Walphos versus biferrocene-based walphos analogues in the asymmetric hydrogenation of alkenes and ketones

Article abstract of DOI:10.1021/om401074a

Two representative Walphos analogues with an achiral 2,2″- biferrocenediyl backbone were synthesized. These diphosphine ligands were tested in the rhodium-catalyzed asymmetric hydrogenation of several alkenes and in the ruthenium-catalyzed hydrogenation of two ketones. The results were compared with those previously obtained on using biferrocene ligands with a C ₂-symmetric 2,2″-biferrocenediyl backbone as well as with those obtained with Walphos ligands. The application of one newly synthesized ligand in the hydrogenation of 2-methylcinnamic acid gave (R)-2-methyl-3- phenylpropanoic acid with full conversion and with 92% ee. The same ligand was used to transform 2,4-pentanedione quantitatively and diastereoselectively into (S,S)-2,4-pentanediol with 98% ee.

Full text of DOI:10.1021/om401074a

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Walphos versus Biferrocene-Based Walphos Analogues in the
Asymmetric Hydrogenation of Alkenes and Ketones
Afrooz Zirakzadeh,†,‡ Manuela A. Groß,†,§ Yaping Wang,∥ Kurt Mereiter,⊥ and Walter Weissensteiner*,†
†Institute of Organic Chemistry, University of Vienna, Wahringer Straße 38, A-1090 Vienna, Austria
̈
‡Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, A-1060 Vienna, Austria
§Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, U.K.
∥College of Pharmaceutical Sciences, Capital Medical University, Beijing, No.10 Xitoutiao, You An Men Beijing 100069,
People’s Republic of China
⊥Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/164SC, A-1060 Vienna,
Austria
S
* Supporting Information
ABSTRACT: Two representative Walphos analogues with an achiral 2,2″-biferrocenediyl backbone were
synthesized. These diphosphine ligands were tested in the rhodium-catalyzed asymmetric hydrogenation of
several alkenes and in the ruthenium-catalyzed hydrogenation of two ketones. The results were compared
with those previously obtained on using biferrocene ligands with a C2-symmetric 2,2″-biferrocenediyl
backbone as well as with those obtained with Walphos ligands. The application of one newly synthesized
ligand in the hydrogenation of 2-methylcinnamic acid gave (R)-2-methyl-3-phenylpropanoic acid with full
conversion and with 92% ee. The same ligand was used to transform 2,4-pentanedione quantitatively and diastereoselectively into
(S,S)-2,4-pentanediol with 98% ee.
The backbone of Walphos analogues such as 1 and 2 with an
R,Sp,Rp absolute configuration were constructed by a Negishi
coupling between (R)-1-(N,N-dimethylamino)ethylferrocene
((R)-3) and (S)-2-bromoiodoferrocene ((S)-4) (analogous to
the reaction of (R)-3 and rac-4 shown in Scheme 1). This
reaction resulted in the intermediate (R,Sp,Rp)-5, which was
converted into the final ligands with a C2-symmetric
biferrocene-2,2″-diyl backbone. It is clear, however, that a
coupling reaction between (R)-3 and (R)-4 would lead to the
diastereomeric intermediate (R,Sp,Sp)-5 with an achiral
biferrocene-2,2″-diyl backbone. Substitution of such an achiral
biferrocene backbone with two nonidentical substituents would
also lead to chiral derivatives, and we were therefore curious as
to how Walphos analogues with an R,Sp,Sp absolute
configuration would perform in asymmetric catalysis.
INTRODUCTION
■
About 10 years ago we reported on the synthesis of a group of
diphosphine ligands, the so-called Walphos ligand family, and
their application in the asymmetric hydrogenation of alkenes,
ketones, and imines.1 All of these ligands are based on a
phenylferrocenylethyl backbone, and they vary only in the
substituents on their phosphino units (R1 and R2; Chart 1).
Chart 1
We report here the synthesis of two biferrocene-based
Walphos analogues (1 and 2) with an R,Sp,Sp configuration and
their application in the rhodium-catalyzed hydrogenation of
alkenes and the ruthenium-catalyzed hydrogenations of two
ketones. The results obtained with these biferrocene ligands are
compared with those of their R,Sp,Rp-configured diastereomers
and those of the corresponding Walphos ligands.
Originally, these derivatives were developed and used as ligands
for hydrogenation catalysts, but a variety of additional
applications have subsequently been reported.2
On the basis of the success of these ligands, we very recently
investigated Walphos analogues with a biferrocene instead of a
ferrocenylaryl backbone (Chart 1).3 In these ligands the aryl
ring of the Walphos backbone is replaced by a ferrocenyl unit.
In asymmetric hydrogenations the Walphos ligands and their
analogous biferrocene compounds showed significantly differ-
ent performances with respect to both product ee values and
absolute configuration.
RESULTS AND DISCUSSION
■
Synthesis of Ligands and Complexes. Ligands (R,Sp,Sp)-
1 and (R,Sp,Sp)-2 were prepared in a way analogous to that
for their R,Sp,Rp-configured diastereomers. However, racemic
Received: November 5, 2013
Published: April 9, 2014
© 2014 American Chemical Society
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Scheme 1. Synthesis of Ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2
Figure 1. Structural features of (R,Sp,Sp)-6, (R,Sp,Sp)-7, and (R,Sp,Sp)-2·2BH3.
2-bromoiodoferrocene (rac-4) was used instead of (R)-2-
bromoiodoferrocene ((R)-4). A Negishi coupling4 of (R)-1-
(N,N-dimethylamino)ethylferrocene with rac-45 gave both
diastereomers of 5 with an overall yield of 77% ((R,Sp,Rp)-5,
45%; (R,Sp,Sp)-5, 32%). The two diastereomers could be
separated by chromatography, and the diastereomer (R,Sp,Sp)-
56 was reacted with n-BuLi and subsequently quenched with
chlorodiphenylphosphine. Oxidation of the resulting amino-
phosphine (R,Sp,Sp)-6 with H2O2 resulted in the formation of
the phosphine oxide (R,Sp,Sp)-7 (52% based on 5), which can
also be obtained directly from 5. Reaction of (R,Sp,Sp)-5 with
n-BuLi followed by treatment with diphenylphosphinyl
chloride gave the phosphine oxide (R,Sp,Sp)-7 in 77% yield.
X-ray diffraction studies on the aminophosphine (R,Sp,Sp)-6
and the aminophosphine oxide (R,Sp,Sp)-7 confirmed their structural
integrity as well as their absolute configurations (Figure 1; for the
crystallographic data see the Experimental Section).
Further reaction of phosphine oxide 7 with bis[3,5-bis-
(trifluoromethyl)phenyl]phosphine or diphenylphosphine in acetic
acid at 70 °C gave the phosphine−phosphine oxides (R,Sp,Sp)-8
(60%) and (R,Sp,Sp)-9.1b In solution the side-chain phosphorus of
(R,Sp,Sp)-9 was found to be rather sensitive to oxidation and the
crude product 9 was therefore used in the last step. Reduction of
phosphine oxides 8 and 9 with polymethylhydrosiloxane/titanium
isopropoxide7 gave the desired ligands (R,Sp,Sp)-1 (92%) and
(R,Sp,Sp)-2 (70% based on 7). A small amount of (R,Sp,Sp)-2 was
then reacted with BH3·THF to give the bis(borane) complex
(R,Sp,Sp)-2·2BH3 (99%). The molecular structure of this
compound was determined by X-ray diffraction (Figure 1 and
Experimental Section). In addition, ligand (R,Sp,Sp)-2 was reacted
with [PdCl2(CH3CN)2] to give the palladium dichloride complex
[PdCl2((R,Sp,Sp)-2)] in 99% yield.
In the complex (R,Sp,Sp)-2·2BH3, as well as in precursors 6
and 7 (Figure 1), the two ferrocene units adopt an anti
arrangement with Fe1−C1−C11−Fe2 dihedral angles of
−178.5 and −177.3° (6), 176.8° (7), and 150.8° (2·2BH3).
In this conformation the diphenylphosphino units of 2 are
oriented trans to each other (torsion angles C2−C1−C11−C12
of 178.0 and 180.0° (6), 178.4° (7), and 158.4° (2·2BH3). The
ligand (R,Sp,Sp)-2 is not very well preoriented for cis
coordination, but it could easily be transformed into the
palladium dichloride complex [PdCl2((R,Sp,Sp)-2)].
Asymmetric Hydrogenations. Both of the newly
synthesized Walphos analogues 1 and 2 with an R,Sp,Sp
absolute configuration were tested as ligands in the asymmetric
hydrogenation of several alkenes and two ketones (Chart 2).
All catalysts for the hydrogenation of alkenes were formed
in situ by reacting the ligands with the metal precursor
[Rh(NBD)2]BF4 (NBD = norbornadiene). The catalysts for
the hydrogenation of ketones were prepared by reaction of the
ligands with the precursor [RuI2(p-cymene)]2. The results
obtained with ligands 1 and 2 of R,Sp,Sp configuration are
summarized in Table 1 together with our previously reported
data for ligands 1 and 2 of R,Sp,Rp configuration and those for
the original Walphos ligands SL-W001 and SL-W002.1,3
The use of ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2 in the
hydrogenation of all substrates (Chart 2) resulted in
quantitative or nearly quantitative conversion. The standard
test substrates (Z)-methyl α-acetamidocinnamate (MAC),
methyl acetamidoacrylate (MAA), dimethyl itaconate (DMI),
and 2-phenylcinnamic acid (PCA) gave only moderate
enantiomeric excesses of up to 84% ee (Table 1, entries 1−8).
For these substrates the corresponding Walphos ligands SL-W001-
1 and SL-W002-1 show significantly better performance (Table 1,
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The biferrocene ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2 were
used in the ruthenium-catalyzed hydrogenations of diketone
acetylacetone (ACA) and the β-keto ester ethyl 3-oxopenta-
noate (EOP). High enantiomeric excesses were obtained
(ACA, 98% ee; EOP, 92% ee; Table 1, entries 13−16), but
in these cases the corresponding Walphos ligands also
performed very well (ACA, 96% ee; EOP, 93% ee).
Chart 2. Substrates Used for Catalyst Screening
In brief, the hydrogenation of substrates MCA, ACA, and
EOP with biferrocene ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2 led to
products with enantiomeric excesses of ≥92%. Furthermore,
the value obtained for MCA (92%) was significantly higher
than that achieved with either of the two Walphos ligands (83%
and 62% ee).
A comparison of the ee values listed in Table 1 shows that,
overall, the Walphos ligands gave the best performance of the
systems tested. Four out of the eight substrates (MAA, IPCA-D,
ACA, and EOP) could be hydrogenated with enantiomeric
excesses greater than 90% (93−97% ee). On using the ligands
(R,Sp,Sp)-1 and (R,Sp,Sp)-2, which are both based on the achiral
2,2″-biferrocenediyl backbone, three of the substrates (MCA,
ACA, and EOP) gave product ee values greater than 90% (92−
98% ee). However, on using ligands (R,Sp,Rp)-1 and (R,Sp,Rp)-2,
which are based on the C2-symmetrical 2,2″-biferrocenediyl
backbone, only one substrate (MAC) gave a product with such
a high enantiomeric excess (91% ee) (Table 1, entry 2). It appears
that, in asymmetric hydrogenations, Walphos ligands and their
biferrocene analogues show significantly different performances.
This finding becomes even more apparent when, in addition
to ee values, the absolute configurations of the products are
considered. This comparison is based on the fact that the side-
chain-substituted ferrocene unit of all ligands used has the R,Sp
absolute configuration. For the substrates MAC, MAA, and
DMI the product absolute configurations obtained with ligands
(R,Sp,Sp)-1 and (R,Sp,Sp)-2 are identical with those obtained
with their Walphos analogues (MAC, MAA, S; DMI, R), while
those achieved with ligands (R,Sp,Rp)-1 and (R,Sp,Rp)-2 vary
with the substitution pattern of the phosphine substituents. The
product with an S configuration was obtained with (R,Sp,Rp)-1,
entries 2, 3, 6, and 8). Surprisingly, with 2-methylcinnamic acid
(MCA) the opposite trend was observed. In this case, the use of
ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2 gave products with 89% and
92% ee, respectively, while the corresponding Walphos ligands
resulted in only 62% and 83% ee (Table 1, entries 9 and 10).8,9
Given the results obtained for MCA, it seemed of interest to
investigate the performance of ligands (R,Sp,Sp)-1 and
(R,Sp,Sp)-2 in the hydrogenation of the structurally related
and commercially interesting cinnamic acid derivative IPCA-
D.1a,7 The use of the original Walphos ligands SL-W001-1 and
SL-W002-1 in the rhodium-catalyzed hydrogenation of IPCA-D
gave products with 94% and 74% ee after isolation (Table 1,
entries 11 and 12). For this sterically much more demanding
substrate, both values are higher than those obtained with MCA
(83% and 62% ee). However, when their biferrocene analogues
(R,Sp,Sp)-1 and (R,Sp,Sp)-2 were applied in the hydrogenation
of IPCA-D the opposite trend was seen. In comparison to
MCA, the product ee values dropped from 89% and 92% ee to
77% and 88% ee, respectively.
a
Table 1. Hydrogenation Results Obtained with Walphos Ligands and Their Biferrocene Analogues
biferrocene
ligand
ee, %
(confign)
biferrocene
ligand
ee, %
(confign)
Walphos
b
ee, %
(confign)
entry substrate
conversn, %
conversn, %
ligand
conversn, %
1
MAC
MAC
MAA
MAA
DMI
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
(R,Sp,Sp)-1
(R,Sp,Sp)-2
100
100
100
100
100
100
100
100
100
100
100
99
61 (S)
80 (S)
65 (S)
75 (S)
77 (R)
59 (R)
80 (S)
84 (S)
89 (R)
92 (R)
77 (S)
88 (S)
96 (S,S)
98 (S,S)
68 (S)
92 (S)
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
(R,Sp,Rp)-1
(R,Sp,Rp)-2
100
100
100
100
99
21 (S)
91 (R)
51 (S)
89 (R)
26 (R)
77 (S)
44 (R)
29 (R)
40 (R)
46 (S)
34 (R)
54 (R)
85 (S,S)
80 (S,S)
75 (S)
33 (S)
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
SL-W001-1
SL-W002-1
100
100
100
100
100
100
100
77
63 (S)
88 (S)
97 (S)
96 (S)
52 (R)
87 (R)
82 (R)
89 (R)
83 (S)
62 (S)
94 (R)
74 (R)
96 (S,S)
85 (R,R)
93 (S)
76 (S)
2
3
4
5
6
DMI
100
100
100
100
100
100
100
100
100
100
94
7
PCA
8
PCA
9
MCA
MCA
IPCA-D
IPCA-D
ACA
99
10
11
12
13
14
15
16
100
100
100
100
100
100
100
100
100
99
ACA
EOP
EOP
100
a
Reaction conditions: for alkenes, 1 mmol of substrate in 2.5 mL of MeOH, reaction time 16 h, 20 °C, hydrogen pressure MAC, MAA, DMI 1 bar,
MCA 20 bar, and PCA, IPCA-D 50 bar, metal precursor [Rh(NBD)2]BF4 (NBD = norbornadiene); for ketones, 2.53 mmol of ACA or 1 mmol of
EOP in 10 mL of MeOH, reaction time 16 h, 80 °C, hydrogen pressure 80 bar, additive HCl(aq), metal precursor [RuI2(p-cymene)]2. Absolute
b
configuration R,Sp.
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whereas (R,Sp,Rp)-2 resulted in the product with an R
configuration (Table 1, entries 1−6). The hydrogenation of
substrates PCA, MCA, and IPCA-D with ligands (R,Sp,Sp)-1
and (R,Sp,Sp)-2, however, resulted in products that had absolute
configurations opposite to those obtained with the correspond-
ing Walphos ligands SL-W001-1 and SL-W002-1 (Table 1,
entries 7−12). The hydrogenation results for ketones ACA and
EOP are more consistent since, with one exception (ACA and
ligand SL-W002-1; Table 1, entry 14), the same product
configuration was detected in all cases (ACA, S,S; EOP, S).
In summary, the original Walphos ligands appear to have a
broader scope of applicability than their biferrocene-based
analogues. The replacement of the backbone phenyl ring of
Walphos-type ligands gave derivatives with either an Sp,Rp- or
Sp,Rp-configured biferrocene backbone. In the hydrogenation of
alkenes and ketones these diastereomeric ligands show signifi-
cantly different performances in comparison to each other and also
in comparison to the corresponding Walphos ligand. From the
experimental results it is clear that the changes in the ligand
backbone are so pronounced that not only do the ee values change
significantly but also, in several cases, the product absolute
configuration of the predominant enantiomer is reversed (for a
comparison of the molecular structures of complexes [PdCl2(SL-
W002-1)], [PdCl2((R,Sp,Rp)-1)], and [PdCl2((R,Sp,Sp)-1)] see
Figure S4, in the Supporting Information).
it seems that for the development of efficient catalytic systems the
search for matching catalyst/substrate pairs is at least as important
as the search for novel catalyst backbones and structures.
EXPERIMENTAL SECTION
■
General Details. All reactions except oxidations with H2O2 were
carried out under an argon atmosphere using standard Schlenk
techniques and dry solvents. Solvents were dried according to standard
procedures under an argon atmosphere and were freshly distilled prior
to use. Tetrahydrofuran (THF) was dried over sodium/benzophe-
none, dichloromethane (DCM) and acetone were dried over P2O5,
Et2O was dried over LiAlH4, MeOH was dried over magnesium
methoxide, and toluene was dried over sodium. Column chromatog-
raphy was performed either on silica gel (Merck, 40−63 μm) or on
aluminum oxide (Merck, aluminum oxide 90). Petroleum ether (PE,
boiling range 60−80 °C), ethyl acetate (EA), and triethylamine (TEA)
were used as the eluents. NMR spectra were recorded either in CDCl3
or in CD2Cl2. Chemical shifts are referenced to CHCl3 (1H, 7.26 ppm)
and CDCl3 (13C, 77.0 ppm) and to CDHCl2 (1H, 5.32 ppm) and
CD2Cl2 (13C, 53.7 ppm). 31P NMR spectra are referenced to 85%
H3PO4 (31P, 0 ppm). For the assignment of peaks, the following
abbreviations were used: s = singlet, bs = broad singlet, d = doublet,
t = triplet, q = quartet, dd = doublet of doublets, m = multiplet.
Coupling constants in 13C NMR spectra are due to 31P−13C or
19F−13C coupling. High-resolution mass spectra were recorded on an
ESI-Qq aoTOF MS system. Optical rotations were measured in
CHCl3. Conversion and ee values were measured by GC and HPLC.
CONCLUSION
■
The newly synthesized ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2
perform very well in the rhodium-catalyzed hydrogenation of
2-methylcinnamic acid (MCA) to give products with
enantiomeric excesses of 89% and 92%, respectively. In the
ruthenium-mediated hydrogenation of acetylacetone (ACA)
and ethyl 3-oxopentanoate (EOP) even higher enantiomeric
excesses could be achieved (ACA, 98%; EOP, 92% ee).
However, for the commercially interesting substrate IPCA-D
the Walphos ligand SL-W001-1 still gives the best results.
The performance of the original R,Sp-configured Walphos
ligands SL-W001-1 and SL-W002-1 in the rhodium-catalyzed
asymmetric hydrogenation of several alkenes and the ruthenium-
catalyzed hydrogenation of two ketones was compared to that of
their analogous biferrocene-based ligands 1 and 2 of R,Sp,Sp and
R,Sp,Rp absolute configuration, respectively. The newly synthesized
ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2 perform particularly well in the
hydrogenation of MCA, ACA, and EOP, but in general they do
not match the performance of the original Walphos ligands. In a
number of cases products with opposite absolute configuration
were formed. The use of the ligands (R,Sp,Sp)-1 and (R,Sp,Sp)-2,
with one exception (MAC, 91% ee), only gave moderate product
ee values. For the diastereomeric biferrocene ligands the R,Sp,Sp
configuration clearly matches much better than the R,Sp,Rp
configuration.
General Atom Numbering Schemes for NMR Assignment.
(Sp)-2-{(R)-1-Bis[3,5-bis(trifluoromethyl)phenyl]phosphino-
ethyl}-(Sp)-2″-diphenylphosphino-1,1″-biferrocene ((R,Sp,Sp)-1).
To a degassed solution of phosphine oxide (R,Sp,Sp)-8 (500 mg, 0.474
mmol) in THF (10 mL) were added PMHS (0.408 mL, 4.74 mmol) and
Ti(O-iPr)4 (0.719 mL, 2.37 mmol). The resulting mixture was heated
under reflux under argon at 75 °C for 3 h. The resulting dark green
solution was cooled to room temperature and transferred to the top of
a column (aluminum oxide, PE/EA/EtOH = 90/10/1) without prior
workup. Elution and subsequent removal of the solvents gave the
crude product as an orange solid. In order to remove excess PMHS, the
crude product was again purified by chromatography (aluminum
oxide, PE/EA = 10/1) to give the pure product as an orange solid
1
(yield: 457 mg, 0.436 mmol, 92%). Mp: 74 °C. H NMR (400 MHz,
CDCl3): δ 1.46 (dd, J1 = 7.1 Hz, J2 = 9.8 Hz, 3H, CH3CH), 3.60 (dd,
J1 = 1.5 Hz, J2 = 2.3 Hz, 1H, H3/H5), 3.62−3.62 (m, 1H, CH3CH),
3.84 (s, 5H, Cp‴), 4.12 (s, 5H, Cp′), 4.19−4.20 (m, 2H, H4 + H3″),
4.30−4.35 (m, 2H, H4″ + H5″), 4.79−4.82 (m, 1H, H3/H5), 7.16−
7.24 (m, 3H, PhC/D-meta + PhC/D-para), 7.29−7.37 (m, 2H, PhC/D
-
ortho), 7.38−7.44 (m, 3H, PhC/D-meta + PhC/D-para), 7.45 (bd, J = 4.7
Hz, 2H, PhA/B-ortho), 7.56 (bd, J = 5.9 Hz, 2H, PhA/B-ortho), 7.65−
7.75 (m, 2H, PhC/D-ortho), 7.77 (bs, 1H, PhA/B-para), 7.89 (bs, 1H,
PhA/B-para). 13C{1H} NMR (100.6 MHz, CDCl3): δ 18.2 (d, J = 6.8
Hz, CH3CH), 29.6 (dd, J1 = 6.3 Hz, J2 = 19.1 Hz, CH3CH), 66.4 (d,
J = 8.8 Hz, C3/C5), 66.8 (C4), 69.9 (C4″), 70.26 (5C, Cp′/Cp‴),
70.28 (5C, Cp′/Cp‴), 71.0 (d, J = 12.5 Hz, C3/C5), 73.1 (d, J = 4.3
Hz, C3″), 73.5 (d, J = 5.1 Hz, C5″), 74.4 (d, J = 16.8 Hz, C1″), 83.4
(bs, C1), 88.8 (d, J = 18.2 Hz, C2), 90.4 (d, J = 28.4 Hz, C2″), 123.0
(q, J = 273.1 Hz, 2C, CF3), 123.1 (q, J = 273.5 Hz, 2C, CF3), 122.1−
122.3 (m, PhA/B-para), 123.3−123.6 (m, PhA/B-para), 127.9−128.1
The replacement of the Walphos ferrocenylphenyl backbone
with a biferrocene unit of either Sp,Sp or Sp,Rp absolute
configuration seems to result in marked structural changes in
the ligands and complexes. These changes are reflected in the
catalysis results, which in most cases differ significantly not only
in product ee values but also in product absolute configurations.
Nevertheless, for each series of ligands matching substrate/
catalyst pairs were identified that gave the corresponding
product with reasonably high enantiomeric excess: i.e., MCA/
(R,Sp,Sp)-2, 92% ee; ACA/(R,Sp,Sp)-2, 98% ee; MAC/(R,Sp,Rp)-
2, 91% ee; MAA/SL-W002-1, 97% ee; DMI/SL-W001-1, 87% ee;
IPCA-D/SL-W002-1, 94% ee; EOP/SL-W001-1, 93% ee. Overall,
(m, 4C, PhC-meta + PhD-meta), 128.1 (PhC/D-para), 129.3 (PhC/D
-
para), 131.7−132.1 (m, 2C, PhA/B-ortho), 132.3 (d, J = 17.7 Hz, 2C,
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PhC/D-ortho), 134.6−135.1 (m, PhA/B-ortho), 135.6 (q, J = 22.9 Hz,
2C, PhC/D-ortho), 137.8, 138.1, 140.1, 140.3 (2C, PhA/B-ipso), 139.4,
139.5, 141.1, 141.2 (2C, PhC/D-ipso). PhA/B-meta not observed.
31P{1H} NMR (162 MHz, CDCl3): δ −21.7 (bs, CH3CHPR2), 9.0
(d, J = 3.9 Hz, Fc-PPh2). HR-MS (ESI, MeOH/MeCN): m/z [M]+
(R,Sp,Sp)- and (R,Sp,Rp)-2″-Bromo-2-[1-(N,N-dimethylamino)-
ethyl]-1,1″-biferrocene ((R,Sp,Sp)-5 and (R,Sp,Rp)-5). To a
degassed solution of (R)-3 (584 mg, 2.27 mmol) in THF (3 mL)
was added dropwise at −78 °C sec-BuLi (1.4 M in cyclohexane, 1.8 mL,
2.52 mmol). The resulting deep red solution was stirred for 1 h at
−78 °C and for 2 h at 0 °C. A solution of ZnBr2 in THF (1.3 M,
2.3 mL, 2.99 mmol) was added, and the reaction mixture was stirred
for a further 40 min at 0 °C. A solution of [Pd2(dba)3]·CHCl3
(118 mg, 0.114 mmol) and tris(2-furyl)phosphine (212 mg, 0.913 mmol)
in THF was prepared. The mixture was degassed and stirred for 20 min
at room temperature to give a dark green clear solution. To this catalyst
solution were transferred a degassed solution of rac-4 (577 mg,
1.476 mmol) in THF (2 mL) and the freshly prepared ferrocenylzinc
compound. The resulting solution was heated under argon at 75 °C
for 19 h. The reaction mixture was cooled to room temperature,
quenched with 5 M NaOH (5 mL), diluted with water, and extracted
with Et2O (3 × 70 mL). The combined organic phases were washed
with water (3 × 50 mL) and brine (2 × 50 mL) and dried over
MgSO4. The mixture was filtered, the solvents were evaporated, and
the crude products were separated by column chromatography on
aluminum oxide. PE eluted excess tfp and PE/Et2O/NEt3 60/1/3
eluted the first diastereomer (R,Sp,Sp)-5 and excess 3, while PE/Et2O/
NEt3 5/5/1 gave the second diastereomer (R,Sp,Rp)-3. Diastereomer
(R,Sp,Sp)-5: yield 32% (249 mg, 0.749 mmol). Derivative (R,Sp,Rp)-5:
calcd 1038.0799 for C50H36F12Fe2P2, found 1038.0806. [α]20 (nm):
λ
−488° (589) (c 0.235, CHCl3).
(Sp)-2-[(R)-1-Diphenylphosphinoethyl]-(Sp)-2″-diphenyl-
phosphino-1,1″-biferrocene ((R,Sp,Sp)-2). To a degassed solution
of crude (R,Sp,Sp)-9 (500 mg, 0.626 mmol) in THF (5 mL) were
added PMHS (0.430 mL) and Ti(O-iPr)4 (711.9 mg, 2.50 mmol). The
resulting mixture was heated under reflux under argon at 75 °C for 4 h.
The resulting dark green solution was cooled to room temperature and
transferred to the top of a column (aluminum oxide, PE/EA/EtOH =
85/15/1) without prior workup. Elution and subsequent removal of
the solvents gave the crude product as an orange solid. In order to
remove excess PMHS, the crude product was suspended in PE/EA
(95/5) and filtered. The product was washed several times with the
same solvent mixture and was dried in vacuo (yield: 340 mg, 4.38
1
mmol, 70%). Mp: 89 °C. H NMR (600 MHz, CD2Cl2): δ 1.50 (dd,
J1 = 7.1 Hz, J2 = 12.2 Hz, 3H, CH3CH), 3.26−3.33 (m, 1H, CH3CH),
3.85 (s, 5H, Cp‴), 4.13−4.15 (m, 1H, H3/H5), 4.14 (s, 5H, Cp′),
4.19−4.21 (m, 3H, H3″ + H5″ + H4), 4.48 (dt, J1 = 0.6 Hz, J2 = 2.6 Hz,
1H, H4″), 4.57−4.59 (m, 1H, H3/H5), 7.02−7.07 (m, 2H, PhB-ortho),
7.10−7.16 (m, 2H, PhD-ortho), 7.17−7.21 (m, 2H, PhB-meta), 7.22−7.28
(m, 3H, PhD-meta + PhB/D-para), 7.33−7.38 (m, 4H, PhA-meta + PhA-
para + PhB/D-para), 7.38−7.41 (m, 3H, PhC-meta + PhC-para), 7.47−
7.52 (m, 2H, PhA-ortho), 7.65−7.70 (m, 2H, PhC-ortho). 13C{1H} NMR
(150.9 MHz, CD2Cl2): δ 20.2 (d, J = 9.9 Hz, CH3CH), 28.6 (dd, J1 = 3.2
Hz, J2 = 7.8 Hz, CH3CH), 66.8 (C4), 67.7 (d, J = 10.9 Hz, C3/C5), 69.9
(C4″), 70.0 (d, J = 11.5 Hz, C3/C5), 70.45 (5C, Cp′/Cp‴), 70.47 (5C,
Cp′/Cp‴), 72.7 (d, J = 4.3 Hz, C3″/C5″), 73.5 (d, J = 15.4 Hz, C1″),
75.1 (bs, C3″/C5″), 83.6 (bs, C1), 91.1 (d, J = 29.0 Hz, C2″), 91.9 (C2),
128.2−128.8 (10C, 8Ph-meta + 2Ph-para), 129.4 (Ph-para), 129.8 (bs,
Ph-para), 132.9 (d, J = 14.1 Hz, 2C, PhB-ortho), 133.0 (d, J = 17.5 Hz,
2C, PhA-ortho), 135.2 (d, J = 19.5 Hz, 2C, PhD-ortho), 135.78 (d, J = 23.1
Hz, 2C, PhC-ortho), 139.7 (d, J = 11.7 Hz, PhC-ipso), 141.5 (d, J = 10.9
Hz, PhA-ipso), PhB-ipso and PhD-ipso not observed. 31P{1H} NMR (243
MHz, CD2Cl2): δ −24.5 (Fc-PPh2), 7.1 (CH3CH-PPh2). HR-MS (ESI,
MeOH/MeCN): m/z [M]+ calcd 766.1304 for C46H40Fe2P2, found
1
yield 45% (344 mg, 0.661 mmol). (R,Sp,Sp)-5: mp 113−115 °C; H
NMR (500.1 MHz, CDCl3) δ 1.39 (d, 3H, J = 6.7 Hz, CH3CH), 2.09
(s, 6H, N(CH3)2), 3.78 (q, J = 6.7 Hz, 1H, CH3CH), 4.09 (s, 5H,
Cp‴), 4.10−4.12 (bs, 6H, Cp′ + H4″), 4.21−4.22 (m, 1H, H3), 4.26
(dd, J1 = J2 = 2.6 Hz, 1H, H4), 4.49−4.51 (m, 1H, H3″), 4.87−4.89
(dd, J1 = 1.5 Hz, J2 = 2.5 Hz, 1H, H5), 5.01−5.03 (m, 1H, H5″);
13C{1H} NMR (125.8 MHz, CDCl3) δ 11.5 (CH3CH), 39.8 (2C,
N(CH3)2), 56.0 (CH3CH), 66.3 (C4″), 66.5 (C4), 67.0 (C3), 69.1
(C5″), 69.5 (C5), 70.2 (5C, Cp′), 71.6 (C3″), 71.8 (5C, Cp‴), 79.0
(Cq), 82.3 (Cq), 82.6 (Cq), 88.8 (Cq); HR-MS (ESI, MeOH/MeCN)
m/z [M + H]+ calcd 520.0026 for C24H27BrFe2N, found 520.0027;
[α]23 (nm): −850 (589) (c 0.725, CHCl3). (R,Sp,Rp)-5: Mp: 89−
λ
1
94 °C; H NMR (400 MHz, CDCl3): δ 1.51 (d, J = 6.9 Hz, 3H,
CH3CH), 1.70 (s, 6H, N(CH3)2), 3.42 (q, J = 6.9 Hz, 1H, CH3CH),
4.18 (dd, J1 = 1.4 Hz, J2 = 2.5 Hz, 1H, H3), 4.26 (dd, J1 = J2 = 2.6 Hz,
1H, H4″), 4.28 (s, 5H, Cp′), 4.36 (bs, 6H, Cp‴ + H4), 4.39 (dd, J1 =
1.5 Hz, J2 = 2.6 Hz, 1H, H5″), 4.45 (dd, J1 = 1.5 Hz, J2 = 2.6 Hz, 1H,
H3″), 4.60 (dd, J1 = 1.4 Hz, J2 = 2.5 Hz, 1H, H5); 13C{1H} NMR
(100.6 MHz, CDCl3): δ 20.1 (CH3CH), 41.1 (2C, N(CH3)2), 55.3
(CH3CH), 66.1 (C4″), 66.5 (C4), 67.0 (C3), 69.6 (5C, Cp′), 69.8
(C3″), 70.1 (C5″), 71.5 (5C, Cp‴), 71.6 (C5), 82.6 (Cq), 82.7 (Cq),
85.7 (Cq), 88.7 (C2); HR-MS (ESI, MeOH/MeCN) m/z [M + H]+
766.1308. [α]20 (nm): −481° (589) (c 0.245, CHCl3).
λ
(Sp)-2-[(R)-1-Diphenylphosphinoethyl]-(Sp)-2″-diphenyl-
phosphino-1,1″-biferrocene−P,P-bis(borane) ((R,Sp,Sp)-2·
2BH3). The derivative (R,Sp,Sp)-2 (100 mg, 0.126 mmol) was
dissolved in THF (2 mL), and the solution was degassed. To the
resulting solution was added dropwise at 0 °C a solution of BH3 in
THF (1 M, 0.38 mL, 0.38 mmol), and the mixture was stirred for 16 h
at room temperature The reaction mixture was quenched at 0 °C with
water (15 mL) and extracted twice with DCM. The combined organic
phases were washed with water, dried over MgSO4, and filtered, and
the solvents were evaporated. The desired product was obtained as an
orange foam (yield: 100.9 mg, 0.125 mmol, >99%). Single crystals
suitable for X-ray structure determination were grown from CH2Cl2/
ethyl acetate by slow evaporation of the solvent. Mp: >180 °C dec. 1H
NMR (400 MHz, CDCl3): δ 0.86-1.90 (6H, BH3), 2.19 (dd, J1 = 7.2
Hz, J2 = 17.4 Hz, 3H, CH3CH), 3.77 (s, 5H, Cp′), 3.80 (t, J = 2.6 Hz,
H4), 3.86−3.89 (m, 1H, H3″), 3.96 (s, 5H, Cp‴), 4.00−4.04 (m, 1H,
H3), 4.05−4.16 (m, 1H, CH3CH), 4.36−4.42 (m, 1H, H3), 4.44 (t,
J = 2.6 Hz, H4″), 4.64−4.68 (m, 1H, H5″), 7.34−7.87 (m, 20H, Ph).
13C{1H} NMR (100.6 MHz, CDCl3): δ 23.7 (d, J = 5.4 Hz, CH3CH),
calcd 520.0026 for C24H27BrFe2N, found 520.0022; [α]20 (nm)
λ
−950° (589), −1062° (578), −1631° (546) (c 0.283, CHCl3).
(R,Sp,Sp)-2-[1-(N,N-Dimethylamino)ethyl]-2″-diphenylphos-
phino-1,1″-biferrocene ((R,Sp,Sp)-6). To a degassed solution of
(R,Sp,Sp)-5 (2.43 g, 4.67 mmol) in THF (30 mL) was added dropwise
at −40 °C a solution of sec-BuLi (1.3 M in cyclohexane, 4.3 mL,
5.6 mmol). The resulting dark red mixture was stirred for 40 min at
−40 °C and warmed to room temperature, and subsequently
chlorodiphenylphosphine (1.1 mL, 6.4 mmol) was added. The mixture
was stirred for 18 h at room temperature and for 1 h at 35 °C. The
reaction was quenched at room temperature with 5 mL of saturated
aqueous NaHCO3, the product was extracted twice with ethyl acetate,
and the combined organic phases were washed with water and brine.
After drying over MgSO4, filtration, and evaporation of the solvents,
the crude product was obtained as an orange solid. After chromato-
graphy (aluminum oxide, PE/EE/NEt3 = 100/1/3) the pure product
was obtained as an orange foam (yield: 1.69 g, 2.70 mmol, 58%).
Single crystals suitable for X-ray structure determination were grown
from ethyl acetate by slow evaporation of the solvent. Mp: 196−
29.6 (d, J = 29.9 Hz, CH3CH), 65.9 (C4), 66.4 (d, J = 15.4 Hz, C1″),
68.2 (bs, C5), 70.0 (d, J = 6.8 Hz, C4″), 70.2 (5C, Cp′), 70.5 (5C,
Cp‴), 72.4 (C3), 72.9 (d, J = 4.3 Hz, C3″), 74.7 (d, J = 7.8 Hz, C5″),
78.9 (d, J = 3.9 Hz, C1), 89.6 (d, J = 13.4 Hz, C2″), 91.4 (d, J = 2.2 Hz,
C2), 128.1−129.1 (8C, Ph-meta), 130.3−131.4 (4C, Ph-para), 132.9 (d,
J = 9.2 Hz, 2C, Ph-ortho), 133.8−134.2 (6C, Ph-ortho), 128.5, 130.0,
130.5, 131.8, 132.4 (Ph-ipso). 31P{1H} NMR (162 MHz, CDCl3): δ 17.4
(bs, Fc-PPh2), 29.4 (bs, CH3CH-PPh2). HR-MS (ESI, MeOH/MeCN):
m/z [M + Na]+ calcd 817.1857 for C46H40Fe2P2Na, found 817.1833;
1
201 °C. H NMR (500.1 MHz, CDCl3): δ 1.34 (d, J = 6.6 Hz, 3H,
CH3CH), 2.19 (s, 6H, N(CH3)2), 3.69 (s, 5H, Cp′), 3.80 (s, 5H,
Cp‴), 3.88 (q, J = 6.6 Hz, 1H, CH3CH), 3.92 (bs, 1H, H3″),
4.18−4.21 (m, 2H, H3 + H4), 4.39 (dd, J1 = J2 = 2.5 Hz, 1H, H4″),
5.34−5.36 (m, 1H, H5″), 5.39−5.42 (m, 1H, H5), 7.26−7.30 (m, 1H,
[α]20 (nm): +371° (589) (c 0.265, CHCl3).
λ
1949
dx.doi.org/10.1021/om401074a | Organometallics 2014, 33, 1945−1952

Organometallics
Article
PhB-para), 7.31−7.36 (m, 2H, PhB-meta), 7.36−7.40 (m, 3H, PhA-meta
+ PhA-para), 7.45−7.49 (m, 2H, PhB-ortho), 7.59−7.63 (m, 2H, PhA-
ortho); PhA pointing toward Cp‴. 13C{1H} NMR (125.6 MHz,
CDCl3): δ 10.2 (CH3CH), 39.9 (2C, N(CH3)2), 56.6 (CH3CH), 65.7
(C3/C4), 66.4 (C3/C4), 67.5 (5C, Cp′), 69.7 (C4″), 70.3−70.7 (6C,
Cp‴ + C5), 72.8 (bs, C5″), 73.0−73.3 (2C, C3″ + C1″), 83.8 (C1),
88.0 (C2), 89.6 (d, J = 22.6 Hz, C2″), 127.9 (d, J = 7.5 Hz, 2C, PhA-
meta), 128.2 (bs, 3C, PhB-meta + PhB-para), 128.8 (PhA-para), 133.1
(d, J = 19.3 Hz, 2C, PhB-ortho), 135.4 (d, J = 22.0 Hz, 2C, PhA-ortho),
139.0 (d, J = 11.3 Hz, PhA-ipso), 140.2 (d, J = 11.3 Hz, PhB-ipso).
31P{1H} NMR (162 MHz, CDCl3): δ −20.0. HR-MS (ESI, MeOH/
MeCN): m/z [M + H]+ calcd 626.1362 for C36H37Fe2NP, found
CH3CH), 3.21 (bs, 1H, Cp), 3.64 (s, 5H, Cp), 3.95−4.09 (m, 3H,
CH3CH + 2 Cp), 4.14 (s, 5H, Cp), 4.50 (bs, 1H, Cp), 5.00 (bs, 1H,
Cp), 5.64 (bs, 1H, Cp), 7.42−7.60 (m, 6H, Ph), 7.68−7.75 (d, J = 6.3
Hz, 2H, Ph), 7.77−7.81 (m, 2H, Ph), 7.82−7.93 (m, 5H, Ph), 7.98 (bs,
1H, Ph). 13C{1H} NMR (150.9 MHz, CDCl3): δ 17.5 (CHCH3), 29.7
(d, J = 19.5 Hz, CHCH3), 66.9 (Cp), 67.3 (Cp), 69.8 (5C, Cp), 70.8 (d,
J = 17.4 Hz, Cp), 71.2 (5C, Cp), 72.6 (Cp), 73.4 (Cp), 75.7 (Cp),
80.2 (Cp), 86.6−87.1 (m, Cp), 121.0−139.5 (Ph), 2 Fc-Cq not
observed. 31P{1H} NMR (243 MHz, CDCl3): δ 7.8 (CH3CHPR2), 30.8
(Fc-P(O)Ph2). HR-MS (ESI, MeOH/MeCN): m/z [M]+ calcd
1054.0748 for C50H46F12Fe2OP2, found 1054.0766. [α]20 (nm):
λ
−116° (589) (c 0.19, CHCl3).
626.1351; [α]23 (nm): −554 (589) (c 0.232, CHCl3).
(Sp)-2-[(R)-1-Diphenylphosphinoethyl]-(Sp)-2″-diphenyl-
phosphinyl-1,1″-biferrocene ((R,Sp,Sp)-9). In a Schlenk flask,
phosphine oxide (R,Sp,Sp)-7 (800 mg, 1.25 mmol) was dissolved
under Ar in freshly distilled acetic acid (20 mL) through which Ar had
been bubbled for several hours. The resulting solution was again
degassed. Subsequently diphenylphosphine (929.5 mg, 4.99 mmol)
was added and the resulting mixture was heated under Ar at 75 °C for
18 h. After the mixture was cooled to room temperature, the acetic
acid was removed under vacuum, the residue was taken up in DCM
(15 mL), and saturated aqueous NaHCO3 was added. The phases
were separated, and the aqueous phase was extracted with DCM. The
combined organic phases were washed with water and brine and dried
over MgSO4. After filtration and evaporation of the solvents, the crude
λ
(R,Sp,Sp)-2-[1-(N,N-Dimethylamino)ethyl]-2″-diphenylphos-
phinyl-1,1″-biferrocene ((R,Sp,Sp)-7). Method A: From (R,Sp,Sp)-6
with H2O2. To a solution of (R,Sp,Sp)-6 (649 mg, 1.04 mmol) in
acetone (150 mL) was added an aqueous solution of H2O2 (30%,
5 mL). The reaction mixture was stirred for 50 min at room
temperature and was then quenched with saturated aqueous Na2S2O3.
The organic material was extracted with EtOAc, the combined organic
phases were washed with water and brine, dried over MgSO4 and
filtered, and the solvents were evaporated. The crude product was
purified by chromatography (aluminum oxide, PE/EA/TEA = 5/1/1),
and the pure product was obtained as a red-orange solid (yield:
608 mg, 0.948 mmol, 91%).
Method B: From (R,Sp,Sp)-5 with ClP(O)Ph2. Synthesis procedure as
described for (R,Sp,Sp)-6: (R,Sp,Sp)-5 (1.220 g, 2.346 mmol) in THF
(26 mL), n-BuLi (1.6 M in hexane, 1.76 mL, 2.815 mmol), and
diphenylphosphinyl chloride (0.6 mL, 3.167 mmol). Purification by
column chromatography (aluminum oxide, PE/EE/NEt3 10/10/1)
yielded 1.164 g (1.815 mmol, 77%) of the pure product as an orange
foam. Single crystals suitable for X-ray structure determination were
grown from ethyl acetate by slow evaporation of the solvent.
1
product was used in the next step without further purification. H
NMR (400 MHz, CDCl3): δ 2.24 (d, J = 6.4 Hz, 3H, CH3CH), 3.58
(s, 5H, Cp′), 3.66−3.71 (m, 1H, Cp), 3.86 (q, J = 6.4 Hz, 1H,
CH3CH), 3.91−3.94 (m, 1H, Cp), 4.01 (t, J = 2.6 Hz, 1H, Cp), 4.11
(s, 5H, Cp), 4.42−4.45 (m, 1H, Cp), 5.05−5.09 (m, 1H, Cp), 5.36
(dd, J1 = 1.5 Hz, J2 = 2.6 Hz, 1H, Cp), 7.72−7.94 (m, 20H, Ph).
31P{1H} NMR (162 MHz, CDCl3): δ 5.8 (Fc-PPh2), 29.9 (CH3CH-
P(O)Ph2). Bisphosphine oxide: 31P{1H} NMR (162 MHz, CDCl3) δ
28.6 (Fc-P(O)Ph2), 36.0 (CH3CH-P(O)Ph2).
Mp: 201−203 °C. 1H NMR (500.1 MHz, CDCl3): δ 1.36 (d, J = 6.1
Hz, 3H, CH3CH), 2.28 (s, 6H, N(CH3)2), 3.42 (bs, 5H, Cp′), 3.78
(bs, 1H, H3″), 4.06 (s, 5H, Cp‴), 4.10 (q, J = 6.1 Hz, 1H, CH3CH),
4.14 (dd, J1 = J2 = 2.6 Hz, 1H, H4), 4.18 (bs, 1H, H3), 4.42−4.45 (m,
1H, H4″), 5.53 (bs, 1H, H5″), 5.91 (bs, 1H, H5), 7.44−7.47 (m, 2H,
PhB-meta), 7.48−7.54 (m, 4H, PhA-meta + PhA-para + PhB-para),
7.77−7.83 (m, 2H, PhB-ortho), 7.85−7.91 (m, 2H, PhA-ortho); PhB
pointing toward Cp‴. 13C{1H} NMR (125.8 MHz, CDCl3): δ 8.7
(CH3CH), 39.5 (2C, N(CH3)2), 57.3 (CH3CH), 67.1 (C4), 68.6
(C3), 69.5 (5C, Cp′), 71.0 (d, J = 12.2 Hz, C4″), 71.2 (5C, Cp‴), 71.8
(C5), 73.8 (d, J = 8.2 Hz, C5″), 76.3 (d, J = 16.6 Hz, C3″), 81.8 (C1),
87.1 (C2), 89.0 (d, J = 9.4 Hz, C2″), 127.8 (d, J = 11.7 Hz, 2C, PhB-
meta), 128.5 (d, J = 11.9 Hz, 2C, PhA-meta), 131.1 (PhA/B-para), 131.7
(PhA/B-para), 132.0 (d, J = 9.4 Hz, 2C, PhA-ortho), 132.1 (d, J = 10.0
Hz, 2C, PhB-ortho), 134.7, 135.0, 135.5, 135.9 (2C, PhA-ipso + PhB-
ipso); 1 Cq (C1″) not observed. 31P{1H} NMR (162 MHz, CDCl3): δ
31.9. HR-MS (ESI, MeOH/MeCN): m/z [M + H]+ calcd 642.1311
Dichloro{(Sp)-2-[(R)-1-diphenylphosphinoethyl-κP]-(Sp)-2″-
diphenylphosphino-κP-1,1″-biferrocene}palladium(II)
([PdCl2(R,Sp,Sp)-(2)]). To a mixture of (R,Sp,Sp)-2 (60 mg, 0.078 mmol)
and bis(acetonitrile)dichloropalladium(II) (20.28 mg, 0.065 mmol) was
added degassed DCM (3 mL). The dark red solution was stirred under
argon at room temperature for 16 h. The solution was filtered under inert
conditions over a pad of Celite. The solvent was removed, and the dark
red solid residue was dried in vacuo (yield: 73 mg, 0.077 mmol, 99%).
1
Mp: >200 °C (unsolvated complex). H NMR (400 MHz, CDCl3): δ
1.76 (dd, J1 = 7.2 Hz, J2 = 12.2 Hz, 3H, CH3CH), 3.30−3.33 (m, 1H,
H3), 3.44 (dd, J1 = 1.5 Hz, J2 = 2.5 Hz, 1H, H5), 3.65−3.68 (m, 1H, H3″),
3.86 (t, J = 2.6 Hz, 1H, H4), 4.16 (s, 5H, Cp′), 4.45 (s, 5H, Cp‴), 4.50 (t,
J = 2.6 Hz, 1H, H4″), 4.77−4.80 (m, 1H, H5″), 5.23−5.31
(m, 1H, CH3CH), 7.10−7.18 (m, 2H, PhD-meta), 7.19−7.25 (m, 1H,
PhD-para), 7.29−7.36 (m, 2H, PhC-meta), 7.36−7.48 (m, 5H, PhA-meta +
PhD-ortho + PhA/C-para), 7.49−7.62 (m, 4H, PhB-meta +PhB-para +
PhA/C-para), 7.73−7.85 (m, 4H, PhA-ortho + PhC-ortho), 8.26−8.35 (m,
2H, PhB-ortho). 13C{1H} NMR (100.6 MHz, CDCl3): δ 22.9 (d, J = 4.8
Hz, CH3CH), 31.5 (d, J = 5.8 Hz, CH3CH), 66.2 (C4), 67.2 (d, J = 2.3 Hz,
C3), 69.5 (5C, Cp′), 70.1 (d, J = 5.2 Hz, C4″), 70.4 (5C, Cp‴), 73.0 (C5),
74.2 (bs, C5″), 75.5 (d, J = 6.0 Hz, C3″), 81.1 (bs, C1), 89.6 (d, J = 7.7 Hz,
C2), 89.9 (d, J = 14.2 Hz, C2″), 127.0 (d, J = 11.5 Hz, 2C, PhA/D-meta),
127.1 (d, J = 12.3 Hz, 2C, PhA/D-meta), 127.7 (d, J = 11.4 Hz, 2C, PhC-
meta), 128.8 (d, J = 10.0 Hz, 2C, PhB-meta), 129.92 (PhA/C/D-para), 129.94
(PhA/C/D-para), 131.0 (d, J = 2.3 Hz, PhB/C/D-para), 131.1 (d, J = 3.0 Hz,
PhB/C/D-para), 132.0 (d, J = 10.0 Hz, 2C, PhA/C-ortho), 133.3 (d, J = 129.6
Hz, PhD-ipso), 133.5 (d, J = 9.2 Hz, 2C, PhB-ortho), 134.8 (d, J = 13.1 Hz,
2C, PhD-ortho), 127.4, 128.5, 129.0, 129.7, 130.6, and 132.1 PhA-ipso, PhB-
ipso, PhC-ipso not distinguishable. C1″ not observed. 31P{1H} NMR (162
MHz, CD2Cl2): δ 28.5 (Fc-PPh2), 48.1 (CH3CH-PPh2). HR-MS (ESI,
MeOH/MeCN): m/z [M − Cl]+ calcd 907.0027 for C46H52ClFe2P2Pd,
for C36H37Fe2NOP, found 642.1311. [α]23 (nm): −272° (589)
λ
(c 0.258, CHCl3).
(Sp)-2-{(R)-1-Bis[3,5-bis(trifluoromethyl)phenyl]phosphinoethyl}-
(Sp)-2″-diphenylphosphinyl-1,1″-biferrocene ((R,Sp,Sp)-8). In a
Schlenk flask, phosphine oxide (R,Sp,Sp)-7 (800 mg, 1.25 mmol) and
bis-(3,5-trifluoromethyl)phenylphosphine (0.86 g, 1.88 mmol) were
dissolved under Ar in freshly distilled acetic acid (20 mL) through which
Ar had been bubbled for several hours. The resulting solution was again
degassed and subsequently heated under Ar at 75 °C for 18 h. The
mixture was cooled to room temperature, the acetic acid was removed
under vacuum, the residue was taken up in DCM (15 mL), and
saturated aqueous NaHCO3 was added. The phases were separated, and
the aqueous phase was extracted with DCM. The combined organic
phases were washed with water and brine and dried over MgSO4. After
filtration and evaporation of the solvents, the crude product was purified
by column chromatography under inert conditions with deoxygenated
solvents on aluminum oxide. The solvent mixture PE/DEE 20/1
removed the excess diphenylphosphine and PE/EE 2/1 eluted the title
compound as an orange foam (yield: 797 mg, 0.749 mmol, 60%). Mp:
found 907.0050; [α]20 (nm): +636 (589) (c 0.115, CHCl3).
λ
Hydrogenations. The substrate (1 mmol) was dissolved under
argon in a degassed solvent (2.5 mL). The catalyst was formed in situ
by stirring a mixture of the ligand and metal precursor in a degassed
solvent (2.5 mL) for 30 min at room temperature The catalyst and the
1
123 °C. H NMR (600 MHz, CDCl3): δ 1.47 (bt, J = 6.5 Hz, 3H,
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substrate solutions were transferred through a stainless steel capillary
into either a glass or a steel autoclave. The argon gas was then replaced
by hydrogen gas (3−5 cycles) and the pressure was set. After
completion of the reaction, the reaction mixture was filtered through a
plug of silica. Conversions and ee values of the product were
determined by either gas chromatography or HPLC. In an effort to
ensure consistency and reproducibility, all hydrogenations were carried
out at least twice.
and corrections for absorption and λ/2 effects were applied with the
program SADABS.10a The structures were solved by direct methods
with the program SHELXS97, and refinement on F2 was carried out
with the program SHELXL97.10b Non-hydrogen atoms were refined
anisotropically. All H atoms were placed in calculated positions and
thereafter refined as riding. The absolute structures of all compounds
could be unambiguously determined by anomalous dispersion effects
and the Flack absolute structure parameter. Important crystallographic
data are provided below.
The following reaction conditions and methods were applied. MAC:
MAC (219.2 mg, 1 mmol); [Rh(NBD)2][BF4] + 1.1 equiv of ligand;
S/C = 25; solvent MeOH (5 mL); p(H2) 1 bar; 20 °C; reaction time
16 h. Analysis data for MAC: GC, column PERMABOND-L-Chirasil-Val
(25 m); 160 °C isothermal; MAC 11.1 min, R 25.4 min, S 28.6 min.
MAA: MAA (143.1 mg, 1 mmol); [Rh(NBD)2][BF4] + 1.1 equiv of
ligand; S/C = 25; solvent MeOH (5 mL); p(H2) 1 bar; 20 °C; reaction
time 16 h. Analysis data for MAA: GC, column PERMABOND-
L-Chirasil-Val (25 m); 110 °C isothermal; MAA 5.3 min, R 8.8 min,
S 10.9 min. DMI: DMI (158.2 mg, 1 mmol); [Rh(NBD)2][BF4] + 1.1 equiv
of ligand; S/C = 25; solvent MeOH (5 mL); p(H2) 1 bar; 20 °C; reaction
time 16 h. Analysis data for DMI: GC, column LIPODEX-E (50 m);
85 °C isothermal; DMI 46.2 min, S 29.5 min, R 30.7 min. MCA: MCA
(162.2 mg, 1 mmol); [Rh(NBD)2][BF4] + 1.1 equiv of ligand; S/C = 25;
solvent MeOH (5 mL); p(H2) 20 bar; 20 °C; reaction time 20 h. Workup
for MCA: after removal of the solvent under reduced pressure, the crude
product was dissolved in DCM and extracted with NaOH (2 M). The
organic phase was discarded. The aqueous phase was made acidic by
addition of aqueous HCl (to pH 1) and was extracted twice with DCM
(2 × 25 mL). The combined organic phases were washed with brine and
dried over MgSO4, and the solvent was removed under reduced pressure.
Subsequently, the residue was transformed into the corresponding methyl
ester. The residue was dissolved in MeOH, and diazomethane in Et2O
was added until the solution turned pale yellow and remained this color.
After the mixture was stirred for 20 min at room temperature, the solvent
was removed carefully under reduced pressure and the residue was filtered
through a short plug of silica, which had been wetted with MeOH.
Analysis data for MCA: HPLC, column Daicel, Chiraldex OB-H;
temperature 25 °C; eluent hexane/iPrOH 97:3; flow rate 0.5 mL/min;
detector DAD; Sig 230 nm; substrate 15.8 min, R 10.7 min, S = 11.6 min.
PCA: PCA (224.2 mg, 1 mmol); [Rh(NBD)2][BF4] + 1.1 equiv of
ligand; S/C = 100; solvent MeOH (5 mL); p(H2) 50 bar; 20 °C; reaction
time 19 h; esterification to the methyl ester see MCA. Analysis data for
MCA: HPLC, column Daicel, Chiraldex OD-H; temperature 25 °C,
eluent hexane/iPrOH 97:3, flow rate 0.5 mL/min; detector DAD; Sig
230 nm; substrate 20 min, R 18 min, S 18.7 min. IPCA-D: IPCA-D
(308.4 mg, 1 mmol); [Rh(NBD)2][BF4] + 1.1 equiv of ligand; S/C = 25;
solvent MeOH (5 mL); p(H2) 50 bar; 20 °C; reaction time 20 h. Analysis
data for IPCA-D: HPLC, column Chiralpak IC; temperature 25 °C;
solvent heptane/EtOH/TFA = 90/10/0.1; flow rate 1.0 mL/min;
detector DAD; Sig 230 nm; IPCA-D 5.6 min, S 8.7 min, R 10.3 min.
ACA: ACA (253.3 mg, 2.53 mmol); [RuI2(p-cymene)]2 + 1.1 equiv of
ligand; S/C = 500; solvent MeOH (10 mL); additive HCl(aq) (240 μL,
1 N); p(H2) 80 bar; 80 °C; reaction time 17 h. Analysis data for ACA:
GC, column PERMABOND-L-Chirasil-Val (25 m); 88 °C isothermal;
ACA 2.0 min, R 8.3 min, S 9.1 min. EOP: EOP (144.2 mg, 1 mmol);
[RuI2(p-cymene)]2 + 1.1 equiv of ligand; S/C = 100; solvent EtOH
(10 mL); additive HCl(aq) (47.4 μL, 1 N); p(H2) 80 bar; 80 °C; reaction
time 16 h. Formation of trifluoroacetate derivative: after removing the
solvent and drying under reduced pressure, to the remaining residue was
added trifluoroacetic anhydride (2 mL). After stirring for 20 min, the
excess trifluoroacetic anhydride was removed by blowing argon over the
solution and the residue was filtered through a short plug of silica, which
had been wetted with MeOH. Analysis data for EOP: GC, column
LIPODEX-E (50 m); 80 °C isothermal; substrate 15.6 min; R 26.6 min;
S 29.7 min.
(R,Sp,Sp)-2·2BH3: compound crystallized as a solvate with a mixture
of disordered CH2Cl2 and ethyl acetate in an estimated 60/40 ratio.
The chemical formula was idealized to (R,Sp,Sp)-2·2BH3·CH2Cl2,
C47H48B2Cl2Fe2P2, Mr = 879.01, orange prism, 0.60 × 0.07 × 0.05 mm,
monoclinic, space group P21 (No. 4), a = 11.3173(3) Å, b = 9.5521(3) Å,
c = 20.2125(5) Å, β = 93.674(2)°, V = 2180.56(10) Å3, Z = 2, μ =
0.893 mm−1, ρcalcd = 1.339 g cm−3, 55105 reflections collected and
merged to 12614 independent data (Rint = 0.039); after squeezing the
disordered solvent with program PLATON10c final R indices (all data)
were R1 = 0.0342, wR2 = 0.0679, 472 parameters, Flack absolute
structure parameter −0.020(6), excursions in difference Fourier map
between −0.23 and 0.43 e Å−3.
(R,Sp,Sp)-6: C36H36Fe2NP, Mr = 625.33, orange block from ethyl
acetate, 0.28 × 0.16 × 0.10 mm, monoclinic, space group P21 (No. 4),
a = 7.3616(3) Å, b = 18.1714(7) Å, c = 22.4087(9) Å, β = 99.319(2)°,
V = 2958.1(2) Å3, Z = 4 (Z′ = 2), μ = 1.061 mm−1, ρcalcd = 1.404 g cm−3,
70046 reflections collected and merged to 17172 independent data (Rint
=
0.090); final R indices (all data) were R1 = 0.0472, wR2 = 0.0847,
727 parameters, Flack absolute structure parameter 0.017(8), excursions
in difference Fourier map between −0.52 and 0.73 e Å−3.
(R,Sp,Sp)-7: C36H36Fe2NOP, Mr = 641.33, orange block from
ethyl acetate, 0.45 × 0.42 × 0.32 mm, monoclinic, space group P21
(No. 4), a = 10.4728(4) Å, b = 8.1019(3) Å, c = 17.7567(6) Å, β =
100.508(2)°, V = 1481.38(9) Å3, Z = 2, μ = 1.064 mm−1, ρcalcd = 1.438
g cm−3, 32255 reflections collected and merged to 8638 independent
data (Rint = 0.028); final R indices (all data) were R1 = 0.0197, wR2 =
0.0516, 373 parameters, Flack absolute structure parameter −0.004(5),
excursions in difference Fourier map between −0.26 and 0.37 e Å−3.
ASSOCIATED CONTENT
* Supporting Information
■
S
Figures, tables with geometric data, and CIF files for the crystal
structures of (R,Sp,Sp)-2·2BH3 (R,Sp,Sp)-6, and (R,Sp,Sp)-7 text
and figures with information on a comparison of the structural
features of complexes [PdCl2(SL-W002-1)], [PdCl2((R,Sp,Rp)-
2)], and [PdCl2((R,Sp,Sp)-2)]. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for W.W.: walter.weissensteiner@univie.ac.at.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the Austrian Science Foundation FWF (project
P23376-N19), the Beijing Nova Program (2009 B 37), the
Educational Council Foundation of Beijing (KM201010025012,
PHR201008395 and PHR201007114), and Solvias AG for their
strong support of this work. UMICORE is kindly acknowledged
for a generous gift of metal complexes.
X-ray Crystallography. Single crystal X-ray diffraction data for
(R,Sp,Sp)-2·2BH3, (R,Sp,Sp)-6, and (R,Sp,Sp)-7 were collected on a
Bruker Kappa APEX-2 CCD diffractometer at T = 100 K using
graphite-monochromated Mo Kα radiation (λ = 0.71073 Å) and
φ- and ω-scan fine-sliced frames covering complete Ewald spheres
with θmax = 30°. The data were integrated with the program SAINT,
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