Aryl ferrophites - A new class of ligands for asymmetric catalysis

Article abstract of DOI:10.1002/ejoc.200600071

Enantiopure lithiated 1,2-ferrocenes, [CpFe{1,2-η⁵-C ₅H₃(Ar)-(Li)}] (Ar = Ph, 4-CF₃C ₆H₄, 1-C₁₀H₇), react readily with PhOP(OR)₂ to yield [CpFe{1,2-η⁵-C₅H ₃(Ar)P(OR)₂}] (R = Ph, 1,1′-biphenyl-based, 1,1′-binaphthyl-based) efficiently. Traditional routes to these species, involving the use of chlorophosphites CIP(OR)₂ were found to be ineffective. These "ferrophite" ligands have been characterised by X-ray crystallography (4 examples) and shown to be effective in both nickel-catalysed addition of AlMe₃ to PhCHO (up to 77 % ee) and copper(I)-catalysed additions of organoaluminium reagents to enones (up to 92 % ee). Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600071

FULL PAPER
DOI: 10.1002/ejoc.200600071
Aryl Ferrophites – A New Class of Ligands for Asymmetric Catalysis
[a]
[a]
[a]
[a]
Victoria E. Albrow, Alexander J. Blake, Ross Fryatt, Claire Wilson, and
Simon Woodward*[
a]
Keywords: Ferrocenyl ligands / P ligands / Phosphites / Asymmetric catalysis
5
Enantiopure lithiated 1,2-ferrocenes, [CpFe{1,2-η -C
5
H
3
(Ar)-
tallography (4 examples) and shown to be effective in both
nickel-catalysed addition of AlMe to PhCHO (up to 77% ee)
and copper( )-catalysed additions of organoaluminium rea-
(
Li)}] (Ar = Ph, 4-CF
PhOP(OR) to yield [CpFe{1,2-η -C
,1Ј-biphenyl-based, 1,1Ј-binaphthyl-based)
3
C
6
H
4
, 1-C10
H
H
7
), react readily with
3
5
2
5
3
(Ar)P(OR)
2
}] (R = Ph,
efficiently.
I
1
gents to enones (up to 92% ee).
Traditional routes to these species, involving the use of chlo-
rophosphites ClP(OR) were found to be ineffective. These
ferrophite” ligands have been characterised by X-ray crys-
2
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
“
Introduction
Results and Discussion
Phosphoramidites [(RO) PNR ] are recent additions to
2
2
the set of so-called “privileged” ligands[ leading to super-
1]
Ligand Synthesis: Kagan has introduced a powerful
methodology for the preparation of planar chiral 1,2-disub-
stituted ferrocenes based on the use of sulfoxide auxili-
lative asymmetric catalysis when coordinated to a range of
metal centres for a variety of processes.[2] The very high
[
6]
aries. Our synthetic route began with (S )-1 prepared
c
levels of enantioselectivity that are often realised with these
ostensively monodentate ligands are not expected if free ro-
from ferrocene by Kagan’s method by use of the known
[
7]
Andersen sulfoxide (Scheme 1). All of the ligands in this
paper could be prepared in either enantiomeric series, but
are shown throughout as originating from natural -men-
thol for consistency. The planar chirality of the ferrocenes
is assigned in agreement with Schlögl’s modified method.[
tation about the P–Mcat bond in the active catalyst [L Mcat-
n
P(OR) (NR )] is present. Recently, it has been suggested
2
2
that phosphoramidites can attain a (P,C=C) chelate coordi-
nation mode A in certain reactions including: nickel-cata-
8]
[3]
lysed alkene dimerisation, ruthenium-catalysed cyclopro-
[
4]
Stereoselective lithiation and trapping with B(OMe)
3
allows
)-2 using literature procedures. Optimal
coupling of (R S )-2 with suitable ArX (X = I, Br) occurred
panation and nickel-promoted additions of AlMe to al-
3
[
9]
[
5]
access to (R S
p c
dehydes. In connection with the latter, we were interested
in providing supportive evidence for a (P,C=C) contact and
simultaneously in discovering new ligands both for this pro-
cess and others. We believed that the ferrocene fragment B
should be an analogue of A and set out to synthesise suit-
able examples of this ligand type, which we called “ferro-
phites”. Throughout this manuscript (R) planar, axial and
centrosymmetric stereochemical chemistry are distin-
guished by the descriptors (R ), (R ) and (R ), respectively,
p
c
with 8 mol-% Pd(dppf)Cl and sodium hydroxide pro-
2
[
9]
motion at reflux within 4 hours to give good yields for
both sterically encumbered and electron-deficient aryl ha-
lides (R S )-3a–c (Scheme 1). Other catalyst systems,
p
c
[10]
including Pd(PPh ) /CsF and Pd(OAc) /X-Phos
/
3
4
2
K PO ·H O, were ineffective. It was not possible to prepare
3
4
2
an electron-rich aryl derivative by using 4-(MeO)C H I un-
6
4
p
a
c
der any of these conditions. For example, the use of
for clarity.
Pd(dppf)Cl led only to low yields of (R S )-3a by pre-
2
p c
sumed phenyl transfer from the dppf ligand. This is in con-
trast to the work of Johannsen who was able to couple 2-
(
MeO)C H I to (R S )-2 using a closely related methodol-
6 4 p c
ogy. In accordance with literature results the formation of
R S )-3a from (S )-1 proceeds with very high selectiv-
(
ity.
p
c
c
[
6,11]
The sulfoxide auxiliary of (R S )-3a was cleaved under
p
c
[
6]
Kagan’s conditions to afford the derived organolithium
[
a] School of Chemistry, The University of Nottingham,
species (S )-4a (Scheme 2). The change in stereochemical
descriptor is caused only by the peculiarities of the CIP
nomenclature (C has greater priority than Li). Such species
p
Nottingham NG7 2RD, UK
Fax: +44-115-951-3564
E-mail: simon.woodward@nottingham.ac.uk
Eur. J. Org. Chem. 2006, 2549–2557
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2549

V. E. Albrow, A. J. Blake, R. Fryatt, C. Wilson, S. Woodward
FULL PAPER
efficient and clean routes to PMe3[14] chemistry that can be
extended to the use of MeLi. We speculated that the equiva-
lent reaction of (S )-4a with P(OPh) would favour the for-
p
3
mation of the desired ferrophite ligand (R )-7a. Indeed, ad-
p
dition of P(OPh) to organolithium species (S )-4a resulted
3
p
in an almost immediate (Ͻ2 min at –78 °C) colour change
in the reaction mixture from deep orange-red to pale
orange-yellow, in contrast to the inefficient chlorophosphite
reactions. On workup the desired product (R )-7a was iso-
p
lated as an orange oil (69%). Compounds (R )-7b,c were
p
similarly prepared in 33 and 56% yield, respectively
(Scheme 2).
We were encouraged by these results to attempt the
equivalent reaction of the anions 4a–c, both with 1,1-bi-
naphthol- and 1,1-biphenol-derived phosphites. The precur-
sor phosphites were easily prepared by the reaction of PCl3
with the appropriate diol in the presence of NEt , to yield
3
the chlorophosphites 6b–c (Scheme 3). Subsequent addition
of phenol and further NEt allowed the isolation of 5b–c in
moderate yield (53–74% based on the diol) after column
3
Scheme 1.
chromatography on silica. Compounds 5 were used within
are known to react readily and stereospecifically with chlo- 72 hours and handled under inert atmosphere when in solu-
rophosphanes R PCl (R = Ph, c-C H ). However, the reac- tion, as they are sensitive to hydrolysis to phosphorus()
2
6
11
tion of (S )-4a with chlorophosphite (RO) PCl species species.
p
2
proved very inefficient, at best only traces of the desired
Reaction of 5b–c with the organolithiums 4a–c pro-
product, even after prolonged heating of the reaction mix- ceeded in a modular fashion to complete a small library
tures, were attained. This seems to be a general problem in of ferrophite ligands (Scheme 2). Overall, compounds 8–10
the preparation of ferrocenyl-based phosphites,[ as pub- were isolated in 8–71% yield depending on the workup con-
lished literature procedures to these compounds are few and ditions. Some of the ligands showed appreciable sensitivity
12]
normally involve the preparation of reactive PCl -function- to acid-catalysed hydrolysis in the order 7 Ϸ 9 Ͻ 8 Ͻ 10
2
alised ferrocenes prior to subsequent reaction with with (R R )-9a being particularly robust but (R S )-10a be-
p
a
p a
[
13]
alcohols.
Some time ago, Luetkens et al. reported that ing very easily hydrolysed. It is of note that the dia-
the reaction of MeMgX with P(OPh) is one of the most stereomeric (S ) axial compounds 10 had to be chromato-
3
a
Scheme 2.
550
2
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Eur. J. Org. Chem. 2006, 2549–2557

Aryl Ferrophites – A New Class of Ligands for Asymmetric Catalysis
FULL PAPER
thermodynamically favoured (R R )-9c (Scheme 4). It is
p
a
likely that the formation of the other ferrophites proceeds
through a similar mechanism, but in these cases the acid-
catalysed rearrangements are much faster and these are at-
tained within minutes in the presence of the phenol gener-
ated upon aqueous quench of the reaction mixture.
Scheme 3.
Scheme 4.
Crystallographic Studies: While the H, 13C NMR spec-
tra of the compounds 7–10 were in agreement with the pro-
posed structures, the 31P NMR shifts (δP = 173.4–206.3
ppm) were somewhat higher than what we initially antici-
pated for these compounds. To ensure that the correct con-
nectivity had been realised, crystallographic studies were
carried out on compounds (R )-8a, (R R )-9a, (R R )-9c
1
graphed on basic alumina to avoid complete decomposi-
tion, and that only (R S )-10b was isolated in analytically
p
a
pure form after further crystallisation. Removal of the phe-
nol by-product from the crude reaction mixtures dramati-
cally improves the sample stabilities as this acts as a proton
source (pK 10.0), catalysing the hydrolytic transformation
a
p
p
a
p a
of Fc-P(OR) to Fc-PH(=O)(OR) (Fc = ferrocenyl frag-
2
and (R S )-10b and their structures are shown in Figure 1,
p
a
ment). The sensitivity of the ligands to hydrolysis accounts
Figure 2, Figure 3 and Figure 4 together with selected bond
length and angle data.
for the low yields of compounds (R )-8b (15%) and (R S )-
p
p a
1
0b (8%) as in all cases, monitoring the reaction mixtures
1
by H NMR spectroscopy and TLC indicated that the ini-
tial formation of the ligand was clean and rapid.
Mechanism for the Formation of the Ligands: Given the
dramatic rate difference in the reaction of the anion (S )-4
p
with P–OPh vs. P–Cl bonds, the coupling of 4c with (R )-
a
5c was closely monitored as this pair reacted somewhat
more slowly than the rest (although the coupling was still
fast and efficient). The selective formation of an initial in-
termediate was evident by TLC (R = 0.12, 4:1 hexane/
f
Et O). On quenching the reaction mixture slowly evolved,
2
and the intermediate was replaced by a new product (R =
f
0.44), later identified as the previously isolated final product
(
R R )-9c by both spectroscopic and crystallographic tech-
p
a
niques. Repeated attempts to crystallise the initial kinetic
product were unsuccessful and led only to its decomposi- Figure 1. View of molecular structure of (R )-8a with ellipsoids
p
drawn at 50% probability level. Selected bond lengths and angles:
P1–C2 1.809(2), P1–O1 1.6575(13), P1–O2 1.6671(14), C1–C11
tion. It could be confirmed that conversion of the interme-
diate required the presence of acid, as deliberate addition
1
.483(3) Å; C1–C2–P1 124.38(14), C2–P1–O1 102.28(7), C2–P1–
of traces of HCl to C D solutions led to very rapid forma-
6
6
O2 94.31(8)°.
1
13
13
tion of (R R )-9c. Spectroscopic studies ( H-, C-,
P
p
a
NMR) of the crude (R = 0.12) intermediate revealed the
In the structure of (R )-8a, the biphenyl unit adopts a
f
p
presence of two very similar species, both of which con- (R ) configuration in the solid state. This suggests perhaps
a
tained binaphthyl and aryl-ferrocene fragments, in an ap- that this configuration is the lowest energy atropisomer.
proximately 3:1 ratio. Crucially, the dry solution IR spectra This supposition is supported by the comparison of two
of the intermediate revealed the presence of a strong, sharp structures from the separate diastereomeric 1,1Ј-binaphthyl
–
1
ν(OH) stretch at 3542 cm . We believe that initial cleavage series: (R R )-9a vs. (R S )-10b. In the latter there is signifi-
p
a
p a
of one of the P–ONaphthyl bonds in (R )-5c, as it is at- cant steric congestion between the binaphthyl ring and the
a
tacked by the nucleophile (S )-4c followed by protonation aryl substituent which is avoided in the former. Relief of
p
with water, leads to the formation of (R R )-11 as a mixture this strain is likely to be the driving force for the facile hy-
p
a
of two epimers at phosphorus as an initial kinetic product. drolysis of compounds 10 and is the probable cause of our
Subsequent acid-catalysed elimination of phenol leads to inability to isolate compound (R S )-10a pure. In (R S )-
p
a
p a
Eur. J. Org. Chem. 2006, 2549–2557
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2551

V. E. Albrow, A. J. Blake, R. Fryatt, C. Wilson, S. Woodward
FULL PAPER
p a
Figure 2. View of molecular structure of (R R )-9a with ellipsoids
drawn at 50% probability level. Selected bond lengths and angles:
P–C2 1.804(2), P–O1 1.6581(14), P–O2 1.6680(15), C1–C11
1
9
.478(3) Å; C1–C2–P 122.45(14), C2–P–O1 102.91(8), C2–P–O2
6.19(8)°.
p a
Figure 4. View of molecular structure of (R S )-10b with ellipsoids
drawn at 50% probability level. Selected bond lengths and angles:
P–C2 1.8030(15), P–O1 1.6544(11), P–O2 1.6617(11), C1–C11
1
9
.489(2) Å; C1–C2–P 138.33(11), C2–P–O1 104.72(6), C2–P–O2
9.68(6)°.
interaction. We speculate that the higher stability of com-
pound 10b relative to compound 10a is due to this interac-
tion. As the ferrophites had been designed as analogues of
Feringa’s ligand (shown as its metal complex in structure
A) it is appropriate to compare their ground-state geome-
tries with that of the other ferrocenyl phosphites for which
crystallographic data are available: Feringa’s ligand itself,
Figure 3. View of molecular structure of one of the two indepen-
dent molecules of (R )-9c with ellipsoids drawn at 50% prob-
ability level. Selected bond lengths and angles: P–C2 1.797(3), P–
O1 1.663(2), P–O2 1.665(2), C1–C11 1.479(4) Å; C1–C2–P
[13b]
[12a]
Reetz’s 12
and Pastor’s 13
(Scheme 5). For the pur-
p a
R
poses of the comparison it is useful to define Cipso and the
two torsion angles φ and φ whose values for the separate
1
2
123.5(2), C2–P–O1 103.81(12), C2–P–O2 95.80(12)°.
ligands are given in Table 1.
The data of Table 1 suggests that the ferrophites should
0b, the centroid–centroid distance between the naphthyl present a structurally similar architecture to Feringa’s li-
ring C11–C20 and one of the binaphthyl rings C21–C30 is gand on metal binding, however there are notable differ-
1
3
1
.65 Å and the interplanar angle between the two rings is ences. The first difference between the ligands is, as ex-
5.2°. These are both in the range expected for a π stacking pected, the longer P–C2 bond length in the ferrophites com-
Scheme 5.
552
2
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Eur. J. Org. Chem. 2006, 2549–2557

Aryl Ferrophites – A New Class of Ligands for Asymmetric Catalysis
FULL PAPER
Table 1. Structural comparison of ferrophites with related ligands.
Compound
Code[a]
P–Cave [Å]
P–Oave [Å]
P···Cipso [Å]
φ
1
[°]
2
φ [°]
[
[
[
[
b]
b]
b]
b]
(
(
(
(
(
(
(
R
R
R
R
R
p
p
p
p
a
)-8a
–
–
–
–
1.8086
1.8038
1.799
1.803
1.802
1.805 (P–N)
1.659
1.6623
1.6631
1.662
1.658
1.664
1.656
1.663
3.418
3.372
3.426
3.767
–
–12.2
–17.0
–15.7
–12.6
–43.3
–53.3
–52.3
55.0
–54.1
54.5
R
R
a
)-9a
)-9b
a
S
a
)-10b
)-12
R
a
GEGQAK
NOPXAR
[
c]
S
a
S
a
)-13
–
[
d]
1
60.9 (Cipso1)
112.7 (Cipso2)
45.9–50.0
R
a
S
c
S
c
)-14
–
3.167 (Cipso
3.778 (Cipso
2.957–3.000
)
)
–52.2
2
“
Feringa”
a
–[e]
–
–
[e]
[e]
–
(R
S
c
S
c
)-A
[
a] Cambridge Crystallographic Database code. [b] This publication. [c] Crystallised from a racemate. [d] Coordinates via personal com-
[4]
[4]
munication W. Leitner (see also ref. ). [e] Range seen for calculated intermediates (B1, B2, C1, C2; structure A M = Ni) in ref. .
pared with the P–N bond length in Feringa’s ligand. Ad- catalysed asymmetric 1,4-reactions are not very well under-
ditionally, the torsion angle φ is much smaller in the ferro- stood. The flexibility seen by Feringa’s ligand is in contrast
1
phites as C1–C2 is conformationally locked in the cyclopen- to the more rigid structure of the ferrophite ligands. Only a
tadienyl ring. Although the two differences (bond length vs. few P,C=C coordination modes have been determined ex-
torsion angle) could potentially cancel each other out, the
Table 2. Selected ligand comparisons in AlMe
3
1,2-addition to
overall difference between the ferrophites and Feringa’s li-
gand is an increased P···Cipso distance in the ferrophite fam-
ily, which consequently suggests a longer, and therefore
weaker, C=C···M binding mode in catalysis. However, di-
rect comparison with the free Feringa ligand 14 cannot be
PhCHO.[
a]
2
taken as representative of that in a putative η -P,C=C bind-
ing mode in the metal complexes. We therefore also com-
pared the ferrophite ligand geometries with those calculated Entry Ligand
for motif A [M = Ni] by Hölscher and Leitner.[ In these
Yield/%
ee [%]
4]
1
2
3
4
5
6
7
(R
a
S
c
S
c
)-Feringa 14
60
96
92
76
96
90
92
16
28
49
73
55
77
calculated structures φ1 is reduced compared to free 14
leading to a reduced Cipso···P distance, significantly smaller
than in our ferrophite ligands. We therefore predicted that
the ferrophites would not be quite as effective in nickel ca-
talysis as the parent Feringa ligand. In the case of copper
catalysis a bimetallic intermediate is thought to occur, and
therefore, the increased P···Cipso distance might now be an
(R )-8a [Ph, biphenyl]
p
(R
p
(R
p
(R
p
(R
p
(R
p
)-8b [1-Nap, biphenyl]
, biphenyl]
3 6 4
)-8c [CF C H
R
a
R
a
R
a
)-9a [Ph, binaphthyl]
)-9a [1-Nap, binaphthyl]
3 6 4
)-9c [CF C H , binaphthyl] 95
[
a] Addition of 2 equiv. of AlMe
L in THF at –20 °C followed by 3 hours reaction at this tempera-
3 2
to benzaldehyde and Ni(acac) /
advantage; although the transition states in most copper- ture. Yield by GC against internal standard, ee by chiral GC.
Table 3. Selected ligand comparisons in organoaluminium 1,4-addition to cyclohexenone.[a]
Entry
Ligand
Cu source
CuTC
Yield/%
ee/%
A. AlEt
3
1
2
3
4
5
(R
a
S
c
S
c
)-Feringa 14
76
92
77
58
78
88
59
92
78
87
(Rp)-8a [Ph, biphenyl]
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
2
2
2
2
(RpRa)-9a [Ph, binaphthyl]
(RpRa)-9b [1-Nap, binaphthyl]
(R
p
a 3 6 4
R )-9c [CF C H , binaphthyl]
2
B. Me AlCH=CMe(Ph)
6
7
(R
(R
a
S
R
c
S
c
)-Feringa 14
54
75–76
85
[
b]
p
a
)-9a [Ph, binaphthyl]
[
a] Addition of 1.4 equiv. of AlMe
3
to 2-cyclohexenone and Cu salt/L in Et
2
O at –30 °C followed by 20 min reaction at this temperature.
[16]
Yield by GC against internal standard, ee by chiral GC. [b] Comparable to that of ref.
Eur. J. Org. Chem. 2006, 2549–2557
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2553

V. E. Albrow, A. J. Blake, R. Fryatt, C. Wilson, S. Woodward
plicitly by X-ray diffraction: M–C contacts with the alkene ses were performed on silica gel, Davisil and Merck Silicagel 60
FULL PAPER
[
15]
F254+366, respectively, or on basic alumina, Acros aluminium oxide,
activated, basic, 50–200. Tetrahydrofuran was freshly distilled un-
der argon from sodium and benzophenone or for larger-scale reac-
tions was degassed and passed through a column of activated alu-
mina. Petroleum ether refers to the fraction with b.p. 40–60 °C. All
other reagents were used as received without further purification.
The sulfoxide 1 was prepared in the (R) configuration by the meth-
carbon atoms in the range 2.3–2.6 Å are the norm,
but
this is of course on the derived metal complexes and not a
structural parameter of the free ligand.
Catalytic Studies: The efficacy of the new ferrophite li-
gands was ascertained by testing them in two reactions:
nickel-catalysed addition of AlMe3 to PhCHO (Table 2)
and copper()-catalysed additions of organoaluminium rea-
gents to enones (Table 3). The enantioselectivities realised cording to literature procedures.[
with the ferrophite ligands in the 1,2-additions were lower
than those attained with the optimal (R S S )-Feringa li-
[6]
odology of Kagan. Compounds 2, 3a and 3c were prepared ac-
9a]
p p a
Crystallographic Data: Yellow-orange crystals of (R )-8a, (R R )-
a
c c
9
a, (R
ether and (R
data were collected using graphite-monochromated Mo-K
p
R
a
)-9c were grown from dichloromethane/light petroleum
)-10b from benzene. All single crystal diffraction
X-radi-
gand 14 (compare Entries 1 vs. 2–7), although the yields
were notably increased. However, the significant ee values
p a
S
α
from the ligands (R R )-9a and (R R )-9c might be taken ation with either a Bruker SMART APEX (8a) or a SMART 1000
p
a
p a
as supportive of a putative C=C···Ni contact in the selective (9a, 9c, 10b) CCD-area detector diffractometer equipped with an
Oxford Cryostream cooling device. All data were collected at
transition state of this reaction. Greater success was at-
150 K. Details of the individual data collections and refinements
tained in asymmetric conjugate addition of organoalumin-
ium reagents to enones. In this case, the greater rigidity of
the ferrophite ligands engendered improved enantio-
selectivities over the Feringa phosphoramidite 14 (Table 3,
Entry 1 vs. 2–5). This was particularly noticeable in our
asymmetric carboalumination-conjugate addition pro-
are given in Table 1. All structures were solved by direct methods
using SHELXS-97 for 8a and SIR-92 for 9a, 9c and 10b. All struc-
tures were refined by least-squares full-matrix refinement against
2
F using SHELXL-97 and all non-H atoms refined with anisotropic
atomic displacement parameters (ADPs). Hydrogen atoms were ge-
ometrically placed and refined as part of a riding model. All atoms
were refined as described above except for the atoms of the C H
5 5
[
16]
cedure,
where we were able for the first time to attain
synthetically useful enantioselectivity values (entries 6 vs. ring in 10b which were modelled over 2 sites with occupancies
7).
0.820(5) and 0.180(5), the minor disorder component of which was
refined with isotropic ADPs. Crystallographic data for all com-
pounds are summarised in Table 4.
Conclusions
CCDC-295725 to -295728 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/datarequest/cif.
A new class of chiral ferrocenyl-based phosphite (ferro-
phite) ligands has been prepared with the aim of mimicking
the π contacts thought to be realised in Feringa’s phos-
phoramidite ligand 14. The X-ray crystallographic data and
the catalytic performance of the ferrophites provide some
supportive evidence that such contacts are viable in the new
ligands class, but these will not be as strong as in the phos-
phoramidite 14. In nickel-catalysed 1,2-additions of AlMe3
to aldehydes the sense of stereoinduction is identical for
both ligand types despite their very different constitutions.
p c
(R S )-2-(Tolyl-4-sulfinyl)-1-(4-trifluoromethylphenyl)ferrocene
5
[
5 3 3 6 4
CpFe{η -1,2-C H (4-CF C H )[S(O)-4-Tol]}] (3c): To a mixture of
the boronic acid 2 (566 mg, 1.54 mmol), palladium(dppf)
dichloride·DCM (100 mg, 0.12 mmol), 4-bromobenzotrifluoride
(
0.31 mL, 2.30 mmol) and toluene (50 mL) under argon was added
sodium hydroxide (2 , 1.5 mL). The solution was heated at reflux
for 4 hours, then cooled and concentrated under reduced pressure.
The crude oil was purified by flash chromatography on silica gel
However, the difference in the degree of stereoselectivity (up (petroleum ether/ethyl acetate/dichloromethane, 7:2:1) to give the
to 77% ee for the ferrophites vs. 92% ee for the optimal product (608 mg, 84%) as an orange crystalline solid. M.p. 73–
7
1
=
C
2
5 °C. IR (CHCl
3
): ν˜ max = 2985.4 ν(CH), 1616.3, 1322.5, 1120.3,
phosphoramidite ligand) supports the suggestion that any
C=C···Ni contact engendered by the ferrophites is less
strong than in the Feringa parent. In asymmetric conjugate
addition of organoaluminium reagents to cyclohexenone,
the ferrophites outperform Feringa’s ligand 14 in the reac-
tions tried thus far suggesting that they will find utility in
this and other asymmetric reactions.
–
1 1
069.0 (br), 1040.2 ν(SO) cm . H NMR (400.1 MHz, CDCl
3
): δ
), 7.61 (d, J = 8.0 Hz, 2 H,
CF ), 7.27 (d, J = 8.0 Hz,
Me), 4.74 (app. dd, J = 2.6, 1.5 Hz, 1 H, C ), 4.49
), 4.27 (app. dd, J = 2.6, 1.5 Hz, 1
7.89 (d, J = 8.0 Hz, 2 H, C
Me), 7.56 (d, J = 8.0 Hz, 2 H, C
H, C
6 4 3
H CF
6
H
4
6
H
4
3
6
H
4
5 3
H
(
app. t, J = 2.6 Hz, 1 H, C
H, C ), 4.22 (s, 5 H, C
NMR (100.6 MHz, CDCl
5 3
H
13
5
H
3
5
H
5
), 2.42 (s, 3 H, C
): δ = 141.4, 140.4 (br), 139.8, 129.9,
29.3, 129.1 (q, J = 32 Hz), 125.4, 125.3 (q, 273 Hz), 125.0 (q,
6
H
4
Me) ppm.
C
3
1
4
1
9
Hz), 93.0, 87.4, 72.2, 71.4, 70.8, 69.8, 21.4 ppm. F NMR
Experimental Section
3
(282 MHz, CDCl ): δ = –63.0 ppm. MS (ES): m/z (%) = 469 (10)
+
+
[
+
M + H] , 330 (70) [M + H – S(O)tol] . HRMS (ES):m/z found [M
General: All reactions involving air sensitive reagents were carried
out under argon using standard Schlenk techniques and glassware
was flame-dried before use. The spectrometers and other instru-
mentation used were as described previously.[ Fluorine NMR
+
H] 469.0516. C24
20 3 19 3
H F FeOS requires 469.0536. C24H F FeOS
(
468.32): calcd. C 61.55, H 4.09; found C 61.55, H, 4.22.
17]
General Procedure for the Preparation of Phosphites. Biphenyl Phos-
phite 5b: Under argon, a mixture of biphenol (1.30 g, 6.98 mmol)
and THF (10 mL) was cooled to –40 °C. To this solution was added
a solution of phosphorus trichloride (0.98 mL, 11.2 mmol) in THF
(9 mL). After 10 min, triethylamine (1.95 mL, 14.0 mmol) was
3
shifts were referenced to CFCl and phosphorus NMR shifts to
phosphoric acid. Potential C–P couplings in the aromatic region
of the carbon NMR spectra have not been listed due to spectral
congestion in this region. Column chromatography and TLC analy-
2554
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2549–2557

Aryl Ferrophites – A New Class of Ligands for Asymmetric Catalysis
FULL PAPER
Table 4. Crystal data for the ligands.
Complex
(R
p
)-8a
21FeO
476.27
(R
p
R
a
)-9a
(R
p
R
a
)-9c
FeO
(R
p
S
a
)-10b
27FeO
626.44
Empirical formula
C
28
H
2
P
C
36
H
25FeO
2
P
C
37
H
24
F
3
2
P
C
40
H
2
P
M
r
576.38
644.38
Cell setting, space group
orthorhombic, P2
1
2
1
2
1
monoclinic, P2
10.0407(11)
12.1436(13)
11.8433(13)
90
1
monoclinic, P2
11.2927(9)
11.9410(9)
22.073(2)
90
1
1 1 1
orthorhombic, P2 2 2
a [Å]
b [Å]
c [Å]
α [°]
9.9774(7)
10.7344(8)
20.7562(15)
90
11.5113(7)
14.7877(8)
17.0437(10)
90
β [°]
90
90
2223.0(3)
4
1.423
100.412(2)
90
1420.3(5)
2
1.348
0.62
96.277(2)
90
2958.6(7)
4
1.447
0.62
90
90
2901.3(5)
4
1.434
γ [°] 3
V [Å ]
Z
–3
D
x
[Mg·m ]
–1
µ (Mo-K ) [mm ]
α
0.77
0.61
Temperature [K]
Crystal form, colour
Crystal size [mm]
150(2)
block, orange
0.50 × 0.39 × 0.26
150(2)
block, orange
0.78 × 0.65 × 0.63
0.819, 1.000
150(2)
150(2)
block, orange
0.66 × 0.59 × 0.50
0.826, 1.000
column, orange
0.56 × 0.26 × 0.18
–
T
min, Tmax
0.707, 0.818
No. of measured, independent and 11902, 5021, 4873
8733, 5688, 5123
31692, 13311, 10376
26455, 6652, 6309
observed reflections I Ͼ 2σ(I)
R
int
0.018
0.014
0.054
0.017
θ
max [°]
27.5
27.6
27.6
27.6
2
2
2
R[F Ͼ 2σ(F )], wR(F ), S
No. of relections
0.029, 0.072, 1.06
5021
0.028, 0.070, 1.02
5688
0.040, 0.092, 0.98
13311
0.024, 0.062, 1.03
6621
No. of parameters
289
0.001
0.33, –0.19
–0.015(12)
362
0.001
0.38, –0.17
0.007(11)
794
0.003
0.58, –0.28
0.00(1)
419
0.002
0.32, –0.15
0.003(9)
(
∆/σ)max
max, ∆ρmin [e·Å ]
Flack parameter
–
3
∆
ρ
added, and the reaction mixture warmed to room temperature. Af-
ter a further 4 hours the mixture was filtered through a frit and
concentrated under reduced pressure. The mixture was then diluted
with THF (50 mL) followed by addition of triethylamine (1 mL,
and concentrated under reduced pressure. Purification by flash
chromatography on silica gel (petroleum ether/Et O, 9:1) afforded
69 % of (R )-7a as an orange oil. IR (CHCl ): ν˜ max = 1593.3,
1488.1, 1162.4, 1106.5, 1071.8, 1023.8, 1001.4, 876.7 cm . H
NMR (400.1 MHz, C ): δ = 7.96 (dd, J = 7.2, 1.2 Hz, 2 H, Ph-
o), 7.45 (dd, J = 7.6, 1.2 Hz, 2 H, Ph-o), 7.32–6.85 (m, 11 H, Ph-
2
p
3
–
1 1
7
.16 mmol) and phenol (470 mg, 5.00 mmol). After 1 hour the mix-
ture was evaporated to dryness. The product was purified by flash
chromatography on silica gel (petroleum ether/Et O, 9:1, dry
loaded) to give the product (1.20 g, 56% based on biphenol) as a
6 6
D
2
m+p), 4.88 (m, 1 H, C
2.4 Hz, 1 H, C ), 4.12 (s, 5 H, C
(100.6 MHz, C
5
H
3
), 4.60 (m, 1 H, C
5
H
3
), 4.27 (app. t, J =
1
3
5
H
3
5
H
5
) ppm. C NMR
1
white solid. H NMR (400.1 MHz, CDCl
1
7
3
): δ = 7.54 (d, J = 1.5 Hz,
H, Ar), 7.52 (d, J = 1.5 Hz, 1 H, Ar), 7.43–7.31 (m, 6 H, Ar),
.27–7.16 (m, 5 H, Ar) ppm. 31P NMR (162 MHz, CDCl
144.9 ppm. Used immediately as attained.
6
D
6
): δ = 156.6, 156.5, 154.9, 154.8, 152.0, 138.3,
130.0, 129.8, 129.6, 129.5, 129.4, 126.9, 124.2, 123.5, 123.3, 121.2,
): δ = 121.2, 121.0, 120.9, 119.3, 119.2, 92.4 (d, J = 20 Hz), 76.2 (d, J =
15 Hz), 73.3 (d, J = 3.0 Hz), 71.0 (d, J = 2.4 Hz), 70.7 (d, J =
3
+
3
1
1
6 6
.8 Hz), 70.5 (5 C) ppm. P NMR (162 MHz, C D ): δ = +174.3
Binaphthyl Phosphite 5c: Compound 5c was prepared according to
the general procedure. Purification by flash chromatography on sil-
+
+
ppm. MS (ES): m/z (%) = 479 (70) [M + H ], 385 (30) [M – OPh ],
62 (100) [M + H – P(OPh)
+
+
2
2
] . HRMS (ES): m/z found [M + H]
ica gel (petroleum ether/Et
2
O, 9:1, dry loaded) afforded 74% of 5c
as a white solid. H NMR (500.1 MHz, CDCl ): δ = 8.01 (d, J =
.0 Hz, 1 H, Ar), 7.96–7.92 (m, 3 H, Ar), 7.58 (d, J = 9.0 Hz, 1 H,
Ar), 7.48–7.34 (m, 7 H, Ar), 7.32–7.75 (m, 2 H, Ar), 7.20 (d, J =
1
479.0872. C28
chloroform).
H24FeO
2
P requires 479.0863.[α] = –68.5 (c = 0.89,
D
3
9
)-2-(Diphenoxyphosphanyl)-1-(1-naphthyl)ferrocene [CpFe{η5-
(R
p
3
8
(
1
1
.5 Hz, 2 H, Ar), 7.17 (t, J = 7.0 Hz, 1 H, Ar) ppm. 1 C NMR
100.6 MHz, CDCl ): δ = 131.7, 131.3, 130.5, 129.9, 129.8 (2 C),
28.4, 128.3, 127.1, 127.0, 126.4, 126.2, 125.3, 125.0, 124.3, 121.7,
20.4, 120.3 ppm. 31P NMR (162 MHz, CDCl
): δ = +146.1 ppm.
1
,2-C
according to the general procedure. Purification by flash
chromatography on basic alumina (petroleum ether/Et O, 9:1) af-
forded 33% of (R )-7b as an orange oil. IR (CHCl ): ν˜ max = 1593.9,
489.5, 1382.0, 1162.1, 1107.9, 1071.6, 1023.8, 1002.7, 876.2 cm .
5 3 8 2
H (1-C10H )[P(OPh) ]}] (7b): Compound 7b was prepared
3
2
3
p
3
Used immediately as attained.
–1
1
1
General Method for Incorporation of the Phosphite. (R
p
)-2-(Diphen-
(Ph){P-
})] (7a): A solution of the sulfoxide 3a (80 mg, 0.20 mmol)
in THF (1 mL) was cooled to –78 °C under argon, then tBuLi
H NMR (500.1 MHz, C
), 8.20 (d, J = 8.0 Hz, 1 H, C10
7.47 (dd, J = 8.5, 7.5 Hz, 1 H, C10
7.17–7.11 (m, 2 H, Ph-m), 6.94 (t, J = 7.5 Hz + unresolved long
1.7  in hexanes, 0.13 mL, 0.22 mmol) was added. After 5 minutes range couplings, 1 H, Ph-p), 6.90–6.84 (m, 2 H, Ph-m), 6.75 (t, J =
6
D
6
): δ = 8.46 (dt, J = 7.0, 1.0 Hz, 1 H,
), 7.77–7.73 (m, 2 H, Ar),
), 7.35–7.24 (m, 4 H, Ar),
5
oxyphosphanyl)-1-phenylferrocene [CpFe(η -1,2-C
OPh)
5
H
3
C
10
H
7
H
7
H
7
(
2
(
triphenyl phosphite (5a) (58 µL, 0.22 mmol) in THF (0.5 mL) was
added, and an instant colour change from dark orange to yellow
was observed. After 5 minutes the reaction was quenched by drop-
7.5 Hz + unresolved long range couplings, 1 H, Ph-p), 6.66 (d, J =
8.5 Hz, 2 H, Ar), 4.96 (app. dd, J = 1.0, Ϸ 0.6 Hz, 1 H, C ),
4.52 (app. q, J = 2.1 Hz, 1 H, C ), 4.35 (app. t, J = 2.5 Hz, 1 H
5
H
3
5
H
3
1
3
wise addition of H
2
O (1 mL) and warmed to room temperature.
C
5
H
3
), 4.29 (s, 5 H, C
5 5 6 6
H ) ppm. C NMR (125.8 MHz, C D ): δ
The phases were separated and the organic layer dried (MgSO
4
)
= 156.8, 156.7, 155.3, 134.2. 134.1, 134.0, 130.5, 130.4, 130.0, 129.3,
Eur. J. Org. Chem. 2006, 2549–2557
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2555

V. E. Albrow, A. J. Blake, R. Fryatt, C. Wilson, S. Woodward
FULL PAPER
1
1
4
28.5, 128.3, 126.7, 126.1, 126.0, 125.3, 123.4, 123.3, 120.9, 120.8,
4.40–4.38 (br. m, 1 H, C
5
H
3
), 4.33 (s, 5 H, C
5
H
5
), 4.26 (app. t, J =
) ppm. C NMR (100.6 MHz, C ): δ = 155.0,
131.2, 130.6, 129.8, 129.3, 127.2, 126.4, 125.9, 125.8, 125.7, 125.2,
): δ = +177.9 ppm. MS (ES): m/z (%) = 125.0, 124.4, 122.6, 122.0, 121.0, 120.6, 75.7, 71.3, 71.2, 70.7 (5 C),
1
3
19.6, 119.5, 93.3 (d, J = 27 Hz), 80.0 (d, J = 14 Hz), 75.1 (d, J =
2.0 Hz, 1 H, C
5
H
3
6 6
D
3
1
.5 Hz), 70.5, 70.2 (d, J = 2.0 Hz), 70.0 (d, J = 3.0 Hz) ppm.
P
NMR (121.5 MHz, C
5
6
D
6
+
+
31
6 6
29 (35) [M + H] , 435 (50) [M – OPh] , 312 (10) [M + H – 69.8 ppm. P NMR (121.5 MHz, C D ): δ = +206.3 ppm. MS
+
+
+
+
2
P(OPh) ] . HRMS (ES): m/z found [M + H] 529.1023. (ES): m/z (%) = 527 (100) [M + H] , 526 (5) [M] , 312 (100) [M +
C
form).
+
+
32
H26FeO
2
P requires 529.1020. [α]
D
= –180.5 (c = 1.99, chloro-
H – P(O
24FeO
form).
2
C
12
H
8
)] . HRMS (ES): m/z found [M + H] 527.0863.
C
32
H
2
P requires 527.0863. [α] = –209.0 (c = 1.00, chloro-
D
p
(R )-2-(Diphenoxyphosphanyl)-1-(4-trifluoromethylphenyl)ferrocene
5
[
5 3 3 6 4 2 p a
CpFe{η -1,2-C H (4-CF C H )[P(OPh) ]}] (7c): Compound 7c (R R )-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]biphenalen-4-
5
was prepared according to the general procedure. Purification by yl)-1-(4-trifluoromethylphenyl)ferrocene [CpFe{η -1,2-C
flash chromatography on silica gel (petroleum ether/Et O, 19:1) af- CF )[P(O )]}] (8c): Compound 8c was prepared accord-
forded 56% of (R )-7c as an orange oil. IR (CHCl ): ν˜ max = 1616.1, ing to the general procedure. Purification by flash chromatography
593.1, 1488.3, 1161.8, 1122.9, 1106.0, 1069.4, 1024.2, 1001.7, on silica gel (petroleum ether/Et O, 19:1) afforded 26% of (R )-
): δ = 7.67 (d, J = 8.0 Hz, 8c as an orange crystalline solid. M.p. 73–75 °C. IR (CHCl ): ν˜ max
5 3
H (4-
2
3
C
6
H
4
2 12 8
C H
p
3
1
8
2
6
2
p a
R
–1 1
77.7 cm . H NMR (400.1 MHz, C
H, Ph-o), 7.35–7.29 (m, 4 H, Ar), 7.12–7.08 (m, 2 H, Ar), 6.98– = 1615.8, 1325.5, 1165.7, 1120.8, 1096.4, 1069.3, 889.9 cm . 1H
.91 (m, 4 H, Ar), 6.90–6.86 (m, 1 H, Ph-p), 6.80–6.77 (m, 1 H, NMR (400.1 MHz, C ): δ = 7.69 (d, J = 8.0 Hz, 2 H, C CF ),
), 4.38 (m, 1 H, C ), 4.15 (app. t, J = 7.32 (d, J = 8.0 Hz, 2 H, C CF ), 7.27 (dd, J = 7.4, 1.9 Hz, 1
), 3.95 (s, 5 H, C H, biphenyl-H3 or 3Ј), 7.26 (dd, J = 7.5, 1.7 Hz, 1 H, biphenyl-H3
) ppm. 13 C NMR
): δ = 156.4, 156.3, 154.7, 142.7, 130.0, 129.5, or 3Ј), 7.19 (dt, J = 8.0, Ϸ 0.8 Hz, 1 H, biphenyl-H6 or 6Ј), 7.11
25.2 (2 C), 123.7, 123.5, 120.9, 120.8, 119.3, 119.3, 90.1 (d, J = (td, J = 7.5, 1.6 Hz, 1 H, biphenyl-H4,4Ј or 5,5Ј), 7.01 (tdd, J =
4 Hz), 76.5 (d, J = 19 Hz), 73.7 (d, J = 4 Hz), 71.6 (d, J = 4 Hz), 7.5, 1.6, Ϸ 0.8 Hz, 1 H, biphenyl-H4,4Ј or 5,5Ј), 6.95 (td, J = 7.5,
6
D
6
3
–
1
6
D
6
6
H
4
3
Ph-p), 4.75 (m, 1 H, C
.5 Hz, 1 H, C
100.6 MHz, C
5
H
3
5
H
3
6
H
4
3
2
(
1
2
7
5
H
3
5 5
H
6 6
D
31
1.0 (d, J = 2 Hz), 70.6 (5 C) ppm. P NMR (121.5 MHz, C
6
D
6
):
Ϸ 0.8 Hz, 1 H, biphenyl-H4,4Ј or 5,5Ј), 6.92 (td, J = 7.5, 1.6 Hz, 1
H, biphenyl-H4,4Ј or 5,5Ј), 6.77 (dd, J = 7.5, Ϸ 0.8 Hz, 1 H, bi-
19
δ = +173.4 ppm. F NMR (282 MHz, C
6
D
6
): δ = –62.3 ppm. MS
+
+
(ES) m/z (%) = 547 (35) [M + H] , 453 (50) [M – OPh] , 330 (10)
phenyl-H6 or 6Ј), 4.39 (m, 1 H, C
(app. t J = 2.4 Hz, 1 H, C ), overlapped by 4.02 (s, 5 H, C
ppm. C NMR (100.6 MHz, C ): δ 152.2, 151.6 (2 C), 142.4,
132.8 (2 C), 131.9, 130.0 (2 C), 129.6 (3 C), 129.0, 125.5 (2 C),
5 3 5 3
H ), 4.23 (m, 1 H, C H ), 4.03
+
]+
[M + H – P(OPh)
2
] . HRMS (ES): m/z found [M + H 547.0716.
5
H
3
5 5
H )
1
3
C
form).
29
H
23
F
3
FeO
2
P requires 547.0737. [α] = –37.2 (c = 1.01, chloro-
D
6
D
6
=
1
7
25.1 (q, J = 218 Hz), 124.9, 122.5, 122.2, 91.6 (d, J = 20 Hz), 74.8,
(
R
p
R
a
)-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]biphenalen-4-
31
4.3 (d, J = 34 Hz), 71.6, 71.5, 71.2 (5 C) ppm. P NMR
5
yl)-1-phenylferrocene [CpFe{η -1,2-C
Compound 8a was prepared according to the general procedure.
Purification by flash chromatography on silica gel (petroleum ether/
5
H
3
(Ph)[P(O
2
C
12
H
8
)]}] (8a):
19
(
6 6 6 6
121.5 MHz, C D ): δ = +203.7 ppm. F NMR (282 MHz, C D ):
+
+
δ = –62.3. MS (ES): m/z (%) = 545 (100) [M + H] , 544 (10) [M] ,
3
H] 545.0557. C29
1
+
30 (90) [M + H – P(O
2
C
12
H
8
)] . HRMS (ES) m/z found [M +
Et
solid. M.p. 147–149 °C. IR (CHCl
165.3, 1096.2, 1033.8, 1001.1, 884.4 cm . H NMR (400.1 MHz,
2
O, 19:1) afforded 49% of (R
p
R
a
)-8a as an orange crystalline
+
H
21
F
3
FeO
2
P requires 545.0581. [α] = –85.4 (c =
D
3
): ν˜ max = 1600.2, 1497.3, 1447.6,
.08, chloroform).
–1 1
1
C
2
6
D
6
): δ = 7.87 (d, J = 8.0 Hz, 2 H, Ph-o), 7.27 (dt, J = 7.6, 2.0 Hz,
(R )-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]dinaphthalen-
p a
R
5
H, Ar), 7.21–7.16 (m, 3 H, Ph-m + Ar), 7.12–7.06 (m, 2 H, Ar), 4-yl)-1-phenylferrocene [CpFe{η -1,2-C
5
3 2 20
H (Ph)[P(O C H12)]}]
7.00 (tdd, J = 7.5, 1.6, Ϸ 0.8 Hz, 1 H, biphenyl-H4,4Ј or 5,5Ј), 6.95
(9a): Compound 9a was prepared according to the general pro-
(td, J = 7.5, 1.1 Hz, 1 H, biphenyl-H4,4Ј or 5,5Ј), 6.89 (td, J = 7.4,
cedure. Purification by flash chromatography on silica gel (petro-
1
1
4
.8 Hz, 1 H, biphenyl-H4,4Ј or 5,5Ј), 6.77 (dd, J = 7.6, Ϸ 0.8 Hz,
H, biphenyl-H6 or 6Ј), 4.50 (m, 1 H, C ), 4.22 (m, 1 H, C ),
.08 (s, 5 H, C ), 4.03 (app. t, J = 2.0 Hz, 1 H, C
): δ = 152.4, 151.8 (2 C), 138.0, 133.0 (2
C), 132.0, 129.9, 129.8, 129.7, 129.6, 129.5, 128.9, 127.0, 125.2, = 8.7 Hz, 2 H, Ar), 7.75 (t, J = 8.7 Hz, 2 H, Ar), 7.65 (t, J =
leum ether/Et
talline solid. M.p. 218–220 °C. IR (CHCl
1360.0, 1324.5, 1106.5, 1070.3, 981.6, 950.0 cm
(500.1 MHz, C ): δ = 8.03 (d, J = 8.0 Hz, 2 H, Ph-o), 7.82 (t, J
2
O, 9:1) afforded 71% of (R
p
R
a
)-9a as an orange crys-
5
H
3
5
H
) ppm.
3
3
): ν˜ max = 1589.5, 1462.2,
1
3
–1 1
5
H
5
5
H
3
C
. H NMR
NMR (100.6 MHz, C
6
D
6
6 6
D
1
24.5, 122.6, 122.1, 93.8 (d, 21 Hz), 73.7, 71.6, 71.3, 70.9 (6 C, m)
7.5 Hz, 2 H, Ar), 7.62 (d, J = 8.7 Hz, 1 H, Ar), 7.34 (t, J = 8.0 Hz,
2 H, Ph-m), 7.31–7.22 (m, 3 H, Ph-p + Ar), 7.20 (d, J = 8.7 Hz, 1
carbon atom was not apparent. 3 P NMR
1
ppm, the CF
121.5 MHz, C
3
(
6
D
6
): δ = +205.2 ppm. MS (ES): m/z (%) = 477 (50)
H, Ar), 7.13–7.07 (m, 2 H, Ar), 4.60 (dd, J = 3.9, 2.0 Hz, 1 H,
+
+
+
13
[
M + H] , 476 (100) [M] , 262 (50) [M + H – P(O
2
C
12
8
H )] . HRMS
P requires
C
5
H
3
), 4.18 (s, 5 H, C
NMR (100.6 MHz, CDCl
133.0, 132.6, 131.6, 131.0, 130.5, 129.5, 129.4, 129.3, 128.4, 128.3,
5
H
5
), 4.00–3.98 (m, 2 H, C
5
H
3
) ppm.
C
+
(
ES): m/z found [M + H] 477.0747. C28
H
22FeO
2
3
): δ = 150.4, 150.3, 149.2, 149.1, 137.5,
4
77.0707. [α] = –149.8 (c = 1.00, chloroform).
D
1
1
27.0 (2 C), 126.8, 126.2, 126.0, 124.9, 124.6, 123.7, 123.6, 122.5,
p a
(R R )-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]biphenalen-4-
21.7, 93.7 (d, J = 27 Hz), 74.0 (2 C), 72.9, 72.5, 70.7 (5 C, m)
5
yl)-1-(1-naphthyl)ferrocene [CpFe{η -1,2-C
P(O )]}] (8b): Compound 8b was prepared according to the
general procedure. Purification by flash chromatography on silica
gel (petroleum ether/Et O, 9:1) afforded 15% of (R )-8b as an
orange crystalline solid. M.p. 191–192 °C. IR (CHCl ): ν˜ max
5
H
3
(1-C10
H
8
)-
31
3
ppm. P NMR (162 MHz, CDCl ): δ = +189.3 ppm. MS (ES):
m/z (%) = 577 (100) [M + H] , 576 (10) [M] , 262 (40) [M + H –
P(O C H12)] . HRMS (ES) m/z found [M + H] 577.0975.
2 20
[
2
C
12
H
8
+
+
+
+
2
p a
R
C
7
36
H
26FeO
5.01, H 4.37; found C 75.19, H 4.32. [α]
chloroform). X-ray crystal structure obtained.
2
P requires 577.1020. C36
H25FeO
2
P (576.41): calcd. C
3
=
D
= –386.0 (c = 1.00,
1
601.0, 1497.1, 1377.4, 1165.9, 1096.3, 890.7 cm–1. H NMR
1
(
400.1 MHz, C ): δ = 8.60 (d, J = 8.0 Hz, 1 H, Ar), 8.48 (d, J =
6 6
D
7
1
7
.2 Hz, 1 H, Ar), 7.79 (d, J = 8.0 Hz, 1 H, Ar), 7.74 (d, J = 8.0 Hz, (R
p a
R )-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]dinaphthalen-
5
H, Ar), 7.51–7.45 (m, 2 H, Ar), 7.42–7.35 (m, 2 H, Ar), 7.34–
4-yl)-1-(1-naphthyl)ferrocene [CpFe{η -1,2-C
[P(O 12)]}] (9b): Compound 9b was prepared according to the
general procedure. Purification by flash chromatography on silica
5 3 8
H (1-C10H )-
.28 (m, 2 H, Ar), 7.18 (td, J = 7.6, 1.2 Hz, 1 H, Ar), 7.11–7.06
),
2 20
C H
(m, 3 H, Ar), 6.99–6.95 (m, 1 H, Ar), 4.60–4.58 (br. m, 1 H, C
5
H
3
2556
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2549–2557

Aryl Ferrophites – A New Class of Ligands for Asymmetric Catalysis
FULL PAPER
+
gel (petroleum ether/Et
orange crystalline solid. M.p. 210–212 °C. IR (CHCl
589.5, 1462.9, 1372.1, 1327.3, 1108.1, 1070.3, 981.6, 950.0 cm .
2
O, 9:1) afforded 61% of (R
p
R
a
)-9b as an
MS (ES): m/z (%) = 667 (100) [M + H
H
[M + H
2
O + Na] , 645 (75) [M +
+
+
3
): ν˜ max
=
2
O] , 312 (20) [M + H – P(O
2
C
H
20
H
12)] . HRMS (ES): m/z found
–
1
O + H]+ 645.1307. C40
1
2
30FeO P requires 645.1277.
3
1
H NMR (400.1 MHz, C
6
D
6
): δ = 8.71 (d, J = 8.4 Hz, 1 H, Ar),
8
7
7
7
.52 (ddd, J = 7.2, 2.0, 1.2 Hz, 1 H, Ar), 7.82–7.73 (m, 6 H, Ar),
Acknowledgments
.68 (d, J = 8.8 Hz, 1 H, Ar), 7.62 (dd, J = 8.8, 0.4 Hz, 1 H, Ar),
.58 (d, J = 8.8 Hz, 1 H, Ar), 7.56 (dd, J = 6.8, 1.2 Hz, 1 H, Ar),
.50 (dd, J = 8.0, 7.2 Hz, 1 H, Ar), 7.43 (dd, J = 6.8, 1.2 Hz, 1 H,
This work was carried out as part of EU contract NMP3-CT-2003-
05267 (LIGBANK). One of us (V.A.) is grateful to the EPSRC
5
Ar), 7.30–7.24 (m, 3 H, Ar), 7.10 (dd, J = 6.8, 1.2 Hz, 1 H, Ar),
and the University of Nottingham for support of a studentship. We
are very grateful to Prof. W. Leitner and Drs. Markus Hölscher and
Giancarlo Franciò (University of Aachen) for sharing unpublished
data with us and for useful discussions. We thank Yvette Mata for
some preliminary catalytic studies.
7
.05 (dd, J = 6.8, 1.2 Hz, 1 H, Ar), 4.60 (app. dd, J = 3.6, 2.4 Hz,
H, C ), 4.30 (s, 5 H, C ), 4.10 (app. t, J = 2.4 Hz, 1 H,
), 4.00 (app. dd, J = 2.4, 1.2 Hz, 1 H, C
): δ = 150.8 (2 C), 149.9 (2 C), 134.2, 133.6 (2
C), 133.4 (2 C), 133.1, 131.8, 131.3, 130.7, 130.6, 129.5, 128.8,
1
C
5
H
3
5 5
H
1
3
5
H
3
5 3
H ) ppm. C NMR
6 6
(100.6 MHz, C D
1
1
7
28.5, 128.3, 127.2, 127.0, 126.4 (2 C), 126.2, 125.8, 125.7, 125.2,
24.8, 124.7, 123.0, 121.8, 94.1 (d, J = 30 Hz), 75.8 (d, J = 3.2 Hz),
[1] T. P. Yoon, E. N. Jacobsen, Science 2003, 299, 1691–1693.
[2] B. L. Feringa, Acc. Chem. Res. 2000, 33, 346–353.
[3] M. Hölscher, G. Franciò, W. Leitner, Organometallics 2004, 23,
5606–5617.
0.8, 70.7, 70.0, 65.7 ppm. 31P NMR (202.5 MHz, C
6
6
D ): δ =
+
+
189.0 ppm. MS (ES): m/z (%) = 627 (100) [M + H] , 626 (10)
+
+
[M] , 312 (10) [M + H – P(O
2
C
20
H
12)] . HRMS (ES) m/z found
+
[4] a) D. Huber, A. Mezzetti, Tetrahedron: Asymm. 2004, 15, 2193–
[
M + H] 627.1122. C40
H
28FeO
2
P requires 627.1176. [α] = –355.2
D
2
197; b) D. Huber, P. G. A. Kumar, P. S. Pregosin, A. Mezzetti,
(c = 1.00, chloroform).
IUPAC Int. Symp. OMCOS13: Book of Abstracts, 17–21 July
2005, P137.
p a
(R R
)-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]dinaphthalen-
5
[5] K. Biswas, A. Chapron, T. Cooper, P. K. Fraser, A. Novak, O.
Prieto, S. Woodward, Pure Appl. Chem. 2006, 78, 511–518.
4
-yl)-1-(4-trifluoromethylphenyl)ferrocene [CpFe{η -1,2-C
CF )[P(O 12)]}] (9c): Compound 9c was prepared ac-
cording to the general procedure. Purification by flash chromatog-
raphy on silica gel (petroleum ether/Et O, 9:1) afforded 44% of
)-9c as an orange crystalline solid. M.p. 236–237 °C. H
NMR (500.1 MHz, C ): δ = 7.86–7.83 (m, 3 H, Ar), 7.80 (d, J
8.2 Hz, 1 H, Ar), 7.77–7.75 (m, 2 H, Ar), 7.66–7.62 (m, 3 H, Ar),
5 3
H (4-
3
C
6
H
4
2 20
C H
[
[
[
6] O. Riant, G. Argouarch, D. Guillaneux, O. Samuel, H. B. Ka-
gan, J. Org. Chem. 1998, 63, 3511–3514 and references within.
7] J. M. Klunder, K. B. Sharpless, J. Org. Chem. 1987, 52, 2602–
2
1
p a
(R R
2604.
6
D
6
8] K. Schlögl, Top. Stereochem. 1967, 1, 39–91.
=
[9] a) J. F. Jensen, M. Johannsen, Org. Lett. 2003, 5, 3025–3028;
b) H. K. Cotton, F. F. Huerta, J.-E. Bäckvall, Eur. J. Org.
Chem. 2003, 2756–2763; c) J. F. Jensen, I. Søtofte, H. O.
Sørensen, M. Johannsen, J. Org. Chem. 2003, 68, 1258–1265;
d) H. L. Pedersen, M. Johannsen, J. Org. Chem. 2002, 67,
7
8
1
.47 (d, J = 8.2 Hz, 2 H, Ar), 7.31–7.27 (m, 2 H, Ar), 7.16 (d, J =
.7 Hz, 1 H, Ar), 7.11–7.07 (m, 2 H, Ar), 4.74 (dd, J = 3.7, 2.0 Hz,
H, C
5
H
3
), 4.13 (s, 5 H, C ), 4.00–3.98 (m, 2 H, C
5
H
5
5 3
H ) ppm.
13
C NMR (100.6 MHz, C D ): δ = 150.5, 150.6, 149.6, 149.6, 142.4,
6
6
7982–7994; e) H. L. Pedersen, M. Johannsen, Chem. Commun.
1
1
33.4, 133.3, 131.9, 131.3, 130.9, 129.6, 129.5, 128.6 (2 C), 127.2,
27.0, 126.6, 126.4, 125.4, 125.3, 125.0, 124.8, 22.6, 121.7, 91.2 (d,
1
999, 2517–2518.
[
10] X. Huang, K. W. Anderson, D. Zim, L. Jiang, A. Klapars, S. L.
Buchwald, J. Am. Chem. Soc. 2003, 125, 6653–6655.
11] V. Albrow, A. J. Blake, A. Chapron, C. Wilson, S. Woodward,
Inorg. Chim. Acta in press.
J = 26 Hz), 74.7 (d, J = 3.0 Hz), 71.6 (2 C), 71.4, 71.0 (5 C) ppm.
3
1
19
P NMR (162 MHz, CDCl
3
): δ = +187.6 ppm. F NMR
[
(282 MHz, C ): δ = –62.4 ppm. MS (ES): m/z (%) = 645 (30) [M
6 6
D
+
+
+
+
C
H] , 644 (20) [M] . HRMS (ES) m/z found [M + H] 645.0892.
[12] Preparation by the reaction of ferrocenyllithiums with chloro-
phosphite species appear limited to: a) S. P. Shum, S. D. Pastor,
G. Rihs, Inorg. Chem. 2002, 41, 127–131 (compound 6, 48%);
b) A. Alexakis, J. Burton, J. Vastra, C. Benhaim, X. Fournioux,
A. van der Heuvel, J.-M. Levêque, F. Masé, S. Rosset, Eur. J.
Org. Chem. 2000, 4011–4027 (compound 35, 23%); c) A. Togni,
in: Metallocenes – Synthesis Reactivity Applications (Eds.: A.
Togni, R. L. Halterman), Wiley-VCH, Weinheim, 1998, vol. 2,
chapter 11 (compound 15, no yield given).
37
H
25FeF
3
O
2
P requires 645.0894. C37
H
25FeF
3
O
2
P (644.40):
calcd. C 68.96, H 3.75; found C 68.57, H 3.77. [α]
.00, chloroform).
D
= –285.8 (c =
1
p a
(R S )-2-(3,5-Dioxa-4-phosphacyclohepta[2,1-a;3,4-aЈ]dinaphthalen-
5
4
-yl)-1-(1-naphthyl)ferrocene [CpFe{η -1,2-C
5 3 8
H (1-C10H )-
[P(O
2
C
20
H12)]}] (10b): Compound 10b was prepared according to
the general procedure. A portion (250 mg) of the crude reaction
mixture was purified by flash chromatography on basic alumina
[
13] a) M. T. Reetz, A. Gosberg, D. Moulin, Tetrahedron Lett. 2002,
4
3, 1189–1191; b) M. T. Reetz, A. Gosberg, R. Goddard, S.-
(
petroleum ether/Et
pound and the proton-quenched product. Recrystallisation of the
mixture (benzene) led to pure (R )-10b as orange crystals (40 mg,
%). The remainder of the crude reaction mixture by flash
2
O, 4:1) to afford a mixture of the target com-
H. Kyung, Chem. Commun. 1998, 2077–2078; c) I. E. Nifant’ev,
L. F. Manzhukova, M. Yu. Antipin, Yu. T. Struchkov, E. E. Ni-
fant’ev, Zhurnal Obshchei Khimii 1995, 65, 756–760.
p a
S
8
[
14] M. L. Luetkens, A. P. Sattelberger, H. H. Murray, J. D. Basil,
J. P. Fackler, Inorg. Synth. 1990, 28, 305–310.
1
chromatography on silica gel led only to decomposition. H NMR
(500.1 MHz, C
6 6
D ): δ = 8.26 (dd, J = 7.1, 1.1 Hz, 1 H, Ar), 7.66 [15] The relevant compounds are: BARQEQ, CIDHUS, GETPUQ,
(
br. d, J = 7.0 Hz, 1 H, Ar), 7.69–7.63 (m, 3 H, Ar), 7.54 (d, J =
HEZGUO, and PAYQUB. X-ray data for these compounds
can be extracted from the Cambridge Crystallographic Datab-
ase.
7
5
7
4
4
.8 Hz, 1 H, Ar), 7.46 (dd, J = 8.6, 2.8 Hz, 1 H, Ar), 7.44–7.34 (m,
H, Ar), 7.32–7.22 (m, 3 H, Ar), 7.21–7.17 (m, 1 H, Ar), 7.14–
.10 (m, 1 H, Ar), 7.04–7.01 (m, 1 H, Ar), 6.99–6.95 (m, 1 H, Ar),
[
16] A. Alexakis, V. Albrow, K. Biswas, M. d’Augustin, O. Prieto,
S. Woodward, Chem. Commun. 2005, 2843–2845.
17] K. Biswas, C. Borner, J. Gimeno, P. J. Goldsmith, D. Ramaz-
zotti, A. L. K. So, S. Woodward, Tetrahedron 2005, 61, 1433–
.67–4.65 (m, 1 H, C
5
H
3
) 4.46 (s, 5 H, C
5
H
5
), overlapped by 4.48–
) ppm;
[
.45 (m, 1 H, C ), 4.28 (app. t J = 2.5 Hz, 1 H, C H
5
H
3
5 3
13
satisfactory C NMR spectra could not be obtained due to degra-
dation in solution: benzene (slow and only sparingly soluble) and
1442.
Received: January 27, 2006
chloroform (rapid). 31P NMR (202 MHz, C
Published Online: March 22, 2006
6
6
D ): δ = +196.8 ppm.
Eur. J. Org. Chem. 2006, 2549–2557
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2557