Iron-catalyzed arylation of aromatic ketones and aldehydes mediated by organosilanes

Article abstract of DOI:10.1002/ejoc.201402023

A simple and efficient iron-catalyzed method for arylation of aromatic carbonyl compounds is reported. The use of 4-% FeCl₃ or Fe(acac) ₃ as the catalyst, in combination with a slight excess of chlorotrimethylsilane and triethylsilane, chlorination of benzylic ketones and aldehydes with subsequent Friedel-Crafts alkylation of arenes is achieved. Although the method is limited by the general constraints associated with Friedel-Crafts alkylation reactions, robust applications for the synthesis of pharmaceutical intermediates and so on can be envisioned. A robust one-pot, iron-catalyzed chlorination Friedel-Crafts alkylation reaction of benzylic carbonyl compounds, mediated by chlorotrimethylsilane and triethylsilane, has been developed to yield substituted diaryl and triaryl building blocks. Copyright

Full text of DOI:10.1002/ejoc.201402023

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DOI: 10.1002/ejoc.201402023
Iron-Catalyzed Arylation of Aromatic Ketones and Aldehydes Mediated by
Organosilanes
Risto Savela,[a] Marcin Majewski,[a] and Reko Leino*[a]
Keywords: Synthetic methods / Homogeneous catalysis / Iron / Silanes
A simple and efficient iron-catalyzed method for arylation of
aromatic carbonyl compounds is reported. The use of 4%
FeCl3 or Fe(acac)3 as the catalyst, in combination with a
slight excess of chlorotrimethylsilane and triethylsilane, chlor-
ination of benzylic ketones and aldehydes with subsequent
Friedel–Crafts alkylation of arenes is achieved. Although the
method is limited by the general constraints associated with
Friedel–Crafts alkylation reactions, robust applications for
the synthesis of pharmaceutical intermediates and so on can
be envisioned.
the field of catalytic benzylations has expanded remarkably.
In recent investigations, the frequent use of benzylating
agents have included acetylated or trimethylsilylated benz-
ylic alcohols,[15] styrene derivatives,[16] benzyl alcohols[17]
and benzyl thiocyanates.[18]
Introduction
The field of iron-catalyzed transformations has rapidly
expanded in the past decade.[1] For example, iron-catalyzed
reductions of organic compounds with organosilanes as the
hydride source have been widely investigated.[2] Typically,
carbonyl compounds are reduced to alcohols by hydro-
silylation followed by subsequent quenching.[3] Reductions
of nitriles, amides and imines to amines have likewise been
reported.[4] Also recently, iron-catalyzed reductions of sulf-
oxides[5] to sulfides, as well as chemo-, regio- and stereo-
selective hydrosilylations of alkenes and alkynes[6] have been
investigated. Furthermore, deoxygenative transformations
of silyl ethers to chlorides[7] and azides[8] and preparations
of ethers through condensation reactions of ketones, alde-
hydes or alcohols,[9] and through reduction of esters[10] have
been described.
Friedel–Crafts-type reactions, in general, have significant
applications in both laboratory and industrial synthesis
with the Friedel–Crafts benzylation being one of the funda-
mental methods used for preparation of diarylalkanes,
which, in turn, are useful intermediates for dyes, pharma-
ceuticals and cosmetics.[11] Representative examples of
pharmaceutical targets that could be obtained by Friedel–
Crafts chemistry are shown in Figure 1. Although the direct
use of carbonyl compounds as alkylating agents in Friedel–
Crafts alkylations is attractive (Scheme 1), such reactions
often suffer from low yields and undesirable side-product
formation as a result of multiple alkylations.[12] Acid-cata-
lyzed reductive Friedel–Crafts reaction between benzalde-
hyde and benzene has been known since 1886,[13] typically
to yield a mixture of products in low yields.[14] Since then,
Figure 1. Representative examples of pharmaceuticals with precur-
sors obtained thorugh Friedel–Crafts alkylation.
Scheme 1. Reductive Friedel–Crafts alkylation.
One of the first examples of catalytic reductive Friedel–
Crafts alkylations utilized Ga2Cl4,[19] with subsequent re-
ports on the use of superacid,[20] and scandium(III) tri-
fluoromethanesulfonate as the catalysts.[21] Other earlier re-
[22]
ported approaches have involved the use of InCl3
and
[23]
InBr3 together with chlorodimethylsilane. Iron-catalyzed
Friedel–Crafts reactions with FeCl3 in the presence of
chlorodimethylsilane and thiophene as the nucleophile have
also been reported.[24] In our ongoing search for applica-
tions of economically viable iron catalysts, in particular
FeCl3,[25] we turned our attention to its potential use in re-
[a] Laboratory of Organic Chemistry Åbo Akademi University,
20500 Åbo, Finland
E-mail: reko.leino@abo.fi
http://www.abo.fi/rlgroup
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402023.
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ductive Friedel–Crafts alkylation reactions in combination Ideally, the arene reagents studied were also used as sol-
with organic silanes. Here, we report the initial results of vents.
our investigation.
Results and Discussion
The aim of the present work was to investigate the use
of FeCl3 as the catalyst, in combination with organosilanes,
for Friedel–Crafts-type alkylation reactions of aromatic
phenones and benzaldehydes with aromatic nucleophiles.
ketones and aldehydes. In the preliminary experiments, ace-
Scheme 3. Reductive arylation reaction of substituted aceto-
tophenone was reacted in an excess of toluene with FeCl3
as the catalyst in the presence of chlorodimethylsilane
(Scheme 2). In contrast to literature precedence,[24] instead
of desired diarylethane A, corresponding reduced ethyl-
benzene C was primarily formed. The selectivity could,
however, be reversed by addition of the organosilane as a
dilute solution by means of a syringe pump. Although
promising at first, this approach proved problematic and
resulted in extensive formation of acyclic and cyclic polydi-
methylsiloxane byproducts, causing purification problems
on the preparative scale. Finally, the selectivity issues were
resolved by switching to the use of chlorotrimethylsilane as
the chlorine source, followed by portionwise addition of a
diluted triethylsilane solution at room temperature. By
using this methodology, formation of corresponding 1-
chloro-1-phenylethane B intermediate was observed with
concomitant suppression of the formation of undesired
polysiloxane byproducts. Instead, only easily separable
hexaethyldisiloxane and 1,1,1-triethyl-3,3,3-trimethyldisi-
loxane compounds were formed as side-products. Earlier, a
similar approach for chlorination of carbonyl compounds
by using In(OH)3 as the catalyst, in combination with
chlorodimethylsilane as both the chlorine and hydride
source, has been reported.[26] The yields obtained were bet-
ter than the combined use of chlorotrimethylsilane and tri-
ethylsilane.[26]
In accordance with the general trends of substituent ef-
fects in electrophilic aromatic substitution reactions, the
formation of ortho meta and para isomers were observed.
However, competition between the first formed 1-chloro-1-
phenylethane intermediate and the added arene nucleophile
took place. For cases in which the intermediate and nucleo-
phile had similar reactivities, tendency towards dimeriza-
tion and potential oligomerization of the formed intermedi-
ate occurred. This was particularly the case for the reactions
of acetophenone with benzene and phenyl bromide, where
in the first reaction very little and in the latter case none of
the desired coupling product was observed (data not
shown). Also, the use of furan or 2-methylfuran as the cou-
pling partner for both acetophenone and benzaldehyde
proved inefficient and resulted in the formation of reddish-
black gelled solutions with only trace amounts of the de-
sired products detected, possibly a result of coordination of
the furan moieties to the iron catalyst, or formation of
cross-linked polymers (data not shown). Accordingly, care-
ful selection of the carbonyl compound and the nucleophile
reagent applied was necessary for optimization of the reac-
tion yields and regioselectivities. Although the best results
and yields were obtained by use of up to a ten-fold excess
of arene nucleophile as the solvent, also close to equimolar
concentrations of arene reagent were briefly screened with
variable results (Table 1, Entries 6, 12 and 13; and Table 2,
Entries 7, 9, 14 and 15). As a potential route for prepara-
tion of e.g., cyclopentadienyl-type ligand precursors for
transition metal complexes, two experiments were carried
out with fluorenone as the starting material (Table 1, En-
tries 14 and 15) providing good yields but only mediocre
regioselectivities.
In general, the benzaldehyde derivatives studied proved
slightly less reactive than the corresponding acetophenones,
which also resulted in poorer regioselectivities in terms of
the ortho, meta and para isomers formed. In contrast to the
Scheme 2. Initially investigated catalyst system for the Friedel–
Crafts arylation reaction.
Under the reaction conditions screened in the present corresponding reaction with acetophenone, the reaction of
work, the desired Friedel–Crafts alkylation took place at benzaldehyde with toluene was very slow, resulting in
elevated temperatures 50–90 °C. The general, optimized cat- Ͻ 50% isolated yield (Table 1, Entry 1; and Table 2, En-
alyst system used for substrate scope investigation is illus- tries 1 and 2), whereas the reaction with benzene proceeded
trated in Scheme 3 with results on the cascade-type chlor- without extensive side product formation providing a higher
ination Friedel–Crafts alkylation reaction sequence of benz- isolated yield. Notably, in accordance with literature prece-
ylic ketones collected in Table 1 and the corresponding re- dence,[33] formation of ethers from benzaldehydes was ob-
actions with benzaldehydes as the electrophile shown in served. The ethers formed could be converted into the cor-
Table 2. For some starting materials further adjustments responding chlorides by further heating of the reaction mix-
were necessary to suppress the potential side reactions, opti- ture with further conversion to form the desired diarylmeth-
mize the reaction yields and to isolate the final products. ane. The compounds prepared in Table 2, Entries 9 and 10,
2
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Iron-Catalyzed Arylation of Aromatic Ketones and Aldehydes
Table 1. Reductive Friedel–Crafts arylation reaction of acetophenones with substituted arenes (citations refer to characterization data in
the literature).[a]
[a] General reaction conditions: Arene reagent used as the solvent unless mentioned otherwise; reaction temperature 50 °C; Et3SiH was
diluted to 1 mL volume with the corresponding arene or dichloromethane solvent and added portionwise at the rate of 0.1 mL/5 min.
[b] Isolated yield for the mixture of isomers unless noted otherwise. [c] Determined by GC–MS; tr = trace. [d] Both isomers isolated and
characterized separately. [e] Reaction commenced at room temp. [f] Reaction temperature 90 °C. [g] Dichloromethane used as the solvent.
[h] Only Me3SiCl used. [i] Reaction carried out at room temp.
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Table 2. Reductive arylation reaction of benzaldehydes with substituted arenes (citations refer to characterization data in the
literature).[a]
[a] General reaction conditions: Arene reagent used as the solvent unless mentioned otherwise; reaction temperature 50 °C; Et3SiH was
diluted to 1 mL volume with the corresponding arene or dichloromethane solvent and added portionwise at the rate of 0.1 mL/5 min.
[b] Isolated yield for the mixture of isomers unless noted otherwise. [c] Determined by GC–MS; tr = trace. [d] Both isomers isolated and
characterized separately. [e] Reaction commenced at room temp. [f] Reaction temperature 90 °C. [g] Dichloromethane used as the solvent.
[h] Only Me3SiCl used. [i] Reaction carried out at room temp.
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Iron-Catalyzed Arylation of Aromatic Ketones and Aldehydes
could be considered as potential precursors for Bifonazole
Mechanistically the reaction can be suggested to proceed
and antihistamine synthesis, such as Cetirizine (Figure 1), through initial hydrosilylation of the carbonyl group fol-
respectively. Unfortunately, particularly with the compound lowed by chlorination of the formed silyl ether by the
of Entry 9, in Table 2, where selectivity towards the para chlorosilane, to yield the corresponding chloride intermedi-
isomer would be desired for potential use as a pharmaceuti- ate and siloxane. As postulated earlier by Baba,[26] sufficient
cal intermediate, significant para selectivity was not ob- oxophilicity and moderate Lewis acidity of the catalyst em-
served. For these compounds, in an effort to improve the ployed are required for the reaction to proceed. In the first
regioselectivity, additional screening experiments were car- exothermic reaction step, siloxane formation functions as
ried out with FeBr3 and FeI3 (produced in situ from iron the driving force for formation of the chloride. It is unclear
and iodine)[27] as the iron catalyst source. The use of FeBr3 at present if the chlorination reaction is fully iron catalyzed
as the catalyst increased the reactivity and decreased the or the formation of a Me3SiCl–FeCl3 type complex, similar
reaction time to one third relative to FeCl3, although the to Me3SiCl–InCl3 complex formation observed earlier by
reaction still required elevated reaction temperatures to pro- Baba et al.,[22a,22b] influences the first reaction steps. Such
ceed. The regioselectivity was not improved. With FeI3, nei- influence appears reasonable, considering that the addition
ther formation of the desired product nor the reaction inter- of chloromethylsilane to the reaction mixture facilitates the
mediate was observed, possibly a result of polymerization dissolution of the FeCl3 catalyst. In the absence of chloro-
of the starting material.
methylsilane, the reaction slowly proceeds as a Clemmens-
The use of highly electron-rich arenes, such as mesity- type reduction. The tentative reaction mechanism from
lene, anisole or thiophene as the nucleophile with benzalde- chlorination to Friedel–Crafts alkylation is illustrated in
hyde, resulted in the formation of triarylmethanes as side Scheme 5. The possible influence of chlorotrimethylsilane
products. Whereas the reaction conditions for Table 2, En- and the siloxane formed in the Friedel–Crafts alkylation of
tries 5, 6 and 8 were optimized primarily for the corre- benzyl chloride with benzene was briefly investigated exper-
sponding diarylderivatives, it was also of interest to investi- imentally. Although the addition of chlorotrimethylsilane
gate the potential formation of triarylmethanes, similarly to helps to keep the FeCl3 catalyst dissolved, it does not signif-
an earlier published method.[34] Here, it was observed that icantly influence the actual alkylation reaction. Addition of
the use of FeCl3 as catalyst, together with at least twofold one equivalent of hexamethylsiloxane, in turn, does not in-
excess of chlorotrimethylsilane at elevated temperatures, re- fluence the dissolution of FeCl3 but slows down the reac-
sulted in diarylation of benzaldehyde used (Table 2, En- tion rate at lower temperatures, possibly owing to coordina-
tries 16–18, and Scheme 4). The use of anisole under similar tion of the siloxane to the iron catalyst, rendering it less
conditions (Table 2, Entry 16) provided a high yield at the active for the desired Friedel–Crafts alkylation reaction. Fi-
expense of regioselectivity. When the same reaction was at- nally, a brief investigation of potential secondary kinetic
tempted with thiophene, the use of FeCl3 as catalyst re- isotope effects was conducted with 2Ј,3Ј,4Ј,5Ј,6Ј-d5-aceto-
sulted in oligomerization of the diarylated product only as a phenone, 2,2,2-d3-acetophenone, as well as acetophenone in
result of significant increase in reactivity of the substituted combination with triethyl(silane-d) without detectable influ-
thiophene. Also, the use of FeCl3 resulted in some degree ence on the rate of the reaction.
of polymerization of the thiophene which made purification
tedious. Finally, it was observed that the use of Fe(acac)3
as catalyst instead of FeCl3 suppressed the side reactions,
including thiophene polymerization. Consequently, the re-
action with 2-methylthiophene was repeated with Fe(acac)3
as catalyst providing the desired triarylmethane (Table 2,
Entry 18) in excellent yield. For reaction of benzaldehyde
with mesitylene to yield the corresponding triarylmethane
(Table 2, Entry 17), various reaction conditions were screen-
ed but only poor yields resulted and without complete selec-
Scheme 5. Tentative mechanism for the iron-catalyzed Friedel–
Crafts alkylation.
tivity towards the desired triaryl compound. Fortunately,
the undesired diaryl compound could be separated from the
reaction mixture by washing with cold ethanol.
Conclusions
To summarize, a simple and efficient iron-catalyzed
method for arylation of aromatic carbonyl compounds has
been developed by using 4 mol-% FeCl3 or Fe(acac)3 as the
catalyst in combination with excess chlorotrimethylsilane
and triethylsilane. In the reactions studied here, the desired
coupling products were obtained in 23–97% yields with re-
gioselectivities ranging from poor to moderate, being sim-
Scheme 4. Reductive arylation reaction of substituted aceto-
ilar to the yields and selectivities obtained earlier[19–23] in
phenone and benzaldehyde with aromatic nucleophiles and the cor-
responding arene as solvent.
studies that used benzylic carbonyl compounds as the benz-
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only to illustrate the best values obtained. The NMR and MS data
are consistent with high purity in each case. Column chromatog-
raphy was performed on RediSep Rf Gold Silica columns (0.020–
0.040 mm).
ylating agents. The developed method was successfully ap-
plied to a wide range of aromatic ketones and aldehydes
and resulted in the isolation of several previously undis-
closed compounds (Table 1, Entries 8–13 and Table 2, En-
tries 10–15) potentially useful as precursors for further
derivatization. Notably, previous studies that used benzylic
carbonyl compounds as starting materials generally re-
ported only NMR and/or GC yields for the products,
whereas in the present work isolated yields for accurately
characterized compounds are given. In contrast to other
catalytic benzylation reactions that use benzylic alcohols or
acetylated derivatives, the present method provides similar
efficiencies, with some variations depending on the reac-
tants used. Benzylic chloride starting materials often have
limited commercial availability, whereas several benzalde-
hyde and acetophenone derivatives are readily available.
The products prepared here would also be accessible
through a multistep reaction route involving carbonyl re-
duction and chlorination of the alcohol formed, followed
by subsequent Friedel–Crafts alkylation, requiring typically
several days to perform. The presently described direct iron-
catalyzed method is robust and allows for the rapid prepa-
ration of diphenylmethane and ethane derivatives, as well
General Procedure for Reaction Work-Up: After cooling to room
temperature, the reaction mixture was diluted with EtOAc (10 mL)
and washed twice with saturated sodium hydrogen carbonate solu-
tion (3 mL). The aqueous phases were combined and washed with
EtOAc (3 mL). The organic fractions were combined, dried with
sodium sulfate, evaporated and purified by flash chromatography.
General Method A: Into the corresponding arene (1 mL) was sus-
pended FeCl3 (11 mg, 0.07 mmol), followed by addition of the aryl
ketone or aryl aldehyde (1.76 mmol), respectively. Next, chlorotri-
methylsilane (0.25 mL, 1.94 mmol) was added to the reaction mix-
ture, which dissolved the FeCl3. Then, triethylsilane (0.30 mL,
1.85 mmol) was diluted with the corresponding arene (total volume
of 1 mL) and added portionwise (0.1 mL/every 5 min). The re-
sulting solution was stirred for a total of 2 h at room temperature
and then heated to 50 °C (or to 90 °C) and stirred until full conver-
sion followed by general work up.
General Method B: Into the corresponding arene (1 mL) was sus-
pended FeCl3 (11 mg, 0.07 mmol), followed by addition of the aryl
aldehyde (1.76 mmol). Next, chlorotrimethylsilane (0.25 mL,
1.94 mmol) was added to the reaction mixture, which dissolved the
as selected triphenylmethane and fluorene derivatives. Al- FeCl3, followed by heating to 50 °C (or to 90 °C). Then, triethylsi-
lane (0.30 mL, 1.85 mmol) was diluted with the corresponding ar-
ene (total volume of 1 mL) and added portionwise (0.1 mL/every
5 min) to the reaction mixture, which then was stirred until full
conversion followed by general work up.
though this new methodology is limited by the general con-
strains that arise from Friedel–Crafts alkylation and the use
of chlorosilane, it can be efficiently applied in selected appli-
cations, including the potential production of complex mol-
ecules and intermediates for pharmaceuticals. In future
work, we aim to expand the methodology towards non-
benzylic aldehydes and ketones. Studies to provide a deeper
understanding for the mechanism of the chlorination reac-
tion are also planned.
General Method C: Into the corresponding solvent (1 mL of arene
or 0.3 mL of dichloromethane) was suspended FeCl3 (11 mg,
0.07 mmol), followed by addition of the aryl ketone or aryl
aldehyde (1.76 mmol). Next, chlorotrimethylsilane (0.25 mL,
1.94 mmol) was added to the reaction mixture, which dissolved the
FeCl3, followed by addition of triethylsilane (0.30 mL, 1.85 mmol),
which was diluted with the respective arene/solvent (total volume
of 1 mL) and added portionwise (0.1 mL/every 5 min). Afterwards
the nucleophile was added (in case of dichloromethane) and stirred
at elevated temperature until full conversion followed by general
work up.
Experimental Section
General Considerations: All chemicals were purchased from com-
mercial sources and were used without further purification unless
mentioned otherwise. The NMR spectra were recorded with a
600 MHz or 500 MHz NMR spectrometer. The 600 MHz instru-
ment was equipped with a BBI-5 mm-Zgrad-ATM probe or BBO-
1-Methyl-4-(1-phenylethyl)benzene (1): Method A with toluene at
50 °C. Total reaction time 5 h, after which the washed crude prod-
uct was purified with flash chromatography with hexane to yield a
colorless oil, yield 78% (268 mg), ratio of isomers p:m:o (1a/1b/1c)
92:1:7. Rf = 0.66 (dichloromethane/hexane, 1:3). Characterization
data is consistent with that published previously.[17i]
1
5 mm-Zgrad probe at 298 K operating at 600.13 MHz for H and
150.92 MHz for 13C. The 500 MHz instrument was equipped with a
BBI-5 mm-Zgrad-ATM probe or BBO-5 mm-Zgrad probe at 298 K
operating at 500.13 MHz for 1H and 125.76 MHz for 13C. The
chemical shifts were calibrated to the residual proton and carbon
resonance of the solvent. Product distributions and purities were
monitored by GC–MS. The GC–MS instrument was
equipped with an MS detector (EI), HP-5MS column
(30 mϫ250 μmϫ0.25 μm), and He was used as the carrier gas with
1,4-Dimethyl-2-(1-phenylethyl)benzene (2): Method A with para-
xylene at 90 °C. Total reaction time 3 h, after which the washed
crude product was purified with flash chromatography with hexane
to yield a colorless oil, yield 66% (246 mg). Rf = 0.66 (dichloro-
methane/hexane, 1:3). Characterization data is consistent with that
published previously.[28]
the following temperature program: injector 250 °C, oven Tinitial
=
50 °C (4 min), rate 10 °C/min, Tfinal = 300 °C, hold 5 min. The pu-
rity of the products is at least 99% unless indicated otherwise. The
HRMS were recorded with Q-TOF with electrospray ionization op-
erated in negative mode. IR spectra were recorded with FT-IR with
Platinum single reflection diamond ATR module. Elemental analy-
sis was performed with FLASH 2000, which resulted, unfortu-
nately, in poor reproducibility for some compounds, particularly
for 11, 26 and 27 for which accurate data could not be obtained.
The results reported for these compounds are, therefore, provided
2,4-Dimethyl-1-(1-phenylethyl)benzene (3): Method A with meta-
xylene at 50 °C. Total reaction time 3 h, after which the washed
crude product was purified with flash chromatography with hexane
to yield a colorless oil, yield 94% (347 mg), ratio of isomers p:o
(3a/3b) 100:trace, Rf = 0.66 (dichloromethane/hexane, 1:3). Charac-
terization data is consistent with that published previously.[29]
1,3,5-Trimethyl-2-(1-phenylethyl)benzene (4): Method A with mesit-
ylene at 90 °C. Total reaction time 3 h, after which the washed
6
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Iron-Catalyzed Arylation of Aromatic Ketones and Aldehydes
crude product was purified with flash chromatography with hexane
to yield a colorless oil, yield 68% (268 mg). Purity: 97%. Rf = 0.57
(dichloromethane/hexane, 1:3). Characterization data is consistent
with that published previously.[28]
(s, 3 H), 2.18 (s, 3 H), 1.54 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR
(CD2Cl2, 125.76 MHz, 25 °C): δ = 144.3, 140.4, 136.6, 136.1, 134.1,
131.5, 129.8, 128.9, 127.6, 127.3, 126.9, 126.7, 37.9, 21.0, 20.8,
19.4 ppm. IR (film): ν
= 2968, 1470, 1439, 1034 cm–1. MS (EI):
˜
max
m/z = 244 [M+]. C16H17Cl (244.76): calcd. C 78.5, H 7.00; found C
1-Methoxy-4-(1-phenylethyl)benzene (5): Method A with anisole at
50 °C. Total reaction time 3 h, after which the washed crude prod-
uct was purified with flash chromatography (0–25% dichlorometh-
ane/hexane) to yield a colorless oil, yield 86% (321 mg), ratio of
isomers p:o (5a/5b) 100:trace. Purity: 97%. Rf = 0.20 (dichloro-
methane/hexane, 1:3). Characterization data is consistent with that
published previously.[30]
78.6, H 6.9.
1,5-Dimethyl-2-[1-(4-nitrophenyl)ethyl]benzene (11): Method A with
meta-xylene at 50 °C. Total reaction time 5 h, after which the
washed crude product was purified with flash chromatography (0–
30% dichloromethane/hexane) to yield a pale yellow oil, which
slowly solidified, yield 87% (398 mg), ratio of isomers p:o:m (11a/
11b/11c) 86:13:1. Rf = 0.31 (dichloromethane/hexane, 1:3). For
major isomer: 1H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 8.09
(td, J = 2.2, 9.2 Hz, 2 H), 7.32 (td, J = 2.2, 9.2 Hz, 2 H), 7.13 (d,
J = 7.9 Hz, 1 H), 7.03 (br. d, J = 7.9 Hz, 1 H), 6.98 (s, 1 H), 4.39
(q, J = 7.5 Hz, 1 H), 2.29 (s, 3 H), 2.17 (s, 3 H), 1.61 (d, J =
7.5 Hz) ppm. 13C NMR (CD2Cl2, 150.92 MHz, 25 °C): δ = 155.0,
146.6, 139.8, 136.6, 136.3, 131.8, 128.9, 127.3, 126.9, 123.9, 41.2,
4-(1-Phenylethyl)phenol (6): Method C with dichloromethane as
solvent. After 2 h at room temperature, phenol (0.50 g, 5.28 mmol)
was added. The reaction mixture was stirred at 50 °C for 3 h. Crude
product was purified by flash chromatography (0–15%, EtOAc/
hex) to yield both isomers separately as colorless oils, yield para
isomer 6a: 40% (140 mg), Purity: 97%. Rf = 0.52 (1:3 EtOAc/hex-
ane); ortho isomer 6b: 17% (59 mg), Rf = 0.62 (1:3 EtOAc/hexane).
Characterization data is consistent with that published pre-
viously.[30]
22.0, 21.0, 19.8 ppm. ν
(solid) = 3074, 2964, 1592, 1342,
˜
max
1110 cm–1. MS (EI): m/z = 255 [M+]. C16H17NO2 (255.32): calcd.
C 75.3, N 5.5, H 6.7; found C 74.6, N 5.5, H 6.7. Inconsistency in
the carbon analysis is possibly a result of volatility issues in the
mass analysis (see also General Considerations).
2-(1-Phenylethyl)thiophene (7): Method A with thiophene at 50 °C.
Total reaction time 4 h, after which the washed crude product was
purified by flash chromatography with hexane to yield a slightly
yellow oil, yield 81% (268 mg), ratio of isomers 2:3 (7a/7b) 81:19.
Rf = 0.52 (dichloromethane/hexane, 1:3). Characterization data is
consistent with that published previously.[30]
2-[1-(4-Fluorophenyl)ethyl]-4-(1,1-dimethylethyl)phenol
(12):
Method C with dichloromethane as solvent and 4-fluoroaceto-
phenone (0.21 mL, 1.76 mmol). After 2 h at room temperature, 4-
tert-butylphenol (0.30 g, 2.02 mmol) was added. The reaction mix-
ture was heated to 50 °C and stirred for 2 h. Crude product was
purified by flash chromatography (0–15% EtOAc/hexane) to yield
a slightly yellow oil, yield 35% (170 mg) Purity = 98%. Rf = 0.49
(1:4 EtOAc/hex). 1H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.25
(d, J = 2.5 Hz, 1 H), 7.24–7.20 (m, 2 H), 7.13 (dd, J = 2.5, 8.4 Hz,
1 H), 6.98 (tt, J = 2.5, 9.1 Hz, 2 H), 6.66 (d, J = 8.4 Hz, 1 H), 4.60
(b, 1 H), 4.39 (q, J = 7.2 Hz, 1 H), 1.61 (d, J = 7.2 Hz, 3 H), 1.29
(s, 9 H) ppm. 13C NMR (CD2Cl2, 150.92 MHz, 25 °C): δ = 161.6
(d, JC,F = 243 Hz), 151.2, 144.0, 142.2 (d, JC,F = 4 Hz), 131.5, 129.4
(d, JC,F = 8 Hz), 125.2, 124.6, 115.5 (d, JC,F = 5 Hz), 115.3, 38.5,
2,4-Dimethyl-1-[1-(4-methylphenyl)ethyl]benzene (8): Method
A
with meta-xylene at 50 °C. Total reaction time 3 h, after which the
washed crude product was purified with flash chromatography with
hexane to yield a colorless oil, yield 69% (272 mg), ratio of isomers
p:o (8a/8b) 97:3. Rf = 0.76 (dichloromethane/hexane, 1:3). 1H NMR
(CD2Cl2, 500.13 MHz, 25 °C): δ = 7.16 (d, J = 8.1 Hz, 1 H), 7.11–
7.06 (m, 4 H), 7.03 (br. d, J = 7.9 Hz, 1 H), 6.98 (br. s, 1 H), 4.28
(q, J = 7.2 Hz, 1 H), 2.32 (s, 3 H), 2.31 (s, 3 H), 2.23 (s, 3 H), 1.58
(d, J = 7.2 Hz, 3 H) ppm. 13C NMR (CD2Cl2, 125.76 MHz, 25 °C):
δ = 143.5, 141.7, 136.2, 135.8, 135.7, 131.5, 129.3, 127.9, 127.0,
126.8, 40.6, 22.4, 21.1, 21.0, 19.9 ppm. IR (film): νmax = 2965, 1511,
˜
34.5, 31.7, 21.2 ppm. IR (film): ν
= 3287, 2964, 1600, 1505,
˜
max
1450, 1371, 1044 cm–1. MS (EI): m/z = 224 [M+]. C17H20 (224.35):
1219, 1125 cm–1. MS (EI): m/z = 272 [M+]. HRMS (ESI): calcd.
calcd. C 91.0, H 9.0; found C 90.9, H 8.9.
for C18H21FO (M – H) 271.1504; found 271.1509.
1-[1-(4-Bromophenyl)ethyl]-2,4-dimethylbenzene (9): Method A with
meta-xylene at 50 °C. Total reaction time 3 h, after which the
washed crude product was purified with flash chromatography with
hexane to yield a colorless oil, yield 87% (445 mg), ratio of isomers
4-Bromo-4Ј-[1-(2-chlorophenyl)ethyl]-1,1Ј-biphenyl (13): Method C
with dichloromethane as solvent and 2Ј-chloroacetophenone
(0.23 mL, 1.76 mmol). After 2 h at room temperature, 4-bromobi-
phenyl (0.47 g, 2.02 mmol) was added. The reaction mixture was
heated to 50 °C and stirred for 2 h. Crude product was purified by
flash chromatography (hexane) to yield a colorless oil, which slowly
solidified, yield 76% (499 mg). Rf = 0.60 (dichloromethane/hexane,
1:3). 1H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.55 (td, J = 2.3,
9.0 Hz, 2 H), 7.50 (td, J = 2.1, 8.7 Hz, 2 H), 7.46 (td, J = 2.3,
9.0 Hz, 2 H), 7.37 (dd, J = 1.6, 7.9 Hz, 1 H), 7.33–7.29 (m, 3 H),
7.27 (dt, J = 1.3, 7.6 Hz, 1 H), 7.18 (dt, J = 1.6, 7.6 Hz, 1 H), 4.68
(q, J = 7.3 Hz, 1 H), 1.64 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR
(CD2Cl2, 150.92 MHz, 25 °C): δ = 145.2, 143.7, 140.2, 138.1, 134.2,
132.2, 130.0, 129.0, 128.9, 128.7, 127.9, 127.4, 127.2, 121.6, 41.1,
1
p:o (9a/9b) 100:trace. Rf = 0.80 (dichloromethane/hexane, 1:3). H
NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.80 (td, J = 2.3, 8.9 Hz,
2 H), 7.11 (d, J = 7.8 Hz, 1 H), 7.04 (td, J = 2.3, 8.9 Hz, 2 H), 7.01
(br. d, J = 7.8 Hz, 1 H), 6.96 (s, 1 H), 4.25 (q, J = 7.2 Hz, 1 H),
2.28 (s, 3 H), 2.18 (s, 3 H), 1.55 (d, J = 7.2 Hz, 3 H) ppm. 13C
NMR (CD2Cl2, 150.92 MHz, 25 °C): δ = 146.2, 140.8, 136.19,
136.15, 131.63, 131.61, 129.9, 127.1, 126.8, 119.7, 40.5, 22.2, 21.0,
19.7 ppm. IR (film): νmax = 2966, 1485, 1450, 1102, 1008 cm–1. MS
˜
(EI): m/z = 288/290 [M+]. C16H17Br (289.21): calcd. C 66.5, H 5.9;
found C 66.4, H 5.9.
1-[1-(2-Chlorophenyl)ethyl]-2,4-dimethylbenzene (10): Method
A
21.4 ppm. ν
(solid) = 3059, 2970, 1472, 1388, 1058 cm–1. MS
˜
max
with meta-xylene at 50 °C. Total reaction time 3 h, after which the
washed crude product was purified with flash chromatography with
hexane to yield a colorless oil, yield 97% (419 mg), ratio of isomers
p:o (10a/10b) 100:trace. Rf = 0.73 (dichloromethane/hexane, 1:3).
(EI): m/z = 370/372 [M+]. C20H16BrCl (371.70): calcd. C 64.6, H
4.3; found C 64.6, H 4.3.
9-(2,4,6-Trimethylphenyl)-9H-fluorene (14): Method A with mesit-
1H NMR (CD2Cl2, 500.13 MHz, 25 °C): δ = 7.36 (dd, J = 1.6, ylene at 50 °C. Total reaction time 7 h, after which the washed
7.7 Hz, 1 H), 7.20–7.13 (m, 2 H), 7.11–7.07 (m, 2 H), 7.00 (br. d, crude product was purified by flash chromatography with hexane
J = 7.9 Hz, 1 H), 6.98 (br. s, 1 H), 4.65 (q, J = 7.3 Hz, 1 H), 2.30
to yield a colorless oil, yield 94% (472 mg), Rf = 0.47 (dichloro-
Eur. J. Org. Chem. 0000, 0–0
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Pages: 12
R. Savela, M. Majewski, R. Leino
FULL PAPER
methane/hexane, 1:3). Characterization data is consistent with that
published previously.[31]
(96 mg), purity: 95%. Rf = 0.57 (1:4 EtOAc/hexane). Characteriza-
tion data is consistent with that published previously.[30]
2-(Phenylmethyl)thiophene (23): Method C with dichloromethane
as solvent. After 2 h at room temperature, thiophene (1.5 mL,
18.7 mmol) was added. The reaction mixture was then heated to
50 °C and stirred for 4 h. Crude product was purified by flash
chromatography with hexane to yield a colorless oil, yield 50%
(157 mg), ratio of isomers 2:3 (23a/23b); 63:37. Rf = 0.62 (dichloro-
methane/hexane, 1:3). Characterization data is consistent with that
published previously.[38]
9-(4-Methoxyphenyl)-9H-fluorene (15): Method A with anisol at
50 °C. Total reaction time 3 h, after which the washed crude prod-
uct was purified by flash chromatography (0–40% dichlorometh-
ane/hexane) to yield both isomers as white solids, yield para isomer
15a: 61% (293 mg). Rf = 0.14 (dichloromethane/hexane, 1:3). ortho
isomer 15b: 35% (166 mg). Rf = 0.29 (dichloromethane/hexane,
1:3). Characterization data is consistent with that published pre-
viously.[32]
4-(Phenylmethyl)-1,1Ј-biphenyl (24): Method C with dichlorometh-
ane as solvent. After 2 h at room temperature, biphenyl (0.55 g,
3.56 mmol) was added. The reaction mixture was heated to 50 °C
and stirred for 3 h. The crude product was purified twice by flash
chromatography (hexane) to yield ortho isomer 24c as a colorless
oil and para isomer 24a as a white solid. para Isomer 24a: yield
36% (155 mg) p:m:o (24a/24b/24c) 97:2:1. Rf = 0.44 (dichlorometh-
ane/hexane, 1:3). ortho Isomer 24b: yield 34% (147 mg). Rf = 0.51
(dichloromethane/hexane, 1:3). Characterization data is consistent
with that published previously.[39]
Diphenylmethane (16): Method B with benzene at 90 °C and 32 mg
(0.14 mmol) of FeCl3. Total reaction time 4 h, after which the
washed crude product was purified with flash chromatography with
hexane to yield a colorless oil, yield 40% (117 mg). Rf = 0.65
(dichloromethane/hexane, 1:3). Characterization data is consistent
with that published previously.[35]
1-Methyl-4-(phenylmethyl)benzene (17): Method B with toluene at
90 °C. Total reaction time 24 h, after which the washed crude prod-
uct was purified with flash chromatography with hexane to yield a
colorless oil, yield 48% (155 mg), ratio of isomers p:m:o (17a/17b/
17c) 53:5:42. Rf = 0.73 (dichloromethane/hexane, 1:3). Characteri-
zation data is consistent with that published previously.[36]
1-Chloro-4-(phenylmethyl)benzene (25): Method B with benzene at
50 °C. Total reaction time: 4 h, after which the washed crude prod-
uct was purified by flash chromatography (hexane) to yield a color-
less oil, yield 68% (243 mg). Rf = 0.58 (dichloromethane/hexane,
1:3). Characterization data is consistent with that published pre-
viously.[40]
1,4-Dimethyl-2-(phenylmethyl)benzene (18): Method B with para-
xylene at 90 °C. Total reaction time 3 h, after which the washed
crude product was purified with flash chromatography with hexane
to yield a colorless oil, yield 78% (269 mg). Rf = 0.73 (dichloro-
methane/hexane, 1:3). Characterization data is consistent with that
published previously.[17i]
1-[(4-Chlorophenyl)methyl]-2,4-dimethylbenzene (26): Method
B
with meta-xylene at 50 °C. Total reaction time 3 h, after which the
washed crude product was purified with flash chromatography with
hexane to yield a colorless oil, yield 72% (309 mg), ratio of isomers
o:m:p p:o:m (26a/26b/26c) 87:13:trace. Rf = 0.80 (dichloromethane/
hexane, 1:3). For the mixture of isomers: 1H NMR (CD2Cl2,
500.13 MHz, 25 °C): δ = 7.27–7.22 (m, 2 H, 26a + 2 H, 26b), 7.12–
7.07 (m, 2 H, 26a + 3 H, 26b), 7.02–6.97 (m, 3 H, 26a + 2 H, 26b),
4.05 (s, 2 H, 26b), 3.93 (s, 2 H, 26a), 2.32 (s, 3 H, 26a), 2.25 (s, 6
H, 26b), 2.20 (s 3 H, 26a) ppm. 13C NMR (CD2Cl2, 125.76 MHz,
25 °C): δ = 140.0, 139.1, 137.5, 136.9, 136.8, 136.6, 135.9, 131.8,
131.6, 130.5, 130.2, 129.7, 128.8, 128.6, 127.1, 126.9, 38.7, 34.7,
2,4-Dimethyl-1-(phenylmethyl)benzene (19): Method B with meta-
xylene at 50 °C. Total reaction time 3 h, after which the washed
crude product was purified with flash chromatography with hexane
to yield a colorless oil, yield 76% (264 mg), ratio of isomers p:o
(19a/19b) 82:18. Rf = 0.67 (dichloromethane/hexane, 1:3). Charac-
terization data is consistent with that published previously.[17i]
1,3,5-Trimethyl-2-[(4-methylphenyl)methyl]benzene (20): Method C
with mesitylene as solvent. Total reaction time 3 h at room temp.
and 2 h at 90 °C, after which the washed crude product was puri-
fied with flash chromatography with hexane to yield a colorless
oil, yield 80% (297 mg). Rf = 0.70 (dichloromethane/hexane, 1:3).
Characterization data is consistent with that published pre-
viously.[37]
21.1, 20.3, 19.7 ppm. IR (film): ν
= 2918, 1488, 1442, 1091,
˜
max
1033 cm–1. MS (EI): m/z = 230 [M+]. C15H15Cl (230.74): calcd. C
78.1, H 6.6; found C 77.5, H 6.4. Inconsistency in the carbon analy-
sis is possibly a result of volatility issues in the mass analysis (see
also General Considerations).
1-Methoxy-4-(phenylmethyl)benzene (21): Method C with dichloro-
methane as solvent. After 2 h at room temperature, anisole
(1.5 mL, 13.8 mmol) was added. The reaction mixture was then
heated to 50 °C and stirred for 4 h. The crude product was purified
by flash chromatography (0–40% dichloromethane/hexane) to yield
both isomers separately as colorless oils, yield para isomer 21a:
51% (178 mg), ratio of isomers p:o (21a/21b) 99:1, Purity = 95%.
Rf = 0.32 (dichloromethane/hexane, 1:3). ortho isomer 21b: 30%
(103 mg). Rf = 0.43. Characterization data is consistent with that
published previously.[37]
2,4-Dimethyl-1-[(4-methylphenyl)methyl]benzene (27): Method
B
with meta-xylene at 50 °C. Total reaction time 3 h, after which the
washed crude product was purified with flash chromatography with
hexane to yield a colorless oil, yield 91% (337 mg), ratio of isomers
p:o (27a/27b) 87:13. Rf = 0.76 (dichloromethane/hexane, 1:3). For
1
the mixture of isomers: H NMR (CD2Cl2, 500.13 MHz, 25 °C): δ
= 7.12–7.01 (m, 6 H, 27a + 5 H, 27b), 6.99–6.93 (m, 1 H, 27a + 2
H, 27b), 4.04 (s, 2 H, 27b), 3.93 (s, 2 H, 27a), 2.33 (s, 3 H, 27a),
2.32 (s, 3 H, 27a, 3 H, 27b), 2.27 (s, 6 H, 27b), 2.23 (s, 3 H,
27a) ppm. 13C NMR (CD2Cl2, 125.76 MHz, 25 °C): δ = 138.2,
137.7, 137.5, 137.2, 136.73, 136.70, 136.2, 135.8, 135.6, 131.4,
130.1, 129.4, 128.9, 128.4, 128.1, 126.9, 126.6, 38.9, 34.9, 21.10,
4-(Phenylmethyl)phenol (22): Method C with dichloromethane as
solvent. After 2 h at room temperature, phenol (0.50 g, 5.28 mmol)
was added. The reaction mixture was then heated to 50 °C and
additional FeCl3 (11 mg, 0.07 mmol) was added after 1 h. The mix-
ture was stirred for additional 1 h. Crude product was purified by
flash chromatography (0–15% EtOAc/hexane) to yield both iso-
mers separately as yellowish oils from which the para isomer 22a
slowly crystallized, yield para isomer 22a: yield 32% (104 mg). Pu-
rity: 97%. Rf = 0.43 (1:4 EtOAc/hexane); ortho isomer 22b: 30%
21.06, 20.4, 19.8 ppm. IR (film): ν
= 2918, 1512, 1442, 1116,
˜
max
1034, 1021 cm–1. MS (EI): m/z = 210 [M+]. C16H18 (210.32): calcd.
C 91.4, H 8.6; found C 88.4, H 8.4. Inconsistency in the carbon
analysis is possibly a result of volatility issues in the mass analysis
(See also General Considerations).
2-[(2,4-Dimethylphenyl)methyl]phenol (28): Method B with meta-
xylene at 50 °C. Total reaction time 2 h, after which the washed
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Date: 08-05-14 17:47:26
Pages: 12
Iron-Catalyzed Arylation of Aromatic Ketones and Aldehydes
crude product was purified with flash chromatography (0–15%
EtOAc/hexane) to yield a colorless oil, yield 39% (144 mg), ratio
ture was heated to 90 °C and stirred for 5 h followed by general
work up and purification by flash chromatography (0–40% dichlo-
romethane/hexane) to yield a colorless liquid, which slowly solidi-
of isomers o:m:p 5:0:95. Rf = 0.50 (1:4 EtOAc/hexane). For major
1
isomer: H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.11 (dt, J = fied, yield 99% (531 mg), ratio of isomers pp:op (31a/31b) 88:12.
1.4, 7.8 Hz, 1 H), 7.02 (s 1 H), 6.96–6.92 (m, 3 H), 6.85 (dt, J =
1.4, 7.8 Hz, 1 H), 6.79 (dd, J = 0.9, 8.2 Hz, 1 H), 4.85 (b, 1 H),
3.92 (s, 2 H), 2.30 (s, 3 H), 2.25 (s, 3 H) ppm. 13C NMR (CD2Cl2,
150.92 MHz, 25 °C): δ = 154.2, 137.0, 136.5, 135.1, 131.5, 130.9,
129.4, 127.9, 127.1, 127.0, 121.2, 115.8, 33.5, 21.0, 19.7 ppm. IR
Rf = 0.21 (dichloromethane/hexane, 1:3). Characterization data is
consistent with that published previously.[41]
1,1Ј-(Phenylmethylene)bis[2,4,6-trimethylbenzene] (32): Into mesit-
ylene (1.7 mL) was suspended FeCl3 (11 mg, 0.07 mmol) and benz-
aldehyde (0.18 mL, 1.76 mmol) was then added. Next, chlorotri-
methylsilane (0.45 mL, 3.52 mmol) was added to the reaction mix-
ture, which dissolved the FeCl3. The mixture was heated to 90 °C
and stirred for 6 h, followed by general work up and purification
by flash chromatography with hexane to yield a colorless oil, which,
when dissolved in ethanol, instantly solidified to a white powder.
The mixture was kept at 4 °C overnight, the powder formed was
separated and dried in vacuo, yield 33% (190 mg). Rf = 0.58
(dichloromethane/hexane, 1:3). Characterization data is consistent
with that published previously.[34]
(film): ν
= 3520, 2917, 1589, 1499, 1452, 1205, 1069 cm–1. MS
˜
max
(EI): m/z = 212 [M+]. HRMS (ESI): calcd. for C15H16O (M – H)
211.1128; found 211.1119.
2-[1-(3-Fluorophenyl)methyl]-4-(1,1-dimethylethyl)phenol
(29):
Method C with dichloromethane as solvent and 3-fluorobenzalde-
hyde (0.19 mL, 1.76 mmol). After 2 h at room temperature, 4-tert-
butylphenol (0.30 g, 2.02 mmol) was added. The reaction mixture
was then heated to 50 °C and stirred for 22 h. Crude product was
purified with flash chromatography (0–15% EtOAc/hexane) to
yield a slightly yellow oil, yield 23% (103 mg). Rf = 0.46 (1:4
2,2Ј-(Phenylmethylene)bis[5-methylthiophene] (33): Into 2-methyl-
thiophene (1.7 mL), was suspended Fe(acac)3 (12 mg, 0.035 mmol)
and after benzaldehyde (0.18 mL, 1.76 mmol) was added. Next,
chlorotrimethylsilane (0.25 mL, 1.94 mmol) was added to the mix-
ture dissolving the FeCl3, reaction was stirred at room temp. for
30 min followed by general work up and purification by flash
chromatography (hexane) to yield a colorless liquid, which slowly
solidified in the freezer to form a white solid, yield 92% (460 mg),
Rf = 0.53 (dichloromethane/hexane, 1:3). Characterization data is
consistent with that published previously.[42]
1
EtOAc/hexane). H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.25
(td, J = 6.2, 8.0 Hz, 1 H), 7.17–7.14 (m, 2 H), 7.04 (d, J = 8.0 Hz,
1 H), 6.93 (br. d, J = 10.2 Hz, 1 H), 6.89 (dt, J = 2.5, 8.4 Hz, 1 H),
6.71 (d, J = 8.4 Hz, 1 H), 4.68 (b, 1 H), 3.97 (s, 2 H), 1.28 (s, 9
H) ppm. 13C NMR (CD2Cl2, 150.92 MHz, 25 °C): δ = 163.4 (d,
JC,F = 244 Hz), 151.7, 144.3, 144.0 (d, JC,F = 7 Hz), 130.2 (d, JC,F
= 10 Hz), 128.4, 125.2, 124.7 (d, JC,F = 2 Hz), 115.7 (d, JC,F
=
21 Hz), 115.4, 113.2 (d, JC,F = 20 Hz), 36.6 (d, JC,F = 2 Hz), 34.3,
31.7 ppm. IR (film): ν
= 3288, 2956, 1615, 1589, 1504, 1234,
˜
max
1180 cm–1. MS (EI): m/z = 258 [M+]. HRMS (ESI): calcd. for
Supporting Information (see footnote on the first page of this arti-
C17H19FO (M – H) 257.1347; found 257.1335.
1
cle): Copies of the H NMR and 13C NMR spectra and GC–MS
chromatograms of all final products.
4-Bromo-4Ј-[(4-fluorophenyl)methyl]-1,1Ј-biphenyl (30): Method C
with dichloromethane as solvent and 4-fluorobenzaldehyde
(0.19 mL, 1.76 mmol). After 2 h at room temperature, 4-bromobi-
phenyl (0.47 g, 2.02 mmol) was added. Temperature was raised to
50 °C and stirred for 4 h. Crude product was purified by flash
chromatography (hexane) to yield both isomers separately with the
ortho isomer as colorless oil which slowly solidified and the para
isomer as a white solid. para Isomer 30a: yield 29% (172 mg). Rf
= 0.43 (dichloromethane/hexane, 1:3). ortho Isomer 30b: yield 22%
(135 mg). Rf = 0.50 (dichloromethane/hexane, 1:3). para Isomer
30a: 1H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.56 (td, J = 2.3,
8.8 Hz, 2 H), 7.50 (td, J = 2.0, 8.3 Hz, 2 H), 7.46 (td, J = 2.4,
8.9 Hz, 2 H), 7.26 (d, J = 8.4 Hz, 2 H), 7.22–7.18 (m, 2 H), 7.00
(tt, J = 2.4, 8.9 Hz, 2 H), 3.99 (s, 2 H) ppm. 13C NMR (DMSO,
150.92 MHz, 25 °C): δ = 161.9 (d, JC,F = 243 Hz), 141.2, 140.2,
138.2, 137.3 (d, JC,F = 3 Hz), 132.2, 130.7 (d, JC,F = 8 Hz), 129.7,
Acknowledgments
Financial support to R. S. from the National Doctoral Program of
Organic Chemistry and Chemical Biology (2010–2013), Stiftelsen
för Åbo Akademi, Orion Farmos Research Foundation and
Magnus Ehrnrooth Foundation is gratefully acknowledged.
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129.0, 121.6, 115.6 (d, JC,F = 21 Hz), 41.0 ppm. νmax (solid) = 2903,
˜
1601, 1508, 1476, 1238 cm–1. MS (EI): m/z = 340/342 [M+].
C19H14BrF (341.22): calcd. C 66.9, H 4.1; found C 66.9, H 4.1.
ortho Isomer 30b: 1H NMR (CD2Cl2, 600.13 MHz, 25 °C): δ = 7.50
(td, J = 2.3, 8.9 Hz, 2 H), 7.34–7.27 (m, 3 H), 7.24–7.20 (m, 2 H),
7.10 (td, J = 2.3, 8.9 Hz, 2 H), 7.89 (br. d, J = 7.4 Hz, 4 H), 3.91
(s, 2 H) ppm. 13C NMR (CD2Cl2, 150.92 MHz, 25 °C): δ = 161.6
(d, JC,F = 243 Hz), 141.4, 141.0, 138.5, 137.5 (d, JC,F = 4 Hz),
131.5, 131.4, 130.7, 130.5, 130.4 (d, JC,F = 4 Hz), 128.3, 126.9,
121.4, 115.3, (d, JC,F = 21 Hz), 38.6 ppm. IR (film): ν
= 3045,
˜
max
1605, 1508, 1474, 1222 cm–1. MS (EI): m/z = 340/342 [M+].
C19H14BrF (341.22): calcd. C 66.9, H 4.1; found C 66.8, H 4.1.
4,4Ј-Dimethoxytrityl (31): Into anisole (1.7 mL) was suspended
FeCl3 (11 mg, 0.07 mmol) and benzaldehyde (0.18 mL, 1.76 mmol)
was added. Next, chlorotrimethylsilane (0.25 mL, 1.94 mmol) was
added to the reaction mixture, which dissolved the FeCl3. The mix-
Eur. J. Org. Chem. 0000, 0–0
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Job/Unit: O42023
/KAP1
Date: 08-05-14 17:47:26
Pages: 12
R. Savela, M. Majewski, R. Leino
FULL PAPER
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Iron-Catalyzed Arylation of Aromatic Ketones and Aldehydes
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Job/Unit: O42023
/KAP1
Date: 08-05-14 17:47:26
Pages: 12
R. Savela, M. Majewski, R. Leino
FULL PAPER
Iron Catalyzed Reactions
R. Savela, M. Majewski,
R. Leino* ........................................ 1–12
Iron-Catalyzed Arylation of Aromatic
Ketones and Aldehydes Mediated by
Organosilanes
A robust one-pot, iron-catalyzed chlorin-
ation Friedel–Crafts alkylation reaction of
benzylic carbonyl compounds, mediated
by chlorotrimethylsilane and triethylsilane,
has been developed to yield substituted di-
aryl and triaryl building blocks.
Keywords: Synthetic methods
/ Homo-
geneous catalysis / Iron / Silanes
12
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