The Mg-oppenauer oxidation as a mild method for the synthesis of aryl and metallocenyl ketones

Article abstract of DOI:10.1002/chem.200600738

Magnesium alkoxides undergo a hydride-transfer oxidation with benzaldehyde as the oxidant. This magnesium variant of the Oppenauer oxidation was used for the synthesis of polyfunctional biaryl ketones. LiCl was found to promote this reaction by enhancing the solubility of magnesium alkoxides. This mild oxidation method was especially useful for preparing ketones bearing a metallocenyl unit as well as various new ferrocenyl ketones and tricarbonylchromium complexes. This last class of ketones was reduced with the CBS catalyst (CBS = Corey-Bakshi-Shibata, diphenyl oxazaborolidine) to chiral benzhydrol complexes with high enantioselectivity enabling an asymmetric synthesis of electronrich or -poor benzhydryl alcohols (up to 94% ee).

Full text of DOI:10.1002/chem.200600738

FULL PAPER
DOI: 10.1002/chem.200600738
The Mg-Oppenauer Oxidation asa Mild Method for the Synthesisof Aryl
and Metallocenyl Ketones
Ralf J. Kloetzing,[b] Arkady Krasovskiy,[a] and Paul Knochel*[a]
Abstract: Magnesium alkoxides under-
go a hydride-transfer oxidation with
benzaldehyde as the oxidant. This mag-
nesium variant of the Oppenauer oxi-
dation was used for the synthesis of
polyfunctional biaryl ketones. LiCl was
found to promote this reaction by en-
hancing the solubility of magnesium
alkoxides. This mild oxidation method
was especially useful for preparing ke-
tones bearing a metallocenyl unit as
well as various new ferrocenyl ketones
and tricarbonylchromium complexes.
This last class of ketones was reduced
with the CBS catalyst (CBS=Corey–
Bakshi–Shibata, diphenyl oxazaboroli-
dine) to chiral benzhydrol complexes
with high enantioselectivity enabling
an asymmetric synthesis of electron-
rich or -poor benzhydryl alcohols (up
to 94% ee).
Keywords: asymmetric synthesis ·
Grignard reagents
·
ketones
·
metallocenes · oxidation
Introduction
for the oxidation of primary and secondary alcohols leading
to the corresponding aldehydes or ketones.[11] The magnesi-
um-Oppenauer oxidation reaction has been used for the
synthesis of several aldehydes and symmetrical ketones,[12]
but acceptable yields were obtained only in dibutyl ether or
Several classes of organometallic intermediates readily un-
dergo acylation reactions leading to polyfunctional ketones
which are present in a great variety of pharmaceutical and
material science related target molecules.[1] As a result of
their high reactivity combined with a high tolerance towards
functional groups, Grignard reagents are useful for the syn-
thesis of polyfunctional ketones. Functionalized aryl- and
heteroaryl-magnesium reagents have become readily availa-
ble from the corresponding organic iodides or bromides
through a halogen–magnesium exchange by the reaction
with the mixed complex iPrMgCl·LiCl[2] or by deprotonation
of aryls and heteroaryls with LiCl-solubilized magnesium
amides.[3] Typical procedures for the preparation of the un-
symmetrical diaryl ketones starting from arylmagnesium re-
agents involve the use of transition metals, such as CuI,[4]
FeIII,[5] NiII,[6] and PdII,[7] or expensive ligands[8] followed by
the addition of corresponding acyl chlorides.
[13]
in diisopropyl ether. The use of THFleads to low yields.
Results and Discussion
Herein, we wish to report that the magnesium variant of the
Oppenauer oxidation represents an efficient method for the
synthesis of biaryl and metallocenyl ketones by using mag-
nesium instead of aluminum alkoxides. The addition of
Grignard reagents 1 to aldehydes 2 gives magnesium alkox-
ides 3 which are readily oxidized to the corresponding ke-
tones 4 by using benzaldehyde as a hydride acceptor with
the formation of benzyl alkoxide
5 as a byproduct
(Scheme 1). In this sequence, the MgII center promotes two
consecutive reactions: the addition of the Grignard reagent
1 to the aldehyde 2 and the hydride-transfer oxidation of
the alkoxide 3.
In 1937, Oppenauer[9,10] found that in the presence of alu-
minum tert-butoxide, acetone acts as a hydrogen acceptor
Thus, benzophenone (4a) was obtained from phenylmag-
nesium chloride and benzaldehyde (2.2 equiv) in 98% yield
(Table 1, entry 1). In this case, the magnesium-Oppenauer
oxidation reaction proceeds at room temperature leading to
the desired ketone with complete conversion after 1 h. With-
out LiCl, the reaction did not go to completion, even after
6 h, and several byproducts were formed. We found that the
presence of LiCl in the reaction mixture dramatically accel-
[a] Dr. A. Krasovskiy, Prof. Dr. P. Knochel
Department Chemie und Biochemie
Ludwig-Maximilians-Universität München
Butenandtstrasse 5–13, Haus F, 81377 München (Germany)
Fax: (+49)89-2180-77680
E-mail: paul.knochel@cup.uni-muenchen.de
[b] Dr. R. J. Kloetzing
Universität Zürich, Organisch-chemisches Institut
Winterthurerstrasse 190, 8057 Zürich (Switzerland)
Chem. Eur. J. 2007, 13, 215 – 227
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
215

Table 1. One-pot synthesis of ketones 4a–m starting from the corre-
sponding Grignard reagents complexed with LiCl.
Entry
Product of type 4[a]
Yield [%][a]
1
2
3
4a: R=H
4b: R=CN
4c: R=OMe
98
90
95
4
5
6
7
4d: R1 =OMe; R2 =H
4e: R1 =CN; R2 =H
4 f: R1 =H; R2 =Br
4g: R1 =CN; R2 =Br
95
92
91
0
Scheme 1. Magnesium-Oppenauer oxidation with benzaldehyde.
erates the magnesium-Oppenauer oxidation reaction. We
propose that the main role of LiCl is to solubilize the result-
ing alkoxide 3 in THFand additionally to activate the car-
bonyl function of benzaldehyde by playing the role of a
Lewis acid. A wide range of functionalized unsymmetrical
diaryl ketones can be prepared (Table 1) from the corre-
sponding magnesium alkoxides. Neither electron-accepting
nor -donating substituents appear to influence the reaction
course (4b–c, entries 2 and 3). Although an ortho-substitu-
ent does not retard the reaction (4d–f, entries 4–6), the pres-
ence of two ortho-substituents inhibited the magnesium-Op-
penauer reaction completely due to the high steric hin-
drance and no ketone was formed (entry 7). Various hetero-
cyclic aryl ketones, such as pyridyl- (4h and 4i), benzothio-
phenyl- (4j), thiophenyl- (4k), and furyl ketones (4l) are
easily prepared. Importantly, the heterocyclic moiety can be
introduced by the magnesium reagent as well or by the alde-
hyde. A polycyclic aromatic Grignard reagent, such as 9-
phenanthrenylmagnesium chloride, leads, after the addition
of benzaldehyde followed by the magnesium-Oppenauer ox-
idation, to the formation of the desired ketone 4m in 94%
yield.
8
4h
89
9
4i
4j
94
85
10
11
12
4k
4l
92
95
As this oxidation reaction enables the synthesis of aro-
matic ketones under very mild conditions, it may be possible
to prepare ketones bearing metallocene units which are not
13
4m
94
À
[a] Dotted lines indicate the C C bond formed during the reaction of the
Grignard reagent with the corresponding aldehyde. [b] Isolated yield of
the analytical pure product.
Abstract in German: Magnesiumalkoholate gehen eine Oxi-
dation durch Hydrid-Transfer mit Benzaldehyd als Oxida-
tionsmittel ein. Diese Magnesium-Variante der Oppenauer-
Oxidation wurde zur Synthese polyfunktioneller Biarylketone
genutzt. Es wurde gefunden, dass LiCl die Reaktion begün-
stigt, indem es die Lçslichkeit der Magnesiumalkoholate
erhçht. Diese milde Oxidationsreaktion ist besonders nütz-
lich, um Ketone mit einer Metalloceneinheit sowie verschie-
dene neue Ferrocenylketone und Tricarbonylchromkomplexe
darzustellen. Letztere wurden mit dem CBS-Katalysator
(CBS=Corey–Bakshi–Shibata, Diphenyloxazaborolidin) zu
chiralen Benzhydrolkomplexen mit hoher Enantioselektivität
reduziert, was eine asymmetrische Synthese elektronenreicher
wie -armer Benzhydrylalkohole erlaubt (bis zu 94% ee).
compatible with common oxidizing agents. First, we tested
this method for the synthesis of ferrocenyl ketones from fer-
rocenyl alcohols. The ferrocenyl alcohols 7a–g are readily
available from the addition of ferrocenyllithium, generated
by a tin–lithium exchange,[14] to various aldehydes (Table 2).
This method affords the benzofuryl and pyridyl alcohols
7a–e in very good yields (entries 1–5). The yield for the in-
dolyl alcohol 7 f is lower, as the electron-rich heterocyclic
À
substituent facilitates the heterolytic cleavage of the C O
bond and the formation of the a-ferrocenyl cation (entries 6,
216
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Chem. Eur. J. 2007, 13, 215 – 227

Aryl and Metallocenyl Ketones
FULL PAPER
Table 2. Synthesis of ferrocenyl alcohols 7a–g from monolithioferrocene
and aldehydes.
tion with benzaldehyde (Scheme 3). The ferrocenyl alcohols
7a–i were deprotonated with iPrMgCl·LiCl in 10 min at 08C
and the resulting magnesium alcoholates were oxidized by
hydride transfer to benzaldehyde (see Table 3).
Entry[a] Product of type 7 Yield Entry[a] Product of type 7
Yield
[%][b]
[%][b]
Scheme 3. Synthesis of the ferrocenyl alcohol 7i.
1
2
87
86
4
5
87
81
The first experiment for the synthesis of metallocenyl ke-
tones from the corresponding alcohols was carried out with
diferrocenylmethanol. Only 5 min after the addition of ben-
zaldehyde, diferrocenyl ketone (10a) precipitated from the
reaction mixture and was isolated by filtration in 85% yield
(Table 3, entry 1). Under the conditions for the Oppenauer
oxidation with aluminum tri-tert-butoxide (1.65 equiv) and
acetone (70 equiv), this ketone was not formed even after
12 h at 608C. The previously unknown benzofuran deriva-
tives 10b,c[16] are obtained after 3 h reaction time (81–91%
yield; entries 2 and 3). It has been reported that attempts to
synthesize the pyridyl ferrocenyl ketones 10d and 10e
failed.[17] However, the magnesium-Oppenauer oxidation en-
ables the preparation of these ketones 10d,e in 66 and 68%
yields after a reaction time of 12 h (entries 4 and 5). The ad-
dition of DMPU as a cosolvent ensured, additionally, the
solubility of the magnesium alcoholates. The use of LiCl
proved to be essential especially for the less soluble alcohol-
ates derived from the pyridine derivatives 7c,d. Without
LiCl, no oxidation was observed. The hydride-transfer oxi-
dation did not proceed with the 2-pydridyl ferrocenyl alco-
hol 7e. After a reaction time of 6 h, N-methylindole deriva-
tive 10 f was isolated in 89% yield (entry 6).[18] The N-tosy-
lindolyl ketone 10g was unexpectedly unstable and was iso-
lated in 52% yield after 6 h reaction time (entry 7). The dia-
stereomeric mixture of alcohol 7h was oxidized by hydride
transfer. Both diastereomers underwent the hydride transfer
and ketone 10h was isolated in 65% yield after a reaction
time of 14 h. It should be noted, that the preparation of the
ketone 10h by ortho-lithiation of sulfoxide 8, transmetalla-
tion to copper, and reaction with benzoyl chloride was not
possible.[19] Thus, the hydride transfer oxidation is the only
access to ketone 10h (entry 8). Finally, the alkyne 10i was
prepared with a reaction time of 16 h and was isolated in
88% yield (entry 9).
3
7
87
76
6
58
[a] All reactions were performed on a 2 mmol scale with the following
ratio: (tri-n-butylstannyl)ferrocene (1.0 equiv), nBuLi (1.0 equiv), and the
aldehyde (1.1 equiv). [b] Isolated yield of analytical pure product.
7). The ferrocenyl alcohol 7h was prepared by ortho-lithia-
tion of sulfoxide 8 and reaction with benzaldehyde. Alcohol
7h was obtained as a mixture of diastereomers in a ratio of
3:7 with an overall yield of 91% (Scheme 2). The diaster-
Scheme 2. Synthesis of the ferrocenyl alcohol 7h.
The synthesis of the ferrocenyl ketones 10a–i was per-
formed in two steps. As monolithioferrocene is readily avail-
able[14] and as it adds smoothly to aldehydes, the alcohols
7a–i could be easily prepared. The magnesium alcoholates
were then formed by deprotonation of the alcohols with
iPrMgCl·LiCl. However, the addition of Grignard reagents
to metallocenyl aldehydes enables the direct preparation of
magnesium alcoholates. Grignard reagents 1, which were
prepared either by insertion of magnesium into aromatic
eomers could neither be separated by column chromato-
graphical purification nor by recrystallization. The ratio of
diastereomers was determined by integration of the
1H NMR spectrum.
Ferrocenyl alcohol 7i was prepared from the aryl iodide
9
[15] by an iodine–magnesium exchange and subsequent reac-
Chem. Eur. J. 2007, 13, 215 – 227
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www.chemeurj.org
217

P. Knochel et al.
Table 3. Synthesis of ferrocenyl ketones 10a–i from ferrocenyl alcohols.
bromides in the presence of LiCl or by an iodine–magnesi-
um exchange with iPrMgCl·LiCl, were added to ferrocene
aldehyde 11, cymantrene aldehyde 12, and tricarbonylchro-
mium benzaldehyde 13 (see Table 4). The resulting magnesi-
um alcoholates were oxidized directly to the corresponding
ketones 14 with benzyldehyde by hydride transfer (Table 4).
3-Benzofuryl ferrocenyl ketone (10b) which was also pre-
pared by the two-step sequence described above (Table 3,
entry 2) was now prepared in a one-pot synthesis starting
from 3-bromobenzofuran. The bromine–magnesium ex-
change, addition to ferrocene alydehyde, and hydride trans-
fer oxidation gave the ketone 10b in 79% yield on a 5 gram
scale.
Entry[a]
Product
Yield [%][b] Reaction time [h]
1
85
0.1
The addition of PhMgCl·LiCl to cymantrene aldehyde
and oxidation with benzaldehyde afforded the ketone 14a in
80% yield.[20] Various aromatic Grignard reagents were also
readily added to tricarbonylchromium benzaldehyde 11
within 10 min at À208C.[21] A stepwise synthesis of the ke-
tones 14c,e,f is not possible as the tricarbonyl chromium
complexes of benzhydrols with electron-donating substitu-
ents are easily decomposed upon isolation. However, the
direct oxidation with benzaldehyde within 12 h at room tem-
perature gave the ketones 14b–l, which were purified by
crystallization.[22,23] With nonfunctionalized or electron-rich
ketones, 65–92% yields were obtained. With halogenated ar-
ylmagnesium reagents, 28–59% yields were observed. The
best results gave the p-bromo derivative 14i (entry 10)
which was isolated in 59% yield. In general, lower yields
are obtained in reactions for which the Grignard reagent
was prepared by the halogen–magnesium exchange instead
of the direct insertion of magnesium turnings. The oxidation
leading to the ketones 14c,e,f (entries 4, 6, and 7) shows that
the Mg-Oppenauer oxidation enables a selective synthesis
of tricarbonylchromium complexes of benzophenones with
complexation of the less electron-rich ring. In contrast, the
direct formation of tricarbonylchromium complexes of sub-
stituted benzophenones by using chromium hexacarbonyl
gives a mixture of products.[24] The complex with the most
electron-rich aromatic ring is formed preferentially with a
low selectivity.
2
3
4
5
91
3
3
81
68[c]
12
66[c]
12
6
6
7
89
52
6
The enantioselectivity of the asymmetric reduction of p-
subsituted benzophenones depends on the interaction with
the p-subsituent and the catalyst. As a result of the remote
positions, these reductions usually proceed with low enantio-
selectivity.[25] However, in the case of complexation with a
tricarbonylchromium unit the CBS reduction[26,27] gives
chiral benzhydrol derivatives[28] with high enantioselectivity
(see Table 5).
The asymmetric reduction was first examined with the tri-
carbonylchromium complex 14c leading to the benzhydrol
15a (Table 5, entry 1). The best results were obtained when
the ketone was reduced with borane–dimethyl sulfide com-
plex and with 20 mol% of the CBS catalyst (S)-CBS within
30 min in THF. After complete conversion of the ketone,
water was added and the reaction mixture was filtered
through silica gel. The filtrate was treated with iodine for
decomplexation. The benzhydrol 15a was isolated in 90%
8
9
65
88
14
16
[a] All reactions were performed on a 1 mmol scale with the following
ratio: alcohol (1.0 equiv), iPrMgCl·LiCl (1.05 equiv), and benzaldehyde
(1.5 equiv). [b] Isolated yield of analytically pure product. [c] DMPU
(DMPU=1,3-dimethyltetrahydropyrimidin-2-one) was used as a cosol-
vent.
218
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Chem. Eur. J. 2007, 13, 215 – 227

Aryl and Metallocenyl Ketones
FULL PAPER
Table 4. Synthesis of metallocenyl ketones 14a–l from metallocenyl aldehydes.
reaction leading to the biphen-
yl derivative 15b (entries 2–4)
could be improved when one
equivalent of N,N-diethylani-
line[29] was added as an addi-
tive to the borane–dimethyl
sulfide complex. When the re-
action was performed at room
temperature the benzhydrol
15b
was
obtained
with
89% ee. All reductions pro-
ceed in almost quantitative
yields. In the case of the p-
methylphenyl ketone 15c the
Entry
Product
Yield [%][a]
enantioselectivity
was im-
proved from 90 (entry 5) to
93% ee (entry 6). The 2-naph-
thyl ketone 15d was reduced
with an enantioselectivity of
only 81% ee without additive
(entry 7) and with 94% ee with
N,N-diethylaniline. The most
substantial improvement was
observed for the p-bromo
ketone 15e, which was reduced
without additive with 55% ee
(entry 9). In presence of N,N-
diethylaniline, 88% ee was ob-
tained (entry 10). Good enan-
tioselectivities were also ob-
served for the p-chlorobenzhy-
drol (15 f; 89% ee; entry 11)
and for the p-iodobenzhydrol
(15g, 86% ee, entry 12). The
1[b]
10b
14a
79
80
2[c]
3[c]
14b: R=H
14c: R=OMe
14d: R=Ph
14e: R=Me
14 f: R=NMe2
14g: R=D
14h: R=Cl
14i: R=Br
14j: R=I
85
73
69
65
92
72
40
59
28
4[d]
5[d]
6[d]
7[d]
8[b]
9[e]
10[e]
11[e]
p-dimethylaminoketone
14 f
was reduced without additive
and lead to the p-dimethylami-
nobenzhydrol 15h in 96%
yield with 84% ee (entry 13).
12[d]
14k
78
Conclusion
We have developed an effi-
cient method for the synthesis
of unsymmetrical aryl and het-
eroaryl ketones starting from
easily accessible Grignard re-
agents and aldehydes. The
13[d]
14l
82
[a] Isolated yield of analytically pure product. [b] Preparation of the Grignard reagent 1 by a bromine–magne-
sium exchange from the corresponding aryl bromide and iPrMgCl·LiCl in 5 h at À408C. [c] The Grignard re-
agent 1 was obtained from Chemetall (Frankfurt). [d] Preparation of the Grignard reagent 1 by insertion of
magnesium turnings into the corresponding aryl bromide. [e] Preparation of the Grignard reagent 1 by an
iodine–magnesium exchange from the corresponding aryl iodide and iPrMgCl·LiCl.
mild
reaction
conditions
enable the preparation of vari-
ous ketones bearing a metallo-
cene unit, of which most were
yield and with 93% ee. This direct decomplexation enables
a formal CBS reduction of the ketone 14c. Attempts to iso-
late the tricarbonylchromium complex of the alcohol failed
as a result of its low stability. The enantioselectivity of the
previously unavailable. The resulting tricarbonylchromium
complexes of unsymmetrical ketones could be efficiently re-
duced by CBS reduction to give chiral benzhydrol deriva-
tives with high enantioselectivity.
Chem. Eur. J. 2007, 13, 215 – 227
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219

P. Knochel et al.
Table 5. Preparation of the benzhydrol derivatives 15a–h.
neat or as a solution in THF. After
10 min benzaldehyde (2.4 mmol) was
added and reaction mixture was
warmed to RT. The mixture was stir-
red at RT. (appropriate time was
checked by GC analysis of reaction
aliquots, the conversion was more
than 98%), then a saturated NH4Cl
solution (20 mL) was added and the
mixture was extracted with ethyl ace-
tate (40 mL). The combined organic
layers were dried (Na2SO4). The
crude material was purified by
column chromatography. Analytical
data was found to match literature
data: 4a,[31] 4b,[5] 4c,[32] 4d,[33] 4e,[34]
4 f,[35] 4h,[36] 4i,[37] 4j,[38] 4l,[39] and
Entry[a]
Product 15
Additive
T [8C]
Yield [%][b]
Enantioselectivity
[% ee][c]
AHCTREUNG
4m,[40]
Compound 4k: White crystals; m.p.
132–1338C); (CDCl3,
1H NMR
.
1
15a: R=OMe
15b: R=Ph
–
–
0
90
93
2
3
4
0
À5
22
quant.
quant.
97
67
86
89
200 MHz): d=7.84 (m, 2H), 7.62 (m,
1H), 7.51 (m, 1H), 7.35 (d, J=
4.0 Hz, 1H), 7.28 ppm (d, J=4.0 Hz,
1H); 13C NMR (CDCl3, 75 MHz): d=
187.0, 149.8, 138.4, 137.9, 136.0, 132.9,
129.4, 128.9, 86.3 ppm; MS (EI,
70 eV): m/z (%): 313 (100) [M]+, 237
(57), 187 (12), 105 (35), 82 (11), 77
[d]
PhNEt2
PhNEt2
[d]
5
6
–
0
22
93
95
90
9
15c: R=Me
[d]
PhNEt2
(24), 51 (8); HR-EIMS: m/z: calcd
7
8
–
0
89
95
81
94
1H7127I16O32S:
313.9262;
12
for
C
11
found: 313.9262.
Synthesis of the ferrocenyl alcohols
7a–i
[d]
[d]
PhNEt2
22
Procedure B: nBuLi (16% solution
in n-hexane, 1.0 equiv) was added to
a solution of (tri-n-butylstannyl)ferro-
9
10
–
0
22
quant.
96
55
88
15e: R=Br
PhNEt2
À1
[d]
[d]
cene (18) in THF(3.3 mLmmol
11
12
13
15 f: R=Cl
15g: R=I
15h: R=NMe2
PhNEt2
PhNEt2
–
22
22
0
quant.
94
90
86
84
(tri-n-butylstannyl)ferrocene)
at
96
À788C. The mixture was then
warmed to RT and stirred for 30 min.
After this time, the mixture was
cooled to À788C and the aldehyde
(1.05 equiv) was added. Liquid alde-
hydes were added without additional
solvent, solid aldehydes as concen-
trated solutions in a small amount of
[a] All reactions were performed on an 0.5 mmol scale with the CBS catalyst (20 mol%). The borane–dimethyl
sulfide complex (1.3 equiv) was added dropwise (30 min). [b] Isolated yield obtained after purification by
column chromatography. [c] The enantiomeric excess was determinded by chiral HPLC (Chiralcel OD-H, OJ,
OB, AD). [d] Borane–dimethyl sulfide complex and N,N-diethylaniline were premixed in a 1:1 ratio.
Experimental Section
THF. The mixture was stirred for 1 h at RT and then a saturated NH4Cl
solution was added and the mixture was extracted with diethyl ether
(30 mLmmolÀ1). The combined organic layers were washed with brine
and dried (MgSO4). The crude material was purified by column chroma-
tography.
General: All reactions were carried out under argon by using standard
Schlenk techniques. Melting points are uncorrected. 1H and 13C NMR
spectra were recorded on a Bruker AMX 300, AMX 600 or Varian VXR
400 S instrument. Chemical shifts (d) are given as ppm relative to the re-
sidual solvent peak ([D1]chloroform 7.25/77.0 ppm; [D6]benzene 7.16/
128.0 ppm; [D6]acetone 2.04/206.7 ppm). IR spectra were recorded on a
Perkin–Elmer 1420 infrared spectrometer. Mass spectra were recorded
on a Finnnigan MAT 95 Q spectrometer. Optical rotations were meas-
ured on a Perkin–Elmer 241 polarimeter (temperature: 208C). Column
chromatography was performed on Merck silica gel 60 (230–400 mesh
ASTM). Enantiomeric excesses were determined by HPLC (Chiralcel,
Daicel Chemical Industries, column was run with n-heptane/isopropanol
as mobile phase and detection was carried out by a diode array UV/Vis
detector at the given wavelength). THFwas dried with sodium/benzophe-
none and distilled. Elemental analyses were performed on an Elementar
vario EL and with a Metrohm Titroprocessor 686.
(a-Hydroxy(3-benzofuryl)methyl) ferrocene (7a): According to proce-
dure B (tri-n-butylstannyl)ferrocene (575 mg, 1.21 mmol) was treated
with nBuLi (0.73 mL, 1.65m, 1.21 mmol) and benzo[b]furan-3-carbalde-
hyde (169 mg, 1.16 mmol). The alcohol 7a was purified by column chro-
matography (silica gel, n-pentane/diethyl ether 15:1 to 3:1) and obtained
as yellow crystals (336 mg, 1.01 mmol, 87%). M.p. 1138C; 1H NMR
(300 MHz, CDCl3): d=7.94–7.89 (m, 1H), 7.86–7.81 (m, 1H), 7.40–7.30
(m, 2H), 7.27 (d, 4J=0.9 Hz, 1H), 5.83 (brd, 3J=2.5 Hz, 1H), 4.34–4.31
(m, 1H), 4.29–4–25 (m, 1H), 4.27 (s, 5H), 4.24–4.21 (m, 1H), 4.21–4.18
(m, 1H), 2.56 ppm (d, 3J=3.6 Hz, 1H); 13C NMR (75 MHz, C6D6): d=
154.9, 145.4, 139.4, 123.5 (CH), 119.2 (CH), 111.1 (CH), 106.7 (CH), 95.1
(CH), 72.3, 68.8 (CH), 68.2 (CH), 68.1 (CH), 67.7 (CH), 66.4 ppm (CH);
IR (KBr): n˜ =3083 (m), 1561 (w), 1524 (w), 1459 (m), 1427 (s), 1402 (m),
1388 (m), 1257 (m), 1243 (m), 1225 (m), 1174 (m), 1105 (s), 1077 (m),
1049 (s), 1035 (m), 1019 (m), 1001 (s), 918 (m), 859 (m), 819 (s), 781 (m),
763 (s), 734 (s), 499 (s), 484 (s), 450 (m), 421 cmÀ1 (m); EIMS (70 eV):
Synthesis of the ketones 4a–m
Procedure A: The titrated[30] Grignard reagent[2] (2 mmol) was cooled to
À208C and the corresponding aldehyde (2.0 mmol) was added dropwise
220
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 215 – 227

Aryl and Metallocenyl Ketones
FULL PAPER
m/z (%): 348 (43) [M]+, 346 (16), 332 (100), 265 (17), 209 (74); HR-
with nBuLi (1.40 mL, 1.58m, 2.21 mmol) and N-methylindole-3-carbalde-
hyde (350 mg, 2.20 mmol). The crude product was recrystallized (n-
hexane/ethyl acetate 15:4). a-Hydroxy(1-methyl-3-indolyl)methylferro-
cene (7 f) was obtained as red/brown crystals (315 mg, 0.912 mmol,
48%). The mother liquor was purified by column chromatography (silica
gel, n-pentane/diethyl ether 9:1 to 1:2 with 5 to 0% triethylamine) to
obtain further product (63 mg, 0.18 mmol, 10%). M.p. 127–1298C (red);
1H NMR (400 MHz, C6D6): d=8.02–7.97 (m, 1H), 7.27–7.19 (m, 3H),
7.03–6.97 (m, 1H), 6.59 (s, 1H), 5.92 (d, J=3.6 Hz, 1H), 4.47–4.45 (m,
1H), 4.18–4.15 (m, 1H), 4.10 (s, 5H), 4.01–3.99 (m, 1H), 3.98–3.96 (m,
1H), 2.86 ppm (s, 3H); 13C NMR (100 MHz, C6D6): d=137.7, 127.3, 126.7
(CH), 122.2, 122.0 (CH), 120.5 (CH), 119.6 (CH), 109.5 (CH), 94.0, 68.9
(CH), 67.9 (CH), 67.8 (CH), 67.8 (CH), 66.5 (CH), 66.4 (CH), 31.8 ppm
(CH3); IR (KBr): n˜ =3539 (s), 3081 (w), 2894 (w), 1540 (w), 1474 (s),
1330 (m), 1251 (m), 1040 (m), 998 (m), 938 (w), 824 (s), 774 (m), 748 (s),
499 (s), 487 cmÀ1 (s); EIMS (70 eV): m/z (%): 345 (76) [M]+, 329 (30),
1H1656Fe16O32S: 348.0271; found: 348.0250.
12
EIMS: m/z: calcd for
C
19
(a-Hydroxy(2-benzofuryl)methyl) ferrocene (7b): According to proce-
dure B, (tri-n-butylstannyl)ferrocene (295 mg, 0.622 mmol) was treated
with nBuLi (0.37 mL, 1.62m, 0.60 mmol) and benzo[b]furan-2-carbalde-
hyde (79 mg, 0.54 mmol). The alcohol 7b was purified by column chro-
matography (silica gel, n-pentane/diethyl ether 20:1 to 3:1) and obtained
as yellow crystals (155 mg, 0.467 mmol, 86%). M.p. 978C; 1H NMR
(300 MHz, C6D6): d=7.44–7.29 (m, 2H), 7.12–7.02 (m, 2H), 6.45 (s, 1H),
5.45 (d, 3J=5.2 Hz, 1H), 4.21–4.18 (m, 1H), 4.15–4.11 (m, 1H), 4.00 (s,
5H), 3.95–3.91 (m, 2H), 2.10 ppm (d, 3J=5.3 Hz, 1H); 13C NMR
(150 MHz, C6D6): d=159.6, 155.3, 128.7, 124.3 (CH), 123.1 (CH), 121.3
(CH), 111.4 (CH), 103.1 (CH), 70.4, 69.0 (CH), 68.4 (CH), 68.3 (CH),
67.6 (CH), 67.1 (CH), 66.8 ppm (CH); IR (KBr): n˜ =3536 (s), 3098 (m),
2920 (w), 1453 (s), 1251 (m), 1172 (m), 1044 (m), 998 (m), 818 (m),
740 cmÀ1 (s); EIMS (70 eV): m/z (%): 332 (26) [M]+, 330 (33) [MÀ2H]+,
315 (100) [MÀOH]+, 249 (15), 194 (29), 165 (21), 121 (12); HR-EIMS:
280 (21), 262 (40), 206 (100), 186 (13); HR-EIMS: m/z: calcd for
12
C
1H1656Fe16O2: 332.0494; found: 332.0475.
19
12
C
1H1956Fe14N16O: 345.0816; found: 345.0833.
m/z: calcd for
20
a-Hydroxy(1-tosyl-3-indolyl)methyl ferrocene (7g): According to proce-
dure B, (tri-n-butylstannyl)ferrocene (927 mg, 1.95 mmol) was treated
with nBuLi (1.40 mL, 1.58m, 2.21 mmol) and N-methylindole-3-carbalde-
hyde (659 mg, 2.20 mmol). The alcohol 7g was purified by column chro-
matography (silica gel, n-pentane/diethyl ether 5:1 to 0:1 with 12.5 to
0% triethylamine) and obtained as yellow crystals (721 mg, 1.49 mmol,
(a-Hydroxy(3-pyridyl)methyl) ferrocene (7c): According to procedure B,
(tri-n-butylstannyl)ferrocene (997 mg, 2.10 mmol) was treated with
nBuLi (1.27 mL, 1.65m, 2.10 mmol) and pyridine-3-carbaldehyde
(237 mg, 2.21 mmol). The alcohol 7c was purified by column chromatog-
raphy (silica gel, n-pentane/diethyl ether 1:2 to diethyl ether/ethyl acetate
5:1) and obtained as yellow crystals (533 mg, 1.82 mmol, 87%). M.p.
1
1
4
76%). M.p. 76–788C (brown); H NMR (300 MHz, C6D6): d=8.28 (d, J=
1018C; H NMR (300 MHz, C6D6): d=8.84 (d, J=2.2 Hz, 1H), 8.45 (dd,
3J=4.9, 4J=2.2 Hz, 1H), 7.52 (ddd, 3J=7.7, 4J=2.2 Hz, 1H), 6.74 (dd,
3J=7.7, 3J=4.9 Hz, 1H), 5.25 (d, 3J=3.1 Hz, 1H), 4.08–4.04 (m, 1H),
3.96 (s, 5H), 3.90–3.86 (m, 3H), 2.63 ppm (d, 3J=3.1 Hz, 1H); 13C NMR
(75 MHz, C6D6): d=149.0 (CH), 148.8 (CH), 139.6, 133.5 (CH), 123.1
(CH), 93.9, 70.1 (CH), 68.8 (CH), 68.4 (CH), 67.5 (CH), 66.1 ppm (CH);
IR (KBr): n˜ =2836 (w), 1421 (m), 1013 (s), 1106 (m), 820 (s), 760 (m),
717 (m), 516 (m), 500 (m), 486 cmÀ1 (s); EIMS (70 eV): m/z (%): 293
8.0 Hz, 1H), 7.75 (d, J=1.0 Hz, 1H), 7.70–7.62 (m, 3H), 7.19–7.13 (m,
1H), 7.08–7.02 (m, 1H), 6.46 (d, J=8.0 Hz, 2H), 5.52 (brs, 1H), 4.14–
4.11 (m, 1H), 4.05–4.02 (m, 1H), 3.98 (s, 5H), 3.92–3.86 (m, 2H), 2.03
(brs, 1H), 1.63 ppm (s, 3H); 13C NMR (75 MHz, C6D6): d=144.4, 136.2,
136.1, 129.9, 129.8, 126.9 (CH), 126.7 (CH), 125.0 (CH), 123.7 (CH),
123.4 (CH), 121.4 (CH), 112.8 (CH), 89.1, 68.8 (CH), 68.2 (CH), 67.7
(CH), 66.8 (CH), 66.0 (CH), 20.9 ppm (CH3); IR (KBr): n˜ =3092 (w),
1597 (w), 1446 (m), 1369 (s), 1274 (w), 1188 (m), 1174 (s), 1120 (s), 1097
(m), 973 (w), 814 (w), 747 (m), 683 (s), 578 (s), 486 cmÀ1 (w); EIMS
(100) [M]+, 228 (73), 154 (27), 138 (22); HR-EIMS: m/z: calcd for
12
C
1H1556Fe14N16O2: 293.0498; found: 293.0493.
16
(70 eV): m/z (%): 485 (100) [M]+, 469 (16), 338.1 (18), 313 (55), 247 (20),
(a-Hydroxy(4-pyridyl)methyl) ferrocene (7d): According to procedure B,
(tri-n-butylstannyl)ferrocene (1.08 g, 2.27 mmol) was treated with nBuLi
(1.38 mL, 1.65m, 2.27 mmol) and pyridine-4-carbaldehyde (259 mg,
2.42 mmol). The alcohol 7d was purified by column chromatography
(silica gel, n-pentane/diethyl ether 1:2 to diethyl ether/ethyl acetate 5:1)
and obtained as yellow crystals (580 mg, 1.98 mmol, 87%). M.p. 1288C;
1H NMR (300 MHz, C6D6): d=8.57–8.53 (m, 2H), 7.12–7.08 (m, 2H),
5.12 (d, 3J=3.5 Hz, 1H), 3.98–3.95 (m, 1H), 3.95 (s, 5H), 3.92–3.88 (m,
2H), 3.87–3.84 (m, 1H), 2.46 ppm (d, 3J=3.5 Hz, 1H); 13C NMR
(75 MHz, C6D6): d=152.3, 150.1 (CH), 121.2 (CH), 93.6, 70.7 (CH), 68.8
(CH), 68.5 (CH), 68.3 (CH), 67.6 (CH), 66.1 ppm (CH); IR (KBr): n˜ =
1599 (s), 1410 (s), 1178 (m), 1107 (m), 1061 (m), 999 (m), 1019 (s), 818
(s), 505 (m), 483 cmÀ1 (s); EIMS (70 eV): m/z (%): 293 (100) [M]+, 277
12
192 (73); HR-EIMS: m/z: calcd for
C
1H2356Fe14N16O332S: 485.0748;
26
found: 485.0723.
A
N
(7h): A solution of (S)-p-tolylferrocenyl sulfoxide (8, 648 mg, 2.00 mmol)
in THF(25 mL) was cooled to À788C and LDA (2.20 mmol, ca. 0.5m in
THF, n-hexane) was added dropwise over 10 min. The mixture was stir-
red for 30 min and benzaldehyde (0.29 mL, 0.30 g, 2.9 mmol) was added.
The mixture was then stirred for 90 min at À788C. After this time,
NaOH (2n, 20 mL) was added and the mixture was warmed to RT.
Water was added, the organic layer was separated and the aqueous phase
was extracted with diethyl ether (180 mL). The combined organic layers
were washed with water and brine, and then dried (MgSO4). The crude
product was purified by column chromatography (silica gel; n-pentane/di-
ethyl ether 8:1 to 1:1). The product 7h (781 mg, 1.81 mmol, 91%) was
obtained as a yellow solid and as a mixture of diastereomers. The ratio
was determined by integration of the 1H NMR spectrum to be 32:68 (A/
(13), 228 (89), 154 (13), 138 (16); HR-EIMS: m/z: calcd for
12
C
1H1556Fe14N16O2: 293.0498; found: 293.0495.
16
(a-Hydroxy(2-pyridyl)methyl) ferrocene (7e): According to procedure B,
(tri-n-butylstannyl)ferrocene (1.15 g, 2.42 mmol) was treated with nBuLi
(1.47 mL, 1.65m, 2.42 mmol) and pyridine-2-carbaldehyde (269 mg,
2.51 mmol). The alcohol 7e was purified by column chromatography
(silica gel, n-pentane/diethyl ether 3:1 to 1:3) and obtained as yellow
crystals (575 mg, 1.96 mmol, 81%). M.p. 1048C; 1H NMR (300 MHz,
1
3
B). H NMR (200 MHz, C6D6): d=7.48 (d, J=8.2 Hz, 2H; B), 7.38–7.28
(m, 2H, 1H; A and B, respectively), 7.25–7.18 (m, 1H; B), 7.15–7.01 (m,
2H, 3H; A and B, respectively), 6.91–6.83 (m, 3H; A), 6.75 (d, 3J=
3
3
8.2 Hz, 2H; B), 6.67 (s, 1H; B), 6.52 (d, J=8.4 Hz, 2H; A), 6.47 (d, J=
3
3
4
5
9.0 Hz, 1H; A), 5.49 (d, J=9.0 Hz, 1H; A), 5.40 (s, 1H; B), 4.45 (s, 5H;
C6D6): d=8.27 (ddd, J=4.8, J=1.9, J=1.3 Hz, 1H), 7.04–6.93 (m, 2H),
3
3
4
3
B), 4.36 (s, 5H; A), 4.30–4.24 (m, 1H; B), 4.09–4.05 (m, 1H; A), 3.97–
3.92 (m, 1H; A), 3.81 (dd, 3J=2.5 Hz, 1H; A), 3.67 (dd, 3J=2.6 Hz, 1H;
B), 3.43–3.37 (m, 1H; B), 1.86 (s, 3H; B), 1.85 ppm (s, 3H; A).
6.55 (ddd, J=6.8, J=4.8, J=2.1 Hz, 1H), 5.52 (d, J=3.3 Hz, 1H), 4.65
(d, 3J=3.3 Hz, 1H), 4.25–4.22 (m, 1H), 4.21–4.18 (m, 1H), 4.15 (s, 5H),
4.00–3.97 (m, 1H), 3.97–3.94 ppm (m, 1H); 13C NMR (75 MHz, C6D6):
d=162.2, 148.0 (CH), 136.1 (CH), 122.1 (CH), 120.9 (CH), 93.0, 71.5
(CH), 69.1 (CH), 68.3 (CH), 68.0 (CH), 67.8 (CH), 66.2 ppm (CH); IR
(KBr): n˜ =3013 (w), 2914 (w), 2690 (w), 1594 (s), 1568 (m), 1476 (m),
1434 (s), 1104 (s), 1075 (m), 1046 (m), 1020 (m), 1003 (s), 811 (s), 754 (s),
502 (m), 484 cmÀ1 (s); EIMS (70 eV): m/z (%): 293 (100) [M]+, 291 (11)
2-[4-(a-Hydroxy(phenyl)methyl)phenyl]ethinyl ferrocene (7i): A solution
N
of 2-(4-iodophenyl)ethinyl ferrocene (99, 206 mg, 0.500 mmol) in THF
(4 mL) was cooled to À308C and iPrMgCl·LiCl (0.42 mL, 1.31m,
0.55 mmol, 1.1 equiv) was added. The mixture was stirred 1 h and then
benzaldehyde (0.070 mL, 73 mg, 0.69 mmol) was added. The resulting
mixture was stirred for 1.5 h at RT and a saturated NH4Cl solution was
added. The mixture was extracted with diethyl ether (40 mL). The com-
bined organic layers were washed with brine and dried (MgSO4). Before
the solvent evaporation, silica gel (5 g) was added. A yellow powder was
[MÀ2H]+, 228 (61), 210 (42), 154 (22); HR-EIMS: m/z: calcd for
12
C
1H1556Fe14N16O2: 293.0498; found: 293.0490.
16
a-Hydroxy(1-methyl-3-indolyl)methyl ferrocene (7 f): According to pro-
cedure B, (tri-n-butylstannyl)ferrocene (913 mg, 1.92 mmol) was treated
Chem. Eur. J. 2007, 13, 215 – 227
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
221

P. Knochel et al.
obtained which was used directly in the purification by column chroma-
tography (silica gel; n-pentane/diethyl ether 8:1 to 3:1). The alcohol 7i
was obtained as yellow oil (155 mg, 0.395 mmol, 79%). 1H NMR
(600 MHz, C6D6): d=7.50 (d, 3J=8.6 Hz, 2H), 7.22 (d, 3J=7.6 Hz, 2H),
7.18–7.09 (m, 4H), 7.06–7.02 (m, 1H), 5.38 (d, 3J=3.1 Hz, 1H), 4.47 (dd,
J=1.7 Hz, 1H), 4.08 (s, 5H), 3.93 (dd, J=1.7 Hz, 1H), 1.49 ppm (d, 3J=
3.1 Hz, 1H); 13C NMR (151 MHz, C6D6): d=144.4, 144.3, 131.7 (CH),
128.5 (CH), 127.6 (CH), 127.0 (CH), 126.9 (CH), 123.5, 89.1, 86.5, 75.9
(CH), 71.8 (CH), 70.3 (CH), 69.2 (CH), 66.0 ppm; IR (KBr): n˜ =3086
(w), 3029 (w), 2904 (w), 2206 (m), 1512 (m), 1453 (m); 1410 (m), 1190
(m), 1107 (m), 1034 (s), 1024 (s), 1014 (s), 1002 (s), 817 (s), 810 (s), 746
(m), 699 (s), 596 (m), 566 (m), 496 cmÀ1 (s); EIMS (70 eV): m/z (%): 392
1.1 mmol) and benzaldehyde (0.15 mL, 0.16 g, 1.5 mmol). DMPU (2 mL)
as a cosolvent was added. After 12 h at RT and 5 h at 458C, workup pro-
cedure 2 was used. Purification by column chromatography (silica gel, n-
pentane/diethyl ether 2:1 to 0:1) gave the ketone 10d (201 mg,
0.690 mmol, 68%) as a red solid. M.p. 918C; 1H NMR (300 MHz, C6D6):
d=9.41 (d, 4J=1.3 Hz, 1H), 8.56 (dd, 3J=4.5, 4J=1.3 Hz, 1H), 7.91 (dd,
3J=8.0, 4J=1.8 Hz, 1H), 6.73 (dd, 3J=8.0, 3J=4.5 Hz, 1H), 4.63 (dd, J=
1.8 Hz, 2H), 4.12 (dd, J=1.8 Hz, 2H), 3.86 ppm (s, 5H); 13C NMR
(75 MHz, C6D6): d=195.9, 152.4 (CH), 149.8 (CH), 135.5, 135.4 (CH),
123.3 (CH), 78.7, 72.8 (CH), 71.6 (CH), 70.4 ppm (CH); IR (KBr): n˜ =
3115 (w), 1624 (vs), 1581 (m), 1448 (s), 1377 (m), 1295 (s), 1023 (m), 828
(m), 823 (m), 752 (m), 712 (m), 497 cmÀ1 (m); EIMS (70 eV): m/z (%):
(100) [M]+, 390 (35) [MÀ2H]+, 376 (13), 254 (39), 252 (27); HR-EIMS:
291 (100) [M]+, 198 (8), 121 (7); HR-EIMS: m/z: calcd for
m/z: calcd for
C
1H2056Fe16O: 392.0858; found: 392.0877.
25
12
12
C
1H1356Fe14N16O: 291.0341; found: 291.0342.
16
Hydride-transfer oxidation of ferrocenyl alcohols
Procedure C: solution of the ferrocenyl alcohol
4-Pyridyl ferrocenyl ketone (10e): According to procedure C, alcohol 7d
(299 mg, 1.02 mmol) was treated with iPrMgCl·LiCl (0.82 mL, 1.30m,
1.1 mmol) and benzaldehyde (0.16 mL, 0.17 g, 1.6 mmol). DMPU
(0.5 mL) was added as a cosolvent. After 12 h at RT and 2 h at 458C,
workup procedure 2 was used. Purification by column chromatography
(silica gel, n-pentane/diethyl ether 2:1 to 0:1) gave the ketone 10e
(196 mg, 0.673 mmol, 66%) as a red solid. M.p. 145–1468C; 1H NMR
(300 MHz, C6D6): d=8.61 (d, 3J=6.2 Hz, 2H), 7.39 (d, 3J=6.2 Hz, 2H),
4.67 (dd, J=2.0 Hz, 2H), 4.14 (dd, J=2.0 Hz, 2H), 3.85 ppm (s, 5H);
13C NMR (75 MHz, C6D6): d=196.6, 150.7 (CH), 146.3, 121.6 (CH), 77.9,
73.0 (CH), 71.5 (CH), 70.4 ppm (CH); IR (KBr): n˜ =3100 (w), 3066 (m),
1640 (vs), 1598 (m), 1548 (m), 1453 (s), 1407 (m), 1377 (s), 1295 (s), 1056
(m), 834 (m), 817 (s), 764 (m), 670 (s), 514 (s), 497 (m), 483 cmÀ1 (m);
A
7 in THF
(3 mLmmolÀ1) was cooled to 08C and iPrMgCl·LiCl (1.05 equiv) was
added. The mixture was stirred for 10 min, then benzaldehyde
(1.50 equiv) was added and the mixture was stirred at RT for the indicat-
ed time. Two types of workup procedures were used. Type 1: The mixture
was diluted with diethyl ether (40 mLmmolÀ1 alcohol) and silica gel
(10 gmmolÀ1 alcohol) was added. The solvent was removed under re-
duced pressure and the resulting powder was used directly for purifica-
tion by column chromatography. Type 2: A saturated NH4Cl solution was
added and the mixture was extracted with diethyl ether (60 mLmmolÀ1
alcohol). The combined organic layer was washed with brine and dried
(MgSO4). The crude product was purified by column chromatography.
EIMS (70 eV): m/z (%): 291 (100) [M]+, 185 (4), 121 (5); HR-EIMS: m/
Diferrocenyl ketone (10a):[41] According to procedure C, diferrocenylme-
thanol (80 mg, 0.20 mmol) was treated with iPrMgCl·LiCl (0.17 mL,
1.30m, 0.22 mmol) and benzaldehyde (0.040 mL, 42 mg, 0.40 mmol).
After 5 min, the red product was isolated by filtration, and then washed
with water and a small amount of diethyl ether. Ketone 11j (67 mg,
12
z: calcd for
C
16
1H1356Fe14N16O: 291.0341; found: 291.0359.
1-Methyl-3-indolyl ferrocenyl ketone (10 f): According to procedure C,
alcohol 7 f (207 mg, 0.600 mmol) was treated with iPrMgCl·LiCl
(0.55 mL, 1.19m, 0.66 mmol) and benzaldehyde (0.090 mL, 94 mg,
0.89 mmol). After 6 h, workup procedure 1 was used. Purification by
column chromatography (silica gel, n-pentane/diethyl ether 10:1 to 1:1)
gave the ketone 10 f (179 mg, 0.533 mmol, 89%) as a red oil. 1H NMR
(600 MHz, C6D6): d=9.07 (d, J=8.2 Hz, 1H), 7.36 (s, 1H), 7.31 (dd, 3J=
8.2, 4J=1.2 Hz, 1H), 7.22 (dd, 3J=8.2, 4J=1.2 Hz, 1H), 6.92 (d, J=
8.2 Hz, 1H), 6.92 (d, J=8.2 Hz, 1H), 4.99 (dd, J=1.9 Hz, 2H), 4.19 (dd,
J=1.9 Hz, 2H), 4.05 (s, 5H), 2.81 ppm (s, 3H); 13C NMR (150 MHz,
C6D6): d=190.2 (CO), 137.4, 134.0 (CH), 123.8 (CH), 123.7, 123.4 (CH),
122.6 (CH), 117.3, 109.5 (CH), 83.1, 70.9 (CH), 70.8 (CH), 70.3 (CH),
32.3 ppm (CH3); IR (KBr): n˜ =2927 (m), 1606 (m), 1525 (m), 1467 (m),
1374 (w), 1269 (w), 1241 (m), 1166 (w), 1125 (w), 1080 (w), 960 (w), 818
(w), 778 (w), 750 (m), 498 cmÀ1 (m, br); EIMS (70 eV): m/z (%): 343.2
0.17 mmol, 85%) was obtained as
a
red solid. 1H NMR (200 MHz,
CDCl3): d=4.99 (dd, J=2.0 Hz, 2H), 4.52 (dd, J=2.0 Hz, 2H), 4.20 ppm
(s, 5H).
3-Benzofuryl ferrocenyl ketone (10b): According to procedure C, alcohol
7a (239 mg, 0.719 mmol) was treated with iPrMgCl·LiCl (0.58 mL, 1.30m,
0.76 mmol) and benzaldehyde (0.11 mL, 0.11 g, 1.1 mmol). After 2 h,
workup procedure 2 (see above) was used. Purification by column chro-
matography (silica gel, n-pentane/diethyl ether 15:1 to 4:1) gave ketone
1
10b (215 mg, 0.651 mmol, 91%) as a red solid. M.p. 172–1738C; H NMR
(300 MHz, C6D6): d=8.65 (d, J=8.0 Hz, 1H), 7.97 (s, 1H), 7.36 (d, J=
8.0 Hz, 1H), 7.21–7.14 (m, 1H), 7.12–7.04 (m, 1H), 4.75 (dd, J=2 Hz,
2H), 4.10 (dd, J=2 Hz, 2H), 3.86 ppm (s, 5H); 13C NMR (75 MHz,
CDCl3): d=193.7 (CO), 156.7, 146.2 (CH), 135.1, 127.1 (CH), 125.0
(CH), 121.9 (CH), 111.1 (CH), 107.2, 78.6, 72.4 (CH), 71.7 (CH),
70.2 ppm (CH); IR (KBr): n˜ =1618 (s), 1552 (m), 1480 (m), 1447 (s),
1382 (m), 1292 (s), 1184 (w), 1120 (s), 1088 (m), 1024 (w), 818 (s), 779
(w), 754 (s), 582 (w), 502 cmÀ1 (m); EIMS (70 eV): m/z (%): 330 (100)
(100) [M]+, 278.1 (6), 249.1 (6), 194.2 (8), 186.1 (4); HR-EIMS: m/z:
12
calcd for
C
1H1756Fe14N16O: 343.0660; found: 343.0649.
20
1-Tosyl-3-indolyl ferrocenyl ketone (10g): According to procedure C, al-
cohol 7g (486 mg, 1.00 mmol) was treated with iPrMgCl·LiCl (0.80 mL,
1.38m, 1.10 mmol) and benzaldehyde (0.15 mL, 0.16 g, 1.5 mmol). After
6 h, workup procedure 1 was used. Purification by column chromatogra-
phy (silica gel, n-pentane/diethyl ether 10:1 to 2:1) gave the ketone 10g
(254 mg, 0.524 mmol, 52%) as a red solid. M.p. 47–488C; 1H NMR
(600 MHz, C6D6): d=8.69 (d, J=8 Hz, 1H), 8.67 (s, 1H), 8.19 (d, J=
8 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.18–7.10 (m, 2H), 6.44 (d, J=8.4 Hz,
2H), 4.89 (dd, J=1.9 Hz, 2H), 4.13 (dd, J=1.9 Hz, 2H), 3.97 (s, 5H),
1.64 ppm (s, 3H); 13C NMR (150 MHz, C6D6): d=191.1 (CO), 145.2,
135.4, 130.1 (CH), 129.7 (CH), 126.9 (CH), 125.9 (CH), 125.0 (CH), 123.9
(CH), 122.1, 113.5 (CH), 81.0, 72.1 (CH), 71.1 (CH), 70.0 (CH), 21.0 ppm
(CH3); IR (KBr): n˜ =1624 (s), 1537 (m), 1446 (s), 1380 (s), 1298 (w),
1217 (m), 1176 (s), 1126 (s), 1086 (m), 1041 (w), 979 (s), 816 (s), 751 (m),
664 (s), 574 cmÀ1 (s); EIMS (70 eV): m/z (%): 483.1 (100) [M]+, 328.1
[M]+, 265 (9) [MÀC5H5]+, 181 (5), 173 (17), 152 (10), 121 (6), 89 (7);
12
HR-EIMS: m/z: calcd for
C
1H1456Fe16O2: 330.0343; found: 330.0319.
19
2-Benzofuryl ferrocenyl ketone (10c): According to procedure C, alcohol
7b (121 mg, 0.364 mmol) was treated with iPrMgCl·LiCl (0.31 mL, 1.23m,
0.38 mmol) and benzaldehyde (0.060 mL, 63 mg, 0.59 mmol). After 11 h,
workup procedure 1 was used. Purification by column chromatography
(silica gel, n-pentane/diethyl ether 20:1 to 2:1) gave the ketone 10c
(97 mg, 0.294 mmol, 81%) as
a
red solid. M.p. 1478C; 1H NMR
(300 MHz, C6D6): d=7.52 (d, J=0.9 Hz, 1H), 7.36–7.31 (m 2H), 7.15–
7.09 (m 1H), 7.05–6.99 (m, 1H), 5.30 (dd, J=2.0 Hz, 1H), 4.25 (dd, J=
2.0 Hz, 1H), 3.93 ppm (s, 5H); 13C NMR (75 MHz, C6D6): d=185.3,
155.6, 155.1, 127.4 (CH), 123.9 (CH), 123.2 (CH), 112.2 (CH), 112.0
(CH), 78.7, 72.8 (CH), 71.4 (CH), 70.4 ppm (CH); IR (KBr): n˜ =3100
(w), 1624 (s), 1612 (s), 1551 (s), 1476 (m), 1446 (s), 1378 (m), 1300 (s),
(35) [MÀTs]+, 300.1 (60), 262.1 (17), 121 (30); HR-EIMS: m/z: calcd for
12
C
1H2156Fe14N16O332S: 483.0592; found: 483.0573.
26
1136 (m), 1056 (m), 744 cmÀ1 (s); EIMS (70 eV): m/z (%): 330 (100)
(SFc)-(2-Benzoylferrocen-1-yl)-p-(S)-tolyl sulfoxide (10h): According to
[M]+, 173 (11); HR-EIMS: m/z: calcd for
C
1H1456Fe16O2: 330.0338;
12
19
procedure C, alcohol 7h (mixture of diastereomers, 694 mg, 1.61 mmol)
was treated with iPrMgCl·LiCl (1.30 mL, 1.30m, 1.69 mmol) and benzal-
dehyde (0.25 mL, 0.26 g, 2.5 mmol). After 14 h at 08C to RT, workup pro-
cedure 2 was used. Purification by column chromatography (silica gel, n-
found: 330.0353.
3-Pyridyl ferrocenyl ketone (10d): According to procedure C, alcohol 7c
(297 mg, 1.01 mmol) was treated with iPrMgCl·LiCl (0.82 mL, 1.30m,
222
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 215 – 227

Aryl and Metallocenyl Ketones
FULL PAPER
pentane/diethyl ether 1:1 to diethyl ether/ethyl acetate 9:1) gave the
Benzoylcymantrene (14a):[19] The Grignard reagent was obtained from
Chemetall (Frankfurt). Benzoylcymantrene (14a) was prepared accord-
ing to procedure D from cymantrene aldehyde (204 mg, 0.879 mmol),
PhMgCl·LiCl (0.64 mL, 1.44m, 0.92 mmol), and benzaldehyde (0.13 mL,
0.14 g, 1.3 mmol). The compound was purified by column chromatogra-
phy (silica gel, n-pentane/diethyl ether 6:1 to 1:1) and crystallization,
giving the product as red crystals (271 mg, 0.851 mmol, 85%). M.p. 70–
ketone 10h (458 mg, 1.07 mmol, 66%) as
a red solid. M.p. 698C
(decomp); 1H NMR (200 MHz, C6D6): d=8.02 (d, 3J=8.0 Hz, 2H), 7.71
(d, 3J=6.8 Hz, 2H), 7.19–7.02 (m, 3H), 6.94 (d, 3J=8.0 Hz, 2H), 4.35–
4.30 (m, 2H), 3.99–3.94 (m, 1H), 3.73 (s, 5H), 2.00 ppm (s, 3H);
13C NMR (100 MHz, C6D6): d=197.0, 144.6, 140.8, 139.7, 131.0 (CH),
130.1 (CH), 129.6 (CH), 129.2 (CH), 125.7 (CH), 101.9, 78.9, 74.7 (CH),
73.4 (CH), 72.7 (CH), 72.1 (CH), 71.7 (CH), 70.8 (CH), 21.7 ppm (CH3);
IR (KBr): n˜ =3083 (w), 2922 (w), 1734 (w), 1640 (vs), 1597 (m), 1576
(m), 1447 (m), 1424 (s), 1375 (m), 1326 (s), 1260 (s), 1166 (m), 1081 (m),
1040 (s), 1005 (m), 872 (m), 814 (m), 729 (m), 700 (m), 501 (m), 477 (m),
461 cmÀ1 (m); EIMS (70 eV): m/z (%): 428 (51) [M]+, 412 (100) [MÀO]+
1
718C; H NMR (300 MHz, [D6]acetone): d=7.90–7.77 (m, 2H), 7.69–7.46
(m, 3H), 5.70 (s, 2H), 5.21 ppm (s, 2H); 13C NMR (75 MHz,
[D6]acetone): d=195.1, 192.8, 139.4, 133.9 (CH), 130.0 (CH), 129.5 (CH),
93.8, 90.1 (CH), 86.2 ppm (CH); IR (KBr): n˜ =3268 (w), 3111 (m), 3070
(w), 2018 (m), 1948 (m), 1926 (s), 1913 (vs), 1639 (s), 1597 (m), 1453 (m),
1443 (m), 1375 (m), 1286 (m), 1170 (w), 1066 (w), 1038 (w), 855 (w), 842
(w), 721 cmÀ1 (w); EIMS (70 eV): m/z (%): 308 (7) [M]+, 252 (16)
, 305 (26), 289 (26), 260 (15), 256 (12), 105 (20), 77 (10); HR-EIMS: m/z:
12
calcd for
C
1H2056Fe32N16O2: 428.052; found: 428.0563.
24
[MÀ2CO]+, 224 (100) [MÀ3CO]+, 132 (20), 55 (10); HR-EIMS: m/z:
2-(4-Benzoylphenyl)ethinyl ferrocene (10i): According to procedure C,
alcohol 7i (83.4 mg, 0.213 mmol) was treated with iPrMgCl·LiCl
(0.17 mL, 1.30m, 0.22 mmol) and benzaldehyde (0.030 mL, 31 mg,
0.30 mmol). After 16 h at RT, workup procedure 2 was used. Purification
by column chromatography (silica gel, n-pentane/diethyl ether 100:1 to
10:1) gave the ketone 10i (73 mg, 0.19 mmol, 88%) as a red solid. M.p.
1538C; 1H NMR (300 MHz, C6D6): d=7.68–7.64 (m, 2H), 7.61 (d, 3J=
8.6 Hz, 2H), 7.44 (d, 3J=8.6 Hz, 2H), 7.15–7.09 (m, 1H), 7.07–7.00 (m,
2H), 4.48 (dd, J=1.9 Hz, 2H), 4.08 (s, 5H), 3.96 ppm (dd, J=1.9 Hz,
2H); 13C NMR (75 MHz, C6D6): d=194.8, 138.2, 136.8, 132.0 (CH), 131.3
(CH), 130.4 (CH), 130.1 (CH), 92.6, 86.1, 72.0 (CH), 70.4 (CH), 69.5
(CH), 65.1 ppm; IR (KBr): n˜ =3100 (w), 2206 (m), 1654 (vs), 1599 (vs),
1448 (m), 1404 (m), 1309 (s), 925 (m), 742 (m), 702 (s), 499 cmÀ1 (m);
12
calcd for
C
1H955 mn16O4: 307.9881; found: 307.9895; elemental analysis
15
calcd (%) for C15H9MnO4 (308.2): C 58.46, H 2.94; found: C 58.28, H
3.33.
Benzoyl tricarbonylchromium benzene (14b): The Grignard reagent was
obtained from Chemetall (Frankfurt). Benzoyl tricarbonylchromium ben-
zene (14b) was prepared according to procedure D from tricarbonylchro-
mium benzaldehyde (242 mg, 1.00 mmol), PhMgCl·LiCl (0.73 mL, 1.44m,
1.05 mmol) and benzaldehyde (0.15 mL, 0.16 g, 1.5 mmol). This com-
pound was purified by column chromatography (silica gel, n-pentane/di-
ethyl ether 6:1 to 1:1) and crystallization, giving the product as red crys-
tals (271 mg, 0.851 mmol, 85%). M.p. 90–918C; 1H NMR (300 MHz,
[D6]acetone): d=7.86–7.78 (m, 2H), 7.71–7.63 (m, 1H), 7.61–7.52 (m,
3
3
3
EIMS (70 eV): m/z (%): 390 (100) [M]+, 121 (4); HR-EIMS: m/z: calcd
2H), 6.21 (d, J=6.3 Hz 2H), 6.00 (t, J=6.3 Hz, 1H), 5.67 ppm (dd, J=
6.3 Hz, 2H); 13C NMR (75 MHz, [D6]acetone): d=233.3, 194.5, 138.2,
133.8 (CH), 130.1 (CH), 130.0 (CH), 99.0, 98.3 (CH), 98.1 (CH),
92.9 ppm (CH); IR (KBr): n˜ =3100 (m), 3074 (w), 1968 (s), 1917 (s), 1885
(vs), 1654 (s), 1596 (m), 1512 (m), 1295 (m), 1267 cmÀ1 (m); elemental
analysis calcd (%) for C16H10CrO4 (318.2): C 60.38, H 3.17; found: C
60.31, H 3.20.
12
for
C
25
1H1856Fe16O: 390.0702; found: 390.0714.
One-pot synthesis of metallocene ketones
Procedure D: The Grignard reagent was prepared first. Type 1 (direct in-
sertion of magnesium): In a two-necked Schlenk flask with reflux con-
denser and tap-funnel, LiCl (1.0 equiv) was dried in vacuo by using a
heat gun for 10 min and then Mg turnings (1.1 equiv) and THF
4-Methoxybenzoyl tricarbonylchromium benzene (14c):[20] According to
procedure D, the Grignard reagent was generated (Type 1) from p-bro-
moanisol (3.74 g, 20.0 mmol), magnesium (535 mg, 22.0 mmol), and LiCl
(848 mg, 20.0 mmol). 4-Methoxybenzoyl tricarbonylchromium benzene
(14c) was prepared from tricarbonylchromium benzaldehyde (832 mg,
3.44 mmol), Grignard reagent (4.40 mL, 0.82m, 3.61 mmol), and benzal-
dehyde (0.52 mL, 0.54 g, 5.2 mmol). Purification by column chromatogra-
phy (silica gel, n-pentane/diethyl ether 8:1 to 1:1) gave the product as red
(0.5 mLmmolÀ1 LiCl) were added.
A solution of the aryl bromide
(1.0 equiv) in THF(0.5 mLmmol À1) was added within 20 min. The mix-
ture started to boil and no cooling bath was used. The mixture was al-
lowed to settle and the concentration of the Grignard reagent in the su-
pernatant liquid was determined by titration with iodine (ca. 0.5 mmol)
in THF(1 mL) at 0 8C. Type 2 (iodine–magnesium exchange): The aryl
À1
iodide was dissolved in THF(1 mLmmol
)
and iPrMgCl·LiCl
1
(1.0 equiv) was added dropwise at À308C. The mixture was stirred for
30 min. Addition and oxidation: A solution of the metallocene aldehyde
in THF(0.5 mLmmol À1) was cooled to À208C and the Grignard reagent
(1.05 to 1.10 equiv) was added. The mixture was stirred for 10 min and it
turned from orange to yellow. The conversion of the aldehyde was
checked for completion by TLC or by GC (in case of the cymantrene al-
dehyde). Benzaldehyde (1.5 equiv) was added and the mixture was then
warmed to RT and stirred for 12 h. The yellow solution turned orange
again. The conversion was checked for completion and the mixture was
diluted with diethyl ether (10 mLmmolÀ1) and silica gel (5 gmmolÀ1) was
added. The solvent was removed and the remaining powder was used di-
rectly for purification by column chromatography. The tricarbonylchro-
mium arenes were crystallized from n-pentane/diethyl ether at 308C.
crystals (875 mg, 2.51 mmol, 73%). M.p. 126–1278C; H NMR (300 MHz,
[D6]acetone): d=7.88 (d, 3J=9.1 Hz 2H), 7.09 (d, 3J=9.1 Hz, 2H), 6.19
(d, 3J=6.3 Hz 2H), 5.95 (t, 3J=6.3 Hz, 1H), 5.71 (dd, 3J=6.3 Hz, 2H),
3.91 ppm (s, 3H); 13C NMR (75 MHz, [D6]acetone): d=233.3, 204.2,
165.0, 132.8 (CH), 130.4, 115.3 (CH), 101.0, 98.2 (CH), 97.8 (CH),
92.9 ppm (CH); IR (KBr): n˜ =3104 (w), 3021 (w), 1955 (vs), 1874 (vs),
1655 (s), 1591 (s), 1570 (m), 1509 (m), 1422 (m), 1258 (s), 1176 (m),
1142 cmÀ1 (m); elemental analysis calcd (%) for C17H12CrO5 (348.3): C
58.63, H 3.47; found: C 58.57, H 3.35.
4-Phenylbenzoyl tricarbonylchromium benzene (14d): According to pro-
cedure D, the Grignard reagent was generated (Type 1) from 4-bromobi-
phenyl (4.66 g, 20.0 mmol), magnesium (535 mg, 22.0 mmol), and LiCl
(848 mg, 20.0 mmol). As a result of the low solubility, a maximum con-
centration of 0.48m was reached. 4-Phenylbenzoyl tricarbonylchromium
benzene (14d) was prepared from tricarbonylchromium benzaldehyde
(484 mg, 2.00 mmol), Grignard reagent (4.58 mL, 0.48m, 2.20 mmol), and
benzaldehyde (0.31 mL, 0.32 g, 3.0 mmol). Purification by column chro-
matography (silica gel, n-pentane/diethyl ether 9:1 to 1:1) and crystalliza-
tion gave the product as red crystals (549 mg, 1.39 mmol, 70%). M.p.
156–1588C; 1H NMR (300 MHz, [D6]acetone): d=7.94 (d, 3J=8.0 Hz,
2H), 7.85 (d, 3J=8.0 Hz, 2H), 6.26 (d, 3J=6.1 Hz, 2H), 6.00 (t, 3J=
6.1 Hz, 1H), 5.73 ppm (dd, 3J=6.1 Hz, 2H); 13C NMR (75 MHz,
[D6]acetone): d=233.0, 194.0, 146.2, 140.9, 136.8, 130.8 (CH), 130.4
(CH), 129.7 (CH), 128.5 (CH), 128.3 (CH), 99.3, 98.2 (CH), 98.0 (CH),
92.8 ppm (CH); IR (KBr): n˜ =3090 (m), 3032 (w), 1958 (s), 1908 (m),
1893 (m), 1873 (vs), 1654 (s), 1603 (m), 1297 (m), 1261 (m), 747 (m),
3-Benzofurylferrocenyl ketone (10b): According to procedure D, the
Grignard reagent was generated (Type 2) from 3-bromobenzofuran[42]
(4.93 g, 25.0 mmol) and iPrMgCl·LiCl (31.6 mL, 0.79m, 25.0 mmol). Var-
iational to procedure D, the ketone was dissolved in only 5 mL THF. Fur-
thermore, the exchange was performed at À408C over 6 h. Ferrocene al-
dehyde (4.45 g, 20.8 mmol) was dissolved in THF(5 mL) and the
Grignard reagent was added at 08C and stirred for 1 h before benzalde-
hyde (4.06 mL, 4.24 g, 40.0 mmol) was added. Purification was carried
out according to procedure D by column chromatography (silica gel, n-
pentane/diethyl ether 40:1 to 2:1; large amounts of solvent are necessary)
and crystallization from ethyl acetate/diethyl ether (1st fraction: 300 mL,
1:2; 2nd fraction from diethyl ether). The ketone 10b was obtained as
red crystals (5.44 g, 16.5 mmol, 79%). For the analytical data, see above.
Chem. Eur. J. 2007, 13, 215 – 227
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
223

P. Knochel et al.
696 cmÀ1 (m); elemental analysis calcd (%) for C22H14CrO4 (394.3): C
67.01, H 3.47; found: C 66.85, H 3.62.
2H), 6.01 (t, 3J=6.4 Hz, 1H), 5.71 ppm (dd, 3J=6.4 Hz, 2H); 13C NMR
(100 MHz, [D6]acetone): d=233.0, 193.6, 139.4, 136.8, 131.9 (CH), 130.3
(CH), 98.6, 98.3 (CH), 98.2 (CH), 92.8 ppm (CH); IR (KBr): n˜ =3100
(m), 1970 (s), 1876 (vs), 1651 (s), 1584 (m), 1510 (m), 1296 (m), 1264 (m),
1088 (w), 918 (w), 844 (w), 760 cmÀ1 (w); elemental analysis calcd (%)
for C16H9ClCrO4 (352.7): C 54.49, H 2.57; found: C 54.38, H 2.82.
4-Methylbenzoyl tricarbonylchromium benzene (14e):[21] According to
procedure D, the Grignard reagent was generated (Type 1) from 4-bro-
motoluene (17.1 g, ca. 12.3 mL, 100 mmol), magnesium (2.67 g,
110 mmol), and LiCl (4.24 g, 100 mmol). 4-Methylbenzoyl tricarbonyl-
chromium benzene (14e) was prepared from tricarbonylchromium ben-
zaldehyde (709 mg, 2.93 mmol), Grignard reagent (4.52 mL, 0.81m,
3.66 mmol), and benzaldehyde (0.56 mL, 0.58 g, 5.5 mmol). Purification
by column chromatography (silica gel, n-pentane/diethyl ether 8:1 to 2:1)
and crystallization gave the product as red crystals (634 mg, 1.91 mmol,
65%). M.p. 112–1148C; 1H NMR (300 MHz, [D6]acetone): d=7.77 (d,
3J=7.5 Hz, 2H), 7.40 (d, 3J=7.5 Hz, 2H), 6.22 (d, 3J=6.3 Hz, 2H), 6.00
(t, 3J=6.3 Hz, 1H), 5.72 (dd, 3J=6.3 Hz, 2H), 2.45 ppm (s, 3H);
13C NMR (75 MHz, [D6]acetone): d=233.1, 194.0, 144.6, 135.3, 130.5
(CH), 130.3 (CH), 99.7, 98.2 (CH), 97.9 (CH), 92.8 (CH), 22.0 ppm
(CH3); IR (KBr): n˜ =3098 (m), 1964 (s), 1891 (vs), 1645 (s), 1604 (s),
1522 (w), 1403 (w), 1294 (m), 1265 (m), 917 (m), 832 (m), 752 cmÀ1 (m);
elemental analysis calcd (%) for C17H12CrO4 (332.3): C 61.45, H 3.64;
found: C 61.26, H 3.56.
4-Bromobenzoyl tricarbonylchromium benzene (14i):[24c] According to
procedure D, the Grignard reagent was generated (Type 2) from 4-
bromo-1-iodobenzene (622 mg, 2.20 mmol) and iPrMgCl·LiCl (1.68 mL,
1.25m, 2.10 mmol). 4-Bromobenzoyl tricarbonylchromium benzene (14i)
was prepared from tricarbonylchromium benzaldehyde (484 mg,
2.00 mmol), Grignard reagent (2.10 mmol), and benzaldehyde (0.31 mL,
0.32 g, 3.0 mmol). Purification by column chromatography (silica gel, n-
pentane/diethyl ether 10:1 to 1:1) and crystallization gave the product as
red crystals (467 mg, 1.18 mmol, 59%). M.p. 136–1378C; 1H NMR
(300 MHz, [D6]acetone): d=7.90–7.69 (m, 4H), 6.22 (d, 3J=6.6 Hz, 2H),
6.01 (t, 3J=6.6 Hz, 1H), 5.71 ppm (dd, 3J=6.6 Hz, 2H); 13C NMR
(75 MHz, [D6]acetone): d=232.8, 193.6, 137.1, 133.2 (CH), 132.1 (CH),
127. 8, 98.4, 98.2 (CH). 98.1 (CH), 92.7 ppm (CH); IR (KBr): n˜ =3098
(m), 1961 (s), 1868 (vs), 1651 (s), 1584 (m), 1510 (m), 1296 (m), 1263 (m),
1009 (w), 839 (w), 759 cmÀ1 (w); elemental analysis calcd (%) for
C16H9BrCrO4 (397.1): C 48.39, H 2.28; found: C 48.37, H 2.37.
4-N,N-Dimethylaminobenzoyl tricarbonylchromium benzene (14 f):[22]
According to procedure D, the Grignard reagent was generated (Type 1)
from 4-bromo-N,N-dimethylaniline (20.0 g, 100 mmol), magnesium
(2.67 g, 110 mmol), and LiCl (4.24 g, 100 mmol). 4-N,N-Dimethylamino-
benzoyl tricarbonylchromium benzene (14 f) was prepared from tricarbo-
nylchromium benzaldehyde (484 mg, 2.00 mmol), Grignard reagent
(2.63 mL, 0.80m, 2.10 mmol), and benzaldehyde (0.31 mL, 0.32 g,
3.0 mmol). Purification by column chromatography (silica gel, n-pentane/
diethyl ether 4:1 to 1:3) gave the product as red crystals (667 mg,
1.85 mmol, 92%). While the crude material was dried with silica gel the
color turned from red to green and then to blue. However, no effect on
the purity or yield was observed. M.p. 138–1398C (brown); 1H NMR
4-Iodobenzoyl tricarbonylchromium benzene (14j): According to proce-
dure D, the Grignard reagent was generated (Type 2) from 1,4-diiodo-
benzene (726 mg, 2.20 mmol) and iPrMgCl·LiCl (1.68 mL, 1.25m,
2.10 mmol). 4-Iodobenzoyl tricarbonylchromium benzene (14j) was pre-
pared from tricarbonylchromium benzaldehyde (484 mg, 2.00 mmol),
Grignard reagent (2.10 mmol), and benzaldehyde (0.31 mL, 0.32 g,
3.0 mmol). Purification by column chromatography (silica gel, n-pentane/
diethyl ether 8:1 to 2:1) and crystallization gave the product as red crys-
tals (248 mg, 0.558 mmol, 28%). M.p. 160–1618C; 1H NMR (300 MHz,
[D6]acetone): d=7.98 (d, 3J=8.4 Hz, 2H), 7.60 (d, 3J=8.4 Hz, 2H), 6.22
(d, 3J=6.5 Hz, 2H), 6.01 (t, 3J=6.5 Hz, 1H), 5.70 ppm (dd, 3J=6.5 Hz,
2H); 13C NMR (75 MHz, [D6]acetone): d=233.0, 194.0, 139.3 (CH),
137.7, 131.7 (CH), 100.6, 98.5, 98.3 (CH), 98.2 (CH), 92.8 ppm (CH); IR
(KBr): n˜ =3099 (m), 1968 (m), 1893 (vs), 1650 (s), 1579 (m), 1510 (m),
1296 (m), 1262 (m), 1142 (w), 1006 (w), 863 (w), 757 cmÀ1 (w); elemental
analysis calcd (%) for C16H9CrIO4 (444.1): C 43.27, H 2.04; found: C
43.25, H 2.32.
3
3
(300 MHz, [D6]acetone): d=7.85 (d, J=9.1 Hz, 2H), 6.80 (d, J=9.1 Hz,
2H), 6.15 (d, 3J=6.3 Hz, 2H), 5.89 (t, 3J=6.3 Hz, 1H), 5.70 (dd, 3J=
6.3 Hz, 2H), 3.10 ppm (s, 6H); 13C NMR (75 MHz, [D6]acetone): d 233.7,
191.1, 155.2, 133.1 (CH), 124.7, 112.2 (CH), 103.8, 98.1 (CH), 97.4 (CH),
92.9 (CH), 40.7 (CH3); IR (KBr): n˜ =3092 (m), 2911 (m), 1949 (s), 1866
(vs), 1636 (m), 1596 (s, br), 1375 (m), 1233 (m), 818 (m), 765 cmÀ1 (m);
elemental analysis calcd (%) for C18H15CrNO4 (361.3): C 59.84, H 4.18, N
3.88; found: C 59.86, H 4.13, N 3.93.
1-Naphthyl tricarbonylchromiumphenyl ketone (14k): According to pro-
cedure D, the Grignard reagent was generated (Type 1) from 1-bromo-
naphthalene (4.14 g, 2.78 mL, 20.0 mmol), magnesium (535 mg,
22.0 mmol), and LiCl (848 mg, 20.0 mmol). 1-Naphthyl tricarbonylchro-
miumphenyl ketone (14k) was prepared from tricarbonylchromium ben-
zaldehyde (242 mg, 1.00 mmol), Grignard reagent (2.14 mL, 0.49m,
1.05 mmol), and benzaldehyde (0.15 mL, 0.16 g, 1.5 mmol). Purification
by column chromatography (silica gel, n-pentane/diethyl ether 8:1 to 1:1)
and crystallization gave the product as red crystals (287 mg, 0.779 mmol,
78%). M.p. 145–1478C; 1H NMR (300 MHz, [D6]acetone): d=8.13 (d,
3J=8.0 Hz 1H), 8.07–7.97 (m, 2H), 7.75 (dd, 3J=7.1, 4J=1.3 Hz, 1H),
7.67–7.55 (m, 3H), 6.21 (dd, 3J=6.5, 4J=1.1 Hz, 2H), 6.07 (t, 3J=6.5 Hz,
1H), 5.64 ppm (dd, 3J=6.5 Hz, 2H); 13C NMR (75 MHz, [D6]acetone):
d=232.8, 195.7, 136.2, 135.2, 132.5 (CH), 131.9, 130.0 (CH), 128.7 (CH),
128.1 (CH), 127.6 (CH), 126.6 (CH), 126.0 (CH), 99.0 (CH), 98.8 (CH),
98.3, 92.2 ppm (CH); IR (KBr): n˜ =3090 (m), 1966 (s), 1894 (vs), 1880
(vs), 1653 (s), 1508 (m), 1295 (m), 1250 (m), 1201 (w), 777 cmÀ1 (m); ele-
mental analysis calcd (%) for C20H12CrO4 (369.2): C 65.22, H 3.28;
found: C 64.95, H 3.30.
4-D-Benzoyl tricarbonylchromium benzene (14g): According to proce-
dure D, the Grignard reagent was generated (Type 1) from 4-D-1-bromo-
benzene[43] (332 mg, 2.10 mmol) and iPrMgCl·LiCl (2.7 mL, 0.79m,
2.1 mmol). Variational to procedure D, the exchange was carried out at
RT. 4-D-Benzoyl tricarbonylchromium benzene (14g) was prepared from
tricarbonylchromium benzaldehyde (484 mg, 2.00 mmol), Grignard re-
agent, and benzaldehyde (0.31 mL, 0.32 g, 3.0 mmol). Purification by
column chromatography (silica gel, n-pentane/diethyl ether 8:1 to 2:1)
and crystallization gave the product as red crystals (462 mg, 1.45 mmol,
72%). M.p. 87–908C; 1H NMR (400 MHz, [D6]acetone): d=7.82 (d, 3J=
8.0 Hz, 2H), 7.56 (d, 3J=8.0 Hz, 2H), 6.21 (d, 3J=6.4 Hz, 2H), 6.00 (t,
3J=6.4 Hz, 1H), 5.71 ppm (dd, 3J=6.4 Hz, 2H); 13C NMR (100 MHz,
[D6]acetone): d=233.0, 194.6, 138.2, 133.5 (t, 2J
(C,D)=24.3 Hz), 130.1
N
(CH), 129.9 (CH), 99.1, 98.3 (CH), 98.2 (CH), 92.9 ppm (CH); IR (KBr):
n˜ =3100 (m), 1968 (s), 1916 (s), 1890 (vs), 1656 (s), 1512 (m), 1295 (m),
1265 (m), 1145 (w), 921 (w), 863 cmÀ1 (w); elemental analysis calcd (%)
for C16H9CrDO4 (319.2): C 60.19, H 3.47; found: C 59.94, H 3.24.
4-Chlorobenzoyl tricarbonylchromium benzene (14h):[24] According to
procedure D, the Grignard reagent was generated (Type 1) from 4-
chloro-1-bromobenzene (3.83 g, 20.0 mmol), magnesium (535 mg,
22.0 mmol), and LiCl (848 mg, 20.0 mmol). 4-Chlorobenzoyl tricarbonyl-
chromium benzene (14h) was prepared from tricarbonylchromium ben-
zaldehyde (484 mg, 2.00 mmol), Grignard reagent (2.62 mL, 0.84m,
2.20 mmol), and benzaldehyde (0.30 mL, 0.31 g, 2.9 mmol). Purification
by column chromatography (silica gel, n-pentane/diethyl ether 20:1 to
2:1) and crystallization gave the product as red crystals (279 mg,
0.791 mmol, 40%). M.p. 103–1058C; 1H NMR (400 MHz, [D6]acetone):
2-Naphthyl tricarbonylchromiumphenyl ketone (14l): According to pro-
cedure D, the Grignard reagent was generated (Type 1) from 2-bromo-
naphthalene (4.15 g, 20.0 mmol), magnesium (535 mg, 22.0 mmol) and
LiCl (848 mg, 20.0 mmol). As a result of the low solubility, a maximum
concentration of 0.67m was reached. 2-Naphthyl tricarbonylchromium-
phenyl ketone (14l) was prepared from tricarbonylchromiumbenzalde-
hyde (484 mg, 2.00 mmol), Grignard reagent (3.28 mL, 0.67m,
2.20 mmol), and benzaldehyde (0.31 mL, 0.32 g, 3.0 mmol). Purification
by column chromatography (silica gel, n-pentane/diethyl ether 9:1 to 1:1)
and crystallization gave the product as red crystals (605 mg, 1.64 mmol,
3
3
3
d=7.84 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.5 Hz, 2H), 6.23 (d, J=6.4 Hz,
224
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 215 – 227

Aryl and Metallocenyl Ketones
FULL PAPER
1
82%). M.p. 97–998C; H NMR (300 MHz, [D6]acetone): d=8.49 (s, 1H),
2.25 (brs, 1H); 13C NMR (75 MHz, CDCl3): d=143.0, 140.9, 137.2, 129.1,
128.4, 127.4, 126.5, 126.4, 76.1, 21.1 ppm; HPLC analysis (OD, n-heptane/
isopropanol 94:6, 0.7 mLminÀ1, 222 nm): tR (min): 17.9 (S), 20.1 (R).
(2-Naphthyl)phenylmethanol (15d):[46] According to procedure E (Type
2), the tricarbonylchromium phenyl ketone 14l (175 mg, 0.475 mmol) was
reduced with the CBS catalyst (1m in toluene, 0.10 mL, 0.10 mmol,
20 mol%) and borane solution (0.71 mL, 0.71 mmol, 1.5 equiv). The de-
complexation was performed with iodine (133 mg, 0.526 mmol). The
8.11–7.99 (m, 3H), 7.86 (dd, 3J=8.6, 4J=1.5 Hz, 1H), 7.72–7.60 (m, 2H),
6.32 (d, 3J=6.5 Hz, 2H), 6.03 (t, 3J=6.5 Hz, 1H), 5.73 ppm (dd, 3J=
6.5 Hz, 2H); 13C NMR (75 MHz, [D6]acetone): d=233.1, 194.4, 136.6,
135.3, 133.7, 131.4 (CH), 130.7 (CH), 130.0 (CH), 129.8 (CH), 129.2
(CH), 128.5 (CH), 126.3 (CH), 99.4, 98.6 (CH), 98.1 (CH), 92.8 ppm
(CH); IR (KBr): n˜ =3094 (w), 1962 (s), 1871 (vs), 1650 (s), 1518 (w),
1501 (w), 1300 (m), 1275 (m), 1234 cmÀ1 (m); elemental analysis calcd
(%) for C20H12CrO4 (369.2): C 65.22, H 3.28; found: C 65.12, H 3.20.
benzhydrol 15d was isolated as
a white crystalline solid (105 mg,
Asymmetric synthesis of benzhydrols from tricarbonylchromium com-
plexes
0.450 mmol, 95%, 94% ee (R)). 1H NMR (400 MHz, C6D6): d=7.60 (s,
1H), 7.48–7.34 (m, 3H), 7.20–7.13 (m, 2H), 7.12–7.04 (m, 2H), 7.01–6.92
(m, 3H), 6.91–6.85 (m, 1H), 5.46 (d, 3J=2.1 Hz, 1H), 1.76 ppm (d, 3J=
2.1 Hz, 1H); 13C NMR (100 MHz, C6D6): d=144.5, 142.1, 133.8, 133.4,
128.6 (CH), 128.5 (CH), 128.4 (CH), 127.9 (CH), 127.6 (CH), 127.1
(CH), 126.3 (CH), 126.0 (CH), 125.5 (CH), 125.4 (CH), 76.3 ppm (CH);
Procedure E: First, a borane solution was prepared at RT. Type 1 (with-
out additive): THFwas added to borane–dimethyl sulfide complex
(0.95 mL, 0.76 g, 10 mmol) until a total volume of 10 mL was reached.
Type 2 (with N,N-diethylaniline as additive): Borane-dimetyl sulfide com-
plex (0.95 mL, 0.76 g, 10 mmol) was dissolved in THF(5 mL) and then
N,N-diethylaniline (1.59 mL, 1.49 g, 10.0 mmol) and THFwere added
until a total volume of 10 mL was reached. CBS reduction: The tricarbo-
nylchromium ketone 14 (ca. 0.5 mmol) was dissolved in THF(2 mL). In
a Schlenk flask the oxazaborolidine (S)-CBS (CBS catalyst, 20 mol%)
was dissolved in THF(0.5 mL). Then the solution of the tricarbonylchro-
mium ketone 14 and the borane solution (1m, 1.4 equiv) were added si-
multaneously at 08C (Type 1, without additive) or at RT (Type 2, with
N,N-diethylaniline as additive) within 30 min. The color changed from
orange to yellow, showing the disappearance of the ketone. After the ad-
dition had been completed, the mixture was stirred for 10 min and then
water (0.1 mL) was added (CAUTION: gas evolution). The mixture was
filtered over a silica pad (40 mL; n-pentane/diethyl ether 1:3). THF
(10 mL), triethylamine (0.1 mL), and iodine (1.1 equiv) were added to
the eluate and the mixture was stirred for 1 h at RT. After this time, a sa-
turated Na2S2O3 solution was added, the organic layer was separated and
the aqueous phase was extracted twice with diethyl ether (10 mL). The
combined organic layers were washed with brine and dried (Na2SO4).
The crude products were purified by column chromatography (silica gel,
n-pentane/diethyl ether 20:1, 6:1, 2:1).
(4-Methoxyphenyl)phenylmethanol (15a):[44] According to procedure E
(Type 1), the tricarbonylchromium phenyl ketone 14c (106 mg,
0.304 mmol) was reduced with the CBS catalyst (28 mg, 0.10 mmol,
33 mol%) and borane solution (0.45 mL, 0.45 mmol, 1.5 equiv). The de-
complexation was performed with iodine (85 mg, 0.33 mmol). The benz-
hydrol 15a was isolated as a white crystalline solid (59 mg, 0.28 mmol,
91%, 93% ee (R)). 1H NMR (400 MHz, C6D6): d=7.34–7.27 (m, 2H),
7.20–7.10 (m, 3H), 7.09–7.01 (m, 2H), 6.71 (d, 3J=8.6 Hz, 2H), 5.50 (s,
1H), 3.26 (s, 3H), 1.79 ppm (brs, 1H); 13C NMR (100 MHz, C6D6): d=
159.5, 145.1, 137.1, 128.5 (CH), 128.3 (CH), 127.3 (CH), 126.9 (CH),
114.0 (CH), 75.8 (CH), 54.7 ppm (CH3); HPLC analysis (OJ, n-heptane/
isopropanol 80:20, 0.8 mLminÀ1, 229 nm): tR (min): 20.3 (R), 22.5 (S).
HPLC analysis (OD, n-heptane/isopropanol 90:10, 1.0 mLminÀ1
228 nm): tR (min): 14.7 (S), 18.0 (R).
,
(4-Bromophenyl)phenylmethanol (15e):[43] According to procedure
E
(Type 2), the tricarbonylchromium phenyl ketone 14i (202 mg,
0.509 mmol) was reduced with the CBS catalyst (1m in toluene, 0.10 mL,
0.10 mmol, 20 mol%) and borane solution (0.61 mL, 0.61 mmol,
1.2 equiv). The decomplexation was performed with iodine (142 mg,
0.560 mmol). The benzhydrol 15e was isolated as a white crystalline solid
(128 mg, 0.486 mmol, 96%, 88% ee (R)). 1H NMR (300 MHz, CDCl3):
d=7.36 (d, 3J=8.5 Hz, 2H), 7.27–7–09 (m, 7H), 5.68 (s, 1H), 2.05 ppm
(s, 1H); 13C NMR (75 MHz, CDCl3): d=143.3, 142.7, 131.5, 128.6, 128.2,
127.8, 126.5, 121.4, 75.6 ppm; HPLC analysis (AD, n-heptane/isopropanol
90:10, 0.75 mLminÀ1, 225 nm): tR (min): 16.7 (R), 18.2 (S).
(4-Chlorophenyl)phenylmethanol (15 f):[41] According to procedure
E
(Type 2), the tricarbonylchromium phenyl ketone 14h (182 mg,
0.516 mmol) was reduced with the CBS catalyst (1m in toluene, 0.10 mL,
0.10 mmol, 20 mol%) and borane solution (0.62 mL, 0.62 mmol,
1.2 equiv). The decomplexation was performed with iodine (144 mg,
0.568 mmol). The benzhydrol 15 f was isolated as a white crystalline solid
(95 mg, 0.52 mmol, quant., 90% ee (R)). 1H NMR (300 MHz, CDCl3):
d=7.29–7.15 (m, 9H), 5.70 (s, 1H), 2.21 (s, 1H); 13C NMR (75 MHz,
CDCl3): d=143.4, 142.2, 133.2, 128.6, 128.5, 127.9, 127.8, 126.5, 75.6 ppm;
HPLC analysis (AD, n-heptane/isopropanol 95:5, 1.0 mLminÀ1, 225 nm)
tR (min): 12.6 (R), 13.7 (S).
(4-Iodophenyl)phenylmethanol (15g): According to procedure E (Type
2), the tricarbonylchromium phenyl ketone 14j (135 mg, 0.304 mmol) was
reduced with the CBS catalyst (1m in toluene, 0.060 mL, 0.060 mmol,
20 mol%) and borane solution (0.36 mL, 0.36 mmol, 1.2 equiv). The de-
complexation was performed with iodine (85 mg, 0.33 mmol). The benz-
hydrol 15g was isolated as a white crystalline solid (89 mg, 0.29 mmol,
94%, 86% ee (R)). M.p. 70–728C; [a]2D0 =À4.8 (c=0.46 in ethanol); IR
(KBr): n˜ =3303 (s, br), 3060 (m), 3026 (m), 2881 (w), 1481 (m), 1451 (m),
1394 (m), 1188 (w), 1002 (s), 788 (s), 749 (s), 695 cmÀ1 (s); 1H NMR
(300 MHz, CDCl3): d=7.66 (d, 3J=8.1 Hz, 2H), 7.38–7.22 (m, 5H), 7.12
(d, 3J=8.1 Hz, 2H), 5.76 (s, 1H), 2.19 ppm (s, br, 1H); 13C NMR
(75 MHz, CDCl3): d=143.4, 143.3, 137.5, 128.6, 128.4, 127.9, 126.5, 93.0,
(p-Biphenyl)phenylmethanol (15b):[45] According to procedure E (Type
2), the tricarbonylchromium phenyl ketone 14d (193 mg, 0.484 mmol)
was reduced with the CBS catalyst (1m in toluene, 0.10 mL, 0.10 mmol,
20 mol%) and borane solution (0.59 mL, 0.59 mmol, 1.2 equiv). The de-
complexation was performed with iodine (137 mg, 0.538 mmol). The
75.7 ppm; EIMS (70 eV): m/z (%): 310 (24) [M]+, 231 (29), 165 (12), 105
1H11127I16O: 309.9855;
12
benzhydrol 15b was isolated as
a
white crystalline solid (124 mg,
(100), 77 (21); HR-EIMS: m/z: calcd for
C
13
1
0.475 mmol, 97%, 89% ee (R)). H NMR (400 MHz, C6D6): d=7.30–7.22
(m, 4H), 7.18–7.13 (m, 3H), 7.06–7.00 (m, 2H), 7.00–6.92 (m, 4H), 6.91–
6.86 (m, 1H), 5.50 (s, 1H), 5.37 (s, 1H), 1.62 ppm (s, 1H); 13C NMR
(100 MHz, C6D6): d=144.7, 143.8, 141.3, 140.6, 129.0 (CH), 128.6 (CH),
127.6 (CH), 127.4 (CH), 127.4 (CH), 127.3 (CH), 127.0 (CH), 76.0 ppm
found: 309.9831; HPLC analysis (AD, n-heptane/isopropanol 90:10,
0.7 mLminÀ1, 235 nm): tR (min): 12.8 (R), 14.4 (S).
(4-N,N-Dimethylaminophenyl)phenylmethanol (15h): According to pro-
cedure E (Type 1), the tricarbonylchromium phenyl ketone 11r (170 mg,
0.470 mmol) was reduced with the CBS catalyst (1m in toluene,
0.090 mL, 0.090 mmol, 20 mol%) and borane solution (0.57 mL,
0.57 mmol, 1.2 equiv). The decomplexation was performed with iodine
(346 mg, 1.36 mmol). The benzhydrol 15h was isolated as a white crystal-
line solid (103 mg, 0.453 mmol, 96%, 84% ee). Purification by column
chromatography was carried out with n-pentane/diethyl ether 8:1 to 1:1
(CH); HPLC analysis (AD, n-heptane/isopropanol 95:5, 0.8 mLminÀ1
254 nm): tR (min): 25.0 (S), 27.4 (R).
,
(4-Methylphenyl)phenylmethanol (15c):[41] According to procedure
E
(Type 2), the tricarbonylchromium phenyl ketone 14e (154 mg,
0.478 mmol) was reduced with the CBS catalyst (1m in toluene, 0.10 mL,
0.10 mmol, 20 mol%) and borane solution (0.52 mL, 0.52 mmol,
1.2 equiv). The decomplexation was performed with iodine (133 mg,
0.526 mmol). The benzhydrol 15c was isolated as a white crystalline solid
(90 mg, 0.46 mmol, 95%, 93% ee (R)). 1H NMR (300 MHz, CDCl3): d=
7.41–7.22 (m, 7H), 7.15 (d, 3J=7.8 Hz, 2H), 5.80 (s, 1H), 2.34 (s, 3H),
(addition of 5 vol% triethylamine). M.p. 688C (turned green); [a]D20
=
1
+33.3 (c=0.51 in ethanol); H NMR (300 MHz, CDCl3): d 7.42–7.16 (m,
7H), 6.69 (d, 3J=8.8 Hz, 2H), 5.77 (d, 3J=3.4 Hz, 1H), 2.92 (s, 6H),
2.13 ppm (d, 3J=3.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=150.2,
144.3, 132.0, 128.3, 127.7, 127.1, 126.3, 112.5, 76.0, 40.6 ppm; IR (KBr):
Chem. Eur. J. 2007, 13, 215 – 227
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
225

P. Knochel et al.
n˜ =3273 (s, br), 3027 (w), 2880 (m), 2799 (m), 1613 (s), 1520 (s), 1444
Chem. Eur. J. 1996, 2, 1533; heterogeneous variants: n) Y. Zhu, G.
Chuah, S. Jaenicke, J. Catal. 2004, 227, 1; o) A. Corma, M. E.
Domine, S. Valencia, J. Catal. 2003, 215, 294; for a review see:
p) E. J. Creyghton, J. C. van der Waal in Fine Chemicals through
Heterogeneous Catalysis (Eds.: R. A. Sheldon, H. Van Bekkum),
Wiley-VCH, Weinheim, 2001, pp. 438–448; a metal-free variant:
q) L. Sominsky, E. Rozental, H. Gottlieb, A. Gedanken, S. Hoz, J.
Org. Chem. 2004, 69, 1492; MSPV-reduction: r) J. R. Ruiz, C. JimØ-
nez-Sanchidriµn, J. M. Hidalgo, J. M. Marinas, J. Mol. Catal. A 2006,
246, 190; s) C. R. Graves, K. A. Scheidt, S T. Nguyen, Org. Lett.
2006, 8, 1229; t) J. Yin, M. A. Huffman, K. M. Conrad, J. D. Arm-
(m), 1342 (s), 1164 (m), 1012 (s), 793 (s), 695 cmÀ1 (m); EIMS (70 eV):
m/z (%): 227 (100) [M]+, 210 (100), 150 (61), 122 (37), 105 (21), 77 (20);
12
HR-EIMS: m/z: calcd for
C
15
1H1714N16O: 309.1305; found: 227.1297;
HPLC analysis (OD-H, n-heptane/isopropanol 80:20; 0.6 mLminÀ1
261 nm): tR (min): 25.8, 27.6.
;
Acknowledgements
strong,
III, J. Org. Chem. 2006, 71, 840; u) S. Fukuzawa, N.
R.J.K. thanks the Stiftung Stipendien-Fonds des VCI (Frankfurt) and the
Bundesministerium für Bildung und Forschung for a scholarship. We
thank the DFG for financial support and Chemetall GmbH (Frankfurt)
for the generous gift of chemicals.
Nakano, T. Saitoh, Eur. J. Org. Chem. 2004, 2863.
[11] For reviews on oxidation reactions see: a) I. W. C. E. Arends, R. A.
Sheldon in Modern Oxidation Methods (Ed.: J. E. Bäckvall), Wiley-
VCH, Weinheim, 2004, pp. 83–118; b) J. le Paih, J.-C. Frison, C.
Bolm in Modern Oxidation Methods (Ed.: J. E. Bäckvall), Wiley-
VCH, Weinheim, 2004, pp. 253–249; c) Asymmetric Oxidation
(Eds.: M. Beller, B. M. Stoltz) in Tetrahedron: Asymmetry 2005, 16,
3451; d) V. Caprio in Comprehensive Organic Functional Group
Transformations II (Eds.: A. R. Katritzky, R. J. K. Taylor), Elsevier,
Oxford, 2005, pp. 135–214.
[12] B. Byrne, M. Karras, Tetrahedron Lett. 1987, 28, 769.
[13] a) V. Schulze, P. G. Nell, A. Burton, R. W. Hoffmann, J. Org. Chem.
2003, 68, 4645; b) B. K. Wilk, J. L. Helom, C. W. Coughlin, Org.
Process Res. Dev. 1998, 2, 407; c) M. Schroeter, Synth. Commun.
2005, 35, 2203.
[1] a) R. K. Dieter, Tetrahedron 1999, 55, 4177; b) N. J. Lawrence, J.
Chem. Soc. Perkin Trans. 1 1998, 1739.
[2] a) A. Krasovskiy, B. F. Straub, P. Knochel, Angew. Chem. 2006, 118,
165; Angew. Chem. Int. Ed., 2006, 45, 159; b) A. Krasovskiy, P. Kno-
chel, Angew. Chem. 2004, 116, 3396; Angew. Chem. Int. Ed. 2004,
43, 3333; c) P. Knochel, W. Dohle, N. Gommermann, F. F. Kneisel, F.
Kopp, T. Korn, I. Sapountzis, V. A. Vu, Angew. Chem. 2003, 115,
4438; Angew. Chem. Int. Ed. 2003, 42, 4302; d) A. E. Jensen, W.
Dohle, I. Sapountzis, D. M. Lindsay, V. A. Vu, P. Knochel, Synthesis
2002, 565.
[3] A. Krasovskiy, V. Krasovskaya, P. Knochel, Angew. Chem. 2006,
118, 3024; Angew. Chem. Int. Ed. 2006, 45, 2958.
[4] a) P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem.
1988, 53, 2390; b) M. J. Rozema, A. Sidduri, P. Knochel, J. Org.
Chem. 1992, 57, 1956; c) P. Knochel, N. Millot, A. L. Rodriguez,
C. E. Tucker, Org. React. 2001, 58, 417.
[5] C. Duplais, F. Bures, I. Sapountzis, T. J. Korn, G. Cahiez, P. Knochel,
Angew. Chem. 2004, 116, 3028; Angew. Chem. Int. Ed. 2004, 43,
2968.
[6] C. Malanga, L. A. Aronica, L. Lardicci, Tetrahedron Lett. 1995, 36,
9185.
[7] a) E. Negishi, V. Bagheri, S. Chatterjee, F. T. Luo, J. A. Miller, T. A.
Stoll, Tetrahedron Lett. 1983, 24, 5181; b) D. Wang, Z. Zhang, Org.
Lett. 2003, 5, 4645.
[8] X.-J. Wang, L. Zhang, X. Sun, Y. Xu, D. Krishnamurty, C. H. Sena-
nayake, Org. Lett. 2005, 7, 5593.
[9] R. V. Oppenauer, Recl. Trav. Chim. Pays-Bas 1937, 56, 137.
[10] For a recent review on the Oppenauer oxidation and the Meerwein–
Schmidt–Ponndorf–Verley reduction (MSPV reduction) see: a) C. R.
Graves, E. J. Campbell S. T. Nguyen, Tetrahedron: Asymmetry 2005,
16, 3460; Theoretical study on the MSPV reduction: b) R. Cohen,
C. R. Graves, S. T. Nguyen, J. M. L. Martin, M. A. Ratner, J. Am.
Chem. Soc. 2004, 126, 14796; for recent examples see: c) T. Ooi, H.
Otsuka, T. Miura, H. Ichikawa, K. Maruoka, Org. Lett. 2002, 4,
2669; d) T. Ooi, T. Miura, Y. Itagaki, H. Ichikawa, K. Maruoka, Syn-
thesis 2002, 279; e) T. Ooi, T. Miura, K. Maruoka, Angew. Chem.
1998, 110, 2524; Angew. Chem. Int. Ed. 1998, 37, 2347; Oppenauer
oxidation with Ir complexes: f) A. N. Ajjou, J.-L. Pinet, Can. J.
Chem. 2005, 83, 701; g) F. Hanasaka, K. Fujita, R. Yamaguchi,Orga-
nometallics 2004, 23, 1490; Oppenauer oxidation with a bimetallic
RhI/RuII catalyst: h) S. Gauthier, R. Scopelliti, K. Severin, Organo-
metallics 2004, 23, 3769; epimerization with MSPV catalysts: i) D.
Klomp, K. Djanashvili, N. C. Svennum, N. Chantapariyavat, C.-S.
Wong, F. Vilela, T. Maschmeyer, J. A. Peters, U. Hanefeld, Org.
Biomol. Chem. 2005, 3, 483; for a mechanistic study with lanthanide-
[14] (Tri-n-butylstannyl)ferrocene) 6 can be used conveniently as a stor-
able precursor for ferrocenyllithium: D. Guillaneux, H. B. Kagan, J.
Org. Chem. 1995, 60, 2502.
[15] C. J. Yu, Y. Chong, J. F. Kayyem, M. Gozin, J. Org. Chem. 1999, 64,
2070.
[16] A synthesis of 2-aryl-3-benzofuryl ferrocenyl ketones has been re-
ported: A. M. El-Khawaga, K. M. Hassan, A. A. Khalaf, Z. Natur-
forsch. Teil B 1981, 36, 119.
[17] a) C. G. Rodríguez-Cendejas, L. S. Liebeskind, E. PeÇa-Cabrera,
ARKIVOC 2005, 250; see also: b) L. S. Liebeskind, J. Srçgl, J. Am.
Chem. Soc. 2000, 122, 11260; c) Y. Yu, L. S. Liebeskind, J. Org.
Chem. 2004, 69, 3554; for syntheses of related compounds see: d) P.
Molina, A. Tµrraga, J. L. López, J. C. Martínez, J. Organomet.
Chem. 1999, 584, 147; e) T.-Y. Dong, B.-R. Huang, M.-C. Lin, M. Y.
Chiang, Polyhedron 2003, 22, 1199.
[18] 3-Indolyl ferrocenyl ketones that are unsubstituted at the 2-position
have not been described yet. 2-Aryl-3-indolyl ferrocenyl ketones
have been reported by Khalaf.[16]
[19] Formed cuprate did not react at any temperature with benzoyl
chloride. Only starting sulfoxide was reisolated after aqueous
workup.
[20] For recent syntheses of benzoyl cymantrene see: a) Z. Zhang, S. D.
Lepore, Tetrahedron Lett. 2002, 43, 7357; b) S. S. Jones, M. D.
Rausch, T. E. Bitterwolf, J. Organomet. Chem. 1993, 450, 27.
[21] For reviews on tricarbonyl chromium complexes see: a) E. P.
Kündig, Top. Organomet. Chem. 2004, 3; b) E. P. Kuendig, R.
Cannas, C.-H. Fabritius, G. Grossheimann, M. Kondratenko, M.
Laxmisha, S. Pache, H. Ratni, F. Robvieux, P. Romanens, S.
Tchertchian, Pure. Appl. Chem. 2004, 76, 689; c) H. G. Schmalz, F.
Dehmel, Transition Metals for Organic Synthesis, 2nd ed., Wiley-
VCH, Weinheim, 2004, pp. 601; d) E. P. Kündig, S. H. Pache, Sci.
Synth. 2002, 2, 155; e) M. J. Morris in Comprehensive Organometal-
lic Chemistry II (Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson),
Pergamon, New York, 1995, pp. 471.
[22] For a synthesis of tricarbonylchromium ketones by cross-coupling
see: B. Gotov, J. Kaufmann, H. Schumann, H.-G. Schmalz, Synlett
2002, 1161.
ACHTREUNG
ACHTREUNG
[23] Oxidaton reactions with tricarbonylchromium complexes with MnO2
or with DMSO/acetic anhydride have been described: a) F. Effen-
berger, K. Schçllkopf, Chem. Ber. 1985, 118, 4377; b) S. G. Levine,
Tetrahedron Lett. 1982, 23, 1239; c) F. Effenberger, K. Schçllkopf,
T. Patonay, M. W. G. de Bolster, L. A. Wessjohann, Adv. Synth.
Catal. 2004, 346, 731; Oppernauer oxidation promoted by Dibal-H:
l) Y.-S. Hon, C.-P. Changa, Y.-C. Wong, Tetrahedron Lett. 2004, 45,
3313; m) M. L. S. Almeida, M. Beller, G.-Z. Wang, J. E. Bäckvall,
226
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 215 – 227

Aryl and Metallocenyl Ketones
FULL PAPER
Chem. Ber. 1985, 118, 4356; for oxidation with oxygen see: d) S. K.
Mandal, A. Sarkar, J. Org. Chem. 1998, 63, 5672.
ella, J. A. Soderquist, Tetrahedron Lett. 2003, 44, 4435; for a survey
on various borane–amine complexes see: e) B. T. Cho, Y. S. Chun, J.
Chem. Soc. Perkin Trans. 1 1999, 2095; for a review on borane com-
plexes of phosphines and amines see: f) B. Carboni, L. Monnier, Tet-
rahedron 1999, 55, 1197; the effect of different solvents on the enan-
tioselecitivity with a comparable catalyst was described in: g) N. J.
Gilmore, S. Jones, Tetrahedron: Asymmetry 2003, 14, 2115; the use
of borane–amine complexes for the hydroboration of olefins was
described: h) H. C. Brown, J. V. B. Kanth, P. V. Dalvi, M. Zaidlewicz,
J. Org. Chem. 1999, 64, 6263; i) H. C. Brown, M. Zaidlewicz, P. V.
Dalvi, Organometallics 1998, 17, 4202.
[24] a) S. Top, G. Jaouen, J. Organomet. Chem. 1979, 182, 381; b) J. Be-
sanÅon, J. Tirouflet, Rev. Chim. Min. 1968, 5, 363; c) N. J. Fitzpatrick,
N. J. Gogan, I. J. King, J. Organomet. Chem. 1979, 166, 45; d) N. J.
Gogan, I. L. Dickinson, J. R. Patterson, J. Organomet. Chem. 1981,
ˇ
214, 65; for an optimized procedure see: e) M. Hudecek, S. Toma, J.
Organomet. Chem. 1990, 393, 115.
[25] a) T. Ohkuma, M. Koizumi, H. Ikehira, T. Yokozawa, R. Noyori,
Org. Lett. 2002, 2, 659; for a review on Ruthenium-catalyzed hydro-
genation see: b) R. Noyori, T. Ohkuma, Angew. Chem. 2001, 113,
40; Angew. Chem. Int. Ed. 2001, 40, 40.
[30] A. Krasovskiy, P. Knochel, Synthesis 2006, 890.
[26] a) E. J. Corey, C. J. Helal, Tetrahedron Lett. 1995, 36, 9153; b) E. J.
Corey, C. J. Helal, Tetrahedron Lett. 1996, 37, 4837; c) D. Delorme,
C. Berthelette, R. Lavoie, E. Roberts, Tetrahedron: Asymmetry
1998, 9, 3963; for a review see: d) E. J. Corey, C. J. Helal, Angew.
Chem. 1998, 110, 2092; Angew. Chem. Int. Ed. 1998, 37, 1986; see
also: e) E. J. Corey, R. K. Bakshi, S. Shibata, J. Am. Chem. Soc.
1987, 109, 5551; f) S. Itsuno, M. Nakano, K. Ito, A. Hirao, N. Owa,
M. Kanda, S. Nakama, J. Chem. Soc. Perkin Trans. 1 1985, 2615.
[27] a) H. G. Schmalz, H. Jope, Tetrahedron 1998, 54, 3457; b) E. P.
Kündig, A. E. García, T. Lomberget, G. Bernardinelli, Angew.
Chem. 2006, 118, 104; Angew. Chem. Int. Ed. 2006, 45, 98.
[31] D. Shukla, W. G. Ahearn, S. Farid, J. Org. Chem. 2005, 70, 6809.
[32] I. Kazmierski, M. Bastienne, C. Gosmini, J.-M. Paris, J. Perichon, J.
Org. Chem. 2004, 69, 936.
[33] R. P. Singh, R. M. Kamble, K. L. Chandra, P. Saravanan, V. K.
Singh, Tetrahedron 2001, 57, 241.
[34] P. Hanson, S. C. Rowell, A. B. Taylor, P. H. Walton, A. W. Timms, J.
Chem. Soc. Perkin Trans. 2 2002, 1126.
[35] P. J. Wagner, J. H. Sedon, A. Gudmundsdottir, J. Am. Chem. Soc.
1996, 118, 746.
[36] S. Couve-Bonnaire, J.-F. Carpentier, A. Mortreux, Y. Castanet, Tet-
rahedron 2003, 59, 2793.
[28] Highly enantioselective syntheses of benzhydrols by addition of or-
ganozinc reagents to aldehydes have been described: a) J. Rudolph,
F. Schmidt, C. Bolm, Adv. Synth. Catal. 2004, 346, 867; b) C. Bolm,
F. Schmidt, L. Zani, Tetrahedron: Asymmetry 2005, 16, 1367; c) S.
ÖzÅubukÅu, F. Schmidt, C. Bolm, Org. Lett. 2005, 7, 1407; d) X. Wu,
X. Liu, G. Zhao, Tetrahedron: Asymmetry 2005, 16, 2299; e) X. Liu,
X. Wu, Z. Chai, Y. Wu, G. Zhao, S. Zhu, J. Org. Chem. 2005, 70,
7432; f) M. Fontes, X. Verdaguer, L. Solµ, M. A. Pericµs, A. Riera, J.
Org. Chem. 2004, 69, 2532; g) A. L. Braga, D. S. Lüdtke, F. Vargas,
M. W. Paix¼o, Chem. Commun. 2005, 2512; h) P.-Y. Wu, H.-L. Wu,
B.-J. Uang, J. Org. Chem. 2006, 71, 833.
[29] The enantioselectivity of the CBS reduction is highly influenced by
amines as additives. For the use of N,N-diethylaniline see: a) H. S.
Wilkinson, G. J. Tanoury, S. A. Wald, C. H. Senanayake, Org. Proc-
ess Res. Dev. 2002, 6, 146; b) C. E. Garrett, K. Prasad, O. Repic, T. J.
Blacklock, Tetrahedron: Asymmetry 2002, 13, 1347; c) A. M. Sal-
unkhe, E. R. Burkhardt, Tetrahedron Lett. 1997, 38, 1523; for the
use of tert-butyltrimethylsilyl amine see: d) R. E. Huertas, J. A. Cor-
[37] V. P. Shamshin, V. A. Aleshina, S. A. Sukhanova, T. I. Kabanova,
Pharm. Chem. J. 2001, 35, 349.
[38] T. Ishiyama, H. Kizaki, T. Hayashi, A. Suzuki, N. Miyaura, J. Org.
Chem. 1998, 63, 4726.
[39] R. Lerebours, A. Camacho-Soto, C. Wolf, J. Org. Chem. 2005, 70,
8601.
[40] K. K. Laali, S. Hollenstein, J. Chem. Soc. Perkin Trans. 2 1998, 897.
[41] Q. Wang, R. Huang, J. Organomet. Chem. 2000, 604, 287.
[42] R. Stoermer, B. Kahlert, Ber. Dtsch. Chem. Ges. 1902, 35, 1633.
[43] For the synthesis of 4-D-1-bromobenzene see: S. Bank, A. Sche-
partz, P. Giammatteo, J. Zubieta, J. Org. Chem. 1983, 48, 3458.
[44] C. Bolm, F. Schmidt, L. Zani, Tetrahedron: Asymmetry 2005, 16,
1367.
[45] J. Rudolph, F. Schmidt, C. Bolm, Adv. Synth. Catal. 2004, 346, 867.
[46] X. Wu, X. Liu, G. Zhao, Tetrahedron: Asymmetry 2005, 16, 2299.
Received: May 26, 2006
Published online: October 6, 2006
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