Synthesis of enantiopure planar chiral bisferrocenes bearing sulfur or nitrogen substituents

Article abstract of DOI:10.1021/om049924b

A new procedure for the preparation of enantiopure planar chiral bisferrocenes bearing potentially metal-coordinating sulfur or nitrogen substituents is reported. The diastereose-lective ortho-lithiation of enantiopure sulfinyl- or oxazolidinylferrocenes followed by treatment with nonenolizable esters leads in a one-pot operation to the corresponding bisferrocenyl carbinols. Due to the presence of a strong hydrogen bond between the hydroxyl group and one of the sulfinyl moieties, the pyrolysis of the bis(sulfinyl)bisferrocene 3a in toluene at 110°C takes place by selective removal of the non-hydrogen-bonded sulfoxide to afford in good yield a tetraferrocene disulfide derivative. Interesting structural information for these novel bi- and tetraferrocenes, deduced by NMR and X-ray crystallography, is also discussed.

Full text of DOI:10.1021/om049924b

Organometallics 2004, 23, 1991-1996
1991
Syn th esis of En a n tiop u r e P la n a r Ch ir a l Bisfer r ocen es
Bea r in g Su lfu r or Nitr ogen Su bstitu en ts
Ramo´n Go´mez Arraya´s, Ine´s Alonso, Olga Familiar, and J uan Carlos Carretero*
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias, Universidad Auto´noma de Madrid,
28049 Madrid, Spain
Received J anuary 29, 2004
A new procedure for the preparation of enantiopure planar chiral bisferrocenes bearing
potentially metal-coordinating sulfur or nitrogen substituents is reported. The diastereose-
lective ortho-lithiation of enantiopure sulfinyl- or oxazolidinylferrocenes followed by treatment
with nonenolizable esters leads in a one-pot operation to the corresponding bisferrocenyl
carbinols. Due to the presence of a strong hydrogen bond between the hydroxyl group and
one of the sulfinyl moieties, the pyrolysis of the bis(sulfinyl)bisferrocene 3a in toluene at
110 °C takes place by selective removal of the non-hydrogen-bonded sulfoxide to afford in
good yield a tetraferrocene disulfide derivative. Interesting structural information for these
novel bi- and tetraferrocenes, deduced by NMR and X-ray crystallography, is also discussed.
In tr od u ction
proved to be very efficient ligands in a variety of metal-
mediated enantioselective processes7,8 (Figure 1).
Since the pioneering work of Hayashi and Kumada
in 1974 on the synthesis of the first chiral ferrocenyl
phosphine,1 the planar chiral 1,2-disubstituted ferrocene
unit has become one of the most useful backbones in
the design of new ligands for enantioselective catalysis.2
More recently this interest has been extended to the
synthesis of enantiopure species with bisferrocene struc-
ture. Among these, the diphosphine PhTRAP, developed
by Ito et al.,3 the triphosphine Pigiphos, described by
Togni et al.,4 the bis azaferrocene I, developed by Fu et
al.,5 and the bisPPFOMe reported by Hayashi6 have
We report herein that enantiopure hydroxymethyl
bisferrocenes having potentially metal-coordinating sul-
fur or nitrogen substituents at the cyclopentadienyl ring
are readily synthesized in a one-step procedure by
diastereoselective ortho-lithiation of enantiomerically
pure sulfinylferrocenes or oxazolidinyl ferrocenes, fol-
lowed by addition of a nonenolizable ester.
Resu lts a n d Discu ssion
In 1993 Kagan et al. described that the ortho-
lithiation of the readily available (R)-tert-butylsulfinyl-
ferrocene (1) is controlled by the sulfinyl group, occur-
* Corresponding author. Fax: +34 91 4973966. E-mail:
juancarlos.carretero@uam.es.
(1) For recent reviews, see: (a) Hayashi, T.; Yamamoto, K.; Kumada,
M. Tetrahedron Lett. 1974, 4405. See also: (b) Hayashi, T.; Mise, T.;
Fukushima, M.; Kagotani, M.; Nagashima, N.; Hamada, Y.; Matsu-
moto, A.; Kawakami, S.; Konishi, M.; Yamamoto, K.; Kumada, M. Bull.
Chem. Soc. J pn. 1980, 53, 1138.
(2) (a) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.-P.; Hou, X.-L. Acc.
Chem. Res. 2003, 36, 659. (b) Togni, A.; Bieler, N.; Burckhardt, U.;
Ko¨llner, C.; Pioda, G.; Schneider, R.; Schnyder, A. Pure Appl. Chem.
1999, 71, 1531. (c) Togni, A. In Metallocenes; Togni, A., Halterman, R.
L., Eds.; Wiley-VCH: Weinheim, Germany, 1998; Vol. 2, Chapter 10.
(d) Richards, C. J .; Locke, A. J . Tetrahedron: Asymmetry 1998, 9, 2377.
(e) Hayashi, T. In Ferrocenes; Togni, A., Hayashi, T., Eds.; VCH:
Weinheim, Germany, 1995; Chapter 2.
(3) For a review, see: (a) Ito, Y.; Kuwano, R. Phosphorus, Sulfur
Silicon Relat. Elem. 1999, 144-146, 469. See also: (b) Kuwano, R.;
Sato, K.; Kurokawa, T.; Karube, D.; Ito, Y. J . Am. Chem. Soc. 2000,
122, 7614. (c) Kuwano, R.; Uemura, T.; Saitoh, M.; Ito, Y. Tetrahedron
Lett. 1999, 40, 1327. (d) Sawamura, M.; Sudo, M.; Ito, Y. J . Am. Chem.
Soc. 1996, 118, 3309. (e) Goeke, A.; Sawamura, M.; Kuwano, R.; Ito,
Y. Angew. Chem., Int. Ed. 1996, 35, 662. (f) Sawamura, M.; Kuwano,
R.; Ito, Y. J . Am. Chem. Soc. 1995, 117, 9602. (g) Sawamura, M.;
Hamashima, H.; Shinoto, H.; Ito, Y. Tetrahedron Lett. 1995, 36, 6479.
(h) Sawamura, M.; Hamashima, H.; Ito, Y.; Tetrahedron 1994, 50, 4439.
(i) Sawamura, M.; Hamashima, H.; Ito, Y. J . Am. Chem. Soc. 1992,
114, 8295.
(4) (a) Fadini, L.; Togni, A. Chem. Commun. 2003, 30. (b) Barbaro,
P.; Togni, A. Organometallics 1995, 14, 3570. See also: (c) Barbaro,
P.; Bianchini, C.; Togni, A. Organometallics 1997, 16, 3004.
(5) (a) Shintani, R.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42, 4082.
(b) Lo, M. M.-C.; Fu, G. C. J . Am. Chem. Soc. 2002, 124, 4572. (c) Lo,
M. M.-C.; Fu, G. C. J . Am. Chem. Soc. 1998, 120, 10270. (d) Lo, M.
M.-C.; Fu, G. C. Tetrahedron 2001, 57, 2621.
(6) (a) Han, J . W.; Tokunaga, N.; Hayashi, T. Helv. Chim. Acta 2002,
85, 3848. (b) Han, J . W.; Tokunaga, N.; Hayashi, T. J . Am. Chem. Soc.
2001, 123, 12915.
(7) For other bisferrocene-based chiral ligands in asymmetric ca-
talysis, see: (a) Xiao, L.; Weissensteiner, W.; Mereiter, K.; Widhalm,
M. J . Org. Chem. 2002, 67, 2206. (b) Tanaka, Y.; Taniguchi, N.;
Kimura, T.; Uemura, M. J . Org. Chem. 2002, 67, 9227. (c) You, S.-L.;
Hou, X.-L.; Dai, L.-X.; Zhu, X.-Z. Org. Lett. 2001, 2, 149. (d) Xiao, L.;
Mereiter, K.; Spindler, F.; Weissensteiner, W. Tetrahedron: Asymmetry
2001, 12, 1105. (e) Nettekoven, U.; Widhalm, M.; Kalchhauser, H.;
Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Lutz, M.; Spek, A. L. J .
Org. Chem. 2001, 66, 759. (f) Longmire, J . M.; Wang, B.; Zhang, X.
Tetrahedron Lett. 2000, 41, 5435. (g) You, S.-L.; Hou, X.-L.; Dai, L.-
X.; Cao, B.-X.; Sun, J . Chem. Commun. 2000, 1933. (h) Kim, S.-G.;
Cho, C.-W.; Ahn, K. H. Tetrahedron 1999, 55, 10079. (i) Larsen, A. O.;
Taylor, R. A.; White, P. S.; Gagne´, M. R. Organometallics 1999, 18,
5157. (j) Song, J .-H.; Cho, D.-J .; J eon, S.-J .; Kim, Y.-H.; Kim, T.-J .;
J eong, J . H. Inorg. Chem. 1999, 38, 893. (k) Cho, D.-J .; J eon, S.-J .;
Kim, H.-S.; Cho, C.-S.; Shim, S.-C.; Kim, T.-J . Tetrahedron: Asymmetry
1999, 10, 3833. (l) Kim, S.-G.; Cho, C.-W.; Ahn, K. H. Tetrahedron:
Asymmetry 1997, 8, 1023. (m) Riant, O.; Sammuel, O.; Flenner, T.;
Taudien, S.; Kagan, H. B. J . Org. Chem. 1997, 62, 6733. For recent
examples on nonchiral bisferrocene-based ligands, see: (n) Dong, T.-
Y.; Huang, B.-R.; Lin, M.-C.; Chiang, M. Y. Polyhedron 2003, 1199.
(o) Salo, E. V.; Guan, Z. Organometallics 2003, 22, 5033. (p) Horikoshi,
R.; Mochida, T.; Torigoe, R.; Yamamoto, Y. Eur. J . Inorg. Chem. 2002,
3197.
(8) For chiral triferrocenes as ligands in enantioselective catalysis,
see: (a) Ganter, C.; Kaulen, C.; Englert, U. Organometallics 1999, 18,
5444. See also: (b) Ganter, C.; Glinsbo¨ckel, C.; Ganter, B. Eur. J . Inorg.
Chem. 1998, 1163.
10.1021/om049924b CCC: $27.50 © 2004 American Chemical Society
Publication on Web 03/20/2004

1992 Organometallics, Vol. 23, No. 9, 2004
Arraya´s et al.
Sch em e 2
Sch em e 3
F igu r e 1. Relevant bisferrocenes used in enantioselective
catalysis.
Sch em e 1
(78% yield). On the other hand, in the case of using ethyl
formate as an example of an unhindered ester, the
corresponding carbonyl intermediate, which is the al-
dehyde 2d , was also selectively obtained as previously
reported by Hua.10d These results from ethyl p-nitroben-
zoate and ethyl formate suggest that in both cases the
sp3 hemiketal intermediate, resulting from the initial
addition of the ortho-lithiated ferrocene, is not able to
evolve into the carbonyl derivative under these very
mild conditions (THF, -78 °C). However, the bisferro-
cenyl carbinol 3d was cleanly obtained by further
addition of ortho-lithiated (R)-1 to the aldehyde 2d
(Scheme 3). Not unexpectedly the acylation reaction
failed in the case of esters having acidic hydrogens at
the R-position such as ethyl acetate, which provided a
complex reaction mixture.
The bisferrocene structure of compounds 3 was firmly
established by NMR and mass spectrometry studies and
unequivocally confirmed by X-ray diffraction analysis
of 3a (Figure 2).13 Single crystals of 3a were obtained
at 4 °C by slow evaporation of a dichloromethane
solution of this compound in a hexane bath. Relevant
information from the crystal structure of 3a is the
presence of a seven-membered hydrogen bond between
the hydroxyl group and one of the sulfinylic oxygens.
The SO‚‚‚H distance is 1.87(4) Å, remarkably shorter
than the sum of the van der Waals radii14 for H and O.
The O‚‚‚H-O angle (θ) is near-linear (171°), and the
directionality at the atom acceptor is appropriate15
(S-O‚‚‚H angle (φ) ) 115°). The length of the S-O bond
that participates in the hydrogen bond (S(1)-O(1)
distance ) 1.502(2) Å) agrees with those reported for
similar cases16 and is only slightly longer than that of
ring with complete selectivity at C-2 (and not at C-5).9
After addition of an appropriate electrophile, planar
chiral 1,2-disubstituted ferrocenes were isolated in high
yields (Scheme 1). By using this methodology several
groups,10 including ours,11 have reported a variety of
new types of planar chiral ferrocenes. Surprisingly,
however, the reaction of lithiated sulfinyl ferrocenes
with esters, which could be a quite simple alternative
to the synthesis of chiral bisferrocene structures, to our
best knowledge, has not been previously described.
Gratifyingly, deprotonation of (R)-1 with t-BuLi (1.2
equiv) in THF at -78 °C, followed by addition of ethyl
benzoate (1.2 equiv, -78 °C), afforded cleanly the
hydroxymethyl bisferrocene 3a as an air-stable red
crystalline solid in 88% yield with ee > 99.5% (HPLC,
Chiralcel OD column). The intermediate ketone 2a was
not detected in the 1H NMR spectrum of the crude
reaction mixture. To examine the influence of the
electronic nature of the aromatic ester in this bisfer-
rocene synthesis,12 we extended the reaction to both
electron-rich and electron-deficient substituted ben-
zoates (Scheme 2). Interestingly, while the methyl
p-methoxybenzoate provided the bisferrocene 3b as the
only product in 72% isolated yield, the ethyl p-nitroben-
zoate afforded exclusively the intermediate ketone 2c
(9) (a) Rebie`re, F.; Riant, O.; Ricard, L.; Kagan, H. B. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 568. See also: (b) Riant, O.; Argouarch, G.;
Guillaneux, D.; Samuel, O.; Kagan, H. B. J . Org. Chem. 1998, 63, 3511.
(c) Diter, P.; Samuel, O.; Taudien, S.; Kagan, H. B. Tetrahedron:
Asymmetry 1994, 5, 549.
(10) (a) Pedersen, H. L.; J ohannsen, M. J . Org. Chem. 2002, 67,
7982. (b) Lotz, M.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed.
2002, 41, 4708. (c) Bolm, C.; Kuhn, T. Isr. J . Chem. 2002, 41, 263. (d)
Lagneau, N. M.; Chen, Y.; Robben, P. M.; Sin, H.-S.; Takasu, K.; Chen,
J .-S.; Robinson, P. D.; Hua, D. H. Tetrahedron 1998, 54, 7301.
(11) (a) Garc´ıa Manchen˜o, O.; Priego, J .; Cabrera, S.; Go´mez
Arraya´s, R.; Llamas, T.; Carretero, J . C. J . Org. Chem. 2003, 68, 3679.
(b) Priego, J .; Garc´ıa Manchen˜o, O.; Cabrera, S.; Carretero, J . C. J .
Org. Chem. 2002, 67, 1346.
(12) For the synthesis of bis(sulfinyl)bisferrocene using a different
approach, see: (a) J ensen, J . F.; Søtofte, I.; Sørensen, H. O.; J ohannsen,
M. J . Org. Chem. 2003, 68, 1258. (b) Cotton, H. K.; Huerta, F. F.;
Backvall, J .-E. Eur. J . Org. Chem. 2003, 2756. (c) Xiao, L.; Mereiter,
K.; Spindler, F.; Weissensteiner, W. Tetrahedron: Asymmetry 2001,
12, 1105.
(13) Crystal structure data for C35H40Fe2O3S2 (3a ): crystal size 0.18
× 0.12 × 0.08 mm3, orthorhombic, space group P212121, a ) 12.09610-
(10) Å, b ) 16.29880(10) Å, c ) 16.5371(2) Å, V ) 3260.32(5) Å3, Z )
4, Fcalcd ) 1.394 Mg m-3, µ ) 8.591 mm-1, 2θmax ) 140.8°, 6035
reflections collected. Refinement on F2 for 6035 reflections and 527
parameters gave GOF ) 1.041, R1 ) 0.0281 and wR2 ) 0.0699 for I >
2σ(I). Absolute structure parameter ) -0.006(3). Residual electron
density -0.215 < ∆F < 0.346 eÅ-3
.
(14) Bondi, A. J . Phys. Chem. 1964, 68, 441 (van der Waals radii
values: H ) 1.20 Å, O ) 1.52 Å, S ) 1.80 Å).
(15) (a) Platts, J . A.; Howard, S. T.; Bracke, B. R. F. J . Am. Chem.
Soc. 1996, 118, 2726. (b) Hay, B. P.; Dixon, D. A.; Bryan, J . C.; Moyer,
B. A. J . Am. Chem. Soc. 2002, 124, 182.

Enantiopure Planar Chiral Bisferrocenes
Organometallics, Vol. 23, No. 9, 2004 1993
F igu r e 2. ORTEP plot for 3a (30% thermal ellipsoids)
showing the atomic numbering of selected atoms. The
hydrogen atoms, except H(2), have been omitted for clarity.
Selected bond lengths (Å) and angles (deg): C(15)-O(2),
1.412(3); C(15)-C(9), 1.539(3); C(15)-C(22), 1.523(3); S(1)-
O(1), 1.502(2); S(2)-O(3) 1.495(2); O(2)-C(15)-C(9), 112.24-
(17); O(2)-C(15)-C(22), 105.36(18); O(1)-H(2)-O(2), 172-
(4); O(1)-S(1)-C(5)-C(9), 0.3(3); O(3)-S(2)-C(23)-C(22),
-134.3(2).
F igu r e 3. 1H NMR spectrum of bisferrocene 3a and
significant NOE cross-peaks.
the non-hydrogen-bonded sulfoxide [S(2)-O(3) distance
) 1.495(2) Å], also lengthened with respect to typ-
ical aryl alkyl sulfoxides.9a,17 On the other hand, the
O(2)‚‚‚S(2) distance (2.90 Å) is shorter than the sum of
the van der Waals radii14 for O and S, which suggests
the presence of a stabilizing donor-acceptor interaction
between them. This kind of interaction had been previ-
ously proposed from conformational studies on â-oxy-
genated sulfoxides18 and has also been observed in the
solid state of other hydroxy sulfoxides.19 This interac-
tion, along with the hydrogen bond, imposes 3a to adopt
a very congested conformation in the solid state (the
sulfinyl group on Fc(2) is 0.54 Å out of the plane of the
cyclopentadienyl ring), in which both ferrocene units are
oriented opposite each other. This can be easily quanti-
fied by measuring the improper dihedral angle (T)
formed by the centroids of each cyclopentadienyl ring.
The usual value for this angle in related Fc-C-Fc
systems20 is in the range 80-110°, while in 3a this angle
is much higher (147°). Interestingly, both ferrocene
units are surrounded by quite different environments.
Thus, the phenyl ring at C15 is placed just in front of
one of the ferrocene moieties [Fe(2)], but in nearly anti
arrangement with regard to the other one [Fe(1)]. On
the other hand, the tert-butyl group on Fc(1) is pointed
away from the Fe(1), whereas the equivalent group on
Fc(2) is directed toward the Fe(2) atom.
To establish whether the conformation of the bisfer-
rocene 3a in solution is similar to that observed in the
solid state, we investigated compound 3a by one- and
two-dimensional NMR in CDCl3. The quite outstanding
differences in the chemical shifts of the two tert-butyl
groups (singlets at 0.62 and 1.70 ppm) and the unsub-
stituted Cp rings (singlets at 3.68 and 4.48 ppm)
indicate that both ferrocene units are in very different
environments (Figure 3). In good accordance with the
X-ray structure, the protons of the tert-butyl group of
ferrocene 1 (t-Bu1, 0.62 ppm) and those of the unsub-
stituted Cp-ring of ferrocene 2 (Cp2, 3.68 ppm) appear
greatly shielded compared to the expected chemical
shifts of such protons in related systems (typically
around 1.0 and 4.5 ppm, respectively). This remarkable
effect, likely caused by the cone anisotropy effect of the
phenyl ring, suggests that complex 3a adopts in solution
a major conformation with the phenyl group situated
between t-Bu1 and Cp2. Similarly, the high deshielding
of the tert-butyl group of ferrocene 2 (t-Bu2, 1.70 ppm),
which is above the aromatic ring, can also be explained
invoking the same cone anisotropy effect of the phenyl
moiety. The intramolecular hydrogen bond between the
hydroxyl group and the sulfinylic oxygen at ferrocene 1
1
is also evident in the H NMR spectra by the presence
of a singlet at 7.12 ppm. In full agreement with the
previous discussion, 2D NOESY experiments revealed
strong NOE cross-peaks of the protons on t-Bu1 with
the ortho-, metha-, and para-protons of the phenyl group
(Ho, Hm, and Hp) and the hydroxyl proton H2, while t-Bu2
showed NOE contacts with the ortho protons Ho (not
with Hm or Hp), H2 and Cp2. The NOE cross signals of
Cp2 with Ho and Hm, along with the absence of NOE
between the protons on the phenyl group and Cp1, were
also structurally relevant. All these NMR spectroscopic
data strongly support for 3a a conformation in solution
very similar to that observed in the crystal.
(16) For an example of an intramolecular hydrogen bond involving
a sulfoxide and a hydroxy group in a seven-membered ring see: Aversa,
M. C.; Baratucci, A.; Bonaccorsi, P.; Bonini, B. F.; Giannetto, P.; Nicolo,
F. Tetrahedron: Asymmetry 1999, 10, 3919.
(17) See for example: (a) Banziger, M.; Klein, S.; Rihs, G. Helv.
Chim. Acta 2002, 85, 1399. (b) Alonso, I. Lo´pez-Solera, I. Raithby, P.
R. Acta Crystallogr., Sect. C 1996, 52, 1548. (c) Casarini, D.; Lunazzi,
L.; Gasparrini, F.; Villani, C.; Cirilli, M.; Gavuzzo, E. J . Org.Chem.
1995, 60, 97.
(18) Carren˜o, M. C.; Carretero, J . C.; Garc´ıa Ruano, J . L.; Rodr´ıguez,
J . H. Tetrahedron 1990, 46, 5649, and references therein.
(19) Abe, H.; Tsuchida, D.; Kashino, S.; Takeuchi, Y.; Harayama.
T. Chem. Pharm. Bull. 1999, 47, 833.
(20) (a) Diferrocenyl(phenyl)methanol: Glidewell, C.; Klar, R. B.;
Lightfoot, P.; Zakaria, C. M.; Ferguson, G. Acta Crystallogr., Sect. B:
Struct. Sci. 1996, 52, 110. (b) 1,1′-Bis(ferrocenyl)-2,2′-dimethylpropan-
1-ol: Sharma, H. K.; Cervantes-Lee, F.; Pannell, K. H. J . Organomet.
Chem. 1992, 438, 183. (c) Diferrocenylmethanol: Ferguson, G.; Glidewell,
C.; Opromolla, G.; Zakaria, C. M.; Zanello, P. J . Organomet. Chem.
1996, 517, 183.
The presence of the S-O(1)‚‚‚H(2) hydrogen bond
produced also some unexpected chemical consequences.
Thus, when compound 3a was treated under typical

1994 Organometallics, Vol. 23, No. 9, 2004
Arraya´s et al.
Sch em e 4
the ferrocene units adopt a conformation very similar
to that of the precursor 3a .
In accordance with this crystal structure, the 1H NMR
spectrum of 4 (Figure 5) shows the disappearance of the
deshielded signal of the tert-butyl group at ferrocene 2
(t-Bu2 in the precursor 3a ) and the presence of shielded
singlets for the remaining tert-butyl group of the sulf-
oxide at ferrocene 1 and the unsubstituted Cp at
ferrocene 2 (0.62 and 3.68 ppm, respectively). The
intramolecular hydrogen bond between the hydroxyl
group and the sulfinylic oxygen is also detected by a
deshielded singlet at 7.51 ppm. On the other hand, the
1H-NOESY spectra of 4 clearly shows the spatial
closeness of the phenyl group to both t-Bu and Cp2
groups (see Figure 5). As far as we know, this is the
first example of an enantiopure tetraferrocene reported
to date.22
F igu r e 4. ORTEP plot for 4 (30% thermal ellipsoids)
showing the atomic numbering of selected atoms. The
hydrogen atoms, except H(2), have been omitted for clarity.
Selected bond lengths (Å) and angles (deg): C(15)-O(2),
1.408(3); C(15)-C(22), 1.520(3); C(15)-C(9), 1.544(3); S(1)-
O(1), 1.495(2); S(2)-S(2A), 2.0538(13); O(2)-C(15)-C(22),
105.51(18); O(2)-C(15)-C(9), 112.33(18); O(1)-H(2)-O(2),
167.6; O(1)-S(1)-C(5)-C(9), 5.5(3); C(22)-C(23)-S(2)-
S(2A), 164.31(19).
Interestingly, this simple procedure for the synthesis
of bisferrocenes can also be applied to compounds
containing chiral nitrogen substituents, such as oxazo-
lidines, which constitute one of the most popular chiral
moieties currently used in enantioselective catalysis.23
Thus, the synthesis of the (S,Rp,S,Rp)-bis(oxazolidinyl)-
bisferrocene 6 was accomplished in a manner similar
to that for bisferrocenes 3. Starting from (S)-tert-
butyloxazolidinylferrocene 5, which was readily ob-
tained from ferrocenecarboxylic acid24 according to
reported procedures,25 its diastereoselective ortho-lithia-
tion with s-BuLi (THF, -78 °C) followed by in situ
treatment with ethyl benzoate afforded the bis(oxazo-
lidinyl)bisferrocene 6 as the main product (44% yield),
along with 20% of the starting oxazolidine. In this ortho-
lithiation process the use of s-BuLi as base seems to be
essential, since attempts of ortho-lithiation with the
(21) Crystal structure data for C62H62Fe4O4S4 (4): crystal size 0.20
× 0.16 × 0.14 mm3, orthorhombic, space group P21212, a ) 14.87200-
(10) Å, b ) 23.0986(2) Å, c ) 7.93910(10) Å, V ) 2727.26(5) Å3, Z ) 4,
Fcalcd ) 1.489 Mg m-3, µ ) 10.172 mm-1, 2θmax ) 140.94°, 17 645
reflections collected, 4994 independent. Refinement on F2 for 4994
reflections and 338 parameters gave GOF ) 1.056, R1 ) 0.0277 and
wR2 ) 0.0734 for I > 2σ(I). Absolute structure parameter ) -0.012-
(3). Residual electron density -0.182 < ∆F < 0.259 e Å-3
.
F igu r e 5. 1H NMR spectrum of 4 and relevant NOE cross-
peaks.
(22) For achiral or racemic tetraferrocenes, see for instance: (a)
Denifl, P.; Hradsky, A.; Bildstein, B.; Wurst, K. J . Organomet. Chem.
1996, 523, 79. (b) Bildstein, B.; Schweiger, M.; Kopacka, H.; Wurst.
K. J . Organomet. Chem. 1998, 553, 73. (c) Bildstein, B.; Skibar, W.;
Schweiger, M.; Kopacka, H.; Wurst, K. J . Organomet. Chem. 2001, 622,
135.
sulfoxide-pyrolysis conditions (heating in toluene at 110
°C for 2.5 h), only the nonassociated sulfinyl group
reacted, affording in reasonable yield (64%) the tetra-
ferrocenyl disulfide 4, resulting presumably from the
dimerization of the unstable sulfenic acid intermediate
(23) For recent reviews, see: (a) Rechari, D.; Lemaire, M. Chem.
Rev. 2002, 102, 3467. (b) J ohnson, J . S.; Evans, D. A. Acc. Chem. Res.
2000, 33, 325. (c) Fache, F.; Schultz, E.; Tommasino, M. L.; Lemaire,
M. Chem. Rev. 2000, 100, 2159. (d) Helmchen, G.; Pfaltz, A. Acc. Chem.
Res. 2000, 33, 336. For chiral bis(oxazolidinyl)bisferrocenes in enan-
tioselective catalysis, see refs 7g and 7k.
(24) Although ferrocenecarboxylic acid is commercially available, it
can be readily prepared by carboxylation of lithiated ferrocene. See,
for instance: Sorensen, H. S.; Larsen, J .; Rasmussen, B. S.; Laursen,
B.; Hansen, S. G.; Skrysdstrup, T.; Amatore, C.; J utand, A. Organo-
metallics 2002, 21, 5243.
1
3 (Scheme 4). The structure of 4 was elucidated by H
NMR and mass spectrometry [(M+) + H ) 1222,
determined by FAB] and unequivocally confirmed by
X-ray crystallography (Figure 4).21 As shown in Figure
4 compound 4 shows a C2 axis (there is only half a
structure in the asymmetric crystallographic unit) and
(25) Bolm, C.; Hermanns, N.; Kesselgruber, M.; Hildebrand, J . P.
J . Organomet. Chem. 2001, 624, 157.

Enantiopure Planar Chiral Bisferrocenes
Organometallics, Vol. 23, No. 9, 2004 1995
solvent was evaporated. The residue was purified by flash
chromatography (element indicated below for each case).
[(RS,RP )-2-(ter t-Bu tylsu lfin yl)fer r ocen yl] (p-Nitr op h e-
n yl) Keton e (2c). Following the general procedure, (R)-1 (100
mg, 0.34 mmol) was treated with t-BuLi (1.7 M in pentane,
260 µL, 0.45 mmol) and ethyl p-nitrophenyl benzoate (67 mg,
0.34 mmol), affording after chromatographic purification (n-
hexanes-EtOAc, 1:4) 2c (118 mg, 78%) as a red solid: [R]D
+134 (c 0.03, CHCl3); mp 135-136 °C. 1H NMR (300 MHz,
CDCl3): δ 8.28 (d, J ) 8.6 Hz, 2H), 7.94 (d, J ) 9.1 Hz, 2H),
4.86 (s, 1H), 4.68 (s, 2H), 4.48 (s, 5H), 1.19 (s, 9H). 13C NMR
(75 MHz, CDCl3): δ 193.0, 149.3, 144.9, 131.7, 130.9, 75.5,
74.4, 72.4, 71.9, 71.4, 65.8, 60.3, 56.8, 23.9. IR (cm-1): 3094
(w), 3063 (w), 1657 (s), 1554 (s), 1474 (s), 1458 (m), 1346 (s),
1321 (s), 1062 (s), 898 (s), 882 (s), 868 (s), 778 (s). MS (FAB+):
m/z 440 [M+ + H, 22], 383 [M+ + H - OH,13]. HRMS
(FAB+): calcd for C21H23NO4S(56Fe) [M+ + H] 440.0619, found
440.0609. Anal. Calcd for C21H22NO4SFe: C, 57.41; H, 4.82.
Found: C, 57.21; H, 4,84.
bulky t-BuLi resulted in the main recovery of the
starting material. The structure of 6 was established
by NMR and mass spectrometry, and its planar (R)
configuration was inferred according to the reported
stereoselectivity for ortho-lithiation of oxazolidinylfer-
rocenes.26
In summary, enantiopure chiral planar bisferrocenes
substituted with sulfur or nitrogen groups are readily
prepared by selective ortho-lithiation of chiral sulfinyl-
ferrocenes and oxazolidinylferrocenes followed by reac-
tion with nonenolizable esters. The study of these
compounds and derivatives as chiral ligands in enan-
tioselective catalysis is underway and will be reported
in due course.
Exp er im en ta l Section
NMR spectra were recorded on a Bruker AMX-300 spec-
trometer [300 MHz (1H), 75 MHz (13C)] at room temperature
in CDCl3 with internal CHCl3 as the reference (7.26 ppm for
1H and 77.0 ppm for 13C). NOESY spectra of 3a and 4 were
recorded at 27 °C on a Bruker AMX-300 and a Bruker DMX-
500 MHz, respectively, the data being collected in phase
applying the method noesytp. Mixing time for both NOESY
spectra was 500 ms. IR spectra were recorded on a Bruker
Vector 22 using KBr pellets. Picks are reported with the
following intensities: s (strong, 67-100%), m (medium, 40-
67%), w (weak, 20-40%), and br (broad). Melting points were
taken in open capillary tubes on a Gallenkamp melting point
apparatus. Optical rotations were measured at 25 °C with a
Perkin-Elmer 241 MC polarimeter. THF, toluene, and dichlo-
romethane were dried over microwave-activated 4 Å molecular
sieves (1 week) before use. Esters were purchased from
commercial sources and used as received. Single crystals of
both compounds were grown by slow diffusion of hexane onto
dichloromethane solutions. Data collections were carried out
at room temperature on a Bruker Smart CCD diffractometer
using graphite-monochromated Cu KR (λ ) 1.54178 Å) and
the 2θ /ω scan method. Absorption correction method SADABS
(v. 2.03) was applied. Both structures were solved by direct
methods (SHELXS-97),27 and the refinement was made by full-
matrix least-squares on F2 (SHELXL-97). Anisotropic param-
eters were used in the last cycle of refinement for all non-
hydrogen atoms. For compound 3a most of the hydrogen atoms
have been found in the difference Fourier map. Only three of
them [H(10), H(11), and H(12)] were included in calculated
positions and refined riding on their respective carbon atoms
with the thermal parameter related to the bonded atoms. For
compound 4 all hydrogen atoms were included in calculated
positions and refined riding on their respective bonded atoms
with the related thermal parameter.
[(RS,RP )-1-(ter t-Bu tylsu lfin yl)-2-for m ylfer r ocen e (2d).10d
Following the general procedure, (R)-1 (100 mg, 0.34 mmol)
was treated with t-BuLi (1.7 M in pentane, 260 µL, 0.45 mmol)
and ethyl formate (36 µL, 0.45 mmol), affording after chro-
matographic purification (n-hexanes-diethyl ether, 1:5) 2d 10d
(78 mg, 71%) as a yellow solid.
Bis[(RS,RP )-2-(ter t-b u t ylsu lfin yl)fer r ocen yl](p h en yl)-
m eth a n ol (3a ). Following the general procedure, (R)-1 (1.85
g, 6.39 mmol) was treated with t-BuLi (1.7 M in pentane, 4.5
mL, 7.41 mmol) and ethyl benzoate (1.5 mL, 8.05 mmol) to
afford, after chromatographic purification (n-hexanes-EtOAc,
4:1), 3a (3.92 g, 90%) as a red solid; [R]D +236 (c 0.09, CHCl3);
1
mp 144-145 °C. H NMR (300 MHz, CDCl3): δ 7.49 (bs, 2H),
7.26 (m, 2H), 7.14 (m, 1H), 7.12 (s, 1H, OH), 4.72 (s, 1H), 4.66
(s, 1H), 4.49 (s, 5H), 4.42 (d, J ) 2.42 Hz, 2H), 4.36 (d, J ) 6.5
Hz, 2H) 3.68 (s, 5H), 1.73 (s, 9H), 0.65 (s, 9H). 13C NMR (75
MHz, CDCl3): δ 151.5, 127.1, 126.4, 102.0, 96.3, 95.0, 78.0,
75.1, 73.4, 72.9, 72.5, 72.3, 72.0, 71.5, 70.2, 69,6, 69.4, 68.9,
68.7, 68.5, 57.3, 56.4, 23.8, 23.7, 23.2, 22.9. IR (cm-1): 3343
(br), 3121 (s), 3070 (s), 1644 (w), 1597 (w), 1489 (s), 1460 (s),
1445 (s), 1412 (s), 1387 (m), 1205 (s), 1062 (vs), 702 (vs). MS
(FAB+): m/z 685 [M+ + H, 10], 368 [M+ + H - OH, 8]. HRMS
(FAB+): calcd for C35H41O3S2(56Fe)2 [M+ + H] 685.1196, found
685.1188. The ee was determined to be >99.9% by HPLC
analysis on a Daicel Chiralpark AD, i-PrOH/hexanes, 1:99,
flow rate 1 mL/min (tR ) 27.3 min for the (-) enantiomer and
29.4 min for the (+) enantiomer).
Bis[(RS,RP )-2-(ter t-b u t ylsu lfin yl)fer r ocen yl](p -m et h -
oxyp h en yl)m eth a n ol (3b). Following the general procedure,
(R)-1 (100 mg, 0.34 mmol) was treated with t-BuLi (1.7 M in
pentane, 260 µL, 0.45 mmol) and methyl p-methoxybenzoate
(28.6 mg, 0.17 mmol) to afford, after chromatographic purifica-
tion (n-hexanes-diethyl ether, 1:6), 3b (89 mg, 72%) as an
orange solid; [R]D +375 (c 0.10, CHCl3); mp 140-141 °C. 1H
NMR (300 MHz, CDCl3): δ 7.13 (s, 1H, OH), 6.83 (d, J ) 1.6
Hz, 2H), 6.68 (d, J ) 1.6 Hz, 2H), 4.76 (m, 1H), 4.53 (s, 5H),
4.45 (m, 2H), 4.41 (m, 2H), 4.36 (m, 1H), 3.77 (s, 3H), 3.47 (s,
5H), 1.77 (s, 9H), 0.74 (s, 9H). 13C NMR (75 MHz, CDCl3): δ
158.3, 144.6, 127.8, 112.3, 97.3, 94.7, 77.9, 74.8, 72.4, 72.3, 71.4,
70.2, 69.6, 69.3, 68.6, 68.4, 57.3, 56.4, 55.4, 24.8, 23.8, 23.0.
IR (cm-1): 3418 (br), 3122 (m), 3070 (m), 1607 (m), 1507 (s),
1300 (s), 1009 (s), 828 (m), 801 (m). MS (FAB+): m/z 715 [M+
+ H, 10], 649 (9), 398 (9). HRMS (FAB+): cald for C36H43O4S2-
(56Fe)2 [M+ + H] 715.1301, found 715.1304. Anal. Calcd for
Gen er a l P r oced u r e for th e Rea ction of (R)-1 w ith
Ester s. To a solution of (R)-tert-butylsulfinyl ferrocene (R)-1
(1.85 g, 6.39 mmol) in THF (60 mL), cooled to -78 °C, was
added dropwise a 1.7 M solution of t-BuLi in pentane (4.5 mL,
7.41 mmol). The reaction mixture was stirred at -78 °C for
1.5 h, and then a solution of the corresponding ester (8.05
mmol) in THF (1 mL) was added and the reaction mixture was
kept at -78 °C. Once the reaction was complete or no evolution
was observed (monitored by TLC), brine was added (10 mL).
The aqueous layer was extracted with AcOEt (2 × 20 mL).
The combined organic layers were dried (MgSO4), and the
C
36H42O4SFe2: C, 60.51; H, 5.92. Found: C, 60.27, H, 6.01.
Bis[(R S ,R P )-2-(t er t -b u t ylsu lfin yl)fe r r oce n yl]m e t h a -
(26) For a review on diastereoselective ortho-lithiation, see: (a)
Snieckus, V. Chem. Rev. 1990, 90, 879. For oxazolines as directing
groups in diastereoselective ortho-lithiation of ferrocene systems: (b)
Richards, C. J .; Mulvaney, A. Tetrahedron: Asymmetry 1996, 7, 1419.
(c) Sammakia, T.; Latham, H. A.; Schaad, D. R. J . Org. Chem. 1995,
60, 10. (d) Nishibayashi, Y.; Uemura, S. Synlett. 1995, 79.
n ol (3d ). To a solution of (R)-1 (53 mg, 0.18 mmol) in THF
(2.5 mL), cooled to -78 °C, was added a 1.7 M solution of
t-BuLi in pentane (139 µL, 0.24 mmol). The mixture was
stirred at -78 °C for 2 h, and a solution of 2d (58 mg, 0.18
mmol) in THF (1 mL) was slowly added. The resulting solution
was stirred at -78 °C for 4 h, and it was treated with saturated
(27) Sheldrick, G. M. SHELX-97 Program for Refinement of Crystal
Structure; University of Go¨ttingen: Germany, 1997.

1996 Organometallics, Vol. 23, No. 9, 2004
Arraya´s et al.
aqueous NH4Cl (5 mL). The layers were separated, and the
aqueous layer was extracted with EtOAc (2 × 10 mL). The
combined organic layers were dried (Na2SO4) and concentrated
to dryness. The residue was purified by flash chromatography
(n-hexane-diethyl ether, 1:3) to afford 3d (72 mg, 66%) as a
green solid; [R]D -158 (c 0.1, CHCl3); mp 139-140 °C. 1H NMR
(300 MHz, CDCl3): δ 6.27 (d, J ) 7.3 Hz, 1H, OH), 5.99 (d, J
) 6.9 Hz, 1H), 5.32 (s, 1H), 5.08 (s, 1H), 4.46 (s, 5H), 4.40 (s,
5H), 4.30 (m, 4H), 1.12 (s, 9H), 1,11 (s, 9H). 13C NMR (75 MHz,
CDCl3): δ 95.0, 93.0, 82.0, 81.7, 77.4, 77.2, 74.3, 72.6, 71.4,
69.3, 69.1, 69.0, 67.5, 63.3, 57.0, 56.7, 23.9. IR (cm-1): 3279
(br), 3095 (m), 3085 (w), 1411 (m), 1076 (s), 1037 (s), 804 (m).
MS (FAB+): m/z 608 [M+, 24], 591 [M+ - OH, 64], 543 (25),
292 (42). HRMS (FAB+): cald for C29H36O3S2(56Fe)2 608.0804,
found 608.0810.
Syn th esis of Tetr a fer r ocen yl Disu lfid e 4. A solution of
bisferrocene 3a (205 mg, 3.0 mmol) in toluene (3.5 mL) was
heated at 100 °C for 2.5 h. Water (5 mL) was added, the layers
were separated, and the aqueous layer was extracted with CH2-
Cl2 (2 × 10 mL). The combined organic layers were dried (Na2-
SO4) and concentrated to dryness. The residue was purified
by flash chromatography (CH2Cl2-EtOAc, 9:1) to afford 4 (236
mg, 64%) as an orange solid; [R]D +1068 (c 0.05, CHCl3); mp
135-136 °C. 1H NMR (500 MHz, CDCl3): δ 7.57 (m, 4H), 7.51
(s, 2H, OH), 7.20 (m, 4H), 7.07 (m, 2H), 4.66 (s, 2H), 4.54 (s,
12H), 4.35 (s, 2H), 4.30 (s, 2H), 3.99 (s, 2H), 3.93 (s, 2H), 3.65
(s, 10H), 0.61 (s, 18H). 13C NMR (125 MHz, CDCl3): δ 150.3,
127.1, 126.7, 126.4, 102.4, 95.1, 88.3, 79.2, 76.2, 72.7, 71.9, 71.3,
70.7, 69.1, 68.6, 66.2, 65.7, 57.3, 23.1. IR (cm-1): 3419 (m),
3000 (s), 2980 (w), 2963 (w), 1638 (w), 1487 (m), 1469 (m), 1409
(m), 1375 (m), 1362 (m), 1106 (m), 1072 (m), 1033 (m). MS
(FAB+): m/z 1222 [M+, 2], 460 (7), 307 (34), 219 (10). HRMS
(FAB+): calcd for C62H62O4S4(56Fe)4 [M+ + H] 1222.0928, found
1222.0798.
cyclohexane (1.8 mL, 2.29 mmol). The reaction was stirred at
-78 °C for 1.5 h, and it was treated with a solution of ethyl
benzoate (396 mg, 2.64 mmol) in THF (1.0 mL). The mixture
was kept at -78 °C for 2.5 h and then treated with brine (10
mL). The two layers were separated, and the aqueous layer
was extracted with AcOEt (2 × 20 mL). The combined organic
layers were dried (MgSO4) and evaporated. The residue was
purified by flash chromatography (n-hexanes-AcOEt, 10:1) to
afford 6 as a orange solid (285 mg, 44%); [R]D +286 (c 0.1,
1
CHCl3); mp 110-111 °C. H NMR (300 MHz, CDCl3): δ 9.24
(s, 1H, OH), 7.44 (d, J ) 7.7 Hz, 2H), 7.24 (t, J ) 8.1 Hz, 2H),
7.15 (t, J ) 6.9 Hz, 1H), 4.79 (s, 1H), 4.69 (s, 1H), 4.40 (t, J )
8 Hz, 1H), 4.25 (s, 5H), 4.18 (m, 3H), 4.10 (m, 2H), 4.04 (s,
5H), 3.73 (s, 1H), 3.55 (m, 2H), 3.22 (t, J ) 9.3 Hz, 1H), 1.01
(s, 9H), 0.65 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 168.2, 166.5,
148.0, 127.6, 126.5, 126.1, 102.5, 99.8, 76.4, 75.3, 74.6, 74.0,
70.9, 70.7, 70.4, 69.7, 69.6, 69.1, 68.8, 68.4, 66.5, 65.5, 53.4,
33.4, 32.8, 26.4, 26.2. IR (cm-1): 3164 (br), 2951 (s), 1652 (s),
1638 (s), 1363 (m), 1295 (m), 1246 (m), 1202 (m), 817 (m). MS
(FAB+): m/z 727 [M+ + H, 100], 644 (14), 323 (10). HRMS
(FAB+): calcd for C41H47N2O3(56Fe)2 [M+ + H] 727.2285, found
727.2304.
Ack n ow led gm en t. Support has been provided by
the DGCIYT (projects BQU2000-0226 and BQU2003-
0508). R.G.A. thanks the MCyT for a “Contrato Ramo´n
y Cajal”. We also acknowledge the Centro de Computa-
cio´n Cient´ıfica (UAM) for access to CSD.
Su p p or tin g In for m a tion Ava ila ble: Tables of atomic
coordinates, thermal parameters, all bond distances and
angles, and experimental data for X-ray diffraction studies of
3a and 4. Copies of 1H and 13C NMR spectra of all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Bis[(S,Rp)-(5-ter t-bu tyloxazolidin yl)fer r ocen yl](ph en yl)-
m eth a n ol (6). To a solution of (S)-(5-tert-butyloxazolidinyl)-
ferrocene (587 mg, 1.89 mmol) in THF (35 mL), cooled to -78
°C, was added dropwise a 1.3 M solution of sec-BuLi in
OM049924B