Regioselective synthesis of functionalized ferrocenylphenols based on cyclocondensation reactions of free and masked 1,3-dicarbonyl dianions

Article abstract of DOI:10.1016/j.jorganchem.2011.01.002

Highly functionalized ferrocenyl-substituted phenols were prepared by cyclization of masked or free dianions with 1,3-dielectrophilic 1-η5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-ones. While the cyclizations of 1,3-bis(silyloxy)-1,3-butadienes (masked d

Full text of DOI:10.1016/j.jorganchem.2011.01.002

Journal of Organometallic Chemistry 696 (2011) 1388e1393
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Journal of Organometallic Chemistry
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Regioselective synthesis of functionalized ferrocenylphenols based on
cyclocondensation reactions of free and masked 1,3-dicarbonyl dianions
,b,
Franziska Bendrath a, Alexander Villinger a, Peter Langer a
*
a Institut für Chemie der Universität Rostock, Albert-Einstein-Straße 3a, Rostock D-18059, Germany
b Leibniz Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Straße 29a, Rostock D-18059, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Highly functionalized ferrocenyl-substituted phenols were prepared by cyclization of masked or free
dianions with 1,3-dielectrophilic 1-h5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-ones. While the
Received 3 November 2010
Received in revised form
21 December 2010
cyclizations of 1,3-bis(silyloxy)-1,3-butadienes (masked dianions) proceed by initial 1,2-addition, the
reactions of free 1,3-dicarbonyl dianions proceed by initial 1,4-addition. Therefore, both regioisomeric
ferrocenylphenols are available from one and the same electrophile dependent on the type of nucleo-
phile and reaction conditions employed. The reactions reported represent the first examples of the
application of formal [3 þ 3] cyclizations to the synthesis of organometallic compounds.
Ó 2011 Elsevier B.V. All rights reserved.
Accepted 4 January 2011
Keywords:
Cyclizations
Dianions
Ferrocenes
Regioselectivity
Silyl enol ethers
1. Introduction
The synthesis of ferrocenyl-substituted p- and o-benzoquinones
has been previously reported [11]. Aryl-substituted ferrocenes have
Aryl-substituted ferrocenes (arylferrocenes) are of considerable
relevance in the field of medicinal chemistry, material sciences and
catalysis. Ferrocenyl-substituted cyclopropanes have been reported
to show anti-inflammatory activity [1]. 3-Aryl-1-ferrocenyl-2-(1H-
1,2,4-triazol-1-yl)-2-propen-1-one derivatives possess anti-
fungicidal activity against C. ara and plant growth-regulatory
activity [2]. Glycosylated ferrocenylphenols show antianemic
activity [3]. Hydroxy-substituted arylferrocenes have been used as
mediators in biosensors [4]. The antiproliferative effect of ferrocifen
drug candidates on malignant pleural mesothelioma cell lines has
been studied (Chart 1) [5]. The optical properties of chiral arylfer-
rocenes have been studied [6]. Ferrocenylsalicylates represent
promising candidates for the development of optical recording
materials [7]. para-Substituted arylferrocenes have been used to
generate shaped carbon nanomaterials (SCNMs), such as carbon
nanotubes (CNTs), amorphous carbon, carbon fibres (CFs) and
carbon spheres (CSs) [8]. Ferrocenylphenols have been successfully
used as Walphos-type ligands in the Ru-, Rh- and Ir-catalyzed
asymmetric hydrogenation of alkenes, ketones, and imines [9].
Chiral ferrocene-based quinone ligands have been employed for
highly selective Negishi cross-coupling reactions [10].
been prepared by application of the SuzukieMiyaura reaction [12].
p-Ferrocenylbenzoic acid, m-, o-, and p-ferrocenylphenol, and m-
and p-ferrocenylnitrobenzene have been prepared by phase-trans-
fer-catalyzed ferrocene arylation using aromatic diazonium salts.
These compounds have been used as intermediates for the synthesis
of ferrocene-containing non-linear-optical materials and of ther-
motropic liquid crystals [13]. The synthesis and condensation reac-
tions of formyl- and acetyl-substituted phenylferrocenes have been
reported [14]. Methoxy- and hydroxy-substituted arylferrocenes are
also known [15]. Aryl-substituted ferrocenes have been prepared
using a palladium
b-diketonate complex as the catalyst [16]. Most of
the previous syntheses of arylferrocenes rely on coupling reactions
of functionalized ferrocenes. The application of these methods tothe
synthesis of functionalized or highly substituted arylferrocenes is
difficult, because of problems related to the low regioselectivity and
low conversion (for sterically encumbered substrates). In recent
years, we have studied the synthesis of functionalized arenes by
formal [3 þ 3] cyclocondensation reactions of 1,3-bis(silyloxy)-1,3-
butadienes which can be regarded as masked 1,3-dicarbonyl dia-
nions [17]. In this context, we have also reported the synthesis of
6-(methylthio)salicylates by cyclization of 1,3-bis(silyloxy)-1,3-
butadienes with 3,3-bis(methylthio)prop-2-en-1-ones [18].
Herein, we report what are, to the best of our knowledge, the first
application of formal [3 þ 3] cyclocondensation reactions to the
regioselective synthesis of organometallic compounds by using
* Corresponding author. Fax: þ49 381 498 6411.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.01.002

F. Bendrath et al. / Journal of Organometallic Chemistry 696 (2011) 1388e1393
1389
Table 1
Synthesis of 4-ferrocenyl-2-hydroxy-6-(methylthio)benzoates 3aeh.
Et
1
2
3
R1
R2
R3
% (3)a
a
a
a
a
a
b
c
a
b
c
d
e
f
a
b
c
d
e
f
H
H
H
H
Me
Me
Me
iPr
Me
Et
H
Et
OMe
H
40
44
31
35
55
60
52
50
Fe
H
(CH2)3Cl
OCH2CH2NMe2
Me
Et
Cl
H
H
H
a
a
g
h
Me
Me
Chart 1. Structure of Z-ferrocifen.
d
a
Yields of isolated products.
O
O
SMe
SMe
solution was slowly warmed from ꢀ78 to 20 ꢁC, when the reaction
was carried out in a highly concentrated solution (4 mL/mmol), and
when an excess (2.0 equiv.) of 2 was employed. Beside decompo-
sition of the starting material, we observed incomplete degrees of
conversion of the cyclocondensation reactions In fact, unreacted 1-
i, ii
R1
Fe
R1
Fe
1a-d
Scheme 1. Synthesis of 1aed. Conditions: i: KOtBu, CS2, THF, 15 min, 0e20 ꢁC; ii: MeI
or Me2SO4, 1.5e10 h, 0e20 ꢁC.
h
5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-one
could
be
recovered. The reaction of 1bed, carrying an alkyl- or chloro-
substituent at the 2-position of the prop-2-en-1-one, with 1,3-bis
(silyloxy)-1,3-butadienes 2bef was not successful, presumably due
to steric reasons.
The formation of 3a can be explained first by reaction of 1a with
TiCl4 to give an allylic cation. The attack of the terminal carbon
atom of 2a onto the activated dithioketene ketal afforded, after
elimination of Me3SiCl, the open-chain intermediate A. Subsequent
cyclization under formal exclusion of Me3SiOTiCl3 gave interme-
diate B. The elimination of MeSH (before or during the aqueous
work-up) and aromatization resulted in the formation of 3a
(Scheme 3). The product, containing the methylthio-group located
ortho to the ester group, was formed with excellent regioselectivity.
1-h
5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-ones as the 1,3-
electrophile. The products, highly functionalized and substituted
arylferrocenes, are not readily available by other methods. In addi-
tion, we have found that the regioselectivity of cyclization can be
controlled by the type of nucleophile employed. While the reactions
of 1,3-bis(silyloxy)-1,3-butadienes (masked dianions) with 1-h5
-
ferrocenyl-3,3-bis(methylthio)prop-2-en-1-ones proceed by initial
1,2-addition, the reactions of free 1,3-dicarbonyl dianions proceed
by initial 1,4-addition. Therefore, both regioisomeric products are
available from one and the same electrophile dependent on the type
of nucleophile and reaction conditions employed. This type of
change of the regioselectivity in formal [3 þ 3] cyclocondensations
has, to the best of our knowledge, not been reported to date.
O
SMe
SMe
OH
O
Fc
2. Results and discussion
ι
1a
OMe
SMe
Our starting point was the synthesis of ferrocenyl-substituted
alkanones by Friedel-Crafts-acylation of alkanoylferrocenes. While
acetylferrocene is commercially available, propanoylferrocene, buta-
noylferrocene and 2-chloroacetylferrocene were prepared according
to known procedures [19]. The base-mediated reaction of these
compounds with carbon disulfide and methyl iodide or dimethyl
Me3SiO
Me3SiO
OSiMe3
OMe
Fc
Fc
3a
2a
MeSH
+ TiCl4
sulfate afforded the 1-h
5-ferrocenyl-3,3-bis(methylthio)prop-2-en-
OH
O
1-ones 1aed (Scheme 1) [20]. The known 1,3-bis(silyloxy)-1,3-buta-
dienes 2aef have been prepared according to the literature [21].
The TiCl4-mediated reaction of 1aed with 1,3-bis(silyloxy)-1,3-
OSiMe3
OMe
OMe
SMe
SMe
butadienes 2aef afforded the 4-
(methylthio)benzoates 3aeh in moderate to good yields (Scheme 2,
Table 1). Due to thermal instability of the 1-
5-ferrocenyl-3,3-bis
h
5-ferrocenyl-2-hydroxy-6-
B
TiCl4
SMe
O
h
(methylthio)prop-2-en-1-ones 1aed, the best yields were obtained
when freshly prepared starting materials were used, when the
Me3SiOTiCl3
Fc
SMe
OMe
O
Me3SiCl
Me3SiO
R3
OSiMe3
OR2
Me3SiO
OH
O
H
R3
SMe
OR2
SMe
2a-f
Cl3TiO
Fc
i
SMe
O
SMe
SMe
A
R1
Fe
R1
Fc =
Fe
3a-h
Fe
1a-d
Scheme 2. Synthesis of 3aeh. Conditions: i: 1) TiCl4, CH2Cl2, ꢀ78 to 20 ꢁC, 16 h; 2) 10%
HCl.
Scheme 3. Possible mechanism for the formation of 3a.

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F. Bendrath et al. / Journal of Organometallic Chemistry 696 (2011) 1388e1393
O
O
OH
O
OH
H
O
R2
H
H
R1
Fe
OCH3
SCH3
CH3
OH
O
R2
H
R1
Fe
H
H3CS
i
SMe O
H
MeS
3a
MeS
Fe
Fe
4a
1a
4a,b
Chart 2. NOESY experiments.
Scheme 4. Synthesis of 4a,b. Conditions: i: 1) LDA, 0 ꢁC, 1 h; 2) 1a, 20 ꢁC, 14 h; 3) HCl
(10%).
acid. In contrast to the TiCl4-mediated syntheses of salicylates 3, the
best yields were obtained when the reaction was carried out in
a more dilute solution (17 mL/mmol). The formation of 4a,b can be
explained by attack of the terminal carbon atom of the dianion onto
the carbon atom attached to the two methylthio groups to give the
open-chain intermediate C. The subsequent cyclization gave
intermediate D and elimination of LiOH (before or during aqueous
work-up) and aromatization resulted in formation of the final
product 4a (Scheme 5). The employment of 1,3-dicarbonyl
Table 2
Synthesis of 3-ferrocenyl-5-(methylthio)phenols 4a,b
4
R1
R2
% (4)a
a
b
Me
Et
H
Me
36
65
a
Yields of isolated products.
compounds derived from b-ketoesters failed (low conversion).
The formation of the other regioisomer, containing the methylthio-
group located para to the ester group, was not observed.
The structures of all products were confirmed by spectroscopic
methods. The hydroxyl protons (1H NMR) of 3aee and 4a,b show
The reaction of 1a with 1,3-dicarbonyl dianions, generated by
twofold deprotonation of 2,4-pentandione and 3,5-heptandione
low field resonances (
d
¼ 10.96e11.86 ppm) which indicate that the
protons are involved in an intramolecular hydrogen bond OeH/O.
In case of 3a,d, a 1H,1H-long-range-coupling is observed between
protons H-3 and H-5 (4J ¼ 1.5 Hz). For 3feh, chemical shifts
between 8.98 ppm and 9.14 ppm were observed for the hydroxyl
protons (1H NMR). Obviously, the presence of a substituent at the 3-
position of the benzoate-moiety causes a high field shift of the
signal of the hydroxyl proton with regard to the corresponding
unsubstituted benzoates. The signals of the methylthio-group of
3aeg,i,j appear at chemical shifts between 14.0 ppm and 16.6 ppm
with 2 equivalents of LDA, resulted in the formation of 3-h
5-fer-
rocenyl-5-(methylthio)phenols 4a,b (Scheme 4, Table 2). Note-
worthy, these compounds are regioisomers of 3aeh and are formed
also with excellent regioselectivity. Since the dicarbonyl dianions
are much more nucleophilic than 1,3-bis(trimethylsilyloxy)-1,3-
butadienes, the reaction could be carried out without using a Lewis
13C NMR), whereas for 3h a low field shift to 19.7 ppm was
O
O
(
OH
O
observed, due to the electron withdrawing effect of the chloro-
substituent located ortho to the methylthio carbon atom. For 3a and
4a, 1H,1H-NOESY NMR experiments were carried out to prove the
structure and the regiochemistry of the cyclization (Chart 2). For 3a,
cross-signals were observed for the protons of the methylthio-
Me
Me
Fc
Me
i
SMe O
MeS
MeS
Fc
MeS
4a
1a
LiOH
OH
O
O
Li
O
Li
Me
Me
Li
O
Fc
MeS
MeS
O
D
Fc
δ+
δ+
O
O
Li
Me
H
MeSLi
O
MeS
Fc
C
Fc =
Fe
Scheme 5. Possible mechanism for the formation of 4a.
Fig. 1. Ortep plot of 3a.

F. Bendrath et al. / Journal of Organometallic Chemistry 696 (2011) 1388e1393
1391
The structures of 3a,e,h were unambiguously confirmed by
X-ray crystal structure analyses (Figs. 1e3).
3. Conclusions
In conclusion, we have reported a regioselective approach to
highly functionalized ferrocenyl-substituted phenols by cyclization
of masked or free dianions with 1,3-dielectrophilic 1-h
5-ferrocenyl-
3,3-bis(methylthio)prop-2-en-1-ones 1. While the reactions of 1,3-
bis(silyloxy)-1,3-butadienes (masked dianions) with 1 proceed by
initial 1,2-addition, the reactions of free 1,3-dicarbonyl dianions
with 1 proceed by initial 1,4-addition. Therefore, both regioisomeric
products are available from one and the same electrophile depen-
dent on the type of nucleophile and reaction conditions employed.
4. Experimental Section
4.1. General procedure for synthesis of 1-h
5-ferrocenyl-3,3-bis
(methylthio)prop-2-en-1-ones 1a-d
To a stirred, ice-cooled solution of KOtBu (18 mmol) in 8 mL of THF
was added a solution of the ferrocenyl alkyl ketone (5 mmol) in 8 mL
of THF. After stirring for 15 min, carbon disulfide (6 mmol) was added
and the solution was vigorously stirred at 0 ꢁC for 90 min. To this
solution dimethyl sulfate (6 mmol) or methyl iodide (10 mmol) was
slowly added and the solution was stirred at 0 ꢁC for further 90 min.
Subsequently, water (50 mL) was added and the mixture was
extractedwithdichloromethane(3ꢂ50mL). Theorganiclayers were
dried(Na2SO4), filtered, andthesolventof thefiltratewas removed in
vacuo. The residue was purified by chromatography (silica gel).
Fig. 2. Ortep plot of 3e.
group with the ortho-proton located at the 5-position of the
benzoate moiety; correlations were observed between the protons
located at C-3 and C-5-position with the adjacent protons of the
linked cyclopentadienyl moiety. For 4a, NOE-correlations were
observed for both protons located ortho to the methylthio-group.
Furthermore, the protons of the acetyl-group and the proton
located at the 4-position of the phenol system correlate with the
protons of the cyclopentadienyl moiety.
4.2. 1-h
5-Ferrocenyl-2-methyl-3,3-bis(methylthio)prop-2-en-1-one
(1b)
Starting with 1-h
5-ferrocenylpropan-1-one (4.07 mmol, 980 mg),
KOtBu (8.14 mmol, 913 mg), CS2 (4.07 mmol, 0.25 mL), MeI (8.14 mmol,
0.51 mL) in 13 mL of THF, 1b was isolated (803 mg, 57%) by chroma-
tography (silica gel, heptanes/EtOAc ¼ 40/1 /5/1) as a red oil. 1H NMR
(300 mHz, CDCl3):
d
¼ 2.10 (s, 3H, CH3), 2.33 (s, 3H, SCH3), 2.35 (s, 3H,
SCH3), 4.22 (s, 5H, CH), 4.53 (m, 2H, CH), 4.73 (m, 2H, CH). 13C NMR
(63 MHz, CDCl3):
¼ 16.0 (SCH3),17.0 (SCH3), 20.6 (CH3), 69.4 (CH), 69.8
(CH), 72.0 (CH), 78.7 (CCO), 132.7 (CCH3), 144.2 (C(SCH3)2), 201.9 (CO).
d
4.3. 2-Ethyl-1-h
5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-one
(1c)
Starting with 1-h
5-ferrocenylbutan-1-one (25.00 mmol, 6.403 g),
KOtBu (90 mmol,10.100 g), CS2 (30 mmol, 3.50 mL), dimethyl sulfate
(30 mmol, 3.70 mL) in 90 mL of THF, 1b was isolated (4.434 mg, 50%)
by chromatography (silica gel, heptanes/EtOAc ¼ 40/1 / 7/1) as
a red oil. 1H NMR (250 mHz, CDCl3):
d
¼ 1.24 (t, 3J ¼ 7.6 Hz, 3H, CH3),
2.09 (s, 3H, SCH3), 2.31 (s, 3H, SCH3), 2.74 (q, 3J ¼ 7.5 Hz, 2H, CH2),
4.22 (s, 5H, CHCp), 4.51 (s, 2H, CHCp), 4.71 (s, 2H, CHCp). 13C NMR
(63 MHz, CDCl3):
d
¼ 13.5 (CH3), 16.3 (SCH3), 17.1 (SCH3), 27.9 (CH2),
69.7 (2xCHCp), 69.9 (5xCHCp), 71.7 (2xCHCp), 80.1 (Cq,Cp), 133.4
(CCH2CH3), 150.7 (C(SCH3)2), 202.1 (CO). IR (ATR, cmꢀ1):
n
¼ 3094
~
(w), 2964 (w), 2919 (w), 2872 (w), 1639 (s). MS (EI, 70 eV): m/z
(%) ¼ 360 (Mþ, 100), 213 (18), 185 (9), 129 (13), 121 (13). HRMS (EI,
70 eV): calcd. for C17H20OFeS2: 360.02995; found 360.029641.
4.4. 2-Chloro-1-h
5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-one
(1d)
Starting with chloroacetylferrocene (1.74 mmol, 458 mg), KOtBu
(3.44 mmol, 386 mg), CS2 (1.74 mmol, 0.11 mL), MeI (3.44 mmol,
Fig. 3. Ortep plot of 3h.

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F. Bendrath et al. / Journal of Organometallic Chemistry 696 (2011) 1388e1393
0.22 mL) in 26 mL of THF, 1d was isolated (250 mg, 40%) by chro-
matography (silica gel, heptanes/EtOAc ¼ 50/1 / 5/1) as a red oil;
1H NMR (300 mHz, CDCl3): ¼ 2.18 (s, 3H, SCH3), 2.45 (s, 3H, SCH3),
4.29 (s, 5H, CH), 4.60 (s, 2H, CH), 4.79 (s, 2H, CH). 13C NMR (75 MHz,
(OCH3), 69.5 (2xCHCp), 69.7 (5xCHCp), 69.9 (2xCHCp), 79.9 (Cq,Cp),
108.6 (CC[O]OCH3), 114.8 (CHAr), 136.4, 138.4, 142.6 (Cq), 157.5
(COH), 171.0 (CO). IR (ATR, cmꢀ1):
n
¼ 3089(m), 2950(w), 2921(m),
~
2848(w), 2825(w), 1732(s), 1651(s), 1594(s), 1557(s). MS (EI, 70 eV):
m/z ¼ 412 (Mꢃ, 75), 381 (19), 380 (100), 337 (7), 322 (14). HRMS (EI;
70 eV) calcd. for C20H20O4FeS (Mꢃ): 412.041459, found: m/
z ¼ 412.04262.
CDCl3):
d
¼ 16.0 (SCH3), 18.6 (SCH3), 70.1 (CH), 70.8 (CH), 73.0 (CH),
77.5 (CCO), 128.1, 136.1 (Cq), 194.2 (CO).
4.5. General procedure for the [3 þ 3]-Cyclocondensation
4.9. Isopropyl 4-h
5-ferrocenyl-2-hydroxy-6-(methylthio)benzoate
(3d)
To a mixture of 1-h
5-ferrocenyl-3,3-bis(methylthio)prop-2-en-
1-one 1 (1.0 mmol) and 1,3-bis(trimethylsilyloxy)-1,3-butadiene 2
(2.0 mmol) in dry CH2Cl2 (4 mL/mmol) was added TiCl4 (1.1 mmol)
at ꢀ78 ꢁC. The reaction mixture was stirred for 14e16 h while
warming to room temperature. After addition of 10% HCl (10 mL per
1 mmol of 1) and extraction with CH2Cl2 (3 ꢂ 50 mL), the combined
organic extracts were dried over Na2SO4, filtered and the solvent
was evaporated in vacuo. The residue was purified by column
chromatography to give products 3aeh.
Starting with 1a (0.5 mmol, 116 mg), 2d (1.0 mmol, 289 mg) and
TiCl4 (0.55 mmol, 0.06 mL) in 2 mL CH2Cl2, 3d was isolated (72 mg,
35%) by chromatography (silica gel, heptanes/EtOAc ¼ 17/1) as a red
solid; mp 79e80 ꢁC 1H NMR (300 MHz, CDCl3):
d
¼ 1.47 (s, 3H, CH
[CH3]2), 1.49 (s, 3H, CH[CH3]2), 2.48 (s, 3H, SCH3), 4.06 (s, 5H, CHCp),
4.38 (m, 2H, CHCp), 4.67 (m, 2H, CHCp), 5.36 (m, 1H, CH[CH3]2), 6.76
(d, 1H, 4J ¼ 1.5 Hz, H-5), 6.85 (d, 1H, 4J ¼ 1.5 Hz, H-3), 11.64 (s, 1H,
OH). 13C NMR (63 MHz, CDCl3)
(2xCHCp), 69.8 (CH[CH3]2), 69.9 (5xCHCp), 70.6 (2xCHCp), 83.0
d
¼ 16.6 (SCH3), 22.0 (CH[CH3]2), 67.1
4.6. Methyl 4-h
5-ferrocenyl-2-hydroxy-6-(methylthio)benzoate
(3a)
(Cq,Cp), 108.3 (Cq), 110.6 (C-3), 113.1 (C-5), 143.6, 146.3 (Cq), 163.4
(COH), 170.0 (CO). IR (ATR, cmꢀ1):
¼ 3083 (w), 2983 (m), 2918
~
n
Starting with 1a (1.0 mmol, 332 mg), 2a (2.0 mmol, 521 mg) and
TiCl4 (1.0 mmol, 0.11 mL) in 2 mL of CH2Cl2, 3a was isolated (152 mg,
40%) by chromatography (silica gel, heptanes/EtOAc ¼ 100/1 /15/
1) as a red solid; mp 166e167 ꢁC; 1H NMR (300 MHz, CDCl3)
(m), 1729 (w), 1639 (s), 1598 (s), 1556 (s), 1514 (w). MS (ESI, 70 eV):
m/z ¼ 410.0636 ([M þ H]ꢃ). Anal. calcd. for C21H22O3FeS (410.31): C,
61.47; H, 5.40; S, 7.81. found: C, 61.364; H, 5.546; S, 8.022.
d
¼ 2.50 (s, 3H, SCH3), 4.01 (s, 3H, OCH3), 4.07 (s, 5H, CHCp), 4.39 (m,
2H, CHCp), 4.67 (m, 2H, CHCp), 6.77 (d, 1H, 4J ¼ 1.5 Hz, H-5), 6.87 (d,
4.10. Methyl 4-ferrocenyl-2-hydroxy-6-(methylthio)-3-(30-
chloropropyl)benzoate (3e)
1H, 4J ¼ 1.5 Hz, H-3), 11.47 (s, 1H, OH). 13C NMR (126 MHz, CDCl3)
d
¼ 15.6 (SCH3), 51.9 (OCH3), 67.2 (2xCHCp), 70.0 (7xCHCp), 83.0
(Cq,Cp), 107.8 (CC[O]OCH3), 110.7 (C-3), 113.3 (C-5), 143.4 (CSCH3),
Starting with 1a (1.0 mmol, 332 mg), 2e (2.0 mmol, 642 mg) and
TiCl4 (1.0 mmol, 0.11 mL) in 2 mL CH2Cl2, 3e was isolated (252 mg,
55%) by chromatography (silica gel, heptanes/EtOAc ¼ 50/1) as
146.8 (Cq), 163.4 (COH), 170.9 (CO). IR (ATR, cmꢀ1):
n
¼ 3089(m),
~
2945(w), 2919(m), 2843(w), 1665(s), 1598(s), 1544(s), 1504(w). MS
(EI, 70 eV): m/z ¼ 382 (Mꢃ, 67), 351 (24), 350 (100), 285 (20), 189
(9). Anal. calc. for C19H18FeO3S (382.254): C, 59.70; H, 4.75; found:
C, 59.52; H, 4.985.
a
d
red solid; mp 132e133 ꢁC 1H NMR (300 MHz, CDCl3):
¼ 1.93e2.03 (m, 2H, CH2), 2.54 (s, 3H, SCH3), 2.88e2.93 (m, 2H,
CH2), 3.53e3.55 (m, 2H, CH2), 4.01 (s, 3H, OCH3), 4.17 (s, 5H, CHCp),
4.36e4.37 (m, 2H, CHCp), 4.50e4.51 (m, 2H, CHCp), 7.13 (s, 1H, Ar),
4.7. Methyl 3-ethyl-4-h
5-ferrocenyl-2-hydroxy-6-(methylthio)
benzoate (3b)
11.86 (s, 1H, OH). 13C NMR (63 MHz, CDCl3)
d
¼ 16.3 (SCH3), 24.5,
32.3 (CH2), 45.4 (CH2Cl), 52.0 (OCH3), 68.7 (2xCHCp), 69.7 (5xCHCp),
70.2 (2xCHCp), 86.5 (Cq,Cp), 107.6 (Cq), 118.0 (CHAr), 123.8, 139.3,
144.5 (Cq), 162.0 (COH), 171.3 (CO). IR (ATR, cmꢀ1):
n
¼ 3079 (w),
Starting with 1a (1.0 mmol, 332 mg), 2b (2.0 mmol, 577 mg) and
TiCl4 (1.0 mmol, 0.11 mL) in 2 mL of CH2Cl2, 3b was isolated (178 mg,
44%) by chromatography (silica gel, heptanes/EtOAc ¼ 100/1 / 25/
~
2997 (w), 2951 (m), 2912 (m), 2873 (w), 1731 (m), 1645 (s), 1592 (s),
1542 (s), 1505 (w). MS (ESI, 70 eV): m/z ¼ 458.04 ([M þ H]ꢃ). Anal.
calcd. for C22H23O3FeSCl (458.78): C, 57.60; H, 5.05; S, 6.99; found:
C, 57.629; H, 4.878; S, 7.326.
1) as a red solid; mp 135e136 ꢁC; 1H NMR (300 MHz, CDCl3)
d
¼ 1.14
(t, 3H, 3J ¼ 7.4 Hz, CH2CH3), 2.76 (q, 2H, 3J ¼ 7.4 Hz, CH2CH3), 4.01 (s,
3H, OCH3), 4.16 (s, 5H, CHCp), 4.35 (m, 2H, CHCp), 4.52 (m, 2H, CHCp),
7.12 (s, 1H, Ar), 11.80 (s, 1H, OH). 13C NMR (63 MHz, CDCl3)
(CH2CH3), 16.4 (SCH3), 20.0 (CH2CH3), 51.9 (OCH3), 68.6 (2xCHCp),
d
¼ 14.2
4.11. Ethyl 4-h
5-ferrocenyl-2-hydroxy-5-methyl-6-(methylthio)
69.6 (5xCHCp), 70.2 (2xCHCp), 86.6 (Cq,Cp), 107.5 (C-1), 117.9 (CHAr),
benzoate (3f)
127.0, 138.6, 144.0 (Cq), 162.0 (COH), 171.4 (CO). IR (ATR, cmꢀ1):
~
n
¼ 3097(w), 3083(w), 2969(m), 2949(w), 2927(m), 2869(w), 1729
Starting with 1b (0.9 mmol, 310 mg), 2h (1.8 mmol, 494 mg) and
TiCl4 (0.9 mmol, 0.1 mL) in 2 mL of CH2Cl2, 3f was isolated (219 mg,
60%) by chromatography (silica gel, heptanes/EtOAc ¼ 100/1 /7/1)
as a deep red solid; mp 148e150 ꢁC; 1H NMR (300 mHz, CDCl3):
(m), 1644(s), 1594(s), 1546(s). MS (EI, 70 eV): m/z ¼ 410 (Mꢃ, 88),
379 (22), 378 (100), 197 (14), 121 (6). Anal. calcd. for C21H22FeO3S
(410.31): C, 61.47; H, 5.40; found: C, 61.276; H, 5.754.
d
¼ 1.45 (t, 3J ¼ 7.0 Hz, 3H, CH2CH3), 2.34 (s, 3H, SCH3), 2.55 (s, 3H,
4.8. Methyl 4-
h
5-ferrocenyl-2-hydroxy-6-methylthio-3-
CH3), 4,23 (s, 5H, CHCp), 4.40 (s, 2H, CHCp), 4.46 (q, 3J ¼ 7.0 Hz, 2H,
methoxybenzoate (3c)
CH2CH3), 4.55 (s, 2H, CHCp), 7.21 (s,1H, Ar), 8.98 (s,1H, OH). 13C NMR
(75 MHz, CDCl3):
(2xCHCp), 69.9 (5xCHCp), 70.7 (2xCHCp), 87.2 (Cq,Cp), 117.9 (CC[O]
d
¼ 14.0, 18.8, 19.8 (CH3), 61.9 (OCH2CH3), 68.4
Starting with 1a (1.0 mmol, 332 mg), 2c (2.0 mmol, 581 mg) and
TiCl4 (1.0 mmol, 0.11 mL) in 2 mL of CH2Cl2, 3c was isolated (125 mg,
31%) by chromatography (silica gel, heptanes/EtOAc ¼ 100/1 /7/1)
OCH2), 119.3 (CHAr), 132.7, 136.8, 144.6 (Cq), 155.8 (COH), 170.0 (CO).
IR (ATR, cmꢀ1):
n
¼ 3331 (m), 3082 (w), 2988 (w), 2918 (w), 1694
~
as a red solid; mp 181e182 ꢁC; 1H NMR(250 MHz, CDCl3)
d
¼ 2.51 (s,
(s), 1590 (m), 1446 (m), 1298 (m), 1235 (s), 1206 (m), 1189 (m), 1120
(m), 1102 (m), 1016 (m). MS (CI, isobutane): m/z (%) ¼ 410 (Mꢃ, 100).
Anal. calcd. for C21H22O3FeS (410.06): C, 61.47; H, 5.40; S, 7.81;
found: C, 61.245; H, 5.563; S, 7.912.
3H, SCH3), 3.78 (s, 3H, OCH3), 4.01 (s, 3H, OCH3), 4.08 (s, 5H, CHCp),
4.41 (s, 2H, CHCp), 4.88 (s, 2H, CHCp), 6.86 (s, 1H, Ar), 11.62 (s, 1H,
OH). 13C NMR (63 MHz, CDCl3)
d
¼ 16.6 (SCH3), 52.1 (OCH3), 59.9

F. Bendrath et al. / Journal of Organometallic Chemistry 696 (2011) 1388e1393
1393
~
4.12. Methyl 5-ethyl-4-
benzoate (3g)
h
5-ferrocenyl-2-hydroxy-6-(methylthio)
(ATR, cmꢀ1):
n
¼ 3091 (w), 2918 (w),1591 (s),1574 (w),1556 (w). MS
(CI, isobutane): m/z (%) ¼ 367 ([M þ H]ꢃ, 100). HMRS (ESI, 70 eV)
calcd. for C19H18FeO2S ([M þ H]ꢃ): 366.0372, found: m/z ¼ 366.0369.
Starting with 1c (1.0 mmol, 360 mg), 2a (2 mmol, 520 mg) and
TiCl4 (1 mmol, 0.11 mL) in 3 mL of CH2Cl2, 3g was isolated (213 mg,
52%) by chromatography (silica gel, heptanes/EtOAc ¼ 100/1 /15/
1) as a brown solid; mp 147e149 ꢁC; 1H NMR (300 mHz, CDCl3):
4.16. 3-h
5-Ferrocenyl-6-methyl-5-methylthio-2-propionylphenol
(4b)
d
¼ 1.05 (t, 3J ¼ 7.3 Hz, 3H, CH2CH3), 2.34 (s, 3H, SCH3), 3.00 (q,
Starting with nBuLi (8.7 mmol, 3.45 mL, 2.5 M/nhexan), diiso-
propylamine (8.7 mmol, 1.21 mL), 3,5-heptandione (3.8 mmol,
0.5 mL) and1a (1.3 mmol, 0.420 g), 4b was isolated (256 mg, 65%) by
chromatography (silica gel, heptanes/EtOAc ¼ 15/1) as a red solid;
3J ¼ 7.3 Hz, 2H, CH2CH3), 4.01 (s, 3H, OCH3), 4.18 (s, 5H, CHCp), 4.33
(s, 2H, CHCp), 4.47 (s, 2H, CHCp), 7.44 (s, 1H, Ar), 9.14 (s, 1H, OH). 13
C
NMR (75 MHz, CDCl3):
(CH2CH3), 52.5 (OCH3), 68.3 (2xCHCp), 69.7 (5xCHCp), 70.5 (2xCHCp),
d
¼ 16.1 (SCH3), 21.0 (CH2CH3), 24.3
mp 152e154 ꢁC 1H (300 MHz, CDCl3)
d
¼ 0.87 (t, 3H, 3J ¼ 7.3 Hz,
87.3 (Cq), 117.1 (CC[O]OCH3), 120.1 (CHAr), 136.7, 139.1, 144.2 (Cq),
CH2CH3), 2.15 (q, 2H, 3J ¼ 7.3 Hz, CH2CH3), 2.22 (s, 3H, SCH3), 2.60 (s,
156.4 (COH), 170.4 (CO). IR (ATR, cmꢀ1):
n
¼ 3239 (br, m), 2959 (w),
~
3H, CH3), 4.10 (s, 5H, CHCp), 4.32 (m, 2H, CHCp), 4.43 (m, 2H, CHCp),
2924 (w), 2866 (w), 1694 (s), 1589 (s), 1402 (m), 1302 (m), 1264 (s),
1227 (s), 1123 (m), 1107 (m), 948 (m), 814 (s), 664 (m). GCeMS (EI,
70 eV): m/z (%): 410 (Mꢃ, 60), 379 (22), 378 (100), 360 (28), 213 (17).
Anal. calcd. for C21H22O3FeS (410.06): C, 61.47; H, 5.40; S, 7.81;
found: C, 61.459; H, 5.576; S, 7.57.
7.25 (s, 1H, Ar), 10.96 (s, 1H, OH). 13C (63 MHz, CDCl3)
d
¼ 9.6
(CH2CH3), 11.8 (CH3), 14.9 (SCH3), 36.6 (CH2CH3), 68.6 (2xCHCp),
69.8 (5xCHCp), 70.4 (2xCHCp), 89.7 (Cq,Cp), 118.5 (CHAr), 119.7, 120.5,
137.9, 144.0 (Cq), 156.0 (COH), 211.0 (CO). IR (ATR, cmꢀ1):
n
¼ 3086
~
(m), 2974(m), 2935(w), 2918(w), 2877(w), 1614(s), 1580(s), 1537(s),
1504(w); MS (EI, 70 eV): m/z ¼ 394 (Mꢃ, 100), 329 (18), 301 (29),
299 (14), 182 (10); HRMS (EI, 70 eV) calcd. for C21H22FeO2S:
394.068341, found: m/z ¼ 394.06844.
4.13. Methyl 5-chloro-4-h
5-ferrocenyl-2-hydroxy-6-(methylthio)
benzoate (3h)
Starting with 1d (0.6 mmol, 216 mg), 2a (1.2 mmol, 313 mg) and
TiCl4 (0.65 mmol, 0.07 mL) in 2 mL of CH2Cl2, 3h was isolated
(125 mg, 50%) by chromatography (silica gel, heptanes/
EtOAc ¼ 100/1 / 7/1) as a red solid; mp 161e162 ꢁC; 1H NMR
Appendix. Supplementary material
CCDC 805305e805307 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
(300 mHz, CDCl3):
d
¼ 2.44 (s, 3H, SCH3), 4.00 (s, 3H, OCH3), 4.24 (s,
5H, CHCp), 4.47 (s, 2H, CHCp), 4.86 (s, 2H, CHCp), 7.23 (s, 1H, Ar), 9.18
(s, 1H, OH). 13C NMR (75 MHz, CDCl3):
(OCH3), 69.8 (2xCHCp), 70.7 (5xCHCp), 71.3 (2xCHCp), 84.4 (Cq,Cp),
d
¼ 19.66 (SCH3), 53.67
118.0 (CC[O]OCH3), 119.6 (CHAr), 129.6, 137.2, 144.3 (Cq), 156.5
References
(COH), 169.7 (CO). IR (ATR, cmꢀ1):
n
¼ 3359 (w), 3081 (w), 2925 (w),
~
1726 (s), 1699 (s), 1588 (s), 1488 (w), 1429 (m), 1368 (s), 1323 (m),
1270 (m), 1228 (s), 1098 (s). MS (ESI, 70 eV): m/z ¼ 414.98661
([M ꢀ H]ꢀ). Anal. calcd. for C19H17ClFeO3S (416.699): C, 54.76; H,
4.11; found: C, 54.64; H, 4.18.
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4.14. General procedure for the cyclization reactions of 1,3-
dicarbonyl dianions
LDA was generated at 0 ꢁC by reaction of nBuLi (6.9 mmol) and
diisopropylamine (6.9 mmol) in dry THF (2.5 mL/mmol nBuLi). To
this mixture was added the dicarbonyl compound (3 mmol). After
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stirring for 1 h at 0 ꢁC, the 1- 5-ferrocenyl-3,3-bis(methylthio)
h
prop-2-en-1-one 1 (1 mmol) was added. After stirring for 14 h and
warming of the mixture to room temperature, the solution was
neutralized by addition of hydrochloric acid (10%). The mixture was
extracted with CH2Cl2 (3 ꢂ 50 mL), dried over Na2SO4, filtered and
the solvent was removed in vacuo. The residue was purified by
column chromatography to give products 4a,b.
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4.15. 2-Acetyl-3-h
5-ferrocenyl-5-(methylthio)phenol (4a)
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Starting with 1a (1.0 mmol, 332 mg), acetylacetone (3.0 mmol,
0.33 mL), nBuLi (6.9 mmol, 2.8 mL, 2.5 M in nhexane) and diiso-
propylamine (6.9 mmol, 1 mL) in 17 mL of THF, 4a was isolated
(104 mg, 36%) by chromatography (silica gel, heptanes/EtOAc ¼ 20/
1 /15/1) as a red solid; mp 103e104 ꢁC; 1H NMR (300 mHz, CDCl3):
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d
¼ 1.90 (s, 3H, CH3), 2.55 (s, 3H, SCH3), 4.14 (s, 5H, CH), 4.35 (s, 2H,
CH), 4.46 (s, 2H, CH), 6.66 (s, 1H, H-6), 7.33 (s, 1H, H-4), 11.45 (s, 1H,
OH). 13C NMR (75 MHz, CDCl3):
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d
¼ 14.6 (SCH3), 31.4 (CH3), 69.0
(2xCHCp), 70.3 (5xCHCp), 71.0 (2xCHCp), 89.6 (Cq), 110.8 (C-6), 120.0
(CC[O]CH3), 121.5 (C-4), 141.6, 146.1 (Cq), 160.2 (COH), 206.2 (CO). IR