Stereoselective synthesis of planar chiral 2,2′-diarylsubstituted ferrocene derivatives as precursors for new 2-phospha[3]ferrocenophanes

Article abstract of DOI:10.1016/j.jorganchem.2012.06.033

Starting from a 1,1′-bis-(S_C)-(methoxymethyl)pyrrolidine functionalized ferrocene, an ortholithiation/iodination/chiral auxiliary removal/Suzuki coupling sequence has been achieved. It affords a convenient, stereoselective access to chiral, C₂-symmetric, tetrasubstituted ferrocene derivatives of (S_pl,S_pl)-configuration, bearing various aryl substituents and acetoxymethyl functions. These α-acetoxy-functionalized ferrocenes may be useful synthetic intermediates. In this work they were used as precursors for two new enantiomerically pure (S_pl,S_pl)-2-phospha[3]ferrocenophanes for organocatalytic purposes.

Full text of DOI:10.1016/j.jorganchem.2012.06.033

Journal of Organometallic Chemistry 716 (2012) 187e192
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Stereoselective synthesis of planar chiral 2,20-diarylsubstituted ferrocene
derivatives as precursors for new 2-phospha[3]ferrocenophanes
*
Mathilde Neel, Armen Panossian, Arnaud Voituriez, Angela Marinetti
Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1, av. de la Terrasse, 91198 Gif-sur-Yvette, Cedex, France
a r t i c l e i n f o
a b s t r a c t
Starting from a 1,10-bis-(SC)-(methoxymethyl)pyrrolidine functionalized ferrocene, an ortholithiation/
iodination/chiral auxiliary removal/Suzuki coupling sequence has been achieved. It affords a convenient,
stereoselective access to chiral, C2-symmetric, tetrasubstituted ferrocene derivatives of (Spl,Spl)-config-
Article history:
Received 27 February 2012
Received in revised form
21 June 2012
uration, bearing various aryl substituents and acetoxymethyl functions. These a-acetoxy-functionalized
Accepted 26 June 2012
ferrocenes may be useful synthetic intermediates. In this work they were used as precursors for two new
enantiomerically pure (Spl,Spl)-2-phospha[3]ferrocenophanes for organocatalytic purposes.
Ó 2012 Elsevier B.V. All rights reserved.
Keywords:
Ferrocenes
Ortho-metalation
Suzuki couplings
Phospha[3]ferrocenophanes
Enantioselective organocatalysis
Planar chirality
1. Introduction
and robust nucleophilic organocatalysts for enantioselective cycli-
zations [7]. Especially catalyst (S,S)-1a (R3Si
¼
Me3Si,
Although ferrocene based chiral phosphines are well known,
ubiquitous ligands in transition metal promoted catalytic processes
[1], their successful applications to enantioselective organocatalysis
are still rare [2]. Notable exceptions are Josiphos-type phosphines
that have been shown recently to be suitable organocatalysts for
the enantioselective borations of olefins [3] as well as for the
asymmetric dimerizations of ketenes [4].
R0 ¼ cyclohexyl) has been applied to number of [3 þ 2] cyclizations
between electron-poor allenes and olefins, by giving high conver-
sion rates and very high enantiomeric excesses [8].
These previous studies demonstrated that the enantiomeric
excesses attained in the catalytic reactions greatly depend on the
nature of the phosphorus substituent, as well as on the nature of the
silyl groups on the Cp rings. Based on those findings, we have envi-
sioned to expand the FerroPHANE family to planar chiral derivatives
displaying aryl groups on the Cp rings, instead of silyl units. Our aim is
to create a markedly different and hopefully favorable chiral envi-
ronment by replacing bowl-shaped silyl substituents by planar
moieties with various sizes. This work gives access to new chiral 2-
phospha[3]ferrocenophanes as well as to intermediate chiral
building blocks that should find utility for various synthetic purposes.
With the aim of developing new series of ferrocene-based
phosphine organocatalysts,
a few years ago we targeted 2-
phospha[3]ferrocenophanes as potentially suitable scaffolds [5,6].
We demonstrated that the planar chiral (S,S)-2-phospha[3]ferro-
cenophanes 1, called FerroPHANEs (Scheme 1), are highly efficient
2. Results and discussion
As stated above, the aim of this work was to modulate the
structure of the planar chiral 2-phospha[3]ferrocenophanes 1 [7a],
by replacing the R3Si groups by aryl units. We envisioned intro-
ducing the aryl groups on the Cp rings via Suzuki-type reactions
and we adapted our general synthetic approach accordingly.
In our approach, the synthesis of the silylated ferrocenophanes 1
involved a diastereoselective di-ortho-lithiation of ferrocene 2
which bears two (S)-(methoxymethyl)pyrrolidine units [9] as the
Scheme 1. General molecular structure of FerroPHANEs.
* Corresponding author. Tel.: þ33 01 69 82 30 36; fax: þ33 01 69 07 72 47.
E-mail address: angela.marinetti@icsn.cnrs-gif.fr (A. Marinetti).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2012.06.033

188
M. Neel et al. / Journal of Organometallic Chemistry 716 (2012) 187e192
Table 1
Optimization of the Suzuki couplings on 4.
a
Ar B(OH)2
Ar
Catalyst
Conditions
(S,S)-5
Yield
(%)
Ph
Ph
Ph
Ph
[Pd(PPh3)4]b
MW, 100 ꢀC, 1 h
MW, 100 ꢀC, 1 h
70 ꢀC, 24 h
MW, 100 ꢀC, 1 h
MW, 100 ꢀC, 1 h
MW, 100 ꢀC, 1 h
MW, 100 ꢀC, 1 h
5a
5a
5a
5a
5b
5c
5d
66
60
60
85
75
72
70
[PdCl2(PPh3)2]b
[PdCl2(SPhos)2]c
[PdCl2(SPhos)2]c
[PdCl2(SPhos)2]c
[PdCl2(SPhos)2]c
[PdCl2(SPhos)2]c
2-naphthyl
1-naphthyld
9-phenanthryld
Scheme 2. Diastereoselective ortho-lithiation/iodination of (S,S)-2.
a
Arylboronic acid: 4 equiv.
10 mol%.
b
c
5 mol%; SPhos ¼ 2-dicyclohexylphosphino-20,60-dimethoxybiphenyl.
chiral auxiliaries. The intermediate dilithiated ferrocene was
trapped then by the desired trialkylsilyl chloride [7b].
d
In THF/toluene/H2O: 2/1/0.1.
In this work, the same strategy has been applied to the dia-
stereoselective synthesis of the ferrocene diiodide 3 (Scheme 2),
which was expected to be a suitable precursor for Suzuki-type
reactions.
To our knowledge these are the first examples of planar chiral
1,10-diaryl substituted ferrocenes produced by two successive
Suzuki couplings, although Suzuki couplings have been applied
previously to the synthesis of both chiral [12] and achiral aryl-
substituted ferrocenes. For instance, methods have been described
for the coupling of iodo- or diiodoferrocenes with aromatic [12b,d]
or heteroaromatic boronic acids or boronates [13]. The reverse
strategy has been applied also, which involves couplings of
ferrocene-boronic acids with aromatic [12a,c,14] or heteroaromatic
halides [15] under palladium catalysis.
Lithiation of (S,S)-2 with sec-BuLi [9b] followed by addition of
1,2-diiodoethane afforded the desired diiodo derivative 3 in good
yield (80% isolated yield). The diastereomers ratio in the crude
reaction mixture was >95:5 and the final diiodide was isolated as
a single isomer after column chromatography. Compound 3 is
assumed to have an Spl,Spl-configuration, based on the known
stereochemical outcome of the ortho-lithiation step on (S,S)-2 [7b].
The reaction has been performed at a gram scale. To get well repro-
ducible results, it is essential to operate these lithiation experiments
in carefully controlled reaction conditions (good quality sec-BuLi,
anhydrous solvents and reactants, controlled reaction temperatures
and times). The final product must be handled and stored in the dark.
The next step of the planned synthetic sequence involves Suzuki
type couplings on the 1,10-diiodoferrocene 3. However, when sub-
jected to Suzuki type reactions with excess phenylboronic acid in the
presence of various palladium catalysts, diiodide 3 gave only
moderate conversion rates. In order to have a hopefully more reactive
substrate, we therefore converted 3 into the corresponding diacetate
4 by heating 3 in acetic anhydride at 90 ꢀC for 18 h (Scheme 3).
Overall, diacetate 4 proved to be a more suitable substrate for
Suzuki type reactions, with respect to 3. Rather sluggish reactions
were observed under thermal conditions, however, an optimization
process (see Table 1 for selected experiments) highlighted the
beneficial effect of microwaves [10] on the reaction rate, as well as
the efficiency of [PdCl2(SPhos)2] [11] as the catalyst. Optimized
reaction conditions entail microwave heating at 100 ꢀC for 1 h of
a mixture of the reactants (ferrocene diiodide : boronic acid
ratio ¼ 1:4) in the presence of Cs2CO3 (5 equivalents) and a 5 mol%
amount of the palladium catalyst. Under these conditions the
double arylation of the ferrocene scaffold produces 5a (Ar]Ph) in
85% isolated yield.
The coupling procedure in Scheme 3 has been extended to the
synthesis of the 2-naphthyl,1-naphthyl and 9-phenanthryl substituted
ferrocenes 5bed, from the corresponding boronic acids. The desired
ferrocenes were obtained in 70e75% isolated yields (Table 1).
Thus, the ortholithiation/iodination/Suzuki coupling sequence
shown in Schemes 2 and 3 affords a convenient, stereoselective
access to chiral, C2-symmetric, tetrasubstituted ferrocene deriva-
tives bearing various aryl substituents. It tolerates aryl groups with
significant steric hindrance such as 9-phenanthryl units.
Owing to the presence of the acetate functions, the new chiral
ferrocenes 5 are potentially useful synthetic intermediates. Notably,
various phosphorus ligands should be available from
5 via
nucleophilic substitution reactions, according to well established
methods [1]. In this work the chiral acetates 5 have been considered
as potential precursors for a new series of 2-phospha[3]ferroceno-
phane derivatives. Conversion of 5 into 2-phospha[3]ferroceno-
phanes involves their reactions with a suitable primary phosphine
and, therefore, cyclization of 5b with cyclohexylphosphine in acidic
conditions was investigated as a representative reaction.
According to the usual procedure [7b], the nucleophilic substi-
tution on 5b was attempted at first by heating 5b with cyclo-
hexylphosphine in acetic acid at 60 ꢀC. The reaction proved
however more challenging than expected and the above conditions
Scheme 3. Synthesis of the 1,10-diiodide 4 and Suzuki couplings.

M. Neel et al. / Journal of Organometallic Chemistry 716 (2012) 187e192
189
recently [21]. Both reactions had been carried out previously by
using FerroPHANE 1a as the catalyst [7a,8a]. These previous results
are recalled in Scheme 5 for comparison purposes.
In the organocatalytic experiments shown in Scheme 5, phos-
phine 6b displayed somewhat lower catalytic activities, compared
to FerroPHANE 1a (58e62% yields, vs. 80e87% yields with catalyst
1a), as well as lower enantioselectivity levels, with enantiomeric
excesses of about 60%.
Thus, aryl-substitution of the Cp ring in the planar chiral fer-
rocenic phosphine 6b does not afford any beneficial effect with
respect to TMS-substitution, in terms of stereoselectivity. Moreover,
the increased air-sensitivity of 6b with respect to 1a, makes its use
as organocatalyst more challenging for routine uses.
Scheme 4. Synthesis of 2-phospha[3]ferrocenophanes, (S,S)-6.
Obviously, these preliminaryexperiments do not rule out possible
applications of phosphines 6 either in otherclasses of organocatalytic
reactions or as chiral ligands in transition metal catalysis. Therefore,
ongoing studies are oriented toward the development of alternative
catalytic applications for the chiral phosphines 6.
failed to produce the desired cyclic phosphine. The cyclization
could be carried out then by using an acetic acid/HBF4 mixture to
generate the electrophilic ferrocenylmethyl cation (Scheme 4).
31P NMR spectrum of the crude reaction mixture showed that
these strongly acidic conditions produce the phosphonium salt of
the expected phosphine. Therefore, after the cyclization step, the
phosphonium salt was deprotonated with diisopropylethylamine
to give the desired trivalent phosphine 6b (Ar ¼ 2-naphthyl, 25%
yield). Phosphine 6b was purified by column chromatography
under argon. The same experimental procedure allowed 6a (Ar]
Ph) to be isolated in 20% yield.
3. Conclusion
In this work we have established a suitable procedure for the
stereoselective synthesis of new tetrasubstituted, planar chiral
ferrocenic derivatives displaying aryl substituents. The procedure
includes a diastereoselective ortho-lithiation and a Suzuki coupling
step which allows to simultaneously introduce the two aryl groups
on the ferrocenic scaffold. The reaction sequence has been applied
here to the synthesis of new planar chiral 2-phospha[3]ferroce-
nophane derivatives. Ongoing studies are oriented toward the use
of the same tetrasubstituted ferrocenic scaffolds in the synthesis of
other phosphorus derivatives for catalytic purposes.
The electron-rich trialkylphosphines 6a,b proved to be highly air
sensitive, which contrasts with the remarkable stability of the
analogous TMS-substituted FerroPHANE 1a (R3Si
¼
Me3Si,
R0 ¼ cyclohexyl) toward air oxidation. Phosphines 6a,b must be
handled under an inert gas atmosphere, while FerroPHANE 1a was
shown to undergo less than 5% oxidation after 24 h in air in a CDCl3
solution.
4. Experimental
According to our initial target of using 6 as nucleophilic chiral
organocatalysts [16], phosphine 6b has been evaluated in the
model [3 þ 2] cyclization reactions shown in Scheme 5. The cycli-
zations between allenoates and electron-poor olefins, including
enones (eq. (a) in Scheme 5), are well known phosphine promoted
processes, leading to the diastereo- and possibly enantioselective
formation of functionalized cyclopentenes with two contiguous
stereogenic centres [7a,17]. Chiral phosphines such as atropiso-
meric Binepines [17e,18], Dipamp [19] and bifunctional, aminoacid
derived phosphines [17f,20] have afforded enantiomeric excesses of
over 90% in reactions of this class. High levels of enantioselectivity
The use of allenic phosphonates as substrates in analogous cycli-
zations (eq. (b) in Scheme 5) has been introduced by our group
4.1. General remarks
All solvents were degassed under argon before use. All reactions
were monitored by thin-layer chromatography (TLC) carried out on
Merck Kiesegel 60 F254 plates, using UV light (254 nm) as a visual-
izing agent and KMnO4 stain and heat as developing agent. Column
chromatography was carried out on Merck silica gel Si60
(40e63
mm). NMR spectra were recorded on Bruker AV500 or
AV300 spectrometers, calibrated using residual non-deuterated
solvent as the internal reference. Chemical shifts are given in
ppm. High resolution mass spectra (HRMS ESIþ) were recorded on
LCT Waters equipment. IR spectra were recorded neat on a Per-
kineElmer FT-IR spectrophotometer. Optical rotations were deter-
mined on a JASCO P-1010 polarimeter. HPLC was performed at
a column temperature of 30 ꢀC on a Waters 2695 Separations
Module equipped with a diode array UV detector. Phosphine 1a was
synthesized according to the previously reported procedure [7].
The air sensitive phosphines 6a and 6b have been purified by flash
chromatography under a light argon pressure; solvents have been
degassed by bubbling argon for 20 min prior to use; after collection
of the desired yellow-orange fractions in a Schlenk tube, the
solvents were removed under vacuum (vacuum line, 10ꢁ2 mmHg).
Et
CO2
Ph
CO
Et
CO2
mo
l%
PR * 10
,
3
•
+
( )
a
toluene, rt
Ph
CO
(
4 5R
S,
)
7
8
9
(
)
-
(
,
R M R' y
c c ohe
=
l
x
),
,
yield 96 ee
%
1a
7
e
PR *
y
l
8
S S
,
e
%
=
=
3
(
,
)
-
,
,
6b 58 yi ld 60 ee
S S
%
%
(
P
O
)(
)
Et
O
2
Ph
CO
P( )(
O
)
2
Et
O
PR *, 10 m l
o %
3
•
+
( )
4.2. Procedures and products characterizations
b
tolu e 12 °
en , 0 C
Ph
CO
4.2.1. (SC,SC,Spl,Spl)-1,10-Diiodo-2,20-bis[((S)-2-(methoxymethyl)
pyrrolidin-1-yl)methyl]-ferrocene (3)
10
8
11
4
,5R
)
S
(
In a dry flask was placed 1,10-bis[((SC)-2-(methoxymethyl)pyrro-
lidin-1-yl)methyl]ferrocene (S,S)-2 (1.0 g, 2.3 mmol). The flask was
purged with argon. Distilled anhydrous diethyl ether (7.5 mL) was
added and the solution was cooled to ꢁ78 ꢀC. sec-Butyllithium
PR *
a
=
-
6b
1
S,S
S,S
(
(
)
3
80 yi ld, 90 ee
,
%
e
%
%
,
-
)
ee
,
62 yield 60
%
Scheme 5. Enantioselective phosphine promoted [3 þ 2] cyclizations.

190
M. Neel et al. / Journal of Organometallic Chemistry 716 (2012) 187e192
(1.35 M solution in cyclohexane, 5.1 mL, 6.8 mmol, 3.0 equiv.) was
added dropwise. The mixture was stirred at ꢁ78 ꢀC for 5 min, then at
ꢁ25 ꢀC for 1 h. A solution of anhydrous 1,2-diiodoethane (1.92 g,
6.8 mmol, 3.0 equiv.) in distilled anhydrous diethyl ether (15 mL) was
added to the resulting orange suspension at ꢁ78 ꢀC. The mixture was
allowedtowarm slowly to room temperatureand stirredfor 3 h inthe
dark (aluminum sheet). AcOEt wasadded until the suspension turned
into a brown solution (1 mL). The resulting solutionwas concentrated
and the mixture was purified by column chromatography on alumina
with an ether/triethylamine gradient (99:1 to 95:5). (SC,SC,Spl,Spl)-1,10-
Diiodo,2,20-bis[((S)-2-(methoxymethyl)pyrrolidin-1-yl)methyl]-fer-
rocene 3 was obtained as an orange oil (80% yield, single diaste-
4.2.5. (S,S)-1,10-bis(acetoxymethyl)-2,20-bis(2-naphthyl)ferrocene
(5b)
(75% yield, orange oil); Rf 0.2 (30% EtOAc/heptanes); 1H NMR
(CDCl3, 500 MHz)
d
(ppm) 7.82 (bs, 2H, HAr), 7.75 (d, J ¼ 7.5 Hz, 2H,
HAr), 7.65 (4H, HAr), 7.55 (d, J ¼ 8.5 Hz, 2H, HAr), 7.49e7.40 (m, 4H,
HAr), 5.30 (d, J ¼ 12.3 Hz, 2H, Cp-CH2), 5.08 (d, J ¼ 12.3 Hz, 2H, Cp-
CH2), 4.65 (s, 2H, HCp), 4.49 (s, 2H, H HCp), 4.22 (s, 2H, H HCp), 2.12 (s,
6H, CH3); 13C NMR (CDCl3, 75 MHz)
d (ppm) 171.0 (MeCO),133.9 (C),
133.4 (C), 132.4 (C), 127.9 (CH), 127.8 (CH), 127.7 (CH), 127.12 (CH),
127.09 (CH), 126.4 (CH), 125.9 (CH), 89.3 (CCp), 79.7 (CCp), 73.46
(CHCp), 73.38 (CHCp), 72.1 (CHCp), 61.7 (Cp-CH2), 21.2 (CH3); IR: nmax
(cmꢁ1) 2357, 1734, 1628, 1600, 1508, 1372, 1236, 1224, 1019, 948,
reomer). Rf 0.25 (2% Et3N/Et2O); 1H NMR (CDCl3, 300 MHz)
d
(ppm)
818, 750; HRMS (ESI), calcd. For C36H30FeNaO4 [M þ Na]þ:
24
4.35 (m, 2H, HCp), 4.12 (m, 4H, HCp), 3.81 (d, J ¼ 13.5 Hz, 2H, Cp-
CH2N), 3.48 (d, J ¼ 13.5 Hz, 2H, Cp-CH2N), 3.48 (dd, J ¼ 9.3 Hz,
J ¼ 4.9 Hz, 2H, CH2O), 3.37 (s, 6H, eOCH3), 3.27 (dd, J ¼ 9.3 Hz,
6.0 Hz, 2H, CH2O), 3.0e2.9 (m, 2H, NCH2), 2.8e2.6 (m, 2H, NCH),
2.22 (m, J ¼ 9.0 Hz, 2H, NCH2), 1.92e1.76 (m, 2H, CH2), 1.7e1.4 (m,
605.1391; found: 605.1390; [
a
]
¼ þ279 (c ¼ 0.2, CHCl3).
D
4.2.6. (S,S)-1,10-bis(acetoxymethyl)-2,20-bis(1-naphthyl)ferrocene
(5c)
(72% yield, orange oil); Rf 0.2 (30% EtOAc/heptanes); 1H NMR
6H, CH2); 13C NMR (CDCl3, 75 MHz)
d
(ppm) 86.3 (CCp), 78.3 (CHCp),
(CDCl3, 300 MHz)
d
(ppm) 7.91 (d, J ¼ 7.2 Hz, 2H, HAr), 7.75 (d,
76.6 (CH2), 73.8 (CHCp), 73.4 (CHCp), 62.0 (NCH), 59.3 (OCH3), 54.4
(CH2), 52.5 (CH2), 47.0 (CCp-I), 28.6 (CH2), 22.8 (CH2); IR: nmax
(cmꢁ1) 2916, 2870, 2804, 1454, 1360, 1339, 1195, 1107, 1094, 1032,
963, 925, 810, 731; HRMS (ESI) calcd. for C24H34FeI2N2NaO2
[M þ Na]þ: 714.9957; found: 714.9958; Elemental analysis: calcd.
for C24H34FeI2N22O52: C, 41.64; H, 4.95; N, 4.05; found: C, 41.56; H,
J ¼ 7.5 Hz, 2H, HAr), 7.72 (d, J ¼ 7.5 Hz, 2H, HAr), 7.68 (d, J ¼ 9.6 Hz,
2H, HAr), 7.38e7.30 (m, 4H, HAr), 7.21 (m, 2H, HAr), 4.90 (d,
J ¼ 12.3 Hz, 2H, Cp-CH2), 4.68 (d, J ¼ 12.3 Hz, 2H, Cp-CH2), 4.60 (m,
2H, HCp), 4.54 (m, 2H, HCp), 4.44 (t, J ¼ 2.5 Hz, 2H, HCp), 1.75 (s, 6H,
CH3); 13C NMR (CDCl3, 75 MHz)
d (ppm) 170.7 (MeCO), 133.6 (C),
133.5 (C), 132.6 (C), 129.8 (CH), 128.2 (CH), 128.1 (CH), 126.2 (CH),
125.8 (CH), 125.7 (CH), 125.4 (CH), 91.1 (CCp), 82.8 (CCp), 75.0 (CHCp),
4.94; N, 4.18; [
a
]
¼ ꢁ68 (c ¼ 0.2, CHCl3).
D
70.8 (CHCp), 70.6 (CHCp), 61.1 (Cp-CH2), 20.7 (CH3); IR: nmax (cmꢁ1
)
4.2.2. (S,S)-1,10-Diiodo-2,20-bis(acetoxymethyl)ferrocene (4)
3054, 2927, 2855, 1730, 1371, 1225, 1018, 778; MS (ESI), m/z 605.1
24
Compound 3 (850 mg, 1.23 mmol) was dissolved in acetic
anhydride (20 mL). The solution was heated at 90 ꢀC for 16 h in
a sealed tube. After evaporation of the solvent in vacuo, purification
by column chromatography (silica gel; heptanes/ether 80:20)
afforded 4 as an orange oil (85% yield). Rf 0.2 (30% EtOAc/heptanes);
[M þ Na]þ; [
a
]
¼ þ145 (c ¼ 1, CHCl3).
D
4.2.7. (S,S)-1,10-bis(acetoxymethyl)-2,20-bis(9-phenanthryl)
ferrocene (5d)
(70%, orange oil); Rf 0.2 (30% EtOAc/heptanes); 1H NMR (CDCl3,
1H NMR (CDCl3, 500 MHz)
d
(ppm) 4.98 (d, J ¼ 12.0 Hz, 2H, Cp-CH2),
500 MHz)
d
(ppm) 8.69 (d, J ¼ 8.1 Hz, 2H, HAr), 8.67 (d, J ¼ 8.4 Hz, 2H,
4.80 (d, J ¼ 12.0 Hz, 2H, Cp-CH2), 4.44 (m, 2H, HCp), 4.37 (m, 2H,
HAr), 8.33 (s, 2H, HAr), 7.79 (d, J ¼ 8.4 Hz, 2H, HAr), 7.75 (d, J ¼ 7.8 Hz,
2H, HAr), 7.70e7.50 (m, 6H, HAr), 7.44 (t, J ¼ 7.2 Hz, 2H, HAr), 5.04 (d,
J ¼ 12.3 Hz, 2H, Cp-CH2), 4.80 (d, J ¼ 12.3 Hz, 2H, Cp-CH2), 4.8e4.7
(4H, HCp), 4.67 (t, J ¼ 2.4 Hz, 2H, HCp), 1.56 (s, 6H, CH3); 13C NMR
HCp), 4.22 (m, J 2H, HCp), 2.09 (s, 6H, CH3); 13C NMR (CDCl3, 75 MHz)
d
(ppm) 170.9 (MeCO), 84.7 (CCp), 79.8 (CHCp), 74.4 (CHCp), 72.0
(CHCp), 62.3 (OCH2), 45.4 (CCp-I), 20.9 (MeCO); IR: nmax (cmꢁ1) 3098,
2965, 1731, 1439, 1365, 1222, 1018, 942, 821, 731; HRMS (ESI), calcd.
(CDCl3, 75 MHz) d (ppm) 170.8 (MeCO),144.2 (C), 132.7 (C), 131.4 (C),
for C16H16FeNaI2O4 [M
þ
Na]þ: 604.8385; found: 604.8371;
131.0 (CH), 130.3 (C), 130.2 (C), 128.7 (CH), 127.0 (CH), 126.9 (CH),
126.5 (CH), 126.2 (CH), 122.8 (CH), 122.6 (CH), 91.8 (CCp), 83.2 (CCp),
75.2 (CHCp), 70.8 (CHCp), 70.4 (CHCp), 61.1 (Cp-CH2), 20.7 (CH3); IR:
25
[
a]
¼ þ33 (c ¼ 0.8, CHCl3).
D
4.2.3. General procedure for the Suzuki cross-coupling reaction
In a microwave glass tube were charged 3 (100 mg, 0.17 mmol),
arylboronic acid (0.68 mmol, 4 equiv.), [PdCl2(SPhos)2] (8.5 mg,
0.0085 mmol, 5 mol%) and cesium carbonate (276 mg, 0.85 mmol, 5
equiv.). The tube was purged with argon, THF (1 mL) and water
(0.1 mL) were added. The mixture was subjected to microwave
irradiation (SEM Discover apparatus) for 1 h at 100 ꢀC. The crude
mixture was filtered through a pad of Celite, using ethyl acetate as
the eluent. Column chromatography of the filtrate (alumina;
heptane/EtOAc 9:1) gave 5aed.
nmax (cmꢁ1) 3058, 2925, 2852, 1730, 1448, 1370, 1223, 1018, 749; MS
24
(ESI), m/z 705.2 [M þ Na]þ; [
a]
¼ þ104 (c ¼ 0.5, CHCl3).
D
4.2.8. (S,S)-2,20-diphenyl-1,10-(2-cyclohexyl-2-phospha-
1,3-propanediyl)ferrocene (6a)
A solution of cyclohexylphosphine (26 mL, 0.21 mmol) in acetic
acid (2 mL) was added dropwise at room temperature to a solution
of 5a (100 mg, 0.21 mmol) in degassed dichloromethane (40 mL).
HBF4 (35
stirred 45 min at room temperature and the solvent was evapo-
rated in vacuo. Dichloromethane (7.5 mL) and DIPEA (36 L,
mL, 0.21 mmol) was added then. The reaction mixture was
m
4.2.4. (S,S)-1,10-bis(acetoxymethyl)-2,20-diphenylferrocene (5a)
0.21 mmol) were added to the crude mixture. After 15 min, the
mixture was evaporated. The residue was purified by flash chro-
matography under argon (silica gel; heptanes/EtOAc 99.5/0.5) to
obtain 6a as an orange solid (20% yield). Rf 0.2 (1% EtOAc/heptanes);
(85% yield, orange oil); Rf 0.2 (30% EtOAc/heptanes); 1H NMR
(CDCl3, 300 MHz) d (ppm) 7.48e7.42 (m, 4H, Ph), 7.33e7.24 (m, 6H,
Ph), 5.19 (d, J ¼ 12.0 Hz, 2H, Cp-CH2), 4.92 (d, J ¼ 12.0 Hz, 2H, Cp-
CH2), 4.53 (br dd, J w 2.0 Hz, 2H, HCp), 4.39 (br dd, J w 2.0 Hz, 2H,
HCp), 4.08 (t, J ¼ 2.4 Hz, 2H, HCp), 2.07 (s, 6H, CH3); 13C NMR (CDCl3,
1H NMR (CDCl3, 500 MHz)
d
(ppm) 7.47 (d, J ¼ 7.5 Hz, 2H, HAr), 7.42
(d, J ¼ 7.5 Hz, 2H, HAr), 7.3e7.2 (m, 6H, HAr), 4.41 (s, 1H, HCp), 4.38 (s,
1H, HCp), 4.37 (s, 1H, HCp), 4.33 (s, 1H, HCp), 3.80 (s, 1H, HCp), 3.41 (s,
1H, HCp), 2.80 (t, J ¼ 13.0 Hz, 1H, PCH2), 2.46 (t, J ¼ 13.0 Hz, 1H,
PCH2), 2.16 (br, 1H), 1.90e1.05 (m, 12H); 13C NMR (CDCl3, 75 MHz)
75 MHz):
d (ppm) 171.0 (MeCO), 136.6 (CCp), 128.9 (CHPh), 128.4
(CHPh), 126.9 (CHPh), 89.3 (CCp), 79.5 (CCp), 73.4 (CHCp), 73.1 (CHCp),
72.3 (CHCp), 61.6 (OCH2), 21.2 (CH3); IR: nmax (cmꢁ1) 2360, 2338,
1737, 1600, 1506, 1446, 1241, 1224, 1020, 945, 766, 701; HRMS (ESI),
d
(ppm) 138.8 (CAr), 138.3 (CAr), 129.6 (CHAr), 128.6 (CHAr), 128.2
calcd. For C28H26FeNaO4 [M þ Na]þ: 505.1078; found: 505.1055;
(CHAr), 127.9 (CHAr), 126.4 (CHAr), 88.6 (CCp), 86.4 (CCp), 79.3 (CHCp),
73.5 (CCp), 73.0 (CCp), 72.8 (CHCp), 71.6 (CHCp), 68.4 (CHCp), 67.6
24
[
a]
¼ ꢁ16 (c ¼ 0.3, CHCl3).
D

M. Neel et al. / Journal of Organometallic Chemistry 716 (2012) 187e192
191
(CHCp), 66.9 (CHCp), 38.2 (d, JCeP ¼ 14.8 Hz, PCH), 30.2 (d,
Appendix A. Supporting material
JCeP ¼ 10.5 Hz, CH2), 29.9 (d, 1JCeP ¼ 8.0 Hz, CH2), 27.0 (CH2), 26.6
(CH2), 22.1 (CH2), 21.7 (CH2). 31P{1H} NMR (CDCl3, 202 MHz)
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.jorganchem.2012.06.033.
d
(ppm) 8.1; IR: nmax (cmꢁ1) 3094, 3070, 2957, 2853, 1704, 1637,
1615, 1523, 1438, 1352, 1197, 1170, 1097, 1078, 938, 865, 816;
24
[
a]
¼ - 194 (c ¼ 0.7, CHCl3).
D
References
4.2.9. (S,S)-2,20-bis(2-naphthyl)-1,10-(2-cyclohexyl-2-phospha-1,3-
propanediyl)ferrocene (6b)
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Weinheim, 2010.
A solution of cyclohexylphosphine (21
acid (2 mL) was added to a solution of 5b (100 mg, 0.17 mmol) in
degassed dichloromethane (40 mL). HBF4 (28 L, 0.17 mmol) was
mL, 0.17 mmol) in acetic
m
added then. The reaction mixture was stirred 45 min at room
temperature and the solvent was evaporated in vacuo. To the crude
residue were added dichloromethane (7.5 mL) and DIPEA (30 mL,
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0.17 mmol). After 15 min, the mixture was evaporated and purified
by flash chromatography under argon (silica gel; heptanes/EtOAc
99.5/0.5) to give 6b as a yellow solid (25% yield). Rf 0.2 (1% EtOAc/
heptanes); 1H NMR (CDCl3, 500 MHz)
d (ppm) 7.9e7.8 (m, 8H, HAr),
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7.64 (t, J ¼ 9.5 Hz, 2H, HAr), 7.55e7.45 (m, 4H, HAr), 4.60 (s, 1H, HCp),
4.52 (s, 2H, HCp), 4.50 (s, 1H, HCp), 3.91 (s, 1H, HCp), 3.52 (s, 1H, HCp),
2.95 (t, J ¼ 13.0 Hz, 1H, PCH2), 2.55 (t, J ¼ 13.5 Hz, 1H, PCH2), 2.30
(dd, J ¼ 13.5 Hz, J ¼ 5.0 Hz, 1H, PCH2), 1.92 (dd, J ¼ 13.5, J ¼ 6.5 Hz,
1H, PCH2), 1.9e1.0 (m, 11H, Cy); 13C NMR (CDCl3, 125 MHz)
d (ppm)
136.3 (CAr), 136.0 (CAr), 133.3 (CAr), 132.2 (CAr), 128.5 (CHAr), 127.94
(CHAr), 127.86 (CHAr), 127.82 (CHAr), 127.78 (CHAr), 127.70 (CHAr),
127.6 (CHAr),127.3 (CHAr),127.2 (CHAr),126.8 (d, JCeP ¼ 3.2 Hz, CHAr),
126.4 (CHAr), 126.2 (CHAr), 125.7 (CHAr), 125.4 (CHAr), 88.4 (CCp),
86.0 (CCp), 82.9 (d, JCeP ¼ 6.5 Hz, CCp), 82.1 (d, JCeP ¼ 3.9 Hz, CCp),
79.3 (CHCp), 77.3 (CHCp), 73.0 (CHCp), 71.9 (CHCp), 67.9 (CHCp), 67.3
(CHCp), 38.9 (d, JCeP ¼ 12.8 Hz, CH), 30.4 (d, JCeP ¼ 12.3 Hz, CH2),
30.0 (d, JCeP ¼ 11.0 Hz, CH2), 27.2e27.0 (2 CH2), 26.6 (CH2), 24.9 (d,
JCeP ¼ 20.6 Hz, CH2), 22.3 (d, JCeP ¼ 19.3 Hz, CH2); 31P{1H} NMR
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d
(ppm) 8.1; IR: nmax (cmꢁ1) 2958, 2925, 1725,
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1600, 1463, 1447, 1269, 1123, 1072, 818, 805, 690; MS (ESI), m/z
24
579.2 [M þ H]þ; [
a]
¼ ꢁ156 (c ¼ 0.9, CHCl3).
D
4.2.10. Catalytic tests: asymmetric [3 þ 2] cyclizations between
allenes and (E)-3-(naphthalen-1-yl)-1-phenylprop-2-en-1-one
A mixture of enone 8 (0.15 mmol, 40 mg), ethyl buta-2,3-
dienoate (0.30 mmol, 35 mg) and phosphine 6b (10 mol %,
0.015 mmol, 8.6 mg) in degassed toluene (0.50 mL) was stirred at r.
t. for 24 h under an argon atmosphere. The crude mixture was
concentrated in vacuo, and the final product 9 was purified by flash
chromatography on silica gel: Rf 0.32 (20% EtOAc/heptanes) Enan-
tiomeric excesses were measured by chiral HPLC: Chiracel OD, 10%
iPrOH/n-heptane, 1 mL/min, 226 nm, retention times: 11.6 min
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Acknowledgments
Authors thank the Institut de Chimie des Substances Naturelles,
the COST Actions CM0802 « PhoSciNet » and CM0905 « ORCA » for
supporting this research.

192
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