The preparation of ferrocene-containing phosphinamine ligands possessing central and planar chirality and their application in palladium-catalysed allylic substitution

Article abstract of DOI:10.1016/j.tet.2021.132088

The preparation of four novel ferrocenylphosphinamine ligands, possessing both planar and central chirality, is described. The absolute configuration of two of the ligands was confirmed by X-ray crystallographic analysis. The palladium complexes of these

Full text of DOI:10.1016/j.tet.2021.132088

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The preparation of ferrocene-containing phosphinamine ligands
possessing central and planar chirality and their application in
palladium-catalysed allylic substitution*
,
*
Keith Meaney a, Richard Goddard b, Raymond P.J. Bronger a, Patrick J. Guiry a
a Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
b Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The preparation of four novel ferrocenylphosphinamine ligands, possessing both planar and central
chirality, is described. The absolute configuration of two of the ligands was confirmed by X-ray crys-
tallographic analysis. The palladium complexes of these new ligands were applied in the allylic alkylation
of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate to study the effect of planar chirality and/or
the trimethylsilyl group. Quantitative yields with ees of up to 77% were obtained with the ligand that
bears both (R)-planar and (R)-central chirality. Application of its trimethylsilyl analogue gave signifi-
cantly lower ees, whereas the presence of the trimethylsilyl group in the ligand that bears (S)-planar and
(R)-central chirality had a beneficial effect on enantioselectivity. Solution 1H NMR spectroscopic studies
of the 1,3-diphenylallyl palladium complexes of two of the ligands revealed the major diastereomer in
solution does not give rise to the major product observed in allylic alkylation, assuming nucleophilic
attack trans to phosphorus.
Received 24 December 2020
Received in revised form
10 March 2021
Accepted 11 March 2021
Available online xxx
Keywords:
Ferrocene ligands
Chiral PN Ligands
Pd-catalysed asymmetric allylic alkylation
Mechanistic studies
© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
1. Introduction
has received much attention. In this respect, a plethora of diphos-
phine and diamine ligands and, more recently, phosphinamine
Since the initial reports by Tjuji [1,2], allylic alkylation has
emerged as one of the most widely studied catalytic reactions in
organic synthesis. Especially asymmetric allylic alkylation, first
reported by Trost [3e5], is nowadays regarded as one of the most
important asymmetric catalytic transformations in organic chem-
istry for the formation of a diversity of bonds to carbon and has
been the subject of several excellent reviews and book chapters
[6e13]. In the last few decades, much research has been devoted to
elucidate the factors that influence the outcome of the reaction,
such as metal, solvent, nucleophile, allylic substrate and ligand,
including mechanistic investigations underpinned by a combina-
tion of structural, spectroscopic and computational studies
[14e22]. In particular, the design and application of chiral ligands
[23e26] ligands have been used to great success, leading to high
enantioselectivities at high conversion. In the latter class of ligands,
electronic desymmetrisation of the allyl encourages preferential
attack of the nucleophile at the allylic carbon trans to phosphorus,
which is more electrophilic due to the larger trans-effect exerted by
phosphorus [27e31]. In combination with steric effects, high
enantioselectivities can be obtained and selected examples include
the Phox ligands 1 developed independently by Williams, Pfaltz,
and Helmchen [32e34], Brown’s axially chiral Quinap ligand 2 [35]
and the pyrrolidine-containing ligands 3e4 which we reported,
Fig. 1 [36e38].
In addition, planar chiral ferrocene ligands have been particu-
larly successful leading to an unprecedented high enantiose-
lectivity of 99.6% ee at full conversion for the alkylation of 1,3-
diphenyl-2-propenyl acetate with dimethyl malonate [39]. Other
phosphinamine ferrocene-containing ligands possessing planar
chirality have been prepared and applied with success in allylic
alkylation and a variety of other asymmetric processes [40]. The
ease of preparation of planar chiral ferrocene compounds through
the use of diastereoselective ortho-metalating groups, including
*
Dedicated to the memory of Professor Jonathan Williams, a brilliant chemist
with pioneering work in P,N ligands and borrowing hydrogen chemistry e a true
gentleman and someone who I was always happy to meet.
* Corresponding author. Centre for Synthesis and Chemical Biology, School of
Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
E-mail address: p.guiry@ucd.ie (P.J. Guiry).
https://doi.org/10.1016/j.tet.2021.132088
0040-4020/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Please cite this article as: K. Meaney, R. Goddard, R.P.J. Bronger et al., The preparation of ferrocene-containing phosphinamine ligands possessing
central and planar chirality and their application in palladium-catalysed allylic substitution, Tetrahedron, https://doi.org/10.1016/
j.tet.2021.132088

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
Fig. 1. Typical P,N ligands applied to the Pd-catalysed allylic alkylation.
amines [41e43], sulfoxides [44], acetals [45], oxazolines [46e48]
azepines [49], sulfoximines [50] and hydrazones [51], certainly
contributed to the wide range of planar chiral ferrocene ligands
reported. We reported the preparation of ferrocenylphosphinamine
ligands of type 5, Fig. 2, possessing both planar and central chirality
obtained through diastereoselective metalation of trans-(2R,5R)-
2,5-dialkyl-1-(ferrocenylmethyl)pyrrolidines and their application
in Pd-catalysed allylic alkylation [52]. The initial example of
Kumada and Hayashi [41], and subsequent related examples from
Togni [42], however, have as their key precursor (R)-N,N-(dimethyl-
(dimethyl-1-ferrocenyl)ethylamine 2 [57]. Unfortunately, no prod-
uct was obtained at either room temperature, 0 ꢀC or ꢁ78 ꢀC. We
then focused on s-butyllithium-mediated deprotonations in ether
and successful lithiation and phosphinylation only occurred
at ꢁ78 ꢀC, affording the 1,2 disubstituted product 3 in a moderate
42% yield. The use of hexane as solvent with TMEDA as additive did
not improve the yield (30%). Although no product was observed by
performing the lithiations at 0 ꢀC, yields were substantially
improved by addition of s-butyllithium at ꢁ78 ꢀC and stirring at
this temperature for 3 h followed by stirring at 0 ꢀC for 1.5 h,
Scheme 1. Subsequent reaction with chlorodiphenylphosphine
1-ferrocenyl)ethylamine 6, which bears an
Thus, interested by the successful application of ferrocene-
containing ligands, bearing an -chiral center, and to extend our
work on pyrrolidine-containing P,N ligands, we wished to develop
novel ferrocene ligands in which the -chiral center is incorporated
a-chiral center.
afforded 3 in 64% yield and 84% de as determined from 1H and 31
NMR spectroscopic analysis.
P
a
The crude mixture was purified by column chromatography on
neutral silica gel, with both diastereomers being isolated. A high
optical rotation of þ425 (c ¼ 0.2, CHCl3) was recorded for the major
diastereomer. Comparison of this optical rotation with those of
known planar chiral ferrocene compounds suggested that the
major diastereomer was (R,R)-9. Crystals of the major diastereomer
suitable for single-crystal X-ray structure determination were
grown from ethanol (crystal - orthorhombic, space group P21,21,21).
Fig. 4 shows the results of the analysis, which established that the
newly introduced planar chirality had the (R)-configuration, while
also confirming the (R)-central chirality in the pyrrolidine ring as
previously established [53].
The ortho-directing properties of (R)-7 are in contrast to the
ortho-directing properties of the related (R)-N,N-(dimethyl-1-
ferrocenyl)ethylamine 6, which afforded 1,2 disubstituted ferro-
cene derivatives in a 92% de, with the major diastereomer pos-
sessing (S)-planar chirality. Therefore a marked change in the
ortho-directing properties was observed when the nitrogen atom
a
in a pyrrolidine unit. We had previously reported the enantiose-
lective preparation of ferrocenepyrrolidine (R)-7 and applied it in
the diastereoselective formation of a series of N,O ligands of type 8
for the diethylzinc-mediated addition to aldehydes [53]. Therefore,
we now wish to report the synthesis and application of novel
ferrocene-phosphinamine ligands (R,R)-9, (R,S)-9, (R,R)-10 and
(R,S)-10 obtained through diastereoselective ortho-metalation of
ferrocenepyrrolidine (R)-7, Fig. 3.. These ligands were tested in the
allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl
malonate anion as nucleophile. In order to rationalise the origin of
enantioselectivity obtained in allylic alkylation, an NMR study of
their palladium h
3-allyl species will also be presented.
2. Results and discussion
Starting from ferrocenepyrrolidine (R)-7, we investigated its
diastereoselective ortho-directing properties and, similar to the
and the a-methyl group are contained within a pyrrolidine ring. By
examination of the possible transition states 11 and 12, the fav-
oured diastereomer can be predicted, Fig. 5.
extensive lithiation studies described for
a-(N,N-dimethylamino)
alkylferrocenes [54,55], various ferrocenyloxazolines [47,56] and
the trans-2,5-dialkyl-ferrocenylpyrrolidines [52], variations of the
alkyllithium reagent, solvent, temperature and lithiation time were
examined for its phosphinylation.
Initial studies towards the lithiation of (R)-5 were carried out
with n-butyllithium in ether, the successful conditions employed
by Hayashi and Ugi for lithiation of closely related (R)-N,N-
In transition state 11, we postulate that the upper cyclo-
pentadienyl ring and the pyrrolidine ring are nearly co-planar, thus
minimising the steric interactions between the pyrrolidine ring and
the iron atom. In addition the methyl group points toward the
ferrocene unit. Although generally this is disfavoured, it allows for
the approach of the alkyllithium towards the nitrogen atom from
Fig. 2. Typical P,N ligands applied to the Pd-catalysed allylic alkylation.
2

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
Fig. 3. Ligands (R,R)-9, (R,S)-9, (R,R)-10 and (R,S)-10.
Scheme 1. Synthesis of (R,R)-9.
alkyllithium in this case is sterically hindered by the pyrrolidine
ring, which is projected upward towards the incoming reagent.
Synthesis of ligands (R,S)-9, (R,R)-10 and (R,S)-10. Although
small quantities of minor diastereomer (R,S)-9 can be obtained, a
more effective synthesis toward formation of (R,S)-9 is desirable. To
this purpose, the trimethylsilyl group is used to temporarily block
the favoured diastereomeric position, an approach first employed
by Richards in analogous ferrocenyloxazoline chemistry [56]. Thus,
lithiation of (R)-7 under the optimal conditions as described pre-
viously determined, followed by
a
quench with chloro-
trimethylsilane gave 13 in 71% yield with 70% de. After purification
by column chromatography on silica gel the major diastereomer
was isolated in 50% yield. Subsequently, the diphenylphosphino
group was introduced by lithiation of (R,R)-13 with s-butyllithium
followed by reaction with chlorodiphenylphosphine to afford the
1,2,3-trisubstituted-ferrocenylpyrrolidine (R,S)-10 in 70% yield.
Next, the trimethylsilyl protecting group was removed by heating
(R,S)-10 with TBAF in THF under reflux for 4 days to give (R,S)-9 in
59% yield, Scheme 2.
Fig. 4. X-Ray single crystal structure of (R,R)-9.
To date only two reports have detailed the effect of ortho-sily-
lation on the properties of ferrocene-based ligands in catalysis.
Firstly, the application of the trimethylsilyl modified ligand 14 in
the allylic alkylation of 1,3-diphenylprop-2-enyl using dime-
thylmalonate anion as the nucleophile led to better enantiocontrol
(ee ¼ 89% (R)-product) compared to the application of its unsily-
lated analogue 15 (ee ¼ 38% (S)) [58], Fig. 6. Secondly, the intro-
duction of a trimethylsilyl group to (R,R)-8a to generate (R,R)-8b
had a pronounced effect in catalysis as the ee increased from 84 to
95% for the diethylzinc addition to aldehydes [53]. Alternatively, the
introduction of the TMS group to (R,S)-8a to generate (R,S)-8b had a
detrimental effect on the enantioselectivity and its sense (from 92%
to ꢁ67%).
Thus, also in our case, in catalysis the intermediate trisubsti-
tuted ferrocenes may show interesting properties due to the tri-
methylsilyl group influencing the conformation of the pyrrolidine
ring. For a full comparison of both planar chirality and the effect of
the trimethylsilyl group, trisubstituted ferrocenephosphinamine
ligand (R,R)-10 was prepared in 93% yield by lithiation of (R,R)-9
followed by reaction with chlorotrimethylsilane, Scheme 3. Crystals
of the major diastereomer suitable for single-crystal X-Ray struc-
ture determination were grown from ethanol (crystal - monoclinic,
space group P21). Fig. 7 shows a view of one of the two independent
Fig. 5. Proposed transition states for lithiation of (R)-7.
above the plane of the upper cyclopentadienyl ring. This is the
favoured transition state, which leads to the (R)-planar chirality.
However in transition state 12, if the nitrogen lone pair points to-
wards the ortho-cyclopentadienyl carbon this would place the
pyrrolidine ring in a non co-planar geometry. Approach of the
3

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
Scheme 2. Synthesis of ligands (R,S)-10 and (R,S)-9.
63e99% yield by reaction of the appropriate phosphinamine ligand
with
3-allyl palladium chloride dimer and sodium tetra-
h
fluoroborate. Two isomeric complexes can be envisaged, namely
one having the central allyl proton pointing above the PeN plane
(endo) and one having the central allyl proton pointing below the
PeN plane (exo). These complexes can interconvert through a h3
-
h1 3 mechanism. For the complexes obtained with ligands (R,R)-9
-h
Fig. 6. Trisubstituted ferrocene ligands 14 and 15.
and (R,S)-9 only one diastereomer was observed by 31P NMR
spectroscopy, whereas the complexes obtained from (R,S)-10 and
(R,R)-10 showed both diastereomers in a 1:1 and 1:24 ratio,
respectively. As the test reaction the alkylation of 1,3-diphenyl-2-
propenyl acetate using dimethylmalonate anion as the nucleo-
phile was investigated, Scheme 4.
Allylic alkylations were carried out on a 0.25 mmol scale of 1,3-
diphenylpropenyl acetate employing 2 mol% of catalyst. The
nucleophile was either added as its preformed sodium salt or it was
formed in situ by addition of N,O-bis(trimethylsilyl) acetamide
(BSA) and a catalytic amount of KOAc. The key results of the allylic
alkylation experiments using the BSA and sodium malonate pro-
cedures are summarised in Tables 1 and 2 e see Supporting Infor-
mation for a full set of results.
Scheme 3. Synthesis of (R,R)-10.
BSA Procedure. Using the BSA procedure moderate to very high
conversions were obtained for all catalysts, although longer reac-
tion times were required for the catalysts obtained from ligands
(R,R)-9 and (R,R)-10. In all cases the (R)-enantiomer was the fav-
oured isomer formed, with the highest ee of 77% obtained using
ligand (R,R)-9 in DMF at room temperature (Table 1, entry 1). By
lowering the reaction temperature from room temperature
to ꢁ25 ꢀC the enantioselectivity decreased from 77% to 71% ee
(Table 1, entry 2). A comparison of the results from catalysis of
diastereomeric ligands (R,R)-9, and (R,S)-9 shows that the (R,R)-
ligand afforded the higher enantioselectivity, with the optimum
being 77% ee with DMF as solvent, compared to 42% ee for the
diastereomeric (R,S)-ligand (Table 1, entry 4). Therefore, the (R,R)-
ligand is the matched case of the two elements of chirality. How-
ever the (R,S)-ligand has higher activity, resulting in high conver-
sions within 2e3 h for reactions in dichloromethane and DMF,
compared to 48 h for the (R,R)-diastereomer (Table 1, entries 3 and
4). A comparison of the role of planar chirality in the trisubstituted
ferrocene derivatives shows that the (R,S)-10 ligand afforded the
product with 57% ee in 90% conversion after 2 h compared to 20% ee
in 40% conversion after 23 h for the diastereomeric (R,R)-10
(Table 1, entries 6 and 8). Interestingly, compared to the optimum
disubstituted phosphinamine ligand which had the (R)-planar
chirality, the optimum trisubstituted ligand bears the opposite (S)-
planar chirality.
Fig. 7. X-Ray structure of one of the two independent molecules of (R,R)-10 in the
crystal.
molecules in asymmetric unit of the crystal, which differ only
slightly in their conformations (see Supporting Information).
3. Allylic alkylation
Investigation of the role played by the bulky trimethylsilyl group
in influencing the properties of the ligand (R,S)-10 in catalysis
compared to the analogous phosphinamine ligand (R,S)-9 shows
that the trisubstituted-ferrocenyl phosphinamine ligand afforded
higher enantioselectivities of 57% ee in DMF compared to 42% ee for
the disubstituted analogue (R,S)-9 (Table 1, entries 4 and 6). The
bulky trimethylsilyl group may restrict the conformation of the
pyrrolidine ring, thereby allowing it to be a more effective chiral
controlling group, which increases the enantioselectivity. From
The enantio-differentiating abilities, the role of planar chirality
and the influence of the trimethylsilyl group in allylic alkylation
employing ligands (R,R)-9 and (R,S)-9 (R,S)-10 and (R,R)-10 were
investigated. The catalyst can either be preformed palladium h3
-
allyl complexes of the ligand or to assume that such complexes are
formed when a slight excess of ligand is added to e.g. Pd2(dba)3 or
h
3-allyl palladium chloride dimer. The former approach was
employed in the present study. The air-stable
tetrafluoroborate complexes of these ligands were prepared in
h
3-allyl palladium
4

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
Scheme 4. Asymmetric allylic alkylation.
Table 1
4. Solution NMR studies
Pd-catalysed Allylic Alkylation using BSA procedure.a
Considerable effort has been made to understand the critical
enantiodifferentiating carbon-carbon bond-forming step from the
initial investigations of Bosnich [59,60] employing diphosphine li-
gands to the more recent work of Brown, Pfaltz, Togni and Helm-
chen employing phosphinamine ligands [27,34,35,61e64]. The key
findings from these studies suggest that the transition state of allyl
palladium complexes contains an allyl group which has reoriented
Entry
Ligand
Solvent
Time (h)
Conversionb (%)
Eec (%) (R)
1
2
3
4
5
6
7
8
(R,R)-9
(R,R)-9
(R,S)-9
DMF
DMFd
DCM
DMF
DCM
DMF
DCM
DMF
48
168
3
2
2
2
6
24
100
88
81
58
73
90
67
40
77
71
28
42
54
57
32
20
(R,S)-9
(R,S)-10
(R,S)-10
(R,R)-10
(R,R)-10
itself into a
h -
2-alkene product-like geometry, rather than the h3
allyl starting complex, thus facilitating nucleophilic attack on the
allyl terminal carbon trans to the phosphorus donor atom. The
lability of the diastereomeric 1,3-diphenylallyl complexes is influ-
enced by such electronic factors and also by intra-complex steric
clashes between the ligand and the allyl. In the case that the 1,3-
diphenylallyl palladium complexes only adopt a syn-syn geome-
try, two isomeric complexes can be envisaged, namely one having
the central allyl proton pointing above the PeN plane (endo) and
one having the central allyl proton pointing below the PeN plane
(exo). Upon nucleophilic attack trans to phosphorus the endo-dia-
stereomer will lead to the product having the opposite configura-
tion of the product obtained through reaction of the exo-
diastereomer, Scheme 5.
a
Reaction conditions: (ligand)Pd(allyl).BF4/allyl/dimethyl malonate/KOAc/
BSA ¼ 1/50/55/1/55. T ¼ room temperature.
b
Determined by 1H NMR spectroscopy.
Ees were determined by HPLC (Chiracel OD column). Configuration was deter-
c
mined by comparison of the optical rotation with literature values.
d
T ¼ ꢁ25 ꢀC.
Table 2
Pd-catalysed Allylic Alkylation using Sodium Malonate Procedure.a
Entry
Ligand
Solvent
T (h)
Conversionb (%)
Eec (%) (R)
1
2
3
4
(R,R)-9
(R,S)-9
(R,S)-10
(R,R)-10
DMF
48
22
5
12
17
92
12
58
24
50
33
DMF
DCMd
DCMd
28
Thus, in an attempt to explain the stereoselectivity obtained
from application of metal complexes of ligands (R,R)-9, (R,S)-9,
(R,S)-10 and (R,R)-10 in allylic alkylation and to gain an insight into
the presence and configuration of the diastereomeric intermediates
a
Reaction conditions: (ligand)Pd(allyl).BF4/allyl/sodium dimethyl malonate ¼ 1/
50/55. T ¼ room temperature.
b
Determined by 1H NMR spectroscopy.
Ees were determined by HPLC (Chiracel OD column), configuration was deter-
c
present in solution, NMR studies of the (1,3-diphenyl-
palladium tetrafluoroborate complexes 16e19 were carried out.
Additionally, for each ligand the (1,1,3-triphenyl-
3-allyl)palladium
h
3-allyl)
mined by comparison of the optical rotation with literature values.
d
15-crown-5 was added.
h
tetrafluoroborate complexes 20e23 were studied since NMR
studies of these complexes provide information on the steric de-
mand exerted by the ligands cis- and trans-to the diphenylphos-
these results, the trend suggests that the trimethylsilyl group has
only a marginal effect on the activity. The presence of the sterically
demanding trimethylsilyl group in (R,R)-10 did not enhance the
enantioselectivity compared to its analogous ligand (R,R)-9 as
lower selectivities are obtained in DMF and acetonitrile (Table 1,
entries 4 and 8). Therefore, the trimethylsilyl group lowers the
observed enantioselectivity in catalysis.
phino
tetrafluoroborate complexes 16e19 and (1,1,3-triphenyl-
palladium tetrafluoroborate complexes 20e23 were prepared by
reaction of ligands 9 and 10 with the respective
3-allyl palladium
moiety.
The
(1,3-diphenyl-
h
3-allyl)palladium
3-allyl)
h
h
chloride dimer and sodium tetrafluoroborate, Scheme 6.
31P NMR spectroscopy was carried out to determine the number
and ratio of different diastereomers formed. 1H NMR and 1He1H
COSY were used to identify the protons of the unsubstituted
cyclopentadienyl ring, the N-methyl group, the trimethylsilyl group
(for complexes derived from ligands (R,R)-10 and (R,S)-10) and the
allyl protons of both intermediates. Subsequent 1D and 2D NOESY
experiments were performed to determine the configurations of
the major and minor intermediates. This procedure is exemplified
by analysis of the complexes derived from ligand (R,R)-9 and all
other complexes were identified in a similar manner e for all
relevant spectra and full analysis, see Supporting Information.
Analysis of 16 by 31P NMR spectroscopy confirmed the presence
of both diastereomeric intermediates as indicated by two peaks in
Sodium malonate procedure. In all cases the (R)-enantiomer was
the favoured isomer formed, again with the highest ee of 58% being
obtained using ligand (R,R)-9 in DMF (Table 2, entry 1). For all
catalysts prepared and irrespective of the solvent applied, low
conversions were obtained when the sodium malonate procedure
was used. The only exception was the catalyst derived from ligand
(R,S)-10 in dichloromethane, which gave 92% conversion after 3 h
(Table 2, entry 3). Addition of 15-crown-5, which is commonly used
to increase the solubility of the anion, gave optimal results for the
catalysts derived from trimethylsilylsubstituted ligands (R,S)-10
and (R,R)-10 when the reactions were performed in dichloro-
methane (Table 2, entries 3 and 4). Comparison of the diastereo-
meric ligands and the effect of the trimethylsilyl group is analogous
to the results obtained applying the BSA procedure.
the spectrum at
d 18.8 and d 21.3 in a 1:1.7 ratio. Further NMR
5

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
Scheme 5. Exo- and endo-diastereomers leads to product having the opposite configuration.
Scheme 6. Synthesis of palladium complexes 16e23.
studies were carried out to determine the configuration of these
isomers in solution. In the 1H NMR spectrum, there were two sin-
glets at
d 3.69 and d 3.70 each representing the unsubstituted
cyclopentadienyl ring of the major and minor diastereomers,
respectively, while the N-methyl group also appeared as a singlet at
d
1.95 (major) and d
2.50 (minor). With the aid of 1He1H COSY the
allyl protons of both intermediates were identified. For the major
isomer, the allyl proton trans to nitrogen appeared as a doublet at
d
5.42, which showed a COSY cross-peak to the central allyl proton
which appeared as an apparent triplet centred at 6.18. This in turn
showed a cross-peak to a multiplet between 5.56e5.64, which
d
d
integrated for slightly more than one proton, and this was assigned
as the allyl proton trans to phosphorus together with an allyl proton
of the minor isomer. The allyl protons of the minor isomer were
identified as a doublet at
this gave a COSY cross-peak to a multiplet at
proton). A COSY cross-peak was observed between this multiplet
and the multiplet at 5.56e5.64, hence the allyl proton trans to
d
3.63 (allyl proton trans to nitrogen) and
Fig. 8. Relevant nOes for complex 16.
d
6.78 (central allyl
d
phosphorus of the minor diastereomer is overlapped by the same
proton of the major diastereomer.
With this information, 2D and 1D NOESY experiments were
carried out to determine the configurationsof the major and minor
intermediates. From the 2D NOESY spectrum, a nOe was observed
between the terminal allyl protons of the major diastereomer
which confirms the syn-syn orientation of the allyl group. Similarly
a nOe between the terminal allyl protons of the minor diastereomer
were also observed. Both N-methyl peaks showed a nOe to an
apparent triplet at
assigned as the proton
diastereomers. A 1D NOESY experiment was also carried out; by
irradiating the multiplet at 5.56e5.64, which represents both allyl
d
2.96 which integrates for 2 protons. This is
a
-to ferrocene for both the major and minor
Fig. 9. Possible configurations of the major diastereomer of 20 in solution.
d
protons trans to phosphorus, nOe enhancements were observed to
each of the allyl protons trans to nitrogen. In addition a nOe was
spectrum was complicated and only the major isomer could be
identified. A doublet at
proton trans to nitrogen. This showed a COSY cross-peak to a
multiplet at 7.05 where the central allyl proton was overlapped by
d 3.16 was noted and assigned as an allyl
observed to the apparent triplet at
d 2.96, and the singlet at d 2.50
representing the N-methyl of the minor diastereomer. This con-
firms the minor diastereomeric intermediate is the exo-syn-syn,
hence the major diastereomer is the endo-syn-syn 16, Fig. 8.
31P NMR spectroscopic analysis of 20 by confirmed the presence
of three of the four possible diastereomers with three singlets at
d
aromatic protons. Therefore the configuration of the major diaste-
reomer in solution is likely to be either of the following two pos-
sibilities where the terminal allyl proton is trans to nitrogen, Fig. 9.
However no nOe was observed that could confirm the
d
17.4, 19.7, and 24.3 present in a ratio of 1:15:3. The 1H NMR
6

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
configuration of the allyl group of the major diastereomer. Another
point to note is that in the preferred isomer the allyl terminus
bearing the geminal diphenyl groups are on the side opposite to the
diphenylphosphine indicating that this area of the ligand/metal
complex had greater steric demand compared to the pyrrolidine
group.
(R)-enantiomer of product. In the case of complex 18, the endo
diastereomer is favoured in an 8:1 endo:exo ratio, which when
alkylated affords the preferred (R)-enantiomer. Also in this case the
trimethylsilyl group reduces the diastereomeric ratio compared to
ligand (R,S)-9, however the endo-isomer is still favoured. Compared
to (R,S)-9 application of (R,S)-10 resulted in a higher ee of 57%,
which indicates that the trimethylsilyl substituents plays a large
role in controlling the course of the reaction favouring alkylation of
the endo-diastereomer.
For the triphenylsubstituted allyl palladium complexes the in-
fluence of planar chirality was evident; (R,R)-9 afforded 3 di-
astereomers in a 1:15:3 ratio, whereas all 4 diastereomers, in a
5:5:3:1 ratio, were observed for ligand (R,S)-9. The trimethylsilyl
derivatives of these ligands had the effect of improving the ratio of
these intermediates in solution. (R,R)-10 only gave 2 diastereomers
in solution in a 5:1 ratio compared to (R,R)-9, while (R,S)-10 showed
improved ratios of diastereomers from 5:5:3:1 to 1:15:3:1 ratios
when compared to (R,S)-9. Furthermore, by changing the planar
chirality from (R) to (S) a huge change in the steric demand occurs;
for 20 and 23 the preferred isomer has the allyl terminus bearing
the geminal diphenyl groups on the side opposite to the diphe-
nylphosphine indicating that this area of the ligand/metal complex
had greater steric demand compared to the pyrrolidine group,
whereas for 22 the pyrrolidine group has the greater steric demand.
Complexes 17e19, and 21e23 were analysed using a similar
approach. The 1H NMR data for the allylic and N-methyl protons of
complexes 16e19 are presented in Table 3.
Like in the case of 20, for the triphenyl-substituted
h
3-allyl
palladium complexes 21e23, the 1H NMR spectra were complex
and assignment of each isomer was not always possible. Only for 22
were we able to characterise the major diastereomer. Table 4
summarises the number and distribution of observed stereoiso-
mers and the configuration of the major stereoisomer(s) of com-
plexes 20e23.
The ratio of ground state diastereomers, the highest obtained
experimental ees and the areas of steric demand are summarised in
Fig. 10. In all cases only the syn-syn diastereomers were observed.
For the diphenylallyl palladium complex of (R,R)-9 the endo:exo
ratio is 1.7:1. Application of ligand (R,R)-9 in catalysis gave the (R)-
enantiomer of product in 77% ee, while the minor diastereomer in
solution was the exo-diastereomer, which would afford the (R)-
enantiomer of product assuming nucleophilic attack trans to
phosphorus. This indicates that the rate of nucleophilic attack on
the minor diastereomer is faster than nucleophilic attack on the
major diastereomer, which might be attributed to favourable allyl
rotation upon nucleophilic attack on the exo-diastereomer, Scheme
7. In the case of the endo-complex the phenyl group trans to ni-
trogen has to rotate towards the sterically demanding
diphenylphosphino-group in order to obtain a transition state in
5. Conclusion
In conclusion, we have presented the synthesis and application
of four novel ferrocenepyrrolidine-phosphine ligands. N-Methyl-
ferrocenepyrrolidine (R)-7 proved to be an effective ortho-metal-
ating group allowing diastereoselective phosphinylation and sily-
lation in 84% de and 70% de, respectively. The ortho-directing
properties of (R)-7 are in contrast to the ortho-directing properties
of related (R)-N,N-(dimethyl-1-ferrocenyl)ethylamine 6, which
afforded the major diastereomer having the (S)-planar chirality. The
best results in the asymmetric allylic alkylation of 1,3-
diphenylprop-2-enyl acetate with dimethylmalonate anion as
nucleophile were obtained with ligand (R,R)-9, which gave quan-
titative yields and ees of up to 77% (R). This is in line with the results
obtained with the non-ferrocene containing pyrrolidine ligands 3
and 4 [36e38], whereas the state of the art PeN (sp3) ligand for this
transformation was reported by Jin in 2005, a ferrocene-containing
ligand 24 (Fig. 11), which afforded the product of alkylation of 1,3-
diphenyl-2-propenyl acetate at full conversion using dime-
thylmalonate (BSA procedure) in 99.6% ee [39].
which allyl has reorientated itself into a
h
2-alkene product-like
geometry, whereas in the case of the exo-complex the phenyl
group trans to nitrogen has to rotate away from the diphenyl-
phosphino group.
Similarly for the trisubstituted ferrocenyl ligand (R,R)-10 the
minor diastereomer gave rise to the preferred (R)-enantiomer in
catalysis. In comparison to the disubstituted ligand (R,R)-9, a lower
ee of 33% was obtained. In this case the added trimethylsilyl group
changed the ratio of the ground state diastereomers from 1.7:1
endo:exo for (R,R)-9 to 2.5:1 (R,R)-10, which might contribute to the
lower enantioselectivity. Additionally, the increased steric demand
of the pyrrolidine group might have an adverse effect on the
‘favourable’ allyl rotation.
Interestingly, ligand (R,S)-10 afforded a lower ee of 42% while
only one diastereomer was present in solution. This diastereomer
was confirmed to be the endo, which would lead to the favoured
Solution NMR studies on the 1,3-diphenylallyl palladium com-
plexes of ligands (R,R)-9 and (R,R)-10 revealed that the major
Table 3
Allylic and N-Methyl protons of complexes 16e19.
N——P
(R,S)-9
(R,S)-10
(R,R)-10
(R,R)-9
Ha
d
¼ 5.42
not observed
Ha
d
¼ 4.72
Ha
Hb
Hc
d
d
d
¼ 5.46
¼ 6.19
¼ 5.73
H
H
NeMe
b d ¼ 6.28
H
H
NeMe
b d ¼ 7.00
c d ¼ 5.49
c d ¼ 5.56e5.64
d
¼ 1.95
d
¼ 2.86
NeMe
Major (71%)
Ha
Hb
Hc
d
¼ 1.99
Major (63%)
Ha
Minor (11%)
Ha
d
¼ 3.63
Ha
d
¼ 5.22
d
¼ 4.98
d
d
d
¼ 3.63
¼ 6.78
¼ 5.56
H
H
NeMe
b d ¼ 6.78
H
H
b d ¼ 6.17
c d ¼ 5.86
H
H
NeMe
b d ¼ 6.53e6.62
c d ¼ 6.53e6.62
c d ¼ 5.56e5.64
d
¼ 2.50
NeMe
d
¼ 1.79
d
¼ 3.37
NeMe
Minor (29%)
d
¼ 2.53
Minor (37%)
Major (100%)
Major (89%)
7

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
Table 4
Number and distribution of observed enantiomers and the configuration of the major enantiomer(s) of complexes 20e23.
Complex
31P (ppm) (% abundance)
Major enantiomer (N—P)
20
d
17.4 (5%), d 19.7 (79%), d 24.3 (16%)
exo or endo
21
22
d
d
12.6 (36%),
d
16.2 (36%),
d
20.1 (21%), 22.1 (7%)
d
Major stereoisomers not identified
10.3 (5%),
d
11.7 (75%),
d
20.3 (15%), d 27.9 (5%)
endo
23
d
19.8 (83%), d 24.3 (17%)
exo or endo
Fig. 10. Summary of the results obtained from allylic alkylation and solution NMR studies.
diastereomer in solution is the exo-diastereomer, which does not
give rise to the observed product in catalysis. The major-
diastereomer of palladium complexes of ligands (R,S)-9 and (R,S)-
10 does give rise to the observed product. The application of these
and related ligands to other asymmetric transformations is ongoing
within these research laboratories and the results will be reported
in due course.
Experimental section
General remarks
All solvents were purified and dried before use. Diethyl ether
and tetrahydrofuran were distilled from sodium/benzophenone
and dichloromethane and toluene were distilled from calcium hy-
dride. When necessary solvents were degassed using three freeze-
thaw cycles. Chemicals were used as received from Aldrich and
Lancaster. Chlorodiphenylphosphine and trimethylsilylchloride
were distilled prior to use. Palladium chloride was kindly provided
by Johnson Matthey. Melting points were determined using a
Gallenkamp melting point apparatus and are uncorrected. Optical
rotation values were measured on a PerkinElmer 241 Polarimeter
where the light source was the sodium D line (
l
¼ 589.3 nm). 1H
NMR spectra were recorded on a JEOL JNM-PMX-270 MHz spec-
trometer, 300 MHz Varian-Unity spectrometer and a 500 MHz
Varian-Unity spectrometer. (1He1H) COSY, (1He1H) NOESY and
(1He13C) HETCOR were recorded on a 300 MHz and a 500 MHz
Varian-Unity spectrometer. Chemical shifts are quoted in ppm
relative to tetramethylsilane and coupling constants (J) are quoted
in Hz. CDCl3 was used as the solvent for all NMR spectra unless
otherwise stated. 67.5 MHz 13C spectra were recorded on a JEOL
spectrometer, 75.4 MHz 13C spectra on a Varian-Unity spectrometer
and 125.7 MHz 13C spectra on a Varian-Unity spectrometer.
121 MHz 31P spectra were recorded on a 300 MHz Varian-Unity
spectrometer and 31P chemical shifts are reported relative to 85%
aqueous phosphoric acid (0.0 ppm). Infra-red spectra were recor-
ded on a Mattson Galaxy Series FTIR 3000 spectrometer. Electron
impact (EI) mass spectra were determined on a VG Analytical 770
mass spectrometer with attached INCOS 2400 data system in the EI
mode unless otherwise stated. Electrospray mass (ES) spectra were
recorded on a VG (Micromass) Quattro with electrospray probe.
Separations by column chromatography were performed using
Merck Silica gel 60 (Art. 9385) and Merck Aluminium Oxide 90 (Art.
Scheme 7. Favourable and unfavourable allyl rotation.
Fig. 11. Optimal PeN(sp3) ligand in Pd-catalysed AA.
8

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
1097). Thin layer chromatography were performed with Merck
Silica gel 60 F254 (Art. 5735) and Merck Aluminium Oxide 60 F254
(Art. 5581). For preparative TLC Merck Silica gel 60 PF254þ366 (Art.
7748). HPLC work was carried out using a Shimadzu LC-10AT VP
machine equipped with a UVeVis detector employing Chiralcel®
OD and OJ columns from Diacel Chemical Industries.
vacuo to give the crude product as an orange oil, which contained
two diastereomers (70% de) in 71% yield. These isomers were iso-
lated by column chromatography on silica (petrol ether/ethyl ace-
tate 15:1 with 2% triethylamine) yielding the major product {2-
[(2R)-1-methylpyrrolidinyl-2-yl)]-(1R)-trimethylsilylferrocene}
(R,R)-13 (0.63 g, 50%) as an orange oil. [
a
]
23þ106.6 (c ¼ 0.4, CHCl3);
D
{2-[(2R)-1-Methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenyl-
phosphine} (R,R)-(9): To a suspension of 1-methyl-(2R)-pyrroli-
din-2-ylferrocene (R)-7 (0.3 g, 1.1 mmol) in dry ether (3 mL)
at ꢁ78 ꢀC, s-butyllithium (1.4 M, 1.2 mL, 1.7 mmol) was added
dropwise over 10 min. This orange coloured solution was stirred for
3 h at this temperature followed by 1.5 h at 0 ꢀC. Next, chlor-
odiphenylphosphine (0.42 g, 1.9 mmol) was added as a solution in
ether (2 mL) and the reaction was stirred at room temperature for
1 h. Subsequently, the reaction mixture is poured onto 10%
ammonium chloride solution (20 mL) and extracted with CH2Cl2
(2 ꢂ 10 mL). The organic layers were combined and washed with
water (20 mL), dried over Na2SO4 and concentrated in vacuo to give
a viscous orange oil. The crude product (1 g), was a mixture of two
diastereomers (84% de), which was purified by column chroma-
tography on silica (petrol ether/ethyl acetate 20:1 with 5% trie-
thylamine) to yield {2-[(2R)-1-methylpyrrolidin-2-yl]-(1R)-
Rf ¼ 0.33 (1:1 petrol/ethyl acetate); IR (NaCl disc) nmax 2952, 2771,
1455, 1326; 1H (300 MHz, CDCl3) 0.28 (s, 9H, SieCH3), 1.36e1.5 (m,
1H, H3’a), 1.6e1.82 (m, 2H, H4’a, H4’b), 2.06e2.16 (m, 1H, H3’b), 2.27
(dd, 1H, J ¼ 17.6, 9.4, H5’a), 2.66 (s, 3H, NeMe), 3.12 (t, 1H, J ¼ 16.4,
8.2, H2’a), 3.14 (t, 1H, J ¼ 15.8, 7.3, H5’b), 4.04 (m, 1H, CpH3), 4.10 (s,
5H, Cp), 4.28 (app t, 1H, J ¼ 2.3, CpH4), 4.44 (br app t, 1H, CpH5); 13
C
(67.5 MHz, CDCl3) 0.73 (SiMe3), 22.3 (C4’), 36.8 (C3’), 42.7 (NMe),
58.3 (C5’), 65.1 (H2’), 67.8 (Cp C1), 68.7 (Cp C4), 68.8 (Cp C3), 68.9
(Cp), 73.7 (Cp C5), 97.8 (Cp C2); m/z (EI) 341 (Mþ, 6%), 268 (8), 258
(5), 121 (4), 84 (14), 56 (3), 43 (5); Found: C 62.91, H 7.98, N 3.94,
C
18H27FeNSi, requires C 63.34, H 7.97, N 4.1.
{2-[(2R)-1-Methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-
ferrocenyldiphenylphosphine} (R,S)-(10): A solution of {2-[(2R)-
1-methylpyrrolidinyl-2-yl)]-(1R)-trimethylsilylferrocene} (R,R)-13
(0.62 g, 1.8 mmol) was made with dry ether (9 mL) and cooled
to ꢁ78 ꢀC. s-Butyllithium (1.4 M, 2 mL, 2.7 mmol) was added
dropwise over 10 min. The resulting orange solution was stirred for
3 h at this temperature followed by 2 h at 0 ꢀC. Next, chlor-
odiphenylphosphine (0.68 g, 3.1 mmol) as a solution in dry ether
(3 mL) was added over 5 min and the reaction mixture was stirred
for 40 min. Subsequently, the reaction mixture was washed with
saturated NaHCO3 (60 mL) and water (50 mL), dried over Na2SO4
and concentrated in vacuo to give a viscous orange oil. Purification
was performed by column chromatography on silica followed by
column chromatography on alumina to yield {2-[(2R)-1-
ferrocenyldiphenylphosphine} (R,R)-9 (0.31 g, 64%) as an orange oil
23
which solidifies over time, m.p. 112e114 ꢀC. [
a
]
D
þ 425 (c ¼ 0.2,
CHCl3); Rf ¼ 0.31 (petrol ether/ethyl acetate 3:1); nmax (KBr) 3052,
2934, 2771, 1433; 1H (300 MHz, CDCl3) 1.65e1.78 (m, 3H, H4’b/H3’b
/
H
4’a), 1.80e1.92 (m, 1H, H3’a), 2.20 (dd, 1H, J ¼ 9.1, 7.9, H5’a), 2.47 (s,
3H, NeCH3), 3.02 (app t, 1H, J ¼ 9.1, 7.3, H5’b), 3.29 (app t, 1H, J ¼ 7.9,
7.6, H2’a), 3.87e3.89 (m, 1H, CpH3), 3.96 (s, 5H, Cp), 4.28e4.29 (m,
1H, CpH4), 4.45e4.46 (m, 1H, CpH5), 7.19e7.20 (m, 4H, m-Ph-H),
7.34e7.37 (m, 4H, o-Ph-H), 7.55e7.60 (m, 2H, p-Ph-H); 13C
(67.5 MHz, CDCl3) 22.5 (C4’), 36.1 (C3’), 42.4 (NMe), 58.1 (C5’), 64.7
methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-ferrocenyldiphenyl
23
(d, 3J
5.4, C2’), 68.7 (CpC4), 71.3 (d, 3J
4.3, CpC5), 72.5 (d, 1J
phosphine} (R,S)-10 (0.67 g, 70%), m.p. 105e107 ꢀC. [
a]
ꢁ 93.8
P,C
P,C
D
¼ 10.7, CpC1), 97.8 (d, 2J
¼ 23.7, CpC2), 127.7 and 127.9 (d, 3J
(c ¼ 0.2, CHCl3); Rf ¼ 0.57 (petrol ether/ethyl acetate 20:1); 1H
(300 MHz, CDCl3) 0.27 (s, 9H), 1.18e1.23 (m, 1H, H4’b), 1.41e1.45 (m,
1H, H4’a), 1.71e1.84 (m, 1H, H3’a), 1.98e2.01 (dd, 1H, J ¼ 18.0, 9.1,
P,C
P,C
¼ 9.7 and 7.5, m-Ph), 128.1 (p-Ph), 132.3 and 135.5 (d, 2J P,C ¼ 18.3
P,C
and 11.5, o-Ph), 138.2 and 140.6 (d, 1J
¼ 8.6, ipso-Ph); 31P
P,C
(121 MHz, CDCl3) ꢁ22.6 m/z (EI) 453 (Mþ, 14%), 268 (28), 183 (24),
121 (85), 84 (76), 56 (50), 42 (50); Found: C 71.48, H 6.29, N 2.99, P
6.98C27H28FeNP, requires C 71.53, H 6.23, N 3.09, P 6.83.
H5’a), 2.04 (s, 3H, NMe), 2.16e2.28 (m, 1H, H3’b), 2.83 (td, 1H,
J ¼ 10.8, 8.9, 2.8, H5’b), 3.11 (td, 1H, J ¼ 11.4, 6.6, 2.7, H2’a), 3.74 (d, 1H,
J ¼ 2.5, CpH4), 4.04 (s, 5H, Cp), 4.16 (d, 1H, J ¼ 2.1, CpH5), 7.21e7.31
(m, 6H, meta/ortho Ph-H), 7.33e7.37 (m, 2H, para Ph-H), 7.48e7.54
(m, 2H, ortho Ph-H); 13C (67.5 MHz, CDCl3) 1.0 (SiMe3), 22.1 (C3’),
Crystal data for (R,R)-9: [C27H28FeNP], from ethanol,
Mr ¼ 453.32, yellow plate, crystal size: 0.12 ꢂ 0.46 ꢂ 0.53 mm3;
a ¼ 8.900(1), b ¼ 14.561(1), c ¼ 17.216(1) Å, V ¼ 2231.1(2) Å3,
T ¼ 100(2) K, orthorhombic, space group P212121 (No. 19), Z ¼ 4,
rcalcd ¼ 1.35 g cmꢁ3, F(000) ¼ 952, Siemens SMART diffractometer,
37.6 (C4’), 42.5 (NMe), 57.5 (C2’), 65.1 (C5’), 69.8 (Cp), 72.6 (d, 2J
P,C
J ¼ 4.5, Cp C5), 72.8 (d, 3J P,C J ¼ 1.9, Cp C3), 75.4 (Cp C4), 78.4 (d, 1J P,C
J ¼ 9.6, Cp C1), 102.1 (d, 2J P,C J ¼ 16.1, Cp C2), 127.8 and 127.9 (d, 3J P,C
l
(Mo Ka) ¼ 0.71073 Å,
m
¼ 0.76 mmꢁ1, 24,554 measured and 8244
J ¼ 6.4 and 6.5, meta Ph), 128.6 (para Ph), 133.1 and 134.9 (d, 2J
P,C
independent reflections (Rint ¼ 0.057), 6821 with I > 2
s(I),
J ¼ 19.4 and 21.5, ortho Ph), 139.1 and 140.2 (d, 1J P,C J ¼ 14.0 and 9.7,
ipso Ph); 31P (121 MHz, CDCl3) ꢁ19.9; ms (EI) 525 (Mþ,15%), 510 (3),
448 (4), 339 (4), 266 (9), 243 (5), 183 (4), 121 (10), 84 (17), 73 (24);
Found: C 67.91, H 6.96, N 2.57; C30H36FeNPSi requires C 68.56, H
6.90, N 2.67.
qmax ¼ 33.2ꢀ, Tmin ¼ 0.725, Tmax ¼ 0.909, direct methods (SHELXS-
97) and least-squares refinement (SHELXL) on Fo2, both programs
€
from G. Sheldrick, University of Gottingen; 271 parameters, H
atoms riding, absolute configuration established (Flack
{2-[(2R)-1-Methylpyrrolidin-2-yl]-(1S)-ferrocenyldiphenyl-
phosphine} (R,S)-(9): A solution of {2-[(2R)-1-methylpyrrolidin-2-
yl]-(3R)-trimethylsilyl-(1S)-ferrocenyldiphenyl phosphine} (R,S)-10
(0.46 g, 0.88 mmol) and tetrabutylammonium fluoride in THF (1 M,
17 mL, 17 mmol) was stirred under nitrogen atmosphere for 4 days
at 70 ꢀC during which a black suspension resulted. Thereafter the
solvent was removed and the residue was added to water (20 mL)
and extracted with CH2Cl2 (2 ꢂ 30 mL). The organic extracts were
washed with brine (20 mL), dried over MgSO4 and concentrated in
vacuo to give a dark red oil. The crude mix was purified by column
chromatography on silica using a gradient eluent (petrol ether/
ethyl acetate from 20:1 to 1:1) to yield {2-[(2R)-1-
parameter ꢁ0.01(1) [2522 quotients]), R1 ¼ 0.0431 (I > 2
s(I)),
wR2 ¼ 0.0934 (all data), Drmax/min ¼ 0.788/-0.701 eÅꢁ3. CCDC
2034873.
{2-[(2R)-1-Methylpyrrolidinyl-2-yl)]-(1R)-trimethylsilyl
ferrocene} (R,R)-(13): To a cooled (ꢁ78 ꢀC) solution of 1-methyl-
(2R)-pyrrolidin-2-ylferrocene (R)-7 (1.0 g, 3.7 mmol) in dry ether
(10 mL), s-butyllithium (1.4 M, 4 mL, 5.6 mmol) was added drop-
wise over 10 min. This yellow suspension was stirred for 3 h at this
temperature followed by 1.5 h at 0 ꢀC. Next, chlorotrimethylsilane
(0.8 g, 7.4 mmol) was added and the reaction mixture was stirred
for an additional hour. Thereafter, the reaction mixture was washed
with saturated sodium hydrogencarbonate (2 ꢂ 60 mL) and
extracted with Et2O (2 ꢂ 60 mL). The combined organic layers were
washed with water (60 mL), dried over MgSO4 and concentrated in
methylpyrrolidin-2-yl]-(1S)-ferrocenyldiphenylphosphine} (R,S)-9
23
(0.16 g, 59%) as an orange solid, m.p. 88e90 ꢀC [
a]
ꢁ 324.3
D
(c ¼ 0.14, CHCl3); Rf ¼ 0.25 (3:1 Petrol/ethyl acetate); IR (KBr) nmax
9

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
3056, 2952, 2780, 1653, 1432, 1216, 1156, 1107, 1025; 1H (500 MHz,
CDCl3) 1.73 (s, 3H, NMe), 1.77 (m, 1H, H4’a), 1.86 (m, 1H, H4’b), 2.19
(m, 1H, H3’b), 2.19 (dd, 1H, J ¼ 12.5, 4.1, H5’a), 2.42 (m, 1H, H3’a), 3.03
(app t, 1H, J ¼ 9.7, 1.6, H5’b), 3.11 (td, 1H, J ¼ 11.9, 8.4, 3.4, H2’a), 3.92
(s, 5H, Cp), 4.01 (br s, 1H, CpH3), 4.39 (app t, 1H, J ¼ 2.5, CpH4), 4.55
(br s, 1H, CpH5), 7.02e7.24 (m, 3H, meta Ph-H), 7.28e7.31 (m, 2H,
ortho Ph-H), 7.34e7.39 (m, 3H, para/meta Ph-H), 7.58e7.64 (m, 2H,
ortho Ph-H); 13C (125.6 MHz, CDCl3) 22.85 (C4’), 35.8 (C3’), 40.7
(NMe), 58.0 (C5’), 63.4 (d, 3J P,C J ¼ 9.8, C2’), 69.5 (d, 3J P,C J ¼ 4.9, Cp
C3), 69.7 (Cp), 70.3 (Cp C4), 71.16 (d, 2J P,C J ¼ 4.2, Cp C5), 75.6 (d, 1J P,C
J ¼ 9.1, Cp C1), 96.4 (d, 2J P,C J ¼ 24.9, Cp C2), 128.1 and 128.2 (d, 3J P,C
J ¼ 5.6, meta Ph), 129.3 (para Ph), 133.0 and 135.5 (d, 2J P,C J ¼ 18.9
reference, R1 ¼ 0.079 (I > 2
s
(I)), wR2 ¼ 0.151 (all data), Drmax/
¼ 0.554/-0.433 eÅꢁ3. CCDC 2034874.
min
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenyl-
phosphine]-[
p-allyl]palladium] tetrafluoroborate: Di-m-chloro-
bis( -allyl)dipalladium (0.033 g, 0.09 mmol), {2-[(2R)-1-
p
methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenylphosphine} (R,R)-9
(0.082 g, 0.18 mmol), and sodium tetrafluoroborate (0.06 g,
0.54 mmol) were placed in a Schlenk under nitrogen. Dried and
degassed chloroform (3 mL) was added giving an orange suspen-
sion which was stirred for 24 h at room temperature. The solid was
filtered off and the solvent was removed in vacuo to give [2-[(2R)-1-
methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenylphosphine]-[p-
allyl]palladium]tetrafluoroborate (0.10 g, 81%) as an orange solid,
and 22.4, ortho Ph), 138.4 and 140.1 (d, 1J
J ¼ 8.4, ipso Ph); 31P
P,C
(121 MHz, CDCl3) ꢁ24.8; ms (EI) 453 (Mþ, 14%), 267 (69), 183 (26),
121 (36), 84 (45); Found: C 71.32, H 6.20, N 3.08; C27H28FeNP re-
quires C 71.53, H 6.23, N 3.09.
m.p. 114e118 ꢀC [
a
]
23 þ372.5 (c ¼ 0.04, CHCl3); IR (KBr) nmax 2922,
D
1638,1434, 1083, 696, 628, 468; 1H (300 MHz, CDCl3) 2.06e2.27 (m,
1H, pyr), 2.36 (m, 1H, allyl-H), 2.4e2.52 (m, 4H, pyr), 2.64 (s, 3H,
NMe), 3.07 (dd, 1H, J ¼ 10.3, 9.7, H5’a), 3.17 (app t, 1H, J ¼ 9.7, 7.3,
{2-[(2R)-1-Methylpyrrolidin-2-yl]-(3S)-trimethylsilyl-(1R)-
ferrocenyldiphenylphosphine} (R,R)-10: To a cooled (ꢁ78 ꢀC)
suspension of {2-[(2R)-1-methylpyrrolidin-2-yl]-(1R)-ferroce-
nyldiphenylphosphine} (R,R)-9 (0.15 g, 0.33 mmol) in dry, degassed
ether (3 mL), was added s-butyllithium (1.4 M, 0.6 mL, 0.826 mmol)
over 10 min. The mixture was stirred for 3.5 h at ꢁ78 ꢀC followed by
1 h at 0 ꢀC and then trimethylsilyl chloride was added and stirring
was continued for 1 h. The reaction was poured onto saturated
NaHCO3 (30 mL) and extracted with ether (20 mL). The organic
layer was separated and washed with water (30 mL), dried over
Na2SO4 and concentrated in vacuo to give a viscous red oil. Purifi-
cation by column chromatography on silica (petrol ether/ethyl ac-
H2’a), 3.40 (d, 1H, J ¼ 8.6, allyl-H), 3.78 (s, 5H, Cp), 3.97 (dd, 1H,
J ¼ 6.4, 4.2, allyl-H), 4.39 (br s, 1H, CpH3), 4.52 (app t, 1H, J ¼ 2.6, 2.5,
CpH4), 4.64 (br s,1H, CpH5), 4.70 (app t,1H, J ¼ 8.6, 5.4, allyl-H), 5.89
(m, 1H, central allyl), 7.08e7.15 (m, 2H, Ph-H), 7.32e7.38 (m, 3H, Ph-
H), 7.69e7.74 (m, 3H, Ph-H), 7.92e7.98 (m, 2H, Ph-H); 31P (121 MHz,
CDCl3) þ18.8 (100%); ms (ES, MeOH) 600 (Mþ ꢁ BF4); Found: C
50.62, H 4.66, N 1.68; C30H33NPFePdBF4 requires C 52.40, H 4.84, N
2.04.
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-
ferrocenyldiphenylphosphine]-[
p
-allyl]palladium]tetra-
fluoroborate: Di- -chloro-bis(
m
p-allyl)dipalladium (0.029 g,
etate
trimethylsilyl-(1R)-ferrocenyldiphenyl
(0.16 g, 93%) as an orange solid, m.p. 126e128 ꢀC. [
10:1)
gave
{2-[(2R)-1-methylpyrrolidin-2-yl]-(3S)-
0.08 mmol),{2-[(2R)-1-methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-
(1S)-ferrocenyldiphenylphosphine} (R,S,R)-10 (0.083 g, 0.16 mmol),
and sodium tetrafluoroborate (0.052 g, 0.47 mmol) were placed in a
Schlenk under nitrogen. Dried and degassed dichloromethane
(3 mL) was added giving an orange suspension which was stirred
for 24 h at room temperature. The solid was filtered off and the
solvent was removed in vacuo to give [2-[(2R)-1-methylpyrrolidin-
phosphine} (R,R,S)-10
23
a
]
þ350
D
(c ¼ 0.1, CHCl3); Rf ¼ 0.8 (Si, 1:1 petrol/ethyl acetate); IR (KBr) nmax
3071, 2953, 2761, 1432, 1246, 1130, 813; 1H (500 MHz, CDCl3) 0.29
(s, 9H, TMS), 1.37 (s, 3H, NMe), 1.68 (m, 1H, H4’b), 1.96 (dd, 1H,
J ¼ 9.0, 8.5, H5’a), 2.18 (m,1H, H4’a), 2.32 (m, 1H, H3’a), 2.81 (app t, 1H,
J ¼ 6.3, 8.1, H5’b), 2.89 (app t, 1H, J ¼ 8.6, 8.5, H2’a), 3.06 (m, 1H, H3’b),
3.93 (d, 1H, J ¼ 2.3, CpH4), 3.96 (s, 5H, Cp), 4.13 (br s, 1H, CpH5),
7.18e7.24 (m, 3H, meta/para Ph-H), 7.25e7.27 (m, 2H, ortho Ph-H),
7.31e7.33 (m, 3H, para/meta Ph-H), 7.55e7.58 (m, 2H, ortho Ph-H);
13C (125.6 MHz, CDCl3) 0.98 (TMS), 23.5 (C4’), 36.7 (C3’), 40.6 (NMe),
57.8 (C5’), 65.8 (C2’), 69.95 (Cp), 74.1 (Cp C4), 74.5 (d, 2J P,C J ¼ 5.7, Cp
C5), 75.4 (d, 2J P,C J ¼ 2.8, Cp C3), 79.2 (d, 1J P,C J ¼ 16.5, Cp C1),102.1 (d,
2J P,C J ¼ 16.9, Cp C2),127.4 (para-Ph),127.5 and 127.95 (d, 3J P,C J ¼ 7.1,
meta-Ph), 128.6 (para-Ph),133.0 and 135.3 (d, 2J P,C J ¼ 19.8 and 21.9,
2-yl]-(3R)-trimethylsilyl-(1S)-ferrocenyldiphenylphosphine]-[p-
allyl] palladium]tetrafluoroborate (0.08 g, 63%) as an orange solid,
m.p. 146e150 ꢀC (decomp). [
a]
23 ꢁ 273.8 (c ¼ 0.13, CHCl3); IR (KBr)
D
nmax 2954, 1435, 1231, 1083, 837, 684, 624; 1H (300 MHz, CDCl3)
0.34 (s, 9H, TMS), 1.43 (m, 1H, H3’a), 1.79e1.94 (m, 2H, H3’b/H4’b),
1.99e2.04 (m, 1H, H4’a), 2.93 (br d, 1H, J ¼ 19.8, allyl-H), 3.01e3.09
(m, 2H, H2’a/H5’a), 3.51 (s, 3H, NMe), 3.53 (m, 1H, allyl-H), 3.88 (s,
5H, Cp), 4.0 (m, 1H, H5’b), 4.18 (m, 1H, allyl-H), 4.36 (app t, 1H,
J ¼ 2.0, CpH4), 4.54 (d, 1H, J ¼ 2.4, CpH5), 4.97 (app t, 1H, J ¼ 6.7, 6.3,
allyl-H), 6.27 (m, 1H, central allyl-H), 7.14e7.22 (m, 2H, Ph-H),
7.36e7.45 (m, 3H, Ph-H), 7.58e7.69 (m, 3H, Ph-H), 7.72e7.76 (m,
2H, Ph-H); 31P (121 MHz, CDCl3) þ14.5 (100%); ms (ES, MeOH) 672
(Mþ ꢁ BF4); Found: C 52.78, H 5.95, N 1.55; C33H41NPSiFePdBF4
requires C 52.17, H 5.44, N 1.68.
ortho-Ph), 140.1 and 141.0 (d, 1J
J ¼ 9.2 and 12.7, ipso-Ph); 31P
P,C
(121 MHz, CDCl3) ꢁ23.5; ms (EI) 525 (Mþ, 27%), 448 (10), 339 (11),
266 (29), 183 (19), 121 (44), 84 (96), 73 (100), 56 (18); Found: C
68.37, H 6.85, N 2.56; C30H36FeNPSi requires C 68.57, H 6.90, N 2.67.
Crystal data for (R,R)-10: [C30H36FeNPSi], from ethanol,
Mr
0.05
¼
525.51,
orange-yellow
prism,
7.2344(1),
crystal
size:
ꢂ
0.06
ꢂ
0.06 mm3;
a
¼
b
¼
17.3214(3),
Allylic alkylation procedures
c ¼ 22.1734(5) Å,
b
¼ 98.564(1)ꢀ, V ¼ 2747.6(1) Å3, T ¼ 100(2) K,
monoclinic, space group P21 (No. 4), Z ¼ 4, rcalcd ¼ 1.27 g cmꢁ3
,
Malonate Ion procedure
F(000)
¼
1112, Nonius KappaCCD diffractometer,
l(Mo
Sodium dimethyl malonate (0.042 g, 0.275 mmol) was placed in
a dry Schlenk which had previously been flushed with nitrogen and
dry degassed solvent (0.3 mL) was added to form a white suspen-
Ka) ¼ 0.71073 Å,
m
¼ 0.67 mmꢁ1, 15,027 measured and 10,191 in-
dependent reflections (Rint
¼
0.072), 6667 with I > 2s(I),
qmax ¼ 26.74ꢀ, Tmin ¼ 0.957, Tmax ¼ 0.973, direct methods (SHELXS-
sion. To this was added a solution of (ligand)palladium(h
3-allyl)
97) and least-squares refinement (SHELXL) on Fo2, both programs
tetrafluoroborate (0.0025 mmol) and (E)-1,3-diphenylprop-2-enyl
acetate (0.063 g, 0.250 mmol) in dry degassed solvent (0.4 mL) to
form a pale orange suspension. Reaction progress was monitored
by TLC (petroleum ether 40e60 ꢀC:diethyl ether: 2:1 as the eluent).
€
from G. Sheldrick, University of Gottingen; 613 parameters, H
atoms riding, absolute configuration established (Flack
parameter ꢁ0.03(2) [2007 quotients]) and confirmed by chiral
10

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
After stirring under nitrogen at room temperature for 24 h, acetic
acid (0.1 mL) was added and the solvent was removed in vacuo.
Water (25 mL) was added and the reaction was extracted into
diethyl ether (25 mL), then washed with water (25 mL) and brine
(25 mL). The solution was dried with MgSO4, filtered and the sol-
vent removed in vacuo to give an orange oil. This was purified by
preparative TLC using silica-gel plates (petroleum ether 40e60 ꢀC/
(17): Di-
m
-chloro-bis(1,3-diphenyl-
p
- allyl)dipalladium (0.013 g,
0.02 mmol), {2-[(2R)-1-methylpyrrolidin-2-yl]-(1S)-ferrocenyldi-
phenylphosphine} (R,S)-9 (0.018 g, 0.04 mmol), and sodium tetra-
fluoroborate (0.022 g, 0.2 mmol) were placed in a Schlenk under
nitrogen. Dried and degassed dichloromethane (0.5 mL) was added
giving an orange suspension which was stirred for 1 h at room
temperature. The solid was filtered off and the solvent was
removed in vacuo to give [2-[(2R)-1-methylpyrrolidin-2-yl]-(1S)-
diethyl ether,
2
:
1) to afford methyl-2-carbomethoxy-3,5-
colourless oil. (R)-methyl-2-
colorless oil:
3.52 (s, 3Н), 3.70 (s, 3H), 3.95 (d, J 10.8,1H), 4.27
diphenylpent-4-enoate as
a
ferrocenyldiphenylphosphine]-[1,3-diphenyl-
p-allyl]palladium]
carbomethoxy-3,5-diphenylpent-4-enoate as
a
tetrafluoroborate 17 (0.033 g, 98%) as an orange solid which contain
23
Rf ¼ 0.37; 1H NMR
d
two diastereomers, m.p. 160 ꢀC (decomp). [
a]
þ9.5 (c ¼ 0.37,
D
(dd, J 8.5, J 10.8, 1H), 6.33 (dd, J 8.5, 15.5, 1H), 6.48 (d, J 15.8, 1H),
7.19e7.44 (m, 10H); nmax (Nujol)/cmꢁ1 1733 and 1600; MS (EI,
70eV): m/z (%) 324 (Mþ, 5), 193 (20), 105 (100) and 91 (27). The
conversion was determined by 1H NMR spectroscopy. The enan-
tiomeric excess was determined by chiral HPLC (Chiralcel OD)
0.46 cm I.D. x 25 cm], 99:1 Hexane/iso-Propanol, flow rate 0.2 mL/
min, RT ¼ (R)-66 min, (S)-71 min.
CHCl3); IR (KBr) nmax 3064, 2964, 2866, 1636, 1490, 1436, 1083, 804,
757, 694, 499; 1H (500 MHz, CDCl3) Major diastereomer: 1.70 (app t,
1H, J ¼ 11.1, 10.8, H4’a), 1.79 (s, 3H, NMe), 1.87e1.95 (m, 1H, H3’b),
1.98e2.03 (m, 1H, H4’b), 2.22e2.29 (m, 1H, H3’a), 2.51 (app t, 1H,
J ¼ 11.1, 9.4, H5’a), 3.61 (s, 5H, Cp), 4.04 (m, 1H, H5’b), 4.06 (br s, 1H,
CpH3), 4.28 (br s, 1H, CpH4), 4.47 (br s, 1H, CpH5), 5.08 (dd, 1H,
J ¼ 11.1, 7.9, H2’a), 5.22 (d, 1H, J ¼ 12.0, allyl-H trans N), 5.86 (app t,
1H, J ¼ 12.3, 10.3, allyl-H trans P), 6.17 (m, 1H, central allyl H), 6.22
(app t, 2H, J ¼ 9.4, 8.4, Ph-H), 6.73 (d, 2H, J ¼ 7.9, Ph-H), 6.81 (t, 2H,
J ¼ 7.6, Ph-H), 6.97 (td, 2H, J ¼ 9.4, 7.6, 1.8, Ph-H), 7.13 (app t, 2H,
J ¼ 7.3, 6.7, Ph-H), 7.22 (m, 2H, Ph-H), 7.29e7.52 (m, 4H, Ph-H), 7.63
(br m, 2H, Ph-H), 7.72 (app t, 2H, J ¼ 7.9, 7.3, Ph-H), 8.20 (dd, 2H,
J ¼ 7.6, 7.3, Ph-H); 31P (121 MHz, CDCl3) þ16.1; MS (ES, MeOH) 752
(Mþ ꢁ BF4); Found: C 58.76, H 5.06, N 0.98; C42H41NPFePdBF4 re-
quires C 60.07, H 4.92, N 1.67.
BSA procedure
A
solution of (ligand)palladium(h
3-allyl)tetrafluoroborate
(0.0025 mmol) in dry degassed solvent (0.5 mL) was added to po-
tassium acetate (0.005 mmol), under a nitrogen atmosphere to
form a suspension. To this suspension was then added 1,3-
diphenylprop-2-enyl acetate (0.063 g, 0.250 mmol), dimethylmal-
onate (0.275 mmol), and N,O-bis(trimethylsilyl)acetamide (BSA),
(0.275 mmol) by syringe. The yellow suspension was allowed to stir
under nitrogen at ambient temperature, the reaction rate moni-
tored by TLC and the reaction mixture purified as for the Malonate
Ion procedure.
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-
ferrocenyldiphenylphosphine]-[1,3-diphenyl-
p
-allyl]palla-
dium]
tetrafluoroborate
(18):
Di-m-chloro-bis(1,3-diphenyl-p-allyl)
dipalladium (0.013 g, 0.019 mmol), {2-[(2R)-1-methylpyrrolidin-2-
yl]-(3R)-trimethylsilyl-(1S)-ferrocenyldiphenylphosphine} (R,S)-10
(0.020 g, 0.038 mmol), and sodium tetrafluoroborate (0.021 g,
0.19 mmol) were placed in a Schlenk under nitrogen. Dried and
degassed dichloromethane (0.5 mL) was added giving an orange
suspension which was stirred for 1 h at room temperature. The
solid was filtered off and the solvent was removed in vacuo to give
[2-[(2R)-1-methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-ferroce-
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenyl-
phosphine]-[1,3-diphenyl-
p
-allyl]palladium]tetrafluoroborate
-allyl)dipalladium (0.015 g,
(16): Di- -chloro-bis(1,3-diphenyl-
m
p
0.022 mmol), {2-[(2R)-1-methylpyrrolidin-2-yl]-(1R)-ferrocenyldi-
phenylphosphine} (R,R)-9 (0.020 g, 0.044 mmol), and sodium tet-
rafluoroborate (0.024 g, 0.22 mmol) were placed in a Schlenk under
nitrogen. Dried and degassed dichloromethane (0.5 mL) was added
giving an orange suspension which was stirred for 1 h at room
temperature. The solid was filtered off and the solvent was
removed in vacuo to give [2-[(2R)-1-methylpyrrolidin-2-yl]-(1R)-
nyldiphenylphosphine]-[1,3-diphenyl-p-allyl]palladium]
tetra-
fluoroborate 18 (0.035 g, 98%) as an orange solid which contain two
23
diastereomers, m.p. 194e196 ꢀC (decomp); [
a
]
ꢁ 53.3 (c ¼ 0.09,
D
ferrocenyldiphenylphosphine]-[1,3-diphenyl-p-allyl]palladium]
CHCl3); IR (KBr) nmax 3064, 2958, 2869, 1434, 1246, 1053, 835, 697;
1H (500 MHz, CDCl3) Major diastereomer: 0.26 (s, 9H, TMS), 1.14 (br
m, 1H, H3’a), 1.39 (br m, 1H, H4’a), 1.55 (br m, 1H, H4’b), 1.71 (br m, 1H,
H3’b), 1.93 (br dd, 1H, J ¼ 10.6, 9.0, H5’a), 2.68 (br app t, 1H, J ¼ 9.0,
8.8, H5’b), 2.82 (br app t, 1H, J ¼ 8.8, 8.5, H2’a), 3.37 (s, 3H, NMe), 4.03
(br s, 1H, CpH4), 4.09 (s, 5H, Cp), 4.38 (d, 1H, CpH5), 4.98 (d, 1H,
J ¼ 10.3, allyl-H trans N), 6.53e6.62 (m, 2H, allyl-H trans P, central
allyl-H); Minor diastereomer 0.25 (s, 9H, TMS), 2.86 (s, 3H, NMe),
3.85 (s, 5H, Cp), 4.33 (d, 1H, J ¼ 2.3, CpH5), 4.72 (d, 1H, J ¼ 11.7, allyl-
H trans N), 5.49 (m, 1H, allyl- H trans P), 7.00 (m, 1H, central allyl);
Major and Minor diastereomers 6.84 (d, 3H, J ¼ 7.9, Ph- H), [6.93
(app t, J ¼ 7.9, 7.6), 6.99 (td, J ¼ 9.9, 5.6, 2.1), 4H, Ph-H], [7.16 (app t,
J ¼ 7.0, 6.2), 7.23 (app t, J ¼ 8.8, 6.5), 2H, Ph-H], 7.36e7.52 (m, 5H,
Ph-H), [7.58e7.6 (m), 7.65 (t, J ¼ 6.7), 3H, Ph-H], 8.45 (br d, 4H,
J ¼ 6.5, Ph-H); 31P (121 MHz, CDCl3) þ12.6 (89%), þ17.2 (11); MS (ES,
tetrafluoroborate 16 (0.033 g, 99%) as an orange solid which contain
23
two diastereomers, m.p. 154e156 ꢀC. [
a]
ꢁ 117.1 (c ¼ 0.035,
D
CHCl3); IR (KBr) nmax 2922, 2853, 1451; 1H (500 MHz, CDCl3) Major
diastereomer: 1.95 (s, 3H, NMe), 2.38 (dd,1H, J ¼ 10.6, 9.1, H5’a), 2.96
(app t, 1H, J ¼ 9.9, 7.9, H2’a), 3.55 (app t, 1H, J ¼ 8.8, 8.5, H5’b), 3.69 (s,
5H, Cp), 3.92 (br s, 1H, CpH3), 4.27 (br s, 1H, CpH4), 4.41 (br s, 1H,
CpH5), 5.42 (d, 1H, J ¼ 12.3, allyl-H trans N), 5.56e5.64 (m, >1H,
allyl-H trans P, (minor allyl-H)), 6.18 (app t, 1H, J ¼ 12.6, central
allyl); Minor diastereomer 2.16 (m, 1H, pyr), 2.26 (m, 1H, pyr), 2.50
(s, 3H, NMe), 2.64 (app t, 1H, J ¼ 8.8, 8.2), 3.70 (s, 5H, Cp), 4.1 (br s,
1H, CpH3), 4.35 (br s, 1H, CpH4), 4.49 (br s, 1H, CpH5), 5.56 (m, 1H,
allyl-H), 6.72 (m, 1H, allyl-H); Major and Minor diastereomers 1.74
(m, 1H, pyr), 2.01 (d, 1H, J ¼ 8.8), 2.42e2.48 (m, 3H, pyr), 2.85 (br m,
1H, pyr), 6.34 (dd, 1H, J ¼ 8.2, 7.9, Ph-H), 6.68 (d, 1H, J ¼ 4.1, Ph-H),
6.84 (d, 1H, J ¼ 7.3, Ph-H), 6.91e7.07 (m, 3H, Ph-H), 7.22(app t, 1H,
J ¼ 7.3, 6.4, Ph-H), 7.40 (m, 2H, Ph-H), 7.45 (br s, 2H, Ph-H), 7.49 (br
s, 1H, Ph-H), 7.58 (d, 2H, J ¼ 6.1, Ph-H), 7.68 (br d, 2H, J ¼ 7.6, Ph-H),
7.78 (t, 2H, J ¼ 7.3, Ph-H), 8.15e8.19 (dd, 1H, J ¼ 7.9, 7.6); 31P
(121 MHz, CDCl3) þ18.8 (37%), þ21.3 (63); MS (ES, MeOH) 752
(Mþ ꢁ BF4); Found: C 59.10, H 4.98, N 1.48; C42H41NPFePdBF4 re-
quires C 60.07, H 4.92, N 1.67.
MeOH) 824 (Mþ
45H49NPFePdBF4 requires C 59.26, H 5.42, N 1.54.
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(3S)-trimethylsilyl-(1R)-
ꢁ
BF4); Found: C 58.02, H 5.39, N 1.47;
C
ferrocenyldiphenylphosphine]-[1,3-diphenyl-
p
-allyl]palla-
dium]
tetrafluoroborate
(19):
Di-m-chloro-bis(1,3-diphenyl-p-allyl)
dipalladium (0.013 g, 0.019 mmol), {2-[(2R)-1-methylpyrrolidin-2-
yl]-(3S)-trimethylsilyl-(1R)- ferrocenyldiphenyl phosphine} (R,R,S)-
10 (0.020 g, 0.038 mmol), and sodium tetrafluoroborate (0.021 g,
[2-[(2R)-1-methylpyrrolidin-2-yl]-(1S)-ferrocenyldiphenyl-
phosphine]-[1,3-diphenyl-p-allyl] palladium]tetrafluoroborate
11

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
0.19 mmol) were placed in a Schlenk under nitrogen. Dried and
degassed dichloromethane (0.5 mL) was added giving an orange
suspension which was stirred for 1 h at room temperature. The
solid was filtered off and the solvent was removed in vacuo to give
[2-[(2R)-1-methylpyrrolidin-2-yl]-(3S)-trimethylsilyl-(1R)-ferroce-
CDCl3) 1.04 (s, 3H, NMe), 1.21e1.36 (m, 6H), 1.61e1.94 (m, 7H), 2.02
(s, 3H, NMe), 2.16e2.54 (m, 6H), 2.60 (s, 3H, NMe), 3.05e3.40 (m,
8H), 3.59 (s, 5H, Cp), 3.64 (s, 5H, Cp), 3.66 (s, 5H, Cp), 3.91e4.54 (m,
20H), 4.89 (m, 4H), 6.04 (m, 2H), 6.22 (m, 2H), 6.56e8.04 (m, 16H,
Ph-H); 31P (121 MHz, CDCl3) þ12.6 (33%), þ16.2 (36), þ20.1
(24), þ22.2 (7); MS (ES, MeOH) 828 (Mþ ꢁ BF4); Found: C 62.59, H
5.32, N 1.24; C48H45NPFePdBF4 requires C 62.95, H 4.95, N 1.53.
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-
nyldiphenylphosphine]-[1,3-diphenyl-p-allyl]palladium]tetra-
fluoroborate 19 (0.035 g, 98%) as an orange solid which contain two
23
diastereomers. M.p 166e168 ꢀC (decomp); [
a
]
ꢁ 14.9 (c ¼ 0.09,
D
CHCl3); IR (KBr) nmax 3056, 2959, 2879, 1437, 1249, 1055, 835; 1H
(500 MHz, CDCl3) Major diastereomer: 0.25 (s, 9H, TMS),1.99 (s, 3H,
NMe), 3.61 (s, 5H, Cp), 4.09 (br s, 1H, Cp H4), 4.24 (br s, 1H, Cp H5),
5.46 (d, 1H, J ¼ 12.0, allyl-H trans N), 5.73 (app t, 1H, J ¼ 12.0, 10.9,
allyl-H trans P), 6.19 (app t, 1H, J ¼ 12.6, 12.3, central allyl); Minor
diastereomer: 0.29 (s, 9H, TMS), 2.53 (s, 3H, NMe), 2.74 (app t, 1H,
J ¼ 9.4, 9.1), 3.59 (s, 5H, Cp), 3.63 (m, 1H, allyl-H trans N), 4.16 (br s,
1H, Cp H4), 4.17 (d, 1H, Cp H5), 5.56 (dd, 1H, J ¼ 9.1, allyl-H trans P),
6.78 (app t, 1H, J ¼ 12.9, 12.0, central allyl-H); Major and Minor
diastereomers: 1.76 (m, 1H), 2.0e2.13 (m, 3H), 2.17 (m, 1H),
2.26e2.43 (m, 3H), 2.49e2.58 (m, 1H), 2.96 (m, 3H), 6.28e6.32 (dd,
2H, J ¼ 8.2, 7.9, Ph-H), 6.69e6.72 (m, 4H, Ph-H), 6.94e7.01 (m, 4H,
Ph-H), 7.05e7.11 (m, 2H, Ph-H), 7.23 (app t, 2H, J ¼ 7.9, 7.0, Ph-H),
7.28e7.55 (m, 10H, Ph-H), 7.58 (d, 2H, J ¼ 5.6, Ph-H), 7.66e7.72
(m, 2H, Ph-H), 7.8 (app t, 3H, J ¼ 7.0, 6.5, Ph-H), 8.2 (dd, 2H, J ¼ 7.9,
7.6, Ph-H); 31P (121 MHz, CDCl3) þ18.7 (29%), þ20.7 (71); MS (ES,
ferrocenyldiphenylphosphine]-[1,1,3-triphenyl-p-allyl]palla-
dium]tetrafluoroborate (22): Di- -chloro-bis(1,1,3-triphenyl-p-
m
allyl)dipalladium (0.017 g, 0.021 mmol), {2-[(2R)-1- methyl-
pyrrolidin-2-yl]-(3R)-trimethylsilyl-(1S)-ferrocenyldiphenylphos-
phine} (R,S,R)-10 (0.023 g, 0.043 mmol), and sodium
tetrafluoroborate (0.024 g, 0.214 mmol) were placed in a Schlenk
under nitrogen. Dried and degassed dichloromethane (0.5 mL) was
added giving an orange suspension which was stirred for 1 h at
room temperature. The solid was filtered off and the solvent was
removed in vacuo to give [2-[(2R)-1-methylpyrrolidin-2-yl]-(3R)-
trimethylsilyl-(1S)-ferrocenyldiphenylphosphine]-[1,1,3-triphenyl-
p
-allyl]palladium]tetrafluoroborate 22 (0.042 g, 98%) as an orange
solid which contains four diastereomers, m.p. 150e154 ꢀC
23
(decomp); [
a
]
ꢁ 79.8 (c ¼ 0.12, CHCl3); IR (KBr) nmax 3048, 2957,
D
1434, 1248, 1083, 838, 696, 624; 1H (500 MHz, CDCl3) Major dia-
stereomer: 0.28 (s, 9H, TMS), 1.28 (br m, 2H, H4’a/H4’b), 1.78 (br m,
1H, H3’a), 2.09 (br m, 2H, H3’b and (minor isomers)), 2.35 (m, 2H, H5’a
and (minor isomers)), 2.54 (s, 3H, NMe), 2.79 (app t, 1H, J ¼ 2.6, 8.5,
MeOH) 824 (Mþ
45H49NPSiFePdBF4 requires C 59.26, H 5.42, N 1.54.
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenyl-
phosphine]-[1,1,3-triphenyl- -allyl]palladium]tetra-
fluoroborate (20): Di- -chloro-bis(1,1,3-triphenyl-
dipalladium (0.014 g, 0.017 mmol), {2-[(2R)-1-methylpyrrolidin-2-
yl]-(1R)-ferrocenyldiphenylphosphine} (R,R)-9 (0.015 g,
ꢁ
BF4); Found: C 58.55, H 5.53, N 1.40;
C
H
2’a), 3.52 (app t, 1H, J ¼ 9.7, 7.9, H5’b), 3.61 (s, 5H, Cp), 3.92 (br s, 1H,
p
CpH4), 4.41 (d, 1H, J ¼ 2.64, CpH5), 4.83 (t, 1H, J ¼ 11.7, allyl-H trans
P), 7.01 (br m, 1H, central allyl- H); Minor diastereomers: 2.84e2.97
(m, 2H), 3.27 (s, 3H, NMe), 4.02 (br s, 1H, CpH4), 4.25 (br s, 1H,
CpH5), 4.26 (s, 5H, Cp), 6.36 (br app t, 1H, J ¼ 10.8, 8.2, allyl-H trans
P), 7.01 (br m, 1H, central allyl-H); Major and Minor diastereomers:
5.99 (br t, 2H, J ¼ 7.4), 6.52 (br m, 2H), 6.87 (t, 2H, J ¼ 7.6), 7.0e7.25
(m, 15H, Ph-H), 7.29e7.94 (m, 16H, Ph-H); 31P (121 MHz,
CDCl3) þ10.3 (6%), þ11.7 (74), þ20.3 (15), þ27.9 (5); MS (ES, MeOH)
900 (Mþ ꢁ BF4); Found: C 61.56, H 5.51, N 1.39; C51H53NPSiFePdBF4
requires C 61.99, H 5.41, N 1.42.
m
p-allyl)
0.033 mmol), and sodium tetrafluoroborate (0.018 g, 0.17 mmol)
were placed in a Schlenk under nitrogen. Dried and degassed
dichloromethane (0.5 mL) was added giving an orange suspension
which was stirred for 1 h at room temperature. The solid was
filtered off and the solvent was removed in vacuo to give [2-[(2R)-1-
methylpyrrolidin-2-yl]-(1R)-ferrocenyldiphenylphosphine]-[1,1,3-
triphenyl-p-allyl]palladium] tetrafluoroborate 20 (0.029 g, 95%) as
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(3S)-trimethylsilyl-(1R)-
an orange solid which contain three diastereomers, m.p.
ferrocenyldiphenylphosphine]-[1,1,3-triphenyl-
dium]
tetrafluoroborate (23): Di-m-chloro-bis(1,1,3-triphenyl-p-allyl)
p
-allyl]palla-
142e143 ꢀC (decomp); [
a
]
23 ꢁ 340 (c ¼ 0.08, CHCl3); IR (KBr) nmax
D
2925, 2856, 1465; 1H (500 MHz, CDCl3) Major diastereomer: 2.02
(m, 1H), 2.16 (m, 1H), 2.25 (dd, 1H, J ¼ 8.4, 10.9, H5’a), 2.37 (m, 1H),
2.40 (s, 3H, NMe), 2.53 (m, 1H), 2.82 (app t, 1H, J ¼ 10.3, 8.1, H5’b),
3.16 (d, J ¼ 11.4, allyl-H trans N), 3.17 (app t, 1H, J ¼ 4.8, 3.4, H2’a),
3.67 (s, 5H, Cp), 4.21 (br s, 1H, CpH3), 4.46 (app t, 1H, J ¼ 2.5, 2.2,
CpH4), 4.65 (br s, 1H, CpH5), 7.05 (d, 1H, J ¼ 12.4, central allyl-H);
Major and Minor diastereomers: 7.02e7.58 (m, 26H, Ph-H), 7.64
(d, 2H, J ¼ 7.3, Ph-H); 31P (121 MHz, CDCl3) þ17.4 (5%), þ19.7
(77), þ24.3 (17); MS (ES, MeOH) 828 (Mþ ꢁ BF4); Found: C 62.20, H
5.03, N 1.30; C48H45NPFePdBF4 requires C 62.95, H 4.95, N 1.53.
[2-[(2R)-1-Methylpyrrolidin-2-yl]-(1S)-ferrocenyldiphenyl-
dipalladium (0.015 g, 0.018 mmol), {2-[(2R)-1-methylpyrrolidin-2-
yl]-(3S)-trimethylsilyl-(1R)- ferrocenyldiphenylphosphine} (R,R,S)-
10 (0.019 g, 0.037 mmol), and sodium tetrafluoroborate (0.021 g,
0.18 mmol) were placed in a Schlenk under nitrogen. Dried and
degassed dichloromethane (0.5 mL) was added giving an orange
suspension, which was stirred for 1 h at room temperature. The
solid was filtered off and the solvent was removed in vacuo to give
[2-[(2R)-1-methylpyrrolidin-2-yl]-(3S)-trimethylsilyl-(1R)-ferroce-
nyldiphenylphosphine]- [1,1,3-triphenyl-p-allyl]palladium]tetra-
fluoroborate 23 (0.035 g, 96%) as an orange solid which contain two
phosphine]-[1,1,3-triphenyl-
fluoroborate (21): Di-
dipalladium (0.018 g, 0.022 mmol), {2-[(2R)-1-methylpyrrolidin-2-
yl]-(1S)-ferrocenyldiphenylphosphine} (R,S)-9 (0.020 g,
p
-
allyl]palladium]tetra-
diastereomers, m.p. 160 ꢀC (decomp); [
a
]
23 ꢁ 345 (c ¼ 0.32, CHCl3);
D
m
-chloro-bis(1,1,3-triphenyl- -allyl)
p
IR (KBr) nmax 2962, 2364, 1564, 1446, 1250, 1066, 831, 752; 1H
(500 MHz, CDCl3) Major diastereomer: 0.32 (s, 9H, TMS), 2.0 (br m,
1H), 2.15 (dd, 1H, H5’a), 2.32 (br m, 2H, H3’a), 2.36 (s, 3H, NMe), 2.62
(br m, 1H), 2.73 (app t, 1H, J ¼ 10.6, 8.2, H5’b), 3.01 (td, 1H, J ¼ 12.9,
8.2, 2.1, H2’a), 3.20 (d, 1H, J ¼ 11.9, allyl-H trans N), 3.55 (s, 5H, Cp),
4.34 (d, 1H, J ¼ 2.6, Cp H4), 4.42 (app t, 1H, J ¼ 2.4, 2.2, Cp H5), 7.08
(m, 1H, central allyl-H); Minor diastereomer: 0.27 (s, 9H, TMS), 3.57
(s, 5H, Cp), 4.23 (d, 1H, J ¼ 2.3, Cp H4), 4.27 (br s, 1H, Cp H5); Major
and Minor diastereomers: 5.99 (br t, 2H, J ¼ 7.4), 6.52 (br m, 2H),
6.87 (t, 2H, J ¼ 7.6), 7.0e7.25 (m, 15H), 7.29e7.94 (m, 16H); 31P
(121 MHz, CDCl3) þ19.8 (84%), þ24.3 (16%); ms (ES, MeOH) 900
(Mþ ꢁ BF4); Found: C 59.99, H 5.64, N 1.27; C51H53NPSiFePdBF4
requires C 61.99, H 5.41, N 1.42.
0.044 mmol), and sodium tetrafluoroborate (0.024 g, 0.22 mmol)
were placed in a Schlenk under nitrogen. Dried and degassed
dichloromethane (0.5 mL) was added giving an orange suspension,
which was stirred for 1 h at room temperature. The solid was
filtered off and the solvent was removed in vacuo to give [2-[(2R)-1-
methylpyrrolidin-2-yl]-(1S)-ferrocenyldiphenylphosphine]-[1,1,3-
triphenyl-p-allyl]palladium] tetrafluoroborate 23 (0.040 g, 98%) as
an orange solid which contains four diastereomers, m.p.
23
146e150 ꢀC (decomp); [
a
]
D
þ145 (c ¼ 0.5, CHCl3); IR (KBr) nmax
2955, 2851, 1635, 1481, 1437, 1083, 753, 682, 492; 1H (500 MHz,
12

K. Meaney, R. Goddard, R.P.J. Bronger et al.
Tetrahedron xxx (xxxx) xxx
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Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
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Acknowledgments
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We wish to thank Enterprise Ireland for a Basic and Strategic
Research Scholarship (SC2003-341) to support R.P.J.B. and Univer-
sity College Dublin for a research demonstratorship to K. M. We also
acknowledge the facilities of the Centre for Synthesis and Chemical
Biology (CSCB), which was funded through the Higher Education
Authority’s Programme for Research in Third-Level Institutions
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
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13