Functional-group attachment and interconversion at a chiral [3]ferrocenophane framework

Article abstract of DOI:10.1055/s-2006-942429

Mannich condensation of 1,1′-diacetylferrocene with dimethylamine followed by catalytic hydrogenation gives the chiral α-dimethylamino[3] ferrocenophane. Both enantiomers are available by resolution. Directed ortho-lithiation/iodination yields the ]ortho-iodo-α-dimethylamino[3] ferrocenophane derivative, whose treatment with acetic anhydride and copper(I) oxide yielded the mono- and diacetoxy-functionalized derivatives. The ortho-phosphorylated α-dimethylamino systems (-PPh₂, -PCy ₂) underwent exchange of the directing NMe₂ group with NH₂ by means of an ammonolysis reaction of the corresponding α-chloride derivatives, which in turn were obtained by treatment of the α-dimethylamino compounds with methylchloroformate. Starting from α-dimethylamino[3]ferrocenophane, the sequence of directed ortho-lithiation (t-BuLi), treatment with p-tosyl azide/sodium pyrophosphate (to yield the ortho-azido[3]ferrocenophane derivative) followed by catalytic hydrogenation gave the ortho-amino and α-dimethylamino[3]ferrocenophane derivatives. The potential use of some of the chelate ferrocenophane ligands in Ru-catalyzed asymmetric hydrogenations was investigated. Seven of the newly synthesized compounds were characterized by X-ray diffraction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942429

PAPER
2191
Functional-Group Attachment and Interconversion at a Chiral
[
3]Ferrocenophane Framework
[
C
3]Ferrocenophan
h
e
Chelates ristian Nilewski, Markus Neumann, Ludger Tebben, Roland Fröhlich, Gerald Kehr, Gerhard Erker*
Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany
Fax +49(251)8336503; E-mail: erker@uni-muenster.de
Received 16 May 2006
Dedicated to Professor Dieter Hoppe on the occasion of his 65 birthday
th
We recently introduced a very convenient synthetic entry
to such bisphosphino[3]ferrocenophane chelate ligand
chemistry, which was based on the intramolecular Man-
Abstract: Mannich condensation of 1,1¢-diacetylferrocene with
dimethylamine followed by catalytic hydrogenation gives the chiral
a-dimethylamino[3]ferrocenophane. Both enantiomers are avail-
able by resolution. Directed ortho-lithiation/iodination yields the nich condensation reaction of 1,1¢-diacetylferrocene with
ortho-iodo-a-dimethylamino[3]ferrocenophane derivative, whose dimethylamine to yield 1.7 Subsequent hydrogenation
,8
treatment with acetic anhydride and copper(I) oxide yielded the
gave the trans-disubstituted dimethylamino[3]ferro-
mono- and diacetoxy-functionalized derivatives. The ortho-phos-
phorylated a-dimethylamino systems (-PPh , -PCy ) underwent ex-
9
cenophane 2 as the major product. We developed a sim-
2
2
ple and effective chiral auxiliary-based racemate cleavage
procedure at this stage, which gave the pure enantiomers
change of the directing NMe group with NH by means of an
2
2
ammonolysis reaction of the corresponding a-chloride derivatives,
which in turn were obtained by treatment of the a-dimethylamino
(
R,R)-2 and (S,S)-2 readily in high yield as synthetic
compounds with methylchloroformate. Starting from a-dimethyl- building blocks for further chiral chelate ligand synthe-
amino[3]ferrocenophane, the sequence of directed ortho-lithiation ses.10 The enantiomerically pure ligands of type 3 were
eventually prepared from 2.3
,6
(
t-BuLi), treatment with p-tosyl azide/sodium pyrophosphate (to
yield the ortho-azido[3]ferrocenophane derivative) followed by cat-
alytic hydrogenation gave the ortho-amino and a-dimethylami-
no[3]ferrocenophane derivatives. The potential use of some of the
The successful use of ligands 3 in asymmetric catalysis
prompted us to initiate the development of further cata-
chelate ferrocenophane ligands in Ru-catalyzed asymmetric hydro- lysts based on this functional [3]ferrocenophane. It turned
genations was investigated. Seven of the newly synthesized com- out that the [3]ferrocenophane systems required the appli-
pounds were characterized by X-ray diffraction.
cation and development of some specific reaction se-
Key words: ferrocene, chelate ligand, amino group, P,N-ligand, quences to allow an easy and selective attachment of
asymmetric hydrogenation, catalysis
various functional groups at the required positions of the
framework. Here we briefly outline and report selected
examples that have led to the introduction of oxygen func-
Recently ferrocene-based chelate ligands have gained tionalities and the regio- and stereoselective attachment of
1
considerable importance in catalytic developments. Of amino groups. Some of the latter systems were tested for
the various ferrocene-derived backbone structures the their potential use in the Ru-catalyzed asymmetric reduc-
[
3]ferrocenophanes seem to be useful for the construction tion of aryl ketone model compounds.
2
of chelate ligands for some interesting specific purposes.
We recently found that palladium catalysts derived from
the bisphosphino[3]ferrocenophane chelates 3 show a re- Introduction of Oxygen Functionalities
markable catalyst performance in alternating olefin/car-
3
bonmonoxide polymerization. With some such systems We chose the acetate function as the oxygen functionality
very high catalyst reactivities were achieved and the main to be selectively attached to the [3]ferrocenophane frame-
4,5
chain chirality alternating (propene–co–CO) copolymer
was formed with high asymmetric induction.
work. All of these reactions were carried out with only ra-
cemic compounds. Principally a variety of donor
6
substituents at the a-position of the C -bridge of the
3
[
3]ferrocenophane could be used to effect a directed func-
H2/Pd
tionalization at the 2-position of its adjacent Cp ring. It
has turned out that the dimethylamino substituent was by
far the best for that purpose.
Fe
Fe
Fe
NMe2
NMe2
PR22
1
Therefore, we treated the dimethylamino[3]ferro-
cenophane system 2 with tert-butyl lithium in diethyl
ether. The resulting lithiated product 4 was not isolated
but generated in situ and then directly quenched by treat-
ment with iodine to give the iodo derivative 5 (isolated in
ca. 50% yield). Compound 5 was then treated with acetic
anhydride in acetonitrile in the presence of copper(I) ox-
R 2P
3; ent-3
1
rac-trans-2
Scheme 1
SYNTHESIS 2006, No. 13, pp 2191–2200
x
x.
x
x
.
2
0
0
6
Advanced online publication: 23.06.2006
DOI: 10.1055/s-2006-942429; Art ID: C03006SS
Georg Thieme Verlag Stuttgart · New York
©

2
192
C. Nilewski et al.
PAPER
ide in a one-pot procedure that eventually resulted in the
replacement of both the dimethylamino and the iodide
substituents by acetate. The reaction takes place stepwise;
1
1,12
metal-assisted nucleophilic substitution
of the a-di-
methylamino substituent is fast and occurs by a double in-
version process resulting in the formation of 7 with
retention of stereochemistry. From a reaction that was
stopped after a reaction time of six hours we were able to
obtain single crystals of the intermediate product 7 that
were characterized by X-ray diffraction. The oxidative re-
1
3
placement of iodide at the ferrocene nucleus was much
slower. It required a total reaction time of 16 hours at re-
flux temperatures to go to completion. The diacetoxy-sub-
stituted [3]ferrocenophane product rac-8 was eventually
isolated in close to quantitative yield (Scheme 2).
1
Complex 5 shows the typical H NMR spectral features
for the protons at the strongly folded C -bridge, which
3
leads to a pronounced differentiation of the pseudo-axial Figure 1 A view of the molecular structure of complex rac-trans-5.
Selected bond lengths (Å) and angles (°): Fe–C1 2.020(2), Fe–C2
and pseudo-equatorial hydrogen resonances [i.e., 2.84 (8-
2
2
.036(2), Fe–C3 2.049(2), Fe–C4 2.047(2), Fe–C5 2.026(2), Fe–C10
.012(2), Fe–C11 2.035(2), Fe–C12 2.059(2), Fe–C13 2.048(2), Fe–
H ), 2.25 (8-H ), 2.79 (9-H) ppm]. The X-ray crystal
ax
eq
structure analysis (Figure 1) shows the presence of a
C14 2.021(2), C14–I 2.085(2), C9–C10 1.511(3), C9–N1 1.481(3),
C8–C9–C10 112.7(2), C6–C8–C9 115.9(2), C1–C6–C8 112.6(2).
chair-like conformation for the C -bridge at the ferro-
3
cenophane nucleus. The larger bridge substituent of rac-
trans-5, namely the dimethylamino group at C9, is orient-
ed in a pseudo-equatorial position, whereas the smaller
methyl group at C6 is oriented pseudo-axially. This has
resulted in a practically undisturbed arrangement of the
ferrocene moiety, which is found in a nearly eclipsed met-
allocene conformation. The ferrocene C14–I and the
The diacetyl-substituted compound 8 features a similar
structure in the crystal (see Figure 2, bottom). The oxygen
atom O1 in this case must reside in the Cp plane but the
adjacent –COCH moiety is again oriented away from the
3
ferrocene core.
bridge C9–NMe vectors are found in a close to gauche
conformational orientation.
2
Attachment of NH Groups
2
The selective attachment of NH groups to the chiral
Single crystals of the a-acetoxy functionalized system 7
were obtained from dichloromethane. The X-ray crystal
structure analysis (Figure 2) shows the typical chair-like
2
[
3]ferrocenophane framework proved to be slightly more
difficult. We first developed a viable synthetic pathway to
replace the NMe substituent in compounds 9 (which in
conformation of the C -bridged framework with the ace-
2
3
turn were readily obtained by treatment of 4 with either
toxy substituent oriented in a pseudo-equatorial position
at the bridge and the methyl group at C6 oriented in a
pseudo-axial position. The bulk of this substituent is con-
sequently oriented away from the core of the ferrocene
framework.
3
,6
ClPPh or ClPCy ) by NH . We first tried this by a vari-
2
2
2
10
ation of the established route, i.e. by exchange with a
benzylic amine followed by reductive cleavage. This
proved to be synthetically unfavorable. However, the fol-
Li
H+
I2
Fe
Fe
Li
Fe
I
Ac2O
MeCN)
(
NMe2
NMe2
NMe2
2
4
5
OAc–
Cu2O
Ac2O
Fe
Fe
Fe
H
OAc
OAc
I
I
AcO
6
7
8
Scheme 2
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

PAPER
[3]Ferrocenophane Chelates
2193
O
C
O
C
Cl
OMe
–Me2N
OMe
Fe
Fe
NMe2
NMe2
R2P
2
R P
Cl
O
C
R = Ph:
rac-9a
R,R,Rpl)-9a
OMe
1
0
(
(
S,S,Spl)-9a
R = cyclohexyl:
R,R,Rpl)-9b
S,S,Spl)-9b
(
(
concd NH3 (aq)
HCl
Fe
Fe
–
Cl
NH2
rac-12a
R2P
R P
2
R = Ph:
rac-11a
R = Ph:
(
(
R,R,Rpl)-11a
S,S,Spl)-11a
(R,R,Rpl)-12a
(S,S,Spl)-12a
R = cyclohexyl:
R,R,Rpl)-11b
S,S,Spl)-11b
R = cyclohexyl:
(R,R,Rpl)-12b
(S,S,Spl)-12b
(
(
Scheme 3
the racemate and the pure enantiomers [i.e. (R,R,R )-11a
pl
and (S,S,S )-11a].
pl
Stereoselective exchange of Cl by NH was effected by
2
treatment of the complexes 11a with concentrated aque-
ous ammonia solution at 110 °C. This led to the clean for-
mation of the a-amino-substituted diphenylphosphino
[
3]ferrocenophanes 12a in ca. 50% yield.
The same route was carried out starting from the dicyclo-
hexylphosphino[3]ferrocenophane dimethylamino deriv-
atives (R,R,R )-9b and (S,S,S )-9b. In these cases the
pl
pl
chloro derivatives 11b were generated in situ by treatment
with the methylchloroformate reagent and then directly
Figure 2 Views of the molecular structures of the acetoxy-functio-
nalized [3]ferrocenophane systems rac-7 (top) and rac-8 (bottom).
Selected bond lengths (Å) and angles (°): 7: C14–I 2.076(3), C9–O1
subjected to the ammonolysis reaction to give (R,R,R )-
pl
1
2b and (S,S,S )-12b, in 26% yields, respectively
pl
(
Figure 3).
1.455(3), O1–C15 1.293(3), C15–O2 1.158(4), C10–C9–O1
107.9(2), C9–O1–C15 120.8(2); 8: C14–O1 1.408(2), O1–C15
1.365(3), C15–O2 1.194(3), C9–O3 1.462(2), O3–C17 1.349(3),
1
The H NMR spectral features of the C6(CH )–C8H –
3
2
C9H(NH ) bridge of complex 12a are very similar to
2
C17–O4 1.195(3), C14–O1–C15 115.6(2), C9–O3–C17 116.4(1).
lowing two-step sequence eventually turned out to be a
practical solution to this problem. The complexes 9 were
first converted to the a-chlorides by treatment with meth-
1
4
ylchloroformate (Scheme 3). This route is probably ini-
tiated by amine attack on the reactive carbonic ester
chloride (to generate 10). This then undergoes the typical
replacement of the in situ formed leaving group by anchi-
meric assistance of the iron center to eventually lead to 11
formed with overall retention of stereochemistry in a typ-
1
1,12
ical two-step double-inversion process.
In the diphe-
Figure 3 CD-spectra of the pair of enantiomers (R,R,R )-12b and
pl
nyl phosphine series the intermediate 11a was isolated as
(
S,S,S )-12b.
pl
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

2
194
C. Nilewski et al.
PAPER
those of the dimethylamino derivative 9a [d(12a)/d(9a)
2
3
.72/2.85 (6-H), 3.06/3.17 (8-H ), 2.13/2.30 (8-H ), and
.69/2.67 (9-H) ppm], so that we can assume these com-
a b
pounds have similar conformational structures in solu-
tion; they were found to have analogous conformations in
the solid state. The X-ray crystal structure analyses of
both the (R,R,R )-12a and (S,S,S )-12a enantiomers
pl
pl
(
Figure 4) show the presence of the typical chair-like
bridge conformation at which the methyl substituent at C6
adopts a pseudo-axial position and the amino substituent
at C9 is found oriented pseudo-equatorially. This conse-
quently brings the C9–NH and the C14–P1 vectors in a
2
close to gauche arrangement relative to each other. The
bulky phenyl substituents at the phosphorus atom in 12a
are both oriented away from the nitrogen substituent so
that a large niche is created between the diphenylphosphi-
no and amino substituents of the chiral chelate [3]ferro-
cenophane framework that seems to almost invite suitable
metal complex fragments for chelate coordination.
We have also attached an amino substituent at the proxi-
mal position of the lower ferrocene Cp ring. Initially, this
proved difficult since attempts by Buchwald–Hartwig
amination or Curtius or Hofmann degradation routes16
15
were not successful.
Eventually the amino substituent could successfully be in-
troduced via a Cp-bound azide (Scheme 4). This route
was carried out for the racemic and the (R,R,R )-enantio-
pl
meric series. Treatment of the dimethylamino[3]ferro-
cenophane 2 with tert-butyl lithium gave 4, as described
above (Scheme 2). The lithio[3]ferrocenophane 4 was
then reacted with tosyl azide followed by
1
7a,b
pyrophosphate
to yield the azido[3]ferrocenophane
1
derivative 14. Compound 14 shows the typical H NMR
spectral pattern of the C -bridge hydrogen atoms at 2.18/
3
2
.78 (8-H /H ), 2.83 (6-H), and 2.97 (9-H) ppm.
a b
Single crystals were obtained from the ortho-azido[3]fer-
rocenophane amine derivative rac-14 that allowed its
characterization by X-ray diffraction. It features the typi-
Figure 4 Views of the structures of the separately synthesized en-
antiomers (R,R,R )-12a (top) and (S,S,S )-12a (bottom). Selected
bond lengths (Å) and angles (°) of the R enantiomer: C14–P1
pl
pl
1
1
1
.821(2), C9–N1 1.469(4), C14–P1–C21 100.2(1), C14–P1–C15
01.8(2), C21–P1–C15 101.1(1), C10–C9–N1 110.8(3), C8–C9–N1
07.1(3).
TsN3
Na4P2O7
Fe
Li
Fe
cal ‘chair-like’ folded conformation of the C -bridge with
the methyl substituent at C6 oriented in a pseudo-axial po-
sition and the dimethylamino substituent at C9 oriented
3
NMe2
NMe2
N
Li
N
pseudo-equatorially. The N substituent at the adjacent
3
4
13
N
ferrocene ortho-position is almost linear and arranged co-
Ts
planar with the mean ferrocene Cp plane. The N vector is
3
oriented away from the substituted [3]ferrocenophane C3-
bridge (Figure 5).
Pd(C)/H2
CH3OH
Fe
N3
Fe
Reduction of the azido group in 14 was achieved by hy-
17c
drogenolysis (H , Pd/C) in methanol. The (R,R,Rpl)
2
enantiomer of the amino[3]ferrocenophane system 15 was
obtained in >90% yield from this last step of the synthetic
sequence. It features the amino IR bands at 3417 and 3325
NMe2
NMe2
NH2
rac-14
rac-15
(R,R,Rpl)-15
–
1
1
(
R,R,Rpl)-14
cm and the typical H NMR spectral pattern of the
bridge hydrogens at 2.33/2.45 (8-H /H ), 2.67 (9-H), and
a
b
Scheme 4
2
.76 (6-H) ppm.
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

PAPER
[3]Ferrocenophane Chelates
2195
Table 1 Asymmetric Hydrogenation of Ketones with in situ Gener-
ated Chelate [3]Ferrocenophane Ligand/[Cp*Ru] Catalystsa
O
OH
R2
R1
R2
R1
R1
R2
Ligand
Time Yield ee
Configu-
(
h)
2
2
3
3
3
3
(h)
84
99
94
94
85
52
6
(%) ration
Ph
Ph
Me
Et
(R,R,R )-12a
15
49
83
80
23
34
76
S
S
S
R
pl
(R,R,R )-12a
pl
1
1
2
-Naphthyl
-Naphthyl
-Naphthyl
Me
Me
Me
Me
Me
(R,R,R )-12a
pl
(S,S,S )-12a
pl
(R,R,R )-12a
S
pl
b
Bu
(R,R,R )-12a
pl
1
-Naphthyl
(R,R,R )-12b
44
S
pl
Figure 5 Molecular structure of rac-14 in the crystal. Selected bond
lengths (Å) and angles (°): N2–N3 1.131(2), C10–C9 1.518(2), C9–
N4 1.477(2), C14–N1–N2 114.1(1), N1–N2–N3 173.6(2), C10–C9–
N4 116.2(1), C9–N4–C15 115.1(1), C9–N4–C16 111.4(1), C16–N4–
C15 110.3(1).
a
Conditions: i-PrOH, r.t., H (2 bar).
Not determined.
2
b
Cl
[(p-cymene)RuCl2]2
Ruthenium-Catalyzed Reactions
Fe
Fe
In some preliminary orientating experiments some of the
ligands were briefly tested in asymmetric hydrogenation
catalysis. In a typical series of experiments the chelate
NH2
NH2
Me
R2P
R2P
Ru
Me
ligands (R,R,R )-12a and (S,S,S )-12a were each treated
Cl
pl
pl
rac-12a
rac-16
1
8
with [Cp*Ru(cod)Cl] using a protocol similar to that de-
Me
1
9
scribed by Ikariya et al. The in situ generated Ru catalyst
system effects the hydrogenation of a variety of ketones
under ambient conditions with moderate yields and enan-
tioselectivities (Table 1). The best result was obtained in
the hydrogenation of 1-acetylnaphthalene which occurred
in 94% yield and 83% ee. It should be noted that the [Ru]/
Scheme 6
(
R,R,R )-12a systems effected the hydrogenation of the
pl
aliphatic ketone 2-hexanone in 52% yield and about 34%
ee. The ligands (R,R,R )-12b and (R,R,R )-15 were close
pl
pl
to unreactive catalysts under these conditions.
Me
CH
O
Me
HO
C
[
Cp*Ru(cod)Cl]
ligand , KOH
#
H2, i-PrOH
#
ligand : (R,R,Rpl)-12a, (S,S,Spl)-12a, (R,R,Rpl)-12b
Scheme 5
Additionally, we briefly tested the new chelate ligands in
2
0
Ru-catalyzed transfer hydrogenation also using the sub-
strates listed in Table 1. The catalysts generated in situ
from the ligands (R,R,R )-12a, (R,R,R )-12b, and
pl
pl
2
1
(
R,R,R )-15 and [(p-cymene)RuCl2]2 actively catalyzed
pl
Figure 6 Molecular structure of the ruthenium complex 16. Selec-
the hydrogen transfer from excess isopropanol but gave ted bond lengths (Å) and angles (°): P1–Ru 2.323(1), Ru–Cl1
.396(1), Ru–N1 2.174(4), Ru–C(15) to C(20) 2.181(5) to 2.288(5),
2
only moderate to low enantioselectivities.
P1–Ru–N1 86.4(1), P1–Ru–Cl1 83.8(1), N1–Ru–Cl1 88.1(1), C9–
N1–Ru 122.1(3).
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

2
196
C. Nilewski et al.
PAPER
From one of a series of control experiments, in which rac- 0.37. Single crystals suitable for X-ray diffraction were grown from
a sat. solution of Et O or CH Cl .
1
2a was treated with [(p-cymene)RuCl ] , we obtained
2
2
2
2
2
1
single crystals of complex 16 (Scheme 6), which were
H NMR (599.9 MHz, CD Cl ): d = 4.36 (m, 1 H, H-13), 4.31 (m,
2
2
2
2
1
3
8
H, H-4), 4.15 (m, 1 H, H-2), 4.11 (m, 1 H, H-12), 3.98 (m, 1 H, H-
characterized by X-ray diffraction. In the crystal there is
a single diastereoisomer (Figure 6) that features an anti-
orientation of the [Ru]–Cl vector and the ferrocene core.
The structure shows quasi-octahedral coordination at the
), 3.96 (m, 1 H, H-11), 3.58 (m, 1 H, H-5), 2.84 (m, 2 H, 6-H, Hax-
), 2.79 (dd, J = 11.5, 1.9 Hz, 1 H, H-9), 2.25 (m, 1 H, H -8), 2.21
eq
(
s, 6 H, H-15), 1.25 (d, J = 7.4 Hz, 3 H, H-7).
1
3
1
6
C{ H} NMR (150.8 MHz, CD Cl ): d = 95.5 (C-1), 83.1 (C-10),
2 2
central ruthenium atom with the h -cymene ligand for-
8
(
2
1.5 (C-5), 78.2 (C-13), 72.0, (C-11), 70.7 (C-4), 69.4 (C-12), 68.8
C-2), 68.0 (C-3), 60.3 (C-9), 45.5 (C-15), 44.8 (C-8), 42.3 (C-14),
8.2 (C-6), 17.0 (C-7).
mally occupying three coordination sites. The P,N-[3]fer-
rocenophane chelate and the remaining chloride ligand
are found coordinated to the available octahedral face of
the cationic complex. We assume that base-induced HCl
elimination from this structure followed by hydrogen
transfer generates the active species in transfer hydroge-
Anal. Calcd for C H FeIN: C, 46.97; H, 4.94; N, 3.42. Found: C,
1
6
20
4
6.93; H, 4.79; N, 3.45.
X-ray crystal structure analysis (CCDC 607481): formula
C H FeIN, M = 409.08, orange crystal 0.35 × 0.30 × 0.20 mm,
2
0
16 20
nation catalyses.
a = 10.557(1), b = 12.531(1), c = 11.306(1) Å, b = 95.29(1)°,
3
–3
–1
In this study we have investigated ways to selectively at- V = 1489.3(2) Å , rcalcd = 1.824 gcm , m = 3.072 mm , empirical
absorption correction (0.413 £ T £ 0.579), Z = 4, monoclinic, space
tach simple oxygen and nitrogen substituents in a straight-
forward manner at the a-position of the bridge and the
adjacent ortho-position at the Cp ring of the chiral [3]fer-
group P2 /c (No. 14), l = 0.71073 Å, T = 198 K, w and j scans,
1
–
1
1
1588 reflections collected (±h, ±k, ±l), [(sinq)/l] = 0.67 Å , 3616
independent (R = 0.030) and 3335 observed reflections [I ≥
int
rocenophane framework. Not all of the attached groups
2
s(I)], 175 refined parameters, R1 = 0.024, wR2 = 0.058, max. re-
–3
themselves will be of value directly, but their underlying sidual electron density 0.44 (–0.81) eÅ , hydrogens are calculated
OH and NH functionalities will probably allow for easy and all refined as riding atoms.
2
and valuable variations of the chelate functionalities.
Since these systems are readily available in each of the
rac-7
Compound rac-5 (1.17 g, 2.86 mmol) and Cu O (0.41 g, 2.86
2
enantiomerically pure forms we are hopeful that new
mmol) were suspended in MeCN (40 mL), then Ac O was added
2
[
3]ferrocenophane chelate ligands derived from these re-
(0.7 mL, 7.15 mmol) and the mixture was refluxed for 6 h. After fil-
lay complexes will become useful building blocks for fu-
ture developments in selective homogeneous catalysis.
tration the crude product was purified via column chromatography
(SiO , cyclohexane–EtOAc, 3:1) to furnish 0.60 g (1.40 mmol,
2
4
0
9%) of a yellow powder along with a second product rac-2 (87 mg,
.24 mmol, 8%); R = 0.81. Single crystals suitable for X-ray dif-
f
Reactions with air- and moisture-sensitive compounds were carried
out in an inert atmosphere (argon) using Schlenk-type glassware or
a glove box. Solvents were dried and distilled under argon prior to
use. The following instruments were used for characterization: mp,
TA instruments differential scanning calorimeter 2010; optical ro-
tation, Perkin-Elmer 351 Polarimeter (25 °C, l = 589 nm, 1 dm cu-
fraction were grown from a solution of CD Cl . The compound was
only characterized by X-ray diffraction and elemental analysis.
2
2
Anal. Calcd for C H FeIO : C, 45.32; H, 4.04. Found: C, 45.43;
H, 3.92.
16 17
2
X-ray crystal structure analysis (CCDC 607479): formula
C H FeIO , M = 424.05, orange crystal 0.35 × 0.30 × 0.30 mm,
–1
1
vette, c 10 mg mL ); NMR spectroscopy: Bruker AC-200P-FT ( H:
1
6
17
2
1
3
31
1
2
00.1 MHz, C: 50.3 MHz, P: 81.0 MHz), ARX 300 ( H: 300.1
a = 6.915(1), b = 7.433(1), c = 14.706(1) Å, a = 80.70(1)°,
1
3
31
1
MHz, C: 75.5 MHz, P: 121.5 MHz), AMX 400 ( H: 400.1 MHz,
C: 100.6 MHz), Varian INOVA 500 ( H: 499.8 MHz, C: 125.7
MHz), and UNITY Plus 600 ( H: 599.1 MHz, C: 150.7 MHz); IR:
Varian 3100 FT-IR Excalibur Series; UV-Vis: Varian Cary I Bio;
CD: JASCO J-600 (c in mol/L); and elemental analyses: Foss-Her-
aeus CHN-O-Rapid. Compounds rac-2, (R,R)-2, (S,S)-2, rac-9a,
3
–3
b = 85.82(1)°, g = 88.86(1)°, V = 743.9(2) Å , r
= 1.893 g cm ,
calcd
1
3
1
13
–1
m = 3.086 mm , empirical absorption correction (0.411 £ T £
1
13
0
.458), Z = 2, triclinic, space group P–1 (No. 2), l = 0.71073 Å,
T = 198 K, w and j scans, 7526 reflections collected (±h, ±k, ±l),
–1
[
(sinq)/l] = 0.67 Å , 3583 independent (R = 0.040) and 3293 ob-
int
served reflections [I ≥ 2s(I)], 183 refined parameters, R1 = 0.028,
wR2 = 0.080, max. residual electron density 0.69 (–1.19) eÅ , hy-
(
R,R,R )-9a, (S,S,S )-9a, (R,R,R )-9b, and (S,S,S )-9b were pre-
–3
pl
pl
pl
pl
3
,6,9,10
pared as previously described by us.
drogens are calculated and all refined as riding atoms.
Data sets for the X-ray crystal structure analyses were collected on
a Nonius Kappa CCD diffractometer, equipped with a rotating an-
rac-8
2
3a
To a solution of rac-5 (6.06 g, 14.8 mmol) in MeCN (60 mL), Ac O
(8.0 mL, 84.8 mmol) and Cu O (2.12 g, 14.8 mmol) were added and
the mixture was refluxed for 16 h. The solvent was removed under
reduced pressure and the residue was extracted with EtOAc. The
crude product was purified by column chromatography (SiO , cy-
ode generator. Programs used: data collection, COLLECT; data
2
2
3b
23c,23d
reduction, Denzo-SMN; absorption correction, SORTAV
2
and Denzo;2 structure solution, SHELXS-97; structure refine-
3e
23f
ment, SHELXL-97;23g and graphics, SCHAKAL.
23h
2
clohexane–EtOAc, 3:1) to furnish 5.15 g (14.5 mmol) of a yellow
rac-5
solid; R = 0.63. Single crystals suitable for X-ray diffraction were
To a solution of the tertiary amino[3]ferrocenophane rac-2 (7.82 g,
f
grown from a solution of CD Cl .
2
4
7.6 mmol) in Et O (250 mL), t-BuLi (1.5 M, hexane; 27.6 mL,
1.4 mmol) was added at 0 °C. After stirring for 30 min at r.t., the
2
2
2
1
H NMR (599.9 MHz, CD Cl ): d = 5.51 (dd, J = 10.7, 3.4 Hz, 1 H,
2
2
solution was cooled to 0 °C and I (14.0 g, 55.2 mmol) was added.
The reaction was stirred at r.t. for 2 h and then quenched with a sat.
solution of Na S O (150 mL). After phase separation the aqueous
phase was extracted with Et O (2 × 60 mL) and dried over MgSO .
2
H-9), 4.30 (m, 1 H, H-5), 4.25 (m, 1 H, H-13), 4.24 (m, 1 H, H-2),
.04 (m, 1 H, H-4), 4.02 (m, 1 H, H-3), 4.00 (m, 1 H, H-11), 3.90
4
2
2
3
(m, 1 H, H-12), 2.80 (m, 2 H, 6-H, H -8), 2.19 (s, 3 H, H-18), 2.13
ax
2
4
(m, 1 H, H -8), 1.93 (s, 3 H, H-16), 1.30 (d, J = 7.3 Hz, 3 H, H-7).
eq
The crude product was purified via column chromatography (SiO2,
MeOH) to furnish 5.74 g (14.0 mmol, 51%) of an orange solid; R =
f
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

PAPER
[3]Ferrocenophane Chelates
2197
1
3
1
C{ H} NMR (150.8 MHz, CD Cl ): d = 170.7 (C-15, C-17), 115.9
Compound 12a
rac-12a
2
2
(
6
(
C-14), 94.2 (C-1), 73.4 (C-4), 73.3 (C-10), 71.0 (C-5), 68.9 (C-2),
8.1 (C-3), 67.9 (C-9), 65.8 (C-11), 64.4 (C-13), 63.7 (C-12), 47.0
C-8), 27.7 (C-6), 21.2 (C-18), 21.1 (C-16), 17.4 (C-7).
A sample of rac-11a (1.27 g, 2.76 mmol) was dissolved in toluene
(9.2 mL) and placed in a Schlenk tube fitted with a Teflon screw
cap. An aq concd solution of NH (4.6 mL) was added and the
sealed flask was heated behind a safety shield for 5 h at 110 °C. The
3
Anal. Calcd for C H FeO : C, 60.70; H, 5.66. Found: C, 60.33; H,
1
8
20
4
5
.53.
X-ray crystal structure analysis (CCDC 607480): formula
C H FeO , M = 356.19, yellow crystal 0.55 × 0.55 × 0.20 mm,
mixture was cooled to r.t. and then a solution of NaHCO (10 mL)
3
was added. The organic phase was separated, a 1 M solution of
NaOH (10 mL) was added to the aqueous phase which was then ex-
tracted with CH Cl (3 × 10 mL). The combined organic phases
1
8
20
4
a = 15.768(1), b = 7.125(1), c = 16.315(1) Å, b = 118.56(1)°,
2
2
3
–3
–1
V = 1609.9(3) Å , r
= 1.470 gcm , m = 0.954 mm , empirical
calcd
were washed with a solution of 1 M NaOH (10 mL), a solution of
NaHCO (10 mL), and then dried over MgSO . The solvent was re-
absorption correction (0.702 £ T £ 0.972), Z = 4, monoclinic, space
group P2 /n (No. 14), l = 0.71073 Å, T = 198 K, w and j scans,
0776 reflections collected (±h, ±k, ±l), [(sinq)/l] = 0.66 Å , 3837
independent (Rint = 0.053) and 2769 observed reflections [I ≥ 2s
I)], 211 refined parameters, R1 = 0.038, wR2 = 0.096, max. resid-
3
4
1
moved in vacuo and the product purified by column chromatogra-
phy (silica gel, MeOH) to furnish a yellow solid (700 mg, 58%);
Rf = 0.53.
–
1
1
(
–
3
ual electron density 0.32 (–0.40) eÅ , hydrogens are calculated and
all refined as riding atoms.
(
R,R,R )-12a
pl
According to the procedure described above ammonolysis of
(
R,R,R )-9a (1.09 g, 2.37 mmol) in toluene (8 mL) with a concd aq
pl
Compound 11a
rac-11a
solution of NH (4 mL) furnished 553 mg (53%) of (R,R,R )-12a;
[
from MeOH at –20 °C.
3
pl
20
–1
a]D +258 (c 1.1 × 10 , MeCN). Single crystals were obtained
NaHCO (5.92 g, 70.6 mmol) was added to a solution of rac-9a
3
(4.12 g 8.82 mmol) in toluene (40 mL) and stirred for 30 min.
Anal. Calcd for C H NPFe⋅0.85H O: C, 68.68; H, 6.15; N, 3.08.
Found: C, 69.17; H, 5.76; N, 2.88; H O present in the sample ac-
cording to NMR spectroscopy.
2
6
26
2
Methylchloroformate (4.10 mL, 52.9 mmol) was added and the
mixture was stirred for 2 h. The suspension was filtered through
celite, the solvent was removed under reduced pressure, and the
crude product was dried for 16 h to remove high boiling by-products
to furnish 3.96 g (8.64 mmol, 98%) of rac-11a. Single crystals suit-
able for X-ray diffraction were grown from a solution of toluene at
2
X-ray crystal structure analysis (CCDC 607477): formula
C H NPFe, M = 439.30, orange crystal 0.30 × 0.15 × 0.10 mm,
a = 8.929(1), b = 14.965(1), c = 15.778(1) Å, V = 2108.3(3) Å ,
2
6
26
3
–
3
–1
–
32 °C.
rcalcd = 1.384 gcm , m = 0.803 mm , empirical absorption correc-
tion (0.795 £ T £ 0.924), Z = 4, orthorhombic, space group P2
No. 19), l = 0.71073 Å, T = 293 K, w and j scans, 12682 reflec-
1
2 2
1 1 1
H NMR (599.9 MHz, CD Cl ): d = 7.51–7.47 (m, 2 H, o-Ph), 7.38–
2
2
(
7
7
1
.35 (m, 3 H, m-Ph, p-Ph), 7.27–7.24 (m, 3 H, m-Ph, p-Ph), 7.24–
.20 (m, 2 H, o-Ph), 4.84 (dd, J = 12.5, 3.1 Hz, 1 H, H-9), 4.56 (m,
H, H-5), 4.36 (m, 1 H, H-11), 4.25 (m, 1 H, H-12), 4.22 (m, 1 H,
–
1
tions collected (±h, ±k, ±l), [(sinq)/l] = 0.66 Å , 5030 independent
(
parameters, R1 = 0.040, wR2 = 0.073, Flack parameter 0.01(1),
max. residual electron density 0.24 (–0.29) eÅ , hydrogen atoms at
N1 from difference Fourier map, others are calculated and refined
as riding atoms.
Rint = 0.048) and 3486 observed reflections [I ≥ 2s(I)], 271 refined
H-2), 3.86 (m, 1 H, H -8), 3.84 (m, 1 H, H-3), 3.69 (m, 1 H, H-13),
ax
–3
3
.60 (m, 1 H, H-4), 2.84 (m, 1 H, H-6), 2.44 (m, 1 H, H -8), 1.28
eq
(
d, J = 7.3 Hz, 3 H, H-7).
1
3
1
C{ H} NMR (150.8 MHz, CD Cl ): d = 140.2 (d, J = 9.3 Hz,
2
2
P,C
i-Ph), 138.3 (d, JP,C = 10.7 Hz, i-Ph), 135.3 (d, J = 20.8 Hz, o-Ph),
P,C
(S,S,S )-12a
pl
1
33.1 (d, JP,C = 18.3 Hz, o-Ph), 129.3 (p-Ph), 128.3 (d, JP,C = 7.3
According to the procedure described above ammonolysis of
(S,S,S )-9a (1.01 g, 2.21 mmol) in toluene (7.4 mL) with a concd aq
solution of NH (3.7 mL) furnished 497 mg (51%) of (S,S,S )-12a;
mp 185.2 °C; [a]D –253 (c 1.1 × 10 , MeCN).
Hz, m-Ph), 128.1 (p-Ph), 128.1 (d, JP,C = 7.3 Hz, m-Ph), 93.3 (C-1),
7.5 (d, JP,C = 18.9 Hz, C-10), 76.0 (d, JP,C = 16.0 Hz, C-14), 75.2
d, JP,C = 4.6 Hz, C-13), 73.7 (d, JP,C = 4.1 Hz, C-11), 72.8 (d,
JP,C = 5.8 Hz, C-5), 70.8 (C-4), 70.4 (C-12), 69.4 (C-2), 68.1 (C-3),
pl
8
(
3
pl
20
–1
IR (ATR): 3049, 2963, 2916, 2860, 1434, 1027 cm–1.
5
6.2 (C-9), 52.4 (d, JP,C = 10.5 Hz, C-8), 29.3 (C-6), 16.4 (C-7).
1H NMR (599.9 MHz, CD
m, 1 H, H-5), 4.27 (m, 1 H, H-11), 4.15 (m, 1 H, H-12), 4.14 (m, 1
H, H-2), 3.85 (m, 1 H, H-3), 3.69 (m, 1 H, H-9), 3.66 (m, 1 H, H-4),
.48 (m, 1 H, H-13), 3.06 (m, 1 H, H -8), 2.72 (m, 1 H, H-6), 2.13
Cl ): d = 7.23–7.45 (m, 10 H, Ph), 4.42
2 2
3
1
1
P{ H} NMR (81.0 MHz, CD Cl ): d = –21.6.
2
2
(
+
+
MS (EI, 70 eV): m/z (%) = 458 (100) [M ], 422 (65) [(M – Cl) ],
75 (77).
2
3
(
a
2
3
3
ddd, J = 13.4 Hz, J = 5.0 Hz, J = 3.4 Hz, 1 H, H -8), 1.61 (br, 2
b
(
R,R,R )-11a
3
pl
H, H-15), 1.26 (d, J = 7.2 Hz, 3 H, H-7).
13
According to the procedure described above NaHCO (1.82 g, 21.6
3
1
C{ H} NMR (150.8 MHz, CD Cl ): d = 140.5 (d, J = 10.2 Hz,
2
2
P,C
mmol, 8.0 equiv) was added to a solution of (R,R,R )-9a (1.26 g,
pl
i-Ph), 138.1 (d, JP,C = 11.0 Hz, i-Ph), 134.0 (d, JP,C = 20.2 Hz, Ph),
32.9 (d, JP,C = 18.4 Hz, Ph), 129.2 (Ph), 128.5 (d, JP,C = 5.6 Hz,
2
.70 mmol, 1 equiv) in toluene (14.5 mL) followed by methylchlo-
1
roformate (1.30 mL, 1.59 g, 16.8 mmol, 6.2 equiv) to furnish 1.23 g
Ph), 128.4 (d, JP,C = 7.6 Hz, Ph), 128.3 (Ph), 93.9 (C-1), 93.0 (d,
JP,C = 18.0 Hz, C-10), 74.5 (d, JP,C = 11.1 Hz, C-14), 73.9 (d,
JP,C = 4.2 Hz, C-11), 73.8 (br, C-13), 73.0 (d, JP,C = 6.0 Hz, C-5),
(
99%) of (R,R,R )-11a.
pl
(
S,S,S )-11a
pl
6
9.8 (C-2), 69.8 (C-4), 68.7 (C-2), 67.9 (C-3), 51.7 (d, JP,C = 6.8 Hz,
According to the procedure described above NaHCO (1.67 g, 19.9
3
C-8), 45.8 (C-9), 27.4 (C-6), 17.7 (C-7).
3
mmol, 8.0 equiv) was added to a solution of (S,S,S )-9a (1.16 g,
pl
1
1
2
.48 mmol, 1.0 equiv) in toluene (12.5 mL) followed by methyl-
chloroformate (1.15 mL, 1.40 g, 14.8 mmol, 6.0 equiv) to furnish
.14 g (quantitative) of (S,S,S )-11a.
P{ H} NMR (81.0 MHz, CD Cl ): d = –19.5.
2 2
+
+
MS (ESI, ES , MeCN): m/z = 440.2 [(M + H) ].
1
pl
UV/Vis (CH Cl ): l (e) = 435 (120), 258 (11300), 228 (12000).
2
2
max
Anal. Calcd for C H NPFe⋅0.41H O: C, 69.90; H, 6.06; N, 3.14.
2
6
26
2
Found: C, 69.34; H, 5.77; N, 2.96.
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

2
198
C. Nilewski et al.
PAPER
X-ray crystal structure analysis (CCDC 607476): formula
Anal. Calcd for C H NPFe: C, 69.17; H, 8.50; N, 3.10. Found: C,
2
6
38
C H NPFe, M = 439.30, yellow crystal 0.30 × 0.30 × 0.15 mm,
a = 8.896(1), b = 14.893(1), c = 15.673(1) Å, V = 2076.5(3) Å ,
68.57; H, 8.62; N, 2.79.
2
6
26
3
–
3
–1
rcalcd = 1.405 gcm , m = 0.816 mm , empirical absorption correc-
(S,S,S )-12b
pl
tion (0.792 £ T £ 0.887), Z = 4, orthorhombic, space group P2 2 2
Prepared according to the procedure described above. (S,S,S )-9b
(469 mg, 0.98 mmol) and NaHCO (658 mg, 7.8 mmol) in toluene
(0.45 mL) were treated with methylchloroformate (0.55 g, 5.80
mmol) in toluene (4.9 mL) to furnish 443 mg of the crude interme-
diate. Ammonolysis of the crude (384 mg) with a concd solution of
ammonia (3 mL) in toluene (4 mL) furnished 101 mg (26%) of
1
1
1
pl
(
No. 19), l = 0.71073 Å, T = 198 K, w and j scans, 13544 reflec-
3
–
1
tions collected (±h, ±k, ±l), [(sinq)/l] = 0.67 Å , 4880 independent
(
R
int
= 0.036) and 4575 observed reflections [I ≥ 2s(I)], 271 refined
parameters, R1 = 0.026, wR2 = 0.059, Flack parameter –0.01(1),
–
3
max. residual electron density 0.23 (–0.24) eÅ , hydrogen atoms at
N1 from difference Fourier map, others are calculated and refined
as riding atoms.
(S,S,S )-12b after chromatographic purification (first MeOH, then
pl
2
589
0
–1
Et O); [a]
–215 (c 1.0 × 10 , CH Cl ).
2
2 2
–
5
CD (c 8.9 × 10 , CH Cl ): De (lmax) = +2.47 (285), –0.64 (328),
2
2
Compound 12b
+1.11 (417).
(
R,R,R )-12b
pl
Anal. Calcd for C H NPFe: C, 69.17; H, 8.50; N, 3.10. Found: C,
A sample of (R,R,R )-9b (814 mg, 1.74 mmol) in toluene (8.7 mL)
was charged with NaHCO (1.18 g, 13.9 mmol, 8 equiv) and the
26 38
pl
6
8.76; H, 8.63; N, 2.84.
3
mixture was stirred for 45 min at r.t. Then methylchloroformate
Compound 14
rac-14
(
0.81 mL, 0.99 g, 10.5 mmol, 6 equiv) was added via syringe. The
mixture was stirred for 5 h, then filtered, and the volatiles removed
in vacuo to give 781 mg of the crude product that apparently con-
A sample of rac-2 (433 mg, 1.53 mmol) in Et O (3 mL) was treated
with t-BuLi (1.5 M in pentane; 1.5 mL, 2.25 mmol, 1.5 equiv) at
2
tained (R,R,R )-11b. This material (715 mg) was dissolved in tolu-
pl
0
°C. After stirring for 1 h at ambient temperature the mixture was
cooled to –78 °C. A solution of p-tosyl azide (450 mg, 2.28 mmol,
.5 equiv) in Et O (3 mL) was added dropwise. The mixture was
ene (6 mL), a concd aq solution of NH (3 mL) was added, and the
3
mixture was heated for 5 h at 110 °C in a sealed (Teflon screw cap)
Schlenk tube behind a safety shield. The mixture was cooled to r.t.,
1
2
stirred at –78 °C for 5 h, warmed to 0 °C, stirred for 10 min, and
then Na P O ⋅10H O (736 mg, 1.65 mmol, 1.1 equiv) in H O (7.5
a sat. solution of NaHCO (5 mL) was added, and the organic phase
3
separated. The aqueous phase was extracted with CH Cl (3 × 10
4
2
7
2
2
2
2
mL) was added. After stirring overnight at r.t. the solvent was re-
moved, the residue was taken up in H O (5 mL), and extracted with
mL). The combined organic solutions were washed with a solution
of NaHCO (10 mL), a solution of 1 M NaOH (10 mL), and then
2
3
CH Cl (3 × 10 mL). The combined organic solutions were dried
dried over MgSO . The solvent was removed in vacuo and the prod-
2
2
4
over MgSO and the solvent was removed in vacuo. The product
uct was purified by column chromatography (silica gel, first MeOH
4
was purified by column chromatography (silica gel, MeOH). The
product was then dissolved in Et O and filtered. Removal of the sol-
vent furnished 176 mg (36%) of pure rac-14; R = 0.27. Single crys-
tals were obtained from a Et O solution by slow evaporation of the
then repeated chromatography with Et O gave the pure product) to
2
furnish 189 mg (26%) of (R,R,R )-12b; R = 0.33 (MeOH); mp
2
pl
–1
f
20
1
08.7 °C; [a]D +238 (c 1.0 × 10 , CH Cl ).
f
2
2
–
5
2
CD (c 8.9 × 10 , CH Cl ): De (lmax) = –2.45 (285), +0.76 (328),
2
2
solvent at –20 °C.
–
1.05 (418).
Anal. Calcd for C H N Fe: C, 59.25; H, 6.23; N, 17.28. Found: C,
–
1
16 20
4
IR (ATR): 3091, 2920, 2849, 1444, 1261, 1079, 1039, 802 cm .
5
9.69; H, 6.10; N, 16.87.
1
H NMR (599.9 MHz, CD Cl ): d = 4.15 (m, 1 H, H-12 or H-13),
2
2
X-ray crystal structure analysis (CCDC 607475): formula
4
.12 (m, 1 H, H-12 or H-13), 4.11 (m, 1 H, H-3 or H-4), 4.10 (m, 1
C H N Fe, M = 324.21, yellow crystal 0.55 × 0.55 × 0.20 mm,
1
6
20
4
H, H-2 or H-3), 4.02 (m, 1 H, H-11), 3.97 (m, 1 H, H-3 or H-4), 3.95
a = 14.760(1), b = 7.348(1), c = 15.120(1) Å, b = 113.48(1)°,
(
(
m, 1 H, H-2 or H-5), 3.60 (m, 1 H, H-9), 2.81 (m, 1 H, H¢-8), 2.59
3
–3
–1
V = 1504.1(2) Å , r
= 1.432 g cm , m = 1.001 mm , empirical
calcd
m, 1 H, H-6), 2.34 [m, 1 H, (P)CH ], 2.12 [m, 1 H, (P)CH], 2.04
2
absorption correction (0.609 £ T £ 0.825), Z = 4, monoclinic, space
[
m, 1 H, H-8], 2.01 [m, 1 H, (P)CH ], 1.87 [m, 1 H, (P)CH ], 1.86
2
2
group P2 /n (No. 14), l = 0.71073 Å, T = 198 K, w and j scans,
1
[
(m, 1 H, (P)CH ], 1.85 [m, 1 H, (P)CH ], 1.77 [m, 1 H, (P)CH ],
–1
2
2
2
9
935 reflections collected (±h, ±k, ±l), [(sinq)/l] = 0.66 Å , 3594
1
.73 [m, 1 H, (P)CH ], 1.69 [m, 1 H, (P)CH ], 1.62 [m, 1 H,
2
2
independent (R = 0.025) and 3333 observed reflections [I ≥
2
sidual electron density 0.35 (–0.35) eÅ , hydrogens are calculated
and all refined as riding atoms.
int
(
P)CH ], 1.61 [m, 1 H, (P)CH], 1.42 [m, 1 H, (P)CH ], 1.38 [m, 1
2
2
s(I)], 193 refined parameters, R1 = 0.026, wR2 = 0.068, max. re-
H, (P)CH ], 1.37 [m, 2 H, (P)CH ], 1.36 [m, 1 H, (P)CH ], 1.27 [m,
–3
2
2
2
2
1
H, (P)CH ], 1.27 (br, 2 H, H-15), 1.22 (d, J = 7.2 Hz, 3 H, H-7),
2
.18 [m, 2 H, (P)CH ], 1.10 [m, 1 H, (P)CH ], 0.98 [m, 1 H,
2
2
(
1
P)CH2].
(
R,R,R )-14
pl
3
1
C{ H} NMR (150.8 MHz, CD Cl ): d = 94.2 (C-1), 93.3 (d,
According to the procedure described above, (R,R,R )-4 (445 mg,
2
2
pl
JP,C = 19.2 Hz, C-10), 78.1 (d, J = 23.6 Hz, C-14), 72.3 (d,
JP,C = 4.4 Hz, C-11), 72.2 (d, JP,C = 4.4 Hz, C-3 or C-4), 71.5 (C-2
or C-5), 69.9 (C-2 or C-5), 69.3 (C-12 or C-13), 68.3 (C-12 or C-
1.57 mmol) was treated with t-BuLi (1.5 M, pentane; 1.60 mL, 2.40
mmol, 1.5 equiv), followed by tosyl azide (477 mg, 2.41 mmol, 1.5
equiv) in Et O (3 mL) and Na P O ⋅10H O (700 mg, 1.57 mmol, 1.0
equiv) in H O (7.5 mL) to furnish 283 mg (55%) of (R,R,R )-14; mp
113.7 °C (dec.); [a]589 +1120 (c 1.0 × 10 , CH Cl ).
2 2
P,C
2
4
2
7
2
1
[
3), 67.9 (C-3 or C-4), 53.2 (d, JP,C = 7.4 Hz, C-8), 46.6 (C-9), 37.1
d, JP,C = 11.4 Hz, (P)CH], 36.4 [d, JP,C = 11.8 Hz, (P)CH], 34.4 [d,
JP,C = 24.5 Hz, (P)CH ], 31.7 [d, J = 16.8 Hz, (P)CH ], 31.5 [d,
2
p
l
2
0
–1
2
P,C
2
–5
CD (c 3.2 × 10 , CH Cl ): De (lmax) = +17.05 (256), +21.76 (272),
–
2
2
JP,C = 10.8 Hz, (P)CH ], 30.4 [d, J = 3.5 Hz, (P)CH ], 30.1
2
P,C
2
0.65 (307),+1.18 (338), +0.22 (391), +2.86 (458).
[
(
(
3
(P)CH ], 28.5 [d, J = 15.5 Hz, (P)CH ], 28.1 [d, J = 6.0 Hz,
2 P,C 2 P,C
–
1
IR (ATR): 2962, 2931, 2877, 2100, 1449, 1038, 801 cm .
P)CH ], 28.0 [d, J = 9.0 Hz, (P)CH ], 27.6 [d, J = 10.8 Hz,
2
P,C
2
P,C
P)CH ], 27.2 (C-6), 26.9 [d, J = 13.5 Hz, (P)CH ], 17.8 (C-7).
1
2
P,C
2
H NMR (599.9 MHz, CD Cl ): d = 4.40 (m, 1 H, C H ), 4.34 (m, 1
2
2
5
4
1
1
H, C H ), 4.17 (m, 1 H, C H ), 4.00 (m, 1 H, C H ), 3.96 (m, 1 H,
P{ H} NMR (81.0 MHz, CD Cl ): d = –13.0.
5 3 5 4 5 4
2
2
C H ), 3.93 (m, 1 H, C H ), 3.92 (m, 1 H, C H ), 2.97 (m, 1 H, H-
9
(m, 1 H, H-8), 1.25 (d, J = 7.2 Hz, 3 H, H-7).
+
+
5
3
5
4
5
3
MS (ESI, ES , MeOH): m/z = 452.2 [(M + H) ].
UV/Vis (CH Cl ): l (e) = 260 (10500), 228 (14800).
), 2.83 (m, 1 H, H-6), 2.78 (m, 1 H, H¢-8), 2.23 (s, 6 H, H-15), 2.18
3
2
2
max
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

PAPER
[3]Ferrocenophane Chelates
2199
1
3
1
C{ H} NMR (150.8 MHz, CD Cl ): d = 98.1 (C-10), 95.0 (C-1),
ture in anhyd degassed i-PrOH (2 mL). The mixture was stirred for
45 min at r.t. and then a solution of the ketone (0.6 M in i-PrOH,
2 mL, 0.12 mmol) was added. The course of the reaction was mon-
itored by GC and the ee values were determined by chiral GC.
2
2
7
6
(
5.6 (C-14), 73.2 (C H ), 70.6 (C H ), 70.5 (C H ), 68.9 (C H ),
6.9 (C H ), 64.6 (C H ), 61.6 (C H ), 59.1 (C-9), 45.2 (C-8), 44.3
C-15), 28.1 (C-6), 17.1 (C-7).
5 4 5 4 5 3 5 4
5
4
5
3
5
3
+
+
MS (EI, 70 eV): m/z (%) = 324.1 (40) [M ], 296.0 (76) [M – N ],
2
rac-16
2
53.0 (100), 160.9 (47), 147.9 (36), 121.9 (22).
A mixture of [(p-cymene)RuCl ] (41 mg, 0.067 mmol) and rac-12a
2
2
UV/Vis (CH Cl ): l (e) = 274 (27100), 228 (17900).
2
2
max
(59 mg, 0.135 mmol) was dissolved in anhyd CH Cl (6.9 mL). The
2 2
mixture was stirred overnight at r.t., then the solvent was removed
in vacuo. The product obtained was used for a series of crystalliza-
Anal. Calcd for C H N Fe: C, 59.25; H, 6.23; N, 17.28. Found: C,
1
6
20
4
5
9.90; H, 6.14; N, 16.81.
tion experiments. Slow diffusion of Et O vapor into a solution of the
2
product in CH Cl gave a few single crystals that were suitable for
Compound 15
rac-15
2
2
X-ray crystal structure analysis (CCDC 607478): formula
C H Cl FeNPRu, M = 745.48, yellow crystal 0.25 × 0.10 × 0.10
A sample of rac-14 (100 mg, 0.31 mmol) was dissolved in MeOH
36 40
2
mm, a = 9.898(1), b = 13.576(1), c = 14.349(1) Å, a = 108.36(1)°,
(3 mL). The solution was degassed by passing argon through it for
3
–3
b = 93.77(1)°, g = 94.43(1), V = 1816.2(3) Å , r = 1.363 gcm ,
5
min. Then 10% Pd/C (12 mg) was added and the mixture was
calc
–
1
m = 1.030 mm , empirical absorption correction (0.783 £ T £
.904), Z = 4, triclinic, space group P–1 (No. 2), l = 0.71073 Å,
T = 198 K, w and j scans, 20311 reflections collected (±h, ±k, ±l),
stirred for 2.5 h at a H pressure of 1 bar. The mixture was filtered
2
0
through Celite and the Celite washed with a small amount of
CH Cl . The solvent was removed and the resulting yellow oil was
2
2
–
1
[
(sinq)/l] = 0.67 Å , 8790 independent (R = 0.059) and 7033 ob-
kept under argon, to furnish 71 mg (77%) of rac-15.
int
served reflections [I ≥ 2s(I)], 383 refined parameters, R1 = 0.056,
IR (ATR): 3417, 3325, 3087, 2955, 2862, 2817, 2769, 2360, 2339,
–3
wR2 = 0.186, max. residual electron density 3.89 (–0.62) eÅ , in a
–
1
1
592, 1484, 1467, 1024, 790, 666 cm .
channel around x,0.5,0.5, could not be described in a chemically
meaningful way, hydrogen atoms calculated and refined as riding
atoms.
1
H NMR (499.8 MHz, CD Cl ): d = 4.23 (m, 1 H, H-3 or H-4), 3.94
2
2
(
1
m, 1 H, H-2), 3.82 (m, 1 H, H-3 or H-4), 3.74 (m, 1 H, H-12 or H-
3), 3.65 (m, 1 H, H-12 or H-13), 3.59 (m, 1 H, H-11), 3.43 (m, 1
3
H, H-5), 3.02 (br, 2 H, H-16), 2.76 (m, 1 H, H-6), 2.67 (dd, J = 9.9
3
2
Hz, J = 3.5 Hz, 1 H, H-9), 2.45 (m, 1 H, H -8), 2.33 (ddd, J = 13.6 Acknowledgment
b
3
3
Hz, J = 5.7 Hz, J = 3.5 Hz, 1 H, H -8), 2.25 (s, 6 H, H-15), 1.25
a
Financial support from the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie is gratefully acknowledged.
3
(
d, J = 7.3 Hz, 3 H, H-7).
1
3
1
C{ H} NMR (125.7 MHz, CD Cl ): d = 106.9 (C-14), 93.1 (C-1),
2
2
7
7.0 (C-5), 75.2 (C-10), 69.8 (C-3 or C-4), 66.4 (C-2), 66.2 (C-3 or
C-4), 65.8 (C-11), 61.9 (C-12 or C-13), 60.8 (C-9), 57.8 (C-12 or C- References
3), 45.8 (C-8), 45.4 (C-15), 27.2 (C-6), 18.4 (C-7).
1
(
1) (a) Josiphos: Togni, A.; Breutel, C.; Schnyder, A.; Spindler,
F.; Landert, H.; Tijani, A. J. Am. Chem. Soc. 1994, 116,
4062. (b) Ferrocenes – Homogeneous Catalysis, Organic
Synthesis, Materials Science; Togni, A.; Hayashi, T., Eds.;
Wiley-VCH: Weinheim, 1995. (c) Metallocenes –
Anal. Calcd for C H N Fe: C, 64.42; H, 7.45; N, 9.39. Found: C,
1
6
22
2
6
3.60; H, 7.01; N, 8.69.
(
R,R,R )-15
pl
Hydrogenation of (R,R,R )-14 (190 mg) according to the procedure
Synthesis, Reactivity, Applications, Vol. 1; Togni, A.;
Halterman, R. L., Eds.; Wiley-VCH: Weinheim, 1995.
(d) Metallocenes – Synthesis, Reactivity, Applications, Vol.
2; Togni, A.; Halterman, R. L., Eds.; Wiley-VCH:
pl
described above in MeOH (5.7 mL) with Pd/C (25 mg) gave 160 mg
2
0
–1
(
93%) of (R,R,R )-15; [a]589 +131 (c 1.0 × 10 , CH Cl ).
pl
5
2
2
–
CD (c 7.9 × 10 , CH Cl ): De (lmax) = –0.22 (258), +0.72 (276),
2
2
Weinheim, 1998. (e) Colacot, T. J. Chem. Rev. 2003, 103,
–
1.31 (300), +0.80 (339), –0.34 (407), +0.42 (462).
3101. (f) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.-P.; Hou,
UV/Vis (CH Cl ): l (e) = 426 (350), 228 (12400).
2
2
max
X.-L. Acc. Chem. Res. 2003, 36, 659; and references cited
Anal. Calcd for C H N Fe: C, 64.42; H, 7.45; N, 9.39. Found: C,
therein.
1
6
20
4
6
4.87; H, 7.47; N, 9.22.
(2) (a) Mernyi, A.; Kratky, C.; Weissensteiner, W.; Widhalm,
M. J. Organomet. Chem. 1996, 508, 209. (b) Gómez-de la
Torre, F.; Jalón, F. A.; López-Agenjo, A.; Manzano, B. R.;
Rodriguez, A.; Sturn, T.; Weissensteiner, W.; Martinez-
Ripoll, M. Organometallics 1998, 17, 4634. (c)Jalón, F. A.;
López-Aganjo, A.; Manzano, B. R.; Moreno-Lara, M.;
Rodriguez, A.; Sturm, T.; Weissensteiner, W. J. Chem. Soc.,
Dalton Trans. 1999, 4031.
(3) Liptau, P.; Seki, T.; Kehr, G.; Abele, A.; Fröhlich, R.; Erker,
G.; Grimme, S. Organometallics 2003, 22, 2226.
(4) Reviews: (a) Drent, E.; Budzelaar, P. H. M. Chem. Rev.
1996, 96, 663. (b) Bianchini, C.; Meli, A. Coord. Chem.
Rev. 2002, 225, 35.
Catalytic Hydrogenation; General Procedure
A Schlenk flask was charged with a solution of ketone (1.90 mmol)
and chelate ligand (0.019 mmol) in anhyd degassed i-PrOH (3.4
mL). Then KOH (0.1 M solution, i-PrOH; 0.19 mL, 0.019 mmol)
was added. This solution was then transferred via cannula into a
Schlenk flask containing [Cp*Ru(cod)Cl] (7.4 mg, 0.019 mmol).
The reaction mixture was stirred and evacuated until the solvent
started to boil. A H pressure of 2 bar was applied and the progress
of the reaction followed by TLC or GC by taking samples. The sol-
vent was removed in vacuo and the mixture filtered through a short
column of silica gel (Et O–pentane). The hydrogenation products
were identified by H NMR spectroscopy and the absolute configu-
ration of the major enantiomer was determined by comparison of
the specific optical rotation with reference compounds (Table 1).
2
2
1
(5) (a) Gambs, C.; Chaloupka, S.; Consiglio, G.; Togni, A.
Angew. Chem. Int. Ed. 2000, 39, 2486; Angew. Chem. 2000,
112, 2602. (b) Gambs, C.; Consiglio, G.; Togni, A. Helv.
Chim. Acta 2001, 84, 3105.
Transfer Hydrogenation; General Procedure
(6) Liptau, P.; Tebben, L.; Kehr, G.; Fröhlich, R.; Erker, G.;
Hollmann, F.; Rieger, B. Eur. J. Org. Chem. 2005, 1909.
[
(p-Cymene)RuCl ] (1.8 mg, 3.0 mmol), chelate ligand (12 mmol),
2 2
and t-BuOK (2.7 mg, 24 mmol) were dissolved at ambient tempera-
Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York

2
200
C. Nilewski et al.
PAPER
(
(
7) (a) Knüppel, S.; Fröhlich, R.; Erker, G. J. Organomet. Chem.
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therein.
1
Chem. Int. Ed. 1999, 38, 1923; Angew. Chem. 1999, 111,
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14.
(
9) Liptau, P.; Knüppel, S.; Kehr, G.; Kataeva, O.; Fröhlich, R.;
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(
(
10) (a) Liptau, P.; Tebben, L.; Kehr, G.; Wibbeling, B.; Fröhlich,
R.; Erker, G. Eur. J. Inorg. Chem. 2003, 3590; corrigendum
p. –4261. (b) Tebben, L.; Kehr, G.; Fröhlich, R.; Erker, G.
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(
1
b) Gokel, G. W.; Marquarding, D.; Ugi, I. J. Org. Chem.
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(
12) (a) Tainturier, G.; y Sok Khay, C.; Gautheron, B. C. R.
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2
207. (c) y Sok Khay, C.; Tainturier, G.; Gautheron, B. J.
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(
e) Manzano, B. R.; Jalón, F. A.; Gómez-de la Torre, F.;
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Sect. A 1990, 46, 467. (g) Structure refinement: Sheldrick,
G. M. SHELXL-97; Universität Göttingen: Germany, 1997.
(h) Keller, E. SCHAKAL; Universität Freiburg: Germany,
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crystallographic data for this paper. These data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/
retrieving.html [or from the Cambridge Crystallographic
Data Centre 12 Union Road Cambridge CB2 1EZ, UK; fax:
+44(1223)336033].
789. (f) Sturm, T.; Weissensteiner, W.; Spindler, F.;
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(
(
(
b) Onishi, M.; Hiraki, K.; Iwamoto, A. J. Organomet.
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(
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Synthesis 2006, No. 13, 2191–2200 © Thieme Stuttgart · New York