Synthesis of planar chiral ferrocenyl cyclopentadienyl chelate ligand precursors

Article abstract of DOI:10.1016/j.tetasy.2013.07.006

Two families of planar chiral ferrocenyl cyclopentadienyl chelate ligands for use in ansa-half sandwich metallocene complexes of catalytically active transition metals are described. The first family was derived in 4-5 steps from an enzymatic resolution of 1-iodo-2-(methylalcohol)ferrocene and possesses a cyclopentadiene derivative [Cp(H) = 1-indenyl, 2-indenyl or Ph₄Cp(H)] directly attached to the ferrocene ring with an adjacent vicinal tether CH ₂Z donor group (Z = OH, OMe, NHMe, NMe₂ or PPh ₂). The second family was derived from a chiral auxiliary approach and has the donor group (Z = PPh₂ or NMe₂) attached directly to the ferrocene ring with an adjacent tether vicinal CH ₂Cp(H) group [Cp(H) = Cp(H), fluorenyl, 1-indenyl, Me ₄Cp(H) or Ph₄Cp(H)].

Full text of DOI:10.1016/j.tetasy.2013.07.006

Tetrahedron: Asymmetry 24 (2013) 1023–1034
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of planar chiral ferrocenyl cyclopentadienyl chelate ligand
precursors
⇑
James C. Anderson , Helen Grounds, György Szalóki
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Two families of planar chiral ferrocenyl cyclopentadienyl chelate ligands for use in ansa-half sandwich
metallocene complexes of catalytically active transition metals are described. The first family was derived
in 4–5 steps from an enzymatic resolution of 1-iodo-2-(methylalcohol)ferrocene and possesses a cyclo-
pentadiene derivative [Cp(H) = 1-indenyl, 2-indenyl or Ph4Cp(H)] directly attached to the ferrocene ring
with an adjacent vicinal tether CH2Z donor group (Z = OH, OMe, NHMe, NMe2 or PPh2). The second family
was derived from a chiral auxiliary approach and has the donor group (Z = PPh2 or NMe2) attached
directly to the ferrocene ring with an adjacent tether vicinal CH2Cp(H) group [Cp(H) = Cp(H), fluorenyl,
1-indenyl, Me4Cp(H) or Ph4Cp(H)].
Received 10 June 2013
Accepted 9 July 2013
Available online 13 August 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
ral pocket around the metal centre. The success of these ap-
proaches has been limited and we postulate that a planar chiral
The development of ligand architecture has had a huge effect on
the catalytic activity of some metals. Chelation of cyclopentadienyl
ligands with a pendant donor atom to certain transition metals
leads to ansa-half sandwich metallocene complexes (Fig. 1). This
ferrocene linker could project a more effective chiral environment
around a catalytically active ansa-half sandwich metallocene.
The superiority of the planar chiral element in ferrocenyl de-
rived ligands, above that of centres of chirality, for the transmis-
sion of asymmetry in chemical reactions has been well
documented.11–15 Purely planar chiral ferrocenes have been less
well investigated,16–22 possibly due to the challenges associated
with their enantioselective syntheses compared to the multitude
of diastereoselective approaches that start, for example, with the
ubiquitous Ugi N,N-dimethyl-1-ferrocenylethylamine that lead to
bidentate Josiphos type ligands.23–25 In our own work, we have
used the Snieckus approach of sparteine mediated enantioselective
directed ortho metallation of N,N-diisopropyl ferrocenecarboxa-
mide26 to access a series of N–P, N–N, N–O and N–S planar chiral
ferrocene chelate ligands (Fig. 2).27,28 In addition we have also syn-
thesised asymmetric chelate ligands via the sparteine mediated
lithiation of the C-2 position of 1,2,3,4,5-pentamethylazaferrocene
(Fig. 2).29
MLn = Metal
L = Linker
Z = Donor
L
MLn
Z
Figure 1. ansa-half sandwich metallocene.
unusual ligand may confer enhanced catalytic activity, due in part
to the inertness of the cyclopentadienyl ligand and the tuning
available from the donor atom, the first example of which was doc-
umented for
a
-olefin polymerisation.1 There are a number of re-
views on the many examples of cyclopentadienyl metal
complexes bearing pendant phosphorus/sulfur/arsenic,2 oxygen3
and amine4 donors. A wide variety of metals have been used and
the number of ansa-half sandwich metallocenes in the literature
is ever increasing. However, there are relatively few examples of
chiral ansa-half sandwich metallocene complexes being used in
asymmetric catalysis.5–10 Chirality is most often conferred on the
complex by centres of chirality present between the chelating
cyclopentadienyl and donor atom groups that help to create a chi-
Fe
NR2
N
N
N
Fe
Z
Fe
PPh2
Ph
Fe
Ph
Z = N,O,P,S
⇑
Corresponding author. Tel.: +44 (0)20 7679 5585.
E-mail address: j.c.anderson@ucl.ac.uk (J.C. Anderson).
Figure 2. Planar chiral bidentate ligands based on ferrocene.
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.07.006

1024
J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
In extending these studies we wished to use a planar chiral fer-
mer is formed (isomers due to the axis of chirality in the inden-1-yl
group) (Fig. 4). The atropisomerism associated with the inden-1-yl
group may aid the selectivity of the metal catalyst. The symmetri-
cal nature of the inden-2-yl functionality in metal complexes
would allow this effect to be investigated.
rocene unit to control the asymmetry of a potential chelate ansa-
half sandwich metallocene. We were aware of only one example
of this type of asymmetric scaffold in the literature, but the two
complexes were not catalytically active (Fig. 3).30
Z
Z
Fe
Fe
MLn
MLn
Fe
Fe
1
2
Ru
Rh
Cl
PPh2
CO
P
P
Ph2
Ph2
Figure 3. Planar chiral ferrocene ansa-half sandwich metallocene.
Figure 4. Potential coordination of indenyl ligands to a metal centre.
2.1. Introduction of chirality
Conceptually, in order to design catalysts for the stereocon-
trolled formation of new
r-bonds to a pro-chiral molecule, we re-
Our attempts to incorporate a cyclopentadienyl type ligand di-
rectly to one of the ferrocene rings using Snieckus’ approach of di-
rected ortho-metallation of ferrocenecarboxamides,26 could be
employed to synthesise the racemic ligands (using TMEDA and di-
rect reaction with 1-indanone) but the asymmetric reaction using
(ꢀ)-sparteine was unsuccessful. The synthesis of the correspond-
ing iodide, and subsequent halogen–lithium exchange and reaction
with 1-indanone allowed the incorporation of a Cp group. How-
ever, chemical manipulation of the resultant tertiary amide to use-
ful functional groups proved problematic. This, coupled with the
fact that the (ꢀ)-sparteine methodology formally delivers only
one enantiomer31 led us to consider an alternative approach that
relied on halogen lithium exchange of an enatiomerically pure ferr-
ocenyl halide. It was known that ( )-alcohol 7 can be resolved
using a lipase enzyme (from Candida Antarctica) and vinyl acetate
to give (pS)-acetate 8 (98% ee) and remaining (pR)-alcohol 7 (95%
ee, >99% after recrystallisation from pet. ether).32 In our hands
the immobilised enzyme could be reused (at least 3 times) with
no noticeable decrease in enantioselectivity and the reaction could
be performed on at least a 50 g scale (Scheme 2). It was found that
the quantity of enzyme and amount of DCM used could be greatly
reduced from the procedure reported in the literature.
quire a chiral metal possessing 4 quadrants of differing size (1,
Scheme 1), with only one side of the metal available for binding.
Upon coordination of a prochiral substrate to the available face
of the metal, the least sterically congested complex 2 should result.
With the prochiral face of the unsaturated system differentiated,
addition of H–Nu (Nu = NR2, SiR3, BR2, CN), will form new stereo-
centres 3 in a controlled fashion. To harness the high configura-
tional metal–ligand stability of the cyclopentadienyl ligand, and
open up the metal centres coordination sphere, we set out to syn-
thesise a new class of planar chiral ferrocenyl chelate ligands 4
containing a cyclopentadienyl group tethered to a donor ligand
with the planar chiral ferrocene controlling the desired topology
5. The planar chiral ferrocene ligand links three quadrants, making
the metal M chiral and differentiates which face of the metal is
available for further coordination. The stabilising effect of the
cyclopentadienyl (Cp) ring and donor atoms Z on the catalytically
active metal centre M and any coordinated reactive intermediates
or products may enhance catalytic transformations at the metal
centre M. A variant of this ligand system 6 can also be envisaged.
Herein we report the syntheses of some enantiomerically pure
chelate ligands 4, which rely upon an enzymatic resolution to
produce either enantiomer of the desired ligands. We also report
the synthesis of an example of ligand 6 which uses directed
ortho-metallation methodology from a chiral acetal attached to
ferrocene.
OAc
I
I
I
OH
OH
Novozym 435
CH2Cl2, 45 oC,
vinyl acetate
Fe
Fe
Fe
+
2. Results and discussion
Initially both the inden-1-yl and inden-2-yl groups were exam-
ined as it was thought that when the inden-1-yl group is bonded to
a metal, the bulky ferrocene group should dictate that only one iso-
(pR)-7, 38%
(pS)-8, 49%
( )-7
Scheme 2. Resolution of ( )-7.
R
S
S
X
R
HX Nu
H
Nu
R'
L
X
M
L
M
R'
R
Nu =
H, NR2, SiR3,
BR2, CN
X = CH2, O, NR
R'
3
M
M
2
1
Z
Z
ferrocene
Cp
Fe
Fe
M
MLn
MLn
Z
6
Cp
4
5
Scheme 1. Design concept.

J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
1025
2.2. Cyclopentadiene type compounds with an oxygen donor
group
OTIPS
OMe
The addition of both the 1-indenyl group (by halogen–lithium
HCl(aq)/
MeOH
Fe
Fe
exchange followed by addition of 1-indanone) and the 2-indenyl
groups (by Negishi cross coupling of 2-bromoindene) was found
to give the highest yields when a non-coordinating substituent
was present on the pseudo-benzylic position (Cp(H)CH2–) of the
donor side chain. An array of compounds were synthesised where
the hydroxyl/acetate group of 7/8 was converted into a range of
donor substituents (N, O or P). The highest yields of the addition
were seen when using TIPS ether 9 (Scheme 3). This may be be-
cause the less bulky groups are able to coordinate to lithium and
make it less reactive and/or are too basic to react with ketones as
well as inhibiting the lithium–zinc transmetallation needed for
Negishi cross-coupling reactions. This was supported by the fact
that no starting material remained at the end of the halogen lith-
ium exchange reactions, with only the proton quenched material
isolated in optimisation experiments. The addition of 1-indanone
to (pR)-9, after halogen–lithium exchange of the iodide, gave the
resultant alcohol (pR)-10 in 98% yield. Dehydration of the alcohol
was achieved by conversion to the mesylate and addition of DIPEA
to give (pS)-11 in 97% yield. The hindered TIPS silyl ether also
proved to be the best substrate for the Negishi cross-coupling of
2-bromoindene to give (pS)-12 in 75% yield (Scheme 3). The 2-
indenyl substituted TIPS ether 12 proved to be much more stable
than the corresponding 1-indenyl compound 11 under acidic con-
ditions. This added stability may be due to the fact that in the 1-
indenyl ligands there is a doubly benzylic position between the
aromatic ring of the indenyl group and the ferrocene Cp ring which
may stabilise any incipient carbocation character. The tetraphenyl-
cyclopentadiene group could be introduced by the reaction of tet-
raphenylcyclopentadienone with 9, after halogen–lithium
exchange, to give alcohol 13 in 80% yield. Reduction using LiAlH4
(2 equiv) gave (pS)-14, albeit in low yield (20%). A range of other
reducing conditions were investigated but all led to degradation
(pS)-11
(pS)-16, 85%
OTIPS
OAc
Fe
AcOH/H2O
THF
Fe
(pS)-11
(pS)-17, 92%
OAc
OH
Fe
Fe
NaOMe/MeOH
Et2O, rt
(pS)-17
(pS)-18, 99%
Scheme 4. Synthesis of 1-indenyl oxygen chelate ligands.
of the substrate. However, increasing the amount of LiAlH4 used
to 20 equiv surprisingly gave alcohol (pS)-15 in 60% along with
(pS)-14 in 20% isolated yield.
All standard conditions for the removal of the TIPS group from
the 1-indenyl compound, to give the alcohol, resulted in degrada-
tion or, under acidic conditions, substitution of the OTIPS group.33
I
HO
i) nBuLi, Et2O
-78oC
OTIPS
OTIPS
OTIPS
MsCl, DIPEA,
CH2Cl2
Fe
Fe
Fe
ii) 1-indanone
(pR)-9
(pR)-10, 98%
(pS)-11, 97%
i) nBuLi, THF, -78 o
C
I
OTIPS
ii) ZnCl2, -78 oC to rt
iii) PdCl2(PPh3)2
DIBAL, reflux
OTIPS
Fe
Fe
iv) 2-bromoindene
(pR)-9
(pS)-12, 75%
Ph
Ph
Fe
Ph
Ph
Ph
Ph
Ph
Ph
Ph
HO
Ph
H
Ph
I
Ph
H
i) nBuLi, Et2O
OTIPS
OTIPS
OH
OTIPS
-78 oC
O
LiAlH4 (20 eq)
THF
Fe
Fe
Fe
ii)
Ph
Ph
(pR)-9
(pR)-13, 80%
(pS)-15, 60%
(pS)-14, 20%
Ph
Ph
Scheme 3. Addition of cyclopentadiene type groups.

1026
J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
No examples of this deprotection reaction for OTIPS ether at the a-
position of a ferrocene compound exist in the literature. Both the
methyl ether (pS)-16 (85% yield) using aqueous HCl and MeOH,
and acetate, (pS)-17 (92% yield) using aqueous acetic acid in THF,
were synthesised presumably by substitution of the –OTIPS group
(Scheme 4). Subsequent basic hydrolysis of acetate 17 gave alcohol
(pS)-18 (99%).
NMeR1
OTIPS
i) TMSCl
Fe
Fe
ii) HNMeR1 (10 eq)
2.3. Cyclopentadiene type compounds with a nitrogen donor
group
(pS)-19, R1 = Me, 92%
(pS)-20, R1 = H, 89%
(pS)-12
It was found that the 2-indenyl amine compounds could be di-
rectly synthesised by the addition of TMSCl to TIPS ethers and sub-
sequent transfer of the reaction mixture onto an excess of the
amine (Scheme 5). Both the dimethylamine 19 and methylamine
20 compounds were synthesised by this route. The direct addition
of the amine to the reaction mixture led to the formation of dimers.
The use of these conditions with the 1-indenyl TIPS ether 11 led to
degradation, presumably due to the sensitivity of the 1-indenyl
compounds to the formation of a doubly benzylic stabilised carbo-
cation in the presence of an acid. Conversion of the alcohol into the
mesylate and subsequent reaction with an excess of the amine
gave the desired dimethylamino 21 and methylamino 22 com-
pounds. The use of a hindered base such as DIPEA was essential
as when less hindered bases such as triethylamine were used the
corresponding quaternary amine salt was produced. Amine nucle-
ophiles added in situ did not displace the triethylamine. The tetra-
phenylcyclopentadiene amine compounds 23 and 24 were
synthesised in a similar manner from the alcohol 15, although
these compounds could not be separated from small amounts of
remaining starting material.
NMeR1
OH
i) MsCl, DIPEA
Fe
Fe
ii) HNMeR1 (10 eq)
(pS)-21, R1 = Me, 85%
(pS)-22, R1 = H, 75%
(pS)-18
Ph
Ph
Ph
Ph
H
Ph
Ph
Ph
H
Ph
NMeR1
OH
Fe
i) TMSCl
Fe
ii) HNMeR1 (20 eq)
(pS)-23, R1 = Me,> 75%
(pS)-24, R1 = H, > 85%
(pS)-15
2.4. Cyclopentadiene type compounds with a phosphorus donor
group
Scheme 5. Synthesis of Cp(H) type nitrogen chelate ligands.
phine and 2 equiv of an electrophile but these require the presence
of a base and in our case an excess of phosphine was used.37,38
The synthesis of the tetraphenylcyclopentadiene compound
proved much more straightforward and could be synthesised from
the alcohol 15 using analogous conditions similar to the synthesis
of the amine ligands (Scheme 7).
The most common phosphino ansa half sandwich metallocenes
in the literature, with a similar tether length to our compounds,
utilise a diphenylphosphine group to coordinate to the metal
(Fig. 3).2 The synthesis of the 1-indenyl phosphine compound
was unsuccessful despite attempting a range of conditions previ-
ously employed for the synthesis of a-substituted ferrocene com-
pounds including the conditions employed for the amino
compounds; refluxing the acetate 17 in acetic acid with diphenyl-
phosphine,23 the use of BH3ꢁPPh2H as a nucleophile,34 via a qua-
2.5. Donor group directly attached to the ferrocene Cp ring
In addition to the compounds above the donor group and Cp(H)
group could be reversed, that is, the Cp(H) group is tethered to the
ferrocene Cp ring with a CH2 linker and the donor group is attached
directly onto the ferrocene Cp ring (see 6, Scheme 1). There is only
one example of a similar ligand in the literature (Fig. 3) where in
addition to the planar chirality of the molecule, there is also a
ternised amine35 or via an -carbocation.36 Complete degradation
a
or recovery of the starting material was observed in these cases.
Similar results were seen in the attempted synthesis of the 2-inde-
nyl phosphine compound; however, when diphenylphosphine was
added to the quaternary amine salt 25, an unusual phosphine
bridged ferrocene dimer 26 was observed (Scheme 6). It is unclear
why the phosphonium cation forms in preference to the 3-coordi-
nate diphenylphosphine. Only a handful of examples exist where a
phosphonium cationic species is synthesised from diphenylphos-
stereogenic centre at the
a-position adjacent to the ferrocene Cp
ring.30 This ligand has been complexed to rhodium or ruthenium
and used in a reconstitutive condensation reaction. The synthesis
of an analogous compound without this stereogenic centre would
Fe
Ph
HPPh2,
MeCN,
reflux
NMe2
MeI,
NMe3I
P
Fe
Fe
Fe
Ph
acetone
(pS)-25, 91%
(pS,pS)-26, 81%
(pS)-19
Scheme 6. Formation of the phosphonium dimer.

J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
1027
Ph
O
Ph
Fe
Cp*
Ph
Ph
PPh2
diene,
NaH, THF
reflux
Ph
Ph
Fe
PPh2
Fe
H
Ph
H
Ph
i) TMSCl
PPh2
OH
(pS)-28
(pS)-31-34
Fe
ii) HPPh2 (1 eq)
Cp* =
CH3
Ph
H3C
Ph
CH3
Ph
(pS)-15
(pS)-27, 74%
CH3
Ph
34, 42%
Scheme 7. Synthesis of phosphino tetraphenylcyclopentadiene ligand.
31, 49%
32, 76%
33, 68%
potentially allow us to probe the effect of each stereochemical
element.
Scheme 9. Synthesis of phosphorus Cp(H) type chelate ligands.
Phosphinoferrocenyl aldehyde 28 is a known compound and
can be accessed in either enantiopure form using Kagan’s chiral
auxiliary approach from ferrocene carboxaldehyde and 1,2,4-
butanetriol.39,40 It was envisaged that our desired ligands, with a
tethered Cp(H) group and donor group directly attached to the fer-
rocene ring, could be synthesised from 28. Bildstein et al. have pre-
3. Conclusion
A number of potential ligands have been synthesised with a
cyclopentadienyl group (1-indenyl, 2-indenyl and tetraphenylcy-
clopentadiene) and an additional tethered donor atom (O, N and
P). The opposite ligands with a donor group (N, P) and tethered
cyclopentadiene group (cyclopentadiene, 1-indenyl, TMCp(H),
TPCp(H) and flourene) were also synthesised. Work is underway
to complex these compounds to metals and screen them in an ar-
ray of asymmetric reactions. It is hoped that the large ferrocene
group and planar chirality of the complexes will provide great
improvements to the current ansa-half sandwich metallocene type
complexes used in catalysis.
viously shown that a Cp(H) group can be introduced at the
a-
ferrocenyl position using a condensation reaction between ferro-
cene carboxaldehyde and cyclopentadiene in the presence of pyr-
rolidine.41 Utilisation of the Bildstein conditions to give 29
followed by a subsequent reduction of the fulvene using LiAlH4
gave the desired diphenylphosphino ligand 30 as a mixture of
Cp(H) alkene isomers (Scheme 8).
The use of this methodology for other Cp(H) derivatives needed
extended reaction times and resulted in poor yields for the conden-
sation reaction. It was thought that this may be due to the poor sol-
ubility of 28 in MeOH, the additional steric hindrance of other
Cp(H) derivatives and the additional stability and hence the lower
reactivity of the deprotonated Cp type anions. We developed an
alternative procedure whereby the Cp(H) derivative was deproto-
nated using sodium hydride and the resultant anion heated at re-
flux with 28; reaction times varied for different analogues from
24 h to 3 d (Scheme 9). This allowed for the synthesis of fluorene
31, indene 32, tetramethylcyclopentadiene (TMCp(H)) 33 and tet-
raphenylcyclopentadiene (TPCp(H)) 34 type ligands.
In order to investigate the dimethylamino family of ligands, 2-
dimethylaminoferrocenyl aldehyde 37 was required. This com-
pound was synthesised from Kagan’s aminoacetal intermediate
3540 using a reductive amination to give 36, prior to removal of
the auxiliary (Scheme 10). As with phosphino aldehyde 28, the
Cp(H) group could be installed by using a condensation between
37 and cyclopentadiene in the presence of pyrrolidine to give 38.
Subsequent reduction of the fulvene using LiAlH4 gave the desired
dimethylamino ligand 39 as a mixture of Cp(H) alkene isomers
(Scheme 10). Ligand 39 was synthesised in racemic form in order
to demonstrate the applicability of our methodology to amino li-
gands in addition to the phosphino ligands. The use of enantiopure
1,2,4-butanetriol should allow for the synthesis of dimethylamino
compounds in enantiopure form.40
4. Experimental
4.1. General
Melting points were recorded on a Stuart Scientific SMP3 appa-
ratus and are uncorrected. Optical rotations were recorded on a
Jasco DIP370 Digital Polorimeter. Infrared spectra were recorded
on a Perkin–Elmer 1600 FTIR instrument as solutions in chloroform
unless otherwise stated. The NMR spectra were recorded on Bruker
AM/Bruker AMX/Bruker AVANCE III spectrometers at 600, 500, 400
and 300 MHz in a solution in CDCl3 unless otherwise stated. Chem-
ical shifts are reported in ppm relative to CHCl3 (1H: 7.27), (13C:
77.2). Coupling constants are reported in Hz and rounded to the
nearest 0.1 Hz. Signal assignments are as follows: b (broad), s (sin-
glet), d (doublet, t (triplet), q (quartet), m (multiplet), dd (doublet
of doublets), etc. Mass spectra were recorded using Thermo Finni-
gan Mat900xp (EI/CI) VG-70se (FAB) and Waters LCT Premier XE
(ES) instruments. Elemental analysis was performed on an Exeter
Analytical Inc. EA440 horizontal load analyser or Hewlett Packard
1100 series. HPLC analysis was acquired on a Hewlett Packard Cap-
illary HP4890A GC analyser.
For all non-aqueous chemistry, glassware was rigorously flame
dried and an inert (N2) atmosphere maintained throughout. All
solvents and chemicals were used as received unless stated
O
PPh2
CpH,
pyrrolidine
MeOH
LiAlH4,
THF
Fe
Fe
PPh2
Fe
PPh2
rt
(pS)-28
(pS)-29, 93%
(pS)-30, 76%
Scheme 8. Synthesis of a phosphorus cyclopentadiene chelate ligand.

1028
J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
OMe
OMe
O
Fe
35
O
Fe
O
Fe
O
O
NH2
NMe2
NMe2
pTSA,
(HCHO)n
acetone/
water
NaBH3CN
37, 61%
36, 58%
O
CpH,
NMe2
pyrrolidine
LiAlH4
Fe
Fe
37
NMe2
Fe
NMe2
MeOH
THF, rt
38, 61%
39, 70%
Scheme 10. Synthesis of nitrogen cyclopentadiene chelate ligand.
otherwise. 2-Bromoindene,42 4-(methoxymethyl)-2-(
a
-aminoferr-
with NH4Cl(aq) (10 mL), taken up in diethyl ether (100 mL), washed
with water (2 ꢂ 50 mL), brine (50 mL), dried over MgSO4 and con-
centrated in vacuo. Purification was achieved using flash column
chromatography (10% diethyl ether/pet. ether, silica) to give the ti-
tle compound as an orange oil (8.28 g, 99%). Rf = 0.34 (pet. ether);
ocenyl)-1,3-dioxane 35,40 (pS)-
a-(diphenylphosphino)ferrocene-
carboxaldehyde 28,40 tetramethylcyclopentadiene (TMCp)43 and
tetraphenylcyclopentadiene (TPCp)44 were synthesised according
to known literature procedures. Chromatographic separations
were performed using Flourochem silica gel 60, 35–70
leum ether with a boiling range 40–60 °C was used.
l
m. Petro-
½
a 2D5
ꢃ
¼ ꢀ31:2 (c 1.00, CHCl3); IR mmax 2943, 2891, 2866, 1462,
1383, 1106, 1070, 1058, 999, 883 cmꢀ1 1H NMR (400 MHz) d
;
1.12–1.21 (21H, m, Si(iPr)3), 4.16 (5H, s, Cpunsub), 4.17 (1H, app t,
J = 2.2, Cpsub), 4.36 (1H, m, Cpsub), 4.42 (1H, dd, J = 2.2, 1.2, Cpsub),
4.58 (2H, s, CpCH2); 13C NMR (100 MHz) d 12.1 (CH), 18.2 (CH3),
42.9 (C), 62.2 (CH2), 67.2 (CH), 68.3 (CH), 71.5 (CH), 74.3 (CH),
89.0 (C); m/z (EI+) 521 (10%, M++Na), 326 (10%, M++HꢀOTIPS),
325 (80%, M+ꢀOTIPS), 229 (42%), 228 (11%), 227 (100%); HRMS C20-
H31FeIOSi calcd 498.0533, found 498.0536; Anal. Calcd for C20H31-
FeIOSi: C, 48.21; H, 6.27. Found: C, 48.70; H, 6.29.
4.2. Synthesis of ferrocene ligands
4.2.1. (pR)-1-Iodo-2-(methylalcohol)ferrocene 732
The title compound was resolved from ( )-7 following a modi-
fied literature procedure.32
(i) Small scale: A solution of ( )-7 (0.45 g, 1.3 mmol) in DCM
(90 mL) was treated with Novozym 435 (0.90 g) and vinyl
acetate (1.3 mL). The suspension was heated to 45 °C with
shaking (shaker bed, 150 rpm). 1H NMR indicated that after
4 h, the reaction had reached 50% conversion. The solution
was filtered to remove the immobilised enzyme and the sol-
vent removed in vacuo. CSP HPLC analysis (Chiracel OD-H,
4.2.3. (pS)-1-(Triisopropylsilylethermethyl)-2-(inden-1-yl)-fer-
rocene 11
A solution of iodide 9 (2.00 g, 4.04 mmol) in diethyl ether
(100 mL) was cooled to ꢀ78 °C and treated with nBuLi (1.6 M in
hexanes, 5.05 mL, 8.08 mmol), after which the solution was stirred
at ꢀ78 °C for 30 min. After this time a solution of 1-indanone
(1.59 g, 12.1 mmol) in THF (12 mL) was added dropwise, the solu-
tion was stirred for 2 h at ꢀ78 °C and allowed to warm to rt over-
night. The solution was quenched with NH4Cl(aq), washed with
water (2 ꢂ 60 mL), brine (60 mL), dried over MgSO4 and concen-
trated in vacuo to give crude 10. A solution of crude 10 (3.54 g)
in DCM (30 mL) was cooled to ꢀ78 °C and treated with MsCl
(0.340 mL, 4.87 mmol) followed by DIPEA (1.71 mL, 10.2 mmol)
and stirred at ꢀ78 °C for 1.5 h. The reaction was quenched with
water (10 mL), washed with water (2 ꢂ 10 mL), brine (5 mL), dried
over MgSO4 and concentrated in vacuo. Purification was achieved
using flash column chromatography (10% diethyl ether/pet. ether)
to give the title compound as an orange oil (2.01 g, 97%). Rf = 0.25
i
eluent: hexane: PrOH, 91:9, flow 0.4 mL/min) determined
(pS)-8 (98% ee), (pR)-7 (95% ee) [tR (minor) = 19.41 min, tR
(major) = 21.42 min]. Compounds 7 and 8 were separated
using flash column chromatography (33% EtOAc/pet. ether)
to give (pS)-8 (0.24 g, 49%) and (pR)-7 (0.17 g, 38%). 1H
NMR was in agreement with the literature data.45 Recrystal-
lisation of (pR)-7 increased the enantiopurity to >99% ee, 90%
recovery.
(ii) Large scale: A solution of ( )-7 (51.3 g, 0.150 mol) in DCM
(2.57 L) was treated with Novozym 435 (15.4 g) and vinyl
acetate (28.7 mL). The suspension was heated to 34 °C with
overhead stirring. LCMS indicated that the reaction had
reached 50% conversion after 4 d. The solution was filtered
to remove the immobilised enzyme and the solvent was
removed in vacuo. Purification and determination of enan-
tiopurity were performed as for the small scale reaction.
(pet. ether); ½a D25
ꢃ
¼ þ75:7 (c 0.93, CHCl3); IR
m
max 2943, 2891, 2866,
1604, 1462, 1392, 1125, 1094, 1050, 999, 908, 882 cmꢀ1
;
1H NMR
(400 MHz) d 1.11–1.19 (21H, m, Si(iPr)3), 3.41 (1H, dd, J = 23.6, 2.0,
IndCH2), 3.49 (1H, dd, J = 23.6, 2.0, IndCH2), 4.13 (5H, s, Cpunsub),
4.28 (1H, app t, J = 2.3, Cpsub), 4.47 (1H, dd, J = 2.3, 1.2, Cpsub),
4.61 (1H, dd, J = 2.3, 1.2, Cpsub), 4.68 (1H, d, J = 11.4, CpCH2), 4.78
(1H, d, J = 11.4, CpCH2), 6.83 (1H, t, J = 2.0, IndCH), 7.26 (1H, app
t, J = 7.4, ArH), 7.40 (1H, app t, J = 7.6, ArH), 7.52 (1H, d, J = 7.4,
ArH), 7.96 (1H, d, J = 7.6, ArH); 13C NMR (100 MHz) d 12.2 (CH),
4.2.2. (pR)-1-Iodo-2-(triisopropylsilylethermethyl)ferrocene 9
A solution of alcohol 7 (5.77 g, 16.7 mmol) in DMF (60 mL) was
treated with imidazole (2.91 g, 41.8 mmol) and TIPSCl (4.24 mL,
20.1 mmol) and stirred at rt for 14 h. The reaction was quenched

J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
1029
18.2 (CH3), 38.4 (CH2), 60.9 (CH2), 67.4 (CH), 69.1 (CH), 69.6 (CH),
69.7 (CH), 81.2 (C), 85.1 (C), 121.2 (CH), 123.8 (CH), 124.5 (CH),
125.9 (CH), 131.6 (CH), 139.9 (C), 144.8 (C), 144.9 (C); m/z (EI+)
509 (12%, M++Na), 314 (23%, M++HꢀOTIPS), 313 (100%, M+ꢀOTIPS),
152 (10%), 150 (16%); HRMS C29H38FeNaOSi calcd 509.1934, found
509.1925.
(CH), 131.1 (CH), 134.7 (C), 135.4 (C), 135.5 (C), 137.1 (C), 138.4
(C), 143.2 (C), 145.9 (C), 151.3 (C); m/z (EI+) 779 (100%, M++Na),
757 (22%, M++H), 757 (38%, M+), 584 (15%, M++HꢀOTIPS); HRMS
C
49H52FeNaO2Si calcd 779.2984, found 779.2973; Anal. Calcd for
49H52FeO2Si: C, 77.75; H, 6.92. Found: C, 77.83; H, 6.92.
C
4.2.6. (pS)-1-(Triisopropylsilylethermethyl)-2-(tetraphenylcyclo-
pentadienyl)ferrocene 14 and (pS)-1-(methylalcohol)-2-(tetra-
phenylcyclopentadienyl)ferrocene 15
4.2.4. (pS)-1-(Triisopropylsilylethermethyl)-2-(inden-2-yl)ferro
cene 12
A solution of (pS)-9 (2.00 g, 4.04 mmol) in THF (70 mL) was
cooled to ꢀ78 °C, treated with nBuLi (1.6 M in hexanes, 3.03 mL,
4.85 mmol) and stirred at ꢀ78 °C for 30 min. A solution of ZnCl2
(0.5 M in THF, 9.70 mL, 4.85 mmol) was added dropwise, the solu-
tion warmed to rt over 30 min and stirred at rt for 1 h. Next,
Pd(PPh3)2Cl2 (0.140 g, 0.200 mmol) in THF (5 mL) was treated with
DIBAL (1 M in THF, 0.400 mL, 0.440 mmol), stirred for 5 min and
added dropwise via cannula to the reaction. The resultant solution
was heated at reflux and a solution of 2-bromoindene42 (1.56 g,
8.08 mmol) in THF (5 mL) added dropwise over 30 min. After
refluxing for 4 d the solution was cooled to rt, quenched with NH4-
Cl(aq) (10 mL), washed with water (2 ꢂ 40 mL), brine (40 mL), dried
over MgSO4 and concentrated in vacuo. Purification was achieved
using flash column chromatography (pet. ether) to give the title
compound as an orange oil (1.47 g, 75%). Rf = 0.31 (pet. ether);
A solution of 13 (1.00 g, 1.40 mmol) in THF (30 mL) was treated
with LiAlH4 (1.08 g, 28.0 mmol), which caused a gas to evolve exo-
thermically and stirred at rt for 10 h. After this time, additional
LiAlH4 (0.500 g, 13.8 mmol) was added and the resultant solution
was stirred at rt for 5 h. The reaction mixture was cooled to 0 °C,
quenched with water (10 mL), washed with water (2 ꢂ 20 mL),
brine (20 mL), dried over MgSO4 and concentrated in vacuo. Purifi-
cation was achieved using flash column chromatography (10%
EtOAc/pet. ether) to give 14 as an orange oil (0.207 g, 20%) and
15 as a yellow oil (0.510 g, 60%).
Compound 14 Rf = 0.62 (10% diethyl ether/pet. ether);
½
a 2D5
ꢃ
¼ þ184:3 (c 0.89, CHCl3); IR mmax 2942, 2885, 1600, 1492,
1452, 1105, 1089, 1069, 999, 908, 883 cmꢀ1 1H NMR (400 MHz)
;
d 0.85–0.98 (21H, m, Si(iPr)3), 2.53 (1H, d, J = 12.7, CpCH2), 3.25
(1H, dd, J = 2.4, 1.6, Cpsub), 3.88 (1H, d, J = 12.7, CpCH2), 3.95 (1H,
app t, J = 2.4, Cpsub), 4.16 (1H, m, Cpsub), 4.22 (5H, s, Cpunsub), 5.29
(1H, s, OH), 6.70–6.72 (2H, m, ArH), 6.82–6.97 (7H, m, ArH),
6.95–7.11 (10H, m, ArH), 7.14–7.35 (8H, m, ArH); 13C NMR
(100 MHz) d 11.8 (CH), 18.1 (CH3), 60.9 (CH2), 65.1 (CH), 65.8
(CH), 66.6 (CH), 69.0 (CH), 70.0 (CH), 82.4 (C), 87.9 (C), 126.2
(CH), 126.5 (CH), 126.7 (CH), 127.7 (CH), 127.7 (CH), 127.9 (CH),
128.4 (CH), 129.3 (CH), 130.1 (CH), 130.2 (CH), 135.9 (C), 136.0
(C), 138.2 (C), 139.7 (C), 142.0 (C), 143.8 (C), 145.3 (C), 147.0 (C);
m/z (EI+) 741 (38%, M++H), 740 (71%, M+); HRMS C49H52FeOSi calcd
740.3131, found 740.3127.
½
a 2D5
ꢃ
¼ þ235:3 (c 1.02, CHCl3); IR mmax 2943, 2866, 1461, 1391,
1130, 1105, 1057, 999, 908, 882 cmꢀ1 1H NMR (400 MHz) d
;
1.18–1.70 (21H, m, Si(iPr)3), 3.72 (1H, d, J = 22.8, IndCH2), 3.79
(1H, d, J = 22.8, IndCH2), 4.07 (5H, s, Cpunsub), 4.26 (1H, app t,
J = 2.5, Cpsub), 4.42 (1H, dd, J = 2.5, 1.5, Cpsub), 4.48 (1H, dd,
J = 2.5, 1.5, Cpsub), 4.74 (1H, d, J = 11.6, CpCH2), 4.95 (1H, d,
J = 11.6, CpCH2), 7.08 (1H, s, IndCH), 7.16 (1H, app dt, J = 7.2, 0.8,
ArH), 7.25 (1H, app t, J = 7.2, ArH), 7.31 (1H, d, J = 7.2, ArH), 7.45
(1H, d, J = 7.2, ArH); 13C NMR (100 MHz) d 12.2 (CH), 18.2 (CH3),
41.0 (CH2), 61.4 (CH2), 67.3 (CH), 69.0 (CH), 69.7 (CH), 70.9 (CH),
81.4 (C), 85.0 (C), 120.1 (CH), 123.4 (CH), 123.8 (CH), 126.4 (CH),
126.6 (CH), 142.7 (C), 145.5 (C), 146.2 (C); m/z (EI+) 510 (10%,
M++HNa), 509 (26%, M++Na), 314 (23%, M++HꢀOTIPS), 313 (100%,
M+ꢀOTIPS), 301 (15%, M+ꢀCOTIPS), 269 (7%); HRMS C29H38FeNa-
OSi calcd 509.1934, found 509.1903; Anal. Calcd for C29H38FeOSi:
C, 71.59; H, 7.87. Found: C, 71.10; H, 7.81.
Compound 15 Rf = 0.45 (10% diethyl ether/pet. ether);
½
a 2D5
ꢃ
¼ þ344:7 (c 0.64, CHCl3); IR mmax 3572, 2928, 1600, 1492,
1452, 1376, 1106, 1073, 1041, 999, 977 cmꢀ1 1H NMR
;
(400 MHz) d 0.39 (1H, t, J = 6.0, OH), 3.28 (1H, dd, J = 12.6, 6.0,
CpCH2), 3.34 (1H, dd, J = 2.4, 1.1, Cpsub), 3.87 (1H, dd, J = 12.6, 6.0,
CpCH2), 4.06 (1H, m, Cpsub), 4.19 (5H, s, Cpunsub), 4.23 (1H, m,
Cpsub), 5.24 (1H, s, CH), 6.76–6.80 (2H, m, ArH), 6.94–6.97 (2H,
m, ArH), 7.00–7.34 (16H, m, ArH); 13C NMR (100 MHz) d 60.0
(CH2), 65.3 (CH), 67.6 (CH), 68.0 (CH), 69.4 (CH), 69.8 (CH), 84.2
(C), 86.2 (C), 126.4 (CH), 126.9 (CH), 127.0 (CH), 127.7 (CH),
128.0 (CH), 128.5 (CH), 129.3 (CH), 130.1 (CH), 130.3 (CH), 135.1
(C), 135.1 (C), 135.5 (C), 137.7 (C), 141.8 (C), 142.7 (C), 145.9 (C),
147.4 (C); m/z (EI+) 607 (100%, M++Na), 584 (52%, M+), 567 (15%,
M+ꢀOH); HRMS C40H32FeNaO calcd 607.1695, found 607.1709.
4.2.5. (pR)-1-(1-Hydroxy-tetraphenylcyclopentadienyl)-2-(triiso
propylsilylether methyl)ferrocene 13
A solution of iodide 9 (0.50 g, 1.0 mmol) in diethyl ether (30 mL)
was cooled to ꢀ78 °C and treated with nBuLi (2.5 M in hexanes,
0.80 mL, 2.0 mmol), and stirred at ꢀ78 °C for 10 min. After this
time the solution was warmed to ꢀ40 °C, stirred for 10 min and
treated with a solution of tetraphenylcyclopentadienone (0.60 g,
1.5 mmol) in THF (25 mL) until the purple colour remained
(15 mL of the solution). The reaction mixture was stirred at
ꢀ40 °C for 1 h, quenched with water (5 mL), washed with water
(2 ꢂ 30 mL), brine (30 mL), dried over MgSO4 and concentrated in
vacuo. The resultant brown foam was purified using flash column
chromatography (5% diethyl ether/pet. ether) to give the title com-
pound as an orange solid (0.60 g, 80%). Rf = 0.34 (5% diethyl ether/
4.2.7. (pS)-1-(Methylethermethyl)-2-(inden-1-yl)ferrocene 16
A solution of TIPS ether 11 (50 mg, 0.100 mmol) in MeOH
(8.6 mL) was cooled to 5 °C and treated with 2 M HCl (1.7 mL)
and stirred at 5 °C for 16 h. The solution was concentrated in vacuo
and taken up in DCM (5 mL), washed with NaHCO3(aq) (2 ꢂ 4 mL),
dried over MgSO4 and concentrated in vacuo. Purification was
achieved using flash column chromatography (50% diethyl ether/
pet. ether) to give the title compound as a yellow/orange oil
(29 mg, 85%). Rf = 0.33 (5% diethyl ether/pet. ether);
pet. ether); mp 82–84 °C; ½a D25
¼ þ413:0 (c 1.20, CHCl3); IR mmax
ꢃ
3684, 3016, 2868, 2400, 1550, 1420, 1202, 1109, 928, 802 cmꢀ1
;
1H NMR (400 MHz) d 1.07–1.08 (21H, m, Si(iPr)3), 3.50 (1H, d,
J = 11.9, CpCH2), 3.54 (1H, d, J = 11.9, CpCH2), 3.64 (5H, s, Cpunsub),
4.10 (1H, m, Cpsub), 4.14 (1H, m, Cpsub), 4.18 (1H, m, Cpsub), 5.15
(1H, s, OH), 6.74–6.79 (2H, m, ArH), 6.82–6.97 (7H, m, ArH),
7.01–7.15 (6H, m, ArH), 7.19–7.32 (3H, m, ArH), 7.58–7.64 (2H,
m, ArH); 13C NMR (100 MHz) d 11.8 (CH), 18.1 (CH3), 60.8 (CH2),
65.6 (CH), 66.8 (CH), 69.1 (CH), 69.2 (CH), 85.6 (C), 88.8 (C), 89.6
(C), 126.2 (CH), 126.4 (CH), 126.8 (CH), 127.0 (CH), 127.1 (CH),
127.3 (CH), 127.4 (CH), 127.8 (CH), 129.7 (CH), 130.1 (CH), 130.8
½
a 2D5
ꢃ
¼ þ110:6 (c 1.08, CHCl3); IR mmax 2930, 2891, 2399, 1469,
1389, 1081, 1096, 1025, 998 cmꢀ1 1H NMR (400 MHz) d 3.42
;
(3H, s, OCH3), 3.43 (1H, dd, J = 23.6, 2.1, IndCH2), 3.48 (1H, dd,
J = 23.6, 2.1, IndCH2), 4.13 (5H, s, Cpunsub), 4.27 (1H, d, J = 10.8,
CpCH2), 4.35 (1H, app t, J = 2.5, Cpsub), 4.47 (1H, dd, J = 2.5, 1.4,
Cpsub), 4.55 (1H, d, J = 10.8, CpCH2), 4.66 (1H, dd, J = 2.5, 1.4, Cpsub),
6.76 (1H, app t, J = 2.1, IndCH), 7.28 (1H, app dt, J = 7.4, 1.0, ArH),
7.41 (1H, dt, J = 7.8, 1.0, ArH), 7.55 (1H, d, J = 7.4, ArH), 7.96 (1H,

1030
J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
d, J = 7.8, ArH); 13C NMR (100 MHz) d 38.5 (CH3), 57.7 (CH2), 68.0
(CH), 69.5 (CH), 69.5 (CH), 69.9 (CH2), 71.0 (CH), 80.4 (C), 82.0
(C), 121.2 (CH), 123.8 (CH), 124.5 (CH), 125.9 (CH), 131.7 (CH),
139.5 (C), 144.8 (C); m/z (EI+) 367 (12%, M++Na), 345 (9%, M++H),
314 (23%, M++HꢀOMe), 313 (100%, M+ꢀOMe), 311 (6%, M+ꢀH2-
OMe); HRMS C21H21FeO calcd 345.0936, found 345.0943.
and concentrated in vacuo. Purification was achieved using flash
column chromatography (10% EtOAc/2% Et3N/pet. ether, basic alu-
mina) to give the title compound as a dark orange oil (0.640 g,
92%). Rf = 0.35 (10% EtOAc/2% Et3N/pet. ether, basic alumina);
½
a 2D5
ꢃ
¼ þ335:9 (c 0.93, CHCl3); IR mmax 2942, 2857, 2817, 2771,
1460, 1393, 1353, 1105, 1043, 1000, 908 cmꢀ1 1H NMR
;
(400 MHz) d 2.30 (6H, s, N(CH3)2), 3.09 (1H, d, J = 12.6, CpCH2),
3.72 (1H, d, J = 22.0, IndCH2), 3.85 (1H, d, J = 22.0, IndCH2), 3.95
(1H, d, J = 12.6, CpCH2), 4.07 (5H, s, Cpunsub), 4.27 (1H, app t,
J = 2.5, Cpsub), 4.34 (1H, m, Cpsub), 4.51 (1H, m, Cpsub), 7.07 (1H, s,
IndCH), 7.17 (1H, app dt, J = 7.3, 0.7, ArH), 7.26 (1H, m, ArH), 7.35
(1H, d, J = 7.4, ArH), 7.45 (1H, d, J = 7.3, ArH); 13C NMR (100 MHz)
d 40.1 (CH2), 44.2 (CH3), 58.0 (CH2), 66.4 (CH), 67.9 (CH), 68.8
(CH), 71.9 (CH), 80.5 (C), 81.3 (C), 119.2 (CH), 122.3 (CH), 122.8
(CH), 125.4 (CH), 125.5 (CH), 141.6 (C), 144.7 (C), 145.2 (C); m/z
(EI+) 358 (75%, M++H), 357 (100%, M+), 314 (8%, M++HꢀNMe2),
313 (48%, M+ꢀNMe2); HRMS C22H23FeN calcd 357.1174, found
357.1175; Anal. Calcd for C22H23NFe: C, 73.96; H, 6.49; N, 3.42.
Found: C, 73.83; H, 6.78; N, 3.74.
4.2.8. (pS)-1-(Methylacetate)-2-(inden-1-yl)ferrocene 17
A solution of TIPS ether 11 (2.00 g, 4.01 mmol) in THF (45 mL)
was treated with AcOH/water (4:1 solution, 80 mL) and stirred at
5 °C for 3 d. The reaction was quenched with NaHCO3(aq)
(100 mL), washed with NaHCO3(aq) (3 ꢂ 50 mL), water
(2 ꢂ 50 mL), brine (50 mL), dried over MgSO4 and concentrated in
vacuo. Purification was achieved using flash column chromatogra-
phy (20% EtOAc/pet. ether) to give the title compound as an or-
ange/yellow solid (1.37 g, 92%). Mp 123–125 °C; Rf = 0.21 (5%
diethyl ether/pet. ether); ½a D25
¼ þ141:2 (c 0.96, CHCl3); IR mmax
ꢃ
2924, 1731, 1459, 1376, 1256, 1106, 1046, 1020, 975, 905 cmꢀ1
;
1H NMR (500 MHz) d 2.10 (3H, s, COCH3), 3.43 (1H, dd, J = 23.2,
2.1, IndCH2), 3.49 (1H, dd, J = 23.2, 2.1, IndCH2), 4.12 (5H, s,
Cpunsub), 4.38 (1H, app t, J = 2.6, Cpsub), 4.54 (1H, dd, J = 2.6, 1.4,
Cpsub), 4.68 (1H, dd, J = 2.6, 1.4, Cpsub), 4.95 (1H, d, J = 11.9, CpCH2),
5.28 (1H, d, J = 11.9, CpCH2), 6.62 (1H, t, J = 2.1, IndCH), 7.28 (1H,
app dt, J = 7.4, 0.8, ArH), 7.41 (1H, app t, J = 7.6, ArH), 7.54 (1H, d,
J = 7.4, ArH), 7.92 (1H, d, J = 7.6, ArH); 13C NMR (100 MHz) d 21.2
(CH3), 38.5 (CH2), 62.2 (CH2), 68.5 (CH), 69.7 (CH), 69.8 (CH), 71.1
(CH), 77.3 (C), 78.4 (C), 121.1 (CH), 123.9 (CH), 124.8 (CH), 125.8
(C), 126.0 (CH), 131.4 (CH), 139.3 (C), 144.6 (C), 171.0 (C); m/z
(EI+) 395 (9%, M++Na), 373 (7%, M++H), 372 (25%, M+), 314 (24%,
M++HꢀOAc), 313 (100%, M+ꢀOAc), 282 (14%), 239 (11%), 227
(14%), 202 (18%), 150 (13%); HRMS C22H20FeO2 calcd 372.0812,
found 372.1626; Anal. Calcd for C22H20FeO2: C, 70.99; H, 5.42.
Found: C, 71.34, H, 5.60.
4.2.11. (pS)-1-(N-Methylaminomethyl)-2-(inden-2-yl)ferrocene
20
A solution of TIPS ether 13 (71 mg, 0.14 mmol) in MeCN/ace-
tone (1:1, 2 mL) was cooled to 0 °C and treated with TMSCl
(45 lL, 0.36 mmol) and stirred for 10 min. After this time the resul-
tant solution was transferred dropwise via cannula onto H2NMe
(2 M solution in THF, 1.45 mL, 2.89 mmol) at 0 °C and stirred for
1 h. The reaction mixture was quenched with water (1 mL),
washed with water (2 ꢂ 1 mL), brine (1 mL), dried over MgSO4
and concentrated in vacuo. Purification was achieved by acid
extraction (8% H3PO4), basified by 2 M NaOH, taken up in DCM,
separated, dried over MgSO4 and concentrated in vacuo to give
the title compound as an orange oil (42 mg, 89%). ½a D25
¼ þ233:5
ꢃ
(c 0.40, CHCl3); IR mmax 3755, 2930, 1605, 1460, 1106, 1001,
4.2.9. (pS)-1-(Methylalcohol)-2-(inden-1-yl)ferrocene 18
828 cmꢀ1 1H NMR (400 MHz) d 2.53 (3H, s, NCH3), 3.67 (1H, d,
;
A solution of acetate 17 (1.65 g, 4.62 mmol) in methanol
(80 mL)/diethyl ether (20 mL) was treated with NaOMe (1.25 g,
23.1 mmol) and stirred at rt for 2 h. After this time the reaction
was concentrated in vacuo, taken up in diethyl ether (30 mL),
washed with water (2 ꢂ 20 mL), brine (20 mL), dried over MgSO4
and concentrated in vacuo to give the title compound as an orange
solid (1.45 g, 99%). Mp 68–70 °C; Rf = 0.35 (30% EtOAc/pet. ether);
J = 22.0, IndCH2), 3.73 (1H, d, J = 22.0, IndCH2), 4.10 (5H, s, Cpunsub),
4.14 (1H, d, J = 13.6, CpCH2), 4.21 (1H, d, J = 13.6, CpCH2), 4.36 (1H,
app t, J = 2.5, Cpsub), 4.53 (1H, dd, J = 2.5, 1.4, Cpsub), 4.71 (1H, dd,
J = 2.5, 1.4, Cpsub), 6.95 (1H, s, IndCH), 7.18 (1H, app dt, J = 7.4,
0.7, ArH), 7.25 (1H, app t, J = 7.4, ArH), 7.36 (1H, d, J = 7.5, ArH),
7.44 (1H, d, J = 7.3, ArH); 13C NMR (100 MHz) d 36.6 (CH3), 41.3
(CH2), 51.0 (CH2), 67.5 (CH), 68.9 (CH), 69.9 (CH), 71.2 (CH), 80.3
(C), 84.5 (C), 120.2 (CH), 123.4 (CH), 124.0 (CH), 125.5 (CH),
126.7 (CH), 142.4 (C), 145.9 (C), 146.1 (C); m/z (EI+) 364 (10%,
M++Na), 343 (41%, M++Na), 314 (23%, M++HꢀNHMe), 313 (100%,
M+ꢀNHMe); HRMS C21H21FeN calcd 343.0167, found 343.0160.
½
a 2D5
ꢃ
¼ þ100:6 (c 0.68, CHCl3); IR mmax 3684, 3606, 2951, 2891,
2879, 2400, 1465, 1380, 1106, 984 cmꢀ1 1H NMR (500 MHz) d
;
1.62 (1H, dd, J = 6.5, 4.7, OH), 3.42 (1H, dd, J = 24.1, 2.2, IndCH2),
3.51 (1H, dd, J = 24.1, 2.2, IndCH2), 4.18 (5H, s, Cpunsub), 4.35 (1H,
app t, J = 2.5, Cpsub), 4.47 (1H, dd, J = 2.5, 1.4, Cpsub), 4.59 (2H, m,
CpCH2), 4.66 (1H, dd, J = 2.5, 1.4, Cpsub), 6.75 (1H, t, J = 2.2, IndCH),
7.28 (1H, app dt, J = 7.4, 1.0, ArH), 7.38 (1H, app t, J = 7.6, ArH), 7.53
(1H, d, J = 7.4, ArH), 7.88 (1H, d, J = 7.6, ArH); 13C NMR (100 MHz) d
38.5 (CH2), 60.1 (CH2), 67.9 (CH), 69.4 (CH), 69.5 (CH), 69.6 (CH),
81.3 (C), 84.9 (C), 121.0 (CH), 123.9 (CH), 124.7 (CH), 126.0 (CH),
131.7 (CH), 139.6 (C), 144.7 (C), 144.8 (C); m/z (EI+) 353 (100%,
M++Na), 331 (25%, M++H), 330 (68%, M+), 314 (20%, M+ꢀO), 313
(84%, M+ꢀOH), 301 (14%); HRMS C20H18FeNO calcd 353.0605,
found 353.0599.
4.2.12. (pS)-1-(N,N-Dimethylaminomethyl)-2-(inden-1-yl)ferro
cene 21
A solution of alcohol 18 (0.34 g, 0.97 mmol) in THF (20 mL) was
cooled to 0 °C and treated with MsCl (0.12 mL, 0.97 mmol) fol-
lowed by DIPEA (0.34 mL, 1.9 mmol) and stirred at 0 °C for 1 h.
The resultant solution was transferred dropwise via cannula onto
HNMe2 (2 M in THF, 4.8 mL, 9.6 mmol) and stirred at 0 °C for 1 h.
After this time the solution was quenched with water (10 mL),
washed water (2 ꢂ 10 mL), brine (5 mL), dried over MgSO4 and
concentrated in vacuo. Purification was achieved by acid extraction
(8% H3PO4), basified by 2 M NaOH, taken up in DCM, separated,
dried over MgSO4 and concentrated in vacuo to give the title com-
4.2.10. (pS)-1-(N,N-Dimethylaminomethyl)-2-(inden-2-yl)ferro
cene 19
A solution of TIPS ether 13 (0.950 g, 1.95 mmol) in MeCN/ace-
tone (1:1, 20 mL) was cooled to 0 °C and treated with TMSCl
(0.617 mL, 4.88 mmol) and stirred for 10 min. After this time the
resultant solution was transferred dropwise via cannula onto
HNMe2 (2 M solution in THF, 19.5 mL, 39.0 mmol) at 0 °C and stir-
red for 1 h. The reaction mixture was quenched with water (5 mL),
washed with water (2 ꢂ 10 mL), brine (10 mL), dried over MgSO4
pound as a brown oil (0.34 g, 82%). ½a D25
¼ ꢀ15:5 (c 1.10, CHCl3); IR
ꢃ
mmax 2943, 2858, 2816, 1693, 1603, 1456, 1368, 1106, 1001,
907 cmꢀ1 1H NMR (400 MHz) d 2.21 (6H, s, N(CH3)2), 3.10 (1H,
;
d, J = 12.6, CpCH2), 3.42 (1H, dd, J = 24.4, 2.2, IndCH2), 3.50 (1H,
dd, J = 24.4, 2.2, IndCH2), 3.68 (1H, J = 12.6, CpCH2), 4.11 (5H, s,
Cpunsub), 4.30 (1H, app t, J = 2.4, Cpsub), 4.37 (1H, dd, J = 2.4, 1.4,
Cpsub), 4.61 (1H, dd, J = 2.4, 1.4, Cpsub), 6.95 (1H, t, J = 2.2, IndCH),

J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
1031
7.26 (1H, app dt, J = 7.4, 0.9, ArH), 7.38 (1H, app t, J = 7.5, ArH), 7.52
(1H, d, J = 7.4, ArH), 7.89 (1H, d, J = 7.7, ArH); 13C NMR (100 MHz) d
36.5 (CH2), 43.1 (CH3), 56.2 (CH2), 65.4 (CH), 67.0 (CH), 67.7 (CH),
69.3 (CH), 79.2 (C), 81.1 (C), 119.2 (CH), 121.8 (CH), 122.4 (CH),
123.9 (CH), 130.3 (CH), 138.2 (C), 142.8 (C), 143.2 (C); m/z (EI+)
430 (8%), 390 (10%, M++O2H), 358 (100%, M++H), 313 (92%, M+-
ꢀNMe2); HRMS C22H24FeN calcd 358.1253, found 358.1253; Anal.
Calcd for C22H23FeN: C, 73.96; H, 6.49; N, 3.92. Found: C, 73.98;
H, 6.68; N, 3.56.
trated in vacuo. 1H NMR analysis indicated 85% conversion to the
title compound (based upon integration of the unsubstituted Cp
ring). 1H NMR (400 MHz) d 2.07 (3H, s, NCH3), 2.52 (1H, d,
J = 13.0, CpCH2), 3.21 (1H, d, J = 13.0, CpCH2), 3.36 (1H, dd, J = 4.5,
2.0, Cpsub), 4.06 (1H, dd, J = 4.5, 2.0, Cpsub), 4.18 (5H, s, Cpunsub),
4.32 (1H, m, Cpsub), 5.32 (1H, s, CpCH), 6.72–7.82 (4H, m, ArH),
6.81–7.36 (20H, m, ArH); HRMS C41H35FeN calcd 597.1277, found
597.1300.
4.2.16. [(pS)-1-(N,N,N-Trimethylammoniummethyl)-2-(inden-2-
yl)ferrocene][iodide] 25
4.2.13. (pS)-1-(N-Methylaminomethyl)-2-(inden-1-yl)ferrocene
22
A solution of 19 (57 mg, 0.160 mmol) in acetone (2 mL) was
A solution of alcohol 18 (50 mg, 0.150 mmol) in THF (2 mL) was
cooled to 0 °C and treated with MeI (45 lL, 0.172 mmol). The reac-
cooled to 0 °C and treated with MsCl (18
l
L, 0.150 mmol) followed
tion was warmed to rt and stirred for 16 h. After this time the reac-
tion was concentrated in vacuo. The resultant brown oil was
dissolved in DCM (2 mL), after which diethyl ether (2 mL) was
added dropwise and the solution filtered to give the title com-
pound as a bright orange solid (70 mg, 91%). Mp 118–120 °C;
by DIPEA (50 L, 0.300 mmol) and stirred at 0 °C for 1 h. The resul-
l
tant solution was transferred dropwise via cannula onto MeNH2
(2 M in THF, 0.750 mL, 1.50 mmol) and stirred at 0 °C for 1 h. Puri-
fication was achieved by acid extraction (8% H3PO4) then basified
by 2 M NaOH, taken up in DCM, separated, dried over MgSO4 and
concentrated in vacuo to give the title compound as an orange
½
a 2D5
ꢃ
¼ þ100:9 (c 0.94, CHCl3); IR mmax 2944, 1604, 1485, 1456,
1370, 1108, 1002, 973, 870 cmꢀ1 1H NMR (500 MHz) d 3.30 (9H,
;
oil (39 mg, 75%). Rf = 0.22 (EtOAc/Et3N); ½a D25
ꢃ
¼ ꢀ87:5 (c 0.92,
s, N(CH3)3), 3.53 (1H, d, J = 22.4, IndCH2), 3.91 (1H, d, J = 22.4,
IndCH2), 4.26 (5H, s, Cpunsub), 4.51 (1H, app t, J = 2.4, Cpsub), 4.60
(1H, dd, J = 2.4, 1.5, Cpsub), 4.94 (1H, dd, J = 2.4, 1.5, Cpsub), 5.09
(1H, d, J = 13.5, CpCH2), 5.50 (1H, d, J = 13.5, CpCH2), 7.19 (1H,
app dt, J = 7.4, 0.9, ArH), 7.25–7.29 (2H, m, IndCH, ArH), 7.49 (1H,
d, J = 7.4, ArH), 7.52 (1H, d, J = 7.5, ArH); 13C NMR (100 MHz) d
42.6 (CH2), 53.0 (CH3), 65.9 (CH2), 70.5 (CH), 70.7 (CH), 71.3 (CH),
71.5 (C), 74.7 (CH), 83.0 (C), 121.2 (CH), 123.7 (CH), 124.9 (CH),
127.0 (CH), 128.9 (CH), 142.1 (C), 143.4 (C), 144.9 (C); m/z (EI+)
372 (100%, M+ꢀI), 313 (85%, M+ꢀNMe3I); HRMS C23H26FeN calcd
372.1409, found 372.1393.
CHCl3); IR mmax 2935, 1666, 1459, 1394, 1106, 1000, 905 cmꢀ1
;
1H
NMR (C6D6, 500 MHz) d 0.6 (1H, b, NH), 2.35 (3H, s, NCH3), 3.15
(1H, dd, J = 23.7, 2.2, IndCH2), 3.24 (1H, dd, J = 23.7, 2.2, IndCH2),
3.48 (1H, d, J = 12.4, CpCH2), 3.70 (1H, d, J = 12.4, CpCH2), 4.06 (5H,
s, Cpunsub), 4.10 (1H, app t, J = 2.5, Cpsub), 4.30 (1H, dd, J = 2.5, 1.5,
Cpsub), 4.52 (1H, dd, J = 2.5, 1.5, Cpsub), 6.88 (1H, t, J = 2.2, IndCH),
7.23 (1H, app dt, J = 7.3, 1.0, ArH), 7.34–7.39 (2H, m, ArH), 7.98
(1H, m, ArH); 13C NMR (C6D6, 125 MHz) d 35.0 (CH3), 38.6 (CH2),
49.4 (CH2), 68.0 (CH), 69.4 (CH), 70.1 (C), 70.2 (CH), 70.3 (CH), 81.6
(C), 121.4 (CH), 124.2 (CH), 125.1 (CH), 126.4 (CH), 132.1 (CH),
140.5 (C), 144.9 (C), 145.5 (C); m/z (EI+) 344 (48%, M+), 313 (100%,
MꢀNHMe); HRMS C21H22NFe calcd 344.1096, found 344.1085.
4.2.17. (pS)-Bis-(2-inden-2-yl-1-ferrocenyl methyl)diphenyl-
phosphonium iodide 26
4.2.14. (pR)-1-(N,N-Dimethylaminomethyl)-2-(tetraphenylcyclo
pentadienyl)ferrocene 23
A solution of 25 (20 mg, 0.040 mmol) in MeCN (1 mL) was trea-
ted with HPPh2 (6 lL, 0.032 mmol) and heated at reflux for 16 h.
A solution of 15 (0.20 g, 0.34 mmol) in MeCN/acetone (1:1,
5 mL) was cooled to 0 °C and treated with TMSCl (0.10 mL,
0.86 mmol) and stirred at 0 °C for 10 min. After this time, the resul-
tant solution was transferred dropwise via cannula onto a solution
of HNMe2 (2 M, THF, 3.5 mL, 6.8 mmol) at 0 °C, and stirred for 1 h.
The reaction mixture was quenched with water (3 mL), washed
with water (2 ꢂ 5 mL), brine (5 mL), dried over MgSO4 and concen-
trated in vacuo. 1H NMR analysis indicated 75% conversion to the
title compound (based upon integration of the unsubstituted Cp
ring). 1H NMR (400 MHz) d 2.01 (6H, s, N(CH3)2), 2.63 (1H, d,
J = 14.5, CpCH2), 3.23 (1H, d, J = 14.5, CpCH2), 3.98 (5H, s, Cpunsub),
3.52–3.56 (2H, m, 2 ꢂ Cpsub), 4.30 (1H, m, Cpsub), 5.37 (1H, s,
CpCH), 6.88–7.40 (4H, m, ArH), 6.81–7.36 (20H, m, ArH); HRMS C42-
H37FeN calcd 611.1436, found 611.1442.
The reaction was quenched with water (0.5 mL), washed with
water (2 ꢂ 1 mL), brine (1 mL), dried over MgSO4 and concentrated
in vacuo. The resultant orange oil was dissolved in DCM (2 mL),
pet. ether. (2 mL) was added dropwise and the solution filtered
to give the title compound as a pale brown solid (13 mg, 81%);
mp 150–152 °C; ½a D25
¼ þ87:7 (c 0.35, CHCl3); IR mmax 3548, 3529,
ꢃ
2942, 2310, 1602, 1480, 1398, 1350, 1107, 1020, 999, 908 cmꢀ1
;
1H NMR (400 MHz) d 2.90 (2H, d, J = 22.4, 2 ꢂ IndCH2), 3.46 (2H,
d, J = 22.4, 2 ꢂ IndCH2), 4.25 (14H, m, 2 ꢂ Cpunsub, 4 ꢂ Cpsub), 4.40
(2H, m, 2 ꢂ CpCH2), 4.44 (2H, m, 2 ꢂ Cpsub), 5.65 (2H, app t,
J = 14.2, 2 ꢂ CpCH2), 6.68 (2H, s, 2 ꢂ IndCH), 7.13–7.20 (6H, m,
ArH), 7.23–7.36 (6H, m, ArH), 7.41–7.55 (6H, m, ArH); 13C NMR
(100 MHz) d 25.2 (CH2), 25.2 (CH2), 42.1 (CH2) 68.1 (CH), 68.9
(CH), 71.3 (CH), 71.4 (CH), 73.9 (C), 81.3 (C), 116.4 (C), 117.1 (C),
120.6 (CH), 123.4 (CH), 124.5 (CH), 126.7 (CH), 127.7 (CH), 129.3
(CH), 129.4 (CH), 134.0 (CH), 134.1 (CH), 134.3 (CH), 134.3 (CH),
142.1 (C), 144.4 (C), 145.1 (C); 31P NMR d 20.0, 20.5; m/z (EI+)
812 (62%, M++HꢀI), 811 (100%, M+ꢀI), 500 (16%, M++HꢀIC20H17Fe),
444 (25%, M++NaꢀIPhC20H17Fe), 400 (14%), 313 (21%, M+ꢀIPPh2-
C20H17Fe); HRMS C52H44Fe2P calcd 811.1876, found 811.1871.
4.2.15. (pR)-1-(N-Methylaminomethyl)-2-(tetraphenylcyclopen
tadienyl)ferrocene 24
A solution of 15 (79 mg, 0.11 mmol) in MeCN/acetone (1:1,
2 mL) was cooled to 0 °C and treated with TMSCl (31 lL,
0.27 mmol) and stirred at 0 °C for 10 min. After this time the resul-
tant solution was transferred dropwise via cannula onto a solution
of H2NMe (2 M, THF, 1.1 mL, 2.1 mmol) at 0 °C, and stirred for 1 h.
The reaction mixture was quenched with water (1 mL), washed
with water (2 ꢂ 1 mL), brine (1 mL), dried over MgSO4 and concen-
4.2.18. (pS)-1-(Diphenylphosphinomethyl)-2-(tetraphenylcyclo
pentadienyl)ferrocene 27
A solution of 15 (58 mg, 0.081 mmol) in MeCN (2 mL) was
cooled to 0 °C and treated with TMSCl (23
red at 0 °C for 10 min. After this time, the resultant solution was
treated with HPPh2 (1.4 L, 0.081 mmol) at 0 °C and stirred for
lL, 0.20 mmol) and stir-
The specific rotation of this compound increased significantly with each
successive reading (ꢀ142.5 after 10 readings). The temperature was seen to increase
slightly upon each reading (by ꢄ0.1 °C) so the value is quoted at 25 °C. The sample
was not degrading, upon cooling the sample back to 25 °C the specific rotation
returned to ꢀ87.5.
l
1 h. The reaction mixture was quenched with water (1 mL),
washed with water (2 ꢂ 1 mL), brine (1 mL), dried over MgSO4
and concentrated in vacuo. Purification was achieved using flash

1032
J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
column chromatography (10% EtOAc/pet. ether) to give the title
4.03 (5H, s, Cpunsub., 4.24 (1H, m, Cpsub), 4.39 (1H, m, Cpsub), 5.94
(1H, m, Cp0CH), 6.08 (1H, m, Cp0CH), 6.18 (1H, m, Cp0CH), 7.03–
7.60 (10H, PPh2); 13C NMR (150 MHz) d 29.9 (CH2), 43.3 (CH2),
69.1 (CH), 69.9 (CH), 70.9 (CH), 71.7 (CH), 75.4 (C), 93.7 (C),
127.4 (CH), 127.8 (CH), 128.0 (d, CH), 128.2 (CH), 129.1 (CH),
130.7 (CH), 132.2 (CH), 132.5 (CH), 135.1 (CH), 137.8 (C), 139.6
(C), 148.1 (C); 31P NMR (162 MHz; CDCl3) d ꢀ23.4; HH; m/z (EI+)
449 (3%, M+H), 448 (11%, M); HRMS C28H25FeP calcd 448.10378,
found 448.10252.
compound as an orange oil (45 mg, 74%). Rf = 0.24 (pet. ether);
½
a 2D5
ꢃ
¼ þ216:1 (c 0.77, CHCl3); IR mmax 3002, 1711, 1492, 1452,
1106, 1073, 1041, 999, 908 cmꢀ1 1H NMR (400 MHz) d 1.80 (1H,
;
dd, J = 16.2, 5.0, CpCH2), 2.54 (1H, d, J = 16.2, CpCH2), 3.36 (1H, m,
Cpsub), 3.79 (1H, m, Cpsub), 3.91 (1H, m, Cpsub), 4.27 (5H, s, Cpunsub),
5.32 (1H, s, CH), 6.77–6.81 (2H, m, ArH), 6.99–7.41 (28H, m, ArH);
13C NMR (100 MHz) d 28.2 (CH2), 65.5 (CH), 66.7 (CH), 68.9 (CH),
70.4.8 (CH), 77.1 (CH), 83.4 (C), 84.7 (C), 126.3 (CH), 126.7 (CH),
126.7 (CH), 127.7 (CH), 127.8 (CH), 127.9 (CH), 128.1 (CH), 128.1
(CH), 128.2 (CH), 128.2 (CH), 128.3 (CH), 128.5 (CH), 128.8 (CH),
129.3 (CH), 130.2 (CH), 130.3 (CH), 132.2 (CH), 132.3 (CH), 133.0
(CH), 133.2 (CH), 135.3 (C), 135.9 (C), 136.7 (C), 137.9 (C), 139.5
(C), 140.8 (C), 141.9 (C), 143.4 (C), 145.9 (C), 147.4 (C); 31P NMR
d ꢀ19.0; m/z (EI+) 754 (54%, M++H), 753 (100%, M+), 752 (100%,
M+ꢀH); HRMS C52H34FeP calcd 753.2392, found 753.2369.
4.2.21. (pS)-1-(Diphenylphosphino)-2-[(9H-fluoren-9-ylidene)
methyl]-ferrocene 31
A solution of fluorene (83 mg, 0.50 mmol) in degassed THF
(5 mL) was treated with sodium hydride (12 mg, 0.50 mmol) fol-
lowed by 2840 (200 mg, 0.50 mmol) at rt. The resultant red solution
was heated at reflux for 18 h. The reaction was concentrated onto
silica and purification was achieved using flash column chromatog-
raphy (5% EtOAc/Pet. ether) to give the title compound as a red so-
lid (138 mg, 49%). Mp 174–176 °C; Rf = 0.57 (10% EtOAc/Pet. ether);
4.2.19. (pS)-1-(Diphenylphosphino)-2-[(cyclopenta-2,4-dienylid-
ene)methyl]-ferrocene 29
Freshly cracked cyclopentadiene (0.08 mL, 1.00 mmol), 2-
(diphenylphosphino)-ferrocenecarboxaldehyde 2840 (100 mg,
0.25 mmol) and pyrrolidine (0.04 mL, 0.50 mmol) were stirred in
degassed MeOH (10 mL) at rt for 3.5 h. The reaction was concen-
trated in vacuo, dried for 2 h under vacuum and purified using
flash column chromatography (10% EtOAc/pet. ether) to give the ti-
tle compound as a red-purple solid (105 mg, 93%). Mp 147–149 °C;
½
a 2D5
ꢃ
¼ þ2580 (c 0.10, CHCl3); IR tmax 3056, 1625, 1602, 1432,
1258, 1170 cmꢀ1 1H NMR (600 MHz) d 4.04 (1H, bs, Cpsub), 4.13
;
(5H, s, Cpunsub), 4.55 (1H, t, J = 2.4, Cpsub), 5.05 (1H, bs, Cpsub),
7.09–7.22 (12H, m, PPh2 and Flu.CH), 7.61–7.65 (2H, m, PPh2),
7.68 (1H, d, J = 6.9, Flu.CH), 7.71 (1H, d, J = 7.5, Flu.CH), 7.72 (1H,
s, CpCH), 7.80 (1H, d, J = 7.3, Flu.CH), 8.14 (1H, d, J = 7.8, Flu.CH);
13C NMR (150 MHz) d 70.6 (CH), 70.7 (CH), 72.4 (CH), 73.4 (CH),
80.2 (C), 87.3 (C), 119.6 (CH), 119.8 (CH), 120.3 (CH), 124.3 (CH),
125.1 (CH), 126.6 (CH), 126.9 (CH), 127.6 (CH), 127.9 (CH), 127.9
(CH), 128.2 (CH), 128.4 (CH), 129.5 (CH), 132.1 (CH), 135.2 (C),
135.2 (CH), 137.1 (C), 137.4 (C), 138.3 (C), 139.4 (C), 139.9 (C),
140.9 (C); 31P NMR (162 MHz) d -21.0; m/z (EI) 547 (2%, M+H),
546 (11%, M), 426 (31%, MꢀFeꢀCp), 425 (100%, MꢀFeꢀCpꢀH);
HRMS C36H27FeP calcd 546.11943, found 546.11936.
Rf = 0.64 (10% EtOAc/pet. ether); ½a D25
ꢃ
¼ þ821:7 (c 0.14, CHCl3); IR
tmax 3068, 1615, 1606, 1420 cmꢀ1
;
1H NMR (400 MHz) d 4.07
(1H, m, Cpsub), 4.11 (5H, s, Cpunsub), 4.69 (1H, t, J = 2.6, Cpsub),
5.14 (1H, m, Cpsub), 6.31 (1H, dt, J = 5.0, 1.7, Fulv), 6.45 (1H, dm,
J = 5.0, Fulv), 6.63 (1H, ddt, J = 5.1, 1.6, 1.9, Fulv), 6.72 (1H, dm,
J = 5.3, Fulv), 7.13–7.27 (5H, m, PPh2), 7.43–7.47 (3H, m, PPh2),
7.48 (1H, d, J = 3.1, CpCH), 7.60–7.67 (2H, m, PPh2); 13C NMR
(100 MHz) d 71.0 (CH.), 71.1 (CH.), 73.0 (CH), 74.3 (CH), 80.6 (C),
85.5 (C), 119.8 (CH), 126.9 (CH), 128.0 (CH), 128.3 (CH), 128.4
(CH), 128.9 (CH), 129.5 (CH), 132.0 (CH), 133.4 (CH-Fulv.), 132.0
(CH), 137.0 (C), 138.1 (CH), 139.4 (C), 142.4 (C); 31P NMR
(162 MHz) d -23.0; m/z (EI+) 447 (28%, M+H), 446 (100%, M), 121
(4%, Cp+Fe); HRMS C28H23FeP calcd 446.08813, found 446.08852.
4.2.22. (pS)-1-(Diphenylphosphino)-2-(1H-inden-1-ylidene)-
methyl)-ferrocene 32
Starting from indene (58 mg, 0.50 mmol) and following the
same procedure as reported for 31 (reflux for 3 h) the title com-
pound was obtained as a dark red solid (189 mg, 76%) which con-
sisted of two inseparable isomers in an 8/2 ratio. Mp 70–72 °C;
4.2.20. (pS)-1-(Diphenylphosphino)-2-[(cyclopenta-1,3-dienyl)
methyl]-ferrocene 30
Rf = 0.63 (10% EtOAc/Pet. ether); ½a D25
¼ þ1543 (c 0.03, CHCl3); IR
ꢃ
tmax 2922, 2852, 1619, 1458, 1258, 1016 cmꢀ1; m/z (EI) 497
(35%, M+H), 496 (100%, M), 431 (3%, MꢀCp); HRMS C32H25FeP
calcd 496.10378, found 496.10335.
To a solution of 29 (50.0 mg, 0.11 mmol) in THF (5.0 mL), LiAlH4
was added (0.08 mL, 0.17 mmol, 2 M in THF) and the resulting
solution was stirred at rt overnight. Water (4 mL) was added and
the mixture was extracted with DCM (2 ꢂ 3 mL), washed with
water (1 ꢂ 2 mL), dried over MgSO4 and concentrated in vacuo.
Purification was achieved using flash column chromatography
(10% EtOAc/pet. ether) to give the title compound as a yellow solid
(38.0 mg, 76%) which consisted of 2 inseparable isomers in a 3/2
ratio. Mp 114–116 °C); Rf = 0.66 (10% EtOAc/pet. ether);
Major isomer: 1H NMR (600 MHz) d 4.02 (1H, m, Cpsub), 4.10 (5H,
s, Cpunsub), 4.64 (1H, t, J = 2.5, Cpsub), 5.10 (1H, m, Cpsub), 6.97 (1H,
dd, J = 5.5, 1.0, IndCH), 7.04 (1H, d, J = 5.5, IndCH), 7.12–7.70 (17H,
m, PPh2 and IndCH and CpCH); 13C NMR (150 MHz) d 70.9 (CH),
71.0 (CH), 72.4 (CH), 73.9 (CH), 79.9 (C), 86.2 (C), aromatic region
is ambiguous, therefore could not be assigned; 31P NMR
(162 MHz) d ꢀ22.6.
½
a 2D5
ꢃ
¼ ꢀ203:9 (c 0.98, CHCl3); IR tmax 3062, 3046, 2898, 2872,
Minor isomer: 1H NMR (600 MHz) d 4.04 (1H, m, Cpsub), 4.11
(5H, s, Cpunsub), 4.59 (1H, t, J = 2.5, Cpsub), 5.11 (1H, m, Cpsub),
6.53 (1H, d, J = 5.3, IndCH), 6.74 (1H, d, J = 5.3, IndCH), 7.12–7.70
(17H, m, PPh2 and IndCH and CpCH); 13C NMR (150 MHz) d 70.9
(CH), 71.1 (CH), 72.0 (CH), 73.6 (CH), 80.5 (C), 86.8 (C), aromatic re-
gion is ambiguous, therefore could not be assigned; 31P NMR
(162 MHz) d ꢀ21.6.
1609, 1583, 1475, 1430, 1362, 1172, 1105 cmꢀ1
.
Major isomer: 1H NMR (600 MHz) d 2.48 (1H, dm, J = 24.2,
Cp0CH2), 2.69 (1H, dm, J = 24.3, Cp0CH2), 3.54 (1H, dm, J = 15.6,
CpCH2Cp0), 3.71 (1H, m, Cpsub), 3.72 (1H, dm, J = 15.2, CpCH2Cp0),
4.03 (5H, s, Cpunsub), 4.24 (1H, m, Cpsub), 4.42 (1H, m, Cpsub), 5.77
(1H, m, Cp0CH), 6.25 (1H, m, Cp0CH), 6.33 (1H, m, Cp0CH), 7.03–
7.60 (10H, PPh2); 13C NMR (150 MHz) d 29.5 (CH2), 41.1 (CH2),
69.0 (CH), 69.8 (CH), 71.0 (CH), 71.9 (CH), 75.3 (C), 92.9 (C),
127.4 (CH), 127. 8 (CH), 128.0 (CH), 128. 2 (CH), 129.1 (CH),
132.5 (CH), 133.6 (CH), 134.5 (CH), 135.2 (CH), 137.8 (C), 139.7
(C), 145.3 (C); 31P NMR (162 MHz; CDCl3) d ꢀ23.1.
4.2.23. (pS)-1-(Diphenylphosphino)-2-((2,3,4,5-tetramethylcy-
clopenta-2,4-dienylidene)methyl)-ferrocene 33
Starting from TMCp (61 mg, 0.50 mmol) and following the same
procedure as reported for 31 (reflux for 16 h) the title compound
was obtained as an orange solid (170 mg, 68%). Mp 95–97 °C;
Minor isomer: 1H NMR (600 MHz) d 2.63 (1H, dm, J = 22.1,
Cp0CH2), 2.69 (1H, dm, J = 22.3, Cp0CH2), 3.61 (1H, dm, J = 15.8,
CpCH2Cp0), 3.73 (1H, m, Cpsub), 3.75 (1H, dm, J = 15.0, CpCH2Cp0),
Rf = 0.70 (5% EtOAc/Pet. ether); ½a D25
ꢃ
¼ þ1891 (c 0.10, CHCl3); IR
tmax 2912, 1615, 1432, 1200, 1165, 1106 cmꢀ1
;
1H NMR

J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
1033
(600 MHz) d 1.82 (3H, s, CH3), 1.84 (3H, s, CH3), 1.92 (3H, s, CH3),
2.01 (3H, s, CH3), 3.92 (1H, m, Cpsub), 4.08 (5H, s, Cpunsub), 4.45
(1H, t, J = 2.4, Cpsub), 4.80 (1H, m, Cpsub), 7.12 (2H, m, PPh2), 7.19
(3H, m, PPh2), 7.21 (1H, s, CpCH), 7.41 (3H, m, PPh2), 7.58 (2H, m,
PPh2); 13C NMR (150 MHz) d 10.1 (CH3), 11.4 (CH3), 11.5 (CH3),
13.9 (CH3), 70.3 (CH), 70.6 (CH), 73.2 (CH), 73.2 (CH), 80.0 (C),
87.7 (C), 122.0 (C), 126.0 (C), 127.9 (CH), 128.2 (CH), 128.2 (CH),
128.3 (CH), 129.3 (CH), 132.2 (CH), 135.2 (CH), 135.6 (C), 137.6
(C), 139.6 (C), 141.3 (C), 145.5 (C); 31P NMR (162 MHz) d ꢀ23.0;
m/z (EI) 503 (5%, M+H), 502 (11%, M); HRMS C32H31FeP calcd
502.15071, found 502.15011.
10.15 (1H, s, CHO); 13C NMR (150 MHz) d 45.8 (CH3), 60.4 (CH),
66.4 (CH), 68.0 (CH), 69.7 (CH), 72.0 (C), 117.7 (C), 193.0 (C); m/z
(EI+) 258 (14%, M+H), 257 (100%, M), 186 (22%, M–CHO–NMe2),
121 (M–CHO–NMe2–Cp); HRMS C13H15FeNO calcd 257.04976,
found 257.04910.
4.2.27. ( )-1-(N,N-Dimethyl)-2-[(cyclopenta-2,4-dienylidene)-
methyl]-ferrocene 38
A solution of 37 (120 mg, 0.47 mmol) in MeOH (20 mL) was
treated with pyrrolidine (0.08 mL, 0.93 mmol) and freshly cracked
cyclopentadiene (0.02 mL, 1.86 mmol) and the reaction was stirred
for 30 min. The mixture was concentrated in vacuo and purified by
flash column chromatography (DCM) to give the title compound as
4.2.24. (pS)-1-(Diphenylphosphino)-2-((2,3,4,5-tetraphenylcy-
clopenta-2,4-dienylidene)methyl)-ferrocene 34
a deep-purple-red oil (86.0 mg, 61%). Rf = 0.31 (DCM); IR
t
max 3096,
Starting from TPCp44 (185 mg, 0.50 mmol) and following the
same procedure as reported for 31 (reflux for 72 h) the title com-
pound was obtained as a red solid (159 mg, 42%). Mp 124–
2943, 2821, 2778, 1621, 1609, 1484, 1451, 1431, 1106 cmꢀ1
;
1H
NMR (600 MHz) d 2.65 (6H, s, N(CH3)2), 4.18 (5H, s, Cpunsub), 4.26
(1H, dd, J = 2.6, 1.3, Cpsub), 4.38 (1H, t, J = 2.7, Cpsub), 4.66 (1H, dd,
J = 2.5, 1.1, Cpsub), 6.36 (1H, dt, J = 5.0, 1.7, Fulv), 6.50 (1H, dt,
J = 5.0, 1.5, Fulv), 6.61 (1H, ddd, J = 5.1, 1.7, 1.5, Fulv), 6.65 (1H,
dm, J = 5.2, Fulv), 7.37 (1H, s, CpCH); 13C NMR (150 MHz) d 46.2
(CH3), 58.0 (CH), 65.4 (CH), 66.7 (CH), 70.4 (CH), 76.0 (C), 117.4
(C), 120.0 (CH), 126.7 (CH), 128.7 (CH), 132.8 (CH), 138.4 (CH),
141.1(C); m/z (EI+) 306 (4%, M+H), 305 (15%, M); HRMS C18H19FeN
calcd 305.08614, found 305.08703.
126 °C; Rf = 0.52 (10% EtOAc/Pet. ether); ½a D25
¼ þ2625 (c 0.02,
ꢃ
CHCl3); IR tmax 3055, 1592, 1484, 1434, 1235, 1216, 1165,
1106 cmꢀ1 1H NMR (600 MHz) d 3.79 (1H, br, Cpsub), 3.86 (1H,
;
br, Cpsub), 4.03 (1H, br, Cpsub), 4.04 (5H, s, Cpunsub), 6.79–7.05
(15H, m, ArH), 7.22–7.25 (4H, m, ArH), 7.31–7.36 (9H, m, ArH),
7.46–7.48 (2H, m, ArH), 7.58 (1H, s, CpCH); 13C NMR (150 MHz) d
70.6 (CH), 71.3 (CH), 72.8 (CH), 74.1 (CH), 82.0 (C), 86.3 (C),
125.8 (CH), 126.0 (CH), 126.1 (CH), 126.5 (CH), 127.2 (CH), 127.3
(CH), 127.5 (CH), 127.7 (CH), 127.9 (CH), 128.2 (CH), 128.2 (CH),
128.5 (CH), 129.2 (CH), 130.4 (CH), 130.6 (CH), 131.1 (C), 131.8
(CH), 132.9 (CH), 134.8 (CH), 135.8 (C), 135.9 (C), 135.9 (C), 136.2
(C), 137.3 (C), 137.6 (C), 139.4 (C), 139.8 (C), 141.0 (CH), 141.1
(CH), 142.1 (C), 144.3 (C); 31P NMR (121 MHz) d ꢀ23.7; m/z (EI)
503 (5%, M+H), 502 (11%, M); HRMS C32H31FeP calcd 446.08813,
found 446.08852.
4.2.28. ( )-1-(Dimethylamino)-2-[(cyclopenta-1,3-dienyl)methyl]-
ferrocene 39
A solution of 38 (70.0 mg, 0.23 mmol) in THF (15 mL) was trea-
ted with LiAlH4 (0.14 mL, 0.28 mmol, 2 M in THF) and the reaction
was stirred for 3 h. Water (10 mL) was then added to the mixture
at 0 °C and the mixture was extracted with diethyl ether
(2 ꢂ 15 mL). The combined organics were dried over MgSO4, con-
centrated in vacuo and purified by flash column chromatography
(1% EtOAc/DCM) to give the title compound as a yellow solid
(49.0 mg, 70%) which consisted of 2 inseparable isomers in a 55/
45 ratio. Mp 52–54 °C, Rf = 0.17 (1% EtOAc/DCM); IR (solid) tmax
4.2.25. ( )-4-(Methoxymethyl)-2-[a-(N,N-dimethyl)-ferrocenyl]-
1,3-dioxane 36
To a suspension of 3540 (300 mg, 0.91 mmol) and paraformalde-
hyde (272 mg, 9.06 mmol) in MeCN (15 mL), NaBH3CN (85.0 mg,
1.36 mmol) was added and the mixture was stirred for 10 min at
rt while the colour changed from orange to yellow. The suspension
was concentrated in vacuo and purified by column chromatogra-
phy (80% EtOAc/pet. ether) to give the title compound as a yellow
solid (190 mg, 58%). Mp 81–83 °C; Rf = 0.41 (80% EtOAc/pet. ether);
IR tmax 3094, 2946, 2871, 2843, 2816, 2771, 1483, 1453, 1421,
3093, 2890, 2826, 2785, 1604, 1490, 1417, 1101 cmꢀ1
;
Major isomer: 1H NMR (600 MHz) d 2.57 (6H, s, N(CH3)2), 2.92
(2H, s, Cp0CH2), 3.51 (1H, d, J = 16.5, CpCH2Cp0), 3.70 (1H, d,
J = 16.7, CpCH2Cp0), 3.89 (1H, m, Cpsub), 3.92 (1H, m, Cpsub), 3.96
(1H, m, Cpsub), 4.14 (5H, m, Cpunsub), 6.09 (1H, s, Cp0CH), 6.25
(1H, d, J = 4.7, Cp0CH), 6.39 (1H, d, J = 3.8, Cp0CH); 13C NMR
(150 MHz) d 30.0 (CH2), 43.7 (CH2), 45.4 (CH3), 56.0 (CH), 62.2
(CH), 66.9 (CH), 69.0 (Cpunsub), 80.3 (C), 112.6 (C), 127.4 (CH),
130.9 (CH), 132.4 (CH), 149.1 (C).
1319, 1115, 1100 cmꢀ1
; d 1.51 (1H, d,
1H NMR (600 MHz)
J = 13.0, CH2CH2CH), 1.79 (1H, dd, J = 13.0, 5.0, CH2CH2CH), 2.64
(6H, s, N(CH3)2), 3.34 (3H, s, OCH3), 3.35 (1H, m, CH2OMe), 3.47
(1H, dd, J = 9.5, 6.3, CH2OMe), 3.92 (1H, s, Cpsub), 3.95 (1H, s, Cpsub),
4.00 (2H, m, OCH and OCH2), 4.18 (5H, s, Cpunsub), 4.25 (1H, s,
Cpsub), 4.30 (1H, dd, J = 10.9, 4.3, OCH2), 5.59 (1H, s, CpCH); 13C
NMR (150 MHz) d 28.2 (CH2), 45.6 (CH3), 56.5 (CH), 59.3 (CH3),
63.2 (CH), 64.0 (CH), 67.1 (CH2), 69.3 (CH), 75.6 (CH2), 76.0 (CH),
79.6 (C), 99.8 (CH), 112.8 (C.); m/z (EI+) 360 (4%, M+H), 359 (18%,
M); HRMS C18H25FeNO3 calcd 359.11784, found 359.11792.
Minor isomer: 1H NMR (600 MHz) d 2.58 (6H, s, N(CH3)2),
2.95 (2H, s, Cp0CH2), 3.49 (1H, d, J = 16.1, CpCH2Cp0), 3.62 (1H,
d, J = 16.4, CpCH2Cp0), 3.89 (1H, m, Cpsub), 3.92 (1H, m, Cpsub),
3.96 (1H, m, Cpsub), 4.14 (5H, m, Cpunsub), 5.96 (1H, s, Cp0CH),
6.42 (1H, d, J = 4.4, Cp0CH), 6.50 (1H, d, J = 4.2, Cp0CH); 13C
NMR (150 MHz)
d 29.1 (CH2), 41.3 (CH2), 45.4 (CH3), 56.1
(CH), 62.1 (CH), 66.8 (CH), 68.9 (CH), 79.8 (C), 112.6 (C), 127.0
(CH), 133.8 (CH), 134.9 (CH), 146.4 (C); m/z (EI+) 308 (23%,
M+H), 307 (100%, M), 242 (MꢀCp), 199 (MꢀCpꢀNMe2); HRMS
4.2.26. ( )-2-(N,N-Dimethyl)-formylferrocene 37
C
C
18H21FeN calcd 307.10179, found 307.10158; Anal. Calcd For
18H21FeN: C, 70.34; H, 6.89; N, 4.56. Found: C, 70.21; H,
A solution of 36 (405 mg, 1.13 mmol) and pTSA.H2O (10.0 mg,
0.06 mmol) in acetone/water (4.0 mL/4.0 mL) was refluxed for
3.5 h. Next, DCM (5 mL) was added and the mixture was washed
with NaHCO3(aq) (1 ꢂ 2 mL), and brine (1 ꢂ 2 mL), dried over
MgSO4 and concentrated in vacuo. Purification was achieved using
flash column chromatography (10% EtOAc/pet. ether) to give the ti-
tle compound as a red oil (178 mg, 61%). Rf = 0.32 (30% EtOAc/pet.
ether); IR tmax 3094, 2950, 2846, 2786, 1666, 1501, 1423,
6.88; N, 4.49%.
Acknowledgments
We thank AstraZeneca, the EPSRC, University College London
and the University of Nottingham for funding, Mr. T. Hollingworth,
Mr. D. Hooper, Mr. J. Hill and Dr. L. Harris for providing mass spec-
tra and Dr. T. Liu for microanalytical data.
;
1106 cmꢀ1 1H NMR (600 MHz) d 2.71 (6H, s, N(CH3)2), 4.29 (6H,
s, Cpsub and Cpunsub), 4.42 (1H, app s, Cpsub), 4.63 (1H, app s, Cpsub),

1034
J. C. Anderson et al. / Tetrahedron: Asymmetry 24 (2013) 1023–1034
25. Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.; Nagashima, N.; Hamada, Y.;
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