mmol)
and TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5k was
isolated asa colourless solid (0.305 g, 50%); mp¼173e174 ꢀC; 1H NMR
1H, ArH), 7.45 (dd, 3J¼8.6 Hz, 4J¼2.0 Hz, 1H, ArH), 7.68e7.71 (m, 1H,
ArH), 7.82 (d, 3J¼8.6 Hz, 1H, ArH), 10.01 (s, 1H, OH); 19F NMR
(282 MHz, CDCl3):
d
d
¼ꢁ63.6 (CF3); 13C NMR (75 MHz, CDCl3):
¼35.1 (CH2), 52.5 (OCH3), 111.7 (C), 113.7 (q, 3J¼4.9 Hz, CHCCF3),
122.4 (C), 123.3 (q, 1J¼271.7 Hz, CF3), 125.9 (CH), 127.9 (CH), 129.9
(300 MHz, CDCl3):
d
¼1.30 (t, 3J¼7.5 Hz, 3H, CH2CH3), 3.17 (q,
(CH), 131.4 (q, 2J¼32.7 Hz, CCF3), 132.4 (q, J¼1.8 Hz, C), 138.3 (C),
3J¼7.5 Hz, 2H, CH2CH3), 3.98 (s, 3H, OCH3), 4.04e4.08 (m, 2H, CH2),
7.55 (dd, 3J¼8.5 Hz, 4J¼1.9 Hz, 1H, ArH), 7.69e7.72 (m, 1H, ArH), 7.83
(d, 3J¼8.5 Hz, 1H, ArH), 9.74 (s, 1H, OH); 19F NMR (282 MHz, CDCl3):
142.6 (C), 146.9 (C), 159.8 (COH), 169.5 (CO); IR (ATR, cmꢁ1):
n
¼3393
~
(m), 3107 (w), 3071 (w), 3045 (w), 3020 (w), 2960 (w), 2924 (w),
2852 (w), 2790 (w), 1747 (w), 1704 (m), 1611 (w), 1586 (m), 1487
(m), 1455 (w), 1439 (m), 1408 (m), 1401 (m), 1339 (m), 1312 (m),
1288 (m), 1263 (m), 1233 (m), 1204 (m), 1179 (m), 1153 (s), 1130 (m),
1121 (m), 1106 (s), 1097 (s), 1065 (m), 1007 (m); MS (EI, 70 eV): m/z
d
¼ꢁ56.0 (CF3); 13C NMR (75 MHz, CDCl3):
¼12.4 (ArCH2CH3), 19.3
d
(ArCH2CH3), 36.7 (q, J¼4.2 Hz, CH2), 53.0 (OCH3), 110.5 (C), 122.5 (C),
123.2 (q, 2J¼32.8 Hz, CCF3), 124.1 (q, 1J¼274.6 Hz, CF3), 125.2 (CH),
128.0 (CH),130.4 (CH),131.5 (C),133.3 (q, J¼2.3 Hz, C),138.3 (C), 144.1
(%)¼388 (81Br, Mþ, 38), 386 (79Br, Mþ, 39), 356 (99), 354 (100), 275
(C), 146.9 (C), 156.9 (COH), 170.5 (CO); IR (ATR, cmꢁ1): ¼3429 (w),
~
n
79
(70), 247 (25), 219 (48); HRMS (EI, 70 eV): calcd for C16
H
BrF3O3
2961 (w), 2938 (w), 2920 (w), 2875 (w), 2853 (w), 2782 (w),1710 (m),
1599 (w), 1583 (w), 1481 (w), 1463 (w), 1454 (w), 1436 (m), 1421 (w),
1396 (m),1369 (m),1325 (m),1310 (m),1291 (m),1268 (m),1217 (m),
1193 (m), 1157 (m), 1134 (m), 1109 (s), 1069 (m), 1057 (m), 1025 (m);
MS(EI, 70 eV):m/z (%)¼416 (81Br, Mþ, 44), 414 (79Br, Mþ, 47), 384 (42),
10
81
(Mþ): 385.97599, found 385.97686; calcd for C16
H
BrF3O3 (Mþ):
10
387.97395, found 387.97417. Anal. Calcd for C16H10BrF3O3 (387.15):
C, 49.64; H, 2.60. Found: C, 49.55; H, 2.64.
4.3.9. Methyl 7-bromo-3-hydroxy-1-(trifluoromethyl)-9H-fluorene-
2-carboxylate (5h). Starting with silyl enol ether 3b (0.567 g,
1.50 mmol), 1,3-bis-silyl enol ether 4a (0.430 g, 1.65 mmol) and
TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5h was iso-
lated as a pale orange solid (0.236 g, 41%); mp¼153e155 ꢀC; 1H
382 (42), 364 (15), 362 (15), 303 (100), 275 (20); HRMS (EI, 70 eV):
79
calcd for C18
H
14
BrF3O3 (Mþ): 414.00729, found 414.00710; calcd for
81
C18
H
BrF3O3 (Mþ): 416.00525, found 416.00544. Anal. Calcd for
14
C18H14BrF3O3 (415.20): C, 52.07; H, 3.40. Found: C, 52.25; H, 3.12.
NMR (300 MHz, CDCl3):
d
¼3.99 (s, 3H, OCH3), 4.03 (q, J¼2.7 Hz, 2H,
4.3.12. Methyl 7-bromo-3-hydroxy-4-n-propyl-1-(trifluoromethyl)-
9H-fluorene-2-carboxylate (5l). Starting with silyl enol ether 3b
(0.560 g, 1.48 mmol), 1,3-bis-silyl enol ether 4d (0.499 g, 1.65 mmol)
and TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5l was
isolated as a colourless solid (0.381 g, 60%); mp¼127e129 ꢀC; 1H
CH2), 7.47 (s, 1H, ArH), 7.53 (dd, 3J¼8.2 Hz, 4J¼1.7 Hz, 1H, ArH), 7.61
(d, 3J¼8.2 Hz, 1H, ArH), 7.65e7.69 (m, 1H, ArH), 9.73 (s, 1H, OH); 19
F
NMR (282 MHz, CDCl3):
d
¼ꢁ56.2 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼36.9 (q, J¼4.2 Hz, CH2), 53.0 (OCH3), 111.2 (q, 3J¼2.2 Hz, C), 111.8
(CH), 122.1 (CH), 123.3 (C), 123.8 (q, 1J¼272.2 Hz, CF3), 126.3 (q,
2J¼32.9 Hz, CCF3), 128.1 (CH), 130.5 (CH), 133.0 (q, J¼2.5 Hz, C), 137.5
(C), 146.2 (C), 146.9 (C), 159.5 (COH), 169.8 (CO); IR (ATR, cmꢁ1):
~
NMR (300 MHz, CDCl3):
d
¼1.11 (t, 3J¼7.4 Hz, 3H, CH2CH3), 1.61e1.77
(m, 2H, CH2CH3), 3.06e3.14 (m, 2H, ArCH2CH2), 3.98 (s, 3H, OCH3),
4.03e4.07 (m, 2H, CH2), 7.55 (dd, 3J¼8.5 Hz, 4J¼1.9 Hz, 1H, ArH),
7.69e7.71 (m, 1H, ArH), 7.75 (d, 3J¼8.5 Hz, 1H, ArH), 9.72 (s, 1H, OH);
n
¼3019 (w), 2964 (w), 1738 (w), 1668 (m), 1614 (w), 1587 (m), 1473
(w), 1443 (m), 1405 (w), 1383 (m), 1344 (m), 1288 (m), 1275 (m),
1254 (m),1222 (m),1207 (m), 1158 (m),1149 (m),1127 (s),1061 (m);
MS (EI, 70 eV): m/z (%)¼388 (81Br, Mþ, 56), 386 (79Br, Mþ, 58), 356
19F NMR (282 MHz, CDCl3):
d
¼ꢁ56.0 (CF3); 13C NMR (75 MHz,
CDCl3):
d
¼14.3 (ArCH3), 21.5 (CH2), 27.9 (CH2), 36.7 (q, J¼4.0 Hz,
ArCH2Ar), 53.0 (OCH3), 110.5 (C), 122.5 (C), 123.2 (q, 2J¼32.5 Hz,
CCF3), 124.1 (q, 1J¼274.4 Hz, CF3), 125.1 (CH), 128.0 (CH), 130.3 (C),
130.4 (CH), 133.3 (q, J¼2.2 Hz, C), 138.4 (C), 144.3 (C), 146.9 (q,
~
(93), 354 (95), 287 (25), 285 (26), 275 (100), 247 (17), 219 (45);
79
HRMS (EI, 70 eV): calcd for C16
385.97606; calcd for C16
H
BrF3O3 (Mþ): 385.97599, found
10
81
H
BrF3O3 (Mþ): 387.97395, found
J¼0.8 Hz, C), 157.0 (COH), 170.5 (CO); IR (ATR, cmꢁ1):
¼3425 (w),
n
10
387.97428. Anal. Calcd for C16H10BrF3O3 (387.15): C, 49.64; H, 2.60.
Found: C, 49.40; H, 2.47.
2957 (w), 2934 (w), 2875 (w), 1711 (m), 1599 (w), 1582 (w), 1477
(w),1468 (w),1454 (w),1438 (m),1420 (w),1398 (m),1373 (m),1331
(m), 1311 (m), 1278 (m), 1251 (m), 1216 (m), 1193 (m), 1157 (m), 1135
(m), 1113 (s), 1073 (m), 1040 (m), 1011 (m); MS (EI, 70 eV): m/z (%)¼
430 (81Br, Mþ, 43), 428 (79Br, Mþ, 41), 398 (29), 396 (27), 369 (30),
4.3.10. Methyl
7-bromo-3-hydroxy-4-methyl-1-(trifluoromethyl)-
9H-fluorene-2-carboxylate (5j). Starting with silyl enol ether 3b
(0.648 g,1.71 mmol),1,3-bis-silyl enol ether 4b (0.522 g,1.90 mmol)
and TiCl4 (0.23 mL, 1.90 mmol) in CH2Cl2 (3 mL), product 5j was
isolated as a pale yellow solid (0.425 g, 62%); mp¼141e143 ꢀC; 1H
367 (28), 317 (100), 289 (14), 232 (25); HRMS (EI, 70 eV): calcd for
79
C19
C19
H
H
BrF3O3 (Mþ): 428.02294, found 428.02296; calcd for
16
81
16
BrF3O3 (Mþ): 430.02090, found 430.02086. Anal. Calcd for
NMR (300 MHz, CDCl3):
d
¼2.63 (s, 3H, ArCH3), 3.98 (s, 3H, OCH3),
C19H16BrF3O3 (429.23): C, 53.17; H, 3.76. Found: C, 52.89; H, 3.82.
4.01e4.05 (m, 2H, CH2), 7.53 (dd, 3J¼8.4 Hz, 4J¼1.9 Hz, 1H, ArH),
7.68 (d, 4J¼1.5 Hz, 1H, ArH), 7.85 (d, 3J¼8.5 Hz, 1H, ArH), 9.83 (s, 1H,
4.3.13. Methyl 3-hydroxy-7-methoxy-1-(trifluoromethyl)-9H-fluo-
rene-2-carboxylate (5m). Starting with silyl enol ether 3c (0.500 g,
1.51 mmol),1,3-bis-silyl enol ether 4a (0.430 g,1.65 mmol) and TiCl4
(0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5m was isolated as
a orange solid (0.355 g, 69%); mp¼134e136 ꢀC; 1H NMR (300 MHz,
OH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ55.9 (CF3); 13C NMR (63 MHz,
CDCl3):
d
¼12.4 (ArCH3), 36.7 (q, J¼4.2 Hz, CH2), 53.0 (OCH3), 110.2
(q, 3J¼2.4 Hz, C), 122.5 (C), 123.0 (q, 2J¼32.5 Hz, CCF3), 124.1 (q,
1J¼274.3 Hz, CF3), 125.1 (C), 125.3 (CH), 127.9 (CH), 130.1 (CH), 132.8
(q, J¼2.3 Hz, C), 138.9 (C), 144.6 (C), 146.7 (q, J¼1.8 Hz, C), 157.1
~
CDCl3):
d
¼3.87 (s, 3H, OCH3), 3.97 (s, 3H, OCH3), 3.99e4.04 (m, 2H,
(COH), 170.5 (CO); IR (ATR, cmꢁ1):
n
¼3412 (m), 3068 (w), 3008 (w),
CH2), 6.94 (dd, 3J¼8.5 Hz, 4J¼2.3 Hz,1H, ArH), 7.03e7.06 (m,1H, ArH),
7.38 (s, 1H, ArH), 7.65 (d, 3J¼8.4 Hz, 1H, ArH), 9.89 (s, 1H, OH); 19F
2958 (w), 2922 (w), 2854 (w), 2784 (w), 1699 (m), 1598 (w), 1584
(w), 1479 (w), 1435 (m), 1395 (m), 1363 (m), 1327 (m), 1291 (m),
NMR (282 MHz, CDCl3):
d
¼ꢁ56.0 (CF3); 13C NMR (75 MHz, CDCl3):

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3664
d
¼37.3 (q, J¼4.2 Hz, CH2), 52.8 (OCH3), 55.5 (OCH3), 109.2 (q,
(CF3); 13C NMR (75 MHz, CDCl3):
d
¼14.3 (ArCH3), 21.4 (CH2), 27.8
3J¼2.2 Hz, C), 109.7 (CH), 110.6 (CH), 114.0 (CH), 122.0 (CH), 124.1 (q,
1J¼274.8 Hz, CF3), 126.0 (q, 2J¼32.6 Hz, CCF3), 131.6 (C), 133.3 (q,
J¼2.5 Hz, C),146.6 (q, J¼1.8 Hz, C),148.4 (C),160.0 (COR),161.1 (COR),
~
(CH2), 37.1 (q, J¼4.1 Hz, ArCH2Ar), 52.8 (OCH3), 55.5 (OCH3),108.7 (q,
J¼2.4 Hz, C), 109.7 (CH), 113.6 (CH), 122.8 (q, 2J¼32.2 Hz, CCF3), 124.3
(q, 1J¼274.7 Hz, CF3), 124.9 (CH), 128.7 (C), 132.4 (C), 133.4 (q,
J¼2.3 Hz, C), 145.5 (C), 147.3 (C), 157.3 (COR), 160.1 (COR), 170.8 (CO);
~
170.2 (CO); IR (ATR, cmꢁ1):
n
¼3401 (w), 3020 (w), 2961 (w), 2935
(w), 2910 (w), 2838 (w),1706 (w),1652 (m),1610 (m),1594 (m),1494
(m),1450 (m),1417 (m),1403 (m),1379 (m),1331 (m),1285 (m),1267
(m), 1248 (m), 1212 (m), 1186 (m), 1151 (m), 1135 (m), 1121 (s), 1107
(s), 1092 (s), 1028 (m); HRMS (ESI, TOF/MS): calcd for C17H12F3O4
((MꢁH)ꢁ): 337.06932, found 337.06944.
IR (ATR, cmꢁ1):
n
¼3338 (w), 3082 (w), 3005 (w), 2947 (w), 2928 (w),
2867 (w), 2843 (w), 2727 (w), 1738 (w), 1698 (m), 1687 (m), 1620
(m), 1598 (m), 148 (w), 1469 (m), 1441 (w), 1403 (w), 1373 (m), 1334
(m), 1310 (m), 1286 (m), 1255 (m),1210 (m), 1163 (m), 1152 (m), 1109
(s), 1034 (m), 1007 (m); MS (EI, 70 eV): m/z (%)¼380 (Mþ, 100), 347
(18), 320 (100), 305 (13); HRMS (EI, 70 eV): calcd for C20H19F3O4
(Mþ): 380.12300, found 380.12296. Anal. Calcd for C20H19F3O4
(380.36): C, 63.15; H, 5.03. Found: C, 62.93; H, 5.06.
4.3.14. Methyl 3-hydroxy-7-methoxy-4-methyl-1-(trifluoromethyl)-
9H-fluorene-2-carboxylate (5n). Starting with silyl enol ether 3c
(0.536 g, 1.62 mmol), 1,3-bis-silyl enol ether 4b (0.494 g,
1.80 mmol) and TiCl4 (0.20 mL, 1.80 mmol) in CH2Cl2 (3 mL),
product 5n was isolated as a pale yellow solid (0.287 g, 50%);
4.3.17. Methyl 2-hydroxy-4-(trifluoromethyl)dibenzo[b,d]furane-1-
carboxylate (5q). Starting with silyl enol ether 3d (0.487 g,
1.61 mmol), 1,3-bis-silyl enol ether 4a (0.469 g, 1.80 mmol) and
TiCl4 (0.20 mL, 1.80 mmol) in CH2Cl2 (3 mL), product 5q was iso-
lated as a colourless solid (0.221 g, 44%); mp¼143e144 ꢀC; 1H NMR
mp¼140e141 ꢀC; 1H NMR (300 MHz, CDCl3):
¼2.62 (s, 3H, ArCH3),
d
3.88 (s, 3H, OCH3), 3.97 (s, 3H, OCH3), 4.00e4.05 (m, 2H, CH2), 6.95
(dd, 3J¼8.7 Hz, 4J¼2.5 Hz, 1H, ArH), 7.08 (d, 4J¼2.7 Hz, 1H, ArH), 7.91
(d, 3J¼8.7 Hz, 1H, ArH), 9.98 (s, 1H, OH); 19F NMR (282 MHz, CDCl3):
(300 MHz, CDCl3):
d
¼4.22 (s, 3H, OCH3), 7.33e7.41 (m, 2H, ArH),
d
¼ꢁ55.7 (CF3); 13C NMR (75 MHz, CDCl3):
d¼12.3 (ArCH3), 37.0 (q,
7.55 (dd, 3J¼8.2 Hz, 3J¼7.2 Hz, 1H, ArH), 7.65 (d, J¼8.3 Hz, 1H, ArH),
J¼4.1 Hz, CH2), 52.8 (OCH3), 55.4 (OCH3), 108.5 (q, 3J¼2.3 Hz, C),
109.7 (CH), 113.3 (CH), 122.6 (q, 2J¼32.4 Hz, CCF3), 123.5 (C), 124.3
(q, 1J¼274.4 Hz, CF3), 125.2 (CH), 132.9 (q, J¼2.4 Hz, C), 133.0 (C),
145.9 (C), 147.1 (C), 157.3 (COR), 160.1 (COR), 170.8 (CO); IR (ATR,
~
8.33 (d, J¼8.3 Hz, 1H, ArH), 11.21 (s, 1H, OH); 19F NMR (282 MHz,
CDCl3):
d
¼ꢁ62.4 (CF3); 13C NMR (75 MHz, CDCl3):
¼52.6 (OCH3),
d
108.8 (C), 112.2 (CH), 114.7 (q, 3J¼4.7 Hz, CH), 120.9 (q, 2J¼34.7 Hz,
CCF3), 122.2 (q, 1J¼272.9 Hz, CF3), 122.4 (C), 123.1 (CH), 124.6 (CH),
125.2 (C), 128.8 (CH), 145.5 (C), 157.5 (C), 158.4 (COH), 170.1 (CO); IR
~
cmꢁ1):
n
¼3082 (w), 3039 (w), 3001 (w), 2956 (w), 2937 (w), 2837
(w), 1738 (w), 1663 (m), 1620 (m), 1593 (m), 1490 (w), 1478 (w),
1456 (m), 1435 (m), 1408 (w), 1388 (m), 1362 (m), 1345 (m), 1305
(m), 1291 (m), 1254 (m), 1218 (m), 1166 (m), 1133 (m), 1111 (s), 1039
(m), 1028 (m), 1005 (m); MS (EI, 70 eV): m/z (%)¼352 (Mþ, 78), 320
(61), 300 (100), 249 (16); HRMS (EI, 70 eV): calcd for C18H15F3O4
(Mþ): 352.09170, found 352.09187.
(ATR, cmꢁ1):
n
¼3141 (w), 3082 (w), 2970 (w), 1672 (m), 1626 (m),
1587 (w), 1504 (m), 1476 (m), 1447 (m), 1408 (m), 1358 (m), 1319
(m), 1279 (m), 1269 (m), 1246 (w), 1215 (s), 1176 (m), 1160 (m), 1146
(m), 1125 (s), 1115 (s), 1092 (s), 1026 (m), 1015 (m); MS (EI, 70 eV):
m/z (%)¼310 (Mþ, 33), 278 (100), 250 (38); HRMS (EI, 70 eV): calcd
for C15H9F3O4 (Mþ): 310.04474, found 310.04476. Anal. Calcd for
C15H9F3O4 (310.23): C, 58.07; H, 2.92. Found: C, 57.63; H, 2.90.
4.3.15. Methyl
4-ethyl-3-hydroxy-7-methoxy-1-(trifluoromethyl)-
9H-fluorene-2-carboxylate (5o). Starting with silyl enol ether 3c
(0.494 g, 1.50 mmol), 1,3-bis-silyl enol ether 4c (0.476 g, 1.65 mmol)
and TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5o was
isolated as a colourless solid (0.201 g, 37%); mp¼140e141 ꢀC; 1H
4.3.18. Methyl 2-hydroxy-3-methyl-4-(trifluoromethyl)dibenzo[b,d]
furane-1-carboxylate (5r). Starting with silyl enol ether 3d (0.457 g,
1.51 mmol), 1,3-bis-silyl enol ether 4b (0.453 g, 1.65 mmol) and
TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5r was isolated
as a colourless solid (0.236 g, 48%); mp¼126e127 ꢀC; 1H NMR
NMR (300 MHz, CDCl3):
d
¼1.31 (t, 3J¼7.5 Hz, 3H, CH2CH3), 3.17 (q,
3J¼7.5 Hz, 2H, CH2CH3), 3.89 (s, 3H, OCH3), 3.97 (s, 3H, OCH3), 4.07 (s,
2H, CH2), 6.97 (dd, 3J¼8.7 Hz, 4J¼2.5 Hz, 1H, ArH), 7.09 (d, 4J¼2.3 Hz,
1H, ArH), 7.88 (d, 3J¼8.7 Hz, 1H, ArH), 9.87 (s, 1H, OH); 19F NMR
(300 MHz, CDCl3):
d
¼2.52 (q, J¼2.2 Hz, 3H, ArCH3), 4.20 (s, 3H,
OCH3), 7.32 (ddd, 3J¼8.3 Hz, 3J¼7.1 Hz, 4J¼1.2 Hz, 1H, ArH), 7.50
(ddd, 3J¼8.3 Hz, 3J¼7.2 Hz, 4J¼1.2 Hz, 1H, ArH), 7.60 (d, 3J¼8.3 Hz,
1H, ArH), 8.22 (d, 3J¼8.3 Hz, 1H, ArH), 11.64 (s, 1H, OH); 19F NMR
(282 MHz, CDCl3):
d
¼ꢁ55.8 (CF3); 13C NMR (75 MHz, CDCl3):
¼12.4
d
(ArCH2CH3), 19.3 (ArCH2CH3), 37.1 (q, J¼4.1 Hz, CH2), 52.8 (OCH3),
55.5 (OCH3), 108.8 (C), 109.8 (CH), 113.7 (CH), 122.8 (q, 2J¼32.4 Hz,
CCF3), 124.4 (q, 1J¼274.1 Hz, CF3), 125.0 (CH), 129.9 (C), 132.3 (C),
133.4 (q, J¼2.5 Hz, C), 145.3 (C), 147.3 (C), 157.1 (COR), 160.2 (COR),
~
(282 MHz, CDCl3):
d
¼ꢁ55.7 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼12.6 (q, J¼3.1 Hz, ArCH3), 52.5 (OCH3), 107.5 (C), 111.9 (CH), 119.7
(q, 2J¼31.9 Hz, CCF3), 121.4 (C), 122.3 (C), 122.8 (CH), 123.5 (q,
1J¼276.0 Hz, CF3),124.7 (CH),126.5 (q, J¼2.0 Hz, C),128.1 (CH),145.9
170.8 (CO); IR (ATR, cmꢁ1):
n
¼3075 (w), 3039 (w), 3007 (w), 2955
(C), 156.8 (C), 157.3 (COH), 170.7 (CO); IR (ATR, cmꢁ1):
n
¼2959 (w),
~
(w), 2933 (w), 2873 (w), 2845 (w), 1670 (m), 1619 (w), 1595 (w),
1492 (w),1467 (w),1436 (w),1402 (w),1372 (m),1342 (m),1305 (m),
1272 (m), 1263 (m), 1241 (m), 1214 (m), 1193 (w), 1161 (m), 1118 (s),
1068 (w), 1062 (w), 1039 (m), 1026 (m); MS (EI, 70 eV): m/z (%)¼366
(Mþ, 100), 319 (25), 306 (77), 291 (18); HRMS (EI, 70 eV): calcd for
C19H17F3O4 (Mþ): 366.10735, found 366.10708. Anal. Calcd for
C19H17F3O4 (366.33): C, 62.29; H, 4.68. Found: C, 62.46; H, 4.90.
1658 (m), 1626 (w), 1505 (w), 1471 (m), 1446 (m), 1406 (m), 1382
(m), 1356 (m), 1320 (m), 1291 (m), 1259 (m), 1235 (m), 1206 (m),
1186 (m), 1133 (s), 1105 (m), 1032 (m), 1016 (m); MS (EI, 70 eV): m/z
(%)¼324 (Mþ, 48), 292 (100), 264 (44), 236 (50), 217 (11); HRMS (EI,
70 eV): calcd for C16H11F3O4 (Mþ): 324.06039, found 324.06044.
4.3.19. Methyl 3-ethyl-2-hydroxy-4-(trifluoromethyl)dibenzo[b,d]fu-
rane-1-carboxylate (5s). Starting with silyl enol ether 3d (0.455 g,
1.50 mmol), 1,3-bis-silyl enol ether 4c (0.476 g, 1.65 mmol) and
TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5s was isolated
as a colourless solid (0.156 g, 31%); mp¼144e145 ꢀC; 1H NMR
4.3.16. Methyl 3-hydroxy-7-methoxy-4-n-propyl-1-(trifluoromethyl)-
9H-fluorene-2-carboxylate (5p). Starting with silyl enol ether 3c
(0.498 g, 1.51 mmol), 1,3-bis-silyl enol ether 4d (0.499 g, 1.65 mmol)
and TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), product 5p was
isolated as a pale yellow solid (0.249 g, 43%); mp¼98e99 ꢀC; 1H
(300 MHz, CDCl3):
d
¼1.28 (t, 3J¼7.4 Hz, 3H, CH2CH3), 3.01 (qq,
3J¼7.4 Hz, J¼1.5 Hz, 2H, CH2CH3), 4.21 (s, 3H, OCH3), 7.33 (ddd,
3J¼8.3 Hz, 3J¼7.2 Hz, 4J¼1.2 Hz, 1H, ArH), 7.50 (ddd, 3J¼8.4 Hz,
3J¼7.2 Hz, 4J¼1.3 Hz, 1H, ArH), 7.61 (d, 3J¼8.5 Hz, 1H, ArH), 8.24 (d,
3J¼8.3 Hz, 1H, ArH), 11.62 (s, 1H, OH); 19F NMR (282 MHz, CDCl3):
NMR (300 MHz, CDCl3):
d
¼1.12 (t, 3J¼7.4 Hz, 3H, CH2CH3), 1.63e1.79
(m, 2H, CH2CH3), 3.05e3.14 (m, 2H, ArCH2CH2), 3.88 (s, 3H, OCH3),
3.97 (s, 3H, OCH3), 4.02e4.06 (m, 2H, ArCH2Ar), 6.97 (dd, 3J¼8.7 Hz,
4J¼2.5 Hz, 1H, ArH), 7.08 (d, 4J¼2.4 Hz, 1H, ArH), 7.81 (d, 3J¼8.7 Hz,
d
¼ꢁ55.1 (CF3); 13C NMR (75 MHz, CDCl3):
¼14.1 (CH2CH3), 20.8 (q,
d
1H, ArH), 9.86 (s, 1H, OH); 19F NMR (282 MHz, CDCl3):
d¼ꢁ55.8
J¼2.7 Hz, ArCH2), 52.5 (OCH3), 107.8 (C), 111.9 (CH), 119.3 (q,

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3665
2J¼32.0 Hz, CCF3), 121.6 (C), 122.3 (C), 122.8 (CH), 123.6 (q,
J¼2.8 Hz, C), 115.7 (CH), 123.9 (q, 1J¼275.1 Hz, CF3), 124.7 (CH), 127.3
(CH), 127.5 (q, 2J¼30.4 Hz, CCF3), 127.9 (CH), 129.2 (CH), 130.5 (C),
132.4 (C),137.9 (C),140.6 (C),156.1 (COH),169.4 (CO); IR (ATR, cmꢁ1):
~
1J¼276.1 Hz, CF3), 124.7 (CH), 128.2 (CH), 132.6 (q, J¼1.9 Hz, C), 146.1
(C), 156.8 (C), 157.3 (COH), 170.8 (CO); IR (ATR, cmꢁ1):
~
n
¼3431 (w),
3142 (w), 3055 (w), 3012 (w), 2970 (w), 2960 (w), 2939 (w), 2878
(w), 1712 (w), 1667 (m), 1633 (w), 1621 (w), 1600 (w), 1582 (w),
1494 (w), 1455 (m), 1438 (m), 1397 (m), 1347 (m), 1273 (m), 1223
(m), 1202 (m), 1150 (m), 1138 (m), 1116 (s), 1075 (m), 1059 (m), 1035
(m), 1016 (m), 1001 (m); MS (EI, 70 eV): m/z (%)¼338 (Mþ, 53), 306
(100), 291 (19), 278 (75), 260 (25), 235 (17); HRMS (EI, 70 eV): calcd
for C17H13F3O4 (Mþ): 338.07604, found 338.07611. Anal. Calcd for
C17H13F3O4 (338.28): C, 60.36; H, 3.87. Found: C, 60.23; H, 3.87.
n
¼3318 (m), 3027 (w), 2964 (w), 2905 (w), 2855 (w), 1699 (m), 1605
(m),1573 (w),1491 (w),1439 (m),1425 (m),1327 (m),1309 (m),1280
(m), 1246 (m), 1217 (m), 1197 (m), 1186 (m), 1163 (m), 1145 (s), 1122
(s), 1042 (m), 1002 (m); MS (EI, 70 eV): m/z (%)¼322 (Mþ, 48), 290
(100), 262 (19), 215 (20), 165 (27); HRMS (EI, 70 eV): calcd for
C17H13F3O3 (Mþ): 322.08113, found 322.08123. Anal. Calcd for
C17H13F3O3 (322.28): C, 63.36; H, 4.07. Found: C, 63.13; H, 4.14.
4.3.23. Methyl 9-hydroxy-7-(trifluoromethyl)-6H-benzo[c]chromene-
10-carboxylate (5w). Starting with silyl enol ether 3f (0.622 g,
1.98 mmol), 1,3-bis-silyl enol ether 4a (0.573 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5w was iso-
lated as a colourless solid (0.112 g, 18%); mp¼115e117 ꢀC; 1H NMR
4.3.20. Methyl
2-hydroxy-3-n-propyl-4-(trifluoromethyl)dibenzo
[b,d]furane-1-carboxylate (5t). Starting with silyl enol ether 3d
(0.447 g, 1.48 mmol), 1,3-bis-silyl enol ether 4d (0.499 g,
1.65 mmol) and TiCl4 (0.18 mL, 1.65 mmol) in CH2Cl2 (3 mL), prod-
uct 5t was isolated as
a
colourless solid (0.265 g, 51%);
(250 MHz, CDCl3):
d¼3.75 (s, 3H, OCH3), 5.02e5.07 (m, 2H, CH2),
mp¼167e169 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼1.07 (t, 3J¼7.4 Hz,
6.97e7.19 (m, 3H, ArH), 7.23e7.36 (m, 2H, ArH), 9.31 (s, 1H, OH); 19F
3H, CH2CH3), 1.58e1.75 (m, 2H, CH2CH3), 2.89e2.99 (m, 2H, ArCH2),
4.21 (s, 3H, OCH3), 7.33 (ddd, 3J¼8.2 Hz, 3J¼7.1 Hz, 4J¼1.2 Hz, 1H,
ArH), 7.50 (ddd, 3J¼8.3 Hz, 3J¼7.1 Hz, 4J¼1.3 Hz, 1H, ArH), 7.61 (d,
3J¼8.2 Hz, 1H, ArH), 8.25 (d, 3J¼8.2 Hz, 1H, ArH), 11.63 (s, 1H, OH);
NMR (235 MHz, CDCl3):
d
¼ꢁ61.4 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼52.3 (OCH3), 65.4 (q, J¼3.7 Hz, CH2), 113.8 (q, 3J¼5.7 Hz, CH),
113.8 (C), 117.6 (CH), 121.6 (CH), 122.6 (C), 123.1 (q, 1J¼274.3 Hz, CF3),
125.7 (C), 128.2 (CH), 130.2 (q, 2J¼31.9 Hz, CCF3), 130.5 (CH), 133.7
19F NMR (282 MHz, CDCl3):
d
¼ꢁ55.1 (CF3); 13C NMR (75 MHz,
(C), 156.0 (C), 158.4 (COH), 170.4 (CO); IR (ATR, cmꢁ1):
n
¼3235 (w),
~
CDCl3):
d
¼14.5 (CH2CH3), 23.2 (CH2CH3), 29.4 (q, J¼2.6 Hz, ArCH2),
3080 (w), 3034 (w), 2958 (w), 2923 (w), 2896 (w), 2855 (w), 1677
(m), 1606 (m), 1581 (m), 1494 (m), 1472 (m), 1441 (m), 1428 (m),
1386 (w), 1351 (m), 1309 (m), 1277 (m), 1235 (m), 1209 (m), 1177
(m), 1158 (m), 1152 (m), 1124 (s), 1112 (s), 1101 (s), 1040 (m), 1027
(m), 1010 (m); MS (EI, 70 eV): m/z (%)¼324 (Mþ, 48), 292 (100), 264
(18), 236 (15); HRMS (EI, 70 eV): calcd for C16H11F3O4 (Mþ):
324.06039, found 324.06009. Anal. Calcd for C16H11F3O4 (324.25):
C, 59.27; H, 3.42. Found: C, 59.37; H, 3.83.
52.5 (OCH3), 107.7 (C), 111.9 (CH), 119.4 (q, 2J¼31.9 Hz, CCF3), 121.6
(C), 122.4 (C), 122.8 (CH), 123.6 (q, 1J¼276.2 Hz, CF3), 124.7 (CH),
128.1 (CH), 131.4 (q, J¼1.8 Hz, C), 146.1 (C), 156.8 (C), 157.5 (COH),
~
170.8 (CO); IR (ATR, cmꢁ1):
n
¼3052 (w), 3015 (w), 2961 (w), 2933
(w), 2875 (w), 1667 (m), 1621 (w), 1599 (w), 1582 (w), 1489 (w),
1469 (m), 1450 (m), 1440 (m), 1396 (m), 1347 (m), 1320 (m), 1272
(m), 1231 (m), 1213 (m), 1201 (m), 1150 (m), 1134 (m), 1117 (s), 1106
(s), 1084 (s), 1038 (m); MS (EI, 70 eV): m/z (%)¼352 (Mþ, 75), 320
(98), 291 (100), 251 (44), 235 (41), 206 (15); HRMS (EI, 70 eV): calcd
for C18H15F3O4 (Mþ): 352.09170, found 352.09202. Anal. Calcd for
C18H15F3O4 (352.31): C, 61.37; H, 4.29. Found: C, 61.30; H, 3.89.
4.3.24. Methyl 9-hydroxy-7-(trifluoromethyl)-6H-benzo[c]chromene-
8-carboxylate (5x). Starting with silyl enol ether 3f (0.622 g,
1.98 mmol), 1,3-bis-silyl enol ether 4a (0.573 g, 2.20 mmol) and
TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5x was iso-
lated as a pale yellow solid (0.309 g, 48%); mp¼152e153 ꢀC; 1H
4.3.21. Methyl 3-hydroxy-1-(trifluoromethyl)-9,10-dihydrophenan-
threne-4-carboxylate (5u). Starting with silyl enol ether 3e
(0.606 g, 1.93 mmol), 1,3-bis-silyl enol ether 4a (0.573 g,
2.20 mmol) and TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL),
product 5u was isolated as a pale yellow solid (0.097 g, 16%);
NMR (250 MHz, CDCl3):
d
¼3.97 (s, 3H, OCH3), 5.17 (q, J¼1.8 Hz, 2H,
CH2), 6.93e7.16 (m, 2H, ArH), 7.28e7.38 (m, 1H, ArH), 7.48 (s, 1H,
ArH), 7.69 (dd, 3J¼7.8 Hz, 4J¼1.5 Hz, 1H, ArH), 9.04 (s, 1H, OH); 19F
NMR (235 MHz, CDCl3):
d
¼ꢁ54.2 (CF3); 13C NMR (75 MHz, CDCl3):
mp¼102e103 ꢀC; 1H NMR (250 MHz, CDCl3):
d¼2.83 (s, 4H, CH2),
d
¼53.1 (OCH3), 65.5 (q, J¼6.6 Hz, CH2), 113.0 (q, 3J¼2.8 Hz, C), 114.0
3.68 (s, 3H, OCH3), 7.06e7.11 (m, 1H, ArH), 7.19e7.33 (m, 4H, ArH),
(CH), 117.5 (CH), 121.0 (C), 122.7 (CH), 123.5 (q, 1J¼275.8 Hz, CF3),
9.28 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
NMR (75 MHz, CDCl3):
d
¼ꢁ61.5 (CF3); 13C
124.1 (CH), 124.6 (C), 126.4 (q, 2J¼32.0 Hz, CCF3), 131.4 (CH), 136.3
~
d
¼24.8 (q, J¼2.3 Hz, CH2), 28.6 (CH2), 52.1
(C), 155.3 (C), 157.7 (COH), 169.0 (CO); IR (ATR, cmꢁ1):
n
¼3307 (w),
(OCH3), 113.9 (q, J¼6.0 Hz, CH), 114.7 (C), 125.9 (CH), 127.3 (CH),
128.3 (CH), 128.7 (CH), 129.5 (C), 132.3 (q, 2J¼30.3 Hz, CCF3), 133.2
(C), 138.2 (C), 138.7 (C), 157.4 (COH), 171.2 (CO); IR (ATR, cmꢁ1):
~
3069 (w), 3024 (w), 2962 (w), 2923 (w), 2851 (w), 1698 (m), 1607
(m), 1503 (w), 1483 (m), 1462 (m), 1443 (m), 1423 (m), 1385 (w),
1367 (m), 1332 (m), 1306 (m), 1275 (m), 1260 (m), 1223 (m), 1188
(m), 1150 (m), 1127 (s), 1116 (m), 1045 (m), 1002 (m); MS (EI, 70 eV):
m/z (%)¼324 (Mþ, 100), 292 (83), 263 (26), 236 (20), 223 (36);
HRMS (EI, 70 eV): calcd for C16H11F3O4 (Mþ): 324.06039, found
324.05948. Anal. Calcd for C16H11F3O4 (324.25): C, 59.27; H, 3.42.
Found: C, 58.94; H, 3.64.
n
¼3334 (w), 3064 (w), 3032 (w), 3016 (w), 2955 (w), 2907 (w),
2853 (w), 1733 (m), 1609 (w), 1595 (w), 1574 (w), 1502 (w), 1456
(w), 1435 (m), 1412 (m), 1359 (m), 1334 (m), 1275 (m), 1264 (m),
1239 (m), 1219 (m), 1204 (m), 1193 (m), 1172 (m), 1146 (s), 1108 (s),
1093 (s), 1043 (m); MS (EI, 70 eV): m/z (%)¼322 (Mþ, 32), 290 (100),
262 (13), 233 (14), 165 (26); HRMS (EI, 70 eV): calcd for C17H13F3O3
(Mþ): 322.08113, found 322.08111.
4.3.25. Methyl 10-ethyl-9-hydroxy-7-(trifluoromethyl)-6H-benzo[c]
chromene-8-carboxylate (5y). Starting with silyl enol ether 3f
(0.620 g,1.97 mmol),1,3-bis-silyl enol ether 4c (0.635 g, 2.20 mmol)
and TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5y was
isolated as a yellow solid (0.363 g, 53%); mp¼102e103 ꢀC; 1H NMR
4.3.22. Methyl 3-hydroxy-1-(trifluoromethyl)-9,10-dihydrophenan-
threne-2-carboxylate (5v). Starting with silyl enol ether 3e
(0.606 g,1.93 mmol),1,3-bis-silyl enol ether 4a (0.573 g, 2.20 mmol)
and TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL), product 5v was
isolated as a colourless solid (0.196 g, 32%); mp¼134e135 ꢀC; 1H
(250 MHz, CDCl3):
d
¼1.46 (t, 3J¼7.4 Hz, 3H, CH2CH3), 2.97 (q,
3J¼7.4 Hz, 2H, CH2CH3), 3.97(s, 3H, OCH3), 5.01(q, J¼1.7 Hz, 2H, CH2),
7.06e7.18 (m, 2H, ArH), 7.35 (ddd, 3J¼7.7 Hz, 3J¼7.7 Hz, 4J¼1.5 Hz,1H,
ArH), 7.72 (dd, 3J¼7.7 Hz, 4J¼1.2 Hz, 1H, ArH), 9.24 (s, 1H, OH); 19F
NMR (250 MHz, CDCl3):
d
¼2.78e2.85 (m, 2H, CH2), 2.94e3.02 (m,
2H, CH2), 3.97 (s, 3H, OCH3), 7.24e7.29 (m, 1H, ArH), 7.30e7.37 (m,
2H, ArH), 7.55 (s, 1H, ArH), 7.68e7.73 (m, 1H, ArH), 8.62 (s, 1H, OH);
NMR (235 MHz, CDCl3):
d
¼ꢁ53.8 (CF3); 13C NMR (75 MHz, CDCl3):
19F NMR (235 MHz, CDCl3):
d
¼ꢁ54.6 (CF3); 13C NMR (75 MHz,
d
¼13.8 (ArCH2CH3), 21.6 (ArCH2CH3), 53.1 (OCH3), 66.9 (q, J¼6.3 Hz,
CDCl3):
d
¼26.0 (q, J¼3.7 Hz, CH2), 28.4 (CH2), 53.0 (OCH3), 113.0 (q,
CH2),111.9 (q, 3J¼2.6 Hz, C),117.5 (CH),122.0 (CH),122.8 (C),123.2 (q,

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3666
2J¼31.9 Hz, CCF3), 123.9 (q, 1J¼275.0 Hz, CF3), 127.9 (C), 128.0 (CH),
d
¼36.9 (q, 4J¼2.6 Hz, CH2), 53.4 (OCH3), 55.6 (OCH3), 110.1 (CH),
130.4 (CH), 132.7 (C), 134.7 (C), 156.6 (C), 157.4 (COH), 169.8 (CO); IR
114.3 (CH), 114.6 (CH), 121.9 (CH), 122.6 (C), 125.7 (q, 2J¼33.5 Hz,
CCF3), 130.8 (C), 140.6 (q, 3J¼2.0 Hz, C), 145.8 (C), 145.9 (C), 146.7 (C),
161.4 (C), 164.1 (CO).
(ATR, cmꢁ1):
n
¼3270 (w), 3043 (w), 3009 (w), 2961 (w), 2930 (w),
~
2871 (w),1934 (w),1688 (m),1592 (m),1489 (w),1438 (m),1410 (m),
1339 (m), 1280 (m), 1267 (m), 1236 (s), 1201 (m), 1165 (m), 1125 (s),
1112 (s), 1061 (m), 1041 (m), 1027 (m), 1001 (m); MS (EI, 70 eV): m/z
(%)¼352 (Mþ, 84), 319 (15), 292 (100), 249 (10); HRMS (EI, 70 eV):
calcd for C18H15F3O4 (Mþ): 352.09170, found 352.09095. Anal. Calcd
for C18H15F3O4 (352.31): C, 61.37; H, 4.29. Found: C, 60.90; H, 4.43.
4.4.3. Methyl 4-(trifluoromethyl)-2-(trifluoromethanesulfonyloxy)-
dibenzo[b,d]furan-1-carboxylate (6c). Starting with benzoate 5q
(0.161 g, 0.52 mmol), pyridine (0.082 g, 1.04 mmol) and tri-
fluoromethanesulfonic anhydride (0.176 g, 0.62 mmol) in CH2Cl2
(5 mL), the product 6c was isolated as a colourless solid (0.211 g,
4.3.26. Methyl 9-hydroxy-10-n-propyl-7-(trifluoromethyl)-6H-benzo
[c]chromene-8-carboxylate (5z). Starting with silyl enol ether 3f
(0.633 g, 2.01 mmol), 1,3-bis-silyl enol ether 4d (0.666 g,
2.20 mmol) and TiCl4 (0.24 mL, 2.20 mmol) in CH2Cl2 (4 mL),
product 5z was isolated as a brownish solid (0.371 g, 51%);
92%); 1H NMR (250 MHz, CDCl3):
d¼4.16 (s, 3H, OCH3), 7.39e7.48
(m, 1H, ArH), 7.58e7.73 (m, 3H, ArH), 8.18 (d, 3J¼8.0 Hz, 1H, ArH);
19F NMR (282 MHz, CDCl3):
d
¼ꢁ73.2 (CF3), ꢁ61.7 (CF3); 13C NMR
(75 MHz, CDCl3):
d
¼53.3 (OCH3), 112.3 (CH), 116.5 (C), 117.6 (q,
2J¼36.0 Hz, CCF3), 117.7 (q, 3J¼4.7 Hz, CH), 120.9 (C), 121.7 (q,
1J¼273.1 Hz, CF3), 124.2 (CH), 124.2 (CH), 126.7 (C), 130.4 (CH), 141.7
(C), 150.9 (C), 157.8 (C), 163.3 (CO).
mp¼112e113 ꢀC; 1H NMR (250 MHz, CDCl3):
d
¼1.12 (t, 3J¼6.3 Hz,
3H, CH2CH3), 1.76e1.95 (m, 2H, CH2CH3), 2.79e2.93 (m, 2H, ArCH2),
3.97 (s, 3H, OCH3), 5.01 (q, J¼1.6 Hz, 2H, CH2), 7.07e7.18 (m, 2H,
ArH), 7.35 (ddd, 3J¼7.7 Hz, 3J¼7.7 Hz, 4J¼1.5 Hz, 1H, ArH), 7.64 (dd,
3J¼7.8 Hz, 4J¼1.4 Hz, 1H, ArH), 9.24 (s, 1H, OH); 19F NMR (235 MHz,
4.4.4. Methyl 10-ethyl-7-(trifluoromethyl)-9-(trifluoromethanesul-
fonyloxy)-6H-benzo[c]chromene-8-carboxylate (6d). Starting with
benzoate 5y (0.137 g, 0.391 mmol), pyridine (0.063 g, 0.8 mmol)
and trifluoromethanesulfonic anhydride (0.135 g, 0.48 mmol) in
CH2Cl2 (4 mL), product 6d was isolated as a colourless solid (0.185 g,
CDCl3):
d
¼ꢁ53.7 (CF3); 13C NMR (75 MHz, CDCl3):
¼14.3 (CH2CH3),
d
22.5 (CH2CH3), 30.4 (ArCH2), 53.1 (OCH3), 66.8 (q, J¼6.3 Hz, CH2),
111.9 (q, 3J¼2.5 Hz, C), 117.5 (CH), 121.9 (CH), 122.8 (C), 123.2 (q,
2J¼31.8 Hz, CCF3), 123.8 (q, 1J¼275.3 Hz, CF3), 128.0 (CH), 130.4 (CH),
131.7 (C), 134.8 (C), 136.6 (C), 156.6 (C), 157.4 (COH), 169.8 (CO); IR
~
98%); 1H NMR (300 MHz, CDCl3):
d
¼1.35 (t, 3J¼7.5 Hz, 3H, CH2CH3),
3.15 (q, 3J¼7.5 Hz, 2H, CH2CH3), 3.96 (s, 3H, OCH3), 5.07 (q, J¼1.4 Hz,
(ATR, cmꢁ1):
n
¼3291 (w), 3042 (w), 3011 (w), 2963 (w), 2928 (w),
2H, ArCH2), 7.13e7.20 (m, 2H, ArH), 7.36e7.43 (m, 1H, ArH),
2866 (w), 1936 (w), 1693 (m), 1593 (m), 1558 (w), 1490 (m), 1473
(m), 1451 (m), 1438 (m), 1412 (m), 1347 (m), 1327 (m), 1299 (m),
1233 (m), 1201 (m), 1125 (s), 1113 (s), 1040 (m), 1015 (m); MS (EI,
70 eV): m/z (%)¼366 (Mþ, 56), 333 (8), 317 (7), 306 (100), 291 (14);
HRMS (EI, 70 eV): calcd for C19H17F3O4 (Mþ): 366.10735, found
366.10679. Anal. Calcd for C19H17F3O4 (366.33): C, 62.29; H, 4.68.
Found: C, 61.77; H, 4.82.
7.61e7.66 (m, 1H, ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ55.7 (CF3),
ꢁ73.0 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼13.8 (CH2CH3), 22.0
(CH2CH3), 53.4 (OCH3), 66.3 (q, J¼5.6 Hz, ArCH2), 117.8 (CH), 121.9
(C), 122.6 (CH), 123.2 (q, 2J¼32.3 Hz, CCF3), 126.2 (C), 127.5 (CH),
131.1 (CH), 135.1 (C), 136.3 (C), 138.9 (C), 144.0 (C), 156.9 (C), 163.7
(CO).
4.4.5. Methyl 10-n-propyl-7-(trifluoromethyl)-9-(trifluoromethane-
sulfonyloxy)-6H-benzo[c]chromene-8-carboxylate (6e). Starting with
benzoate 5z (0.073 g, 0.199 mmol), pyridine (0.032 g, 0.4 mmol) and
trifluoromethanesulfonic anhydride (0.068 g, 0.24 mmol) in CH2Cl2
(2 mL), product 6e was isolated as a colourless solid (0.094 g, 95%);
4.4. General procedure for the synthesis of triflates 6aee
To a stirred solution of benzoate (1.0 equiv) in CH2Cl2 (10 mL per
1.0 mmol of benzoate) pyridine (2.0 equiv) was added at ꢁ78 ꢀC
and the reaction mixture was stirred for 10 min followed by addi-
tion of trifluoromethanesulfonic anhydride (1.2 equiv). The tem-
perature of the reaction mixture was allowed to rise to 0 ꢀC over
a period of 4 h. The solvent was removed in vacuo and the residue
was purified by column chromatography (silica gel, CH2Cl2).
1H NMR (250 MHz, CDCl3):
d
¼1.03 (t, 3J¼7.3 Hz, 3H, CH2CH3),
1.61e1.80 (m, 2H, CH2), 3.01e3.13 (m, 2H, CH2), 3.95 (s, 3H, OCH3),
5.06 (q, J¼1.4 Hz, 2H, ArCH2), 7.12e7.21 (m, 2H, ArH), 7.34e7.44 (m,
1H, ArH), 7.55e7.62 (m, 1H, ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ55.7 (CF3), ꢁ73.0 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼13.8
(CH2CH3), 22.8 (CH2), 30.6 (CH2), 53.4 (OCH3), 66.3 (q, J¼5.6 Hz,
ArCH2), 117.8 (CH), 122.0 (C), 122.5 (CH), 123.1 (q, 2J¼32.3 Hz, CCF3),
126.1 (C), 127.4 (CH), 131.1 (CH), 135.2 (C), 136.2 (C), 137.7 (C), 144.0
(C), 156.9 (C), 163.7 (CO).
4.4.1. Methyl 1-(trifluoromethyl)-3-(trifluoromethanesulfonyloxy)-
9H-fluorene-2-carboxylate (6a). Starting with benzoate 5a (0.094 g,
0.305 mmol),
pyridine
(0.047 g,
0.6 mmol)
and
tri-
fluoromethanesulfonic anhydride (0.102 g, 0.36 mmol) in CH2Cl2
(3 mL), product 6a was isolated as a colourless solid (0.125 g, 95%);
4.5. General procedure for the synthesis of compounds 7aeg
1H NMR (300 MHz, CDCl3):
d
¼4.00 (s, 3H, OCH3), 4.15 (s, 2H, CH2),
7.43e7.50 (m, 2H, ArH), 7.59e7.63 (m, 1H, ArH), 7.80e7.84 (m, 1H,
A stirred solution of triflates 6aee (1.0 equiv), boronic acid
(1.3 equiv), potassium phosphate (1.6 equiv) and tetrakis(-
triphenylphosphine)palladium(0) (0.03 equiv) in dioxane (1 mL),
was heated to 90 ꢀC for 5 h. The reaction mixture was cooled to
20 ꢀC and worked up with a saturated solution of ammonium
chloride (5 mL). The organic layer was separated and extracted with
diethylether (3ꢂ10 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-
heptane/EtOAc 20:1).
ArH), 7.86 (s, 1H, ArH); 19F NMR (282 MHz, CDCl3):
d¼ꢁ58.7 (CF3),
ꢁ73.6 (CF3); 13C NMR (75 MHz, CDCl3):
¼36.9 (CH2), 53.4 (OCH3),
d
115.7 (CH), 120.9 (CH), 123.9 (C), 125.2 (CH), 126.0 (q, 2J¼33.4 Hz,
CCF3), 127.6 (CH), 129.6 (CH), 137.9 (C), 141.2 (C), 143.6 (C), 145.7 (C),
146.6 (C), 164.0 (CO).
4.4.2. Methyl 7-methoxy-1-(trifluoromethyl)-3-(trifluoromethanesul-
fonyloxy)-9H-fluorene-2-carboxylate (6b). Starting with benzoate
5m (0.196 g, 0.579 mmol), pyridine (0.092 g, 1.16 mmol) and tri-
fluoromethanesulfonic anhydride (0.197 g, 0.7 mmol) in CH2Cl2
(6 mL), product 6b was isolated as a colourless solid (0.266 g, 98%);
4.5.1. Methyl 3-phenyl-1-(trifluoromethyl)-9H-fluorene-2-
carboxylate (7a). Starting with triflate 6a (0.108 g, 0.252 mmol),
phenylboronic acid (0.040 g, 0.33 mmol), potassium phosphate
(0.086 g, 0.40 mmol) and tetrakis(triphenylphosphine)palla-
dium(0) (0.009 g, 0.008 mmol) in dioxane (1 mL), product 7a was
1H NMR (300 MHz, CDCl3):
d
¼3.89 (s, 3H, OCH3), 3.98 (s, 3H, OCH3),
4.08 (s, 2H, CH2), 6.99 (dd, 3J¼8.5 Hz, 4J¼2.4 Hz, 1H, ArH), 7.11 (d,
4J¼2.3 Hz, 1H, ArH), 7.67e7.73 (m, 2H, ArH); 19F NMR (282 MHz,
CDCl3):
d
¼ꢁ73.6 (CF3), ꢁ58.7 (CF3); 13C NMR (75 MHz, CDCl3):

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3667
isolated as a colourless solid (0.061 g, 68%); mp¼124 ꢀC; 1H NMR
(0.068 g, 0.32 mmol) and tetrakis(triphenylphosphine)palla-
dium(0) (0.007 g, 0.006 mmol) in dioxane (1 mL), product 7d was
isolated as a colourless solid (0.068 g, 90%); mp¼101 ꢀC; 1H NMR
(300 MHz, CDCl3):
d
¼3.65 (s, 3H, OCH3), 4.18 (s, 2H, CH2),
7.39e7.47 (m, 7H, ArH), 7.58e7.64 (m, 1H, ArH), 7.78e7.83 (m, 1H,
ArH), 7.92 (s, 1H, ArH); 19F NMR (282 MHz, CDCl3):
¼ꢁ57.9 (CF3);
13C NMR (75 MHz, CDCl3):
d
(300 MHz, CDCl3):
d
¼3.76 (s, 3H, OCH3), 7.37e7.51 (m, 6H, ArH),
d
¼37.1 (q, J¼2.6 Hz, CH2), 52.4 (OCH3),
7.54e7.62 (m, 1H, ArH), 7.67e7.68 (m, 2H, ArH), 7.98 (d, 3J¼8.0 Hz,
120.4 (CH), 124.1 (q, 1J¼271.7 Hz, CF3), 124.1 (q, 2J¼32.2 Hz, CCF3),
124.4 (CH), 125.0 (CH), 127.2 (CH), 128.0 (CH), 128.3 (CH), 128.4
(CH), 128.7 (CH), 129.7 (q, J¼2.6 Hz, C), 139.1 (C), 139.5 (C), 140.2 (q,
J¼2.2 Hz, C), 140.4 (C), 143.5 (C), 144.2 (C), 168.4 (CO); IR (ATR,
~
1H, ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ61.2 (CF3); 13C NMR
(75 MHz, CDCl3):
d
¼52.5 (OCH3), 112.2 (CH), 116.0 (q, 2J¼34.5 Hz,
CCF3), 121.4 (C), 122.6 (CH), 122.8 (q, 1J¼271.4 Hz, CF3), 123.7 (CH),
124.0 (C), 125.7 (q, 3J¼4.4 Hz, CH), 127.9 (CH), 128.5 (CH), 128.6 (CH),
129.0 (CH), 129.2 (C), 135.5 (C), 139.3 (C), 151.4 (C), 157.1 (C), 168.1
~
cmꢁ1):
n
¼3031 (w), 3009 (w), 2948 (w), 2852 (w), 1723 (s), 1614
(w), 1498 (w), 1479 (w), 1451 (w), 1431 (m), 1403 (m), 1365 (m),
1297 (m), 1284 (m), 1263 (m), 1218 (m), 1204 (m), 1187 (m), 1171
(m), 1155 (m), 1142 (m), 1117 (s), 1041 (m), 1024 (m); MS (EI,
70 eV): m/z (%)¼368 (Mþ, 100), 337 (68), 317 (14), 309 (57), 288
(19), 239 (31); HRMS (EI, 70 eV): calcd for C22H15F3O2 (Mþ):
368.10187, found 368.10217.
(CO); IR (ATR, cmꢁ1):
n
¼3084 (w), 3037 (w), 2996 (w), 2945 (w),
2927 (w), 2854 (w), 1725 (m), 1599 (w), 1485 (m), 1475 (m), 1451
(w), 1430 (m), 1405 (m), 1359 (m), 1324 (m), 1308 (m), 1288 (m),
1270 (m), 1243 (m), 1212 (m), 1189 (m), 1157 (m), 1145 (m), 1116 (s),
1106 (s), 1075 (m), 1042 (m), 1026 (m), 1014 (m); MS (EI, 70 eV): m/z
(%)¼370 (Mþ, 100), 339 (82), 291 (26), 242 (16); HRMS (EI, 70 eV):
calcd for C21H13F3O3 (Mþ): 370.08113, found 370.08086.
4.5.2. Methyl
3-(4-tolyl)-7-methoxy-1-(trifluoromethyl)-9H-fluo-
rene-2-carboxylate (7b). Starting with triflate 6b (0.071 g,
0.151 mmol), 4-tolylboronic acid (0.027 g, 0.20 mmol), potassium
phosphate (0.051 g, 0.24 mmol) and tetrakis(triphenylphosphine)
palladium(0) (0.006 g, 0.005 mmol) in dioxane (1 mL), product 7b
was isolated as a colourless solid (0.053 g, 85%); mp¼118e120 ꢀC;
4.5.5. Methyl 2-(4-tolyl)-4-(trifluoromethyl)dibenzo[b,d]furane-1-
carboxylate (7e). Starting with triflate 6c (0.089 g, 0.200 mmol),
4-tolylboronic acid (0.035 g, 0.26 mmol), potassium phosphate
(0.068 g, 0.32 mmol) and tetrakis(triphenylphosphine)palla-
dium(0) (0.007 g, 0.006 mmol) in dioxane (1 mL), product 7e was
isolated as a colourless solid (0.076 g, 99%); mp¼108e109 ꢀC; 1H
1H NMR (300 MHz, CDCl3):
d
¼2.42 (s, 3H, CH3), 3.66 (s, 3H, OCH3),
3.88 (s, 3H, OCH3), 4.12 (s, 2H, CH2), 6.96 (dd, 3J¼8.5 Hz, 4J¼2.4 Hz,
1H, ArH), 7.13 (d, 4J¼2.0 Hz, 1H, ArH), 7.24 (d, 3J¼8.0 Hz, 2H, ArH),
7.32 (d, 3J¼8.1 Hz, 2H, ArH), 7.67 (d, 3J¼8.5 Hz, 1H, ArH), 7.77 (s, 1H,
NMR (300 MHz, CDCl3):
d
¼2.43 (s, 3H, ArCH3), 3.80 (s, 3H, OCH3),
7.24e7.30 (m, 2H, ArH), 7.31e7.37 (m, 2H, ArH), 7.37e7.43 (m, 1H,
ArH), 7.57 (ddd, 3J¼8.4 Hz, 3J¼7.3 Hz, 4J¼1.3 Hz, 1H, ArH), 7.70 (d,
ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ57.9 (CF3); 13C NMR (75 MHz,
3J¼8.3 Hz,1H, ArH), 7.74 (s,1H, ArH), 7.97 (d, 3J¼8.0 Hz,1H, ArH); 19
F
CDCl3):
d
¼21.2 (CH3), 37.1 (q, J¼2.6 Hz, CH2), 52.4 (OCH3), 55.5
NMR (282 MHz, CDCl3):
d
¼ꢁ61.2 (CF3); 13C NMR (75 MHz, CDCl3):
(OCH3), 110.1 (CH), 113.7 (CH), 121.2 (CH), 123.5 (CH), 123.9 (q,
2J¼31.8 Hz, CCF3), 124.1 (q, 1J¼274.9 Hz, CF3), 128.4 (C), 128.5 (CH),
129.0 (CH),132.1 (C), 136.8 (C), 137.7 (C), 139.5 (q, J¼2.6 Hz, C), 140.5
~
d
¼21.2 (ArCH3), 52.6 (OCH3), 112.2 (CH), 116.0 (q, 2J¼34.4 Hz, CCF3),
121.5 (C), 122.5 (CH), 122.8 (q, 1J¼272.2 Hz, CF3), 123.7 (CH), 123.9
(C), 125.7 (q, 3J¼4.4 Hz, CH), 128.4 (CH), 128.9 (CH), 129.4 (C), 129.1
(CH), 135.4 (C), 136.4 (C), 137.8 (C), 151.2 (q, J¼1.8 Hz, C), 157.1 (C),
~
(C),144.2 (C),145.5 (C),160.5 (C),168.6 (CO); IR (ATR, cmꢁ1):
n
¼3000
(w), 2949 (w), 2923 (w), 2837 (w),1733 (m),1713 (m),1610 (m),1584
(w),1557 (w),1518 (w),1489 (m),1449 (m),1426 (m),1401 (m),1363
(m),1311 (m),1298 (m),1285 (m),1259 (m),1208 (m),1173 (m),1150
(s), 1117 (s), 1042 (m), 1024 (m); MS (EI, 70 eV): m/z (%)¼412 (Mþ,
100), 381 (40), 353 (18); HRMS (ESI-TOF/MS): calcd for C24H18F3O3
((MꢁH)ꢁ): 411.1214, found 411.1221.
168.2 (CO); IR (ATR, cmꢁ1):
n
¼3077 (w), 2959 (w), 2917 (w), 2851
(w), 2748 (w), 2529 (w), 1730 (m), 1658 (m), 1583 (m), 1467 (w),
1423 (m), 1380 (w), 1356 (m), 1277 (m), 1243 (s), 1212 (s), 1166 (s),
1152 (s), 1115 (m), 1071 (m); MS (EI, 70 eV): m/z (%)¼384 (Mþ, 100),
353 (67), 255 (13); HRMS (EI, 70 eV): calcd for C22H15F3O3 (Mþ):
384.09678, found 384.09696.
4.5.3. Methyl
3-(4-chlorophenyl)-7-methoxy-1-(trifluoromethyl)-
4.5.6. Methyl 10-ethyl-9-(4-tolyl)-7-(trifluoromethyl)-6H-benzo[c]
chromene-8-carboxylate (7f). Starting with triflate 6d (0.075 g,
0.155 mmol), 4-tolylboronic acid (0.035 g, 0.26 mmol), potassium
phosphate (0.068 g, 0.32 mmol) and tetrakis(triphenylphosphine)
palladium(0) (0.007 g, 0.006 mmol) in dioxane (1 mL), product 7f
was isolated as a colourless solid (0.063 g, 95%); mp¼131e132 ꢀC;
9H-fluorene-2-carboxylate (7c). Starting with triflate 6b (0.071 g,
0.151 mmol), 4-chlorophenylboronic acid (0.031 g, 0.20 mmol),
potassium phosphate (0.051 g, 0.24 mmol) and tetrakis(-
triphenylphosphine)palladium(0) (0.006 g, 0.005 mmol) in di-
oxane (1 mL), product 7c was isolated as a colourless solid (0.046 g,
71%); mp¼134e136 ꢀC; 1H NMR (300 MHz, CDCl3):
d¼3.66 (s, 3H,
1H NMR (300 MHz, CDCl3):
d
¼1.02 (t, 3J¼7.4 Hz, 3H, CH2CH3), 2.41
OCH3), 3.88 (s, 3H, OCH3), 4.12 (s, 2H, CH2), 6.96 (dd, 3J¼8.5 Hz,
4J¼2.3 Hz, 1H, ArH), 7.13 (d, 4J¼2.0 Hz, 1H, ArH), 7.32e7.46 (m, 4H,
ArH), 7.68 (d, 3J¼8.5 Hz, 1H, ArH), 7.73 (s, 1H, ArH); 19F NMR
(s, 3H, OCH3), 2.80 (q, 3J¼7.4 Hz, 2H, CH2CH3), 3.45 (s, 3H, OCH3),
5.09e5.13 (m, 2H, ArCH2), 7.07e7.17 (m, 4H, ArH), 7.21 (d, 3J¼7.9 Hz,
2H, ArH), 7.29e7.37 (m, 1H, ArH), 7.75 (dd, 3J¼7.9 Hz, 4J¼1.4 Hz, 1H,
(282 MHz, CDCl3):
d
¼ꢁ57.9 (CF3); 13C NMR (75 MHz, CDCl3):
d
¼37.1
ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ55.3 (CF3); 13C NMR (75 MHz,
(q, J¼2.6 Hz, CH2), 52.5 (OCH3), 55.5 (OCH3), 110.1 (CH), 113.8 (CH),
121.3 (CH), 123.2 (CH), 124.0 (q, 1J¼274.9 Hz, CF3), 124.1 (q,
2J¼32.1 Hz, CCF3), 128.4 (q, J¼2.6 Hz, C), 128.5 (CH), 130.0 (CH), 131.9
(C), 134.2 (C), 138.1 (C), 139.2 (C), 140.1 (q, J¼2.2 Hz, C), 144.4 (C),
~
CDCl3):
d
¼15.2 (CH2CH3), 21.3 (CH3), 24.4 (CH2CH3), 52.1 (OCH3),
66.5 (q, J¼5.1 Hz, ArCH2), 117.5 (CH), 119.6 (q, 2J¼31.2 Hz, CCF3),
122.0 (CH), 123.1 (C), 123.8 (q, 1J¼275.4 Hz, CF3), 127.6 (CH), 128.4
(CH), 130.0 (CH), 130.0 (CH), 132.2 (C), 132.2 (C), 134.0 (C), 134.5 (C),
137.6 (C), 141.3 (C), 143.6 (C), 157.0 (C), 167.8 (CO); IR (ATR, cmꢁ1):
~
145.5 (C), 160.6 (C), 168.3 (CO); IR (ATR, cmꢁ1):
n
¼3003 (w), 2951
(w), 2836 (w), 1732 (m), 1609 (m), 1585 (w), 1556 (w), 1488 (m),
1449 (m), 1427 (m), 1395 (m), 1364 (m), 1311 (m), 1296 (m), 1287
(m), 1266 (m), 1210 (m), 1174 (m), 1151 (m), 1117 (s), 1088 (m), 1040
(m), 1020 (m); MS (EI, 70 eV): m/z (%)¼432 (Mþ, 100), 401 (24), 373
(13), 366 (14), 199 (12); HRMS (ESI-TOF/MS): calcd for C23H17ClF3O3
((MþH)þ): 433.0813, found 433.0808.
n
¼3033 (w), 2981 (w), 2942 (w), 2923 (w), 2876 (w), 2852 (w),1721
(m),1606 (w),1584 (w),1573 (w),1556 (w),1514 (w),1487 (w),1465
(m), 1446 (w), 1438 (w), 1421 (w), 1409 (w), 1378 (w), 1342 (m),
1331 (m), 1303 (m), 1271 (w), 1238 (m), 1207 (m), 1186 (m), 1173
(m), 1148 (m), 1117 (s), 1062 (m), 1040 (m), 1025 (m), 1015 (m); MS
(EI, 70 eV): m/z (%)¼426 (Mþ, 100), 397 (14), 391 (12); HRMS (EI,
70 eV): calcd for C25H21F3O3 (Mþ): 426.14373, found 426.14365.
4.5.4. Methyl 2-phenyl-4-(trifluoromethyl)dibenzo[b,d]furane-1-
carboxylate (7d). Starting with triflate 6c (0.090 g, 0.203 mmol),
phenylboronic acid (0.032 g, 0.26 mmol), potassium phosphate
4.5.7. Methyl 9-phenyl-10-n-propyl-7-(trifluoromethyl)-6H-benzo[c]
chromene-8-carboxylate (7g). Starting with triflate 6e (0.079 g,

€
S. Buttner et al. / Tetrahedron 68 (2012) 3654e3668
3668
9. Ding, W.; Pu, J.; Zhang, C. Synthesis 1992, 635.
0.158 mmol), phenylboronic acid (0.032 g, 0.26 mmol), potassium
phosphate (0.068 g, 0.32 mmol) and tetrakis(triphenylphosphine)
palladium(0) (0.007 g, 0.006 mmol) in dioxane (1 mL), product 7g
was isolated as a colourless solid (0.040 g, 59%); mp¼111e113 ꢀC;
10. For cyclocondensations, see: (a) Guan, H.-P.; Hu, C.-M. Synthesis 1996, 1363; (b)
Guan, H.-P.; Hu, C.-M. J. Fluorine Chem. 1996, 78, 101; (c) Guan, H.-P.; Hu, Q.-S.;
Hu, C.-M. Chin. J. Chem. 1996, 14, 87 For the metalation of (trifluoromethyl)
arenes and subsequent coupling with electrophiles, see: (d) Marzi, E.; Mongin,
F.; Spitaleri, A.; Schlosser, M. Eur. J. Org. Chem. 2001, 2911; (e) Dmowski, W.;
Piasecka-Maciejewska, K. J. Fluorine Chem. 1996, 78, 59 For DielseAlder re-
actions, see: (f) Abubakar, A. B.; Booth, B. L.; Suliman, N. N. E.; Tipping, A. E. J.
Fluorine Chem. 1992, 56, 359; (g) Barlow, M. G.; Suliman, N. N. E.; Tipping, A. E. J.
Fluorine Chem. 1995, 70, 59; (h) Volochnyuk, D. M.; Kostyuk, A. N.; Sibgatulin,
D. A.; Chernega, A. N.; Pinchuk, A. M.; Tolmachev, A. A. Tetrahedron 2004, 60,
2361; (i) Volochnyuk, D. M.; Kostyuk, A. N.; Sibgatulin, D. A.; Chernega, A. N.
Tetrahedron 2005, 61, 2839.
11. (a) Gambaryan, N. P.; Simonyan, L. A.; Petrovskii, P. V. Izv. Akad. Nauk. SSSR,
Ser. Khim. 1967, 918; (b) Hojo, M.; Masuda, R.; Kokuryo, Y.; Shioda, H.;
Matsuo, S. Chem. Lett. 1976, 499; (c) Hojo, M.; Masuda, R.; Sakaguchi, S.;
Takagawa, M. Synthesis 1986, 1016; (d) Colla, A.; Martins, M. A. P.; Clar, G.;
Krimmer, S.; Fischer, P. Synthesis 1991, 483; (e) Hojo, M.; Masuda, R.; Okada,
E. Synthesis 1989, 215 Reviews: (f) Nenaidenko, V. G.; Sanin, A. V.; Ba-
lenkova, E. S. Russ. Chem. Rev. 1999, 68, 437; (g) Billard, T. Chem.dEur. J.
2006, 12, 974; (h) Druzhinin, S. V.; Balenkova, E. S.; Nenajdenko, V. G. Tet-
rahedron 2007, 63, 7753.
1H NMR (300 MHz, CDCl3):
d
¼0.79 (t, 3J¼7.4 Hz, 3H, CH2CH3),
1.44e1.59 (m, 2H, CH2), 2.77e2.90 (m, 2H, CH2), 3.54 (s, 3H, OCH3),
5.20e5.25 (m, 2H, ArCH2), 7.19e7.29 (m, 2H, ArH), 7.34e7.41 (m, 2H,
ArH), 7.41e7.57 (m, 4H, ArH), 7.81 (dd, 3J¼7.9 Hz, 4J¼1.4 Hz, 1H,
ArH); 19F NMR (282 MHz, CDCl3):
d
¼ꢁ55.3 (CF3); 13C NMR (75 MHz,
CDCl3):
d
¼13.8 (CH2CH3), 23.7 (CH2), 33.4 (CH2), 52.1 (OCH3), 66.5
(q, J¼5.1 Hz, ArCH2), 117.5 (CH), 120.1 (q, 2J¼31.2 Hz, CCF3), 122.0
(CH), 123.2 (C), 123.7 (q, 1J¼275.3 Hz, CF3), 127.5 (CH), 127.7 (CH),
127.9 (CH), 130.0 (CH), 130.1 (CH), 131.9 (q, J¼3.0 Hz, C), 132.5 (C),
134.6 (C), 137.1 (C), 141.3 (C), 142.2 (C), 157.0 (C), 167.7 (CO); IR (ATR,
~
cmꢁ1):
n
¼3058 (w), 3029 (w), 2992 (w), 2963 (w), 2946 (w), 2928
(w), 2870 (w), 1731 (m), 1605 (w), 1583 (w), 1553 (w), 1488 (m),
1465 (m), 1440 (m), 1421 (w), 1407 (w), 1377 (w), 1341 (m), 1309
(m), 1278 (m), 1233 (m), 1206 (m), 1174 (s), 1151 (m), 1122 (s), 1088
(m), 1076 (m), 1045 (m), 1016 (m); MS (EI, 70 eV): m/z (%)¼426 (Mþ,
100), 377 (21), 314 (10); HRMS (ESI-TOF/MS): calcd for C25H22F3O3
((MþH)þ): 427.1516, found 427.1517.
12. Zanatta, N.; Barichello, R.; Bonacorso, H. G.; Martins, M. A. P. Synthesis 1999, 765.
13. For a review of 1,3-bis(silyl enol ethers) in general, see: Langer, P. Synthesis
2002, 441.
14. Mamat, C.; Pundt, T.; Schmidt, A.; Langer, P. Tetrahedron Lett. 2006, 47, 2183.
€
15. Buttner, S.; Riahi, A.; Hussain, I.; Yawer, M. A.; Lubbe, M.; Langer, P. Tetrahedron
2009, 65, 2124.
€
16. Hussain, I.; Riahi, A.; Yawer, M. A.; Gorls, H.; Langer, P. Org. Biomol. Chem. 2008,
References and notes
6, 3542.
€
17. Buttner, S.; Lubbe, M.; Reinke, H.; Fischer, C.; Langer, P. Tetrahedron 2008, 64,
7968.
1. (a) Fluorine in Bioorganic Chemistry; Filler, R., Kobayasi, Y., Yagupolskii, L. M., Eds.;
Elsevier: Amsterdam, 1993; (b) Filler, R. Fluorine Containing Drugs in Organo-
fluorine Chemicals and their Industrial Application; Pergamon: New York, NY,1979,
Chapter 6; (c) Hudlicky, M. Chemistry of Organic Compounds; Ellis Horwood:
Chichester, 1992; (d) Kirsch, P. Modern Fluoroorganic Chemistry; VCH: Weinheim,
2004; (e) Chambers, R. D. Fluorine in Organic Chemistry; Blackwell/CRC: 2004.
2. (a) Ryckmanns, T.; Balancon, L.; Berton, O.; Genicot, C.; Lamberty, Y.; Lallemand,
€
18. Mamat, C.; Pundt, T.; Dang, T. H. T.; Klassen, R.; Reinke, H.; Kockerling, M.;
Langer, P. Eur. J. Org. Chem. 2008, 492.
19. (a) Chan, T.-H.; Brownbridge, P. J. Am. Chem. Soc. 1980, 102, 3534; (b) Molander,
G. A.; Cameron, K. O. J. Am. Chem. Soc. 1993, 115, 830.
20. Nguyen, V. T. H.; Bellur, E.; Appel, B. Synthesis 2006, 2865.
21. Lexikon Naturstoffe; Steglich, W., Fugmann, B., Lang-Fugmann, S., Eds.; Thieme:
Stuttgart, 1997.
22. (a) Chui, C.-H.; Wong, RS.-M.; Gambari, R.; Cheng, GY.-M.; Yuen, M. C.-W.; Chan,
K.-W.; Tong, S.-W.; Lau, F.-Y.; Lai, P. B.-S.; Lam, K.-H.; Ho, C.-L.; Kan, C.-W.;
Leung, K. S.-Y.; Wong, W.-Y. Bioorg. Med. Chem. 2009, 17, 7872; (b) Misaki, K.;
Matsui, S.; Matsuda, T. Chem. Res. Toxicol. 2007, 20, 277.
ꢀ ꢀ
B.; Passau, P.; Pirlot, N.; Quere, L.; Talaga, P. Bioorg. Med. Chem. Lett. 2002, 12,
261; (b) Malamas, M. S.; Sredy, J.; Moxham, C.; Katz, A.; Xu, W.; McDevitt, R.;
Adebayo, F. O.; Sawicki, D. R.; Seestaller, L.; Sullivan, D.; Taylor, J. R. J. Med. Chem.
2000, 43, 1293; (c) Ciha, A. J.; Ruminski, P. G. J. Agric. Food Chem. 1991, 39, 2072.
3. (a) Albrecht, H. A.; Beskid, G.; Georgopapadakou, N. H.; Keith, D. D.; Konzel-
mann, F. M.; Pruess, D. L.; Rossman, P. L.; Wei, C. C.; Christenson, J. G. J. Med.
Chem. 1991, 34, 2857; (b) Albrecht, H. A.; Beskid, G.; Christenson, J. G.; Deitcher,
K. H.; Georgopapadakou, N. H.; Keith, D. D.; Konzelmann, F. M.; Pruess, D. L.;
Wie, C. C. J. Med. Chem. 1994, 37, 400; (c) Song, C. W.; Lee, K. Y.; Kim, C. D.;
Chang, T.-M.; Chey, W. Y. J. Pharmacol. Exp. Ther. 1997, 281, 1312; (d) De Voss, J. J.;
Sui, Z.; DeCamp, D. L.; Salto, R.; Babe, L. M.; Craik, C. S.; Ortiz de Montellano, P.
R. J. Med. Chem. 1994, 37, 665; (e) Anjaiah, S.; Chandrasekhar, S.; Gree, R. Adv.
Synth. Catal. 2004, 346, 1329; (f) Iorio, M. A.; Paszkowska, R. T.; Frigeni, V. J. Med.
Chem. 1987, 30, 1906.
23. Yang, H.; Chou, G.-X.; Wang, Z.-T.; Guo, Y.-W.; Hu, Z.-B.; Xu, L.-S. Helv. Chim. Acta
2004, 87, 394.
24. Wu, R.; Schumm, J. S.; Pearson, D. L.; Tour, J. M. J. Org. Chem. 1996, 61, 6906.
25. Belfield, K. D.; Schafer, K. J.; Mourad, W.; Reinhardt, B. A. J. Org. Chem. 2000, 65,
4475.
26. Epperson, J. R.; Bruce, M. A.; Catt, J. D.; Deskus, J. A.; Hodges, D. B.; Karageorge,
G. N.; Keavy, D. J.; Mahle, C. D.; Mattson, R. J.; Ortiz, A. A.; Parker, M. F.; Takaki,
K. S.; Watson, B. T.; Yevich, J. P. Bioorg. Med. Chem. 2004, 12, 4601.
27. (a) Knop, W. Justus Liebigs Ann. Chem. 1844, 49, 103; (b) Ingolfsdottir, K. Phy-
tochemistry 2002, 61, 729.
28. (a) Ames, D. E.; Opalko, A. Synthesis 1983, 234; (b) Xu, H.; Fan, L.-L. Chem.
Pharm. Bull. 2008, 56, 1496.
ꢀ
ꢀ
4. (a) Popp, J. L.; Musza, L. L.; Barrow, C. J.; Rudewicz, P. J.; Houck, D. R. J. Antibiot.
1994, 47, 411; (b) Chen, T. S.; Petuch, B.; MacConnell, J.; White, R.; Dezeny, G.
J. Antibiot. 1994, 47, 1290; (c) Lam, K. S.; Schroeder, D. R.; Veitch, J. M.; Colson, K. L.;
Matson, J. A.; Rose, W. C.; Doyle, T. W.; Forenza, S. J. Antibiot. 2001, 54, 1.
5. (a) Schmidbaur, H.; Kumberger, O. Chem. Ber. 1993, 126, 3; (b) Dinger, M. B.; Hen-
derson, W. J. Organomet. Chem. 1998, 560, 233; (c) Liedtke, J.; Loss, S.; Widauer, C.;
29. Ryu, J.-Y. Chemosphere 2008, 71, 1100.
30. Lin, Y.-L.; Wang, W.-Y.; Kuo, Y.-H.; Liu, Y.-H. Chem. Pharm. Bull. 2001, 49, 1098.
31. Kostecki, K.; Engelmeier, D.; Pacher, T.; Hofer, O.; Vajrodaya, S.; Greger, H.
Phytochemistry 2004, 65, 99.
32. (a) Saito, N.; Shiotani, K.; Kinbara, A.; Sato, Y. Chem. Commun. 2009, 4284; (b)
Jayanth, T. T.; Jeganmohan, M.; Cheng, C. H. J. Org. Chem. 2004, 69, 8445; (c)
Quintana, I.; Boersma, A. J.; Pena, D.; Perez, D.; Guitian, E. Org. Lett. 2006, 8,
3347.
33. Dellagreca, M.; Fiorentino, A.; Monaco, P.; Pinto, G.; Previtera, L.; Zarelli, A. J.
Chem. Ecol. 2001, 27, 257.
€
Grutzmacher, H. Tetrahedron 2000, 56, 143; (d) Schneider, S.; Tzschucke, C. C.;
Bannwarth, W. In Multiphase Homogeneous Catalysis; Cornils, B., Herrmann, W. A.,
Horvath, I. T., Leitner, W., Mecking, S., Olivier-Booubigou, H., Vogt, D., Eds.; Wiley
VCH: 2005; Chapter 4, p 346; (e) Clarke, D.; Ali, M. A.; Clifford, A. A.; Parratt, A.; Rose,
P.; Schwinn, D.; Bannwarth, W.; Rayner, C. M. Curr. Top. Med. Chem. 2004, 7, 729.
6. Reviews: (a) Wittkopp, A.; Schreiner, P. R. The Chemistry of Dienes and Polyenes;
John Wiley & Sons Ltd: 2000; Vol. 2; (b) Schreiner, P. R. Chem. Soc. Rev. 2003, 32,
289 See also: (c) Wittkopp, A.; Schreiner, P. R. Chem.dEur. J. 2003, 9, 407; (d)
Kleiner, C. M.; Schreiner, P. R. Chem. Commun. 2006, 4315; (e) Kotke, M.; Schreiner,
P. R. Synthesis 2007, 5, 779 Review: Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 1701.
7. Review: McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555.
~
ꢀ
ꢀ
34. Reim, S.; Lau, M.; Adeel, M.; Hussain, I.; Yawer, M. A.; Riahi, A.; Ahmed, Z.;
Fischer, C.; Reinke, H.; Langer, P. Synthesis 2009, 445.
35. CCDC-865738e865741 contains all crystallographic details of this publication
and is available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or
can be ordered from the following address: Cambridge Crystallographic Data
Centre, 12 Union Road, GB-Cambridge CB21EZ; Fax: (þ44)1223-336-033; or
deposit@ccdc.cam.ac.uk
ꢀ
8. (a) Paratian, J. M.; Sibille, S.; Perichon, J. J. Chem. Soc., Chem. Commun. 1992, 53;
(b) Tordeux, M.; Langlois, B.; Wakselman, C. J. Chem. Soc., Perkin Trans. 1 1990,
2293.