Biomimetic transfer hydrogenation of 2-alkoxy- and 2-aryloxyketones with iron-porphyrin catalysts

Article abstract of DOI:10.1016/j.tet.2008.01.083

In situ generated iron porphyrins are applied as homogeneous catalysts in the transfer hydrogenation of α-substituted ketones. Using 2-propanol as hydrogen donor various protected 1,2-hydroxyketones are reduced to the corresponding mono-substituted 1,2-di

Full text of DOI:10.1016/j.tet.2008.01.083

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3867e3876
www.elsevier.com/locate/tet
Biomimetic transfer hydrogenation of 2-alkoxy- and
2-aryloxyketones with ironeporphyrin catalysts
*
Stephan Enthaler, Bjorn Spilker, Giulia Erre, Kathrin Junge, Man Kin Tse, Matthias Beller
¨
Leibniz-Institut fu¨r Katalyse e.V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, D-18059 Rostock, Germany
Received 24 April 2007; received in revised form 14 January 2008; accepted 19 January 2008
Available online 30 January 2008
Abstract
In situ generated iron porphyrins are applied as homogeneous catalysts in the transfer hydrogenation of a-substituted ketones. Using 2-prop-
anol as hydrogen donor various protected 1,2-hydroxyketones are reduced to the corresponding mono-substituted 1,2-diols in good to excellent
yield. Under optimized reaction conditions catalyst turnover frequencies up to 2500 hꢀ1 have been achieved.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
A much less explored reaction is the transition metal-cata-
lyzed reduction of 1,2-hydroxyketones. Among the different
reductions, the transfer hydrogenation with 2-propanol as non-
toxic hydrogen donor is practical and easy to perform.2,3 Until
now only a few number of applications were reported using Rh
or Ru based metal catalysts in the reduction of protected 1,2-
hydroxyketones, which is in contrast to the well-studied reduc-
tion of acetophenone.4
The relevance of 1,2-diols is impressively shown by the pro-
duction of ethylene and propylene glycol on multi-million ton
scale for the synthesis of polymers and anti-freeze compounds.
In addition, more complex 1,2-diols and their derivatives consti-
tute interesting building blocks for a variety of biologically
active compounds.
In general, synthetic approaches to 1,2-diols are based on oxi-
dative processes of olefins. Typical processes include the epoxi-
dation of C]C double bonds with peracids or hydroperoxides
and subsequent hydrolysis, and the dihydroxylation of olefins
in the presence of osmium catalysts (Scheme 1).1
A major challenge for catalytic hydrogenations is the substi-
tution of expensive and rare transition metals (Ir, Rh, Ru) by
ubiquitous available, inexpensive and less toxic metals. Conse-
quently, the use of iron catalysts is especially desirable.5 Up to
now, homogeneous iron catalysts have been mostly used for
O
OH
R2
R3
HO
R1
R4
R2
R3
Hydrogenation
Dihydroxylation
OR5
R2
R1
R1
R4
R3
O
Epoxidation
Ring-
opening
Reduction
R2
R3
R1 O
R4
O
R1
R2
Scheme 1. Possible approaches to 1,2-diols.
* Corresponding author. Tel.: þ49 381 1281 113; fax: þ49 381 1281 5000.
E-mail address: matthias.beller@catalysis.de (M. Beller).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.083

3868
S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
Table 1
Influence of iron salts in the transfer hydrogenation of 2-methoxyacetophe-
none 4
carbonecarbon bond formation, such as olefin polymerizations,
cross couplings and cycloadditions as well as reduction of nitro
compounds.6 However, much less attention was directed to-
wards iron-catalyzed transfer hydrogenation. Only the groups
of Noyori,7 Vancheesan,8 Bianchini,9 Gao,10 and Morris11 re-
ported the utilization of iron salts and iron complexes, contain-
ing tetradentate phosphines9 or aminophosphines,10 in the
reduction of ketones and a,b-unsaturated carbonyl compounds
to yield alcohols and a,b-saturated carbonyl compounds.12
More recently, we established two iron-based methods for the
effective transfer hydrogenation of aryl-alkyl as well as alkyl-
alkyl ketones utilizing 2-propanol as the hydrogen source.13
On the one hand we applied a combination of iron salts, triden-
tate amines and phosphines as catalysts and on the other hand an
in situ catalyst composed of an iron salt and porphyrins has been
used (Scheme 2).13 Unfortunately, both catalyst systems faced
some difficulties with a-substituted alkyl-aryl ketones. Herein
we report for the first time the successful hydrogenation of
a-alkoxy- and a-aryloxy-substituted acetophenones in the pres-
ence of ironeporphyrin complexes.
O
OH
OMe
OMe
[Fe]/1a
NaOH, 2-PrOH
4 h, 100 °C
4
5
Entry
Iron source
Yielda [%]
1
d
FeF2
<1
>99
>99
37
2
3
FeCl2
FeCl2
4b
5
FeCl3
FeBr2
FeI2
>99
>99
>99
>99
>99
>99
>99
>99
>99
6
7
8
Fe(acac)2
Fe(acac)3
FeSO4$7H2O
CpFe(CO)2I
Fe(III)citrate$H2O
Fe3(CO)12
9
10
11
12c
13
Reaction conditions: 0.0038 mmol in situ catalyst (0.0038 mmol Fe-source or
0.0013 mmol Fe3(CO)12 and 0.0038 mmol 1a in 1.0 mL 2-propanol for 16 h at
65 ꢁC), 0.19 mmol NaOH in 0.5 mL 2-propanol, 0.38 mmol 2-methoxyaceto-
phenone 4 in 0.5 mL 2-propanol, 4 h at 100 ꢁC.
2. Results and discussion
a
Yield was determined by GC analysis (30 m HP Agilent Technologies 50e
300 ꢁC) with diglyme as internal standard.
For exploratory experiments the hydrogenation of 2-me-
thoxyacetophenone was used as a model reaction. Typically,
the pre-catalyst is prepared by stirring a solution of 1 mol %
iron salt and 1 mol % 1a in 2-propanol (1.0 mL) for 16 h at
65 ꢁC. After addition of 50 mol % base the mixture is heated
for 5 min at 100 ꢁC and the substrate 2-methoxyacetophenone
4 is added. At first, the influence of different iron precursors on
the reaction rate was studied (Table 1). To our delight full con-
version is obtained in all cases within 4 h. Obviously, the for-
mation of the active catalyst is independent from the Fe-salt
and is complete for all stated pre-catalysts under standard con-
ditions. Without any Fe present no conversion took place and
using FeCl2 without ligand gave only 37% yield. From a point
of view of practical convenience we chose FeCl2 as iron
source in combination with porphyrin ligands for further
investigations.
b
No ligands are added.
Fe(III)citrate was recrystallized before use.14
c
It is well known that type and also amount of base are im-
portant parameters for obtaining reasonable quantities of prod-
uct in transfer hydrogenations. Thus, we investigated
frequently used bases, such as NaOH, KOH and KOtBu. In
all cases excellent yields are achieved, except for LiOH and
Cs2CO3 (Table 2). Diminishing the base of concentration to
5e10 mol % resulted in a decrease of yield of 2-methoxy-1-
phenylethanol 5, while 25 mol % of base still gave excellent
yield within 2 h. Noteworthy, in the absence of base no trans-
fer of hydrogen occurred (Table 2, entry 15). In addition, nitro-
gen-containing bases (e.g., pyridine, NEt3, DBU) were tested,
but only unsatisfactory results were attained (conversion:
<1%).
R
1a R = p-Cl-C6H4
Next, we focused our attention on the influence of the reac-
tion temperature (Table 2, entries 1 and 10e14). An optimal
catalyst activity was obtained in the range of 60e100 ꢁC.
However, even at lower temperature a moderate yield was at-
tained (40 ꢁC, conversion: 18%). To support the formation of
the active catalyst at low temperature two different activation
methods were carried out.
NH
N
N
1b R = C6H5
1c R = p-C6H4NMe3Tos
1d R = C6F5
1e R = 4-pyridyl
R
R
HN
R
MeO2C(H2C)2
On the one hand, substitution of strong coordinating chlo-
ride anions by weaker BFꢀ4 anions via addition of AgBF4
was done. On the other hand activation of the catalyst by light
irradiation (PerkineElmer PE300BF lamp with hot mirror,
w380e770 nm) has been tried. Surprisingly, both procedures
led to complete deactivation of the catalysts with respect to
hydrogenation reaction.
(CH2)2CO2Me
NH
N
N
N
N
N
Cl
Fe
N
HN
MeO2C(H2C)2
(CH2)2CO2Me
(CH2)2CO2H
HO2C(H2C)2
coproporphyrin I (2)
chlorprotoporphyrin IX Fe (III) (3)
In order to further improve the catalyst system we applied
different porphyrin ligands (1ae3) under the optimized
Scheme 2. Selection of applied porphyrin ligands.13

S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
3869
Table 2
Influence of temperature and base in the Fe-catalyzed transfer hydrogenation
of 2-methoxyacetophenone 4
Table 3
Screening of different porphyrins in the Fe-catalyzed transfer hydrogenation of
2-methoxyacetophenone 4
O
OH
O
OH
OMe
OMe
OMe
FeCl2/1a
OMe
FeCl2/Porphyrin
base, 2-PrOH, 4 h
NaOH, 2-PrOH, 2 h
4
5
4
5
Entry
Base
Base [mol %]
Temp [ꢁC]
Yielda [%]
Entry
Ligand
Catalyst loading [mol %]
Yielda [%]
TOFb [hꢀ1
]
1
NaOH
KOH
50
50
50
50
50
50
50
50
50
50
50
50
50
50
d
5
100
100
100
100
100
100
100
100
100
25
>99
>99
49
1
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
2
0.5
>99
42
>99
2100
>99
1500
>99
900
2
2
0.01
0.5
3
LiOH
3
>99
30
4
NaOiPr
KOtBu
NaOtBu
K2CO3
Na2CO3
Cs2CO3
NaOH
NaOH
NaOH
NaOH
NaOH
d
>99
>99
>99
>99
97
4
0.01
0.5
5
5
>99
18
6b
7
6
0.01
0.5
7
>99
23
>99
1150
>99
1200
>99
1850
>99
1300
8
8
0.01
0.5
9
37
<1
9
>99
24
10c
11
12d
13
14
15e
16e
17e
18e
19e
10
11
12
13
14
0.01
0.5
40
40
18
<1
>99
37
2
0.01
0.5
60
80
>99
>99
<1
3
>99
26
3
0.01
100
100
100
100
100
Reaction conditions: 0.0019 mmol or 0.038 mmol in situ catalyst
(0.0019 mmol or 0.038 mmol FeCl2 and 0.0019 mmol or 0.038 mmol porphyrin
in 1.0 mL 2-propanol for 16 h at 65 ꢁC), 0.095 mmol or 0.0019 mmol sodium
hydroxide in 0.5 mL 2-propanol, 0.38 mmol 2-methoxyacetophenone 4 in
0.5 mL 2-propanol, 2 h at 100 ꢁC.
NaOH
NaOH
NaOH
NaOH
17
55
10
25
50
>99
>99
a
Reaction conditions: 0.0038 mmol in situ catalyst (0.0038 mmol FeCl2 and
0.0038 mmol 1a in 1.0 mL 2-propanol for 16 h at 65 ꢁC), 0.19 mmol base in
0.5 mL 2-propanol, 0.38 mmol 2-methoxyacetophenone 4 in 0.5 mL 2-propa-
nol, 4 h at described temperature.
Yield was determined by GC analysis (30 m HP Agilent Technologies
50e300 ꢁC) with diglyme as internal standard.
b
Turnover frequencies were determined after 2 h.
a
Yield was determined by GC analysis (30 m HP Agilent Technologies
50e300 ꢁC) with diglyme as internal standard.
b
t
A mixture of solvents was used BuOH and 2-propanol 1:4.
c
O
OH
Light assisted reaction, thereby only the visible range was applied since the
ultraviolet range was shielded.
OMe
OMe
FeCl2/1a
NaOH, 2-PrOH, 2 h
d
Addition of 2 equiv AgBF4 with respect to FeCl2.
Reaction time: 2 h.
e
4
5
60
50
40
30
20
10
0
3000
2500
2000
1500
1000
500
conditions, namely 0.5 or 0.01 mol % Fe catalyst (FeCl2 and
the corresponding porphyrin in a ratio of 1:1), sodium hydrox-
ide (25 mol % or 0.5 mol %) at 100 ꢁC (Table 3). In case of
0.5 mol % catalyst loading for all ironeporphyrin catalysts ex-
cellent conversion was attained. For 0.01 mol % catalyst load-
ing best performance was achieved with the meso-substituted
porphyrin 1a (Table 3, entry 2). Substitution at the meso-phe-
nylic system of porphyrin with electron withdrawing groups
(1c and 1d) lowered the catalyst activity. Furthermore, an ex-
cellent turnover frequency of 1850 hꢀ1 was observed with
a porphyrin substituted at the b-pyrrolenic positions (Table 3,
entry 12). The complex chloroprotoporphyrin IX Fe(III) 3 was
utilized without catalysts pre-formation as described for all
other representatives, and good turnover numbers were deter-
mined (Table 3, entries 13 and 14). Reducing the catalyst load-
ing to 0.01 mol % turnover frequencies up to 2100 hꢀ1 were
realized (Table 3, entries 1e3).
2500
2450
2100
1850
1200
//
//
0
0
5
amount of water [mol%]
10
25
50
500
Figure 1. The influence of water addition on hydrogenation of 2-methoxyace-
tophenone 4. Reaction conditions: 0.038 mmol in situ catalyst (0.038 mmol
FeCl2 and 0.08 mmol 1a in 1.0 mL 2-propanol for 16 h at 65 ꢁC), 1.9 mmol
NaOH in 0.5 mL 2-propanol, the corresponding amount of water, 0.38 mmol
substrate in 0.5 mL 2-propanol, temperature: 100 ꢁC, reaction time: 2 h. Yield
was determined by GC analysis (30 m HP Agilent Technologies 50e300 ꢁC)
with diglyme as internal standard.
Notably, the addition of small amounts of water
(5e10 mol %) accelerated the transfer hydrogenation com-
pared to the water-free conditions and turnover frequencies
up to 2500 hꢀ1 were achieved. Higher amounts of water (up
to 500 mol %) hampered the reaction (Fig. 1).

3870
S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
Table 4
Reduction of a-substituted ketones in the presence of iron catalyst containing
porphyrin 1a
Under optimized conditions (vide supra), we compared the
activity of thecatalytic system forthe reduction of acetophenone
6, ortho-methoxyacetophenone 8 and 2-methoxyacetophenone
4. Here, the yield of 1-phenylethanol 7, ortho-methoxy-1-phe-
nylethanol 9 and 2-methoxy-1-phenylethanol 5 was monitored
during the reaction.
OH
O
FeCl2/1a
X
X
R4
R4
R1
R1
NaOH, 2-PrOH, 100 °C, 2 h
R2
R2
R3
R3
The attained curves are shown in Figure 2. The reduction of
2-methoxyacetophenone proceeded without any induction pe-
riod or deactivation process. Similar behaviour was observed
for ortho-methoxyacetophenone, albeit a slight deceleration
occurred after nearly 100 min. Nevertheless, full conversion
was reached after 7 h. In case of acetophenone the reduction
process was significantly slower. After 8 h a deactivation
took place. Notably, the activities are in agreement with the
oxidation potentials of the applied ketones (2-methoxyaceto-
phenone, E0¼213 mV; ortho-methoxyacetophenone, E0¼
141 mV;15 acetophenone, E0¼118 mV).
Entry
1
Substrate
Product
Conv. [%]
O
OH
OMe
OMe
>99
4
5
OH
O
O
O
2
3
92
10
10a
O
OH
OH
O
O
>99a
In order to demonstrate the usefulness of our method the
catalyst containing ligand 1a was tested in the hydrogenation
of several hydroxy-protected 1,2-hydroxyketones (Table 4).
In general, the substrates were synthesized by reacting
2-bromo ketones with different alcohols in the presence of
a base.16 A first set of experiments was dedicated to the variation
of the protecting group. Good to excellent yield was obtained by
changing the methoxy group by phenoxy substituents. Best results
were achieved with the p-chlorophenoxy substituent (Table 4,
Cl
Cl
11a
11
t-Bu
t-Bu
O
O
O
4
97
12
12a
O
i-Pr
OH
i-Pr
O
O
5
6
7
74a
i-Pr
i-Pr
R1
R1
O
OH
[Fe]/1a
13
13a
R2
R2
Na-2-OPr, 2-PrOH, 100 °C
OH
O
43
5 R1 = H; R2 = OMe
7 R1 = H; R2 = H
9 R1 = OMe; R2 = H
O
4 R1 = H; R2 = OMe
6 R1 = H; R2 = H
8 R1 = OMe; R2 = H
O
14
14a
OH
O
O
O
100
90
80
70
60
50
40
30
20
10
0
48
15
15a
OH
O
O
O
8
>99a
16
16a
O
OH
O
O
9
Ph
17
Ph
17
83a
MeO
MeO
7
9
5
O
OH
10
11
12
<1a
OAc
18
OAc
18a
0
100
200
300 400
time [min]
500
600
700
O
OH
O
O
<1a
<1b
Si
19
Si
Figure 2. Comparative study between acetophenone 6, ortho-methoxyaceto-
phenone 8 and 2-methoxyacetophenone 4. Reaction conditions: 0.0038 mmol
in situ catalyst (0.0038 mmol FeCl2 and 0.0038 mmol 1a in 1.0 mL 2-propanol
for 16 h at 65 ꢁC), 0.19 mmol base in 0.5 mL 2-propanol, 0.76 mmol substrate
in 0.5 mL 2-propanol, temperature: 100 ꢁC. Yield was determined by GC anal-
ysis (7: 50 m Lipodex E, 95e150 ꢁC, 7: 50 m Lipodex E, 90e180 ꢁC, 9: 30 m
HP Agilent Technologies 50e300 ꢁC) with diglyme as internal standard.
19a
O
OH
OH
OH
20
20a

S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
3871
Table 4 (continued)
Entry
Substrate
Product
OH
Conv. [%]
O
13
OH
21
<1b
OH
Ph
Ph
21a
O
O
OH
O
3 (<1)c
N
N
14
22
22a
Reaction conditions: 0.0019 mmol in situ catalyst (0.0019 mmol FeCl2 and
0.0019 mmol porphyrin in 1.0 mL 2-propanol for 16 h at 65 ꢁC),
0.095 mmol sodium hydroxide in 0.5 mL 2-propanol, 0.34 mmol substrate in
0.5 mL 2-propanol, 2 h at 100 ꢁC. Yield was determined by GC analysis
(30 m HP Agilent Technologies 50e300 ꢁC).
a
1H NMR.
b
Decomposition.
Reaction time: 24 h.
c
Figure 3. Cyclic voltammograms of porphyrins with FeCl2 in 0.1 mol/L
TBA$BF4 in 2-PrOH. Start at 0 V in positive direction with 10 mV/s at plati-
num microelectrode.
entry 3). Increasing the bulkiness at o- and o0-position the con-
version decreased significantly (Table 4, entry 5), while substi-
tution only at o-position led to excellent conversion of the
desired product (Table 4, entry 4). Substitution on the acetophe-
none skeleton by a p-methyl or p-methoxy group gave good to
full conversion. In addition, indanone and pinacolin based sub-
strates were synthesized and tested in this transfer hydrogena-
tion, thereby moderate conversions were obtained (Table 4,
entries 6 and 7). Unfortunately, variation of the hydroxyl pro-
tecting group to the common acetyl and tert-butyldimethylsilyl
groups displayed an inactivity of the presented catalyst (Table 4,
entries 10 and 11). The hydrogenation of 2-hydroxy-acetophe-
none20and2-hydroxy-2-methyl-1-phenylpropan-1-one21were
not successful since decomposition was observed. In addition, 2-
morpholino-acetophenone 22, which is a promising precursor for
1,2-amino alcohols, was subjected to the transfer hydrogenation
protocol. Unfortunately, no conversion was observed even if the
reaction time was extended to 24 h (Table 4, entry 14).
In order to get further informations about the presented cata-
lytic system we carried out electrochemical investigations of
the in situ catalysts containing ligands 1aee. Cyclic voltam-
metry has been established as a useful tool for studying the
electrochemical properties of porphyrins and metalloporphy-
rins.17 The measurement conditions were as close to the reac-
tion conditions as possible. However, under strong basic
conditions, no reliable measurements were possible, due to
low catalyst solubility at room temperature. Therefore mea-
surements were performed in the absence of base. The temper-
ature dependence of the potentials according to the Nernst
equation have to be similar for all Fe-porphyrins and should
be in the range of 20e30 mV between room temperature
and the reaction temperature of 100 ꢁC. The electrochemical
analysis is presented in Figure 3.
resulted from free FeCl2 (light yellow coloured solution) or
incomplete Fe(II)-porphyrin formation can be excluded.18
Most likely the difference in oxidation currents results from
different solubilities of the Fe-porphyrins, since the diffusion
coefficients should be similar. The porphyrins without FeCl2
(violet coloured solution) generate only a small oxidation cur-
rent in the region above ca. 0.6 V, which is shown by the cyclic
voltammogram of the porphyrin 1a without FeCl2 (Fig. 3).
This oxidation current was also observable in the curves of
the Fe(II)-porphyrins in the same potential range.
The second oxidation steps visible in all curves (0.5e0.6 V)
cannot clearly be interpreted under the applied conditions. Most
likely the second oxidation step is caused by formation of other
complexes, since 2-propanol and chloride ions are present in the
solution, which are possible ligands for the axial position. Dur-
ing oxidation of Fe(II)- to Fe(III)-porphyrin one anion has to
fulfil the unsaturated situation at the Fe(III) centre analogue
to compound 3 as shown in Scheme 2. At the same time it
has to be considered that Fe(II)-porphyrins can also be coordi-
nated with two axial ligands (six-coordinated Fe(II)).17,19 The
small amount of dissolved chloride results probably in slower
kinetics of the Fe(III)-porphyrin formation, seen by the revers-
ible potential values (Table 5).
Due to the influence of the axial ligand a change or different
coordination of the porphyrins at the axial positions results in
a shift of potential (with an excess of chloride the potentials
shift to lower values with higher reversibility).17 The half-
wave potentials for the first oxidation step resulting from the
Table 5
Half-wave potentials and values for reversibility
All cyclic voltammograms illustrate clearly the oxidation of
Fe(II) to Fe(III) in the potential range above ca. 0.2 V versus
SCE. The small (negative) reduction currents result probably
from Fe(III) contamination of the FeCl2 or from oxidation of
FeCl2 from other impurities (e.g., O2). From the colour
of the solutions (light brown to red-brown) and the height of
oxidation current (compared to 5 mmol/L FeCl2) the curves
Compound
TOF
E1/2 vs SCE [mV]
Slope [mV]
1d
1e
1150
1200
1500
2100
d
326
339
338
330
380
525
146
141
152
204
205
61
1b
1a
FeCl2
Ferrocene
d

3872
S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
measurements under these conditions are presented in Table 5.
Under conditions identical with those for the porphyrins the
ferrocenium/ferrocene couple has a half-wave potential of
525 mV and a slope of 61 mV (E1/2¼480 mV in 0.1 mol/L
TBA$PF6/CH2Cl2).20 With the half-wave potentials of the
Fe-porphyrins no correlation with the TOF can be found. In
addition following our standard protocol the formation of the
pre-catalyst was studied by in situ mass spectroscopy. After
stirring FeCl2 and ligand 1a for 16 h at 65 ꢁC the correspond-
ing iron complex21 formed by elimination of 2 equiv of HCl
was detected, which is in agreement with previous reports.22
However, the actual active Fe-species is still unclear.
(300 MHz, CDCl3): d¼8.02e7.98 (m, 2H); 7.64e7.58 (m,
1H); 7.53e7.46 (m, 2H); 7.31e7.22 (m, 2H); 7.01e6.90 (m,
3H); 5.28 (s, 2H, CH2). 13C NMR (75.5 MHz, CDCl3):
d¼194.5; 157.9; 134.5; 133.8; 129.5; 128.8; 128.1; 121.6;
114.7; 70.7. IR (KBr): 3387 w; 3060 w; 2897 w; 2843 w;
2749 w; 1928 w; 1708 s; 1599 s; 1499 s; 1480 m; 1449 m;
1433 m; 1386 w; 1341 w; 1303 m; 1292 m; 1250 s; 1228 s;
1189 m; 1175 m; 1094 m; 1076 m; 1028 w; 1001 m; 975
m; 921 w; 886 w; 872 m; 751 s; 688 s; 665 m; 614 w; 584
w; 555 w; 511 m; 414 w. MS (EI): m/z (%)¼212 ([Mþ],
26); 105 (100); 77 (43); 51 (12). HRMS calculated for
C14H14O2: 214.09883; found: 214.098506.
In conclusion, we have demonstrated the successful exten-
sion of the Fe-catalyzed transfer hydrogenation to a-hydroxy-
protected ketones. Under optimized conditions turnover
frequencies up to 2500 hꢀ1 were achieved. The scope and lim-
itation of the catalyst were demonstrated on reduction of 10
different ketones with good to excellent yields.
3.2.2. 2-(4-Chlorophenoxy)-acetophenone (11)
Refluxing time: 12 h, crystallized from 2-propanol,
7.8 mmol scale. Yield: 73% (white plates). Mp¼87e88 ꢁC.
1H NMR (300 MHz, CDCl3): d¼8.01e7.96 (m, 2H); 7.66e
7.56 (m, 1H); 7.54e7.47 (m, 2H); 7.26e7.20 (m, 2H);
6.90e6.83 (m, 2H); 5.26 (s, 2H, CH2). 13C NMR
(75.5 MHz, CDCl3): d¼194.0; 156.6; 134.3; 134.0; 129.4;
128.9; 128.0; 126.5; 116.1; 70.9. IR (KBr): 3375 w; 3060 w;
2901 w; 2851 w; 2737 w; 1699 s; 1596 s; 1581 m; 1490 s;
1448 m; 1437 s; 1409 w; 1385 w; 1338 w; 1317 w; 1289 s;
1231 s; 1172 m; 1106 m; 1096 m; 1089 m; 1075 m; 1001
m; 983 s; 921 w; 870 w; 830 s; 813 m; 786 w; 756 s; 701
w; 686 s; 634 w; 587 m; 508 m; 476 w; 457 w; 441 w; 422
w; 406 w. MS (EI): m/z (%)¼246 ([Mþ], 15); 105 (100); 77
(30). HRMS calculated for C14H11ClO2: 246.04421; found:
246.044678.
3. Experimental section
3.1. General
1H and 13C NMR spectra were recorded on Bruker Spec-
trometer 400 and 300 (1H: 400.13 MHz, and 300.13 MHz;
1
13C: 100.6 MHz, and 75.5 MHz). The calibration of H and
13C spectra was carried out either on solvent signals (d
(CDCl3)¼7.25 and 77.0) or TMS. Mass spectra were recorded
on an AMD 402 spectrometer. IR spectra were recorded as
KBr pellets or Nujol mulls on a Nicolet Magna 550. All ma-
nipulations were performed under argon atmosphere using
standard Schlenk techniques. Unless specified, all chemicals
are commercially available and used as received. 2-Propanol
was used without further purification (purchased from Fluka,
dried over molecular sieves). Sodium 2-propylate and sodium
tert-butylate were prepared by reacting sodium with 2-propa-
nol or tert-butanol, respectively, under an argon atmosphere
(stock solution). Ketone 8 was dried over CaH2, distilled in
vacuum and stored under argon. Substrates 18 and 19 were
used without further purifications. Porphyrins 1a and 1d
were synthesized according to literature protocols.23 Fe(III)-
citrate was recrystallized from water/ethanol before use since
it was purchased in technical grade.
3.2.3. 2-(2-tert-Butyl-4-methylphenoxy)-acetophenone (12)
Refluxing time: 12 h, crystallized from 2-propanol,
6.0 mmol scale. Yield: 44% (white needles). Mp¼94e95 ꢁC.
1H NMR (300 MHz, CDCl3): d¼8.05e8.00 (m, 2H); 7.66e
7.59 (m, 1H); 7.55e7.48 (m, 2H); 7.13 (d, 1H, J¼2.26 Hz);
6.96 (ddd, 1H, J¼8.10, 2.26, 0.75 Hz); 6.76 (d, 1H,
J¼8.22 Hz); 5.29 (s, 2H, CH2); 2.30 (s, 3H, CH3); 1.43 (s,
9H, C(CH3)3). 13C NMR (75.5 MHz, CDCl3): d¼194.5;
154.8; 138.4; 134.7; 133.7; 130.3; 128.8; 128.1; 127.8;
127.1; 112.3; 71.0; 34.7; 29.9; 20.8. IR (KBr): 3399 w; 3051
w; 2958 s; 2901 m; 2856 m; 2733 w; 1709 s; 1598 m; 1581
w; 1499 s; 1448 m; 1439 m; 1404 w; 1386 m; 1357 w;
1287 m; 1266 m; 1244 m; 1226 s; 1181 w; 1156 w; 1107
m; 1074 w; 1020 w; 1001 m; 980 s; 930 w; 919 w; 876 w;
861 m; 802 s; 751 s; 687 s; 655 m; 584 m; 491 m. MS (EI):
m/z (%)¼282 ([Mþ], 64); 267 (21); 249 (21); 161 (11); 121
(13); 119 (16); 117 (14); 105 (100); 91 (33); 77 (29). HRMS
calculated for C19H22O2: 282.16143; found: 282.162186.
3.2. General procedure for the synthesis of substrates
A solution of 2-bromo ketone (10.1 mmol), phenol
(10.1 mmol), K2CO3 (15 mmol) in acetone (15 mL) was re-
fluxed for 3 h. The solvent was removed in vacuum and the res-
idue dissolved in ethyl acetate/diethyl ether and washed with
water and brine. After drying over Na2SO4 the solvent was re-
moved and the crude product was purified by crystallization.
3.2.4. 2-(2,6-Di-iso-propylphenoxy)-acetophenone (13)
Refluxing time: 12 h, crystallized from 2-propanol,
5.6 mmol scale. Yield: 34% (yellow crystals). Mp¼60e
1
65 ꢁC. H NMR (300 MHz, CDCl3): d¼8.01e7.95 (m, 2H);
3.2.1. 2-Phenoxy-acetophenone (10)
7.66e7.59 (m, 1H); 7.55e7.47 (m, 2H); 7.16 (s, 3H); 5.12
(s, 2H, CH2); 3.34 (sept, 2H, J¼6.91 Hz, CH); 1.25 (d, 12H,
J¼6.87 Hz, CH3). 13C NMR (75.5 MHz, CDCl3): d¼193.9;
153.0; 141.6; 133.7; 128.8; 127.8; 125.2; 124.3; 76.7; 26.5;
Flash column chromatography (eluent: ethyl acetate/n-hex-
ane 4:1), recrystallized from 2-propanol, 10.1 mmol scale.
Yield: 39% (white crystals). Mp¼60e61 ꢁC. 1H NMR

S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
3873
24.1. IR (KBr): 3442 br; 3063 w; 3028 w; 2967 s; 2868 m;
1706 s; 1597 m; 1580 w; 1451 m; 1429 m; 1381 w; 1371
w; 1360 m; 1334 m; 1255 m; 1227 m; 1185 s; 1163 m;
1100 m; 1085 m; 1075 w; 1058 w; 1042 w; 1001 w; 992 w;
972 m; 934 w; 854 w; 801 m; 763 m; 755 s; 692 m; 648 w;
617 w; 586 w; 556 w; 521 w; 472 w; 434 w. MS (EI): m/z
(%)¼296 ([Mþ], 10); 176 (83); 161 (100); 147 (20); 133
(16); 105 (59); 91 (44); 77 (28); 43 (11). HRMS calculated
for C20H24O2: 296.17708; found: 296.176483.
871 m; 816 m; 749 s; 711 w; 690 m; 609 w; 584 m; 551 w;
517 w; 498 w; 461 w. MS (EI): m/z (%)¼226 ([Mþ], 15);
119 (100); 91 (24); 77 (10). HRMS calculated for C15H14O2:
226.09883; found: 226.099202.
3.2.8. 2-Phenoxy-40-methoxyacetophenone (17)
Refluxing time: 16 h, crystallized from 2-propanol, 8.7 mmol
scale. Yield: 74% (off-white needles). Mp¼54e55 ꢁC. 1H NMR
(300 MHz, CDCl3): d¼7.96e7.89 (m, 2H); 7.24e7.16 (m, 2H);
6.93e6.84 (m, 5H); 5.13 (s, 2H, CH2); 3.80 (s, 3H, CH3). 13
C
3.2.5. 2-Phenoxy-2,3-dihydro-1H-inden-1-one (14)
NMR (75.5 MHz, CDCl3): d¼193.1; 164.0; 158.0; 130.5;
129.0; 127.6; 121.5; 114.7; 114.0; 70.7; 55.5. IR (KBr): 3442
br; 3056 w; 3006 w; 2955 w; 2934 w; 2840 w; 1960 m; 1687
s; 1653 w; 1601 s; 1511 m; 1497 s; 1459 m; 1419 w; 1368 m;
1314 m; 1265 s; 1245 m; 1226 s; 1171 s; 1154 w; 1116 m;
1075 m; 1032 m; 976 s; 884 m; 835 m; 789 m; 769 m; 751 s;
691 m; 631 w; 608 m; 582 m; 543 w; 511 w; 492 w. MS (EI):
m/z (%)¼242 ([Mþ], 10); 135 (100); 77 (18). HRMS calculated
for C15H14O3: 242.09375; found: 242.093706.
Refluxing time: 16 h, 9.5 mmol scale. Yield: 56% (off-
white crystals). Mp¼75e78 ꢁC. 1H NMR (300 MHz,
CDCl3): d¼7.85 (d, 1H, J¼7.72 Hz); 7.67 (dt, 1H, J¼7.44,
1.13 Hz); 7.50e7.41 (m, 2H); 7.37e6.99 (m, 2H); 7.10e
6.99 (m, 3H); 5.09 (dd, 1H, J¼7.54, 4.52 Hz, CH); 3.73 (dd,
1H, J¼7.54, 16.95 Hz, CH2); 3.19 (dd, 1H, J¼16.95,
4.33 Hz, CH2). 13C NMR (75.5 MHz, CDCl3): d¼201.7;
157.9; 150.6; 135.9; 134.6; 129.5; 128.2; 126.7; 124.6;
121.7; 115.7; 77.8; 34.1. IR (KBr): 3413 br; 3063 w; 3039
w; 3028 w; 2916 w; 2906 w; 1716 s; 1608 m; 1597 m; 1587
m; 1493 m; 1474 m; 1464 m; 1431 w; 1325 w; 1299 m;
1276 m; 1250 m; 1233 s; 1208 w; 1174 w; 1156 w; 1080
m; 1070 m; 1038 w; 1020 w; 1005 m; 956 w; 913 m; 889
w; 753 s; 725 m; 691 m; 618 w; 607 w; 502 w; 455 w. MS
(EI): m/z (%)¼224 ([Mþ], 53); 131 (100); 103 (32); 94 (11);
77 (25). HRMS calculated for C15H12O2: 224.08318; found:
224.083160.
3.2.9. 2-Oxo-2-phenylethyl acetate (18)
2-Hydroxy-1-phenylethanone (8.0 mmol) was dissolved in
dichloromethane (10 mL) and acetic anhydride (8.0 mmol), pyr-
idine (8.5 mmol) and 4-dimethylaminopyridine (0.08 mmol)
were added. The solution was stirred for 2 h under refluxing con-
ditions. The mixturewas washed with water and brine. After dry-
ing over Na2SO4 the solvent was removed and yellow crystals
were obtained. Yield: 83%. Mp¼48e50 ꢁC. 1H NMR
(300 MHz, CDCl3): d¼7.93e7.88 (m, 2H); 7.63e7.56 (m,
1H); 7.51e7.44 (m, 2H); 5.34 (s, 2H, CH2); 2.22 (s, 3H, CH3).
13C NMR (75.5 MHz, CDCl3): d¼192.0; 170.3; 134.1; 133.8;
128.7; 127.6; 65.9; 20.4. IR (KBr): 3460 w; 3375 w; 3064 m;
2982 w; 2937 m; 1741 s; 1699 s; 1599 m; 1581 w; 1493 w;
1452 m; 1423 m; 1374 m; 1321 w; 1280 m; 1244 s; 1228 s;
1185 m; 1087 m; 1077 m; 1047 m; 1020 m; 996 m; 970 m;
849 m; 812 m; 757 m; 688 m; 634 m; 597 m; 566 m; 483 m;
443 w; 414 w. MS (EI): m/z (%)¼178 ([Mþ], 1); 105 (100); 77
(34); 51 (10); 43 (14). HRMS calculated for C15H14O3:
178.06245; found: 178.063004.
3.2.6. 3,3-Dimethyl-1-phenoxybutan-2-one (15)
Refluxing time: 16 h, 11.2 mmol scale. Yield: 92% (off-
1
white crystals). Mp¼33e36 ꢁC. H NMR (300 MHz, CDCl3)
d¼7.32e7.24 (m, 2H); 7.00e6.93 (m, 1H); 6.91e6.84 (m,
2H); 4.87 (s, 2H, CH2); 1.25 (s, 9H, C(CH3)3). 13C NMR
(75.5 MHz, CDCl3): d¼209.4; 158.0; 129.5; 121.4; 114.6;
68.8; 43.1; 26.3. IR (KBr): 3420 br; 3105 w; 3065 w; 3043
w; 2973 m; 2931 m; 2872 w; 2846 w; 2747 w; 1721 s; 1678
w; 1599 m; 1587 m; 1494 s; 1461 m; 1446 m; 1431 m;
1386 w; 1365 m; 1329 w; 1291 m; 1234 s; 1179 m; 1152
w; 1113 m; 1078 w; 1052 s; 1026 w; 1000 m; 990 s; 962
m; 935 w; 880 m; 825 m; 766 s; 759 s; 693 m; 587 w; 545
w; 522 m. MS (EI): m/z (%)¼192 ([Mþ], 33); 108 (13); 77
(26); 57 (100); 41 (16). HRMS calculated for C12H16O2:
192.11448; found: 192.114302.
3.2.10. 2-(tert-Butyldimethylsilyloxy)-1-phenylethanone
(19)
2-Hydroxy-1-phenylethanone (8.0 mmol) was dissolved in
dichloromethane (10 mL) and imidazole (8.5 mmol) was added.
After stirring for 10 min at room temperature tert-butyldime-
thylchlorosilane (8.5 mmol) was added dropwise, while rapidly
a white precipitate was formed. The mixture was stirred for 5 h
at room temperature. Water was added and the organic layer was
washed with water and brine. After removal of the solvent a yel-
low oil was obtained. Yield: 89%. 1H NMR (300 MHz, CDCl3):
d¼7.95e7.89 (m, 2H); 7.61e7.42 (m, 3H); 4.93 (s, 2H, CH2);
0.94 (s, 9H, C(CH3)3); 0.13 (s, 6H, Si(CH3)2). 13C NMR
(75.5 MHz, CDCl3): d¼197.4; 134.9; 132.2; 128.6; 127.9;
67.4; 25.8; 18.5; ꢀ5.4. IR (KBr): 2953 w; 2929 m;
2885 w; 2856 m; 1705 s; 1599 m; 1581 w; 1472 m; 1449 m;
1390 w; 1362 w; 1288 m; 1254 m; 1229 m; 1151 s; 1025 w;
1002 m; 974 s; 939 w; 834 s; 777 s; 753 s; 712 m; 688 s; 670
3.2.7. 2-Phenoxy-40-methylacetophenone (16)
Refluxing time: 16 h, crystallized from 2-propanol,
9.4 mmol scale. Yield: 51% (colourless crystals). Mp¼62e
1
63 ꢁC. H NMR (300 MHz, CDCl3): d¼7.94e7.88 (m, 2H);
7.33e7.24 (m, 4H); 7.02e6.91 (m, 3H); 5.25 (s, 2H, CH2);
2.43 (s, 3H, CH3). 13C NMR (75.5 MHz, CDCl3): d¼194.1;
158.0; 144.8; 132.1; 129.54; 129.48; 128.2; 121.6; 114.6;
70.7; 21.8. IR (KBr): 3441 br; 3063 w; 3036 w; 2919 w;
2902 w; 2847 w; 1695 s; 1606 s; 1587 m; 1576 m; 1498 s;
1455 w; 1433 m; 1411 m; 1385 w; 1292 m; 1254 m; 1236
s; 1208 m; 1192 m; 1174 m; 1149 w; 1124 w; 1113 w;
1092 m; 1075 w; 1044 w; 1027 w; 1001 m; 979 m; 885 m;

3874
S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
s. MS (EI): m/z (%)¼251 ([MþþH], 16); 193 (66); 181 (10); 149
(dd, 1H, J¼8.48, 3.38 Hz, CH); 4.08e3.95 (m, 2H, CH2);
2.70 (br, 1H, OH). 13C NMR (75.5 MHz, CDCl3): d¼157.0;
139.4; 129.4; 128.6; 128.3; 126.2; 126.1; 115.8; 72.6; 72.5.
IR (KBr): 3313 br; 3059 w; 3032 w; 2933 w; 2875 w; 1596
m; 1581 m; 1491 s; 1453 m; 1388 w; 1345 w; 1290 m;
1242 s; 1196 w; 1169 m; 1093 m; 1066 m; 1039 m; 1006
m; 914 m; 864 w; 825 m; 801 m; 749 m; 700 m; 671 m;
633 w; 616 m; 559 w; 507 m. MS (EI): m/z (%)¼248
([Mþ], 21); 142 (34); 128 (70); 107 (100); 91 (12); 79 (31).
HRMS calculated for C14H13ClO2: 248.05986; found:
248.059204.
(12); 135 (13); 105 (100); 75 (73).
3.2.11. 2-Morpholino-acetophenone (22)
Morpholine (62 mmol) was added dropwise to a solution of
2-bromoacetophenone (7.5 mmol) in THF (15 mL). A white
precipitate was formed while the mixture was refluxed for one
day. An aqueous solution of NaHCO3 was added. After extrac-
tion with diethyl ether the organic layer was washed with aque-
ous solution of NaOH and dried over Na2SO4. The crude product
was purified by flash column chromatography (eluent: ethyl ac-
etate/n-hexane 1:1) to yield a brownish oil. Yield: 89%. 1H NMR
(300 MHz, CDCl3): d¼8.02e7.97 (m, 2H); 7.60e7.55 (m, 1H);
7.50e7.43 (m, 2H); 3.83 (s, 2H, C(O)CH2); 3.79 (m, 4H, CH2);
2.62 (m, 4H, CH2). 13C NMR (75.5 MHz, CDCl3): d¼172.0;
160.9; 131.9; 129.6; 128.1; 67.1; 66.4; 64.4; 41.7; 40.6. IR
(KBr): 3415 w; 3060 m; 2970 m; 2852 m; 2762 w; 1924 w;
1674 s; 1598 s; 1558 m; 1493 w; 1449 s; 1384 s; 1314 m;
1300 m; 1271 s; 1230 m; 1176 m; 1113 s; 1069 m; 1047 w;
1022 m; 1006 m; 981 w; 931 w; 876 w; 840 w; 812 w; 788 w;
757 w; 722 m; 693 w; 674 w; 593 w; 547 w; 449 w. MS (EI):
m/z (%)¼205 ([Mþ], 2); 100 (100); 77 (18); 56 (21). HRMS cal-
culated for C12H15O2N: 205.10973; found: 205.109149. Rf
(ethyl acetate/n-hexane 1:1)¼0.14.
3.3.3. 2-(2-tert-Butyl-4-methylphenoxy)-1-phenylethanol
(12a)
1
Mp¼61e64 ꢁC (colourless crystals). H NMR (300 MHz,
CDCl3): d¼7.53e7.32 (m, 5H, Ph); 7.13 (d, 1H, J¼2.13 Hz,
Ph); 6.98 (ddd, 1H, J¼8.29, 2.26, 0.75 Hz, Ph); 6.78 (d, 1H,
J¼8.09 Hz, Ph); 5.21 (dd, 1H, J¼7.35, 4.71 Hz, CH); 4.18e
4.08 (m, 2H, CH2); 2.67 (br, 1H, OH); 2.31 (s, 3H, CH3);
1.41 (s, 9H, C(CH3)3). 13C NMR (75.5 MHz, CDCl3):
d¼155.0; 139.9; 137.7; 129.9; 128.5; 128.1; 127.7; 127.1;
126.3; 112.2; 73.5; 72.9; 34.7; 30.0; 20.8. IR (KBr): 3570
m; 3030 w; 2994 w; 2856 m; 2917 m; 2867 m; 1605 w;
1581 w; 1497 s; 1451 s; 1406 m; 1389 m; 1359 m; 1327 w;
1294 m; 1264 m; 1228 s; 1198 m; 1151 m; 1095 m; 1060
m; 1033 s; 1001 w; 934 w; 911 m; 881 w; 854 m; 809 m;
764 m; 702 s; 624 w; 602 w; 592 w; 553 w; 516 w; 493 w.
MS (EI): m/z (%)¼284 ([Mþ], 27); 164 (31); 149 (100); 121
(18); 107 (17); 91 (21); 77 (16). HRMS calculated for
C19H24O2: 284.17708; found: 284.176978.
3.3. General procedure for the catalytic transfer
hydrogenation
In a 10 mL Schlenk tube, the in situ catalyst (0.0038 mmol)
is prepared stirring a solution of FeCl2 (0.0038 mmol) and por-
phyrin (0.0038 mmol) in 1.0 mL 2-propanol for 16 h at 65 ꢁC.
The pre-catalyst system is reacted with sodium hydroxide
(0.38 mmol in 0.5 mL 2-propanol) and 2-methoxyacetophe-
none (0.38 mmol in 0.5 mL 2-propanol) for 2 h at 100 ꢁC.
The solution is cooled to room temperature and filtered over
a plug of silica. The conversion was measured by GC without
further manipulations and the products were isolated by col-
umn chromatography or crystallization.
3.3.4. 2-(2,6-Di-iso-propylphenoxy)-1-phenylethanol (13a)
1
Mp¼67e69 ꢁC (colourless crystals). H NMR (300 MHz,
CDCl3): d¼7.46e7.26 (m, 5H); 7.09 (s, 3H); 5.16 (dd, 1H,
J¼7.53, 4.40 Hz, CH); 3.92e3.82 (m, 2H, CH2); 3.29 (sept,
2H, J¼6.91 Hz, CH(CH3)2); 3.10 (br, 1H); 1.22 (dd, 12H,
J¼6.90, 1.29 Hz). 13C NMR (75.5 MHz, CDCl3): d¼152.4;
141.6; 139.8; 128.4; 128.0; 126.1; 125.8; 124.9; 79.3; 73.3;
26.4; 24.04; 24.00. IR (KBr): 3064 m; 3030 m; 2963 s;
2927 s; 2868 m; 1604 w; 1589 w; 1454 s; 1384 m; 1362 m;
1327 m; 1255 m; 1182 s; 1100 m; 1047 s; 1020 s; 936 w;
913 m; 861 w; 834 w; 802 m; 755 m; 700 s; 682 w; 623 w;
590 w; 527 w. MS (EI): m/z (%)¼298 ([Mþ], 8); 178 (51);
163 (100); 107 (15); 91 (16); 77 (11). HRMS calculated for
C20H26O2: 298.19273; found: 298.192353.
3.3.1. 2-Phenoxy-1-phenylethanol (10a)
Mp¼48e50 ꢁC (white crystals). 1H NMR (300 MHz,
CDCl3): d¼7.40e7.15 (m, 7H, Ph); 6.92e6.80 (m, 3H, Ph);
5.03 (dd, 1H, J¼8.67, 3.20 Hz, CH); 4.03e3.88 (m, 2H,
CH2); 2.55 (br, 1H, OH). 13C NMR (75.5 MHz, CDCl3):
d¼158.3; 139.6; 129.5; 128.5; 128.2; 126.3; 121.3; 114.6;
73.2; 72.5. IR (KBr): 3302 br; 3060 w; 3028 w; 2932 w;
2877 w; 1598 s; 1585 m; 1498 s; 1453 m; 1389 w; 1346 w;
1303 m; 1292 m; 1249 s; 1196 m; 1172 m; 1152 w; 1098
m; 1078 m; 1067 m; 1046 m; 1028 m; 995 w; 917 m; 884
w; 863 m; 792 w; 754 s; 701 s; 692 s; 637 m; 615 m; 594
m; 541 m; 512 m. MS (EI): m/z (%)¼214 ([Mþ], 12); 108
(100); 94 (46); 79 (60); 51 (18). HRMS calculated for
C14H14O2: 214.09883; found: 214.098407.
3.3.5. 2-Phenoxy-2,3-dihydro-1H-inden-1-ol (14a)
Colourless crystals. During the reaction a mixture of diaste-
1
reomers were formed in a ratio of 1:3 (D1/D2). H NMR
(400 MHz, CDCl3): d¼7.56e6.93 (m); 5.34 (d, 1H,
J¼4.12 Hz, D1); 5.28 (d, 1H, J¼5.22 Hz, D2); 5.08e5.02
(m, 1H, D2); 4.98e4.89 (m, 1H, D1); 3.53 (dd, 1H,
J¼16.37, 6.92 Hz, D1); 3.20 (d, 2H, J¼4.40 Hz, D2); 2.98
(dd, 1H, J¼16.37, 5.32 Hz, D1); 2.81 (br, OH). 13C NMR
(100.6 MHz, CDCl3): d¼157.7; 142.4; 139.5; 139.2; 129.6;
129.5; 128.9; 128.6; 127.3; 125.1; 125.0; 124.8; 124.5;
121.7; 121.6; 121.0; 115.8; 115.5; 85.4; 80.3; 75.6; 36.4;
3.3.2. 2-(4-Chlorophenoxy)-1-phenylethanol (11a)
Mp¼46e48 ꢁC (white crystals). 1H NMR (300 MHz,
CDCl3): d¼7.48e7.19 (m, 7H); 6.87e6.80 (m, 2H); 5.11

S. Enthaler et al. / Tetrahedron 64 (2008) 3867e3876
3875
35.9. IR (Nujol): 3182 w; 2723 w; 1598 m; 1585 m; 1496 m;
1459 s; 1377 s; 1291 m; 1250 s; 1207 w; 1170 w; 1155 w;
1118 m; 1073 w; 1050 w; 1020 w; 1001 w; 879 w; 849 w;
779 w; 746 s; 723 m; 693 m; 639 w; 511 w; 413 w. MS
(EI): m/z (%)¼226 ([Mþ], 19); 133 (100); 115 (21); 103
(21); 94 (61); 77 (29); 65 (11). HRMS calculated for
C15H14O2: 226.09883; found: 226.099031.
PC with GPES 4.9 software. A three-electrode arrangement
with a platinum microelectrode (25 mm diameter) as the work-
ing electrode, a saturated calomel electrode (SCE) as reference
electrode and a platinum counter electrode (16 mm2 area) was
used. All potentials in the following are cited against SCE. All
measurements were carried out in 2-PrOH at room tempera-
ture. As supporting electrolyte we used 0.1 mol/L tetra-n-butyl-
ammonium tetrafluoraborate. Due to the low solubility at
room temperature all solutions of porphyrins with FeCl2
were saturated solutions. For some porphyrins (e.g., com-
pound 3) solubility was too low to see any currents. Revers-
ibility was determined by plotting E versus log[(IaꢀI)/IꢀIc]
for the nearly linear range of the forward scan and determining
the slope for the quasi-reversible electrode reactions. Anodic
diffusion current (Ia) and cathodic diffusion current (Ic) are
determined from the results of a sigmoidal fit with Microcal
Origin 7.5.
3.3.6. 3,3-Dimethyl-1-phenoxybutan-2-ol (15a)
1
Mp¼31e33 ꢁC (colourless crystals). H NMR (300 MHz,
CDCl3): d¼7.33e7.24 (m, 2H); 7.00e6.88 (m, 3H); 4.14 (dd,
1H, J¼9.23, 2.45 Hz, CH); 3.86 (m, 2H, CH2); 2.35 (br, 1H,
OH); 1.01 (s, 9H, C(CH3)3). 13C NMR (75.5 MHz, CDCl3):
d¼158.6; 129.5; 121.1; 114.6; 77.2; 69.3; 33.5; 26.0. IR
(KBr): 3272 br; 3035 w; 2954 s; 2876 m; 1601 m; 1586 m;
1499 s; 1459 m; 1393 w; 1366 m; 1338 m; 1296 m; 1245 s;
1190 w; 1174 m; 1152 w; 1095 m; 1079 m; 1044 m; 1020 m;
1020 m; 1005 m; 992 w; 942 w; 926 m; 902 m; 895 m; 821 w;
754 s; 692 m; 598 w; 572 w; 513 m; 402 w. MS (EI): m/z
(%)¼194 ([Mþ], 26); 119 (10); 108 (63); 94 (100); 87 (19); 77
(22); 69 (14); 57 (24); 41 (17). HRMS calculated for
C12H18O2: 194.13013; found: 194.129870.
Acknowledgements
We thank Mrs. S. Buchholz and Dr. C. Fischer (both Leib-
niz-Institut fur Katalyse e.V. an der Universitat Rostock) for
¨
¨
excellent analytical assistance and Prof. Jeroschewski for gen-
eral discussions. Generous financial support from the state of
Mecklenburg-Western Pomerania and the BMBF as well as
the Deutsche Forschungsgemeinschaft (Leibniz-price) are
gratefully acknowledged.
3.3.7. 2-Phenoxy-1-(40-methylphenyl)ethanol (16a)
1
Mp¼50e51 ꢁC (colourless crystals). H NMR (300 MHz,
CDCl3): d¼7.34e7.14 (m, 6H); 6.98e6.85 (m, 3H); 5.05
(dd, 1H, J¼8.64, 3.36 Hz, CH); 4.04e3.97 (m, 2H, CH2);
2.87 (br, 1H, OH); 2.34 (s, 3H, CH3). 13C NMR (75.5 MHz,
CDCl3): d¼158.3; 137.8; 136.7; 129.5; 129.2; 126.2; 121.1;
114.5; 73.2; 72.3; 21.1. IR (KBr): 3297 br; 3027 w; 2912 w;
2880 w; 1932 w; 1599 m; 1586 m; 1514 m; 1498 s; 1460
m; 1388 m; 1340 m; 1293 m; 1250 s; 1195 m; 1180 m;
1172 m; 1151 w; 1090 s; 1045 m; 1021 m; 995 w; 975 w;
943 w; 916 m; 886 w; 868 m; 838 w; 815 m; 756 s; 716 w;
693 m; 616 w; 597 m; 575 w; 537 m; 513 m; 487 w; 464
w; 403 w. MS (EI): m/z (%)¼228 ([Mþ], 6); 121 (100); 108
(68); 105 (15); 65 (11). HRMS calculated for C15H16O2:
228.11448; found: 228.114429.
References and notes
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3.3.8. 2-Phenoxy-1-(40-methoxyphenyl)ethanol (17a)
Yellow oil. 1H NMR (300 MHz, CDCl3): d¼7.32e7.15 (m,
4H); 6.92e6.77 (m, 5H); 4.98 (dd, 1H, J¼8.67, 3.39 Hz, CH);
4.00e3.87 (m, 2H, CH2); 3.73 (s, 3H, CH3); 2.77 (br, 1H). 13
C
NMR (75.5 MHz, CDCl3): d¼159.4; 158.3; 131.7; 129.5;
127.5; 121.2; 114.6; 113.9; 73.2; 72.1; 55.3. IR (KBr): 3440
br; 3072 w; 3044 w; 2999 w; 2929 m; 2831 w; 1728 w;
1612 m; 1600 m; 1587 m; 1514 s; 1497 s; 1456 m; 1303 m;
1245 s; 1174 m; 1154 w; 1114 w; 1080 m; 1036 m; 912 w;
867 w; 832 m; 755 m; 692 m; 639 w; 596 w; 552 w; 511 w.
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244.10940; found: 244.109218.
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¨
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3876
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