Synthesis, molecular structure, and catalytic evaluation of centrostereogenic ferrocenophane phosphines

Article abstract of DOI:10.1021/om3011245

1,1′-[(1R)-1-Diarylphosphino-1,3-propanediyl]ferrocenes, where aryl = phenyl, 2-tolyl, 4-tolyl, mesityl, 4-anisyl, 4-(trifluoromethyl)phenyl, were prepared as new chiral ferrocenophane phosphines featuring only central chirality in good yields by the reaction of the corresponding chiral alcohol, 1,1′-[(1R)-1-hydroxy-1,3-propanediyl]ferrocene, and diarylphosphines in the presence of chlorotrimethylsilane and sodium iodide. These phosphines were studied as ligands in palladium(II) complexes and further evaluated in two mechanistically different model catalytic reactions, namely in Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate, and in enantioselective aza-Morita-Baylis-Hillman reactions of aromatic N-sulfonyl imines with methyl vinyl ketone.

Full text of DOI:10.1021/om3011245

Article
pubs.acs.org/Organometallics
Synthesis, Molecular Structure, and Catalytic Evaluation of
Centrostereogenic Ferrocenophane Phosphines
̌
̌
Petr Stepnicka,* Karel Skoch, and Ivana Císarova
́
̌
̌
̌
Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, 12840 Prague 2, Czech Republic
S
* Supporting Information
ABSTRACT: 1,1′-[(1R)-1-Diarylphosphino-1,3-propanediyl]ferrocenes,
where aryl = phenyl, 2-tolyl, 4-tolyl, mesityl, 4-anisyl, 4-(trifluoromethyl)-
phenyl, were prepared as new chiral ferrocenophane phosphines featuring
only central chirality in good yields by the reaction of the corresponding
chiral alcohol, 1,1′-[(1R)-1-hydroxy-1,3-propanediyl]ferrocene, and diary-
lphosphines in the presence of chlorotrimethylsilane and sodium iodide.
These phosphines were studied as ligands in palladium(II) complexes and
further evaluated in two mechanistically different model catalytic reactions,
namely in Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate, and in enantioselective
aza-Morita-Baylis-Hillman reactions of aromatic N-sulfonyl imines with methyl vinyl ketone.
̌
recently, Sebesta et al. extended the chemistry of PPFA- and
INTRODUCTION
■
Josiphos-type ferrocenophane ligands to [5]ferrocenophanes,7
while Takahashi and Ogasawara demonstrated the viability of a
ring-closing metathesis route toward bridged phosphaferro-
cenes.8
The enormous practical success of chiral phosphinoferrocene
ligands1,2 has prompted the design of new phosphinoferrocene
donors with modified structures. Among these compounds,
analogues with bridged cyclopentadienyl rings, typically [3]-
ferrocenophane derivatives, emerged as structurally interesting
congeners, largely owing to their constrained geometry (Chart
1). Already in 1996, Weissensteiner et al.3,4 reported the
In parallel, nonchiral ferrocenophane phosphines having the
phosphorus atom in the middle of the ferrocenophane bridge of
different lengths were developed by Hey-Hawkins (E in Chart
2)9,10 and Curnow (F in Chart 2),11 resulting from metathesis
Chart 1
Chart 2
reactions of the respective dicyclopentadienide salts and
iron(II) chloride. C2-symmetric, planar chiral counterparts of
the former compound (FerroPHANE in Chart 2) were
introduced by Marinetti et al.12 and extensively evaluated as
organocatalysts (chiral Lewis bases) for enantioselective [3 + 2]
cyclization reactions.13
From the previous list, it becomes obvious that the vast
majority of ferrocenophane phosphines reported to date are
either achiral or combine planar and central chirality. The only
synthesis of ferrocenophane phosphinoamines (A) and
diphosphines (B) as congeners of the archetypical PPFA and
Josiphos type ligands (Chart 1), in which one of the two
functional moieties available is attached to the ansa bridge. A
few years later, Erker and co-workers5 reported the formally
homologous compounds C and D (Chart 1) possessing an
additional chirality center within the butane-1,3-diyl ansa chain.
The synthesis of C- and D-type compounds capitalized upon
the newly discovered efficient Mannich-type condensation of
1,1′-diacetylferrocene with secondary amines that provided an
elegant route to the parent chiral [3]ferrocenophane.6 Most
Received: November 22, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
compound possessing only central chirality appears to be 1,1′-
[(1R,3R)-1-(dimesitylphosphino)-3-methyl-1,3-propanediyl]-
ferrocene (G in Chart 2), which was prepared by Erker et al.
and studied for its reactivity toward tris(pentafluorophenyl)-
borane.14 The lack of C-only chiral ferrocenophane phosphines
led us to design and study C-chiral monophosphine donors
derived from [3]ferrocenophane.15 With this contribution, we
report the preparation and structural characterization of these
compounds and their Pd(II) complexes and the evaluation of
their catalytic performance in model Pd-catalyzed asymmetric
allylic alkylations and in Lewis base mediated aza-Morita-Baylis-
Hillman reactions.
RESULTS AND DISCUSSION
■
Synthesis of the Phosphine Ligands. Ferrocene mono-
phosphines featuring only central chirality, viz 1,1′-[(1R)-1-
(diarylphosphino)-1,3-propanediyl]ferrocenes ((R)-2), were
prepared by a simple one-pot procedure from chiral alcohol
(R)-1 (Scheme 1). This alcohol, which was obtained in several
Figure 1. PLATON plot of the molecular structure of compound (R)-
3 showing the atom-labeling scheme and displacement ellipsoids at the
30% probability level. Note that carbon atoms in the aromatic rings are
numbered consecutively; hence, only the labels of the pivotal carbon
atoms and their adjacent carbon atoms are shown for clarity.
Scheme 1. Preparation of [3]Ferrocenophane Phosphines 2
corroborates both the formulation and the chirality at the
stereogenic carbon atom. Structural data for (R)-3 are
presented and discussed below together with those of Pd(II)
complexes obtained from phosphine (R)-2a.
Compounds (R)-2a−f and (R)-3 were characterized by
multinuclear NMR spectroscopy and by mass spectrometry
with electron impact and electrospray ionization. IR spectra and
optical rotations were recorded only for the archetypal
representative (R)-2a and its sulfide (R)-3, which could be
efficiently purified by crystallization.20 The 31P{1H} NMR
spectra of phosphines 2a−f display a single resonance, whose
position varies with the substituents at the benzene rings (δP
from ca. −27 for (R)-2b to ca. −2 for (R)-2a); the 31P{1H}
NMR signal of the phosphine sulfide (R)-3 appears shifted to a
steps from [3]ferrocenophane-1-one16 as described in the
literature,17 was reacted successively with iodotrimethylsilane
(generated in situ from chlorotrimethylsilane and sodium
iodide)18 and the appropriate diarylphosphine in dry
acetonitrile to afford the corresponding ferrocenophane
phosphines 2a−f in good to excellent isolated yields. The
phosphinylation reaction19,4a proceeded smoothly with the
retention of configuration at the stereogenic carbon atom. The
secondary phosphine was used in excess, as it prevents the
oxidation of the ferrocenophane phosphines during the
subsequent workup and chromatographic purification. At-
tempts at obtaining an analogue bearing the dicyclohexylphos-
phine moiety were unsuccessful; only the starting alcohol was
recovered from the reaction mixture.
In order to prepare a better crystallizing, simple derivative
suitable for structure determination, the parent phosphine (R)-
2a was converted to its corresponding phosphine sulfide (R)-3
by sulfidation with elemental sulfur (Scheme 2). Subsequent
crystallization from hot acetonitrile afforded single crystals
suitable for X-ray diffraction analysis. The view of the molecular
structure of phosphine sulfide (R)-3 shown in Figure 1
1
lower field (δP 49.3). The H NMR spectra of 2a−f and 3
comprise signals due to the five nonequivalent hydrogens
within the ferrocenephane bridge and eight signals of the
diastereotopic ferrocene protons, both forming characteristic
1
patterns (for the “aliphatic” part of the H NMR spectrum of
(R)-2a, see Figure 2). Finally, the 13C{1H} NMR spectra of
2a−f and 3 display three characteristic phosphorus-coupled
doublets for the carbon atoms constituting the ansa bridge
(C5H4CH2, δC ca. 25 (3JPC = 11−14 Hz); C5H4CHP, δC ca.
33−36 (1JPC = 7−16 Hz); C5H4CH2CH2:, δC ca. 39−40 (3JPC
=
24−39 Hz)) and 10 signals for carbons in the ferrocene moiety,
among which those due to the pivotal Cipso carbons appear
characteristically shifted to lower field (δC 85−86). In addition,
1
the H and 13C{1H} NMR spectra further comprise signals of
the diastereotopic aryl substituents at phosphorus and their
substituents (CH3, OCH3, and CF3).21
Compounds 2a−f and 3 exert similar fragmentation patterns
in their electron impact ionization (EI) mass spectra. The
plausible early fragmentation pathway is presented in Scheme 3.
In the first step, the molecular cation radical loses its phosphine
substituent to afford a relatively stable22 ferrocenophane cation
observed at m/z 255 (base peak in all spectra). The molecules
Scheme 2. Preparation of Phosphine Sulfide (R)-3
+
of phosphine sulfide fragment analogously, eliminating PSPh2 .
The complementary fragment ions are also seen (2a and 3, m/z
B
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1
Figure 2. Aliphatic region of H NMR spectrum of (R)-2a showing the assignment of the signals.
standing in solution (see the Supporting Information, Figure
S1). Yet another Pd(II) complex containing only one
phosphine molecule and an auxiliary 2-[(dimethylamino)-
methyl]phenyl C,N-chelating ligand (LNC) was obtained by a
bridge-splitting reaction from the dimer [(LNC)PdCl]2 (Scheme
5). Complexes trans-4, cis-4, and 5 were characterized by
Scheme 3. Plausible Fragmentation Pathway for Phosphines
2
a
Scheme 5. Preparation of Monophosphine Complex 5
185 (PPh2 ) and 183 ([PPh2 − 2 H]+; 2b−e, Ar2P+, Ar = an
+
a
LNC =2-[(dimethylamino-κN)methyl]phenyl-κC1.
aryl). The ions at m/z 255 subsequently decompose to give
ions at m/z 149 and, finally, the usual ferrocene fragments such
as [C5H5Fe]+ and Fe+. It is noteworthy that the ESI MS spectra
of 2 and 3 also display the ions of the dephosphinylated species
at m/z 225 in addition to the expected pseudomolecular ions
([M + X]+, where X = H, Na, K; M+ was seen for (R)-2a).
Preparation of Palladium(II) Complexes. In view of
catalytic reactions intended for testing, the coordination
properties of (R)-2a as the prototypical representative were
assessed in Pd(II) complexes. Thus, the reaction of
[PdCl2(cod)] (cod = η2:η2-cycloocta-1,5-diene) with 2 molar
equiv of the phosphine in dichloromethane proceeded quickly
and cleanly to afford the diphosphine complex trans-4 (Scheme
4). An isomeric compound, cis-4, was isolated serendipitously
from the reaction mixture after Pd-catalyzed allylic alkylation
(see below). NMR measurements in CDCl3 solution revealed
that cis-4 is always accompanied by the thermodynamically
favored trans isomer, to which it partially isomerizes upon
conventional spectroscopic methods and elemental analysis. In
addition, their solid-state structures were determined by single-
crystal X-ray diffraction analysis (Figures 3−5).
In the ESI mass spectra, the isomeric complexes cis- and
trans-4 display only weak signals due to the pseudomolecular
ions [M + Na]+ at m/z 1019, the dominant species being ions
resulting from the loss of the chloride ligands ([M − Cl −
HCl]+ at m/z 925),23 all with characteristic isotopic patterns.
Complex 5 has a similar response, showing only a weak signal
due to [M + Na]+ (m/z 708) and a strong signal due to
fragment ions arising by the loss of Pd-bound chloride ([M −
Cl]+ at m/z 650).
The NMR spectra of the Pd(II) complexes exert several
notable features. In 1H NMR spectra of cis-4 and 5, one of the
ferrocene CH protons in a position adjacent to the phosphine
substituent24 appears shifted markedly to higher fields (cis-4, δH
3.05; 5, δH 2.89). This proton is very likely directed toward the
center of one phenyl substituent and thus experiences an
increased shielding by this magnetically anisotropic aromatic
ring. No similar effect is seen for trans-4 (δH 3.64), in
accordance with the solid-state structural data.25 In the 13C
NMR of cis- and trans-4, the signals of carbons close to the
phosphorus atom (phenyl ring and CH2CHP in the bridge) are
observed as apparent and/or nonbinomial triplets that typically
arise from virtual coupling in symmetric diphosphine
complexes.26 The spectrum of monophosphine complex 5
obviously lacks such features. In this case, however, the 3JPC and
4JPH coupling constants associated with the signals of the
a
Scheme 4. Preparation of Diphosphine Complex trans-4
a
cod = η2:η2-cycloocta-1,5-diene.
C
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 3. PLATON plot of molecule 1 in the structure of trans-4. Displacement ellipsoids are scaled to the 30% probability level.
Figure 4. PLATON plot of the complex molecule in the structure of cis-4·2CH2Cl2. Displacement ellipsoids are scaled to the 30% probability level.
CH2NMe2 arm indicate a trans-P−N arrangement,27 which is
indeed in line with the crystal structure data. The 31P NMR
chemical shifts increase in the order trans-4 (δP 30.6) < cis-4 (δP
42.9) < 5 (δP 48.7), thereby reflecting the influence of the
donor atom in a trans position.28
Description of the Crystal Structures. Views of the
molecular structures of (R)-3, trans-4, cis-4·2CH2Cl2, and
5·2CHCl3 are presented in Figures 1 and 3−5, respectively.
Parameters describing the geometry of the ferrocenophane
moieties in these compounds are summarized in Table 1. The
conformations of the ferrocenophane units in all structures are
similar to that of pristine 1,1′-(1,3-propanediyl)ferrocene (i.e.,
the parent [3]ferrocenophane).29 The cyclopentadienyl rings
assume a practically ideal synclinal eclipsed conformation.
Perhaps not surprisingly, the largest mutual rotation of the η5
rings (3.5(1)°) is seen for one ligand moiety in the structure of
the sterically congested complex cis-4. The Fe−ring centroid
distances fall into the range 1.6340(7)−1.645(2) Å, while the
individual Fe−C distances increase slightly but statistically
significantly on going from the pivotal ferrocene Cipso to the
opposite CHβ−CHβ′ edge (Cipso < C-α < C-β), owing to
D
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 5. PLATON plot of the complex molecule in the structure of
5·2CHCl3. Displacement ellipsoids enclose the 30% probability level.
constraints imposed by the three-carbon ansa bridge. This is
clearly manifested by the tilt angles being 8.8(1)−10.6(2)°.
The vectors of the C(Cp)−C(bridge) bonds practically
bisect the cyclopentadienyl ring and the methylene carbon in
the center of the bridge is directed to the side, departing by
0.730(1)−0.748(3) Å from the plane defined by atoms C1,
C11, C13, and C6. Because of the chirality, the C−P bond
points to the side of the bridge apex in a practically identical
position, as indicated by the ψ angles in Table 1. A notable
difference among the structures is seen in the orientation of the
phosphine moiety toward the pivotal ferrocenophane unit
(Figure 6). In the case of (R)-3, the PS bond is directed to
the apex of the three-carbon bridge, while in all Pd(II)
complexes the corresponding P−Pd bonds connecting the
ligand to the relatively bulky metal fragments extend away from
the ferrocenophane unit.
Compounds trans-4, cis-4, and 5 show the expected square-
planar-like coordination geometry (Figure 7 and Table 2)
typical for Pd(II) complexes,30 though with a different degree
of distortion. The distortion apparently arises from different
steric demands of the ligands and, in the case of 5, also from the
presence of the relatively small C,N-chelate ring and unlike
Pd−donor distances. The least pronounced deformation is seen
for trans-4, in which the phosphine moieties occupy mutually
opposite positions (note that his compound crystallizes with
two practically identical but crystallographically independent
molecules in the asymmetric unit of the triclinic cell; for an
overlap of the independent molecules, see the Supporting
Information, Figure S2). In the corresponding cis isomer, the
spatial interactions of the bulky phosphine moieties result in
twisting of the coordination plane and in changes of the
interligand angles (the P1−Pd−P2 angle is the most opened),
which then significantly depart from the ideal 90° (see Figure
7). It is also noteworthy that a pair of the phosphorus-bound
phenyl groups in cis-4 are rotated so that they allow for a
structure-stabilizing intramolecular π···π stacking interaction
(C(114−119) vs C(214−219); see Figure 4). The distance of
the centroids of the interacting benzene rings is 3.685(1) Å,
and the ring planes are mutually tilted by only 5.17(9)°. The
most severe deformation is observed for 5, where the
desymmetrizing effects (i.e., spatial intractions, chelation, and
variation of the Pd−donor bond lengths) operate in synergy.
E
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 6. View along the centroid−centroid direction of the ferrocenophane moieties in (a) (R)-3 and (b) 5, illustrating the conformation of the
ferrocenophane unit and the orientation of the “appended moiety” (sulfur or the coordinated metal center), from which only the pivotal atoms are
shown for clarity.
Despite the distortion, however, the Pd−donor distances
(Table 2) are found within the common ranges and compare
31
well with those reported for [(μ-L)PdCl2]2 and for (μ-
d p p f ) [ P d ( L N C ) C l ] 2 , 3 2 w h e r e
L
=
1 , 1 ′ - b i s -
[(diphenylphosphino)methyl]ferrocene and dppf = 1,1′-bis-
(diphenylphosphino)ferrocene. In addition, the observed bond
distances clearly demonstrate the structural impact of trans
influence.28 For instance, the Pd−P bond lengths decrease in
the order trans-4 > cis-4 > 5, reflecting the trans influence of the
donor atoms in positions trans to phosphorus atom (phosphine
> Cl− > amine). The inverse trend is observed for the Pd−Cl
separations, which is again in line with the sequence of the
trans-influencing ligands (aryl > phosphine > Cl−).
Catalytic Tests with Phosphines 2. The series of the
newly prepared chiral phosphinoferrocenes 2 has been
catalytically evaluated in two chemically dissimilar reactions:
as ligands for palladium catalyzed asymmetric allylic alkylation
(Tsuji-Trost reaction)33 and as chiral Lewis bases in the aza
variant of the Morita−Baylis−Hillman reaction,34 which both
represent useful tools for the stereoselective construction of
new C−C bonds and the preparation of functional molecules.
For testing in palladium-catalyzed asymmetric allylic
alkylation, we chose the alkylation of 1,3-diphenylallyl acetate
(6) with an instant C-nucleophile generated in situ from
dimethyl malonate/BSA (BSA = N,O-bis(trimethylsilyl)-
acetamide) to give allylmalonate 7 (Scheme 6), which is
usually used as a benchmark test for new ligands. The catalytic
results are presented in Table 3.
Figure 7. Interligand and interplanar angles describing the
coordination geometry of of trans-4, cis-4 ·2CH2Cl2, and 5·2CHCl3.
Values are given in degrees. ω (shown in red) is the dihedral angle
subtended by the halves of the coordination plane (left vs right as
presented in the figure).
Table 2. Coordination Bond Lengths for trans-4, cis-
4·2CH2Cl2, and 5·2CHCl3 (in Å)
trans-4
molecule 1
2.3285(7)
molecule 2
2.3257(8)
The reaction performed in the presence of 5 mol % of
palladium and 10 mol % of phosphine 2a afforded the
Pd1−P1
Pd1−P2
Pd1−Cl1
Pd1−Cl2
Pd2−P3
Pd2−P4
Pd2−Cl3
Pd2−Cl4
2.3248(7)
2.2980(7)
2.3064(8)
2.3340(8)
2.2984(7)
2.3093(8)
Scheme 6. Model Allylic Alkylation of Acetate 6 with
a
Dimethyl Malonate/BSA
cis-4·2CH2Cl2
5·2CHCl3
Pd−P1
Pd−P2
Pd−Cl1
Pd−Cl2
2.2858(5)
2.2862(5)
2.3589(5)
2.3463(5)
Pd−P
2.2581(7)
2.4116(6)
2.141(2)
2.000(2)
Pd−Cl
Pd−N
Pd−C26
a
BSA = N,O-bis(trimethylsilyl)acetamide.
F
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
electron-poor alkenes catalyzed by Lewis bases (phosphines
and amines) came to the fore during the recent development of
asymmetric organocatalytic processes.34 The fact that the
Morita−Baylis−Hillman (MBH) reaction is 100% atom
economic and affords highly functionalized products makes it
synthetically very attractive, particularly in its asymmetric
variant. This is turn initiated a search for suitable base catalysts.
Among phosphine donors, those recently employed in Morita−
Baylis−Hillman reactions include compounds derived from the
chiral binaphthyl38 and spirobiindane units.39 Chiral ferrocene
phosphines have still found only a limited use in this reaction.40
For the catalytic evaluation of chiral phosphines 2, we chose
the aza variant of the MBH reaction,41 namely the commonly
used addition of N-sulfonyl benzylidene imines 8 to methyl
vinyl ketone, affording chiral sulfonamides 9 (Scheme 7).
Table 3. Summary of Catalytic Results for Pd-Catalyzed
Allylic Alkylation of 1,3-Diphenylallyl Acetate (6) with
Dimethyl Malonate
a
e
f
entry
ligand
yield (%)
ee (%)
1
2
2a
98
23
95
3
37
36
37
n.d.
29
b
2a
2a
c
3
4
2b
5
2c
97
1
6
2d
7
2e
98
44
<1
<1
50
34
8
2f
d
9
trans-4
d
10
cis-4
a
Conditions: [PdCl(η3-C3H5)]2 (2.5 mol %), ligand 2 (10 mol %,
2:Pd = 2:1), substrate 6 (0.25 mmol), dimethyl malonate and BSA
Scheme 7. Addition of Methyl Vinyl Ketone to Aromatic
Imines 8a−e
(0.75 mmol each) in 3 mL of dry dichloromethane. The results are an
a
b
c
average of two independent runs. Molar ratio 2a:Pd = 1:1. Reaction
d
in the presence of KOAc (10 mol %). Reaction in the presence of the
e
1
defined Pd complex (5 mol % Pd). The yield was determined by H
f
NMR. Enantiomeric excess was determined by 1H NMR with the aid
of chiral lanthanide shift reagent [Eu(tfc)3]. n.d. = not determined.
alkylation product in practically quantitative yield but with only
37% ee (Table 3, entry 1). Decreasing the amount of ligand to
1 molar equiv with respect to palladium (5 mol % Pd, Pd:2a =
1:1; entry 2) dramatically decreased the conversion (23% after
24 h), while the enantioselectivity remained practically
unchanged. Finally, the addition of potassium acetate (entry
3), which typically accelerates the reaction, had virtually no
effect on both the conversion and ee.
a
R1/R2 = 4-CH3C6H4SO2/H (a), PhSO2/H (b), 4-CH3C6H4SO2/Me
(c), 4-CH3C6H4SO2/MeO (d), 4-CH3C6H4SO2/Cl (e).
The reaction of N-tosylimine 8a with 2 mol equiv of the
ketone in the presence of 10 mol % of chiral phosphine 2a
performed at room temperature for 5 h afforded 9a in 27%
yield and with 97% ee (Table 4, entry 1). Unfortunately, the
reaction was only poorly chemoselective, affording various side
products, among which the product of double addition 1042
and heterocycles 11 and 1243 (Scheme 8) were identified by
NMR analysis. The formation of such products was observed in
reactions mediated by strong Lewis bases (e.g., PBu3 and
The following experiments carried out with the remaining
ligands at a Pd:2 molar ratio of 1:2 showed that the
introduction of substituents at positions 2 and 6 of the
phosphorus-bound arene ring has a detrimental effect on the
catalyst activity (entries 4 and 6). Substituents in position 4
affected both reaction parameters. Practically complete
conversions were obtained with catalysts containing phosphines
2c,e, whereas that based on 2f as the least electron-rich
phosphine furnished a relatively lower yield (42%). In terms of
enantioselectivity, the best results were obtained with the
catalyst based on 2e, bearing the electron-donating p-anisyl
substituents. The generally good catalytic activity (conversions)
but relatively poor enantioselectivity of the Pd-2 catalytic
systems are in accordance with previous reports suggesting that
electronic discrimination of allylic termini (achieved typically
via trans influence of the donor atoms of a chelating ligand) has
a decisive influence on the enantioselectivity in the cases where
no is sufficient steric differentiation is provided by a rigid,
donor-symmetric chelate ligand (chiral pocket).35 Such
discrimination, however, does not occur in the presumed
symmetric intermediate [Pd(η3-1,3-Ph2C3H3)(2)2]+, containing
two identical and mutually movable monodentate donors.
It is also noteworthy that the (defined) dichloride complexes
cis- and trans-4 did not catalyze the alkylation reaction (Table 3,
entries 9 and 10). Indeed, the formation of cis-4, which was
isolated from the reaction mixture, may well represent a
deactivation process during which the π-bound allyl is
isoeletronically replaced with two chloride anions coming
presumably from the palladium precursor and, perhaps, from
the halogenated solvent.
Table 4. Summary of Catalytic Results for the Model Aza-
Morita−Baylis−Hillman Reaction
a
b
e
entry cat.
solvent
additive
none
yield (%)
27
ee (%) [confign]
1
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
CDCl3
CHCl3
CH2Cl2
MeCN
toluene
MeOH
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
97 [S]
32 [S]
33 [S]
16 [S]
80 [S]
n.d.
2
5% PhCO2H
5% PhCO2H
5% PhCO2H
5% PhCO2H
5% PhCO2H
MS 4 Å
76
58
34
41
12
38
3
4
5
6
7
94 [S]
17 [S]
n.d.
c
8
MS 4 Å
4 (23 )
traces
9
MS 4 Å
c
10
11
12
13
MS 4 Å
<1 (traces )
n.d.
MS 4 Å
n.d.
67
n.d.
MS 4 Å
14 [S]
12 [S]
d
2f
MS 4 Å
96
a
Conditions: imine (0.5 mmol), methyl vinyl ketone (1.0 mmol), and
2 (50 μmol, 10 mol %) were reacted in 2 mL of solvent at room
temperature for 5 h (unless noted otherwise). The results are an
average of two independent runs. The yield was determined by H
NMR spectroscopy using anisole as an internal standard. Conversion
after 168 h. Reaction time 24 h. The ee values were determined by
HPLC analysis on a chiral column. The configuration was determined
by a comparison of optical rotation with literature values (for details,
see the Experimental Section). n.d. = not determined.
b
1
c
d
e
Described first in 1968 by Morita36 and developed by Baylis
and Hillman few years later,37 the addition of C-nucleophiles to
G
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 8. Side Products Identified in the aza-MBH
Reaction of Imine 8a with Methyl Vinyl Ketone
Table 5. Catalytic Results for aza-Morita-Baylis-Hillman
a
Reactions with Different Imine Substrates
b
c
imine
R1
R2
additive
yield (%) ee (%) [confign]
8b
8b
8c
8d
8e
PhSO2
PhSO2
Ts
H
5% PhCO2H
MS 4 Å
41
27
49
28
9
20 [S]
91 [S]
78 [S]
ca. 57 [S]
n.d.
H
Me
MeO
Cl
MS 4 Å
Ts
MS 4 Å
Ts
MS 4 Å
a
PhPMe2)34b and may take place during chromatographic
purification if unreacted methyl vinyl ketone is available. The
presence of chemically similar byproducts prevented the
isolation of pure 9a, and therefore, the yield of the addition
product had to be determined directly by NMR analysis of the
reaction mixture using anisole as an internal standard.
Conditions: imine (0.5 mmol), methyl vinyl ketone (1.0 mmol), and
2 (50 μmol, 10 mol %) were reacted in 2 mL of CDCl3 at room
temperature for 5 h. The yield was determined by H NMR using
anisole as an internal standard. The enantiomeric excess (ee) was
determined by HPLC analysis on a chiral column. The configuration
was determined by a comparison of optical rotation with the literature
data (for details, see the Experimental Section).
b
1
c
Benzoic acid (5 mol %) was then added to the reaction
mixture to facilitate proton transfer in an intermediate resulting
from addition of the imine to activated ketone, which is
believed to be the rate-determining step of the aza-Morita−
Baylis−Hillman reaction.44 Indeed, the yield of 9a significantly
increased, albeit on account of stereoselectivity (entry 2). Both
of these reaction parameters varied greatly upon changing the
solvent (entries 3−6). A good ee of 80% but still a relatively
low yield was obtained in toluene. Other solvents tested
afforded considerably worse results.
The reaction in chloroform, which proceeded most rapidly,
was chosen for a further optimization. Upon the addition of 4 Å
molecular sieves that could prevent the hydrolysis of the imine
substrate, the conversion slightly improved while the ee
remained nearly the same as in the system without any additive
(94%, entry 7). Such conditions were selected for an evaluation
of the influence of the ligand structure (entries 7−13).
Surprisingly, none of the compounds completing the series of
2-type phosphines afforded better results than the parent
representative 2a. For instance, phosphines 2c,e bearing
electron-donating groups afforded 9a in only low yields, while
imine 8a was completely consumed. This can be explained by
an acceleration of the followup reactions affording compounds
10−12. In contrast, phosphines with sterically demanding and
electron-donating phosphine substituents (2b,d) reacted much
more slowly. The yields of 9a achieved with these phosphines
were low even after extended reaction times (23% for
phosphine 2b after 7 days), but the majority of the starting
imine remained unreacted. Finally, compound 2f bearing the
electron-withdrawing trifluoromethyl group reacted rather
quickly and chemoselectively. Nonetheless, the enantioselec-
tivity was relatively low. In view of these results, the following
experiments with different substrates were carried out only with
phosphine 2a (Table 4).
Reactions with imines 8a,b differing in the sulfonyl
protecting group (cf. entries 2 and 7 in Table 4 and entries 2
and 3 in Table 5) revealed similar trends. However, the latter
substrate containing the smaller phenylsulfonyl substituent
afforded lower yields, a slightly lower enantioselectivity in the
reaction performed in the presence of molecular sieves, and a
considerably worse ee for the reaction in the presence of 5 mol
% of benzoic acid. Introduction of substituents to the
benzylidene moiety also affected the reaction outcome. The
best results were obtained with unsubstituted imine 8a. Other
N-tosylimines bearing methyl, methoxy, and chloro substituents
in position 4 of the benzylidene group all gave lower ee’s,
though not always lower conversions (cf. entry 7 in Table 4 and
entries 3−5 in Table 5).
CONCLUSION
■
Phosphines 2 of the general formula Ar2PR, where Ar is an aryl
group and R is 1,1′-[(1R)-1,3-propanediyl-1-yl]ferrocene,
reported in this study represent the first ferrocenophane
monophosphines containing a stereogenic carbon atom as the
sole chirality source. These compounds are structurally
modular, combining the rigid chiral ferrocenophane and the
diarylphosphino moieties. Since the synthesis of a 2-type ligand
makes use of the readily available diarylphosphines, it allows for
easy structural modifications (ligand tailoring) through
changing of the diarylphosphine moiety. Compounds 2 form
ordinary phosphine complexes from the usual Pd(II)
precursors. However, their structural properties often result in
distortion of the coordination environments. When applied as
chiral donors to Pd-catalyzed asymmetric alkylation, phos-
phines 2 afford only modest results, which can be rationalized
by the absence of electronic discrimination and mobility of the
phosphine ligands in the presumed reaction intermediates
[Pd(η3-allyl)(2)2]+. On the other hand, the compounds afford
promising results when employed as chiral Lewis bases in aza-
Morita−Baylis−Hillman reactions, particularly in terms of
enantioselectivity (ee up to 97%). We believe that mechanis-
tically similar reactions are worthy of further investigations
aimed mainly at improving the overall chemoselectivity.
EXPERIMENTAL SECTION
■
Materials and Methods. All syntheses were carried out under an
argon atmosphere with exclusion of direct daylight. Compounds (R)-
1,17 [PdCl2(cod)],45 [(LNC)PdCl]2,46 6,47 and 8a48 were synthesized
according to literature procedures. Toluene and methanol were freshly
distilled from sodium metal and sodium methoxide, respectively.
Chloroform and chloroform-d used for catalytic experiments were
distilled from CaH2. Anhydrous acetonitrile and dichloromethane were
purchased from Sigma-Aldrich. Other chemicals (Sigma-Aldrich) and
solvents (Lachner) used for crystallizations and chromatography were
used as received.
NMR spectra were measured with a Varian UNITY Inova 400
spectrometer at 298 K. Chemical shifts (δ/ppm) are given relative to
internal tetramethylsilane (1H and 13C) or to external 85% H3PO4
(31P). The assignment of the NMR signals is based on COSY-90 and
gradient-selected 13C HSQC and 13C HMBC measurements. IR
spectra were recorded on an FTIR Nicolet Magna 760 instrument.
Electron impact ionization (EI) mass spectra including high-resolution
(HR) data were obtained with a GCT Premier spectrometer (Waters).
Low-resolution electrospray ionization (ESI) mass spectra were
recorded with an Esquire 3000 (Bruker) spectrometer using
methanolic solutions. High-resolution ESI MS spectra were obtained
with an LTQ Orbitrap XL spectrometer (Thermo Fisher Scientific).
H
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Optical rotations were determined with an automatic polarimeter
Autopol III (Rudolph Research) at room temperature (optical path 2
(td, J′ = 2.4, 1.3 Hz, 1 H, C5H4), 3.97−4.02 (m, 2 H, C5H4), 4.03 (dt,
J′ = 2.5, 1.4 Hz, 1 H, C5H4), 4.05 (m, 1 H, C5H4), 4.18 (dt, J′ = 2.5,
1.3 Hz, 1 H, C5H4), 6.93 (m, 1 H, C6H4), 6.97−7.07 (m, 2 H, C6H4),
7.15 (m, 1 H, C6H4), 7.18−7.26 (m, 3 H, C6H4), 7.43 (m, 1 H, C6H4).
cm). Melting points were determined on a Buchi B-540 apparatus.
̈
General Procedure for the Synthesis of Phosphines 2. A
flame-dried Schlenk tube was charged with the alcohol (R)-1 and
sodium iodide, flushed with argon, and sealed with a septum. Dry
acetonitrile was introduced, and the mixture was stirred until the solids
completely dissolved. Then, neat chlorotrimethylsilane was added,
causing an immediate separation of a fine white solid (NaCl). After the
mixture was stirred for 15 min, the appropriate phosphine was
introduced and the stirring was continued at room temperature
overnight (18−20 h).
3
13C{1H} NMR (CDCl3): δ 21.26 (d, JPC = 22 Hz, CH3), 21.50 (d,
3JPC = 21 Hz, CH3), 24.95 (d, 3JPC = 11 Hz, C5H4CH2), 36.47 (d, 1JPC
= 12 Hz, CHP), 38.77 (d, 2JPC = 27 Hz, C5H4CH2CH2), 67.36 (d, JPC
= 8 Hz, CH of C5H4), 67.37 (CH of C5H4), 67.64 (CH of C5H4),
67.78 (CH of C5H4), 68.64 (CH of C5H4), 69.22 (CH of C5H4), 71.33
(CH of C5H4), 71.42 (d, JPC = 2 Hz, CH of C5H4), 85.55 (C-CH2 of
C5H4CH2), 85.63 (d, 2JPC = 17 Hz, C-CH of C5H4CHP), 125.42 (CH
of C6H4), 125.93 (CH of C6H4), 128.21 (CH of C6H4), 128.33 (CH
2
2
The reaction was terminated by addition of saturated aqueous
NaCl, the orange organic layer was separated, and the milky white
aqueous phase was extracted with diethyl ether (3 × 5 mL). The
combined organic layers were dried over magnesium sulfate, filtered,
and evaporated with chromatography grade alumina. The crude
preadsorbed product was transferred onto the top of a chromato-
graphic column (alumina, hexane) and eluted with hexane to remove
excess secondary phosphine. The solvent was then changed to hexane/
diethyl ether (1/2), which led to the development of a yellow band.
This band was collected and evaporated under vacuum to afford the
pure product.
of C6H4), 129.47 (d, JPC = 5 Hz, CH of C6H4), 130.22 (d, JPC = 4
Hz, CH of C6H4), 130.62 (CH of C6H4), 132.36 (d, 3JPC = 2 Hz, CH
of C6H4), 136.37 (d, 1JPC = 13 Hz, C-P of C6H4), 137.50 (d, 1JPC = 18
2
Hz, C-P of C6H4), 142.67 (d, JPC = 25 Hz, C-Me of C6H4CH3),
143.04 (d, 2JPC = 27 Hz, C-Me of C6H4CH3). 31P{1H} NMR (CDCl3):
δ −27.1 (s). ESI+ MS: m/z 225 ([M − P(C6H4Me)2]+), 439 ([M +
H]+, 461 ([M + Na]+), 477 ([M + K]+). EI+ MS: m/z (relative
abundance) 438 (9, M•+), 225 (100, [M − P(C6H4Me)2]+), 214 (28,
HP(C6H4Me)2•+), 147 (9, C5H4FeC2H3 ), 122 (31, P(C6H4Me)+),
+
+
+
121 (8, C5H5Fe+), 91 (5, C7H7 ), 78 (35, C6H6 ), 56 (4, Fe+). HRMS:
calcd for C27H27FeP 438.1200, found 438.1192.
1,1′-[(1R)-1-(Diphenylphosphino)-1,3-propanediyl]ferrocene ((R)-
2a). Following the general procedure, (R)-1 (723 mg, 2.99 mmol),
NaI (1.16 g, 7.75 mmol), ClSiMe3 (1.0 mL, 7.9 mmol) and
diphenylphosphine (1.3 mL, 7.56 mmol) were reacted in 15 mL of
acetonitrile to afford (R)-2a as an orange solid (1.16 g). This solid
product was further crystallized from hot acetonitrile and isolated as
orange needlelike crystals (1.01 g, 82%).
1,1′-{(1R)-1-[Bis(4-methylphenyl)phosphino]-1,3-propanediyl}-
ferrocene ((R)-2c). Starting with alcohol (R)-1 (450 mg, 1.86 mmol),
NaI (696 mg, 4.65 mmol), ClSiMe3 (0.59 mL, 4.65 mmol) and di-4-
tolylphosphine (1.0 g, 4.7 mmol) in 20 mL of acetonitrile, the general
procedure gave phosphine (R)-2c as an orange solid (715 mg, 87%).
1H NMR (CDCl3): δ 1.66 (m, 1 H, C5H4CH2), 1.87 (m, 1 H,
C5H4CH2CH2), 2.16 (m, 1 H, C5H4CH2CH2), 2.24 (s, 3 H, CH3),
2.37 (s, 3 H, CH3), 2.39 (m, 1 H, C5H4CH2), 2.58 (ddd, J = 11.8, 6.4,
2.4 Hz, 1 H, CHP), 3.80 (dt, J′ = 2.5, 1.3 Hz, 1 H, C5H4), 3.91 (td, J′ =
2.4, 1.2 Hz, 1 H, C5H4), 3.94 (td, J′ = 2.4, 1.2 Hz, 1 H, C5H4), 3.98
(dt, J′ = 2.5, 1.2 Hz, 1 H, C5H4), 4.02 (dt, J′ = 2.4, 1.3 Hz, 1 H, C5H4),
4.05 (m, 2 H, C5H4), 4.12 (dt, J′ = 2.5, 1.3 Hz, 1 H, C5H4), 6.96 (m, 2
H, C6H4), 7.12 (m, 2 H, C6H4), 7.20 (m, 2 H, C6H4), 7.48 (m, 2 H,
C6H4). 13C{1H} NMR (CDCl3): δ 21.22 (CH3), 21.37 (CH3), 24.94
(d, 3JPC = 11 Hz, C5H4CH2), 36.32 (d, 1JPC = 11 Hz, CHP), 39.38 (d,
1
Mp: 155.5−157.0 °C dec (MeCN). H NMR (CDCl3): δ 1.68 (m,
1 H, C5H4CH2), 1.89 (m, 1 H, C5H4CH2CH2), 2.19 (m, 1 H,
C5H4CH2CH2), 2.41 (ddd, 1 H, J = 14.3, 4.5, 2.7 Hz, C5H4CH2), 2.61
(ddd, 1 H, J = 11.7, 6.4, 2.3 Hz, CHP), 3.77 (dt, J′ = 2.6, 1.3, 1 H,
C5H4CHP), 3.90 (td, J′ = 2.5, 1.3 Hz, 1 H,C5H4CH2), 3.94 (dt, J′ =
2.4, 1.3 Hz, 1 H, C5H4CH2), 3.99 (dt, J′ = 2.6, 1.3 Hz, 1 H, C5H4CH2),
4.03 (dt, J′ = 2.5, 1.3, 1 H, C5H4), 4.06 (m, 2 H, C5H4), 4.13 (dt, J′ =
2.6, 1.3 Hz, 1 H, C5H4CHP), 7.12−7.24 (m, 5 H, PPh2), 7.38−7.44
(m, 3 H, PPh2), 7.57−7.63 (m, 2 H, PPh2). 13C{1H} NMR (CDCl3): δ
3
2JPC = 25 Hz, C5H4CH2CH2), 67.05 (d, JPC = 9 Hz, CH of C5H4),
3
1
24.90 (d, JPC = 11 Hz, C5H4CH2), 36.31 (d, JPC = 12 Hz, CHP),
67.40 (CH of C5H4), 67.60 (CH of C5H4), 67.71 (CH of C5H4), 69.02
(CH of C5H4), 69.20 (CH of C5H4), 71.31 (CH of C5H4), 71.71 (d,
JPC = 2 Hz, CH of C5H4), 85.92 (C-CH2 of C5H4CH2), 128.63 (d, 3JPC
2
39.32 (d, JPC = 26 Hz, C5H4CH2CH2), 66.99 (d, JPC = 9 Hz, CH of
C5H4), 67.42 (CH of C5H4), 67.56 (CH of C5H4), 67.75 (CH of
C5H4), 69.03 (CH of C5H4), 69.23 (CH of C5H4), 71.31 (CH of
C5H4), 71.63 (d, JPC = 2 Hz, CH of C5H4), 85.77 (C-CH2 of
3
= 7 Hz, CHmeta of C6H4), 129.34 (d, JPC = 8 Hz, CHmeta of C6H4),
2
2
133.02 (d, JPC = 18 Hz, CHortho of C6H4), 133.76 (d, JPC = 20 Hz,
CHortho of C6H4), 138.07 (C-Me of C6H4), 139.22 (C-Me of C6H4).
The signals due to C-P of C6H4 and C-CHP of C5H4CHP were not
found. 31P{1H} NMR (CDCl3): δ −3.4 (s). ESI+ MS: m/z 225 ([M −
P(C6H4Me)2]+), 439 ([M + H]+, 461 ([M + Na]+), 477 ([M + K]+).
EI+ MS: m/z (relative abundance) 438 (9, M•+), 225 (100, [M −
2
C5H4CH2), 86.06 (d, JPC = 17 Hz, C-CH of C5H4CHP), 127.72 (d,
2JPC = 7 Hz, CHortho of PPh2), 128.20 (CHpara of PPh2), 128.52 (d, 2JPC
3
= 7 Hz, CHortho of PPh2), 129.11 (CHpara of PPh2), 133.10 (d, JPC
=
18 Hz, CHmeta of PPh2), 133.75 (d, JPC = 20 Hz, CHmeta of PPh2),
137.61 (d, 1JPC = 16 Hz, Cipso of PPh2), 137.64 (d, 1JPC = 14 Hz, Cipso
of PPh2). 31P{1H} NMR (CDCl3): δ −1.7 (s). ESI+ MS: m/z 225 ([M
− PPh2]+), 410 (M+), 433 ([M + Na]+), 449 ([M + K]+). EI+ MS: m/
z (relative abundance) 410 (13, M•+), 225 (100, [M − PPh2]+), 185
3
P(C6H4Me)2]+), 214 (10, HP(C6H4Me)2•+), 147 (9, C5H4FeC2H3 ),
+
+
122 (18, P(C6H4Me)•+), 121 (8, C5H5Fe+), 91 (4, C7H7 ), 78 (7,
+
C6H6 ), 56 (4, Fe+). HRMS: calcd for C27H27FeP 438.1200, found
+
+
(10, PPh2 ), 183 (11, C12H8P+), 147 (14, C5H4FeC2H3 ), 121 (14,
C5H5Fe+), 108 (17, PPh+), 56 (8, Fe+). HRMS: calcd for C25H23FeP
410.0887, found 410.0883. IR (DRIFTS): νmax 3071 w, 3024 w, 2937
w, 2908 m, 2841 w, 1479 w, 1433 m, 1223 w, 1194 w, 1039 w, 1031 m,
998 w, 899 w, 857 w, 810 s, 746 s, 738 s, 695 vs, 552 w, 515 s, 506 s,
477 m cm−1. Anal. Calcd for C25H23FeP (410.3): C, 73.19; H, 5.65.
Found: C, 72.94; H, 5.78. [α]D = +36.7°.
438.1194.
1,1′-{(1R)-1-[Bis(2,4,6-trimethylphenyl)phosphino]-1,3-
propanediyl}ferrocene ((R)-2d). The reaction of alcohol (R)-1 (358
mg, 1.48 mmol), NaI (554 mg, 3.70 mmol), ClSiMe3 (0.47 mL, 3.7
mmol), and dimesitylphosphine (1.0 g, 3.7 mmol) performed in 60
mL of acetonitrile and isolation as described above afforded phosphine
(R)-2d as an orange foamy solid (691 mg, 94%).
1H NMR (CDCl3): δ 1.79 (m, 1 H, C5H4CH2), 2.03 (m, 1 H,
1,1′-{(1R)-1-[Bis(2-methylphenyl)phosphino]-1,3-propanediyl}-
ferrocene ((R)-2b). Alcohol (R)-1 (450 mg, 1.86 mmol), NaI (696 mg,
4.65 mmol), ClSiMe3 (0.59 mL, 4.65 mmol) and di-2-tolylphosphine
(1.0 g, 4.7 mmol) were reacted in 35 mL of acetonitrile according to
the general procedure to give phosphine (R)-2b as an orange solid
(762 mg, 93%).
para
C5H4CH2CH2), 2.10 (s, 3 H, CH3
of C6H2Me3), 2.22 (s, 3 H,
para
ortho
CH3 of C6H2Me3), 2.34 (s, 6 H, CH3
of C6H2Me3), 2.41 (s, 6
ortho
H, CH3
of C6H2Me3), 2.41−2.53 (m, 2 H, C5H4CH2 and
C5H4CH2CH2), 3.55 (ddd, J = 11.4, 4.2, 1.7 Hz, 1 H, CHP), 3.68 (dt,
J′ = 2.6, 1.3 Hz, 1 H, C5H4), 3.77 (td, J′ = 2.6, 1.3 Hz, 1 H, C5H4),
3.89 (m, 1 H, C5H4), 3.92 (m, 1 H, C5H4), 4.01−4.05 (m, 3 H, C5H4),
4.16 (dt, J′ = 2.6, 1.3 Hz, 1 H, C5H4), 6.59 (dq, 4JHH = 0.6, 4JPH = 2.7
1H NMR (CDCl3): δ 1.76 (m, 1 H, C5H4CH2), 1.91 (m, 1 H,
C5H4CH2CH2), 2.27 (s, 3 H, CH3) 2.29 (m, 1 H, C5H4CH2CH2),
2.38 (d, 4JPH = 1.4 Hz, 3 H, CH3), 2.45 (ddd, J = 14.0, 4.3, 2.4 Hz, 1 H,
C5H4CH2), 2.57 (ddd, J = 11.5, 5.5, 2.0 Hz, 1 H, CHP), 3.65 (dt, J′ =
2.6, 1.3 Hz, 1 H, C5H4), 3.83 (td, J′ = 2.6, 1.3 Hz, 1 H, C5H4), 3.93
4
4
Hz, 2 H, CH of C6H2Me3), 6.78 (dq, JHH = 0.6, JPH = 2.7 Hz, 2 H,
para
CH of C6H2Me3). 13C{1H} NMR (CDCl3): δ 20.65 (CH3
of
C6H2Me3), 20.81 (CH3para C6H2Me3), 22.61 (d, 3JPC = 7 Hz, CH3
ortho
I
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
ortho
of C6H2Me3), 22.75 (d, 3JPC = 6 Hz, CH3
of C6H2Me3), 24.95 (d,
C5H4), 7.25−7.31 (m, 2 H, C6H4), 7.39−7.42 (m, 2 H, C6H4), 7.65−
3
7.71 (m, 4 H, C6H4). 13C{1H} NMR (CDCl3): δ 24.83 (d, JPC = 12
3JPC = 14 Hz, C5H4CH2), 33.54 (d, 1JPC = 16 Hz, CHP), 40.66 (d, 2JPC
= 39 Hz, C5H4CH2CH2), 67.07 (d, JPC = 7 Hz, CH of C5H4), 67.79
(CH of C5H4), 67.86 (CH of C5H4), 68.16 (CH of C5H4), 69.19 (CH
of C5H4), 70.80 (d, JPC = 2 Hz, CH of C5H4), 71.25 (CH of C5H4),
Hz, C5H4CH2), 36.34 (d, 1JPC = 13 Hz, CHP), 39.26 (d, 2JPC = 26 Hz,
3
C5H4CH2CH2), 66.98 (d, JPC = 9 Hz, CH of C5H4), 67.68 (CH of
C5H4), 67.78 (CH of C5H4), 68.23 (CH of C5H4), 69.46 (CH of
2
C5H4), 69.57 (CH of C5H4), 71.47 (CH of C5H4), 71.53 (d, JPC = 2
84.91 (C-CH2 of C5H4CH2), 86.40 (d, JPC = 18 Hz, C-CH of
2
C5H4CHP), 129.11 (d, 3JPC = 4 Hz, CH of C6H2Me3), 130.45 (d, 3JPC
Hz, CH of C5H4), 85.10 (d, JPC = 16 Hz, C-CHP of C5H4CHP),
1
5
2
= 2 Hz, CH of C6H2Me3), 131.20 (d, JPC = 19 Hz, Cortho of
85.38 (C-CH2 of C5H4CH2), 123.93 (qd, JFC = 272, JPC = 4 Hz,
CF3), 124.58 (dq, 3JPC = 7, 3JFC = 4 Hz, CHmeta of C6H4), 125.46 (dq,
3JPC = 7, 3JFC = 4 Hz, CHmeta of C6H4), 130.45 (q, 2JFC = 33 Hz, C-CF3
C6H2Me3), 132.78 (d, 2JPC = 33 Hz, Cortho of C6H2Me3), 136.89 (Cpara
of C6H2Me3), 137.86 (Cpara of C6H2Me3), 141.68 (d, 1JPC = 13 Hz, C-
P of C6H2Me3), 143.58 (d, JPC = 14 Hz, C-P of C6H2Me3). 31P{1H}
of C6H4), 131.47 (q, 2JFC = 33 Hz, C-CF3 of C6H4), 133.29 (d, 2JPC
=
1
2
NMR (CDCl3): δ −10.1 (s). ESI+ MS: m/z 225 ([M −
P(C6H2Me3)2]+), 495 ([M + H]+, 517 ([M + Na]+), 549 ([M + K
+ O]+). EI+ MS: m/z (relative abundance) 494 (12, M•+), 373 (13,
[M − C5H5Fe]+), 270 (96, HP(C6H2Me3)2•+), 255 (86, C17H19P+),
225 (95, [M − P(C6H2Me3)2]+), 150 (100, HPC6H2Me3•+), 147 (9,
18 Hz, CHortho of C6H4), 134.04 (d, JPC = 20 Hz, CHortho of C6H4),
141.93 (d, 1JPC = 10 Hz, C-P of C6H4), 142.12 (d, 1JPC = 8 Hz C-P of
C6H4). 31P{1H} NMR (CDCl3): δ −2.4 (s). 19F NMR (CDCl3): δ
−63.1 (s). ESI+ MS: m/z 225 ([M − P(CF3C6H4)2]+), 546 (M+), 585
([M + K]+). EI+ MS: m/z (relative abundance) 546 (24, M•+), 225
+
C5H4FeC2H3 ), 135 (74, C8H8P+), 121 (10, C5H5Fe+), 105 (60,
(100, [M − P(C6H4CF3)2]+), 147 (16, C5H4FeC2H3 ), 145 (8,
+
+
C8H8 ), 91 (26, C7H7 ), 56 (17, Fe+). HRMS: calcd for C31H35FeP
C6H4CF3 ), 121 (14, C5H5Fe+), 56 (7, Fe+). HRMS: calcd for
+
+
494.1826, found 494.1821.
C27H21F6FeP 546.0640, found 546.0634.
1,1′-{(1R)-1-[Bis(4-methoxyphenyl)phosphino]-1,3-propanediyl}-
ferrocene ((R)-2e). When reacted according to the general procedure,
alcohol (R)-1 (392 mg, 1.62 mmol), sodium iodide (608 mg, 4.06
mmol), ClSiMe3 (0.51 mL, 4.06 mmol), and bis(4-methoxyphenyl)-
phosphine (1.0 g, 4.1 mmol) in 20 mL of dry acetonitrile gave the
crude product, which was isolated as follows. After the excess
phosphine was removed by elution with hexane/diethyl ether (95/5),
the product was eluted with hexane/diethyl ether (1/1; yellow band).
Since the product is highly air sensitive and was partly oxidized, it was
chromatographed once again under inert conditions (flash chromatog-
raphy on alumina with preadsoprtion, elution with diethyl ether) to
afford pure (R)-2e as an orange yellow solid. Yield: 513 mg (67%).
1H NMR (CDCl3): δ 1.65 (m, 1 H, C5H4CH2), 1.87 (m, 1 H,
C5H4CH2CH2), 2.15 (m, 1 H, C5H4CH2CH2), 2.40 (ddd, J = 14.2, 4.5,
2.6 Hz, 1 H, C5H4CH2), 2.52 (ddd, J = 11.7, 6.5, 2.2 Hz, 1 H, CHP),
3.72 (s, 3 H, OCH3), 3.78 (dt, J′ = 2.5, 1.3 Hz, 1 H, C5H4), 3.83 (s, 3
H, OCH3), 3.90 (td, J′ = 2.3, 1.2 Hz, 1 H, C5H4), 3.94 (td, J′ = 2.4, 1.2
Hz, 1 H, C5H4), 3.98 (td, J′ = 2.4, 1.3 Hz, 1 H, C5H4), 4.02 (dt, J′ =
2.5, 1.3 Hz, 1 H, C5H4), 4.05 (m, 2 H, C5H4), 4.11 (dt, J′ = 2.5, 1.3
Hz, 1 H, C5H4), 6.71 (m, 2 H, C6H4), 6.94 (m, 2 H, C6H4), 7.16 (m, 2
H, C6H4), 7.52 (m, 2 H, C6H4). 13C{1H} NMR (CDCl3): δ 24.96 (d,
Preparation of 1,1′-[(1R)-1-(Diphenylthiophosphinoyl)-1,3-
propanediyl]ferrocene ((R)-3). Phosphine (R)-2a (84 mg, 0.20
mmol) and elemental sulfur (7 mg, 0.22 mmol) were allowed to react
in dry toluene (5 mL) at room temperature for 20 h. The reaction
mixture was evaporated, and the residue was filtered through a plug of
silica gel (elution with dichloromethane) to afford pure phosphine
sulfide (R)-3 after evaporation. Yield: 89 mg (98%), yellow orange
solid. X-ray-quality crystals were grown by slow cooling of an
acetonitrile solution.
1
Mp: 224.7−252.2 °C dec (MeCN). H NMR (CDCl3): δ 1.75 (m,
1 H, C5H4CH2), 2.26 (m, 2 H, C5H4CH2CH2), 2.50 (dt, J = 14.6, 3.3
Hz, 1 H, C5H4CH2), 2.99 (td, J = 10.5, 2.8 Hz, 1 H, CHP), 3.77 (m, 1
H, C5H4), 3.90 (td, J = 2.5, 1.3 Hz, 1 H, C5H4), 3.94 (td, J = 2.4, 1.3
Hz, 1 H, C5H4), 4.04−4.06 (m, 2 H, C5H4), 4.06−4.09 (m, 2 H,
C5H4), 4.60 (m, 1 H, C5H4), 7.24−7.30 (m, 2 H, PPh2), 7.32−7.38
(m, 1 H, PPh2), 7.48−7.56 (m, 3 H, PPh2), 7.61−7.68 (m, 2 H, PPh2),
8.02−8.08 (m, 2 H, PPh2). 13C{1H} NMR (CDCl3): δ 25.16 (d, 3JPC
=
1
2
14 Hz, C5H4CH2), 36.67 (d, JPC = 5 Hz, CHP), 40.55 (d, JPC = 53
Hz, C5H4CH2CH2), 67.53 (CH of C5H4), 67.62 (CH of C5H4), 68.01
(d, JPC = 2 Hz, CH of C5H4), 68.09 (CH of C5H4), 69.61 (CH of
2
C5H4), 69.77 (CH of C5H4), 71.44 (CH of C5H4), 72.07 (d, JPC = 4
Hz, CH of C5H4), 80.34 (d, 2JPC = 2 Hz, C-CHP of C5H4CHP), 85.32
3JPC = 11 Hz, C5H4CH2), 36.75 (d, 1JPC = 7 Hz, CHP), 39.22 (d, JPC
2
2
(C-CH2 of C5H4CH2), 127.90 (d, JPC = 12 Hz, CHortho of PPh2),
= 24 Hz, C5H4CH2CH2), 55.07 (OCH3), 55.22 (OCH3), 66.99 (d, JPC
= 8 Hz, CH of C5H4), 67.43 (CH of C5H4), 67.60 (CH of C5H4),
67.82 (CH of C5H4), 69.07 (CH of C5H4), 69.26 (CH of C5H4), 71.35
(CH of C5H4), 71.73 (d, JPC = 2 Hz, CH of C5H4), ca. 85.7 (br s, C-
CHP of C5H4CHP), 85.91 (C-CH2 of C5H4CH2), 113.59 (d, 3JPC = 8
2
4
128.61 (d, JPC = 12 Hz, CHortho of PPh2), 131.03 (d, JPC = 3 Hz,
4
CHpara of PPh2), 131.49 (d, JPC = 3 Hz, CHpara of PPh2), 131.51 (d,
3JPC = 9 Hz, CHmeta of PPh2), 131.69 (d, JPC = 10 Hz, CHmeta of
3
1
1
PPh2), 131.90 (d, JPC = 79 Hz, Cipso of PPh2), 132.44 (d, JPC = 80
Hz, Cipso of PPh2). 31P{1H} NMR (CDCl3): δ 49.3 (s). MS EI+: m/z
(relative abundance) 442 (18, M•+), 225 (100, [M − PSPh2]+), 186
3
Hz, CH of C6H4), 114.28 (d, JPC = 8 Hz, CH of C6H4), 134.48 (d,
2JPC = 19 Hz, CH of C6H4), 135.15 (d, JPC = 21 Hz, CH of C6H4),
2
+
(6, HPPh2•+), 147 (9, C5H4FeC2H3 ), 121 (8, C5H5Fe+), 108 (11,
160.01 (C-OMe of C6H4OCH3), 160.70 (C-OMe of C6H4OCH3).
The signals due to C-P of PC6H4 were not found. 31P{1H} NMR
(CDCl3): δ −4.7 (s). ESI+ MS: m/z 225 ([M − P(C6H4OMe)2]+),
471 ([M + H]+, 493 ([M + Na]+). EI+ MS: m/z (relative abundance)
470 (11, M•+), 246 (4, HP(C6H4OMe)2•+), 225 (100, [M −
PPh+), 56 (4, Fe+). ESI+ MS: m/z 225 ([M − P(S)Ph2]+), 410 ([M −
S]+), 442 (M+), 465 ([M + Na]+), 481 ([M + K]+). HRMS: calcd for
C25H23FePS 442.0608, found 442.0616. Anal. Calcd for C25H23FePS
(442.3): C, 67.88; H, 5.24. Found: C, 67.75; H, 5.19.
+
P(C6H4OMe)2]+), 147 (8, C5H4FeC2H3 ), 138 (16, HPC6H4OMe+),
Synthesis of trans-4. A solution of [PdCl2(cod)] (28.5 mg, 0.010
mmol) in dry dichloromethane (6 mL) was added dropwise to a
solution of (R)-2a in the same solvent (82 mg, 0.020 mmol in 1 mL).
The resulting deep red solution was stirred for 30 min and then
evaporated under vacuum. The residue was treated with pentane
(twice, 2 mL) under sonication and then dried under vacuum, yielding
trans-4 as a fine orange-red solid (92 mg, 92%). Crystals suitable for X-
ray diffraction analysis were obtained by recrystallization from
dichloromethane/hexane.
+
121 (10, C5H5Fe+), 91 (4, C7H7 ). HRMS: calcd for C27H27FeO2P
470.1098, found 494.1095.
1,1′-[(1R)-1-{Bis[4-(trifluoromethyl)phenyl]phosphino}-1,3-
propanediyl]ferrocene ((R)-2f). Alcohol (R)-1 (125 mg, 0.52 mmol),
NaI (116 mg, 0.78 mmol), ClSiMe3 (0.10 mL, 0.78 mmol), and bis[4-
(trifluoromethyl)phenyl]phosphine (0.25 g, 0.78 mmol) were reacted
in 10 mL of acetonitrile. The reaction mixture was worked up as
described above, except that hexane/diethyl ether (3/1) was used to
elute the product during column chromatography. Phosphine (R)-2f
was isolated as a yellow solid (165 mg, 58%).
1H NMR (CDCl3): δ 1.66 (dd, J = 12.0, 2.5 Hz, 1 H,
C5H4CH2CH2), 1.94 (td, J = 12.6, 2.5 Hz, 1 H, C5H4CH2), 2.46
(dt, J = 15, 3.2 Hz, 1 H, C5H4CH2), 2.98−3.05 (m, 1 H,
C5H4CH2CH2), 3.05 (dt, J = 2.6, 1.3 Hz, 1 H, C5H4), 3.65 (dt, J =
10.6, 4.5 Hz, 1 H, CHP), 3.81 (dt, J = 2.5, 1.3 Hz, 1 H, C5H4), 3.89
(m, 2 H, C5H4), 3.95 (m, 2 H, C5H4), 4.08 (dt, J = 2.5, 1.3 Hz, 1 H,
C5H4), 4.14 (dt, J = 2.6, 1.3 Hz, 1 H, C5H4), 7.29−7.47 (m, 6 H,
PPh2), 7.50−7.57 (m, 2 H, PPh2), 7.72−7.78 (m, 2 H, PPh2). 13C{1H}
1H NMR (CDCl3): δ 1.70 (m, 1 H, C5H4CH2), 1.92 (m, 1 H,
C5H4CH2CH2), 2.16 (m, 1 H, C5H4CH2CH2), 2.44 (ddd, J = 13.5, 4.5,
2.6 Hz, 1 H, C5H4CH2), 2.64 (ddd, J = 11.8, 6.3, 2.3 Hz, 1 H, CHP),
3.78 (dt, J′ = 2.5, 1.3 Hz, 1 H, C5H4), 3.95 (td, J′ = 2.5, 1.3 Hz, 1 H,
C5H4), 3.97 (td, J′ = 2.4, 1.2 Hz, C5H4), 4.01 (dt, J′ = 2.5, 1.3 Hz, 1 H,
C5H4), 4.05 (dt, J′ = 2.5, 1.3 Hz, 1 H, C5H4), 4.07−4.12 (m, 3 H,
J
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
2
NMR (CDCl3): δ 25.77 (virtual t, JPC = 7 Hz, C5H4CH2), 34.93
(virtual t, JPC = 11 Hz, CHP), 39.55 (virtual t, JPC = 6 Hz,
C5H4CH2CH2), 67.46 (CH of C5H4), 67.79 (CH of C5H4), 67.86
(CH of C5H4), 68.10 (CH of C5H4), 68.93 (CH of C5H4), 69.39 (CH
of C5H4), 71.91 (CH of C5H4), 73.26 (CH of C5H4), 81.39 (Cipso of
C5H4), 86.36 (Cipso of C5H4), 127.37 (virtual t, JPC = 22 Hz, Cipso of
PPh2), 127.50 (virtual t, JPC = 5 Hz, CH of PPh2), 127.83 (virtual t, JPC
= 5 Hz, CH of PPh2), 128.44 (virtual t, JPC = 21 Hz, Cipso of PPh2),
130.34 (CHpara of PPh2), 130.46 (CHpara of PPh2), 134.54 (virtual t,
JPC = 6 Hz, CH of PPh2), 135.11 (virtual t, JPC = 6 Hz, CH of PPh2).
31P{1H} NMR (CDCl3): δ 30.6 (s). ESI+ MS: m/z 25 ([M − Cl −
HCl]+), 1019 (weak, [M + Na]+). IR (DRIFTS): νmax 3090 w, 3052 w,
2936 w, 2907 w, 2843 w, 1482w, 1434 s, 1333 w 1290 w, 1156 m, 1102
m, 1043 w, 1031 m 999 w, 903 m, 851 w, 807 m, 751 m 699 s, 660 w,
630 w, 612 w, 518 m, 497 s, 481 w, 454 w, 420 w cm−1. Anal. Calcd for
C50H46Cl2Fe2P2Pd·0.6CH2Cl2 (1048.7): C, 57.94; H, 4.54. Found C,
57.93; H, 4.53. The presence of clathrated solvent was verified by
NMR spectroscopy.
Isolation of cis-4. Complex cis-4 was isolated from the reaction
mixture remaining after Pd-catalyzed asymmetric allylic alkylation (see
below). A reddish orange band, which remained adsorbed on the top
of the chromatographic column after complete removal of the
“organic” reaction products (silica gel, hexane/ethyl acetate 3/1),
was eluted by increasing the polarity of the mobile phase (hexane/
ethyl acetate 1/1). The resulting deep orange band was collected and
evaporated. Subsequent crystallization of the evaporation residue from
dichloromethane/hexane (liquid-phase diffusion) afforded the solvate
cis-4·2CH2Cl2 as red prisms. The yield was not determined.
15 Hz, C5H4CH2), 39.90 (d, 1JPC = 26 Hz, CHP), 40.76 (d, JPC = 11
Hz, C5H4CH2CH2), 49.17 (d, 3JPC = 3 Hz, NCH3), 51.50 (d, 3JPC = 2
Hz, NCH3), 67.38 (CH of C5H4), 67.48 (d, JPC = 1 Hz, CH of C5H4),
67.66 (CH of C5H4), 67.97 (CH of C5H4), 68.87 (CH of C5H4), 69.27
3
(CH of C5H4), 71.91 (CH of C5H4), 73.10 (d, JPC = 3 Hz, NCH2),
73.56 (d, 3JPC = 2 Hz, CH of C5H4), 81.19 (d, 2JPC = 2 Hz, C-CHP of
C5H4), 86.35 (C-CH2 of C5H4), 122.04 (CH of C6H4), 123.47 (CH of
C6H4), 125.07 (d, JPC = 6 Hz, CH of C6H4), 127.42 (d, JPC = 10 Hz,
CH of PPh2), 127.88 (d, 1JPC = 43 Hz, Cipso of PPh2), 127.91 (d, JPC
=
10 Hz, CH of PPh2), 129.32 (d, JPC = 43 Hz, Cipso of PPh2), 130.22
1
(d, JPC = 2 Hz, CHpara of PPh2), 131.08 (d, JPC = 2 Hz, CHpara of
4
4
PPh2), 134.56 (d, JPC = 11 Hz, CH of PPh2), 136.51 (d, JPC = 13 Hz,
CH of PPh2), 137.67 (d, 3JPC = 11 Hz, CH of C6H4), 147.84 (d, 2JPC
=
2 Hz, Cipso of C6H4), 152.10 (Cipso of C6H4). 31P{1H} NMR (CDCl3):
δ 48.7 (s). ESI+ MS: m/z 650 ([M − Cl]+), 708 (weak, [M + Na]+).
IR (DRIFTS): νmax 3459 br w, 3075 m, 3051 m, 2909 m, 2847 m,
1580 m, 1481 m, 1451 m, 1436 s, 1399 w, 1358 w, 1333 w, 1289 w,
1246 w, 1212 w, 1185 w, 1159 w, 1099 m, 1043 m, 1030 m, 997 m,
973 w, 905 m, 861 m, 845 m, 805 m, 740 s, 696 s, 662 w, 630 w, 613
w, 551 w, 520s, 501 s, 501 s, 484 m, 460 m, 421 w cm−1. Anal. Calcd
for C34H35ClFeNPPd·2CHCl3 (925.0): C, 46.74; H, 4.03; N, 1.51.
Found: C, 46.56; H, 3.90; N, 1.34.
Catalytic Tests in Asymmetric Allylic Alkylations. Catalytic
experiments were carried out as described in the literature.49 A flame-
dried Schlenk flask was charged with a stirring bar, [PdCl(η3-C3H5)]2
(2.3 mg, 6.3 μmol), and the appropriate chiral phosphine 2 (25 or 12.5
μmol; see Table 3), flushed with argon, and sealed with a rubber
septum. Dry dichloromethane (1 mL) was introduced, and the
resulting solution was stirred at room temperature for 30 min. Then,
racemic 1,3-diphenylallyl acetate (6; 63.1 mg, 0.25 mmol in 1 mL of
dichloromethane) was added and the mixture was stirred for another 5
min before a mixture of dimethyl malonate (90 μL, 0.75 mmol) and
N,O-bis(trimethylsilyl)acetamide (BSA; 0.19 mL, 0.75 mmol) in
dichloromethane (1 mL) was added as the last component. The
resulting mixture was stirred at room temperature for 24 h, whereupon
it typically turned from yellow to red.
The reaction mixture was diluted with dichlormethane (3 mL) and
washed with saturated aqueous NH4Cl solution (2 × 5 mL). The
organic layer was dried over magnesium sulfate and evaporated,
leaving a residue which was purified by column chromatography (silica
gel, hexane/ethyl acetate 3/1). The first band containing the starting
allyl acetate was discarded, and the following one containing the
alkylation product and unreacted malonate (if any) was collected and
evaporated. Conversion (yield) was obtained by integration of 1H
NMR spectra recorded in C6D6. Enantiomeric excess was determined
after addition of tris[3-(trifluoromethylhydroxymethylene)-
(+)-camphorato]europium(III) ([Eu(tfc)3]).50 Analytical data for the
alkylation product 7 are given in the Supporting Information.
Catalytic Tests in Asymmetric aza-Morita-Baylis-Hillman
Reactions. A flame-dried Schlenk tube was charged with the
appropriate imine (0.50 mmol), chiral phosphine 2 (50 μmol), anisole
(0.50 mmol, internal standard), and the additive (only if appropriate;
either 300 mg of dry 4 Å molecular sieves or 25 μmol of benzoic acid),
flushed with argon, and sealed with a rubber septum. Dry solvent
(typically CDCl3, 2 mL) was introduced, followed immediately by
methyl vinyl ketone (1.0 mmol). The resultant mixture was stirred at
1H NMR (CDCl3): δ 2.02 (m, 2 H, CH2), 2.39 (br s, 1 H, CH2),
2.59 (m, 1 H, CH2), 3.64 (dt, J = 2.5, 1.3 Hz, 1 H, C5H4), 3.73 (m, 1
H, C5H4), 3.70−3.86 (m, 4 H, 3× CH of C5H4 + CHP), 3.84 (td J =
2.5, 1.2, Hz, 1 H, C5H4), 3.87 (td, J = 2.5, 1.3 Hz, 1 H, C5H4), 3.98 (dt,
J = 2.4, 1.4 Hz, 1 H, C5H4), 6.56 (virtual t, J = 7.4 Hz, 2 H, PPh2), 6.66
(br s, 2 H, PPh2), 7.00 (virtual t, J = 7.5 Hz, 1 H, PPh2), 7.41−7.46 (m,
2 H, PPh2), 7.56−7.61 (m, 1 H, PPh2), 7.94−8.00 (m, 2 H, PPh2).
13C{1H} NMR (CDCl3): δ 25.70 (nonbinomial t, JPC = 7 Hz,
C5H4CH2), 40.56 (nonbinomial t, J = 5 Hz, CHP), 43.68 (d, J = 29
Hz, C5H4CH2CH2), 67.00 (CH of C5H4), 67.56 (d, JPC = 7 Hz, CH of
C5H4), 67.86 (CH of C5H4), 69.42 (2 C, CH of C5H4), 72.01 (CH of
C5H4), 73.89 (CH of C5H4), 77.21 (CH of C5H4), 81.00 (Cipso of
C5H4), 81.15 (Cipso of C5H4), 125.41 (d, JPC = 49 Hz, Cipso of PPh2),
127.43 (virtual t, JPC = 5 Hz, CH of PPh2), 127.62 (virtual t, JPC = 5
Hz, CH of PPh2), 128.22 (virtual dd, JPC = 47 and 5 Hz, Cipso of PPh2),
129.59 (CHpara of PPh2), 131.75 (virtual t, JPC = 6 Hz, CH of PPh2),
132.05 (CHpara of PPh2), 137.89 (virtual t, JPC = 6 Hz, CH of PPh2).
31P{1H} NMR (CDCl3): δ 42.9 (s). ESI+ MS: m/z 925 ([M − Cl −
HCl]+), 1019 (weak, [M
+
Na]+). Anal. Calcd for
C50H46Cl2Fe2P2Pd·0.2CH2Cl2 (1014.8): C, 59.41; H, 4.61. Found:
C, 59.39; H, 4.50. The amount of residual solvent was corroborated by
NMR spectroscopy.
Preparation of Complex 5. A solution of the dimer [(LNC)-
PdCl2]2 (20.7 mg, 37.5 μmol) in dichloromethane (2 mL) was added
to solid phosphine (R)-2a (31 mg, 75 μmol). The resulting clear
orange solution was stirred for 90 min and evaporated under vacuum.
The residue was washed with pentane and dried under vacuum to
afford 5 as an orange powdery solid (50 mg, quantitative). X-ray-
quality crystals of 5·2CHCl3 were grown by liquid-phase diffusion of
hexane into a solution in chloroform.
1
room temperature overnight, and a small aliquot was analyzed by H
NMR spectroscopy. The rest was evaporated under reduced pressure,
and the residue was purified by flash column chromatography (silica
gel, hexane/ethyl acetate 3/1). Following evaporation, the residue was
analyzed with HPLC on a suitable chiral column. Stereochemistry of
the dominating enantiomer was established by a comparison of optical
rotation with the literature values.51
Prior to the catalytic experiments with phosphines (R)-2a−f, the
reactions were always performed with triphenylphosphine. Following
evaporation of the reaction mixture, the racemic products 9a−e were
isolated by column chromatography over silica gel using a hexane/
ethyl acetate mixture as the eluent (the composition of the mobile
phase was gradually changed from 9/1 to 2/1). They were used as
reference standards and for calibration of the HPLC analytical
1H NMR (CDCl3): δ 1.79 (m, 1 H, C5H4CH2CH2), 2.04 (td, J =
12.0, 2.7 Hz 1 H, C5H4CH2), 2.48 (m, 1 H, C5H4CH2), 2.71 (d, 4JHH
=
2.4 Hz, 3 H, NCH3), 2.89 (s, 1 H, C5H4), 2.98 (d, 4JHH = 3.1 Hz, 3 H,
2
4
NCH3), 3.39 (m, 1 H, C5H4CH2CH2), 3.60 (dd, JHH = 13.5, JPH
=
3.4 Hz, 1 H, NCH2), 3.66 (t, J = 11 Hz, 1 H, CHP), 3.80 (m, 1 H,
C5H4), 3.88 (m, 1 H, C5H4), 3.91 (m, 1 H, C5H4), 3.94 (m, 1 H,
C5H4), 3.98 (m, 1 H, C5H4), 4.09 (m, 2 H, C5H4), 4.43 (d, 2JHH = 13.5
Hz, 1 H, NCH2), 6.25 (td, J = 7.8, 1.3 Hz, 1 H, C6H4), 6.32 (br t, J =
7.8 Hz, 1 H, C6H4), 6.73 (td, J = 7.3, 1.2 Hz, 1 H, C6H4), 6.91 (dd, J =
7.3, 1.4 Hz, 1 H, C6H4), 7.21−7.27 (m, 2 H, PPh2), 7.32−7.40 (m, 3
H, PPh2), 7.43−7.49 (m, 1 H, PPh2), 7.56−7.62 (m, 2 H, PPh2),
7.99−8.05 (m, 2 H, PPh2). 13C{1H} NMR (CDCl3): δ 25.48 (d, 3JPC
=
K
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
methods. Characterization data for 9a−e are available as Supporting
Petolz, G.; Kollar
́
, L. J. Organomet. Chem. 2000, 595, 93. (f) Jalon
́
, F.
̈
Information.
A.; Manzano, B. R.; Gomez-de la Torre, F.; Lopez-Agenjo, A. M.;
́
́
X-ray Crystallography. Full-set diffraction data ( h, k, l; θmax
=
́
Rodrıguez, A. M.; Weissensteiner, W.; Sturm, T.; Mahía, J.; Maestro,
27.5°, data completeness ≥99.8%) were collected with a Nonius
Kappa diffractometer equipped with an Apex2 detector (Bruker) and
Cryostream Cooler (Oxford Cryosystems) at 150(2) K using graphite-
monochromated Mo Kα radiation (λ = 0.71073 Å). The structures
were solved by direct methods (SHELXS-8752) and refined by full-
matrix least squares based on F2 (SHELXL-9752). The non-hydrogen
atoms were refined with anisotropic displacement parameters. The
hydrogens were included in their calculated positions and refined as
riding atoms with Uiso(H) assigned to a multiple of Ueq of their
bonding atom. Relevant crystallographic data and structure refinement
parameters are presented as Supporting Information (Table S1).
Geometric data and structural drawings were obtained with a recent
version of the PLATON program.53 The numerical values are rounded
with respect to their estimated deviations (ESDs) given to one decimal
place.
M. J. Chem. Soc., Dalton Trans. 2001, 2417. (g) Sturm, T.;
́
Weissensteiner, W.; Spindler, F.; Mereiter, K.; Lopez-Agenjo, A. M.;
Manzano, B. R.; Jalon
(h) Cayuela, E.; Jalo
Weissensteiner, W.; Mereiter, K. J. Am. Chem. Soc. 2004, 126, 7049.
́
, F. A. Organometallics 2002, 21, 1766.
n, F. A.; Manzano, B. R.; Espino, G.;
́
́
(i) Carrion, M. C.; Garcıa-Vaquero, E.; Jalon, F. A.; Manzano, B. R.;
́
́
Weissensteiner, W.; Mereiter, K. Organometallics 2006, 25, 4498.
(j) Sturm, T.; Abad, B.; Weissensteiner, W.; Mereiter, K.; Manzano, B.
R.; Jalon
C.; Jalon
Mereiter, K. J. Organomet. Chem. 2006, 691, 1369.
(4) (a) An A-type compound bearing the CH2PPh2 group at the
́
, F. A. J. Mol. Catal. A: Chem. 2006, 255, 209. (k) Carrion
, F. A.; Lopez-Agenjo, A.; Manzano, B. R.; Weissensteiner, W.;
́
, M.
́
́
̌
cyclopentadienyl ring has been also reported: Sebesta, R.; Bilcí
Horvat
iminophosphines, see: Sebesta, R.; Skvorcova,
2009, 694, 1898.
(5) Selected references: (a) Liptau, P.; Seki, T.; Kehr, G.; Abele, A.;
Frohlich, R.; Erker, G.; Grimme, S. Organometallics 2003, 22, 2226.
̌
k, F.;
́
h, B. Eur. J. Org. Chem. 2008, 5157. (b) For related phosphine-
̌
̌
́
A. J. Organomet. Chem.
ASSOCIATED CONTENT
* Supporting Information
■
̈
S
(b) Liptau, P.; Tebben, L.; Kehr, G.; Wibbeling, B.; Frohlich, R.; Erker,
̈
Text giving analytical data for the products of the catalytic
reactions, an NMR profile for the isomerization of cis-4 to trans-
4 (Figure S1), an overlap of the crystallographic independent
molecules of trans-4 (Figure S2), a summary of crystallographic
data (Table S1), figures giving NMR spectra, and CIF files and
tables giving crystallographic data. This material is available free
of charge via the Internet at http://pubs.acs.org.
G. Eur. J. Inorg. Chem. 2003, 3590. (c) Liptau, P.; Tebben, L.; Kehr,
G.; Frohlich, R.; Erker, G.; Hollmann, F.; Rieger, B. Eur. J. Org. Chem.
̈
2005, 1909. (d) Unverhau, K.; Lubbe, G.; Wibbeling, B.; Frohlich, R.;
̈
Kehr, G.; Erker, G. Organometallics 2010, 29, 5320. (e) Lubbe, G.;
̈
Frohlich, R.; Kehr, G.; Erker, G. Inorg. Chim. Acta 2011, 369, 223.
̈
(6) Representative examples: (a) Knuppel, S.; Frohlich, R.; Erker, G.
̈
̈
J. Organomet. Chem. 2000, 595, 308. (b) Tebben, L.; Neumann, M.;
Kehr, G.; Frohlich, R.; Erker, G.; Losi, S.; Zanello, P. Dalton Trans.
̈
AUTHOR INFORMATION
Corresponding Author
*E-mail: stepnic@natur.cuni.cz.
Notes
2006, 1715.
■
̌
̌
(7) (a) Sebesta, R.; Almassy, A.; Císarova, I.; Toma, S. Tetrahedron:
Asymmetry 2006, 17, 2531. (b) Sebesta, R.; Skvorcova,
Tetrahedron: Asymmetry 2010, 21, 1910.
̌
́
̌
̌
́ ́
A.; Horvath, B.
(8) Ogasawara, M.; Watanabe, S.; Nakajima, K.; Takahashi, T. J. Am.
Chem. Soc. 2010, 132, 2136.
The authors declare no competing financial interest.
(9) Hocher, T.; Cinquantini, A.; Zanello, P.; Hey-Hawkins, E.
Polyhedron 2005, 24, 1340.
̈
ACKNOWLEDGMENTS
■
(10) The related phosphine possessing the 1,2,3-triphenyl-2-
phosphapropan-1,3-diyl bridge was also reported: (a) Blanco, C.;
Ruiz, A.; Godard, C.; Fleury-Bregeot, N.; Marinetti, A.; Claver, C. Adv.
́
Synth. Catal. 2009, 351, 1813. (b) Blanco, C.; Godard, C.; Zangrando,
E.; Ruiz, A.; Claver, C. Dalton Trans. 2012, 41, 6980 and ref 12a.
(11) Adams, J. J.; Curnow, O. J.; Huttner, G.; Smail, S. J.; Turnbull,
M. M. J. Organomet. Chem. 1999, 577, 44.
This work was financially supported by the Czech Science
Foundation (Project No. P207/10/0176) and is a part of the
long-term research plan of the Faculty of Science, Charles
University in Prague, supported by the Ministry of Education,
Youths and Sports of the Czech Republic (Project No.
MSM0021620857).
́
(12) (a) Fleury-Bregeot, N.; Panossian, A.; Chiaroni, A.; Marinetti, A.
REFERENCES
(1) (a) Ferrocenes: Ligands, Materials and Biomolecules; Step
Eur. J. Inorg. Chem. 2007, 3853. (b) Neel, M.; Panossian, A.; Voituriez,
A.; Marinetti, A. J. Organomet. Chem. 2012, 716, 187.
■
̌
̌
nick
̌
a, P.,
(13) (a) Voituriez, A.; Panossian, A.; Fleury-Breg
P.; Marinetti, A. J. Am. Chem. Soc. 2008, 130, 14030. (b) Voituriez, A.;
Panossian, A.; Fleury-Bregeot, N.; Retailleau, P.; Marinetti, A. Adv.
́
eot, N.; Retailleau,
Ed.; Wiley: Chichester, U.K., 2008. (b) Ferrocenes: Homogeneous
Catalysis, Organic Synthesis, Materials Science; Togni, A., Hayashi, T.;
Eds.; Wiley-VCH: Weinheim, Germany, 1995. (c) Togni, A. In
Metallocenes: Synthesis, Reactivity, Applications; Togni, A., Halterman, R.
L., Eds.; Wiley-VCH: Weinheim, Germany, 1998; Vol. 2, Chapter 11,
pp 685−721.
(2) For recent reviews, see: (a) Atkinson, R. C. J.; Gibson, V. C.;
Long, N. J. Chem. Soc. Rev. 2004, 33, 313. (b) Barbaro, P.; Bianchini,
C.; Giambastiani, G.; Parisel, S. L. Coord. Chem. Rev. 2004, 248, 2131.
́
Synth. Catal. 2009, 351, 1968. (c) Pinto, N.; Neel, M.; Panossian, A.;
Retailleau, P.; Frison, G.; Voituriez, A.; Marinetti, A. Chem.Eur. J.
2010, 16, 1033. (d) Voituriez, A.; Pinto, N.; Neel, M.; Retailleau, P.;
Marinetti, A. Chem. Eur. J. 2010, 16, 12541. (e) Neel, M.; Gouin, J.;
Voituriez, A.; Marinetti, A. Synthesis 2011, 2003.
(14) (a) Huber, D. P.; Kehr, G.; Bergander, K.; Frohlich, R.; Erker,
̈
G.; Tanino, S.; Ohki, Y.; Tatsumi, K. Organometallics 2008, 27, 5279.
(b) For a study into the reaction of 2-vinyl-G (and related
(c) Gomez
2006, 45, 7674.
́ ́
Arrayas, R.; Adrio, J.; Carretero, J. C. Angew. Chem., Int. Ed.
compounds) with B(C F ) , see: Voss, T.; Sortias, J.-B.; Frohlich, R.;
̈
(3) For the preparation, catalytic use, and structural studies with
ligands A and B, see: (a) Kutschera, G.; Kratky, C.; Weissensteiner,
W.; Widhalm, M. J. Organomet. Chem. 1996, 508, 195. (b) Mernyi, A.;
Kratky, C.; Weissensteiner, W.; Widhalm, M. J. Organomet. Chem.
6
5 3
Kehr, G.; Erker, G. Organometallics 2011, 30, 584.
(15) Structurally related (but non-ferrocenophane and nonchiral)
ferrocene phosphines bearing the phosphorus atom in a β position
with respect to the ferrocene moiety have received some attention in
́ ́ ́
1996, 508, 209. (c) Gomez-de la Torre, F.; Jalon, F. A.; Lopez-Agenjo,
̌
́
the recent past: (a) Step
̌
nick
̌
a, P.; Císaro
̌
va,
́
I.; Schulz, J. Organo-
va, I. J. Organomet.
A.; Manzano, B. R.; Rodrıguez, A.; Sturm, T.; Weissensteiner, W.;
̌
́
metallics 2011, 30, 4393. (b) Step
̌
nick
̌
a, P.; Císaro
̌
́
Martınez-Ripoll, M. Organometallics 1998, 17, 4634. (d) Jalon
́
, F. A.;
́
Chem. 2012, 716, 110. (c) Roy, D.; Mom, S.; Royer, S.; Lucas, D.;
Hierso, J.-C.; Doucet, H. ACS Catal. 2012, 2, 1033. (d) Gorunova, O.
N.; Livantsov, M. V.; Grishin, Y. K.; Kataeva, N. A.; Kochetkov, K. A.;
Lop
́
ez-Agenjo, A.; Manzano, B. R.; Moreno-Lara, M.; Rodrıguez, A.;
Sturm, T.; Weissensteiner, W. J. Chem. Soc., Dalton Trans. 1999, 4031.
́
(e) Sturm, T.; Weissensteiner, W.; Mereiter, K.; Kegl, T.; Jeges, G.;
L
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Churakov, A. V.; Kuz’mina, L. G.; Dunina, V. V. Polyhedron 2012, 31,
37. (e) Schuecker, R.; Weissensteiner, W.; Mereiter, K.; Lotz, M.;
Spindler, F. Organometallics 2010, 29, 6443. (f) Lotz, M.; Schuecker,
R.; Mereiter, K.; Knochel, P. Organometallics 2010, 29, 6503.
(16) Rosenblum, M.; Banerjee, A. K.; Danieli, N.; Fish, R. W.;
Schlatter, V. J. Am. Chem. Soc. 1963, 85, 316.
(17) Cayuela, E. M.; Xiao, L.; Sturm, T.; Manzano, B. R.; Jalon, F. A.;
Weissensteiner, W. Tetrahedron: Asymmetry 2000, 11, 861.
(18) Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225.
(19) For applications of this methodology in ferrocene chemistry,
(35) This can be exemplified by a different catalytic performance of
phosphinoferrocene carboxamides that coordinate as P,P- or O,P-
̌
̌ ́ ̌ ̌
va, I.; Stepnicka, P. New J. Chem. 2009,
chelates: (a) Lamac,
33, 1549. (b) Lamac,
Organometallics 2007, 26, 5042.
̌
M.; Císaro
̌
̌ ́ ̌ ̌
M.; Tauchman, J.; Císarova, I.; Stepnicka, P.
̌
(36) Morita, K.; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn. 1968, 41,
2815.
(37) Baylis, A. B.; Hillman, M. E. D. German Patent 2155113, 1972;
Chem. Abstr. 1972, 77, 34147q.
(38) Wei, Y.; Shi, M. Acc. Chem. Res. 2010, 43, 1005.
(39) Takizawa, S.; Kiriyama, K.; Ieki, K.; Sasai, H. Chem. Commun.
2011, 47, 9227.
(40) (a) Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc. 2005, 127,
3790. (b) For an example of an MBH reaction with simple
phosphinoferrocenes, see: Pereira, S. I.; Adrio, J.; Silva, A. M. S.;
Carretero, J. C. J. Org. Chem. 2005, 70, 10175.
(41) For an early report, see: Perlmutter, P.; Teo, C. C. Tetrahedron
Lett. 1984, 25, 5951.
̌
̌
see: (a) Sebesta, R.; Toma, S.; Saliso
̌
va,
́
M. Eur. J. Org. Chem. 2002,
̌
̌
692. (b) Lamac,
2005, 690, 4285 and ref 15a.
̌
M.; Císaro
̌
va,
́
I.; Step
̌
nicka, P. J. Organomet. Chem.
(20) Only the archetypal representative (R)-2a was successfully
crystallized from hot acetonitrile. Phosphines (R)-2b−f do not
crystallize well.
(21) The assignment of NMR spectra is based on the conventional
1H, 13C{1H}, and 31P{1H} spectra and on H−H (COSY-90) and C−H
correlated (gradient-selected 13C HSQC and HMBC) 2-D spectra.
(22) The stabilization of this ferrocenophane cation can be expected
to be similar in nature to that observed in the ferrocenylmethylium ion
(42) Shi, M.; Xu, Y.-M. J. Org. Chem. 2003, 68, 4784.
(43) Shi, M.; Xu, Y.-M. Eur. J. Org. Chem. 2002, 696.
(44) (a) Shi, Y.-L.; Shi, M. Adv. Synth. Catal. 2007, 349, 2129.
́
(b) Mansilla, J.; Saa, J. M. Molecules 2010, 15, 709.
+
(FcCH2 ): Gleiter, R.; Bleiholder, C.; Rominger, F. Organometallics
(45) Drew, D.; Doyle, J. R. Inorg. Synth. 1972, 13, 47.
(46) Cope, A. C.; Friedrich, E. C. J. Am. Chem. Soc. 1968, 90, 909.
(47) Acetate 6 was prepared by acylation of the commercially
available racemic 1,3-diphenylprop-2-en-1-ol as described in the
literature: Watson, I. D. G.; Styler, S. A.; Yudin, A. K. J. Am. Chem.
Soc. 2004, 126, 5086.
2007, 26, 4850 and references cited therein.
̌
(23) Step
̌ ̌ ́ ̌
nicka, P.; Podlaha, J.; Gyepes, R.; Polasek, M. J. Organomet.
Chem. 1998, 552, 293.
(24) The fact that the shifted signal is due to ferrocene α-CH located
at the side of the bridge apex is supported by the 2D NMR spectra,
which associate this high-field 1H NMR signal with the carbon
resonance showing a coupling with the proximal phosphorus atom (cf.
3JPC = 2 Hz for complex 5).
(48) Lu, K.; Kwon, O. Org. Synth. 2009, 86, 212.
̌
̌ ́ ̌ ̌
(49) Tauchman, J.; Císarova, I.; Stepnicka, P. Dalton Trans. 2011, 40,
11748.
(25) Compare the H···Cg distances for the ferrocene α-CH close to
the ansa bridge (Cg = ring centroid) in cis-4 (H···Cg = 3.01 (Fe1)/
3.05 (Fe2) Å), 5 (H···Cg = 2.89 Å), and trans-4 (H···Cg = 3.90 (Fe1)/
2.85 (Fe2), and 3.71 (Fe3)/2.79 (Fe4) Å).
(50) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron
Lett. 1986, 27, 191.
(51) Lei, Z.-Y.; Ma, G.-N.; Shi, M. Eur. J. Org. Chem. 2008, 22, 3817.
(52) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
(53) Spek, A. L. Acta Crystallogr., Sect. D 2009, 65, 148.
(26) (a) Pregosin, P. S.; Kunz, R. W. 31P and 13C NMR of Transition
Metal Phosphane Complexes. In NMR Basic Principles and Progress;
Diehl, P.; Fluck, E.; Kosfeld, R., Eds.; Springer: Berlin, 1979; Vol. 16,
chapter E, p. 65 ff and references therein. (b) Hersh, W. H. J. Chem.
Educ. 1997, 74, 1485.
(27) Representative examples involving phosphinoferrocene ligands:
̌
(a) Step
̌
nick
(b) Stepnick
P.; Císarova,
Císarova, I.; Step
985. (e) Tauchman, J.; Císaro
2009, 28, 3288. (f) Schulz, J.; Císaro
metallics 2012, 31, 729.
̌
a, P.; Lamac,
a, P. Inorg. Chem. Commun. 2004, 7, 426. (c) Step
I. Organometallics 2003, 22, 1728. (d) Lamac,
̌ ̌ ́
M.; Císarova, I. Polyhedron 2004, 23, 921.
̌
̌
̌
̌
̌
nick
M.;
̌
̌ ̌
nicka, P. Collect. Czech. Chem. Commun. 2007, 72,
̌
a,
̌
́
̌
̌
́
̌
́ ̌
va, I.; Stepnicka, P. Organometallics
̌
̌
́ ̌ ̌
va, I.; Stepnicka, P. Organo-
̌
(28) (a) Appleton, T. G.; Clark, H. C.; Manzer, L. E. Coord. Chem.
Rev. 1973, 10, 335. (b) Hartley, F. R. The Chemistry of Platinum and
Palladium; Applied Science: London, 1973; Chapter 11, p 299.
(29) Hillman, M.; Austin, J. D. Organometallics 1987, 6, 1737.
(30) Hartley, F. R. The Chemistry of Platinum and Palladium; Applied
Science: London, 1973; Chapter 2, pp 8−26.
(31) Yamamoto, Y.; Tanase, T.; Mori, I.; Nakamura, Y. J. Chem. Soc.,
Dalton Trans. 1994, 3191.
(32) Ma, J.-F.; Yamamoto, Y. Inorg. Chim. Acta 2000, 299, 164.
(33) (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395.
(b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921.
(c) Trost, B. M. J. Org. Chem. 2004, 69, 5813. (d) Hayashi, T. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993;
Chapter 7.1, pp 325−365. (e) Graening, T.; Schmalz, H.-G. Angew.
Chem., Int. Ed. 2003, 42, 2580. (f) Rios, I. G.; Rosas-Hernandez, A.;
Martin, E. Molecules 2011, 16, 970.
(34) Recent reviews: (a) Basavaiah, D.; Reddy, B. S.; Badsara, S. S.
Chem. Rev. 2010, 110, 5447. (b) Ma, G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y.
Chem. Commun. 2009, 5496. (c) Masson, G.; Housseman, C.; Zhu, J.
Angew. Chem., Int. Ed. 2007, 46, 4614. (d) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811.
M
dx.doi.org/10.1021/om3011245 | Organometallics XXXX, XXX, XXX−XXX