Ferrocene derivatives as receptors to explore ammonium cation-π interactions

Article abstract of DOI:10.1039/b313422a

The potential importance in biology of ammonium-arene cation-π interactions has fostered the development of a model system that uses ferrocene as a scaffold that can rotate groups with respect to each other while maintaining them at a fixed distance. The preparation of 1-benzyl-1′-N,N- dimethylaminomethylferrocene methiodide is reported along with the solid state structure of it and its precursor. Clear evidence is presented for an intermolecular ammonium-arene interaction. The results are analyzed in the context of existing arene-ammonium ion contacts.

Full text of DOI:10.1039/b313422a

View Article Online / Journal Homepage / Table of Contents for this issue
P A P E R
Ferrocene derivatives as receptors to explore ammonium
cation–p interactions
Jiaxin Hu,a Leonard J. Barbourb and George W. Gokel*a
a
Departments of Molecular Biology & Pharmacology and Chemistry, Division of Bioorganic
Chemistry, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Ave.,
St. Louis, MO 63110, USA. E-mail: ggokel@molecool.wustl.edu; Fax: þ1 314/362-9298;
Tel: þ1 314/362-9297
b
Department of Chemistry, University of Stellenbosch, 7602, Matieland, South Africa
Received (in Durham, UK) 23rd October 2003, Accepted 15th April 2004
First published as an Advance Article on the web 16th June 2004
The potential importance in biology of ammonium–arene cation–p interactions has fostered the development of
a model system that uses ferrocene as a scaffold that can rotate groups with respect to each other while
maintaining them at a fixed distance. The preparation of 1-benzyl-10-N,N-dimethylaminomethylferrocene
methiodide is reported along with the solid state structure of it and its precursor. Clear evidence is presented
for an intermolecular ammonium–arene interaction. The results are analyzed in the context of existing
arene–ammonium ion contacts.
occur involving the sidechain residues of Lys or Arg with the
Introduction
p-donors Phe, Tyr, or Trp by either interchain or intrachain
proximity. The possibility of such interactions was recognized
two decades ago by Burley and Petsko, who searched the Pro-
tein Data Bank for indications of proximity between sidechain
amino groups and arenes.32 Ammonium ion interactions with
arenes were also studied using this technique.33 We report here
the development of a chemical model system designed to probe
such ammonium ion–arene interactions.
Cation–p interactions are of enormous potential importance in
biological systems where one in every 11 amino acid sidechains
is the p-donor benzene, phenol, or indole. These are the respec-
tive aromatic residues of the amino acids phenylalanine (Phe,
F), tyrosine (Tyr, Y), and tryptophan (Trp, W). Pioneering
work by Stucky and coworkers showed that lithium metal
reduction of naphthalene led to arene-bound lithium cations.1
Potassium cation interactions with benzene were demonstrated
by Kebarle and coworkers in 1981 by using mass spectrome-
try.2 More recently, several labs have developed model sys-
tems3–5 to study cation–p interactions in solution. The field
was reviewed in 1997.6 Important work in this area has
continued to appear regularly.4,5,7–18
We have long been interested in the problem of defining the
cation–p interaction specifically for the alkali metal cations
Naþ and Kþ because these are the most abundant metal
cations in vivo. Solution and solid state work that we con-
ducted in the 1980s failed to provide definitive evidence for
interactions of these ions with either Naþ or Kþ when the p-
donors were benzene, alkene, or alkyne.19,20 The latter studies
were conducted with lariat ether receptor molecules. Remark-
ably, minor alterations to the sidechains of these earlier sys-
tems21,22 led to a large number of solid state structures that
clearly show cation–p interactions. These involve sodium and
potassium cations with alkenes,23 alkynes,24 benzene, phenol,25
and indole.26,27 Aromatic residues such as imidazole (the histi-
dine sidechain arene)28 and pentafluorophenyl,29 which were
expected not to form p-complexes, did not show cation–p
interactions under similar circumstances. We have recently
reviewed these results.30,31
Results and discussion
The lariat ether system that we employed successfully to study
alkali metal cation–p interactions could be used to complex
þ
ammonium ion, NH4
,
but not substituted ammonium
cations.34 Further, lariat ethers could not be employed for
the study of guanidinium cation unless rather large macrocyc-
lic rings were used.35 The latter was not an appealing prospect
as studies with alkali metal cations showed that the sidearm’s
position within the receptor could be critical to the success of
p-donor interactions.27 We therefore turned our consideration
to other structural scaffolds. It was essential that the scaffold
could enforce proximity between cation and p-donor without
restricting the interaction. An attractive possibility was the
organometallic sandwich complex ferrocene.36
Our experience using ferrocene as a scaffold that can
undergo rotation on its ‘‘molecular ball bearing’’37,38 sug-
gested its use in this application. Ferrocene (1) has several use-
ful and unusual properties in the context of supramolecular
chemistry. The two aromatic rings of ferrocene are parallel
˚
and separated by 3.25 A. They rotate with respect to each
Ammonium ion–p complexes are also of great potential
interest in biology. The p-donor sidechains of the amino acids
are as above. The potential cation–p interaction would involve
the sidechain residues of either lysine (Lys, K) or arginine
(Arg, R), i.e. amino or guanidine. Note that lysine and arginine
occur to the extent of about 1 in 9 amino acids in all known
protein sequences. Both the lysine amino group (pKa 10.5)
and arginine’s guanidine (pKa 12.8) are fully protonated at
physiological pH (ꢀ7.4). Thus, cation–p interactions could
other on an iron atom—a low energy ‘‘ball bearing.’’ Syn-
thetic access is gained readily by acylation of ferrocene’s elec-
tron rich arenes. Although its use in the present work was not
anticipated, the potential for redox switching37 and metal ion
donation39 by ferrocene enhanced our interest in this scaffold.
After our own effort in this area began, a report appeared in
which ferrocene was used as a b-turn mimetic.40 The latter stu-
dies were not directed to cation–p interactions, but the use of
ferrocene to enforce sidechain proximity is similar in concept
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 9 0 7 – 9 1 1
907

View Article Online
to our own approach. An earlier paper reported that ferrocene,
when 1,10-disubstituted by two valine esters, formed intra-
molecular hydrogen bonds that stabilized a syn sidearm
conformation.41
Corey–Pauling–Koltun (CPK) molecular models suggested
that when a p-donor and an ammonium cation were present
on the 1- and 10-rings of ferrocene, they could rotate into
proximity if such an interaction was favorable. This is illu-
strated in Scheme 1 for 1-benzyl-10-trimethylammoniomethyl-
ferrocene, 2. Compound
2
was designed to exploit
ferrocene’s rotational dynamics in the hope that evidence for
an ammonium–p interaction would be obtained. The syn and
anti conformations of 2 represent the two structural extremes
for this compound. When anti, there should be no intramole-
cular ammonium–p interaction. In the syn conformation, such
an interaction might be detectable either in solution or by
X-ray methods.
In designing 2, we searched the Cambridge Structural Data-
base (CSD) to guide our choice of molecules. Two solid state
structures of interest are 1,10-dibenzylferrocene (CSD: NUY-
QAZ)42 and 1,10-bis(2-pyridinomethylaminocarbonyl)ferro-
cene (JATPUP)43 (Fig. 1). Dibenzylferrocene (3) is in an
extended conformation in which the two cyclopentadiene rings
are anti and the sidechains are pointed in opposite directions.
The structure of 3 has been rendered using the program
X-Seed44–46 such that ferrocene is in the space-filling (CPK)
metaphor and the chains are represented as sticks. This was
done to show the extent to which the cyclopentadienyl rings
envelop Fe(II).
The structure of picolinamine derivative 4 has two arms, as
does 3, but they are positioned on the same side of ferrocene.
The organometallic residue is in the syn arrangement and the
sidechains exhibit N–Hꢁ ꢁ ꢁN hydrogen bonding. The latter
example supports the notion that when a weak force inter-
action occurs in the sidechain, the conformation of ferrocene
will be appropriate to sustain it. The structures are shown in
Fig. 1.
Fig. 1 1,10-Disubstituted ferrocenes 3 and 4 are in conformations in
which the sidearms are, respectively, anti and syn.
yield as a red oil. The latter proved to be unstable and partially
decomposed during flash column chromatography. In subse-
quent preparations, it was reduced immediately with
LiAlH4–AlCl3 to afford 7, 1-benzyl-10-N,N-dimethylamino-
methylferrocene (88%), as a red oil that solidified after lengthy
drying under high vacuum. Evaporation of a hexane solution
containing 7 at 0 ꢂC for 3 weeks afforded yellow parallelepi-
peds, mp 48–49 ꢂC. These crystals proved to be useful for X-
ray analysis. Finally, compound 7 was treated with excess
CH3I overnight to afford the ammonium salt 2 as a yellow
solid in 90% yield. Crystallization from acetone gave 2 as light
yellow rhombohedroids, mp ¼ 172–174 ꢂC.
Solid state structure of 7
Single crystal X-ray structures of compounds 2 and 7 have
been obtained by direct methods. The structure of dimethyla-
minoferrocene derivative 7 is shown in Fig. 2. Ferrocene’s
cyclopentadienide rings and their attached sidearms are in
the anti arrangement. It is clear that there is no intramolecular
interaction and none was expected. There is, however, a mole-
cule of water that H-bonds between amino nitrogens in
adjacent molecules. The bridging water molecule forms an
Synthesis of 2
Our initial strategy was to acylate ferrocene (1) with benzoyl
chloride and to use the deactivating effect of the acylated ring
to direct a Mannich condensation to the (opposite) 10-ring. The
well-known benzoylation proceeded uneventfully but the Man-
nich condensation on C5H5FeC5H4CO–C6H5 failed to afford
the aminomethylated product. An alternate attempt involved
benzoylation, as above, followed by treatment of benzoylferro-
cene with N,N-dimethylcarbamoyl chloride and aluminium
chloride. Only starting materials were recovered in this
reaction.
˚
=
O–Hꢁ ꢁ ꢁN bond that is (dO–N ) 2.85 A in length and the
O–Hꢁ ꢁ ꢁN bond angle is nearly linear, i.e. 170ꢂ. The distance
˚
between nitrogens in adjacent molecules is 5.9 A and the cen-
troid-to-centroid distance between adjacent benzene rings is
essentially the same. The interplane distance of the cyclopenta-
˚
dienes in ferrocene is 3.33 A and the Cp rings are parallel. No
interaction between the sidearms is apparent.
The successful approach to 2 is shown in Scheme 2. Ferro-
cene was treated with N,N-dimethylcarbamoyl chloride
[(CH3)2NCOCl] and AlCl3 at ambient temperature for 20 h.
N,N-Dimethylferrocenecarboxamide 5 (obtained as yellow
needles, 42%) was acylated with PhCOCl (2 equiv) and AlCl3
(3 equiv). 1-Benzoyl-10-N,N-dimethylferrocenecarboxamide
(6, C6H5–CO–C5H4FeC5H4–CONMe2) was obtained in 62%
Although the structure of precursor 7 exhibits some interest-
ing features, the goal was to detect ammonium ion cation–p
interactions in 2. We surmised that the most favorable
cation–p interaction would be intramolecular. The structure
of compound 2 is shown in Fig. 3. The asymmetric unit
consists of two separate molecules in different conformations.
In one molecule, the benzene ring turns upward from the
Scheme 1
Scheme 2
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
908
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 9 0 7 – 9 1 1

View Article Online
Fig. 2 Solid state structure showing two molecules of 7 linked by a
water molecule.
Fig. 4 Three molecules of 2 showing ammonium ion to arene
contact. Note the disorder in the right and left monomers.
ferrocene ring plane at an angle of 107ꢂ, as in the structure of
7. The other monomer is disordered. The benzyl sidearm in the
latter has two possible directions while the lower part of the
ferrocene is fixed. The two arrangements are shown in the left
hand structure of Fig. 3. In neither position is there proximity
to the benzyl group, and the intramolecular trimethyl-
ammonium cation is essentially vertical to the ferrocene unit.
The trimethylammonium sidearms adopt similar positions in
the two molecules—they turn downward from the ferrocene
ring plane at an angle of 111 . The iodide anions are 4.47 A
˚
and 4.66 A distant from the nearer nitrogen. The sidearms in
neither structure are in the anti arrangement. Instead, the side-
arms are roughly on the same side of the ferrocene in each case
but the dihedral angles are 105ꢂ, 69ꢂ, and ꢃ63ꢂ. There does not
appear to be any intramolecular cation–p interaction.
The intermolecular contacts in GOFGOX, GOVSOZ, and
˚
HIBMEK are likewise short, all being approximately 4.4 A.
In GOVSOZ, however, the closest benzene ring is angled sig-
˚
nificantly and the closest carbon is ꢀ4.23 A from the nitrogen
˚
atom, but the centroid is ꢀ4.8 A away. The nitrogen atom of
˚
tetra-n-butylammonium ion in HIBMEK is ꢀ4.2 A from the
nearest phenoxy ring in the bismuth complex shown. The
interaction is along a line only 17ꢂ from perpendicular. A spe-
cial situation arises for GOFGOX, in which benzene rings are
both inter- and intramolecular with respect to the ammonium
nitrogen atom. The ammonium salt’s arene is folded back so
that there is contact between it and its intramolecular ammo-
nium ion. In addition, the ammonium nitrogen is proximate
to the benzene rings present in the resorcinarene. All distances
ꢂ
˚
˚
are in the range 4.5–4.7 A.
Fig. 4 shows the intermolecular cation–p interaction of three
molecules of 2—contributed by two unit cells. The dotted lines
indicate contacts between benzene and ammonium ions. The
trimethylammonium cation of the central ferrocene is almost
vertical at the top of the nearby benzene ring. The nearest
An ammonium–p interaction in a substituted ferrocene
The most closely related example that we can find in the litera-
ture is a compound (8, Fig. 6) reported as part of an effort to
develop compounds that mimic hexesterol, hydrogenated
diethylstilbesterol.51 Indeed, this is the only example of an
intramolecular contact in a ferrocene that we have found. In
this study, one of the benzene rings was replaced by ferrocene.
The structure of this compound is reported in the aforemen-
tioned paper and appears in the Cambridge Structural
Database as LIFZAX. Our own measurement of its nitrogen
˚
methyl carbon is 4 A away from the benzene centroid. The
þ
˚
ammonium cation (N ) is 4.66 A from the centroid. A second,
similar contact occurs in an adjacent pair. A line dropped from
nitrogen to the arene’s centroid makes an angle of about 12ꢂ
from vertical. The distance between the cationic nitrogen atom
˚
and the arene’s centroid is 4.7 A.
Compounds exhibiting close ammonium-arene contacts
˚
to centroid distance is 4.70 A. Note that the arene and
ammonium ion interaction is intramolecular rather than
A search of the CSD revealed five compounds that have close
˚
(ꢄ4.7 A) contacts between a benzene centroid and a quatern-
ary nitrogen atom. Structural drawings of four of these are
shown in Fig. 5. Each structure is identified by its CSD
descriptor, namely GOFGOX,47 GOVSOZ,48 HIBMEK,49
and WOLWAV.50 Three of the four are organometallic com-
plexes and another three of four involve interactions between
different molecules, one of which contains the arene and one
that incorporates the ammonium ion. The only intramolecular
example is the platinum complex WOLWAV. The distance
between quaternary nitrogen and the proximate arene is
ꢂ
˚
ꢀ4.4 A but a line from nitrogen to the centroid is 23 from
perpendicular. Even so, the contact is short and the interaction
is therefore significant.
Fig. 3 Structure of 10-benzylferrocenylmethyltrimethylammonium
iodide, 2, showing two molecules present in the unit cell. The left hand
structure is disordered.
Fig. 5 Systems having close quaternary ammonium to arene
contacts, labeled by their CSD descriptors: GOFGOX, GOVSOZ,
HIBMEK, and WOLWAV.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 9 0 7 – 9 1 1
909

View Article Online
on a Thomas-Hoover apparatus in open capillaries and are
uncorrected. Thin layer chromatographic (TLC) analyses were
performed on silica gel HLO F-254 (0.25 mm thickness), Scien-
tific Adsorbents, Inc. Combustion analyses were performed by
Atlantic Microlab, Inc., Atlanta, GA, and are reported as
percents. Commercially available solvents and salts were used
without further purification.
Ferrocene, 1, was obtained commercially and crystallized
from heptane prior to use.
Fig. 6 Solid state structure of 8 as reported in the literature.51
1-Benzyl-10-N,N-dimethylaminomethylferrocene methiodide, 2
intermolecular and the interacting residues are on the same
cyclopentadienyl ring, unlike the situation for 2.
Compound 7 (see below, 0.20 g, 0.6 mmol) and CH3I (1 mL)
were mixed in 10 mL CH2CI2 and stirred at room temperature
overnight. The reaction mixture was concentrated, washed
with ether, and maintained under high vacuum for 16 h, during
which time the residue solidified. Crystallization from acetone
afforded 2 (0.26 g, 90%) as an orange solid, mp 172–174 ꢂC.
1H-NMR (CDCI3): 3.21 (s, 9H, –CH3 ꢅ 3), 3.72 (s, 2H,
–CH2Ph), 4.21–4.28 (m, 6H, ferrocene), 4.48 (m, 2H, ferro-
cene), 4.64 (s, 2H, –CH2NME3), 7.18–7.28 (m, 5H, phenyl).
13C-NMR: 35.40, 52.47, 66.93, 69.14, 69.94, 71.29, 72.08,
72.68, 89.67, 126.04, 128.33, 128.69, 141.29. Anal. Calcd for
C21H26NIFe: C, 53.10; H, 5.47; N, 2.95%. Found: C, 53.39;
H, 5.49; N, 3.05%.
The contact between an arene and trimethylammonium is
necessarily limited in distance by the methyl group hydrogens.
This is shown in Fig. 7. Tetramethylammonium cation is
shown in panels A and B in the ball and stick and space filling
metaphors, respectively. The solvent accessible surface, which
reflects the closest approach of a p-donor, is shown in panel
C. In principle, the best contact is the one that has both the
shortest distance and the most favorable orientation. The ideal
interaction between benzene and a point charge would be
along a line perpendicular to the aromatic ring. In their study
of protein structures, Burley and Petsko found that ‘‘[t]he
normalized frequency distribution of 1556 amino–aromatic
32
˚
contact distances. . . reaches a maximum at about 4.75 A.’’
The findings of Burley and Petsko with respect to bond
angle were less clear. The intermolecular interaction between
two molecules of 2 can be determined from the crystal struc-
ture data. A line drawn from the centroid of one molecule of
Crystal data for 2
Molecular formula: C21H26NIFe; M ¼ 475.18, 0.35
ꢅ 0.30 ꢅ 0.20 mm3, triclinic, space group P1 (No. 2),
¯
˚
˚
a ¼ 9.7909(15), b ¼ 13.640(2), c ¼ 15.018(2) A, a ¼
2 to the nitrogen of a second molecule is 4.70 A. The line
3
ꢂ
diverges from perpendicular by ꢀ19ꢂ. It is currently unclear
how packing forces influence the angle but the intermolecular
p–Nþ distance is clearly appropriate for a cation–p contact.
˚
94.261(3), b ¼ 92.364(3), g ¼ 97.445(3) , V ¼ 1980.5(5) A ,
Z ¼ 4, Dc ¼ 1.594 g cmꢃ3, F000 ¼ 952, MoKa radiation,
l ¼ 0.71073 A, T ¼ 173(2)K, 2ymax ¼ 54.2ꢂ, 12 560 reflections
˚
collected, 8549 unique (Rint ¼ 0.0401). Final GooF ¼ 1.279,
R1 ¼ 0.1182, wR2 ¼ 0.2179,
R indices based on 5885
reflections with I > 2s(I) (refinement on F2), 370 parameters,
243 restraints. Lp and absorption corrections applied,
m ¼ 2.322 mmꢃ1
.
N,N-Dimethylferrocenecarboxamide, 5
N,N-Dimethylcarbamoyl chloride (4.30 g, 40 mmol) in CH2Cl2
(10 mL) was added dropwise to a suspension of AlCl3 (5.40 g,
40 mmol) in CH2Cl2 (10 mL) while cooling and the mixture
stirred for 10 min (ice bath). The clear solution thus obtained
was added dropwise to a CH2Cl2 (15 mL) solution of ferrocene
(3.72 g, 20 mmol) at 0 ꢂC. The reaction mixture was stirred at
room temperature for 20 h, poured into ice–water, and
extracted with CH2Cl2 (3 ꢅ 20 mL). The organic layers were
combined, washed with saturated Na2CO3 (30 mL) and water
(30 mL) and then dried over MgSO4 . Flash column chromato-
graphy (silica gel, eluted with 1 : 4 Me2CO–hexanes) afforded 5
as yellow needles, (2.15 g, 42%) which was recrystallized from
hexanes, mp ¼ 114–115 ꢂC (lit.52 mp ¼ 119–121 ꢂC).
Fig. 7 Molecular models of tetra-n-butylammonium cation in (A)
the ball and stick and (B) space-filling metaphors. Model C shows the
calculated solvent exposed surface.
Conclusion
The search for cation–p interactions is both of great current
interest and of the profoundest potential importance in bio-
logy. The receptor system that is presented here was designed
to probe cation–p interactions and does so. In principle, the
cation–p interaction observed with 2 could either be intra- or
intermolecular. For compound 2, the significant interaction
that is observed is between the benzene ring of one molecule
and the trimethylammonium ion of a second. The observed
bond distance and angle comport with literature values. In
principle, this system may be used for more subtle analyses
of these interactions and such studies are under way.
1-Benzoyl-10-N,N-dimethylferrocenecarboxamide, 6
Benzoyl chloride (0.77 g, 5.5 mmol) in 30 mL CH2Cl2 was
added dropwise to a suspension of AlCl3 (1.10 g, 8.1 mmol)
in 20 mL CH2Cl2 while cooling to ꢃ30 ꢂC. N,N-dimethylferro-
cenecarboxamide (0.70 g, 2.7 mmol) in 20 mL CH2Cl2 was
then added dropwise during 10 min. The reaction mixture
was stirred at ꢃ30 ꢂC for 1 h, and at 0 ꢂC for 5 h, poured into
ice–water, extracted with CH2Cl2 (3 ꢅ 20 mL), the organic
layers were combined and washed with saturated Na2CO3
(30 mL), and water (30 mL). After drying (MgSO4), flash col-
umn chromatography (silica gel, eluted with 1 : 4 Me2CO–hex-
anes) afforded 3 as a dark red oil (0.6 g, 62%). IR: 3088, 2927,
Experimental
1H-NMR spectra were recorded at 300 MHz in CDCl3 unless
otherwise specified. Chemical shifts are reported in ppm. Infra-
red spectra were recorded on a Perkin-Elmer 1310 infrared
spectrophotometer and were calibrated against the 1601
cmꢃ1 band of polystyrene. Melting points were determined
1636, 1619, 1499, 1449, 1395, 1376, 1286 cmꢃ1 1H-NMR
.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
910
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 9 0 7 – 9 1 1

View Article Online
12 J. Wouters, Protein Sci., 1998, 7, 2472–2475.
(CDCl3): 3.01 (s, 6H, –CH3), 4.33–5.30 (m, 8H, ferrocene),
7.48–7.89 (m, 5H, PhH). 13C-NMR: 36.20, 38.84, 71.42,
72.23, 72.96, 74.74, 78.85, 80.42, 128.06, 128.18, 131.65,
139.33, 169.11, 198.50.
13 W. Zhonge, J. P. Gallivan, Y. Zhang, L. Li, H. A. Lester and
D. A. Dougherty, Proc. Natl. Acad. Sci. USA, 1998, 95,
12 088–12 093.
14 O. M. Cabarcos, C. J. Weinheimer and J. M. Lisy, J. Chem. Phys.,
1999, 110, 8429–8435.
1-Benzyl-10-N,N-dimethylaminomethylferrocene 7
15 B. T. King, B. C. Noll and J. Michl, Collect. Czech. Chem.
Commun., 1999, 64, 1001–1012.
16 J. B. Nicholas, B. P. Hay and D. A. Dixon, J. Phys. Chem. A,
1999, 103, 1394–1400.
AlCl3 (0.44 g, 3.3 mmol) was dissolved in 20 mL ether and was
added dropwise to a suspension of LiAlH4 (0.13 g, 3.3 mmol)
in 20 mL ether. Compound 6 (0.60 g, 1.7 mmol) in 10 mL ether
was added dropwise to the reductive mixture. After addition, it
was refluxed for 2 h. H2O was added to destroy the reductive
agents. 30 mL 2 M NaOH solution was added, and the water
layer was extracted with ether. The organic layer was dried
with MgSO4 , concentrated, and flash column chromatography
(silica gel, eluted with 1 : 2 Me2CO–hexanes, with 1% Et3N)
afforded 7 as a red oil (0.5 g, 88%), which solidified under high
vacuum. Crystallization from hexanes afforded yellow crystals,
mp ¼ 48–49 ꢂC. IR: 3084, 3028, 2936, 2812, 2765, 1603, 1495,
1454, 1039, 1021 cmꢃ1. 1H-NMR (CDCl3): 2.15 (s, 6H, –CH3),
3.22 (s, 2H, –CH2NMe2), 3.66 (s, 2H, –CH2Ph), 4.02–4.10 (m,
8H, ferrocene), 7.15–7.25 (m, 5H, phenyl). 13C-NMR: 35.75,
44.67, 58.91, 68.05, 68.70, 69.06, 70.67, 83.25, 87.91, 125.83,
128.15, 128.25, 141.43. Anal. Calcd for C20H23NFe: C,
72.12; H, 6.91; N, 4.21%. Found: C, 72.24; H, 6.82; N, 4.13%.
17 R. C. Dunbar, J. Phys. Chem. A, 2000, 104, 8067–74.
18 D. Feller, Chem. Phys. Lett., 2000, 322, 543–548.
19 R. D. Gandour, F. R. Fronczek, V. J. Gatto, C. Minganti, R. A.
Schultz, B. D. White, K. A. Arnold, D. Mazzocchi, S. R. Miller
and G. W. Gokel, J. Am. Chem. Soc., 1986, 108, 4078–4088.
20 K. A. Arnold, A. M. Viscariello, M. Kim, R. D. Gandour,
F. R. Fronczek and G. W. Gokel, Tetrahedron Lett., 1988,
3025–3028.
21 E. S. Meadows, S. L. De Wall, L. J. Barbour and G. W. Gokel,
J. Am. Chem. Soc., 2001, 123, 3092–3107.
22 J. Hu, L. J. Barbour and G. W. Gokel, Proc. Natl. Acad. Sci.
USA, 2002, 99, 5121–5126.
23 J. Hu, L. J. Barbour and G. W. Gokel, Chem. Commun., 2001,
1858–1859.
24 J. Hu, L. J. Barbour and G. W. Gokel, J. Am. Chem. Soc., 2001,
123, 9486–9487.
25 S. L. De Wall, L. J. Barbour and G. W. Gokel, J. Am. Chem. Soc.,
1999, 8405–8406.
26 S. L. De Wall, E. S. Meadows, L. J. Barbour and G. W. Gokel,
J. Am. Chem. Soc., 1999, 121, 5613–5614.
27 J. Hu, L. J. Barbour and G. W. Gokel, J. Am. Chem. Soc., 2002,
124, 10 940–10 941.
Crystal data for 7
28 J. Hu, L. J. Barbour, R. Ferdani and G. W. Gokel, Chem.
Commun., 2002, 1810–1811.
29 S. L. De Wall, E. S. Meadows, L. J. Barbour and G. W. Gokel,
Proc. Natl. Acad. Sci. USA, 2000, 97, 6271–6276.
30 G. W. Gokel, S. L. D. Wall and E. S. Meadows, Eur. J. Org.
Chem., 2000, 2967–2978.
31 G. W. Gokel, L. J. Barbour, R. Ferdani and J. Hu, J. Acc. Chem.
Res., 2002, 35, 878–86.
32 S. K. Burley and G. A. Petsko, FEBS Lett., 1986, 203, 139–143.
33 M. Meot-Ner and C. A. Deakyne, J. Am. Chem. Soc., 1985, 107,
474–479.
34 R. A. Schultz, E. Schlegel, D. M. Dishong and G. W. Gokel,
J. Chem. Soc., Chem. Commun., 1982, 242–243.
35 K. Madan and D. J. Cram, J. Chem. Soc., Chem. Commun., 1975,
427–8.
36 M. Rosenblum, Chemistry of the Iron Group Metallocenes: Ferro-
cene, Ruthenocene, Osmocene, Interscience Publishers, New York,
1965.
Molecular formula: C40H48Fe2N2O; M ¼ 684.50, 0.25
ꢅ 0.25 ꢅ 0.10 mm3, monoclinic, space group C2/c (No. 15),
˚
a ¼ 31.690(5), b ¼ 5.9141(9), c ¼ 19.117(3) A, bꢃ¼3
3
ꢂ
˚
110.715(3) , V ¼ 3351.2(9) A , Z ¼ 4, Dc ¼ 1.357 g cm
,
˚
F000 ¼ 1448, MoKa radiation, l ¼ 0.71073 A, T ¼ 173(2)K,
2ymax ¼ 54.2ꢂ, 9145 reflections collected, 3688 unique
(Rint ¼ 0.0488). Final GooF ¼ 0.997, R1 ¼ 0.0433, wR2 ¼
0.0861, R indices based on 2640 reflections with I > 2s(I)
(refinement on F2), 208 parameters, 0 restraints. Lp and
absorption corrections applied, m ¼ 0.900 mmꢃ1. CCDC refer-
ence numbers 222951–222952. See http://www.rsc.org/
suppdata/nj/b3/b313422a/ for crystallographic data in .cif or
other electronic format.
37 J. C. Medina, I. Gay, Z. Chen, L. Echegoyen and G. W. Gokel,
J. Am. Chem. Soc., 1991, 113, 365–366.
Acknowledgements
38 J. C. Medina, C. Li, S. G. Bott, J. L. Atwood and G. W. Gokel,
J. Am. Chem. Soc., 1991, 113, 366–367.
39 J. C. Medina, T. T. Goodnow, S. Bott, J. L. Atwood, A. E. Kaifer
and G. W. Gokel, J. Chem. Soc., Chem. Commun., 1991, 290–292.
40 D. R. van Staveren, T. Weyhermueller and N. Metzler-Nolte,
Dalton Trans,, 2003, 210–220.
We thank the Petroleum Research Fund, administered by the
American Chemistry Society, for a grant (PRF 37197-AC4)
that supported this work.
41 R. S. Herrick, R. M. Jarret, T. P. Curran, D. R. Dragoli, M. B.
Flaherty, S. E. Lindyberg, R. A. Slate and L. C. Thornton, Tetra-
hedron Lett., 1996, 37, 5289–5292.
42 J. J. Byrne, A. Rebello, P. Y. Chavant, M. T. Averbuch-Pouchot
and Y. Vallee, Z. Kristallogr. – New Cryst. Struct., 1998, 213, 180.
43 J. D. Carr, S. J. Coles, W. W. Hassan, M. B. Hursthouse, K. M.
A. Malik and J. H. R. Tucker, J. Chem. Soc., Dalton. Trans.,
1999, 57–62.
44 L. J. Barbour, http://www.x-seed.net/, 2003.
45 L. J. Barbour, J. Supramol. Chem., 2001, 1, 189–191.
46 J. L. Atwood and L. J. Barbour, Cryst. Growth Des., 2003,
3, 3–8.
47 K. Murayama and K. Aoki, Chem. Lett., 1998, 301–302.
48 T. B. Wen, B. S. Kang, C. Y. Su, D. X. Wu, L. G. Wang, S. Liao
and H. Q. Liu, Bull. Soc. Jpn., 1998, 71, 2339–2343.
49 P. Hodge, S. C. James, N. C. Norman and A. G. Orpen, J. Chem.
Soc., Dalton Trans., 1998, 4049–4054.
References
1
2
3
J. J. Brooks, W. Rhine and G. D. Stucky, J. Am. Chem. Soc.,
1972, 94, 7346–7351.
J. Sunner, K. Nishizawa and P. Kebarle, J. Phys. Chem., 1981, 85,
1814–1820.
P. C. Kearney, L. S. Mizoue, R. A. Kumpf, J. E. Forman, A.
McKurdy and D. A. Dougherty, J. Am. Chem. Soc., 1993, 115,
9907–9919.
4
5
K. Aoki, K. Maruyama and H. Nishiyama, J. Chem. Soc., Chem.
Commun., 1995, 2221–2222.
F. Inokuchi, Y. Miyahara, T. Inazu and S. Shinkai, Angew.
Chem., Int. Ed. Engl., 1995, 34, 1364–1366.
6
7
J. C. Ma and D. A. Dougherty, Chem. Rev., 1997, 97, 1303–1324.
O. M. Cabarcos, C. J. Weinheimer and J. M. Lisy, J. Chem. Phys.,
1998, 108, 5151–5154.
8
9
K. Murayama and K. Aoki, Inorg. Chim. Acta, 1998, 36–42.
F. Nachon, L. Ehret-Sabatier, D. Loew, C. Colas, A. van
Dorsselaer and M. Goeldner, Biochemistry, 1998, 37, 10 507–13.
50 G. Ferguson, Y. Li, A. J. McAlees, R. McCrindle and K. Xiang,
Organometallics, 1999, 18, 2428–2439.
10 S. M. Ngola and D. A. Dougherty, J. Org. Chem., 1998, 63,
4566–4567.
11 A. Y. Ting, I. Shin, C. Lucero and P. G. Schultz, J. Am. Chem.
Soc., 1998, 120, 7135–7136.
51 B. Malezieux, M. Gruselle, L. L. Troitskaya, V. I. Sokolov and
J. Vaissermann, Organometallics, 1994, 13, 2979–2986.
52 T. H. Galow, J. Rodrigo, K. Cleary, G. Cooke and V. M. Rotello,
J. Org. Chem., 1999, 64, 3745–3746.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 9 0 7 – 9 1 1
911