Syntheses of homochiral 1,2-ferrocene-functionalized Lewis acids and acid/base pairs

Article abstract of DOI:10.1016/j.jorganchem.2011.03.026

We report a facile approach for the synthesis of homochiral 1,2-disubstituted ferrocene-functionalized Lewis acids and acid/base pairs. The synthesis is based on chiral induction facilitated by the ortho sulfinyl subsitutent in S-Fc{S(O)p-tol}, S-1, to ob

Full text of DOI:10.1016/j.jorganchem.2011.03.026

Journal of Organometallic Chemistry 696 (2011) 2528e2532
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Syntheses of homochiral 1,2-ferrocene-functionalized Lewis acids and
acid/base pairs
,
1
2
*
*
Inke Siewert , Dragoslav Vidovic , Simon Aldridge
Inorganic Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QR, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
We report a facile approach for the synthesis of homochiral 1,2-disubstituted ferrocene-functionalized
Lewis acids and acid/base pairs. The synthesis is based on chiral induction facilitated by the ortho sul-
finyl subsitutent in S-Fc{S(O)p-tol}, S-1, to obtain the key intermediate S,Sp-1,2-fc{S(O)p-tol}(BMes2),
S,Sp-2a (p-tol ¼ C6H4Me-4, Mes ¼ C6H2Me3-2,4,6). Subsequent substitution of the eS(O)p-tol substituent
in S,Sp-2a gives access to a range of enantiomerically pure Sp-1,2-ferrocene-functionalized Lewis acids
and acid/base pairs including the first homochiral 1-phosphino-2-borylferrocene. Enantiomeric excesses
(e.e.s) of >95% have typically been achieved using this methodology.
Received 1 February 2011
Received in revised form
15 March 2011
Accepted 24 March 2011
Keywords:
Lewis acid/base pair
Planar chirality
Enantioselective synthesis
Ferrocenes
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
Lewis acid/base and acids pairs. This simple synthetic approach is
also applicable to enantiomerically pure 1,2-diborylferrocenes
The planar chirality exhibited by 1,2-disubstituted ferrocenes
bearing non-identical substituents has long been exploited in
asymmetric induction [1]. Non-racemic systems of this type have
typically been accessed by ortho-lithiation chemistry directed by
a pendant chiral substituent [1e4]. Somewhat surprisingly, until
now, there have been no literature reports of enantiomerically pure
1-phosphino-2-borylferrocenes [5], despite the fact that such
intrinsically dissymmetric systems have the ability ꢀ in the pres-
ence of a suitable degree of steric shielding to function as frustrated
Lewis pairs (FLPs), a highly topical class of reagent in non-metal
based small molecule activation [6]. As part of an ongoing
program in borylferrocene chemistry [7], we therefore report
a simple two-step synthesis of compounds of this type from the
readily available precursor S-Fc{S(O)p-tol}, S-1 [4b,8,9]. Thus, we
demonstrate that the key chiral intermediate S,Sp-1,2-fc{S(O)p-
tol}(BMes2), S,Sp-2a, can be converted into a range of homochiral
systems which despite their potential for chiral anion recognition
have yet to be realised synthetically.
2. Results and discussion
Recently, we reported a versatile two-step synthesis of racemic
1,2-ferrocene-functionalized Lewis acids and acid/base pairs from
the readily available precursor 1,10-dibromoferrocene, 3 [7f].
The key step in this synthesis is the isomerisation of 1-bromo-
10-lithioferrocene in presence of tetramethylpiperidine (TMP) to
1-bromo-2-lithioferrocene, which can then be reacted with
dimesitylboron fluoride to form rac-1,2-fc(BMes2)Br, 4 (Scheme
1). A further lithiation/transmetallation reaction cascade there-
fore generates the racemic 1,2-difunctionalized ferrocenes 2 from
simple 1,10-disubstituted precursors. In the context of the current
study, we have also demonstrated that 4 can be converted into the
single diastereomer Lewis acid/base product S,Sp-1,2-fc{S(O)p-
tol}(BMes2), S,Sp-2a by employing the chiral electrophile
(1R,2S,5R)-(ꢀ)-menthyl(S)-p-toluenesulfinate.
* Corresponding authors. Tel.: þ44 0 1865 285201; fax: þ44 0 1865 272690.
E-mail addresses: inke.siewert@chemie.uni-goettingen.de (I. Siewert), simon.
aldridge@chem.ox.ac.uk (S. Aldridge).
The formation of the homochiral Lewis acid/base pair S,Sp-2a
inspired us to investigate its capability to act as a starting material
for a range of homochiral 1,2-ferrocene-functionalized Lewis acids
and acid/base pairs, by exploiting controlled substitution of the
sulfinyl substituent to yield enantiomerically pure products
[4,8,10]. S,Sp-2a is obtained in poor yield (necessarily <50%) via the
route described in Scheme 1, due to the accompanying formation of
URL: http://users.ox.ac.uk/~quee1989
Present address: Georg-August-Universität Göttingen, Institut für Anorganische
1
Chemie, Tammannstr 4, D-37077 Göttingen, Germany.
2
Present address: Division of Chemistry and Biological Chemistry, School of
Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang
Link 637371, Singapore.
0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.03.026

I. Siewert et al. / Journal of Organometallic Chemistry 696 (2011) 2528e2532
2529
Scheme 2. Synthesis of S,Sp-2a; key reagents and conditions: (i) LDA, 20 min, ꢀ78 ꢁC,
then FBMes2, ꢀ78 ꢁC, 1 h; (ii) wet, non-coordinating solvents.
Scheme 1. Synthesis of 2; key reagents and conditions: (i) nBuLi, ꢀ78 ꢁC, 30 min, then
tetramethylpiperidine, ꢀ40 ꢁC, 2 h, then FBMes2, ꢀ78 ꢁC to room temperature, over-
n
night; (ii) BuLi/N,N,N0,N0-tetramethylethylenediamine or tBuLi, ꢀ78 ꢁC, then
(1R,2S,5R)-(ꢀ)-menthyl(S)-p-toluenesulfinate, PPh2Cl or B(OEt)3 (for S,SP-2a, rac-2b
and rac-2c, respectively), ꢀ78 ꢁC to room temperature.
the latter case, the enhanced rate of hydrolysis of the conjugate acid
[rac-1,2-fc(CH2NMe2H)(BMes2)]þ (to give [rac-1,2-fc(CH2NMe2H)
{B(OH)(Mes)}]þ and mesitylene) suggests that protonation of the
pendant Lewis base function may provide a facile route for
substitution of the mesityl group [7g].
Given that the synthesis of the key homochiral intermediate
S,Sp-2a can now be established in an efficient manner, we set out to
investigate the possibility for exploiting substitution chemistry at
the sulfinyl group in the synthesis of a range of related 1,2-ferro-
cenediyl derivatives. Thus, the reaction of S,Sp-2a with tbu-
tyllithium at ꢀ78 ꢁC leads within minutes to the deep purple
lithium salt Sp-1,2-fc(Li)(BMes2), which is capable of reacting with
various electrophiles to form homochiral Lewis bifunctional acids
or acid/base pairs (Scheme 3).
The reaction of Sp-1,2-fc(Li)(BMes2) with chlorodiphenylphosphine
leads to the formation of the Lewis acid/base pair Sp-2b, the spectro-
scopic data for which are in agreement with those for rac-2b [7f].
Multinuclear NMR spectroscopy indicates a tri-coordinate boron
centre (dB ¼ 77 ppm) and the 31P chemical shift for Sp-2b is also within
the range expected for a ‘free’ (i.e. uncoordinated) triarylphosphine
the second diastereomer S,Rp-2a, which is removed by fractional
crystallization. Hence, we decided to utilize a more convenient
synthesis of S,Sp-2a, by employing a route adapted from that first
employed by Kagan and co-workers [4b]. Kagan et al. showed that
S-1 can be deprotonated diastereoselectively in the ortho position
by lithium diisopropylamide (LDA) and subsequent reactions with
P- or Si-based electrophiles generated diasteromerically pure 1,2-
fc(E){S(O)p-tol} (E ¼ Me3Si, PPh2$BH3) [4b]. By analogy with this
route we investigated the reaction of S-1 with LDA and subsequent
quenching with the B-electrophile dimesitylboron fluoride
(Scheme 2). After work up and purification, S,Sp-2a was isolated in
reasonable yield (62%) and high diastereomeric excess (d.e. >95%).
This model system was chosen to probe synthetic methodology, as
boranes of the type (aryl)BMes2 are typically of sufficient bulk to
prevent coordination of phosphine donors, and tend to be conve-
niently air and moisture stable.
S,Sp-2a is stable towards moisture and air as a solid, or as
a solution in coordinating solvents such as diethyl ether, thf or ethyl
acetate. In non-coordinating solvents such as benzene or chloro-
form traces of water lead to its decomposition to form S,Sp-1,2-fc
{S(O)p-tol}{B(OH)(Mes)}, S,Sp-5, in which one mesityl substituent
has been replaced by a hydroxyl function (Scheme 2). Character-
isation of this compound by multinuclear NMR, mass spectrometry,
elemental microanalysis and single crystal X-ray diffraction is
consistent with its formulation as S,Sp-5. The 11B chemical shift for
example, is shifted upfield (dB ¼ 48 ppm) compared to that of S,Sp-
(
dP ¼ ꢀ20.6 ppm) [13], thereby implying an ‘unquenched’ FLP formu-
lation in solution [15]. In similar fashion, the reaction of Sp-1,2-
fc(Li)(BMes2) with diphenylphosphinic chloride leads to the formation
of the corresponding phosphine oxide Sp-2d in reasonable (60%) yield
2a (dB ¼ 74 ppm) due to the
p-donor properties of the hydroxyl
group [11]. Crystals of S,Sp-5 suitable for X-ray crystallography were
obtained by slow evaporation of a saturated solution in hexane. The
result of these studies is shown in Fig. 1.
The molecular structure shows that the sulfinate
and ꢀB(Mes)(OH) groups are located in the anticipated 1- and 2-
positions and that only the Sp-isomer is present (Flack parameter
0.03). As expected, the tolyl residue orientates itself anti to the non-
substituted cyclopentadienyl ligand [4] with the consequent
alignment of the oxygen atom of the sulfinate group presumably
reflecting the origins of selectivity in the ortho-lithiation chemistry
which leads to the Sp-isomer in the previous synthetic step. The
distance between the hydrogen atom of the hydroxyl group and the
oxygen atom of the sulfinate, as well as the associated OHO-angle
are consistent with the presence of an intermolecular hydrogen
bond [d(O.H) ¼ 1.852(4) Å (cf. 2.72 Å for the sum of the van der
Waals’ radii of hydrogen and oxygen) [12], :OꢀH.O ¼ 169.8(3)ꢁ].
Evidence for the retention of such an interaction in solution is
provided by a low-field shifted resonance for the ꢀOH proton in the
1H NMR spectrum (dH ¼ 10.75 ppm). Chemically, the presence of
the sulfinyl moiety adjacent to the ꢀBMes2 group appears to
facilitate the hydrolytic cleavage of the otherwise robust mesityl
CꢀB bond (cf. the stability to moisture of FcBMes2); similar
behaviour is found for rac-1,2-fc(CH2NMe2)(BMes2). Moreover in
Fig. 1. Molecular structure of S,Sp-5 with hydrogen atoms (except H391) omitted for
clarity and thermal ellipsoids set at the 40% level. Selected bond distances (Å) and
angles (ꢁ): B(38)ꢀO(39) ¼ 1.345(7), S(49)ꢀO(50) ¼ 1.519(4), O(39)ꢀH(391) ¼ 0.813,
O(50)ꢀH(391) ¼ 1.852(4), O(50)ꢀH(391)ꢀO(39) ¼ 169.8(3).

2530
I. Siewert et al. / Journal of Organometallic Chemistry 696 (2011) 2528e2532
incorporating more electron withdrawing ꢀBR2 groups, simply by
reversing the order of borane and secondary electrophile quenching
steps. Such systems may find application in asymmetric non-metal
hydrogenation catalysts; related homochiral bifunctional Lewis
acids are under investigation with respect to applications in enan-
tioselective anion recognition.
3. Conclusions
The current investigations detail an efficient route to the versa-
tile synthetic intermediate Sp-1,2-fc{S(O)p-tol}(BMes)2, S,Sp-2a.
Furthermore, by exploiting S,Sp-2a and a range of secondary elec-
trophiles, we have established a straightforward method of gener-
ating a class of homochiral Lewis acid and acid/base pairs of the type
Sp-1,2-fc(BMes2)(E) {E ¼ ꢀPPh2, ꢀP(O)Ph2, ꢀB(OH)2, ꢀB((þ)-
pinandiolate)}. Determination of the chirality of these 1,2-difunc-
tionalized ferrocenes confirms highly selective formation of the Sp-
derivatives with enantiomeric excesses of 95% or more.
Scheme 3. Synthetic applications of S,Sp-2a; key reagents and conditions: (i) tBuLi,
5 min, then P(O)Ph2Cl, ꢀ78 ꢁC to room temperature, overnight; (ii) tBuLi, 5 min, then
PPh2Cl, ꢀ78 ꢁC to room temperature, overnight; (iii) tBuLi, 5 min, then B(OEt)3, ꢀ78 ꢁC,
1.5 h, then H2O; (iv) (þ)-pinanediol, 3 Å molecular sieves, acetone, 75 ꢁC, 32 h.
4. Experimental section
after column chromatography. Additionally, rac-2d was synthesized
from rac-4 according to Scheme 1 for the purpose of comparative chiral
HPLC analysis. Characterisation of these products by multinuclear
NMR, mass spectrometry and elemental microanalysis is consistent
with their formulation as 2d. Thus, the 31P chemical shift for 2d
4.1. General considerations and physical methods
Manipulations of air-sensitive reagents were carried out in
a glove-box, or else by means of Schlenk-type techniques involving
the use of a dry argon or nitrogen atmosphere. HPLC grade solvents
were purified, dried and degassed prior to use by a commercial
available Braun Solvent Purification System (SPS 500). The known
compounds S-1-Fc{S(O)p-tol}, S-1 [8], rac-1,2-fcBMes2(Br), rac-4
[7f], rac-fc{B(OH)2}(BMes2), rac-2d [7f], and FBMes2 [17] were
prepared according to the literature procedure. Tetramethylpiper-
idine (TMP), N,N,N0,N0-tetramethylethylenediamine (TMEDA),
chlorodiphenylphosphine (Ph2PCl), diphenylphosphinic chloride
(Ph2P(O)Cl) and triethoxyborane (B(OEt)3) were distilled and
degassed prior using and stored over 3 Å molecular sieves. 1H and
13C NMR spectra were measured on a Bruker AVII 500 FT-NMR or
Varian Mercury VX-300 spectrometer with [D]chloroform as
a solvent. The 1H and 13C NMR spectra were calibrated against the
residual proton or natural abundance 13C resonances of [D]chloro-
form (dH ¼ 7.26 ppm, dC ¼ 77.0 ppm). Mass spectra were measured
by the EPSRC National Mass Spectrometry Service Centre, Swansea
University; elemental microanalyses were carried out at London
Metropolitan University. Experimental details concerning chiral
HPLC analyses are given in the Suporting Information.
(
dP ¼ 25.3 ppm) is within the range expected for a triarylphosphine
oxide [13], and the 13C NMR spectrum shows coupling between the 31
P
nucleus and the carbon atoms of the phenyl substituents as well as
those of the cyclopentadienyl ligand. HPLC analysis of Sp-2d performed
with a Chiralcel OD column revealed an enantiomeric excess of 95%
(see Supporting Information). Interestingly, in contrast to the related
sulfinyl derivative 2a, 2d is stable towards water even in non-
coordinating solvents. Given the similar basicities reported for diaryl
sulfoxides and triarylphosphine oxides [14], it seems likely that the
greater steric demands of the phosphine oxide substituent reduce the
propensity for intramolecular processes leading to BꢀC bond breakage.
The reaction of Sp-1,2-fc(Li)(BMes2) with triethoxyborane leads to
the formation of boronic acid Sp-2c with an enantiomeric excess
higher than 95%. The spectroscopic data for Sp-2c are in agreement
with those reported for the racemic compound rac-2c [7f]. Sp-2c
forms the corresponding trimeric boroxime under anhydrous
conditions and thus could not be reliably analysed by chiral HPLC.
Hence, the corresponding pinanediol esters rac- and Sp-1,2-fc{B((þ)-
C10H16O2)}(BMes2), (þ)-2e, were synthesized and investigated by
multinuclear NMR and mass spectroscopy (Scheme 3). In particular,
the proton NMR spectrum of the diastereomeric mixture (þ)-rac-2e
shows two distinct resonances for the cyclopentadienyl CH proton
adjacent to the pinanediolate-boronic ester function in the expected
ratio of 1:1. These signals are separated by ca. 20 Hz and thus offer the
basis for determination of the diastereomeric excess by integration of
the corresponding peaks in the spectrum of (þ)-Sp-2e. It is also
noteworthy that all of the remaining 1H environments (with the
exception of that for the unsubstituted cyclopentadienyl ligand) give
rise to well resolved pairs of signals in the 1H spectrum of (þ)-rac-2e,
while the analogous spectrum of (þ)-Sp-2e shows exclusively one set
of signals (see Supporting Information). Thus, a d.e. of >95% is
demonstrated for (þ)-Sp-2e, and by implication an e.e. of >95% for
the formation of the boronic acid Sp-2c.
4.2. Syntheses
S,Sp-1,2-fc{S(O)p-tol}(BMes2), S,Sp-2a: To a solution of S-1
(400 mg, 1.23 mmol) in thf (20 mL) at ꢀ78 ꢁC was added LDA
(0.68 mL of a 2 M solution in THF/pentane, 1.35 mmol). After 20 min
at ꢀ78 ꢁC FBMes2 (473 mg,1.76 mmol), dissolved in thf (10 mL), was
added. The reaction mixture was stirred for 1 h at ꢀ78 ꢁC before
water (20 mL), ether (10 mL) and dichloromethane (20 mL) were
added. The organic layer was washed with water and brine, dried
over MgSO4 and volatiles were removed in vacuo. The resulting
orange powder was washed with hexane (7 mL) and diethyl ether
(10 mL). Yield: 440 mg (0.77 mmol, 62%) [11].
Sp-1,2-fc(PPh2)(BMes2), Sp-2b: To a solution of Sp-2a (200 mg,
0.35 mmol) in thf (15 mL) at ꢀ78 ꢁC was added tbutyllithium
(0.2 mL of a 1.6 M solution pentane, 0.35 mmol). After stirring for
5 min, chlorodiphenylphosphine (0.2 mL, 1.1 mmol) was added and
the reaction mixture warmed to ambient temperature overnight.
Subsequently water (20 mL) and diethyl ether (20 mL) were added.
The aqueous layer was extracted with diethyl ether and the organic
layer washed with water and brine, dried over MgSO4 and volatiles
The current study shows that a range of homochiral bifunctional
Lewis acids and acid/base pairs is readily available via a route
involving selective ortho direction by a sacrificial sulfinyl function.
Although the prototype FLP systems synthesized using this
approach are unlikely to be Lewis acidic enough to heterolytically
cleave H2 as they stand [16], the general synthetic methodology
should allow for the synthesis of 1,2-difunctionalized ferrocenes

I. Siewert et al. / Journal of Organometallic Chemistry 696 (2011) 2528e2532
2531
then removed in vacuo. The crude reaction mixture was purified by
column chromatography (silica gel, hexane/ethyl acetate 10:1) and
then recrystallised from minimum hexane at ꢀ30 ꢁC. Yield: 81 mg
(1.21 mmol, 38%). The spectroscopic data are in agreement with
those in literature reported for the racemic compound [7f].
gel, hexane/ethyl acetate 10:1). Yield: 164 mg (0.26 mmol, 60%).
The spectroscopic data are in agreement with those for the racemic
compound. Chiral HPLC revealed an enantiomeric excess of 95%
(see Supporting Information).
Sp-1,2-fc{B(OH)2}(BMes2), S-2c: To
a solution of S,Sp-2a
t
(250 mg, 0.43 mmol) in thf (10 mL) at ꢀ78 ꢁC was added bu-
tyllithium (0.3 mL of a 1.6 M solution pentane, 0.49 mmol). After
stirring for 5 min, triethoxyborane (0.50 mL, 2.9 mmol) was added
and the solution stirred for 1.5 h at ꢀ78 ꢁC. Subsequently water
(20 mL) and diethyl ether (20 mL) were added. The aqueous layer
was extracted with diethyl ether and the organic layer washed with
water and brine, dried over MgSO4 and volatiles then removed in
vacuo. The crude reaction mixture was purified by column chro-
matography (silica gel, hexane/ethyl acetate 5:2). Yield: 178 mg
(0.37 mmol, 87%). The spectroscopic data are in agreement with
those in literature reported for the racemic compound [7f].
(D)-2,3-pinanediol ester of rac- and Sp-2c, þ-2e: (þ)-2,3-
pinanediol (2 equiv.), 2c (1 equiv.) and 3 Å molecular sieves were
heated in acetone in a sealed tube at 75 ꢁC for 32 h. Subsequently
the reaction mixture was filtered and volatiles removed in vacuo.
Excess (þ)-pinanediol was removed by a filtration through a plug of
silica gel (hexane/ethyl acetate 20:1).
rac-1,2-fc{P(O)Ph2}(BMes2), rac-2d: To a solution of 4 (250 mg,
0.49 mmol) in thf (10 mL) at ꢀ78 ꢁC was added nbutyllithium
(0.3 mL of a 1.6 M solution pentane, 0.49 mmol) and TMEDA
(0.10 mL, 0.67 mmol). After stirring for 30 min, diphenylphosphinic
chloride (0.20 mL, 1.05 mmol) was added and the reaction mixture
warmed to ambient temperature overnight. Subsequently water
(20 mL) and diethyl ether (20 mL) were added. The aqueous layer
was extracted with diethyl ether and the organic layer washed with
water and brine, dried over MgSO4 and volatiles then removed in
vacuo. The crude reaction mixture was purified by column chro-
matography (silica gel, hexane/ethyl acetate 5:2). Yield: 225 mg
(0.35 mmol, 72%). Spectroscopic data for rac-2d: 1H NMR (300 MHz,
[D]chloroform, ꢀ40 ꢁC, ppm) dH ¼ 7.91 (m, 2H, CH of Ph), 7.50 (m,
3H, CH of Ph), 7.32 (m, 3H, CH of Ph), 7.15 (m, 2H, CH of Ph), 6.97
(s, 1H, CH of Mes), 6.71 (s, 1H, CH of Mes), 6.46 (s, 1H, CH of Mes),
5.52 (s, 1H, CH of Mes), 4.70 (m, 1H, C5H3), 4.63 (m, 1H, C5H3), 4.59
(m, 1H, C5H3), 3.90 (s, 5H, C5H5), 3.09 (s, 3H, p-CH3 of Mes), 2.37 (s,
3H, o-CH3 of Mes), 2.31 (s, 3H, o-CH3 of Mes), 1.97 (s, 3H, o-CH3 of
Mes), 1.88 (s, 3H, o-CH3 of Mes), 1.70 (s, 3H, p-CH3 of Mes). 1H NMR
(300 MHz, [D]chloroform, 20 ꢁC, ppm): dH ¼ 7.95 (m, 2H, CH of Ph),
7.49 (m, 3H, CH of Ph), 7.34 (m, 2H, CH of Ph), 7.26 (m, 1H, CH of Ph),
7.12 (m, 2H, CH of Ph), 6.48 (s br., 4H, aromatic CH of Mes), 4.68
(m, 1H, C5H3), 4.62 (m, 2H, C5H3), 3.93 (s, 5H, C5H5), 2.11 (s br., 18H,
CH3 of Mes). 13C NMR (75 MHz, [D]chloroform, 20 ꢁC, ppm):
dC ¼ 137.9 (br., p-Cquart of Mes), 135.0 (J ¼ 103.8 Hz, Cquart of Ph),
133.3 (J ¼ 104.8 Hz, Cquart of Ph), 131.0 (J ¼ 2.8 Hz, p-Cquart of Ph),
130.6 (J ¼ 9.1 Hz, CH of Ph), 129.7 (J ¼ 2.8 Hz, p-CH of Ph), 129.5
(J ¼ 9.6 Hz, CH of Ph),128.1 (J ¼ 11.6 Hz, CH of Ph),127.8 (CH of Mes),
127.4 (J ¼ 12.2 Hz, CH of Ph), 95.6 (br., CCp-P(O)Ph2), 82.2
(J ¼ 12.0 Hz, C5H3), 75.0 (J ¼ 16.2 Hz, C5H3), 72.6 (J ¼ 10.4 Hz, C5H3),
70.9 (C5H5), 23.6 (br., o-CH3 of Mes), 20.9 (p-CH3 of Mes), boron-
bound quaternary carbon atoms of the mesityl groups not
Spectroscopic data for Sp-1,2-fc{B((D)-C10H16O2)}(BMes2),
(þ)-Sp-2e: 1H NMR (500 MHz, [D]chloroform, 20 ꢁC, ppm):
dH ¼ 6.71 (s, 4H, CH9 of Mes), 4.84 (q, 1H, J ¼ 1.2 Hz, CH3), 4.66 (dt,
1H, J ¼ 0.8, 2.3 Hz, CH2), 4.56 (q, 1H, J ¼ 1.2 Hz, CH1), 4.13 (s, 5H,
CH5), 3.89 (dd, 1H, J ¼ 1.3, 8.4 Hz, CH12), 2.25 (s, 7H, CH7 and CH18),
2.15 (s, 13H, CH6 and CH16), 1.87 (m, 1H, CH16), 1.80, (m, 3H, CH17,
CH18, CH15, 1.23 (1, 3H, CH21), 1.18 (s, 3H, CH14), 0.78 (s, 3H, CH20).
13C NMR (125 MHz, [D]chloroform, 20 ꢁC, ppm): dC ¼ 143.7 (C11),
139.5 (C10), 137.0 (C8), 127.7 (C9), 85.7 (C1), 85.3 (C13), 78.2 (C3), 77.5
(C12), 73.7 (C2), 70.5 (C5), 51.2 (C17), 39.5 (C17), 38.0 (C19), 35.4 (C18),
28.4 (C14), 27.1 (C21), 25.9 (C16), 24.0 (C10), 23.6 (C6), 21.0 (C7). 11
B
(96 MHz, [D]chloroform, 20 ꢁC, ppm): dB ¼ 91 (BMes2), 39 (B(OR)2).
MS (ESIþ): exact mass (calc. for M þ Naþ, 11B isotopomer) 635.29,
(meas.) 625.35 (100%), exact mass (calc. for M þ Kþ, 11B isotopomer)
651.27, (meas.) 651.32 (100%). Spectroscopic data for (þ)-Rp-2e,
assigned from the racemic mixture: 1H NMR (500 MHz, [D]chlo-
roform, 20 ꢁC, ppm): dH ¼ 6.69 (s, 4H, CH9), 4.80 (q, 1H, J ¼ 1.2 Hz,
CH3), 4.66 (dt, J ¼ 0.8, 2.3 Hz, CH2), 4.54 (q, 1H, J ¼ 1.1 Hz, CH1), 4.15
(dd, 1H, J ¼ 1.4, 7.1 Hz, CH12), 4.13 (s, 5H, CH6), 2.22 (s, 6H, CH6), 2.13
(s, 13H, CH7 and CH16), 2.00 (m, 2H, CH16, CH18), 1.91 (m 1H, CH15),
1.67 (m, 1H, CH17), 1.26 (s, 3H, CH21), 1.20 (s, 3H, CH14), 0.79 (s, 3H,
CH20). 13C NMR (125 MHz, [D]chloroform, 20 ꢁC, ppm): dC ¼ 143.712
(C11), 139.459 (C10), 137.0 (C8), 127.7 (C9), 86.2 (C1), 85.1 (C13), 78.7
(C3), 77.6 (C12), 73.4 (C2), 70.1 (C5), 51.1 (C15), 39.6 (C17), 38.0 (C19),
34.6 (C18), 28.7 (C14), 27.1 (C21), 26.3 (C16), 24.0 (C10), 23.6 (C6), 21.0
(C7). 11B (96 MHz, [D]chloroform, 20 ꢁC, ppm): dB ¼ 91 (BMes2), 39
(B(OR)2).
observed. 31P (121 MHz, [D]chloroform, 20 ꢁC, ppm): dP ¼ 25.3. 11
B
S,Sp-fc{S(O)p-tol}{BOH(Mes)}, S,Sp-5: S,Sp-2a (80 mg,
0.14 mmol) was dissolved in 10 mL of wet chloroform. The solution
was stirred for 5 h at ambient temperature and volatiles then
removed in vacuo. The yellow residue was dissolved in hot hexane,
filtered and stored at 4 ꢁC, whereupon S,Sp-5 precipitated as yellow
needles within 2 h. The crystals were washed with cold hexane and
dried in vacuo (56 mg, 12 mmol). Yield: 85% (52 mg, 0.11 mmol).
Crystals suitable crystals for X-ray crystallography were obtained
by slow evaporation of a saturated solution of S,Sp-5 in hexane.
Spectroscopic data for S,Sp-5: 1H NMR (500 MHz, [D]chloroform,
20 ꢁC, ppm): dH ¼ 10.75 (s, 1H, BOH), 7.43 (d, J ¼ 8.3 Hz, 2H, CH of
Tol), 7.19 (d, J ¼ 8.1 Hz, 2H, CH of Tol), 6.72 (s br, 2H, CH of Mes), 5.02
(m, 1H, C5H3), 4.54 (m, 1H, C5H3), 4.49 (s, 5H, C5H5), 4.10 (m, 1H,
C5H3), 2.34 (s br., 3H, o-CH3 of Mes), 2.33 (s, 3H, p-CH3 of Tol), 2.24
(s, 3H, p-CH3 of Mes) and 1.48 (s br., 3H, o-CH3 of Mes). 13C NMR
(125 MHz, [D]chloroform, 20 ꢁC, ppm): dC ¼ 141.7, 140.8 (Cquart of
(96 MHz, [D]chloroform, 20 ꢁC, ppm): dB ¼ 87. MS (ESIþ): exact
mass (calc. for M-Mesꢂ, 11B isotopomer) 515.1398, (meas.) 515.1378
(100%), exact mass (calc. for M þ Hþ, 11B isotopomer) 635.2332,
(meas.) 635.2318 (10%). Elemental microanalysis: (calc. for
C40H40BFeOP) C 75.73, H 6.36, (meas.) C 75.88, H 6.46%.
Sp-1,2-fc{P(O)Ph2}(BMes2), Sp-2d: To a solution of S,Sp-2a
t
(250 mg, 0.43 mmol) in thf (10 mL) at ꢀ78 ꢁC was added bu-
tyllithium (0.27 mL of a 1.6 M solution in pentane, 0.43 mmol). After
stirring for 5 min, diphenylphosphinic chloride (166 mL, 0.87 mmol)
was added and the reaction mixture warmed to ambient temper-
ature overnight. Subsequently water (20 mL) and diethyl ether
(20 mL) were added. The aqueous layer was extracted with diethyl
ether and the organic layer was washed with water and brine, dried
over MgSO4 and volatiles were then removed in vacuo. The crude
reaction mixture was purified by column chromatography (silica

2532
I. Siewert et al. / Journal of Organometallic Chemistry 696 (2011) 2528e2532
Tol), 139.4 (br., o-Cquart of Mes), 137.2 (p-Cquart of Mes), 129.6 (CH of
Tol), 127.1 (CH of Mes), 124.1 (CH of Tol), 99.7 (CCp-S(O)p-tol) 79.1,
74.2, 72.8 (C5H3), 70.8, (C5H5), 21.9 (br., o-CH3 of Mes), 21.2 (p-CH3
of Tol), 21.1 (p-CH3 of Mes), boron-bound quaternary carbons not
(b) D. Marquarding, H. Klusacek, G. Gokel, P. Hoffmann, I. Ugi, Angew. Chem.
Int. Ed. Engl. 9 (1970) 371e372.
[3] For ortho-lithiation of ferrocenes bearing an acetal substituent see, for
example (a) O. Riant, O. Samuel, H.B.J. Kagan, J. Am. Chem. Soc. 115 (1993)
5835e5836;
observed. 11B (96 MHz, [D]chloroform, 20 ꢁC, ppm):
d
¼ 49. MS
(b) O. Riant, O. Samuel, T. Flessner, S. Taudien, H.B.J. Kagan, J. Org. Chem. 62
(1997) 6733e6745.
(ESIþ): exact mass (calc. for M-Mesꢂ, 11B isotopomer) 351.0313,
(meas.) 351.0315 (100%), exact mass (calc. for M þ Hþ, 11B iso-
topomer) 471.1252, (meas.) 471.1250 (70%). Elemental microanal-
ysis: (calc. for C26H27BFeO2S) C 66 41, H 5.79; (meas.) C 66.36,
H 5.81%. Crystallographic data for S,Sp-5: C26H27BFeO2S, Ortho-
rhombic, P 212121, a ¼ 8.7249(3), b ¼ 23.1012(7), c ¼ 24.1762(8) Å,
V ¼ 4872.9(3) Å3, Z ¼ 8, Dx ¼ 1.282 Mg mꢀ3, Mr ¼ 470.22, T ¼ 150(2)
K. 25,210 reflections collected, 8921 independent [R(int) ¼ 0.074];
R1 ¼ 0.0613, wR2 ¼ 0.1051 for observed unique reflections
[4] For ortho-lithiation of ferrocenes bearing
a sulfinyl substituent see, for
example (a) F. Rebiere, O. Riant, L. Ricard, H.B. Kagan, Angew. Chem. Int. Ed.
Engl. 32 (1993) 568e570;
(b) O. Riant, G. Argouarch, D. Guillaneux, O. Samuel, H.B. Kagan, J. Org. Chem.
63 (1998) 3511e3514.
[5] To our knowledge the only spectroscopic report of a 1,2-derivatized ferrocene
system featuring boron and phosphorus functionalities is that of a oxaza-
phospholidene oxide: D. Vinci, N. Mateus, X. Wu, F. Hancock, A. Steiner, J. Xiao
Org. Lett. 8 (2006) 215e218.
[6] For a recent review of frustrated Lewis pairs, see: D.W. Stephan, G. Erker
Angew. Chem. Int. Ed. 49 (2010) 56e76.
[7] (a) C. Bresner, S. Aldridge, I.A. Fallis, C. Jones, L.-L. Ooi, Angew. Chem. Int. Ed.
44 (2005) 3606e3609;
[I > 2
s
(I)]; R1 ¼ 0.1026, wR2 ¼ 0.1256 for all unique reflections.
Goodness of fit ¼ 0.9466, max. and min. residual electron densities:
(b) C. Bresner, J.K. Day, N.D. Coombs, I.A. Fallis, S. Aldridge, S.J. Coles,
M.B. Hursthouse, Dalton Trans. (2006) 3660e3667;
(c) J.K. Day, C. Bresner, I.A. Fallis, L.-L. Ooi, D.J. Watkin, S.J. Coles, L. Male,
M.B. Hursthouse, S. Aldridge, Dalton Trans. (2007) 3486e3488;
(d) J.K. Day, C. Bresner, N.D. Coombs, I.A. Fallis, L.-L. Ooi, R.W. Harrington,
W. Clegg, S. Aldridge, Inorg. Chem. 47 (2008) 793e804;
0.85 and ꢀ0.70 e Å3. Flack parameter: 0.03(2).
Acknowledgements
(e) A.E.J. Broomsgrove, D. Addy, C. Bresner, I.A. Fallis, A.L. Thompson,
S. Aldridge, Chem. Eur. J. 14 (2008) 7525e7529;
(f) I.R. Morgan, A. Di Paolo, D. Vidovic, I.A. Fallis, S. Aldridge, Chem. Commun.
(2009) 7288e7290;
(g) A.E.J. Broomsgrove, D. Addy, A. Di Paolo, I.R. Morgan, C. Bresner, V. Chislett,
I.A. Fallis, A.L. Thompson, D. Vidovic, S. Aldridge, Inorg. Chem. 49 (2010)
157e173;
We thank the EPSRC for funding and for access to the National
Mass Spectrometry Service Centre, Swansea University. We are
thankful to Matthew Tredwell for performing the chiral HPLC
measurements and the helpful discussion and advice. IS is grateful
to the DFG for financial support.
(h) I.R. Morgan, A.E.J. Broomsgrove, P. Fitzpatrick, D. Vidovic, A.L. Thompson,
I.A. Fallis, S. Aldridge, Organometallics 29 (2010) 4762e4765;
(i) C. Bresner, D.A. Haynes Addy, A.E.J. Broomsgrove, P. Fitzpatrick, D. Vidovic,
A.L. Thompson, I.A. Fallis, S. Aldridge, New J. Chem. 34 (2010) 1652e1659.
[8] H.K. Cotton, F.F. Huerta, J.-E. Bäckvall, Eur. J. Org. Chem. 15 (2003) 2756e2763.
[9] The Schlögel nomenclature is used to describe the planar chirality at the 1,2-
disubstituted ferrocenes (a) K. Schlögl, Monatsh. Chem. 95 (1964) 576;
(b) K. Schlögl, Top. Stereochem 1 (1967) 39.
Appendix A. Supplementary material
Proton NMR spectra of 3e and detailed information about the
procedure of the chiral HPLC as well as the resulting spectra are
provided in the electronic supplementary material of this article.
Full details of the structure determination (except structure factors)
have been deposited with the Cambridge Crystallographic Data
Centre as CCDC 810592. Copies of this information may be obtained
free of charge from The Director, CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: þ44 1223 336 033; e-mail: deposit@ccdc.cam.ac.
uk or www: http://www.ccdc.cam.ac.uk).
[10] Further examples (a) M. Lotz, K. Polborn, P. Knochel, Angew. Chem. Int. Ed. 41
(2002) 4708e4711;
(b) H.L. Pedersen, M. Johannsen, Chem. Commun. (1999) 2517e2518.
[11] Corrected NMR data for S,Sp-2a [7f]: 1H NMR (500 MHz, [D]chloroform, 20 ꢁC,
ppm):
d
H ¼ 7.54 (d, 2H, J ¼ 8.2 Hz, CH of Tol), 7.24 (2H, overlaps with CDCl3
signal, CH of Tol), 6.73 (s, 4H, CH of Mes), 4.61 (m, 2H, C5H3), 4.43 (t, J ¼ 1.5 Hz,
1H, C5H3), 4.12 (s, 5H, C5H5), 2.41 (s, 3H, p-CH3 of Tol), 2.32 (s, 12H, o-CH3 of
Mes), 2.24 (s, 6H, p-CH3 of Mes). 13C NMR (75 MHz, [D]chloroform, 20 ꢁC,
ppm):
d
C ¼ 140.8, 140.1 (Cquart of Tol), 139.8 (o-Cquart of Mes), 137.3 (p-Cquart
of Mes), 129.0 (CH of Tol), 128.1 (CH of Mes), 125.1 (CH of Tol), 100.5 (CCp-S(O)
p-tol), 80.4, 72.8, 71.8 (C5H3), 71.2, (C5H5), 24.6 (br, o-CH3 of Mes), 21.4 (p-CH3
of Tol), 21.0 (p-CH3 of Mes), boron-bound quaternary carbons not observed.
Appendix. Supplementary data
11B (96 MHz, [D]chloroform, 20 ꢁC, ppm):
[12] A. Bondi, J. Phys. Chem. 68 (1964) 441e451.
dB ¼ 74.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.jorganchem.2011.03.026.
[13] L.D. Quin, J.G. Verkade, Phosphorus-31 NMR Spectral Properties in
Compound Characterization and Structural Analysis. Wiley-VCH, Chichester,
1994.
References
[14] (a) pKa(Ph2SOHþ) ¼ ꢀ2.54; pKa(Ph3POHþ) ¼ ꢀ2.10 in aqueous media. See:
D. Landini, G. Modena, G. Scorrano, F. Taddei J. Am. Chem. Soc. 91 (1969)
6703e6707;
[1] See for example (a) T.J. Colacot, Chem. Rev. 103 (2003) 3101e3118;
(b) F. Benoit, H.B. Kagan, Adv. Synth. Catal. 349 (2007) 493e507;
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Chichester, 2008;
(d) L. Dai, X.L. Hou (Eds.), Chiral Ferrocenes in Asymmetric Catalysis: Synthesis
and Application, Wiley, Chichester, 2009.
[2] For ortho-lithiation of (N, N-dimethylamino)methyl ferrocene (Ugi’s amine)
see, for example (a) D. Marquarding, H. Klusacek, G. Gokel, P. Hoffmann, I. Ugi,
J. Am. Chem. Soc. 92 (1970) 5389e5393;
(b) E.M. Arnett, E.J. Mitchell, T.S.S.R. Murty, J. Am. Chem. Soc. 96 (1974)
3875e3891.
[15] The enantiomeric excess of the product could not be determined due to its
very low polarity.
[16] G.C. Welch, D.W. Stephan, J. Am. Chem. Soc. 129 (2007) 1880e1881.
[17] J.J. Eisch, B. Shafii, J.D. Odom, A.L. Rheingold, J. Am. Chem. Soc. 112 (1990)
1847e1853.