Preparation of ferrocene-containing phosphinamine ligands possessing central and planar chirality and their application in palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1021/jo016391x

The preparation of {2-(Sp)-[(trans-(2R,5R)-2,5-dialkylpyrrolidinyl)methyl]}ferrocenyldiphenyl phosphines, new ferrocenylphosphinamine ligands possessing one site of planar and two stereogenic centers, is described trans-(2R,5R)-2,5-Dialkyl-1-(ferrocenylmethyl)pyrrolidines were diastereoselectively lithiated and quenched with chlorodiphenylphosphine. For the dimethyl ligand, chemical yields of up to 65% and des of up to 90% were obtained whereas the diethyl ligand afforded lower chemical yields (10%) and des of 78%. Diastereomerically pure material was obtained in both cases after a single recrystallization from ethanol. (S)-Planar chirality was confirmed by X-ray crystallographic analysis of the dimethyl ligand. The palladium complexes of the new ligands were applied in the allylic alkylation of 1,3-diphenylprop-2-enyl acetate with reasonable chemical yields and moderate ees of up to 36% and 38% when dimethyl malonate and dimethyl methyl malonate were employed as nucleophiles, respectively. Importantly, it was found that the new ligands possessing the combination of planar and central chirality gave the opposite enantiomeric alkylation products compared to ligands which possess only the central chirality of the trans-2,5-dimethylpyrrolidinyl moiety. Solution NMR studies of the 1,3-diphenylallyl palladium complex of the dimethyl ligand revealed the presence of only the exo-configured allyl diastereomer.

Full text of DOI:10.1021/jo016391x

J . Org. Chem. 2002, 67, 4209-4217
4209
P r ep a r a tion of F er r ocen e-Con ta in in g P h osp h in a m in e Liga n d s
P ossessin g Cen tr a l a n d P la n a r Ch ir a lity a n d Th eir Ap p lica tion in
P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic Alk yla tion
Annette Farrell,† Richard Goddard,§ and Patrick J . Guiry*,†
Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research,
Department of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland, and Max-Planck-Institut
fu¨r Kohlenforschung, Kaiser-Wilhelm-Platz 1,45470 Mu¨lheim an der Ruhr, Germany
p.guiry@ucd.ie
Received December 19, 2001
The preparation of {2-(Sp)-[(trans-(2R,5R)-2,5-dialkylpyrrolidinyl)methyl]}ferrocenyldiphenyl phos-
phines, new ferrocenylphosphinamine ligands possessing one site of planar and two stereogenic
centers, is described. trans-(2R,5R)-2,5-Dialkyl-1-(ferrocenylmethyl)pyrrolidines were diastereose-
lectively lithiated and quenched with chlorodiphenylphosphine. For the dimethyl ligand, chemical
yields of up to 65% and des of up to 90% were obtained whereas the diethyl ligand afforded lower
chemical yields (10%) and des of 78%. Diastereomerically pure material was obtained in both cases
after a single recrystallization from ethanol. (S)-Planar chirality was confirmed by X-ray crystal-
lographic analysis of the dimethyl ligand. The palladium complexes of the new ligands were applied
in the allylic alkylation of 1,3-diphenylprop-2-enyl acetate with reasonable chemical yields and
moderate ees of up to 36% and 38% when dimethyl malonate and dimethyl methyl malonate were
employed as nucleophiles, respectively. Importantly, it was found that the new ligands possessing
the combination of planar and central chirality gave the opposite enantiomeric alkylation products
compared to ligands which possess only the central chirality of the trans-2,5-dimethylpyrrolidinyl
moiety. Solution NMR studies of the 1,3-diphenylallyl palladium complex of the dimethyl ligand
revealed the presence of only the exo-configured allyl diastereomer.
In tr od u ction
sulfoximines13 and hydrazones,14 promote highly diaste-
reoselective ortho-metalations, thus allowing for the
preparation of planar chiral ferrocene compounds. A
further example is (S)-(2-methoxymethylpyrrolidin-1-yl)-
ferrocene 3, developed by Ganter, which directs lithiation
through the ether oxygen to afford phosphinamine ligand
4.15 The asymmetric lithiation of (S)-(2-methyl)piperdin-
1-yl)ferrocene 5 was initially claimed by Aratani to afford
up to 94% diastereoselectivity.16 However, this was
corrected to 67% diastereoselectivity favoring (S) planar
chirality in subsequent work by Ugi.17 Although the
phosphinamine ligand 6 was not prepared, ligands 4 and
6 do not contain a symmetrically substituted pyrrolidine
or piperidine ring, respectively, which limits their po-
tential application in asymmetric catalysis.
The ability of enantiopure ligands to induce asymmetry
in reactions occurring within the coordination sphere of
the transition metal to which they are bound, has led to
the development of an active area of research in their
design and application in asymmetric catalysis.1,2 A range
of diphosphine and phosphinamine ferrocene-containing
ligands possessing planar chirality have been prepared
and applied with success in a variety of processes.3,4 The
initial example of Kumada and Hayashi 1, and subse-
quent related examples from Togni, have as their key
precursor (R)-N,N-(dimethyl-1-ferrocenyl)ethylamine 2.5,6
Amine 2, and a range of other ortho-metalating groups,
including sulfoxides,7 acetals,8 oxazolines,9-11 azepines,12
* To whom correspondence should be addressed. E-mail: p.guiry@
ucd.ie. Tel +353-1-716-2309. Fax +353-1-716-2127.
† University College Dublin.
§ Max-Planck-Institut fu¨r Kohlenforschung.
(1) Noyori, R. In Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994.
(2) Ojima, I. In Catalytic Asymmetric Synthesis; VCH: Weinheim,
1993; p 325.
(3) Togni, A., Hayashi, T. In Ferrocenes; VCH: Weinheim, 1995;
Chapter 2.
(4) Richards, C. J .; Locke, A. J . Tetrahedron: Asymmetry 1998, 9,
2337.
We have recently reported the preparation of phosphi-
namine ligands 7-10,18 bearing an enantiopure C2-
(5) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotari, M.; Nagashima,
N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi, M.; Yama-
moto, K.; Kumada, M. Bull. Chem. Soc. J pn. 1980, 53, 1138.
(6) Togni, A.; Bieler, N.; Burckhardt, U.; Kollner, C.; Pioda, G.;
Schneider, R.; Schnyder, A. Pure Appl. Chem. 1999, 71, 1531 and
references therein.
(7) Rebiere, F.; Riant, O.; Ricard, L.; Kagan, H. B. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 568.
(8) Kagan, H. B.; Samuel, O.; Riant, O. J . Am. Chem. Soc. 1993,
115, 5835.
(10) Richards, C. J .; Damalidis, T.; Hibbs, D. E.; Hursthouse, M. B.
SynLett 1995, 74.
(11) Nishibayashi, Y.; Uemura, S. SynLett 1995, 79.
(12) Wildhalm, M.; Mereiter, K.; Bourghida, M. Tetrahedron: Asym-
metry 1998, 9, 2983.
(13) Bolm, C.; Kesselgruber, M.; Muniz, K.; Raabe, G. Organome-
tallics 2000, 19, 1648.
(14) Enders, D.; Peters, R.; Lochtman, R.; Raabe, G. Angew. Chem.,
Int. Ed. 1999, 38, 2421.
(9) Sammakia, T.; Latham, H. A. J . Org. Chem. 1995, 60, 6002.
10.1021/jo016391x CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/10/2002

4210 J . Org. Chem., Vol. 67, No. 12, 2002
Sch em e 1. Syn th esis of P yr r olid in es 11 a n d 12
Farrell et al.
symmetric trans-2,5-disubstituted pyrrolidine unit and
have described their application in palladium-catalyzed
allylic substitution,19 iridium-catalyzed enantioselective
imine reduction,20 the palladium-catalyzed asymmetric
intermolecular Heck reaction,21 and a mechanistic study
of their palladium η3-allyl species.22
three steps from N,N-(dimethylamino)methylferrocene
16, Scheme 1.
The first step converted 16 into ferrocenyl(methyl)-
acetate 17 in 99% yield using Hayashi’s acylation pro-
cedure.5 The reaction of 17 with allylamine afforded
(ferrocenylmethyl)prop-2-enylamine 18 in 82% yield and
subsequent deprotection,28 in a modification of literature
procedures for deallylation using palladium(0) catalysis
and N,N′-dimethylbarbituric acid as the allyl scavenger,
gave ferrocenylmethylamine 13 in 77% yield.29,30 Using
the standard procedure for pyrrolidine ring formation,
13 was reacted with (2S,5S)-hexanediol cyclic sulfate 14
to give trans-(2R,5R)-2,5-dimethyl-1-(ferrocenylmethyl)-
pyrrolidine 11 in an optimized 56% yield. Similarly,
trans-(2R,5R)-2,5-diethyl-1-(ferrocenylmethyl)pyrroli-
dine 12 was formed in 73% yield from the reaction of 13
with (3S,6S)-octanediol cyclic sulfate 14.
The directed diastereoselective ortho-lithiation of trans-
(2R,5R)-2,5-dialkyl-1-(ferrocenylmethyl)pyrrolidines 11
and 12 and subsequent treatment with chlorodiphen-
ylphosphine was then investigated. The process was
found to be sensitive to the 2,5-dialkyl substituent, the
alkyllithium reagent used, the reaction temperature, and
the solvent (Scheme 2 and Table 1). The yields quoted
refer to the overall yields obtained and not those for the
major diastereomers formed.
It was therefore of interest to prepare the analogous
trans-(2R,5R)-2,5-dialkyl-1-(ferrocenylmethyl)pyrroli-
dines 11 and 12 and to study their ability to direct
diastereoselective metalation as a route to ferrocenylphos-
phinamine ligands possessing both planar chirality and
stereogenic centers. We now report the preparation of two
such ligands and the determination of the absolute
configuration of the trans-(2R,5R)-2,5-dimethyl-substi-
tuted example by X-ray crystallography. In addition, the
application of these ligands in palladium-catalyzed allylic
substitution and a spectroscopic study of their palladium
η3-allyl species will be presented.
With 11, use of n-butyllithium in either ether or hexane
at -78 °C or ambient temperature, conditions previously
successful for the directed lithiation of amine 16,31 failed
to afford any product. A change to sec-butyllithium in
ether gave a 65% yield in 80% de which was optimized
Resu lts a n d Discu ssion
The key step in the synthesis of 11 and 12 was the
cyclocondensation of ferrocenylmethylamine 13 with
enantiopure 2,5-dimethyl- or 2,5-diethyl-1,4-diol cyclic
sulfate 14 and 15 and similar, successful routes to trans-
2,5-disubstituted pyrrolidines have used appropriately
substituted 1,4-dimesylates23-25 or 1,4-diacetates.26,27 The
required ferrocenylmethylamine 13 was prepared in
(21) Guiry, P. J .; Hennessy, A. J .; Cahill, J . P. Topics Catal. 1997,
4, 311.
(22) Cahill, J . P.; Cunneen, D.; Guiry, P. J . Tetrahedron: Asymmetry
1999, 10, 4157.
(23) Short, R. P.; Kennedy, R. M.; Masamune, S. J . Org. Chem. 1989,
54, 1755-1756.
(24) Chong, J . M.; Clarke, I. S.; Koch, I.; Olbach, P. C.; Taylor, N. J .
Tetrahedron: Asymmetry 1995, 6, 409-418.
(25) Sweet, J . A.; Cavallari, J . M.; Price, W. A.; Ziller, J . W.;
McGrath, D. V. Tetrahedron: Asymmetry 1997, 8, 207-211.
(26) Schwink, L.; Knochel, P. Tetrahedron Lett. 1997, 38, 3711.
(27) Woltersdorf, M.; Kranich, R.; Schmalz, H.-G. Tetrahedron 1997,
53, 7219.
(15) Ganter, C.; Wagner, T. Chem. Ber. 1995, 128, 1157.
(16) Aratani, T.; Gonda, T.; Nozaki, H. Tetrahedron Lett. 1969, 10,
2265.
(17) Gokel, G.; Hoffmann, P.; Kleimann, K.; Klusacek, H.; Mar-
guarding, D.; Ugi, I. Tetrahedron Lett. 1970, 11, 1771.
(18) Cahill, J . P.; Bohnen, F.; Goddard, R.; Kru¨ger, C.; Guiry, P. J .
Tetrahedron: Asymmetry 1998, 9, 3831.
(19) Cahill, J . P.; Guiry, P. J . Tetrahedron: Asymmetry 1998, 9,
4301.
(28) Ferrocenylmethyl(N-benzylamine) was prepared but attempts
at debenzylation failed.
(29) Garro-Helion, F.; Merzouk, A.; Guibe, F. J . Org. Chem. 1993,
58, 6109.
(30) Lemaire-Audoire, S.; Savignac, M.; Dupuis, C.; Genet, J .-P. Bull.
Soc. Chim. Fr. 1995, 132, 1157.
(20) Cahill, J . P.; Lightfoot, A. P.; Goddard, R.; Rust, J .; Guiry, P.
J . Tetrahedron: Asymmetry 1998, 9, 4307.
(31) Slocum, D. W.; Rockett, B. W.; Hauser, C. R. J . Am. Chem. Soc.
1965, 87, 1244.

Ferrocene-Containing Phosphinamine Ligands
J . Org. Chem., Vol. 67, No. 12, 2002 4211
Sch em e 2. Dia ster eoselective Lith ia tion of P yr r olid in es 11 a n d 12
Ta ble 1. Dia ster eoselectivity of Or th o-lith ia tion of
tr a n s-(2R,5R)-2,5-Dia lk yl-1-(fer r ocen ylm eth yl)p yr r olid in es
11 a n d 12
amine
RLi
T [°C]
time [h]
yield [%]
de [%]
11
11
11
11
11
11
11
12
n-BuLia
n-BuLia
s-BuLib
s-BuLib
s-BuLib
t-BuLib
t-BuLib
n-BuLib
-78
25
25
25
0
25
0
25
1
1
1
5
1
1
1
1
-
-
-
-
65
37
20
30
10
10
80c
80
90
82
90
78c
Hexane or Et2O as solvent. Et2O as solvent. c >100:1 after
a
b
a single recrystallization from EtOH.
F igu r e 1. X-ray crystal structure of (SP,R,R)-19a .
to >100:1 de after a single recrystallization from ethanol.
The key resonances for de determination by 1H NMR
were the unsubstituted cyclopentadienyl ring of the major
diastereomer at δ 4.01 and of the minor diastereomer at
δ 3.97. Alternatively, the de could be determined using
31P NMR as the major diastereomer resonated at δ
-22.32 and the minor diastereomer at δ -16.5. A longer
reaction time of 5 h led to a decreased chemical yield of
37% and lowering of the reaction temperature to 0 °C
gave a de of 90% but a lower yield of 20%. Lithiation with
tert-butyllithium at 25 °C gave a yield of 30% and 82%
de and lowering the reaction temperature to 0 °C gave a
90% de in a poor 10% yield. The lithiation of 12 proved
much more difficult and only use of n-butyllithium in
ether at 25 °C gave 20 in 10% yield and a 78% de, which
was increased to >100:1 de after a single recrystallization
F igu r e 2. Proposed interactions of alkyllithium reagent with
amines 11 and 12. [The lower cyclopentadienyl ring has been
omitted for clarity].
The major product was therefore assigned (S) planar
chirality, which was suggested by comparison of its
optical rotation with known ferrocenyl compounds.5,33 We
propose that (S)-planar chirality is preferred due to the
orientation of the pyrrolidinyl methyl groups and their
interaction with the incoming lithiating reagent. If the
lithium reagent coordinates in the position leading to the
favored diastereomer by approaching the substituted Cp
ring from above, then the 2-methyl of the pyrrolidine is
oriented away from the alkyllithium approach, structure
21, Figure 2. However, if the lithium reagent coordinates
to the nitrogen to remove the proton to give the (R)-
planar product, the 5-methyl causes a repulsive interac-
tion with the approaching alkyllithium reagent, structure
22. These are similar arguments to those made by Ganter
in the lithiations of 315 and by Uemura in the lithiation
of ferroceneoxazolines.11
This is the first example of a diastereoselective ortho-
metalation directed by a trans-2,5-dialkyl-substituted
pyrrolidine nitrogen atom. It is clear that there is a subtle
interplay between the steric bulk of the alkyllithium rea-
gent and that of the 2,5-dialkyl group. The more hindered
2,5-diethyl-substituted pyrrolidine fails to afford any
product with sec- or tert-butyllithium. The less sterically
hindered 2,5-dimethyl-substituted pyrrolidine gives prod-
uct with both sec- and tert-butyllithium, although the
latter proceeds in poorer yield but with higher de.
1
from ethanol. In this case the de was calculated by H
NMR spectroscopy as the unsubstituted cyclopentadienyl
ring of the major diastereomer occurred at δ 4.01 and in
the minor diastereomer appeared at δ 3.96.
Crystals of the major diastereomer obtained from the
directed phosphinylation of 11 were suitable for X-ray
structure determination and the result of this analysis
is summarized in Figure 1.32 The compound crystallizes
in the chiral space group P21 with two independent
molecules in the asymmetric unit. Despite their different
crystal environments the two molecules adopt almost
identical conformations (rms deviation for non-H atoms
0.200 Å) in which the open face of the pyrrolidinyl group
lies approximately parallel to one of the phenyl rings of
the phosphine. The intramolecular distance of the N atom
from the mean plane through the C atoms of the phenyl
group is 3.39(2) Å (mean).
(32) Crystal data for (SP,R,R)-19: C29H32FeNP, Mw ) 481.4, orange
plate 0.02 × 0.08 × 0.64 mm, monoclinic P21 [No. 4], a ) 7.4699(7), b
) 33.466(3), c ) 9.8599(9) Å, â ) 95.349(3)°, U ) 2454.1(4) Å3, T )
100 K, Z ) 4, Dx ) 1.303 g cm-3, λ ) 0.71073 Å, µ(Mo-KR) ) 0.696
mm-1 Nonius KappaCCD diffractometer, 2.07 < θ < 32.23°, Gaussian
absorption correction (Tmin 0.83473, Tmax 0.98593), 10074 measured
reflections, 7518 independent, 4147 with I > 2(I). Structure refined
2
by least-squares using Chebyshev weights on Fo to R1 ) 0.081 [I >
2σ(I)], wR2 ) 0.260, absolute configuration determined [Flack param-
eter -0.02(4)], 581 parameters, H atoms riding, S ) 1.004, residual
(33) Nishibayashi, Y.; Arikawa, Y.; Ohe, K.; Uemura, S. J . Org.
Chem. 1996, 61, 1172.
electron density +0.761/-1.320 e Å-3
.

4212 J . Org. Chem., Vol. 67, No. 12, 2002
Farrell et al.
Sch em e 3
Ta ble 2. Ap p lica tion of 19a a n d 20a to th e
Sch em e 4. P a lla d iu m Ca ta lyzed Allylic
Alk yla tion of Aceta te 22
P a lla d iu m -Ca ta lyzed Asym m etr ic Allylic Alk yla tion of
1,3-d ip h en ylp r op -1-en yl Aceta te 22a
temp yield
[°C]
ee [%]c
entry ligand
method
NaMal
solvent
CH2Cl2
[%]b
(config)d
1
2
3
4
5
6
7
8
9
19a
19a
19a
19a
19a
19a
19a
19a
20a
20a
7
25
25
25
25
25
25
0
69
53
25
70
49
22
41
23
71
64
62
89
36 (S)
12 (S)
14 (S)
26 (S)
24 (S)
14 (S)
12 (S)
24 (S)
20 (S)
18 (S)
55 (R)19
90 (R)19
NaMal[e] CH2Cl2
NaMal
NaMal
BSA
BSA
BSA
BSA
BSA
BSA
BSA
DMF
CH3CN
CH2Cl2
CH3CN
CH2Cl2
CH3CN
CH2Cl2
CH3CN
DMF
The application of these new ferrocenylphosphinamine
ligands in enantioselective palladium-catalyzed allylic
alkylation allowed for a direct comparison with ligands
7 and 8 and the influence of the planar element of
chirality was determined.
0
25
25
0
10
11
12
8
BSA
CH3CN
25
a
In performing allylic substitutions it is possible to use
as the catalyst either preformed palladium (η3-allyl)
complexes of the ligand or to assume that such complexes
are formed when a slight excess of ligand is added to
either Pd2(dba)3 or a η3-allyl palladium chloride dimer.
The latter approach was used for (SP,R,R)-20 whereas
the air-stable η3-allyl palladium tetrafluoroborate salt of
ligand (SP,R,R)-19 was prepared in quantitative yield,
Scheme 3. [Hereafter for clarity, (SP,R,R)-19 will be
referred to as 19a and (SP,R,R)-20 as 20a .]
The reaction was carried out over 24 h in the presence of 1
mol % of preformed catalyst 21 or in situ formed catalyst from
b
ligand 20a using either NaMal or BSA method. Isolated yield
after silica gel chromatography. c Enantiomeric excesses were
determined by 1H NMR using Eu(hfc)3 as the chiral shift reagent.
d
Assignment is based on the sign of the optical rotation and
comparison with the literature.34 e 15-Crown-5 added to reaction.
tive, it resulted in both a lower ee and chemical yield
(entry 2). Changing solvent to acetonitrile or dimethyl-
formamide gave lower ees (26 and 14%, respectively), and
the chemical yield in the latter case was poor (25%,
entries 3 and 4). Dichloromethane and acetonitrile were
used as solvents for the BSA procedure, but in all cases,
despite investigating a variety of reaction conditions, the
yields and ees were lower than those observed using the
malonate procedure. Palladium complexes of 20a afforded
higher chemical yields but gave disappointingly low ees
of 18-20%, again favoring the (S)-product 25. For
comparative purposes the yields and ees obtained in a
previous study using palladium complexes of 7 and 8 are
included in Table 2 (entries 11 and 12).19 A direct
comparison of 19a with 7 shows that the latter gave a
higher ee of 55% but of the opposite enantiomer. Simi-
larly, 20a gave a 90% ee favoring (R)-25 while 8 gave an
optimum ee of 20% favoring (S)-25. This indicates that
in the case of the ferrocene-containing P,N ligands 19a
and 20a , the planar element of chirality influences the
stereoselectivity to a greater extent than the two stereo-
genic centers of the trans-2,5-disubstituted pyrrolidine
moiety. This leads to a mismatch of the chiral elements
present in ligands 19a and 20a .
In an attempt to increase the enantioselectivites
induced by catalyst 23 we also examined the influence
of increasing the size of nucleophile. Thus, the reaction
of acetate 24 with dimethyl methyl malonate was studied,
Scheme 5. The results of these investigations are given
in Table 3.
The yields in all cases were higher than those observed
when dimethyl malonate was the nucleophile. The ma-
lonate procedure gave low to moderate enantioselectivi-
ties (16-38%) and even lower (10-16%) enantioselectiv-
The structure of palladium{(2-[(trans-(2R,5R)-2,5-
dimethylpyrrolidinyl)methyl]}ferrocenyl diphenylphos-
phine(η3-allyl)tetrafluoroborate 23 was confirmed by
1
spectroscopic methods. The high field H NMR spectrum
was broad at room temperature, but the 31P NMR
spectrum showed two peaks at 16.3 and 15.1 ppm in a
ratio of 8:1, indicating the existence of both diastereo-
meric endo- and exo-intermediates in solution. [Nomen-
clature note: the endo-isomer is defined here as that allyl
configuration in which the central allyl proton points
above the plane of the P-Pd-N chelate].
Once prepared, the asymmetry-inducing abilities of the
palladium complexes of 19a and 20a were tested in what
has become one of the standard reactions in allylic
alkylation, namely that between dimethylmalonate and
racemic 1,3-diphenylprop-2-enyl acetate 24 to afford
enantioenriched malonate product 25, Scheme 4. The
results obtained are summarized in Table 2.
The malonate nucleophile can be preformed as its
sodium salt (NaMal) or prepared in situ by Trost’s
procedure using N,O-bis(trimethylsilyl)acetamide (BSA)
and catalytic quantities of potassium acetate.35 Using the
malonate procedure, the highest enantioselectivity for
ligand 19a was found to be a moderate 36% (S) when
dichloromethane was employed as solvent (entry 1).
When 15-crown-5, which is generally used to enhance the
solubility of the sodium salt, was employed as an addi-
(34) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
566.
(35) Trost, B. M.; Murphy, D. J . Organometallics 1985, 4, 1143.

Ferrocene-Containing Phosphinamine Ligands
J . Org. Chem., Vol. 67, No. 12, 2002 4213
Sch em e 5
contains an allyl group which has reoriented itself into
a product-like geometry, thus facilitating nucleophilic
attack on that allyl terminal carbon trans to the phos-
phorus donor atom. The lability of the diastereomeric 1,3-
diphenylallyl complexes is influenced by such electronic
factors and also by intra-complex steric clashes between
the ligand and the allyl. Solution NMR studies on these
key intermediates would allow us to determine the ratio
of endo- to exo-diastereomers and to gain some insight
as to the influence of the planar chiral element of the
1,2-disubstituted ferrocene and the alkyl groups at the
stereogenic centers of the pyrrolidine. In the present
study it would allow for a direct comparison between the
solution behavior of the 1,3-diphenylallyl complexes of
the trans-2,5-dialkylpyrrolidinyl-containing phosphin-
amine ligands 7-10 and 19a .22
Ta ble 3. Ap p lica tion of P a lla d iu m Com p lex 23 to th e
Asym m etr ic Allylic Alk yla tion of Aceta te 22 w ith
Dim eth yl Meth yl Ma lon a tea
entry method solvent temp [°C] yield [%]b ee [%]c (config)d
1
2
3
4
5
6
7
8
NaMal CH2Cl2
NaMal CH3CN
NaMal DMF
NaMal THF
25
25
25
25
25
25
25
25
72
79
37
58
85
79
83
70
36 (R)
38 (R)
34 (R)
16 (R)
12 (R)
16 (R)
10 (R)
16 (R)
BSA
BSA
BSA
BSA
CH2Cl2
CH3CN
THF
Hence the η3-1,3-diphenylallyl palladium tetrafluo-
roborate salt 30 was prepared in quantitative yield
following literature precedent by the reaction of 19a with
di-µ-chloro-bis(1,3-diphenyl-π-allyl)dipalladium, Scheme
7.44
DMF
a
The reaction was carried out over 24 h in the presence of 1
mol % of preformed catalyst 23 using either NaMal or BSA
method. Isolated yield after silica gel chromatography. c Enan-
b
The 31P spectrum of the resultant complex showed a
single peak at 34.4 ppm, indicating the presence of only
one diastereomeric intermediate. At room temperature
tiomeric excesses were determined by 1H NMR using Eu(hfc)3 as
d
the chiral shift reagent. Assignment is based on the sign of the
optical rotation and comparison with the literature.34
1
the H NMR spectrum was broad, and it was necessary
to reduce the temperature until sharp peaks were
observed at -55 °C, Figure 3.
ities when the BSA procedure was employed. In all cases
the (R)-enantiomer of 26 was the favored enantiomer
formed indicating the same sense of asymmetric induc-
tion as for the dimethyl malonate case. [Note: the
assignment of configuration is opposite for 25 and 26 as
the malonate substituent priority changes.]
The pyrrolidine methyl groups were inequivalent and
appear as doublets at 1.18 and 1.41 ppm with coupling
constants of 6.35 Hz. To distinguish the methyl groups
(Me2′ and Me5′) required the examination of the 1H
NOESY spectrum to determine which methyl showed a
cross-peak to one of the Fc-CH2 peaks. It was found that
the methyl at 1.41 ppm showed such a cross-peak to one
of protons of the Fc-CH2, which appears as a double
doublet at 4.38-4.42 ppm. With the aid of 1H-1H COSY,
all of the pyrrolidine proton peaks were subsequently
identified, the CH2 multiplets were observed at 1.66-
1.70 ppm for H3b′ and H4a′ and at 1.95-2.03 pm for H3a′
and H4b′. The methine protons appeared at 3.47-3.50
ppm for H5′ and at 3.69-3.72 ppm for H2′. The remaining
proton of the Fc-CH2 appeared as a multiplet at 4.74-
4.78 ppm. The unsubstituted cyclopentadienyl ring ap-
peared as a singlet at 4.01 ppm, and the protons of the
substituted ring at 4.32-4.35 ppm for H5, 4.63-4.65 ppm
for H4, and 5.13-5.16 ppm for H3. Full assignment of the
allyl protons was facilitated by DQF-COSY experiments.
In this fashion, the central allyl proton was determined
to be a broad multiplet at 8.87-8.92 ppm, the allyl proton
trans to nitrogen was under the methine multiplet for
H5′ at 3.47-3.50 ppm and the allyl proton trans to
phosphorus appeared under one of the Fc-CH2 multiplets
at 4.74-4.78. With these peaks assigned, it was then
In an attempt to explain the enantioselectivities ob-
served with palladium complexes of ligand 19a , solution
NMR studies were carried out on its cationic palladium-
(II) 1,3-diphenylallyl intermediates. The information thus
garnered could be useful for future rational ligand design.
For palladium complexes of phosphinamine ligands, the
generally accepted mechanism of allylic alkylation in-
volves the initial association of a palladium(0) phosphin-
amine species to the olefinic fragment of racemic 1,3-
diphenylprop-2-enyl acetate 24 to give diastereomeric η2-
palladium(0) species 27 which undergo oxidative addition
to give cationic palladium(II) η3-intermediates 28-endo
and 28-exo, Scheme 6 [note: only two of the four possible
η2-palladium(0) species 27 are shown for clarity]. Inter-
mediates 28 interconvert, thus allowing racemic material
the possibility to afford enantiomerically enriched prod-
uct. Carbon-carbon bond formation with soft nucleo-
philes then occurs outside the coordination sphere to
afford, after olefin dissociation from 29, the allylated
product as either the (R)-25 or (S)-25 enantiomer (when
the nucleophile is dimethyl malonate).36
A considerable effort has been made to understand this
critical enantiodifferentiating carbon-carbon bond-form-
ing step from the initial investigations of Bosnich37,38
employing diphosphine ligands to the more recent work
of Brown, Pfaltz, Togni, and Helmchen employing phos-
phinamine ligands.39-43 The key findings from the latter
studies suggest that the ground state of complex 28
1
necessary to further examine the H NOESY spectrum
to decide whether the major enantiomer was of endo or
exo configuration.
(40) von Matt, P.; Lloyd-J ones, G. C.; Pfaltz, A.; Macko, L.; Neu-
burger, M.; Zehnder, M.; Ruegger, H.; Pregosin, P. S. Helv. Chim. Acta
1995, 78, 265-284.
(41) Togni, A.; Bruckhardt, U.; Gramlich, V.; Pregosin, P. S.;
Salzmann, R. J . Am. Chem. Soc. 1996, 118, 1031.
(42) Sprinz, J .; Kiefer, M.; Helmchen, G.; Huttner, G.; Walter, O.;
Zsolnai, L.; Reggelin, M. Tetrahedron Lett. 1994, 35, 1523.
(43) Kollmar, M.; Goldfuss, B.; Reggelin, M.; Rominger, F.; Helm-
chen, G. Chem. Eur. J . 2001, 7, 4913.
(36) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395.
(37) Auburn, P. R.; MacKenzie, P. B.; Bosnich, B. J . Am. Chem. Soc.
1985, 107, 2033.
(38) MacKenzie, P. B.; Whelan, J .; Bosnich, B. J . Am. Chem. Soc.
1985, 107, 2047.
(39) Claridge, T. D. W.; Long, J . M.; Brown, J . M.; Hibbs, D.;
Hursthouse, M. B. Tetrahedron 1997, 53, 4035.
(44) Togni, A.; Rihs, G.; Pregosin, P. S.; Ammann, C. Helv. Chim.
Acta 1990, 73, 723.

4214 J . Org. Chem., Vol. 67, No. 12, 2002
Farrell et al.
Sch em e 6
Sch em e 7
F igu r e 4. (a) Side view of X-ray structure of Pd dichloride
complex of 7. (b) Important NOEs allowing assignment of
diastereomer.
of ligand 7 where a 5:2 ratio of endo:exo diastereomers
was observed.22 This comparison highlights the influence
that planar chirality exerts on the 1,3-diphenylallyl
orientation, presumably through interactions between
the diphenylphosphinoferrocene unit and the allyl frag-
ment.
F igu r e 3. 1H NMR of 1,3-diphenylallyl palladium complex
30 at -55 °C.
The implication of the current NMR study is that the
nucleophile attacks trans to phosphorus in the major
diastereomer. The ground state favors one diastereomer
exclusively and the low ees observed could be due to the
flexibility at the Fc-CH2 position as observed by other
workers with ferrocenyl ligands lacking a stereogenic
center at the R-methyl position. In addition, it could be
that the six-membered chelate is strongly bent and that
this leads to further, rapidly interconverting isomers. We
are currently testing metal complexes of ligand 19a and
related ferrocene-containing P,N ligands in other asym-
metric transformations and the results of these investi-
gations will be reported from these laboratories in due
course.45
There were two critical NOEs which allowed its
unambiguous assignment, and the side view of the X-ray
structure of the palladium dichloride complex of 718 is
given to aid in the visualization of the relevant NOEs,
Figure 4(a). The central allyl proton showed a NOE to
the methine proton (H2′) and the Me5′, which is only
possible if the allyl complex adopts the exo configuration
and rolls slightly in a counterclockwise direction, Figure
4b. The methine proton H2′ also shows a weak NOE to
the aromatic region, possibly to an ortho-proton of the
allyl phenyl trans to phosphorus. Hence, the major
diastereomer is assigned the exo configuration of the
π-allyl which gives rise to the preferred (S)-enantiomer
of 25. This is in contrast to the intermediates observed
in the corresponding 1,3-diphenylallyl palladium complex
(45) Farrell, A.; Meaney, K.; Guiry, P. J . Unpublished results.

Ferrocene-Containing Phosphinamine Ligands
J . Org. Chem., Vol. 67, No. 12, 2002 4215
dissolved in diethyl ether, and an excess of 1 M HCl was added
(2 × 30 mL). The combined aqueous layers were basified using
1 M NaOH, and the product was extracted with diethyl ether
(3 × 30 mL), dried (Na2SO4), and concentrated to yield 1 g of
crude 18 as a red brown oil. This oil was purified using column
chromatography, alumina, diethyl ether/hexane 2:1 yielding
Con clu sion
In conclusion, two new ferrocene-containing phosphin-
amine ligands possessing both planar chirality and
stereogenic centers were prepared in five steps from
(N,N-dimethylamino)methylferrocene. The key and final
step was a directed diastereoselective phosphinylation
which proceeded in 80% de and 65% yield for the trans-
(2R,5R)-2,5-methyl-1-(ferrocenylmethyl)pyrrolidine 11 and
in 78% de but poor chemical yield for trans-(2R,5R)-2,5-
diethyl-1-(ferrocenylmethyl)pyrrolidine 12. A single re-
crystallization from ethanol afforded diastereomerically
pure material in both cases. Their palladium complexes
were applied in the allylic alkylation of 1,3-diphenylprop-
2-enyl acetate with reasonable chemical yields and
moderate ees of up to 36% when dimethyl malonate and
38% when dimethyl methyl malonate was employed as
the nucleophile. Importantly, it was found that use of the
new ligands, possessing both planar chirality and the two
stereogenic centers in the trans-2,5-dialkylpyrrolidine
groups, resulted in alkylation products that were enan-
tiomeric to those obtained using palladium complexes of
the 7 and 8, containing the chiral trans-2,5-dialkylpyr-
rolidine groups alone. Clearly, the planar chirality of the
ferrocenyl unit plays an important role in the stereose-
lectivity. Moreover, its influence appears to be contrary
to that of the two stereogenic centers. Solution NMR
studies enabled the results of the catalytic studies to be
elucidated and reveal that the 1,3-diphenylallyl unit in
the palladium complex of (SP,R,R)-19 exists in solution
solely as the exo-configured allyl diastereomer.
18 (809 mg, 82%): Found: C, 65.70; H, 6.72; N, 5.29; C14H17
-
1
FeN requires C, 65.85; H, 6.69; N, 5.05; H NMR (270 MHz):
δ 1.46 (br.s, 1H), 3.27 (dd, J 1.3, 6.0, 2H), 3.51 (s, 2H), 4.08
(app. t, J 1.74, 2H), 4.12 (s, 5H), 4.19 (app. t, J 1.65, 2H), 5.15
(dq, J 17.2, 10.3, 1.5, 2H), and 5.84-5.99 (m, 1H); 13C NMR
(67.8 MHz): δ 48.3, 52.1, 67.8, 68.4, 70.2, 86.8, 115.9, and
136.7; νmax(CH2Cl2)/cm-1 1642 and 1270; MS (EI, 70 eV): m/z
(%): 254 [M+] (10), 199 (100), 134 (17), 121 (71), and 56 (30).
F er r ocen ylm et h yla m in e (13). Palladium(tetrakis(tri-
phenylphosphine)) (136 mg, 10 mol %) and N,N-dimethylbar-
bituric acid (NDMBA) (550 mg, 3 equiv) were placed in a dry
Schlenk under nitrogen. To this was added a solution of 18
(300 mg, 1 mmol) in dry degassed dichloromethane (2.5 mL
per mmol of amine). The solution was stirred at 40 °C for 3 h.
Hexane was added to remove the palladium byproducts and
unreacted N,N-dimethylbarbituric acid. The remaining solid
was dissolved in diethyl ether (100 mL) and extracted with 1
M HCl (4 × 20 mL). The combined aqueous layers were
basified with 1 M NaOH and extracted with diethyl ether to
yield 13 (192 mg, 77%) as an orange oil: Found: C, 61.17; H,
6.09; N, 6.21; C11H13FeN requires C, 61.43; H, 6.09; N, 6.04;
1H NMR δ 1.60 (br. s, 2H), 3.54 (s, 2H), 4.11 (app. t, J 1.83,
2H), 4.14 (s, 5H), and 4.16 (app. t, J 1.83, 2H); 13C NMR δ
41.4, 67.1, 67.8, 68.4, and 91.1; νmax(CH2Cl2)/cm-1 3100 and
1244; MS (EI, 70 eV): m/z (%): 215 [M+] (47), 199 (18), 121
(41), and 56 (100).
tr a n s-(2R,5R)-2,5-Dim et h yl-1-(fer r ocen ylm et h yl)p yr -
r olid in e (11). Amine 13 (400 mg, 1.86 mmol) and (S,S)-2,5-
dimethyl cyclic sulfate (334 mg, 1 equiv) were refluxed in dry
tetrahydrofuran for 16 h. The resulting precipitate indicated
the presence of the zwitterionic amine-sulfate species. The
Schlenk was evacuated under nitrogen and cooled to -78 °C
and n-butyllithium (1.27 mL, 1.1 equiv) added. The mixture
was warmed to room temperature and then refluxed for 72 h.
Diethyl ether was added to the solution which was then
washed with 10% ammonium chloride, water, and brine and
extracted into diethyl ether. This extract was dried (MgSO4)
and concentrated to yield 359 mg of crude material which was
purified using column chromatography, alumina, hexane/
diethyl ether 2:1, to yield 11 (309 mg, 56%) as an orange oil
Exp er im en ta l Section
1
Gen er a l Rem a r k s. H (270 or 400 MHz), 13C (67.5 or 125
MHz), and 31P (109.3 MHz) spectra were recorded at room
temperature in CDCl3. Chemical shifts (δ) are given in parts
per million relative to CHCl3 (7.26, 1H), CDCl3 (77.0, 13C), and
85% aqueous phosphoric acid (0.0, 31P). Coupling constants are
given as absolute values expressed in hertz. Low resolution
electron-impact MS spectra were measured at an ionization
potential of 70 eV. Isomers were assumed to have the same
response factors. Elemental analyses were performed by Ms
Anne Connolly, Department of Chemistry, University College
Dublin. Infrared spectra were recorded on a Perkin-Elmer
infrared FT spectrometer. Optical rotation values were mea-
sured on a Perkin-Elmer polarimeter. Melting points were
determined in open capillary tubes in a Gallenkamp melting
point apparatus and are uncorrected. Thin-layer chromatog-
raphy (TLC) was carried out on aluminum sheets precoated
with silica gel 60 F 254 (0.25 mm, Macherey-Nagel). Column
chromatography separations were performed using Merck
Kieselgel 60 (Art. 7734), Merck Alumina (Art. 1097) or Merck
Alumina (Art. 1104) as stated. Solvents were dried im-
mediately before use by distillation from standard drying
agents.46 Dimethylaminomethylferrocene, chlorodiphenylphos-
phine, N,N-dimethylbarbituric acid, allylamine and (+)-(3S,6S)-
2,5-octanediol were used as received from commercial sources.
Ferrocenylmethyl acetate (17) was prepared according to a
procedure developed by Hayashi.5 Palladium(tetrakis(tri-
phenylphosphine)) was prepared by literature procedures.47
(F er r ocen ylm eth yl)p r op -2-en yla m in e (18). To a solution
of ferrocenylmethyl acetate (1 g, 3.8 mmol) and methanol (14
mL) was added freshly distilled allylamine (3.14 mL, 4.6
mmol), and the mixture was refluxed for 6 h under a nitrogen
atmosphere. The solvent was evaporated, crude product was
which crystallized on cooling: Found: C, 68.69; H, 7.08; N,
20
4.71; C17H23FeN requires C, 68.69; H, 7.01; N, 4.66; [R]D
)
-82.2 (c ) 0.5, CHCl3); 1H NMR δ 0.99 (d, J 6.22, 6H), 1.25-
1.36 (m, 2H), 1.94-2.02 (m, 2H), 2.96-3.01 (m, 2H), 3.34 (d,
J 13.01, 1H), 3.54 (d, J 13.00, 1H), 4.06-4.09 (m, 2H), 4.11 (s,
5H), 4.22 (app. t, J 1.28, 2H), and 4.26 (app. t, J 1.28, 2H); 13
C
NMR δ 16.9, 30.6, 47.2, 55.1, 67.5, 67.9, 68.5, 69.5, 70.0, 85.9;
ν
max(CH2Cl2)/cm-1 1365; MS (EI, 70 eV): m/z (%): 298 [M+]
(22%), 199 (100), 121 (63), and 56 (58).
tr a n s-(2R,5R)-2,5-Dieth yl-1-(fer r ocen ylm eth yl)p yr r o-
lid in e (12). Amine 13 (272 mg, 12 mmol) and (2S,2S)-2,5-
diethyl cyclic sulfate (263 mg, 1 equiv) were refluxed in dry
tetrahydrofuran for 48 h. The resulting precipitate indicated
the presence of the zwitterionic amine-sulfate species. The
Schlenk was evacuated under nitrogen, cooled to -78 °C and
n-butyllithium (0.545 mL, 1.1 equiv) added. The mixture was
warmed to room temperature and then refluxed for 72 h.
Diethyl ether was added to the solution which was then
washed with 10% ammonium chloride, water, and brine and
extracted into diethyl ether. This extract was dried (MgSO4)
and concentrated to yield 300 mg of crude trans-(2R,5R)-2,5-
diethyl-1-(ferrocenylmethyl)pyrrolidine. This was purified us-
ing column chromatography, alumina, hexane/diethyl ether
2:1, to yield 12 (298 mg, 73%) as an orange oil: Found: C,
69.98; H, 8.26; N, 4.25; C19H27FeNP requires C, 70.15; H, 8.37;
20
1
N, 4.30; [R]D ) -47.2 (c ) 0.5, CHCl4); H NMR δ 0.81 (t, J
7.5, 6H), 1.06-1.10 (m, 2H), 1.41-1.48 (m, 2H), 1.63-1.69 (m,
2H), 1.80-1.85 (m, 2H), 2.69-2.76 (m, 2H), 3.45 (d, J 13.00,
1H), 3.55 (d, J 13.01, 1H), 4.04-4.07 (m, 2H), 4.10 (s, 5H),
(46) Perrin, D. D.; Armarego, W. L. F. In Purification of Laboratory
Chemicals, 3rd ed.; Pergamon: Oxford, 1998.
(47) Hegedus, L. S. In Organometallics in Synthesis; Schlosser, M.,
Ed.; Wiley: New York, 1994; p 448.

4216 J . Org. Chem., Vol. 67, No. 12, 2002
Farrell et al.
4.15-4.18 (m, 1H), and 4.21-4.25 (m, 1H); 13C NMR δ 10.9,
22.9, 27.5, 46.8, 62.2, 67.5, 67.8, 68.5, 69.5, 70.0, and 86.1; νmax
(CH2Cl2)/cm-1 2312; MS (EI, 70 eV): m/z (%): 325 [M+] (20%),
199 (100), and 121 (25).
Allylic Alk yla tion P r oced u r es. Ma lon a te Ion P r oce-
d u r e. 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 acetonitrile (0.3 mL) was
added to form a white suspension. To this was added a solution
ofeither palladium{2SP-[(trans-(2R,5R)-2,5-dimethylpyrrolidinyl)-
methyl]}ferrocenyldiphenylphosphine(allyl)tetrafluoroborate
(1.8 mg, 0.0025 mmol) or in situ prepared catalyst [di-µ-chloro-
bis(π-allyl)dipalladium (0.0025 mmol) and {2SP-[(trans-(2R,5R)-
2,5-diet h ylpyr r olidin yl)m et h yl]}fer r ocen yldiph en ylph os-
phine (0.005 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 40-60 °C:diethyl ether: 2:1 as the
eluent). 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) and then washed with
water (25 mL) and brine (25 mL). The solution was dried with
MgSO4, filtered, and the solvent removed in vacuo to give an
orange oil. This was purified on silica gel plates (eluent )
petroleum ether 40-60 °C:diethyl ether; 2:1) to afford 25 [when
dimethyl malonate was the nucleophile], (S)-methyl-2-car-
bomethoxy-3,5-diphenylpent-4-enoate as a colorless oil: Rf )
0.37; 1H NMR δ 3.51 (s, 3Η), 3.70 (s, 3H), 3.95 (d, J 11.2, 1H),
4.26 (dd, J 8.8, J 11, 1H), 6.33 (dd, J 8.8, 5.6, 1H), 6.47 (d, J
15.6, 1H), and 7.33-7.18 (m, 10H); νmax (Nujol)/cm-1 1733 and
1600; MS (EI, 70 eV): m/z (%) 324 (M+, 5), 193 (20), 105 (100),
and 91 (27).
Similarly, this procedure afforded [when dimethyl methyl
malonate was the nucleophile], (R)-ethyl-2-carbomethoxy-3,5-
diphenylpent-4-enoate 26 as a colorless oil: 1H NMR δ 1.48
(s, 3H), 3.62 (s, 3H), 3.70 (s, 3H), 6.43-6.49 (d, J 15.75, 1H),
6.67-6.72 (m, 1H), and 7.29-7.45 (m, 10H); νmax(Nujol)/cm-1
1735 and 1600.
BSA P r oced u r e. A solution of palladium{2SP-[(trans-(2R,
5R)-2,5-dimethylpyrrolidinyl)methyl]}ferrocenyldiphenylphos-
phine(allyl)tetrafluoroborate (1.8 mg, 0.0025 mmol) in dry
degassed solvent (0.5 mL) was added to potassium acetate
(0.005 mmol), under a nitrogen atmosphere to form a suspen-
sion. To this suspension were then added 1,3-diphenylprop-
2-enyl acetate (0.063 g, 0.250 mmol), dimethylmalonate (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
monitored by TLC and the reaction mixture purified as for
the Malonate Ion procedure.
Deter m in a tion of En a n tiom er ic Excess. The ee was
found by 1H NMR spectroscopy from the spectrum obtained
after adding 20-30 µL of a 0.2 M solution of tris[3-(heptafluo-
ropropylhydroxymethylene)-(+)-camphorato]europium (III) to
10-15 mg of methyl 2-carbomethoxy-3,5-diphenylpent-4-
enoate in CDCl3 (0.5 mL). The methoxy groups of methyl
2-carbomethoxy-3,5-diphenylpent-4-enoate resonate at 3.51
and 3.70 ppm. Following the addition of the chiral shift reagent
and subsequent formation of diastereomers, four methoxy
peaks are present in the 1H spectrum. The methoxy peak
originally at 3.70 ppm is changed to two peaks at 3.74 and
3.76 ppm, and the relative integration of these peaks gives
the ee value. If the right-hand peak of these two is larger than
this is typical of the (S)-enantiomer in excess which was
confirmed by comparing the optical rotation obtained with
literature values.35
P a lla d i u m {2S P -[(t r a n s -(2R ,5R )-2,5-d i m e t h y lp y r -
r olidin yl)m eth yl]}fer r ocen yldiph en ylph osph in e(diph en -
yla llyl)tetr a flu or obor a te (30). Di-µ-chloro-bis(1,3-diphenyl-
π-allyl)dipalladium (24 mg, 0.5 equiv), {2SP-[(trans-(2R,5R)-
2,5-d im et h ylp yr r olid in yl)m et h yl]}fer r ocen yld ip h en -
ylphosphine (28 mg, 5.82 mmol) and sodium tetrafluoroborate
(19 mg, 3 equiv) were placed in a Schlenk under an atmosphere
of nitrogen. Degassed dichloromethane (1.5 mL) was added
via syringe to give a red suspension which was stirred for 1 h.
The solvent was removed in vacuo to yield 30 (54.9 mg, 100%)
as an orange powder: mp 163-165 °C (dec); Found: C, 53.85;
H, 5.49; N, 1.73; C32H37BF4FeNPPd requires C, 53.70; H, 5.21;
{2SP-[(tr a n s-(2R,5R)-2,5-Dim eth ylpyr r olidin yl)m eth yl]}-
fer r ocen yld ip h en yl p h osp h in e (19). To a solution of trans-
(2R,5R)-2,5-dimethyl-1-(ferrocenylmethyl)pyrrolidine (143 mg,
78 mmol) in dry diethyl ether under nitrogen at room tem-
perature was added sec-butyllithium (0.40 mL, 1.1 equiv) and
stirred for 5 h. Chlorodiphenylphosphine (0.086 mL, 1 equiv)
was added, and the solution was refluxed for 1 h. The solution
was diluted with diethyl ether, washed with 10% ammonium
chloride, water, and brine, and extracted with diethyl ether.
The solution was dried (MgSO4) and concentrated to yield 205
mg of crude product. This was purified using column chroma-
tography, alumina, hexane/diethyl ether 4:1 to yield 83 mg of
a mixture of diastereomeric products as a yellow solid which,
after a single recrystallization from hot ethanol, yielded 19
as a single diastereomer (63 mg, 27%): mp 107-110 °C;
Found: C, 72.37; H, 6.58; N, 2.78; C29H32FeNP requires C,
20
1
72.36; H, 6.70; N, 2.91; [R]D ) -32.2 (c ) 0.25, CHCl3); H
NMR δ 0.86 (d, J 6.22, 6H), 0.83-0.89 (m, 2H), 1.39-1.45 (m,
2H), 2.62-2.69 (m, 2H), 3.24 (d, J 10.69, 1H), 3.65-3.67 (m,
1H), 3.98 (d, J 10.44, 1H), 4.01 (s, 5H), 4.17-4.20 (m, 1H),
4.40-4.43 (m, 1H), 7.07-7.10 (m, 4H), 7.37-7.39 (m, 2H), and
7.56-7.59 (m, 4H); 13C NMR δ 16.2, 30.1, 44.9, 53.8, 68.3, 69.6,
71.6, 72.4, 91.7, 127.2-129.0, 130.8-132.7, 135.3, 138.1, and
140.4; 31P NMR δ -22.32; νmax (CH2Cl2)/cm-1 3045, 2983 and
1264; MS (EI, 70 eV): m/z (%): 481 [M+] (100%), 383 (36),
121 (99), and 55 (85).
{2SP -[(tr a n s-(2R,5R)-2,5-Dieth ylp yr r olid in yl)m eth yl]}-
fer r ocen yld ip h en ylp h osp h in e (20). To a solution of trans-
(2R,5R)-2,5-diethyl-1-(ferrocenylmethyl)pyrrolidine (111 mg,
64 mmol) in dry diethyl ether under nitrogen at room tem-
perature was added n-butyllithium (0.40 mL, 1.1 equiv) and
stirred for 1 h. Chlorodiphenylphosphine (0.012 mL, 1 equiv)
was added, and the solution was refluxed for 1 h at 35 °C.
The solution was diluted with diethyl ether, washed with 10%
ammonium chloride, water, and brine, and extracted with
diethyl ether. The solution was dried (MgSO4) and concen-
trated to yield 126 mg of crude product. This was purified using
column chromatography, alumina, hexane/diethyl ether 4:1 to
yield a mixture of diastereomeric products as a yellow solid (9
mg). Successful recrystallization from ethanol yielded 20 as a
single diastereomer (7 mg, 10%): mp 80-83 °C; Found: C,
72.96; H, 7.16; N, 2.53; C31H37FeNP requires C, 72.94; H, 7.30;
20
1
N, 2.74; [R]D ) -82.5 (c ) 0.2, CHCl3); H NMR δ 0.71 (t, J
7.32, 6H), 0.85-0.88 (m, 2H), 1.07-1.10 (m, 2H), 1.27-1.31
(m, 2H), 1.68-1.75 (m, 2H), 2.42-2.48 (m, 2H), 3.40 (d, J
12.96, 1H), 3.67-3.69 (m, 1H), 3.99 (s, 5H), 4.02 (m, 1H), 4.19-
4.21 (m, 1H), 4.38-4.41 (m, 1H), 7.17-7.21 (m, 4H), 7.36-
7.39 (m, 2H), and 7.17-7.21 (m, 4H); 13C NMR δ 10.9, 22.1,
26.9, 44.9, 61.3, 68.6, 69.5, 71.6, 72.6, 91.9, 127, 132, 135, 138.2,
and 140.48; 31P NMR δ -22.40; νmax(CH2Cl2)/cm-1 3032, 2984,
and 1271; MS (EI, 70 eV): m/z (%): 509 [M+] (100%), 383 (78),
324 (68), 199 (14), and 183 (63).
P a lla d i u m {2S -[(t r a n s -(2R ,5R )-2,5-d i m e t h y lp y r -
r olid in yl)m eth yl]}fer r ocen yl d ip h en ylp h osp h in e(a llyl)-
tetr a flu or obor a te (23). Di-µ-chloro-bis(π-allyl)dipalladium
(12.6 mg, 0.5 equiv), {2SP-[(trans-(2R,5R)-2,5-dimethylpyr-
rolidinyl)methyl]}ferrocenyldiphenyl phosphine (33 mg, 6.86
mmol), and sodium tetrafluoroborate (22.6 mg, 3 equiv) were
placed in a Schlenk under nitrogen. Degassed chloroform (1.5
mL) was added via syringe to give a yellow suspension which
was stirred for 24 h. The solid was removed by filtration and
the solvent removed in vacuo to yield 23 (44 mg, 100%) as a
brown solid: mp 176-178 °C (dec); Found: C, 53.85; H, 5.49;
N, 1.73; C32H37BF4FeNPPd requires C, 53.70; H, 5.21; N, 1.96;
1H NMR δ 1.31-1.39 (m, 6H), 1.98-2.09 (m, 1H), 3.39-3.43
(m, 4H), 3.47-3.55 (m, 1H), 3.64 (s, 5H), 3.76-3.81 (m, 1H),
4.35-3.40 (m, 2H), 4.38-4.45 (m, 2H), 4.42-4.44 (m, 1H),
4.52-4.55 (m, 1H), 4.76-4.78 (m, 1H), 5.05-5.11 (m, 1H),
6.07-6.10 (m, 1H), 7.05-7.09 (m, 4H), 7.19-7.25 (m, 2H), and
7.59-7.68 (m, 4H); 31P NMR δ 16.3 and 15.1; MS (ES): 629
[M - BF4].

Ferrocene-Containing Phosphinamine Ligands
J . Org. Chem., Vol. 67, No. 12, 2002 4217
1
N, 1.96; H NMR δ 1.18 (d, J 6.83, 3H), 1.41 (d, J 6.35, 3H),
thanks to Anne-Marie Carroll and David Connolly for
a critical reading of this manuscript.
1.66-1.70 (m, 2H), 1.95-2.03 (m, 2H), 3.47-3.50 (m, 1H),
3.69-3.72 (m, 2H), 4.01 (s, 5H), 4.32-4.35 (m, 1H), 4.38-4.42
(d, J 13.67, 1H), 4.63-4.65 (m, 1H), 4.74-4.78 (m, 2H), 5.13-
5.16 (m, 1H), 7.29-7.63 (m, 18H), 7.79-7.89 (m, 2H), and
8.87-8.92 (m, 1H); 31P NMR δ 34.4; νmax (CH2Cl2)/cm-1 3054,
2973, and 1079; m/z (ESI +) 781.51 (M - BF4).
Su p p or tin g In for m a tion Ava ila ble: Tables of X-ray
crystal data, atomic coordinates, bond lengths, bond angles,
and anisotropic thermal parameters for 19a , relevant spectra
for compounds 11, 12, 18, 19a , 20a , 23, and 30. This material
is available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We thank Enterprise Ireland for
the award of a Research Scholarship (BR/95/052) and
UCD for a Research Demonstratorship to A.F. Many
J O016391X