Bis(perfluoroalkyl) phosphino-oxazoline: A modular, stable, strongly π-accepting ligand for asymmetric catalysis

Article abstract of DOI:10.1021/jo3011717

A new class of stable, strongly π-accepting and modular bis-(perfluoroalkyl)-phosphine-oxazoline ligands (FOX) as CO mimics was prepared. It was demonstrated that these ligands, when coordinated to palladium catalysts, promote the asymmetric alkylation of monosubstituted allyl substrates with excellent regio- and enantioselectivity. Solid and solution structure analysis of the FOX-ligated Pd-allyl intermediate reveals that the combination of relative steric and strong trans influences presented by the P(CF ₃)₂ moiety gave rise to the excellent selectivity.

Full text of DOI:10.1021/jo3011717

Article
pubs.acs.org/joc
Bis(perfluoroalkyl) Phosphino-Oxazoline: A Modular, Stable, Strongly
π‑Accepting Ligand for Asymmetric Catalysis
Zongjian Hu, Yuguang Li, Kai Liu, and Qilong Shen*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, People’s Republic of China
S
* Supporting Information
ABSTRACT: A new class of stable, strongly π-accepting and modular bis-
(perfluoroalkyl)-phosphine-oxazoline ligands (FOX) as CO mimics was prepared. It
was demonstrated that these ligands, when coordinated to palladium catalysts,
promote the asymmetric alkylation of monosubstituted allyl substrates with
excellent regio- and enantioselectivity. Solid and solution structure analysis of the
FOX-ligated Pd-allyl intermediate reveals that the combination of relative steric and
strong trans influences presented by the P(CF3)2 moiety gave rise to the excellent selectivity.
oxazoline moiety required for asymmetric induction can be
easily fine-tuned through modification of the substituents.
Herein, we report a facile three-step synthesis of bis-
(perfluoroalkyll) phosphino- oxazoline ligands (FOX) and
their applications in palladium-catalyzed asymmetric alkylation
of monosubstituted allyl substrates with excellent regio- and
enantioselectivity. A palladium(II) π-allyl intermediate was
isolated and characterized by single crystal X-ray diffraction to
explore the origins of high selectivity of the catalyst.
INTRODUCTION
■
Homogeneous asymmetric catalysis has grown enormously in
recent years and has contributed significantly to the preparation
of both chiral pharmaceuticals and bulk fine chemicals.1 The
design, synthesis and development of coordination chemistry of
a few classes of chiral ligands,2 such as BINAP3 and its
derivatives,4 Josiphos,5 and oxazoline ligands (BOX6 and
PHOX7,8) plays a critical role in the development of numerous
asymmetric reactions and remains a field of intense research
effort (Figure 1).9 Typically, these ligands are good σ-donors,
weak π-acceptors and often have a wide range of accessible
steric and electronic properties for fine-tuning the reactivity and
selectivity.10 On the other hand, ligands that are moderate σ-
donors and strong π-acceptors, such as CO, NO and PF3, are
much less frequently used in asymmetric reactions because
these ligands cannot be modified. They are often used as
ligands in metal complexes as starting materials and catalyst
precursors.11 We envisioned that if a family of sterically tunable
new ligands that are electronically strong π-acceptors similar to
CO could be created, it would be possible to develop new
catalytic reactions that would find applications in organic
synthesis and in the production of highly valuable pharma-
ceuticals and bulk chemicals.
Toward this end, inspired by the wide applications of the
oxazoline ligands such as bisoxazolines (BOX), phosphine-
oxazolines (PHOX)7,13 and their derivatives,8,14,15 we designed
a new family of tunable bis(perfluoroalkyl) phosphino-oxazo-
line ligands (FOX). Perfluorinated alkyl phosphines
(Rf)xPR(3−x) have been known to be strongly π-accepting
since 1960s.12 It was anticipated that this strongly π-accepting
phosphine would display significant ligand trans influence upon
coordination to a transition metal center. The reduction of
electron density at the transition metal center might destabilize
its high oxidation states and make it more reactive. In addition,
low electron density of the metal center enhances the Lewis
acidic character of the catalyst, which can be advantageous for
asymmetric catalysis.15 Furthermore, the chirality on the
RESULTS AND DISCUSSION
■
Preparation of Bis(perfluoroalkyl) Phosphino-oxazo-
line Ligands. Our synthesis pathway toward ligands 3 and 6 is
depicted in Scheme 1. Starting from commercially available 2-
bromobenzoic acid, the oxazoline ring 2a−d was formed by
condensation with readily available chiral amino-alcohol and
ring closure in the presence of TsCl and Et3N. Lithium-
bromide exchange of the resulting aryl bromide with sBuLi at
−78 °C, followed by treatment with triphenylphosphite
((PhO)3P),16 gave the phosphite intermediates in high yields
as determined by 31P NMR spectroscopy, which were used
without further purification. Treatment of the phosphite
intermediates with Ruppert−Prakash reagent CF3TMS or
C2F5TMS in the presence of CsF provided the ligands 3a−h
in good to excellent 37−71% yields.12i−l Ferrocene-based
ligands 6a−h were prepared according to the analogous one-
pot sequence in 30−51% yields. Ligands 6a−h were obtained
with high diastereoselectivity according to the 19F and 31P
NMR spectroscopies of the crude reaction mixtures. The
ligands were purified by flash column chromatography on silica
gel.
The structures of ligands 3 and 6 were characterized by
NMR and MS spectroscopy. Structure of ligand 6c was further
confirmed by single crystal X-ray diffraction (Figure 2).
Received: June 14, 2012
Published: August 27, 2012
© 2012 American Chemical Society
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Figure 1. Chiral ligands for asymmetric catalysis.
Scheme 1. Synthesis of Bis(perfluoroalkyl)phosphino
a
Oxazoline Ligands
Figure 2. The ORTEP view of 6c.
stronger π-acceptors than aryl-substituted phosphite and
phosphine ligands. Interestingly, the ν(CO) stretch frequency
in complex 7 is much lower than those in [((CF3)2PCH2CH2P-
(CF3)2)Mo(CO)4] and [(CF3-DIOP)Mo(CO)4)], indicating
that the synergistic effect of two perfluoroalkylphosphino
groups on the ν(CO) of the Mo-complexes.
a
Reagents and conditions: (a) (i) Amino alcohol, EDCI, HOBT, room
temperature, 6 h; (ii) TsCl, Et3N, room temperature, 12 h. (b) (i) s-
BuLi, TMEDA, Et2O, −78 °C for ligand 3 and n-BuLi, TMEDA, Et2O,
−78 °C for ligand 6; (ii) P(OPh)3, −100 °C to room temperature, 1
h; (iii) CF3TMS/CsF, room temperature, overnight or C2F5TMS/
CsF, 40 °C, overnight. (c) (i) (COCl)2, room temperature, 2 h;
amino-alcohol; then Et3N, CH2Cl2, room temperature, 8 h; (ii) TsCl,
Et3N, room temperature, 12 h.
Palladium-Catalyzed Asymmetric Allylic Alkylation
with FOX 3 or 6 as the Ligand. As a test ground for the
effectiveness of our ligand design, we studied palladium-
catalyzed asymmetric allylic alkylation of monosubstituted allyl
substrates in the presence of ligand 3a−h or 6a−h. The
palladium-catalyzed allylic alkylation reaction is one of the most
thoroughly studied transition-metal-catalyzed reactions.18
While excellent enantioselectivity for 1,3-disubstituted allyl
substrates has been achieved, monosubstituted allyl substrates
have been more challenging. Pioneering works by Hayashi,
Pfaltz, Dai and Hou have shown that branched products were
achieved only using catalysts with a few well-designed
ligands.19,20 These studies have shown that to achieve good
regio- and enantioselectivity, a bidentate ligand with differ-
entiated trans influences at the two coordination sites was of the
utmost importance. In addition, a large group at the chiral
ligand backbone is necessary to shield the less substituted
terminal of the π-allylpalladium intermediate. As a result, the
nucleophile attacks the more substituted position of the allylic
intermediate that is trans to the stronger trans-directing
coordination site to afford the branched product. In views of
these previous observations, we reasoned that the strong π-
accepting properties of FOX could provide even greater trans
influence for the phosphorus coordination site and lead to high
selectivity.
Notably, ligands 3 and 6 are air and moisture stable either as
liquid or solid, or in deuterated chloroform for one week, as
determined by 19F NMR spectroscopy.
Comparison of the π-Accepting Properties of FOX
Ligands with Phosphite and Phosphine. To compare the
π-accepting properties of FOX ligands with phosphite and
phenyl substituted phosphines, three cis-(L2)molybdenum
tetracarbonyl complexes were prepared, and IR spectra of
these complexes were studied to determine ν(CO). Direct
thermal substitution of ligand 3d, phosphite oxazoline or
PHOX with Mo(CO)6 in refluxing toluene gave the
tetracarbonyls 7−9 as pure crystalline solids in excellent yields.
Complexes 7−9 are highly soluble in benzene and have been
fully characterized by NMR, IR and element analyses. The
analytical data are consistent with monomeric octahedral
complexes. Structure of complex 8 was further confirmed by
single crystal X-ray diffraction (Figure 3).
A comparison of ν(CO) from IR spectra of complexes 7−9
and several other known cis-L2Mo(CO)4 phosphine system is
given in Table 1. As anticipated, the ν(CO) stretch frequency
in complex 7 is much higher than those in complex 8 with
posphite moiety and complex 9 or [(DPPE)Mo(CO)4] with
phosphine moiety, which indicates that ligands 3 are much
We initially examined the reaction of (E)-cinnamyl acetate
with dimethyl malonate in the presence of 4.0 mmol %
Pd(dba)2 and 4.0 mol % of various bis(perfluoroalkyl)-
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Figure 3. The ORTEP views of complex 8.
1−11.5/1 regioselectivity and 72−94% enantioselectivity
(Table 2, entries 1−4). Similar trends were observed for the
reactions in the presence of ligand 3e−h, 6a−d and 6e−h.
Reactions using ligand 3 gave similar enantioselectivity as those
using 6. However, the regioselectivity of the product was
significantly higher when 3 was used as the ligand. For example,
reaction of (E)-cinnamyl acetate with dimethyl malonate in the
presence of 4.0 mmol % Pd(dba)2 and 4.0 mol % of 3d
occurred to full conversion to give the product with 11.5/1
regioselectivity and 94% ee, while the same reaction using 6d as
the ligand gave the product with 4/1 regioselectivity and 93%
ee (Table 2, entries 4 and 12). Reactions using bis-
(pentafluoroethyl)phosphino-oxazoline derivatives as the ligand
gave slightly higher enantioselectivity than those using
bis(trifluoromethyl)phosphino-oxazoline derivatives as the
ligand. However, the regioselectivity of the product using
bis(pentafluoroethyl)phosphino-oxazoline derivatives as the
ligand was slightly lower than those using bis(trifluoromethyl)-
phosphino-oxazoline derivatives as the ligand (Table 2, entries
1−4 and 5−8). Thus, the best conditions were found to be
using a combination of 4.0 mol % of Pd(dba)2/3d as the
catalyst (Table 2, entry 4). The absolute configuration of the
product was assigned as (S) by comparison the measured
optical rotations and HPLC retention times with the ones
reported in literature. As a control, we also conducted an
Table 1. Comparison of ν(CO) Stretch Frequency in IR
Spectra of cis-L2Mo(CO)4
t
experiment with Bu-PHOX as the ligand for the reaction of
(E)-cinnamyl acetate with dimethyl malonate. Only the linear
product was observed as determined by 1H NMR spectroscopy
of the crude product.
With the optimized reaction condition established, a series of
monosubstituted allyl substrates were studied, and the results
are summarized in Table 3. In general, reactions of both
cinnamyl acetate or carbonate derivatives proceeded to full
conversion within 8 h to provide the branched product in
excellent regio- and enantioselectivity. For cinnamyl acetate or
carbonate derivatives, we have determined that the regio- and
enantioselectivity are moderately sensitive to electronic effects
of the substrates. For example, reaction of 4-methoxy-
substituted cinnamyl carboxylate gave the desired branched
product in 92% ee and 19:1 branched:linear selectivity (Table
3, entry 7), while reaction of 4-chlorophenyl-substituted
phosphino oxazoline ligands using bis(trimethylsilyl)-acetamide
(BSA) and 3.0 mol % LiOAc as the base. In general, sterically
more hindered ligand gave higher regio- and enantioselectivity.
For example, reactions catalyzed by the palladium complexes
derived from ligand 3a−d occurred to full conversion with 1/
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Importantly, Pd/FOX is an efficient catalyst not only for the
asymmetric alkylation of cinnamyl substrates but also for
branched substrates 13. Good regio- and enantioselectivity
were obtained with phenyl or 1-napththyl substrates (Table 3,
entries 19−22). Few high regio- and enantioselective
palladium-catalyzed allylic subsitutions of branched monosub-
stituted substrates have been reported. The current catalyst
based on perfluoroalkyl phosphine ligand shows an advantage
over the conventional phosphine ligands.
Table 2. Evaluation of the Effects of FOX Ligand in
Palladium-Catalyzed Asymmetric Alkylation of
a
Monosubstituted Allyl Substrate
b
c
entry
ligand
time (h)
10:11
ee (%)
Reaction of 2-buten-3-yl acetate with dimethyl malonate
under the optimized conditions occurred smoothly to give the
linear product as the major product.
1
3a
3b
3c
3d
3e
3f
8
8
8
8
8
8
8
8
4
4
4
4
4
4
4
4
1/1
72
92
88
94
88
61
60
97
77
91
87
93
72
90
86
96
2
3.4/1
5/1
3
Comparison to Palladium Catalysts Containing Other
Ligands. In general, linear products are favored for the
palladium-catalyzed allylic alkylation. Only a few ligands with
strong π-accepting properties have been designed to achieve
high regio- and enantioselectivity for the allylic alkylation of
monosubstituted allyl substrates. We then compared the
selectivity of our Pd/Fox system with other previous reported
palladium catalyst for the alkylation of of 3-(1′-naphthyl)-1-
propen-3-yl acetate or 3-phenyl-1-propen-3-yl acetate. Excellent
regio- and enantioselectivities were observed in the reaction
with 3-(1′-naphthyl)-1-propen-3-yl acetate when Pfaltz’s ligand
3i,19d 3j,19e Hou and Dai’s ligand 3k19c and our FOX ligand 3d
was used. The regioselectivities were much lower for other less
sterically hindered substrates such as 3-phenyl-1-propen-3-yl
acetate when 3i or 3k was used as the ligand. In contrast,
reaction of 3-phenyl-1-propen-3-yl acetate with malonate in the
presence of catalyst generated from ligand 3k and 3d occurred
with excellent regio- and enantioselectivity.
4
11.5/1
0.58/1
2.31/1
2/1
5
6
7
3g
3h
6a
6b
6c
6d
6e
6f
8
9/1
9
0.64/1
1/1
10
11
12
13
14
16
16
1.4/1
4/1
1.4/1
1.5/1
2.5/1
4.3/1
6g
6h
a
Reagents and conditions: 4.0 mol % Pd(dba)2, 4.0 mol % ligand, 0.5
mmol cinnamyl acetate, 1.5 mmol dimethyl malonate, 1.5 mol BSA,
3.0 mol %, 1,2-dichloroethane (2 mL), room temperature.
Determined by H NMR spectroscopy of the crude. Determined
by HPLC.
b
c
1
Isolation of the Palladium(II) π-Allyl Complex Ligated
FOX Ligand 3d.21 To probe the origin of the high selectivity,
we prepared a palladium(II) π-allyl complex ligated by FOX
ligand 3d. Addition of 3d to a solution of [Pd(cinnamyl)Cl]2 in
CH2Cl2 in the presence of AgSbF6 formed [Pd(3d)(η3-
cinnamyl)]SbF6 14, which was characterized as a 2.7:1 ratio
of exo/endo stereoisomers in solution at room temperature by
NMR spectroscopic methods. The ratio of exo/endo stereo-
isomers was increased to 3.0/1 at 0 °C and 4.3/1 at −20 to
−40 °C. Interestingly, single crystal X-ray diffraction analysis of
14 revealed that two exo isomers coexisted in the crystal, both
of which have the phenyl group trans to P(CF3)2. In both
isomers, Pd−C bonds trans to P (2.275 and 2.302 Å) are longer
than those trans to N (2.129 and 2.112 Å), indicating stronger
trans influence of the P(CF3)2 moiety (Figure 4).22
substrate generated the product in 92% ee with slightly lower
branched:linear selectivity of ∼6:1 (Table 3, entry 11).
Reactions of sterically hindered 2-substituted cinnamyl
acetates or carbonates occurred to give the branched product
in slightly lower regio- and enantioselectivity than those meta-
or para-substituted substrates. For example, reaction of 2-
methoxy-substituted cinnamyl carboxylate gave the desired
branched product in 64% ee and 13.3:1 branched:linear
selectivity when 3d was used as the ligand (Table 3, entry
18). The enantioselectivity was improved to 88% ee when 3h
was used as the ligand, but the regioselectivity was lowered
slightly to 10/1 (Table 3, entry 19). In most cases, substrates
with electron-withdrawing group on the phenyl ring generated
the products with lower b/l ratios than those with electron-
donating group. The one exception is the reaction of 3-
methoxyl-substituted cinnamyl carbonate that occurred with
high regio- and enantioselectivity (Table 3, entry 20). Since
there is high regio- and enantioselectivity for the reaction of 3-
(1′-naphthyl)-1-propen-3-yl acetate or carbonate, one would
expect that sterically hindered substrates might give similar
selectivity. In contrast, when 2-chloro- or 2-methoxy-
substituted cinnamyl carbonate was used, much lower
enantioselectivity was observed.
DISCUSSION
■
On the basis of the observation of solution and solid structure
of the intermediate [Pd(3d)(η3-cinnamyl)]SbF6 14, we
proposed a working model to explain the high regio- and
enantioselectivity of the Pd/Fox system for the allylic alkylation
(Figure 5). Because of the steric effect of two trifluoromethyl
groups, two diastereomeric π-allyl intermediates exo-14 and
endo-14, in which the less hindered terminal methylene group
is positioned to the bis(trifluoromethyl)phosphino moiety, are
formed when the substrate is oxidatively added to Pd(0)(3d)
complex. The two isomers undergo fast isomerization that is
much faster than the following nucleophilic substitution.
Nucleophic attack of methyl malonate anion to exo-14 leads
to the (S)-isomer of the product, while attack to endo-14 leads
to the (R)-isomer. In addition, nucleophic attack of methyl
malonate anion to exo-14 is much fast than those to endo-14.
The preferred product arises by reaction at the allylic C trans to
Typically, reactions using bis(pentafluoroethyl)phosphino-
oxazoline derivatives as the ligand gave slightly higher
enantioselectivity than those using bis(trifluoromethyl)-
phosphino-oxazoline derivatives as the ligand. However, the
regioselectivity of the product using bis(pentafluoroethyl)-
phosphino-oxazoline derivatives as the ligand was slightly lower
than those using bis(trifluoromethyl)phosphino-oxazoline
derivatives as the ligand (Table 3, entries 1−2 or 3−4).
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a
Table 3. Enantioselective Palladium-Catalyzed Asymmetric Alkylation of Monosubstituted Allyl Substrates
b
c
d
entry
12 or 13
R
X
ligand
10/11
ee (%)
yield (%)
1
12a
12a
12b
12b
12c
12d
12e
12f
Ph
Ph
Ph
Ph
OAc
3d
3h
3d
3h
3d
3h
3d
3h
3d
3h
3d
3h
3d
3h
3d
3h
3d
3d
3h
3d
3h
3d
3d
92/8
93
97
92
95
94
96
92
94
93
95
92
96
81
87
99.5
99.6
87
64
88
92
83
88
85
97
98
96
98
95
98
96
96
96
98
95
97
95
95
96
97
95
96
95
95
96
96
97
2
OAc
90/10
92/8
3
OCO2Me
OCO2Me
OAc
4
86/14
96/4
5
1-naphthyl
1-naphthyl
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
4-ClC6H4
2-furan
6
OCO2Me
OAc
91/9
7
95/5
8
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OAc
93/7
9
12g
12g
12h
12h
12i
94/6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
92/8
86/14
82/18
88/12
88/12
80/20
83/17
86/14
93/7
12i
2-furan
12j
3-ClC6H4
3-ClC6H4
2-ClC6H4
2-MeOC6H4
2-MeOC6H4
3-MeOC6H4
Ph
12j
12k
12l
OCO2Me
OCO2Me
OCO2Me
OCO2Me
OAc
12l
91/9
12m
13a
13b
13c
94/6
93/7
Ph
95/5
1-naphthyl
OAc
89/11
a
Reagents and conditions: 4.0 mol % Pd(dba)2, 4.0 mol % ligand, 0.5 mmol monosubstituted allyl substrate, 1.5 mmol dimethyl malonate, 1.5 mol
b
c
1
BSA, 3.0 mol % LiOAc in 1,2-dichloroethane (2 mL), room temperature. Determined by H NMR spectroscopy of the crude. Determined by
HPLC. Yields are for mixture of branch/linear isomers.
d
Table 4. Comparison of Regio- And Enantioselectivity of Pd/Fox System with Other Palladium Catalysts
P of the exo or endo isomer because of the well-known trans
influence of the ligand.
achieved. The high regio- and enantioselectivity in Pd/FOX
system indicated the fast syn/anti equilibrium was established
before the nucleophilic attack of the π-allyl intermediate.
In the case of the branched substrates, both syn and anti η3 π-
allyl palladium intermediates are generated when the branched
substrate is oxidatively added to Pd(0), and nucleophilic attack
can take place either at the terminal or the internal position of
the allyl fragment to give the linear (E or Z) or the branched
product, respectively. The less stable anti intermediate generally
undergoes isomerization to the more stable syn intermediate,
and evantually an equilibrium is established. If the nucleophilic
attack of the π-allyl palladium intermediates is slower than the
isomerization, high regio- and enantioselectivity can be
CONCLUSION
■
In conclusion, we have introduced a new class of stable,
strongly π-accepting and modular bis(perfluoroalkyl)-phos-
phine-oxazoline ligands (FOX) for asymmetric catalysis. We
also showed that palladium complexes with these novel ligands
effectively catalyzed the asymmetric alkylation of monosub-
stituted allyl substrates in good regioselectivity and excellent
enantioselectivity. Crystal structure of palladium intermediate
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19F, 31P NMR spectra were recorded on 300 (or 400), 100.5, 376, 121
1
(or 162) MHz spectrometer. H NMR and 13C NMR chemical shifts
were determined relative to internal standard TMS at δ 0.0, and 19F
NMR chemical shifts were determined relative to CFCl3 as internal
standard. 31P NMR spectra were referenced to an external 85% H3PO4
signal (0.0 ppm). All reactions were monitored by TLC, 19F NMR or
31P NMR spectroscopy. Flash column chromatograph was performed
on silica gel (300−400 mesh) unless otherwise stated.
General Procedure for the Synthesis of Ligands 3 and 6.
Method A. A solution of s-BuLi in cyclohexane (1.5 M, 11.3 mL, 16.9
mmol) was added to a vigorously stirred suspension of the
corresponding aryl oxazoline (14.0 mmol) in anhydrous diethyl
ether (25 mL) at −78 °C under argon. The reaction mixture was
stirred at −78 °C for 15 min, and TMEDA (2.2 mL, 17 mmol) was
added. The mixture was cooled to −100 °C in a diethyl ether/dry ice/
liquid nitrogen bath for 15 min before P(OPh)3 (3.8 mL in 5 mL
anhydrous diethyl ether, 17 mmol) was added slowly over 5 min. The
reaction mixture was allowed to warm to room temperature over 2 h.
The reaction was monitored by 31P NMR spectroscopy until there was
no change in the peak corresponding to P(OPh)3.22 TMSCl (30
mmol) was added, and the mixture was stirred for 2 h at room
temperature. The mixture was filtrated under argon, and the solvent
was evaporated under reduced pressure. Dioxane (40 mL) was added,
followed by the addition of CsF (4.5 g, 29 mmol) and TMSCF3 (4.5
mL, 29.0 mmol).12i If the starting material was not completely
converted to the corresponding bis(trifluoromethyl)phosphine ligand
after 8 h as monitored by 31P NMR spectroscopy, TMSCF3 (6.3 mL,
51 mmol) was added in one portion. The reaction was stirred at room
temperature and monitored by 19F and 31P NMR spectroscopy. The
solvent was evaporated in vacuo, and the residue was purified by
column chromatography (petroleum ether/CH2Cl2 = 5/1) to give the
desired ligand.
Method B. TMEDA (1.7 mL, 13 mmol) and a solution of n-BuLi in
hexane (5.2 mL, 2.5 M, 13 mmol) was added to a vigorously stirred
suspension of the corresponding chiral oxazolinylferrocene (10 mmol)
in anhydrous diethyl ether (25 mL) at −78 °C under argon. The
reaction mixture was stirred at −78 °C for 30 min and at 0 °C for 2 h.
The mixture was cooled to −100 °C in a diethyl ether/dry ice/liquid
nitrogen bath for 15 min before P(OPh)3 (3.84 mL in 5 mL anhydrous
diethyl ether, 13 mmol) was added slowly over 5 min and then
warmed to room temperature. The reaction mixture was stirred at
room temperature for 2 h until there was no change in the peak
corresponding to P(OPh)3 as monitored by 31P NMR spectroscopy.22
The solvent was evaporated in vacuo, and diether ether (50 mL) was
added followed by addition of CsF (3.4 g, 22 mmol) and TMSCF3
(3.4 mL, 22 mmol). If the starting material was not completely
converted to the corresponding bis(trifluoromethyl)phosphine ligand
after 8 h as monitored by 31P NMR spectroscopy, TMSCF3 (4.3 mL,
28 mmol) was added in one portion.12i The reaction was stirred at
room temperature and monitored by 19F and 31P NMR spectroscopy.
The solvent was evaporated in vacuo, and the residue was purified by
column chromatography (petroleum ether/CH2Cl2 = 5/1) to give the
desired ligand.
Figure 4. Crystal structure of the complex [Pd(3d)(cinnamyl)]SbF6
14. Hydrogen atoms are omitted for clarity. Selected bond length [Å]
and angles [°]: Pd1−C14 2.129 (5), Pd1−C15 2.180 (5), Pd1−C16
2.275 (5), C14−C15 1.389 (8), C15−C16 1.389 (9), Pd2−C38 2.112
(7), Pd2−C39 2.134 (7), Pd2−C40 2.302 (8), C38−C39 1.381 (12),
C39−C40 1.273 (11); N1−Pd1−P1 87.65 (11), N2−Pd2−P2 87.88
(13), C14−C15−C16 119.7 (6), C34−C35−C36 120.7 (7).
Figure 5. Working model for high selectivity in Pd-catalyzed allylic
alkylation.
(S)-2-(2-(Bis(trifluoromethyl)phosphino)phenyl)-4-phenyl-4,5-di-
hydrooxazole 3a. The product was prepared according to the method
A as a colorless liquid in 61% yield (3.4 g): [α]D30.4 = −68.4 (c 0.9895,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 4.26 (t, J = 8.8 Hz, 1 H), 4.83
(dd, J = 10.4, 8.4 Hz, 1 H), 5.48 (t, J = 9.6 Hz, 1 H), 7.25−7.37 (m, 5
H), 7.58−7.63 (m, 2 H), 7.97−8.02 (m, 2 H) ppm; 13C NMR (100
MHz, CDCl3) δ 70.3, 75.6, 126.6, 127.8, 128.8, 129.7, 129.8, 131.5,
131.6, 133.1 (d, J = 25.5 Hz), 134.0, 141.3, 163.6 (d, J = 2.9 Hz) ppm;
31P NMR (81 MHz) δ −3.91 (m) ppm; 19F NMR (376 MHz) δ −52.0
[Pd(3d)(cinnamyl)]SbF6 reveals that the combination of
relative steric and strong trans influence presented by P(CF3)2
gives rise to the excellent selectivity. The easy preparation,
stability toward air and moisture and strong π-accepting
properties of FOX ligands are especially appealing. Expanding
the scope of the ligands for a variety of reactions is under
investigation.
(dq, J = 75.6, 47.8, 7.5 Hz, 6 F) ppm; MS (ESI) m/z (%) 392.1 [M +
H]+, 391.1 [M]+; HRMS (MALDI-FT) m/z [M + H]+ Calcd for
C17H13NOF6P 392.0634, found 392.0637; IR (KBr) ν = 3066, 3032,
2971, 2905, 1652, 1175, 1125 cm−1.
EXPERIMENTAL SECTION
■
General Information. All reactions were performed under Ar
atmosphere using oven-dried glassware. Solvents were distilled under
Ar atomosphere before use. Diethyl ether and dioxane were distilled
from sodium benzophenone ketal. 1,2-Dichloroethane and dichloro-
methane were distilled from calcium hydride. Commercially available
(S)-4-Benzyl-2-(2-(bis(trifluoromethyl)phosphino)phenyl)-4,5-di-
hydrooxazole 3b. The product was prepared according to the method
28.6
A as a colorless liquid in 57% yield (3.2 g): [α]D = +2.6 (c 0.9450,
reagents were used as received without further purification. H, 13C,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 2.76 (dd, J = 14.0, 8.4 Hz, 1
1
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Article
H, CH2), 3.22 (dd, J = 14.0, 5.6 Hz, 1 H, CH2), 4.16 (t, J = 8.2 Hz, 1
H), 4.38 (t, J = 9.0 Hz, 1 H), 5.48 (m, 1 H), 7.30−7.33 (m, 3 H),
7.36−7.40 (m, 2 H), 7.60−7.65 (m, 2 H), 7.96−7.99 (m, 1 H), 8.05−
8.08 (m, 1 H) ppm; 13C NMR (100 MHz, CDCl3) δ 41.4, 68.1, 72.9,
126.7, 128.6, 129.3, 129.35, 129.4, 131.4, 131.5, 133.1 (d, J = 25.5 Hz),
133.9, 137.6, 162.8 (d, J = 3.0 Hz) ppm; 31P{1H} NMR (81 MHz) δ
−5.28 (sept, J = 69 Hz) ppm; 19F{1H} NMR (376 MHz) δ −52.0
(app d, J = 68.9 Hz, 6 F) ppm; MS (ESI) m/z (%) 406.4 [M + H]+,
405.1 [M]+; HRMS (MALDI-FT) m/z [M + H]+ Calcd for
C18H15NOF6P 406.0790, found 406.0799; IR (KBr) ν = 3065, 3029,
2927, 2855, 1655, 1177, 1125 cm−1.
ppm; 13C NMR (100 MHz, CDCl3) δ 18.2 (d, J = 1.1 Hz), 18.3 (d, J =
1.9 Hz), 32.7, 70.8, 73.5, 129.9 130.0, 130.3, 132.3, 136.0 (d, J = 33.2
Hz), 136.5, 161.9 ppm; 31P NMR (162 MHz) δ −9.2 to −10.9 (m)
ppm; 19F NMR (376 MHz) δ −110 (m, 4 F), −81.6 (m, 6 F) ppm;
MS (ESI) m/z (%) 458.0 [M + H]+, 457.1 [M]+; HRMS (MALDI-
FT) m/z [M + H]+ Calcd for C16H15NOF10P 458.0726, found
458.0712.
(S)-2-(2-(Bis(pentafluoroethyl)phosphino)phenyl)-4-tert-butyl-
4,5-dihydrooxazole 3h. The product was prepared according to the
method A as a colorless liquid in 47% yield (3.1 g): [α]D22.8 = −19.6 (c
0.3300, CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.95 (s, 9 H), 4.11 (t,
J = 8.0 Hz, 1 H), 4.22 (t, J = 8.4 Hz, 1 H), 4.34 (t, J = 8.8 Hz, 1 H),
7.52 (dt, J = 27.2, 7.6 Hz, 2 H), 7.86 (t, J = 6.4 Hz, 1 H), 8.05 (d, J =
8.0 Hz, 1 H) ppm; 13C NMR (100 MHz, CDCl3) δ 25.8(d, J = 1.5
Hz), 34.1, 69.3, 77.4, 130.0, 130.1, 130.3, 132.4, 136.1 (d, J = 34.3 Hz),
136.7, 161.8 ppm; 31P{1H} NMR (162 MHz) δ −8.8 to −10.5 (m);
19F{1H} NMR (376 MHz) δ −109.9 (m, 4 F), −81.6 (d, J = 13.9 Hz, 3
(S)-2-(2-(Bis(trifluoromethyl)phosphino)phenyl)-4-isopropyl-4,5-
dihydrooxazole 3c. The product was prepared according to the
method A as a colorless liquid in 65% yield (3.2 g): [α]D29.3 = −5.0 (c
1
1.2920, CHCl3); H NMR (400 MHz, CDCl3) δ 0.97 (dd, J = 28.0,
6.4 Hz, 6 H), 1.83 (m, 1 H), 4.18 (m, 2 H), 4.48 (m, 1 H), 7.57−7.64
(m, 2 H), 7.94−7.97 (m, 1 H), 7.99−8.01 (m, 1 H) ppm; 13C NMR
(100 MHz, CDCl3) δ 18.4, 32.6, 71.4, 73.0, 129.0 129.04, 131.1, 131.6,
132.6 (d, J = 23.0 Hz), 133.5, 162.0 (d, J = 3.7 Hz) ppm; 31P NMR
(81 MHz) δ −5.06−2.53 (m) ppm; 19F NMR (376 MHz) δ −51.8
(dq, J = 64.1, 57.8, 8.2 Hz, 6 F) ppm; MS (ESI) m/z (%) 358.5 [M +
H]+, 357.1 [M]+; HRMS (MALDI-FT) m/z [M + H]+ Calcd for
C14H15NOF6P 358.0790, found 358.0796; IR (KBr) ν = 2965, 2934,
2910, 2877, 1657, 1366, 1177, 1126 cm−1.
(S)-2-(2-(Bis(trifluoromethyl)phosphino)phenyl)-4-tert-butyl-4,5-
dihydrooxazole 3d. The product was prepared according to the
method A as a colorless liquid in 71% yield (3.8 g): [α]D30.3 = +6.8 (c
1.3260, CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.98 (s, 9 H), 4.16 (t,
J = 12.2 Hz, 1 H), 4.26 (t, J = 15.0 Hz, 1 H), 4.41 (t, J = 12.4 Hz, 1 H),
7.56−7.63 (m, 2 H), 7.92−7.80 (m, 2 H) ppm; 13C NMR (100 MHz,
CDCl3) δ 25.8, 33.8, 69.8, 76.8, 129.2 129.3, 131.2, 131.3, 132.8 (d, J =
23.5 Hz), 133.7, 162.1 (d, J = 3.8 Hz) ppm; 31P{1H} NMR (81 MHz)
δ −2.81 (m) ppm; 19F{1H} NMR (376 MHz) δ −52.0 (dq, J = 75.8,
61.8, 7.5 Hz, 6 F) ppm; MS (ESI) m/z (%) 372.4 [M + H]+, 371.1
[M]+; HRMS (MALDI-FT) m/z [M + H]+ Calcd for C15H17NOF6P
372.0947, found 372.0945; IR (KBr) ν = 2961, 2908, 2872, 1658,
1177, 1126 cm−1.
F), −81.5 (d, J = 20.7 Hz, 3 F) ppm; MS (ESI) m/z (%) 472.1 [M +
H]+, 471.1 [M]+; HRMS (MALDI-FT) m/z [M + H]+ Calcd for
C17H17NOF10P 472.0883, found 472.0882.
[(S,Sp)-4,5-Dihydro-4-phenyl-2-oxazolyl]-(2-(bis(trifluoromethyl)-
phosphino)-ferrocene 6a. The product was prepared according to the
method B as an orange solid in 39% yield (1.9 g): mp 103−105 °C;
28.6
1
[α]D = −157.9 (c 0.2155, CHCl3); H NMR (300 MHz, CDCl3,
TMS) δ 4.21 (t, J = 7.8 Hz, 1 H), 4.34 (s, 5 H), 4.71 (s, 2 H), 4.75 (d,
J = 8.7 Hz, 1 H), 5.15 (s, 1 H), 5.30 (d, J = 10.8 Hz, 1 H), 7.30 (m, 3
H), 7.39 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3, TMS) δ 69.9,
71.5, 73.4, 73.9, 73.93, 74.1 (m), 75.0, 76.6 (d, J = 23.0 Hz), 126.4,
127.6, 128.8, 142.5, 165.4 (d, J = 3.8 Hz) ppm; 19F NMR (376 MHz,
CDCl3) δ −50.57 (dq, J = 74.9, 8.2 Hz, 3 F), −55.44 (dq, J = 60.6, 8.2
Hz, 3 F) ppm; 31P NMR (162 MHz, CDCl3) δ −6.97 (m) ppm; MS
(MALDI) m/z (%) 500.0 [M + H]+, 499.0 [M]+. Anal. Calc. for
C21H16F6FeNOP, Calcd: C, 50.53; H, 3.23; N, 2.81. Found: C, 50.59;
H, 3.12; N, 2.72.
[(S,Sp)-4,5-Dihydro-4-(phenylmethyl)-2-oxazolyl]-(2-(bis-
(trifluoromethyl)phosphino)-ferrocene 6b. The product was pre-
pared according to the method B as an orange solid in 40% yield (2.05
28.6
1
g): mp 77−79 °C; [α]D = −145.3 (c 0.1760, CHCl3); H NMR
(300 MHz, CDCl3, TMS) δ 2.74 (d, J = 5.1 Hz, 1 H), 2.92 (d, J = 13.5
Hz, 1 H), 3.95 (t, J = 6.3 Hz, 1 H), 4.06 (s, 5 H), 4.12 (m, 1 H), 4.49
(d, J = 17.1 Hz, 2 H), 4.88 (s, 1 H), 7.18 (s, 5 H) ppm; 13C NMR (100
MHz, CDCl3, TMS) δ 40.1, 66.7, 70.3, 72.1, 72.6, 72.62, 72.9 (m),
75.9 (d, J = 15.2 Hz), 125.6, 127.5, 128.8, 136.5, 163.3 (d, J = 4.6 Hz)
ppm; 19F NMR (376 MHz, CDCl3) δ −50.43 (dd, J = 74.3, 8.5 Hz, 3
F), −55.07 (dd, J = 59.9, 7.1 Hz, 3 F) ppm; 31P NMR (162 MHz,
CDCl3) δ −6.83 (m) ppm; MS (MALDI) m/z (%) 514.0 [M + H]+,
513.0 [M]+. Anal. Calc. for C22H18F6FeNOP, Calcd: C, 51.49; H, 3.54;
N, 2.73. Found: C, 51.46; H, 3.41; N, 2.58.
[(S,Sp)-4,5-dihydro-4-(1-methylethyl)-2-oxazolyl]-(2-(bis-
(trifluoromethyl)phosphino)-ferrocene 6c. The product was prepared
according to the method B as an orange solid in 51% yield (2.4 g): mp
45−46 °C; [α]D29.1 = −209.3 (c 0.1865, CHCl3); 1H NMR (300 MHz,
CDCl3, TMS) δ 0.98 (d, J = 6.6 Hz, 3 H), 1.02 (d, J = 6.6 Hz, 3 H),
1.80 (m, 1 H), 4.02 (m, 1 H), 4.09 (m, 1 H), 4.29 (s, 5 H), 4.34 (m, 1
H), 4.64 (s, 2 H), 5.02 (s, 1 H) ppm; 13C NMR (100 MHz, CDCl3,
TMS) δ 17.4, 31.6, 69.4, 70.3, 71.5, 71.9, 72.1 (d, J = 3.8 Hz), 72.6
(m), 76.6 (d, J = 25.0 Hz), 162.3 (d, J = 4.6 Hz) ppm; 19F NMR (376
MHz, CDCl3) δ −50.46 (dq, J = 74.3, 8.2 Hz, 3 F), −54.85 (dq, J =
58.7, 8.2 Hz, 3 F) ppm; 31P NMR (162 MHz, CDCl3) δ −10.98 (m)
ppm; MS (MALDI) m/z (%) 466.0 [M + H]+, 465.0 [M]+. Anal. Calc.
for C18H18F6FeNOP, Calcd: C, 46.48; H, 3.90; N, 3.01. Found: C,
46.78; H, 3.85; N, 3.02.
(S)-2-(2-(Bis(pentafluoroethyl)phosphino)phenyl)-4-phenyl-4,5-
dihydrooxazole 3e. The product was prepared according to the
method A as a colorless liquid in 41% yield (2.8 g): [α]D24.2 = 13.3 (c
0.3400, CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.31 (t, J = 8.7 Hz, 1
H), 4.84 (t, J = 9.0 Hz, 1 H), 5.50 (t, J = 9.0 Hz, 1 H), 7.34−7.44 (m, 5
H), 7.62 (dt, J = 7.2, 19.2 Hz, 2 H), 8.01 (t, J = 6.6 Hz, 1 H), 8.17 (t, J
= 7.5 Hz, 1 H) ppm; 13C NMR (75.45 MHz, CDCl3) δ 70.8, 75.3,
126.6, 127.7, 128.7, 130.2, 130.3, 130.7, 132.5, 135.8 (d, J = 33.3 Hz),
136.6, 141.6, 163.6 ppm; 31P NMR (121.5 MHz) δ −7.7 to −9.6 (m)
ppm; 19F NMR (282.3 MHz) δ −110.1 (m, 4 F), −82.0 (m, 6 F) ppm;
MS (ESI) m/z (%) 492.0 [M + H]+, 491.1 [M]+; HRMS (MALDI-
FT) m/z [M + H]+ Calcd for C19H13NOF10P 492.0570, found
492.0576.
(S)-4-Benzyl-2-(2-(bis(pentafluoroethyl)phosphino)phenyl)-4,5-
dihydrooxazole 3f. The product was prepared according to the
method A as a colorless liquid in 37% yield (2.6 g): [α]D24.2 = +8.0 (c
1
0.3150, CHCl3); H NMR (400 MHz, CDCl3) δ 2.77 (dd, J = 13.6,
8.4 Hz, 1 H, CH2), 3.20 (dd, J = 13.6, 5.6 Hz, 1 H, CH2), 4.17 (t, J =
7.2 Hz, 1 H), 4.38 (t, J = 8.4 Hz, 1 H), 4.64−4.72 (m, 1 H), 7.22−7.33
(m, 5 H), 7.54 (dt, J = 22.8, 7.6 Hz, 2 H), 7. 86 (t, J = 5.6 Hz, 1 H),
8.09 (d, J = 7.6 Hz, 1 H) ppm; 13C NMR (75 MHz, CDCl3) δ 41.4,
68.6, 72.4, 126.6, 128.5, 129.3, 129.9, 130.0, 130.6, 132.4, 135.7 (d, J =
32.4 Hz), 136.5, 137.5, 162.6 ppm; 31P{1H} NMR (161.9 MHz) δ
−8.8 to −10.5 (m) ppm; 19F{1H} NMR (376 MHz) δ −110 (m, 4 F),
−81.5 (m, 6 F) ppm; MS (ESI) m/z (%) 506.0 [M + H]+, 505.1 [M]+;
HRMS (MALDI-FT) m/z [M + H]+ Calcd for C20H15NOF10P
506.0726, found 506.0733.
[(S,Sp)-4-(1,1-Dimethylethyl)-4,5-dihydro-2-oxazolyl]-(2-(bis-
(trifluoromethyl)-phosphino)-ferrocene 6d. The product was pre-
pared according to the method B as an orange solid in 32% yield (1.5
(S)-2-(2-(Bis(pentafluoroethyl)phosphino)phenyl)-4-isopropyl-
4,5-dihydrooxazole 3g. The product was prepared according to the
method A as a colorless liquid in 45% yield (2.9 g): [α]D28.2 = −16.3 (c
29.1
1
g): mp 104−106 °C; [α]D = −241.5 (c 0.1780, CHCl3); H NMR
(300 MHz, CDCl3, TMS) δ 0.91 (s, 9 H), 3.94 (t, J = 8.7 Hz, 1 H),
4.19 (m, 1 H), 4.28 (s, 5 H), 4.33 (m, 1 H), 4.64 (s, 2 H), 4.91 (s, 1
H) ppm; 13C NMR (100 MHz, CDCl3, TMS) δ 24.8, 32.7, 68.0, 70.2,
71.8, 71.9, 72.6 (m), 75.3 (d, J = 3.7 Hz), 77.8 (d, J = 25.0 Hz), 162.4
1
0.3650, CHCl3); H NMR (400 MHz, CDCl3) δ 0.83 (dd, J = 20.8,
6.8 Hz, 6 H), 1.70 (m, 1 H), 4.02 (m, 2 H), 4.28 (m, 1 H), 7.40 (dt, J
= 25.6, 7.6 Hz, 2 H), 7.75 (t, J = 5.6 Hz, 1 H), 7.95 (t, J = 7.2 Hz, 1 H)
7963
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(d, J = 4.6 Hz) ppm; 19F NMR (376 MHz, CDCl3) δ −50.46 (dq, J =
73.1, 8.2 Hz, 3 F), −55.53 (dq, J = 56.8, 8.2 Hz, 3 F) ppm; 31P NMR
(162 MHz, CDCl3) δ −6.01 (m) ppm; MS (MALDI) m/z (%) 480.1
[M + H]+, 479.1 [M]+. Anal. Calc. for C19H20F6FeNOP, Calcd: C,
47.62; H, 4.21; N, 2.92. Found: C, 47.68; H, 4.36; N, 2.97.
starting material 12 or 13, the mixture was diluted with CH2Cl2 (20
mL) and washed twice with ice-cold saturated aqueous ammonium
chloride. The organic phase was dried over anhydrous Na2SO4 and
then concentrated under reduced pressure. The regioselectivity of the
reaction was determined by 1H NMR spectroscopy of the crude
product. The residue was purified by preparative TLC (EtOAc/
petroleum ether = 1/15) to give the crude product. The enantiomeric
purities were determined by chiral HPLC after purification with
comparison to those of the racemic product that was obtained by the
palladium-catalyzed allylic alkylation using (rac)-BINAP as the ligand.
Dimethyl-3-phenyl-1-butene-4,4-dicarboxylate 10a and 10b
(Table 3, entries 1−4, 21−23).19c Eluent: petroleum ether/ethyl
acetate = 15/1. 122 mg (98%, combined yield of 10a and 11a):
[(S, Sp)-4, 5-Dihydro-4-phenyl-2-oxazolyl]-(2-(bis-
(pentafluoroethyl)phosphino)-ferrocene 6e. The product was
prepared according to the method B as an orange solid in 38% yield
22.5
(2.3 g): [α]D
= 3.3 (c 0.8050, CHCl3); 1H NMR (300 MHz,
CDCl3, TMS) δ 4.10 (t, J = 8.4 Hz, 1 H), 4.29 (s, 5 H), 4.64 (s, 1 H),
4.70 (s, 2 H), 5.18 (m, 2 H), 7.17−7.34 (m, 5 H) ppm; 13C NMR (75
MHz, CDCl3, TMS) δ 69.8, 71.6, 73.3, 73.34, 73.8, 74.9, 75.4, 76.3,
77.3, 126.5, 127.5, 128.7, 142.2, 165.7 ppm; 19F NMR (282 MHz,
CDCl3) δ −113.6 to −109.3 (m, 3 F), −106.0 (dd, J = 52.2, 299.2 Hz,
1 F), −82.4 (t, J = 17.8 Hz, 3 F), −81.8 (s, 3 F) ppm; 31P NMR (162
MHz, CDCl3) δ −1.39 to 0.39 (m) ppm; MS (MALDI) m/z (%)
600.1 [M + H]+, 599.0 [M]+; HRMS (MALDI-FT) m/z [M + H]+
Calcd for C23H17F1054FeNOP 598.0279, found 598.0279.
29.3
1
[α]D = −29.8 (c 1.0160, CHCl3); H NMR (CDCl3, 300 MHz) δ
3.50 (s, 3 H), 3.75 (s, 3 H), 3.88 (d, J = 11.0 Hz, 1 H), 4.10 (dd, J =
11.0, 8.1 Hz, 1 H), 5.09 (d, J = 10.2 Hz, 1 H), 5.13 (d, J = 17.1 Hz, 1
H), 6.0 (ddd, J = 17.1, 10.2, 8.1 Hz, 1 H), 7.21−7.32 (m, 5 H) ppm;
13C NMR (CDCl3, 100 MHz) δ 49.7, 52.3, 52.5, 57.3, 116.6, 127.1,
[(S,Sp)-4,5-Dihydro-4-(phenylmethyl)-2-oxazolyl]-(2-(bis-
(pentafluoroethyl)phosphino)-ferrocene 6f. The product was pre-
pared according to the method B as an orange liquid in 30% yield (1.8
g): [α]D24.2 = −34.1 (c 0.2800, CHCl3); 1H NMR (400 MHz, CDCl3,
TMS) δ 2.74 (dd, J = 7.6, 13.6 Hz, 1 H), 3.07 (dd, J = 4.8, 13.6 Hz, 1
H), 4.02 (t, J = 8.0 Hz, 1 H), 4.20 (s, 5 H), 4.30 (t, J = 9.2 Hz, 1 H),
4.42 (m, 1 H), 4.59 (s, 1 H), 4.77 (s, 1 H), 5.08 (s, 1 H), 7.21−7.32
(m, 5 H) ppm; 13C NMR (75 MHz, CDCl3, TMS) δ 41.0, 67.4, 71.3,
71.5, 72.9, 73.4, 75.2, 76.8, 77.2, 126.5, 128.3, 129.7, 137.4, 164.4 (d, J
= 3.8 Hz) ppm; 19F NMR (282 MHz, CDCl3) δ −109.0 (m, 3F),
−104.4 to −105.6 (dd, J = 54.4, 297.5 Hz, 1 F), −82.0 (s, 3 F), −81.6
(s, 3 F) ppm; 31P NMR (162 MHz, CDCl3) δ −0.83 (m) ppm; MS
(MALDI) m/z (%) 614.1 [M + H]+, 613.0 [M]+; HRMS (MALDI-
FT) m/z [M + H]+ Calcd for C24H19F1054FeNOP 612.0435, found
612.0442.
127.7, 128.6, 137.8, 139.9, 167.8, 168.2 ppm; HPLC (chiralcel OD-H
column, 214 nm, 99/1 hexane/isopropanol, flow = 0.7 mL/min) tR =
12.85 (R), 13.92 (S) min.
Dimethyl-3-(1′-naphthyl)-1-butene-4,4-dicarboxylate 10c and
10d (Table 3, entries 5−6 and 24).19c Eluent: petroleum ether/
ethyl acetate = 15/1. 146 mg (98%, combined yield of 10c and 11c):
28.3
1
[α]D = −35.8 (c 0.8025, CHCl3); H NMR (CDCl3, 300 MHz) δ
3.39 (s, 3 H), 3.79 (s, 3 H), 4.17 (d, J = 10.9 Hz, 1 H), 5.04 (dd, J =
10.9, 8.1 Hz, 1 H), 5.11 (d, J = 10.2 Hz, 1 H), 5.16 (d, J = 17.1 Hz, 1
H), 6.08 (ddd, J = 17.1, 10.2, 8.1 Hz, 1 H), 7.37−7.57 (m, 4 H), 7.74
(d, J = 7.4 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 8.24 (d, J = 8.6 Hz, 1
H) ppm; 13C NMR (CDCl3, 100 MHz) δ 44.0, 52.3, 52.5, 56.9, 117.0,
123.2, 124.3, 125.1, 125.6, 126.1, 127.6, 128.8, 131.3, 134.0, 136.0,
137.5, 167.7, 168.3 ppm; HPLC (chiralcel OD column, 220 nm, 97/3
hexane/isopropanol, flow = 0.7 mL/min) tR = 8.98 (R), 9.75 (S) min.
Dimethyl-3-(4′-methoxyphenyl)-1-butene-4,4-dicarboxylate 10e
and 10f (Table 3, entries 7−8).19c Eluent: petroleum ether/ethyl
acetate = 15/1. 134 mg (96%, combined yield of 10e and 11e):
[(S,Sp)-4,5-dihydro-4-(1-methylethyl)-2-oxazolyl]-(2-(bis-
(pentafluoroethyl)phosphino)-ferrocene 6g. The product was
prepared according to the method B as an orange solid in 40% yield
22.7
1
28.7
1
(2.3 g): [α]D = −52.7 (c 0.0.3900, CHCl3); H NMR (300 MHz,
CDCl3, TMS) δ 0.92 (d, J = 6.3 Hz, 3 H), 0.98 (d, J = 6.9 Hz, 3 H),
1.75 (m, 1 H), 3.96−4.07 (m, 2 H), 4.26 (s, 5 H), 4.32 (t, J = 8.1 Hz, 1
H), 4.60 (s, 1 H), 4.69 (s, 1 H), 5.10 (s, 1 H) ppm; 13C NMR (75
MHz, CDCl3, TMS) δ 18.0, 18.4, 32.5, 70.2, 71.4, 72.3, 72.7 (d, J = 4.0
Hz), 73.3, 75.0, 76.8, 77.1, 163.7 (d, J = 4.0 Hz) ppm; 19F NMR (282
MHz, CDCl3) δ −109.4 to −113.6 (m, 3F), −104.8 to −106.1 (dd, J =
52.2, 297.8 Hz, 1 F), −82.4 (t, J = 17.8 Hz, 3 F), −82.0 (s, 3 F) ppm;
31P NMR (162 MHz, CDCl3) δ −1.4 to 0.37 (m) ppm; MS (MALDI)
[α]D = −23.6 (c 0.4635, CHCl3); H NMR (CDCl3, 300 MHz) δ
3.50 (s, 3 H), 3.74 (s, 3 H), 3.78 (s, 3 H), 4.06 (dd, J = 10.7, 8.0 Hz, 1
H), 5.05−5.12 (m, 2 H), 5.98 (ddd, J = 17.1, 10.2, 8.0 Hz, 1 H), 6.83
(d, J = 6.7 Hz, 1 H), 7.15 (d, J = 6.7 Hz, 1 H) ppm; 13C NMR (CDCl3,
100 MHz) δ 48.8, 52.3, 52.4, 55.1, 57.4, 113.8, 113.9, 116.1, 128.8,
138.0, 158.5, 167.8, 168.1 ppm; HPLC (chiralcel OD column, 220 nm,
90/10 hexane/isopropanol, flow = 0.7 mL/min) tR = 9.35 (R), 10.48
(S) min.
Dimethyl-3-(4′-methylphenyl)-1-butene-4,4-dicarboxylate 10g
(Table 3, entries 9 and 10).19c Eluent: petroleum ether/ethyl acetate
m/z (%) 566.1 [M + H]+, 565.0 [M]+; HRMS (MALDI-FT) m/z [M
+ H]+ Calcd for C20H19F1054FeNOP 564.0435, found 564.0447.
[(S,Sp)-4-(1,1-Dimethylethyl)-4,5-dihydro-2-oxazolyl]-(2-(bis-
(pentafluoroethyl)-phosphino)-ferrocene 6h. The product was
prepared according to the method B as an orange solid in 40% yield
29.0
= 15/1. 128 mg (98%, combined yield of 10g and 11g): [α]D
=
1
−31.7 (c 1.3040, CHCl3); H NMR (CDCl3, 300 MHz) δ 2.30 (s, 3
H), 3.51 (s, 3 H), 3.73 (s, 3 H), 4.07 (dd, J = 10.9, 8.2 Hz, 1 H), 5.07
(d, J = 9.4 Hz, 1 H), 5.11 (d, J = 17.0 Hz, 1 H), 5.98 (ddd, J = 17.1,
9.4, 8.2 Hz, 1 H), 7.10 (s, 4 H) ppm; 13C NMR (CDCl3, 100 MHz) δ
17.3, 45.6, 48.6, 48.8, 53.6, 112.6, 124.0, 125.6, 132.9, 133.2, 134.3,
164.1, 164.5 ppm; HPLC (chiralcel OD-H column, 214 nm, 99/1
hexane/isopropanol, flow = 0.7 mL/min) tR = 10.82 (R), 11.79 (S)
min.
22.8
1
(2.3 g): [α]D = −110.8 (c 0.1350, CHCl3); H NMR (300 MHz,
CDCl3, TMS) δ 0.95 (s, 9 H), 3.87 (dd, J = 7.9, 10.2 Hz, 1 H), 4.12 (t,
J = 8.4 Hz, 1 H), 4.25−4.31 (m, 6 H), 4.62 (s, 1 H), 4.69 (app t, J =
2.4 Hz, 1 H), 5.04 (s, 1 H) ppm; 13C NMR (100 MHz, CDCl3, TMS)
δ 25.8, 29.7, 33.5, 68.8, 71.4, 72.6 (d, J = 3.3 Hz), 73.1, 75.0, 76.2, 77.5,
163.2 ppm; 19F NMR (282 MHz, CDCl3) δ −109.3 to −113.2 (m, 3
F), −104.7 to −105.9 (dd, J = 53.6, 299.5 Hz, 1 F), −82.4 (t, J = 17.8
Hz, 3 F), −81.9 (s, 3 F) ppm; 31P NMR (162 MHz, CDCl3) δ −0.63
to −1.81 (m) ppm; MS (MALDI) m/z (%) 580.1 [M + H]+, 579.1
[M]+. Anal. Calc. for C21H20F10FeNOP, Calcd: C, 43.55; H, 3.48; N,
2.42. Found: C, 43.69; H, 3.85; N, 2.20.
Dimethyl-3-(4′-chlorophenyl)-1-butene-4,4-dicarboxylate 10h
(Table 3, entries 11 and 12).19c Eluent: petroleum ether/ethyl
acetate = 15/1. 137 mg (97%, combined yield of 10h and 11h):
31.1
1
[α]D = −19.6 (c 1.6160, CHCl3); H NMR (CDCl3, 400 MHz) δ
3.52 (s, 3 H), 3.74 (s, 3 H), 3.81 (d, J = 11.2 Hz, 1 H), 4.07 (dd, J =
11.2, 8.0 Hz, 1 H), 5.09−5.13 (m, 2 H), 5.90 (dt, J = 8.9, 17.7 Hz, 1
H), 7.16 (d, J = 8.4 Hz, 2 H), 7.26 (d, J = 8.8 Hz, 2 H) ppm; 13C NMR
(CDCl3, 100 MHz) δ 48.9, 52.5, 52.6, 57.1, 117.0, 127.4, 128.6, 128.8,
129.3, 130.0, 137.2, 167.6, 167.9 ppm; HPLC (chiralcel OD column,
220 nm, 99/1 hexane/isopropanol, flow = 0.7 mL/min) tR = 16.38
(R), 20.91 (S) min.
General Procedure for the Pd-Catalyzed Allylic Alkylation of
12 or rac-13.19c Pd(dba)2 (11 mg, 0.020 mmol) and ligand (S)-3d or
(S)-3h (0.020 mmol) were dissolved in dry (CH2Cl)2 (2.0 mL) and
then stirred for 30 min at room temperature under an atmosphere of
argon. To this solution were successively added 12 or rac-13 (0.5
mmol), dimethylmalonate (0.17 mL, 1.5 mmol), N,O-bis-
(trimethylsilyl)acetamide (BSA) (0.37 mL, 1.5 mmol), and lithium
acetate (1.0 mg, 0.015 mmol). The mixture was stirred at room
temperature and monitored by TLC. After the disappearance of the
Dimethyl-3-(2′-furanyl)-1-butene-4,4-dicarboxylate 10i (Table 3,
entries 13 and 14).23 Eluent: petroleum ether/ethyl acetate = 15/1.
29.3
113 mg (95%, combined yield of 10i and 11i): [α]D = −39.6 (c
0.9065, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 3.63 (s, 3 H), 3.73 (s,
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3 H), 3.86 (d, J = 9.9 Hz, 1 H), 4.20 (dd, J = 9.6, 9.0 Hz, 1 H), 5.15 (d,
J = 4.8 Hz, 1 H), 5.18 (d, J = 12.0 Hz, 1 H), 5.91 (ddd, J = 18.3, 9.9,
8.4, Hz 1 H), 6.10 (d, J = 3.0 Hz, 1 H), 6.28 (m, 1 H), 7.33 (m, 1 H)
ppm; 13C NMR (CDCl3, 75 MHz) δ 43.2, 52.5, 52.6, 55.4, 106.4,
110.2, 118.1, 134.6, 141.8, 152.9, 167.7, 167.72 ppm; HPLC (chiralcel
OJ-H column, 220 nm, 95/5 hexane/isopropanol, flow = 0.7 mL/min)
tR = 16.80 (S), 17.99 (R) min.
d, J = 6.8 Hz, 1 H), 4.19 (t, J = 9.2 Hz, 1H), 4.39 (dd, J = 9.2, 2.8 Hz, 1
H), 6.15 (trans to P, d, J = 14.0, 10.4 Hz, 1 H), 6.38 (central, ddd, J =
19.2, 12.0, 7.2 Hz, 1H), 7.46−7.55 (aryl region, m, 3 H), 7.80−7.91
(aryl region, m, 4 H), 8.09 (t, J = 8.8 Hz, 1 H), 8.42 (t, J = 6.8 Hz, 1
H) ppm; 19F NMR (75% isomer, 376 MHz, CDCl3) δ −56.19 (dq, J =
89.5, 7.1 Hz, 3 F), −56.19 (dq, J = 101.1, 7.1 Hz, 3 F) ppm; 1H NMR
(25% isomer, CDCl3, 400 MHz) δ 0.83 (s, 9 H), 2.94 (d, J = 8.4 Hz, 1
H), 3.46 (anti to central, trans to N, d, J = 12.0 Hz, 1 H), 3.74 (syn to
central, trans to N, d, J = 9.2 Hz, 1 H), 4.21 (m, 1 H), 4.36 (m, 1 H),
5.58 (trans to P, t, J = 12.4 Hz, 1 H), 6.31 (central, m, 1 H), 7.46−7.55
(aryl region, m, 3 H), 7.66 (d, J = 6.0 Hz, 2 H), 7.80−7.91 (aryl region,
m, 2 H), 8.07 (m, 1 H), 8.42 (m, 1 H) ppm; 19F NMR (25% isomer,
376 MHz, CDCl3) δ −55.57 (dq, J = 89.1, 7.1 Hz, 3 F), −52.14 (dq, J
= 95.5, 7.1 Hz, 3 F) ppm; 31P NMR (both major isomers, 81 MHz,
CDCl3) δ 35.4 (m, 1H) ppm; 13C NMR (CDCl3, 100 MHz) δ 24.2,
33.7, 69.9, 72.4, 111.3, 111.5, 112.77, 112.8, 113.4, 113.42, 130.0,
131.2, 133.9, 134.1, 135.2, 135.3, 135.7, 165.1(d, J = 2.2 Hz, CN)
ppm. Anal. Calc. for C24H25F12NOPPdSb (830.60) Calcd: C, 34.70; H,
3.03; N, 1.69. Found: C, 34.52; H, 3.19; N, 1.47.
Dimethyl-3-(3′-chlorophenyl)-1-butene-4,4-dicarboxylate 10j
(Table 3, entries 15 and 16). Eluent: petroleum ether/ethyl acetate
29.3
= 15/1. 137 mg (97%, combined yield of 10i and 11i): [α]D
=
1
−21.2 (c 0.4135, CHCl3); H NMR (CDCl3, 400 MHz) δ 3.53 (s, 3
H), 3.74 (s, 3 H), 3.82 (d, J = 11.2 Hz, 1 H), 4.06 (dd, J = 10.8, 8.4 Hz,
1 H), 5.10 (m, 2 H), 5.91 (m, 1 H), 7.11 (dd, J = 6.8, 2.0 Hz, 1 H),
7.21 (m, 3 H) ppm; 13C NMR (CDCl3, 100 MHz) δ 44.5, 47.8, 47.9,
52.3, 112.5, 121.6, 122.6, 123.3, 125.1, 126.9, 132.3, 137.3, 162.8, 163.1
ppm; HPLC (chiralcel AD-H column, 214 nm, 99/1 hexane/
isopropanol, flow = 0.7 mL/min) tR = 14.60 (S), 15.97 (R) min.
Dimethyl-3-(2′-chlorophenyl)-1-butene-4,4-dicarboxylate 10k
(Table 3, entry 17). Eluent: petroleum ether/ethyl acetate = 15/1.
30.3
134 mg (95%, combined yield of 10k and 11k): [α]D = −36.9 (c
General Procedure for Preparation of Mo-Complexes 7,
9.12c In the dark, a mixture of Mo(CO)6 (0.10 g, 0.38 mmol) and
ligand 3d or (S)-4-tert-butyl-2-2(diphenylphosphino)phenyl)-4,5-
dihydrooxazoline (tBuPHOX) (0.30 mmol) in toluene (3.0 mL) was
refluxed for 2−3 h. The reaction was monitored by 19F NMR or 31P
NMR spectroscopy. After the disappearance of the peak corresponding
to the ligand, the solvent was removed in vacuo. The residue was
dissolved in petroleum ether and filtered through filter paper. The
filtrates were concentrated and gave the Mo complexes as red solids.
General Procedure for Preparation of Mo-Complex 8.26 In a
Schlenk flask, to a Et2O solution (5 mL) of (4S)-2-(2-(dinaphtho[2,1′-
d:1′,2′-f ][1,3,2]dioxoaphosphenpin-4-yl)phenyl)-4-isopropyl-4,5-dihy-
drooxazole (0.13 g, 0.49 mmol) at −80 °C was added dropwise a
precooled solution of s-BuLi (0.38 mL, 1.3 M in cyclohexane). The
mixture was stirred for 10 min, and ClP(NEt2)2 (0.10 g, 0.49 mmol)
was added slowly. The mixture was allowed to warm up to room
temperature and was stirred for 1−2 h. The volatiles were removed in
vacuo, and toluene (10 mL) was added. The solution was filtered
through a pad of Celite. 31P NMR spectrum of the crude product
showed a single resonance at δ 97.4 ppm. (R)-binapthol (0.49 mmol,
0.14 g) was then added, and the mixture was heated under reflux for
12 h. After cooling to room temperature, the solvent was removed, and
the residue was washed twice with pentane and diethyl ether. The solid
was dissolved in toluene (10 mL), and the solution was filtered
through a short plug of Celite. 31P NMR spectrum of the solution
showed a single resonance at δ 199.9 ppm. Mo(CO)6 (0.133 g, 0.500
mmol) was added, and the reaction mixture was heated under reflux
for 1−2 h. After cooling to room temperature, the mixture was filtered,
and the solvent was removed in vacuo. The residue was purified by
recrystallization with CH2Cl2 and pentane to give the desired Mo
complex as a slightly orange crystals (0.28 g, 80.3%).
0.9330, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 3.54 (s, 3 H), 3.74 (s,
3 H), 4.02 (d, J = 10.5 Hz, 1 H), 4.65 (t, J = 9.0 Hz, 1 H), 5.10 (m, 2
H), 5.93 (dt, J = 17.7, 8.9 Hz, 1 H), 6.14 (ddd, J = 17.0, 10.1, 8.6 Hz, 1
H), 7.16 (m, 1 H), 7.22 (dd, J = 1.5, 7.8 Hz, 2 H), 7.36 (d, J = 7.8 Hz,
1 H) ppm; 13C NMR (CDCl3, 100 MHz) δ 45.6, 52.4, 52.5, 55.8,
117.6, 126.9, 128.1, 128.5, 129.5, 130.0, 136.0, 137.4, 168.0, 169.2
ppm; HPLC (chiralcel OD-H column, 214 nm, 99/1 hexane/
isopropanol, flow = 0.7 mL/min) tR = 14.12 (R), 17.22 (S) min.
Dimethyl-3-(2′-methoxyphenyl)-1-butene-4,4-dicarboxylate 10l
(Table 3, entry 18 and 19). Eluent: petroleum ether/ethyl acetate =
15/1. 132 mg (95%, combined yield of 10l and 11l): [α]D27.1 = −33.2
(c 1.050, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 3.47 (s, 3 H), 3.73
(s, 3 H), 3.83 (s, 3 H), 4.17 (d, J = 10.8 Hz, 1 H), 4.32 (dd, J = 10.8,
8.4 Hz, 1 H), 5.02 (m, 2 H), 6.09 (dq, J = 10.0, 8.0 Hz, 1 H), 6.84 (m,
2 H), 7.14 (m, 2 H) ppm; 13C NMR (CDCl3, 100 MHz) δ 45.9, 52.1,
52.2, 55.2, 55.3, 110.9, 116.6, 120.5, 127.9, 128.1, 129.2, 136.8, 157.0,
168.0, 168.5 ppm; HPLC (chiralcel OD-H column, 214 nm, 995/5
hexane/isopropanol, flow = 0.7 mL/min) tR = 8.87 (R), 9.83 (S) min.
Dimethyl-3-(3′-methoxyphenyl)-1-butene-4,4-dicarboxylate 10m
(Table 3, entry 20).24 Eluent: petroleum ether/ethyl acetate = 15/1.
29.3
132 mg (95%, combined yield of 10m and 11m): [α]D = −31.1 (c
0.6195, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 3.56 (s, 3 H), 3.77 (s,
3 H), 3.82 (s, 3 H), 3.90 (d, J = 10.8 Hz, 1 H), 4.12 (dd, J = 10.8, 8.3
Hz, 1 H), 5.12 (d, J = 10.4 Hz, 1 H), 5.17 (dt, J = 1.3, 16.9 Hz, 1 H),
6.00 (ddd, J = 17.2, 10.1, 8.3 Hz, 1 H), 6.78−6.81 (m, 2 H), 6.85 (d, J
= 7.8 Hz, 1 H), 7.25 (td, J = 7.8, 1.0 Hz, 1 H) ppm; 13C NMR (CDCl3,
100 MHz) δ 49.7, 52.4, 52.5, 55.0, 57.1, 112.3, 113.6, 116.6, 120.0,
129.5, 137.5, 141.4, 159.6, 167.7, 168.0 ppm; HPLC (chiralcel OD-H
column, 214 nm, 99/1 hexane/isopropanol, flow = 0.7 mL/min) tR =
18.69 (R), 20.59 (S) min
28.8
Complex 7 (0.15 g, 86.3%): mp 87−88 °C; [α]D = +270.4 (c
General Procedure for the Preparation of Pd(3d)(cinnamyl)-
SbF6 Complex.25 KCl (1.40 g, 18.8 mmol) was added to a solution of
PdCl2 (1.76 g, 10.0 mmol) in 18 mL of deionized water. A red-brown
solution was formed after 5 min. Eighteen milliliters of deionized water
and cinnamyl chloride (5.0 g, 33 mmol) was added. The mixture was
stirred at room temperature for 24 h. A green-yellow solid
[Pd(cinnamyl)Cl]2 was filtered and used without further purification
(2.5 g, 96.5%).
A solution of AgSbF6 (0.352 g, 1.03 mmol) in methanol (4.0 mL)
was added to a solution of ligand 4 (0.3 g, 1.05 mmol) and complex 21
(0.26 g, 0.5 mmol) in CH2Cl2 (10 mL). After being stirred at room
temperature for 1 h in the dark, the solution was filtered through a
short plug of Celite. The solid was washed with CH2Cl2 (5.0 mL × 3).
The filtrates were combined and concentrated in vacuo. The residue
0.0620, PhCH3); IR vmax solid 2970.5, 2900.4, 2872.4, 2043.8, 1941.6,
1
1918.4, 1900.2, 1874.6, 1878.7, 1862.9 cm−1; H NMR (C6D6, 400
MHz) δ 1H NMR (400 MHz, C6D6) δ 0.65 (s, 9 H), 3.35 (dd, J = 9.2,
8.0 Hz, 1 H), 3.64 (dd, J = 8.4, 2.4 Hz, 1 H), 3.69 (dd, J = 9.6, 2.0 Hz,
1 H), 6.82−6.91 (m, 2 H), 7.72 (m, 1 H), 7.94 (t, J = 7.2 Hz, 1 H)
ppm; 13C NMR (100 MHz, C6D6) δ 25.7, 35.5, 67.9, 86.3 (d, J = 2.8
Hz), 132.1, 132.12, 132.25, 132.34, 132.5 (m), 133.0 (d, J = 1.9 Hz),
166.7 (d, J = 5.5 Hz), 204.3 (d, J = 8.8 Hz, CO), 205.7 (d, J = 8.7 Hz,
CO), 211.0 (d, J = 41.2 Hz, CO), 215.1 (d, J = 10.2 Hz, CO) ppm;
31P{1H} NMR (162 MHz) δ 66.17 (sept, J = 79.2 Hz); 19F{1H} NMR
(376 MHz) δ −37.18 (dq, J = 80.1, 2.2 Hz, 3 F), −33.71 (dq, J = 79.0,
8.3 Hz, 3 F) ppm. Anal. Calc. for C19H16F6MoNO5P (580.97) Calcd:
C, 39.40; H, 2.78; N, 2.42. Found: C, 39.45; H, 2.59; N, 2.05.
28.9
was purified by recrystallization with CHCl3 and pentane to give
Complex 9 (0.16 g, 89.6%): mp 157 °C; [α]D
= +537.5 (c
28.5
slightly yellow crystals (14, 0.40 g, 91.5%): mp 224−226 °C; [α]D
=
0.0465, PhCH3); IR vmax solid 2960.8, 2009.5, 1942.6, 1909.3, 1893.6,
1846.4 cm−1; H NMR (C6D6, 400 MHz) δ H NMR (400 MHz,
C6D6) δ 0.45 (s, 9 H), 3.35 (m, 1 H), 3.68 (m, 2 H), 6.69 (t, J = 7.6
Hz, 1 H), 6.77 (dt, J = 8.4, 0.8 Hz, 1 H), 6.87 (t, J = 8.0 Hz, 1 H), 6.96
(m, 3 H), 7.04 (m, 3 H), 7.35 (m, 2 H), 7.58 (m, 2 H), 7.93 (dq, J =
1
1
−134.9 (c 0.1120, CHCl3); IR vmax solid 2965.7, 1618.9, 1586.3,
1571.4, 1192.2, 1150.0, 656.4 cm−1; H NMR (75% isomer, CDCl3,
1
400 MHz) δ 0.53 (s, 9 H), 2.86 (dd, J = 9.2, 2.8 Hz, 1 H), 3.16 (anti to
central, trans to N, d, J = 11.6 Hz, 1 H), 4.17 (syn to central, trans to N,
7965
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4.0, 1.6 Hz, 1 H) ppm; 13C NMR (100 MHz, C6D6) δ 26.0, 34.9, 68.2,
83.6 (d, J = 2.8 Hz), 128.4, 128.5, 128.7, 128.8, 129.7 (t, J = 1.4 Hz),
129.8, 130.3 (d, J = 2.1 Hz), 131.9, 131.97, 131.98, 132.0, 133.0, 133.1,
134.0, 134.2, 134.4, 137.0, 137.3, 168.6 (d, J = 0.9 Hz), 207.3 (d, J =
8.4 Hz, CO), 210.0 (d, J = 9.2 Hz, CO), 216.6 (d, J = 33.8 Hz, CO),
220.8 (d, J = 7.4 Hz, CO) ppm; 31P{1H} NMR (162 MHz) δ 35.6
ppm. Anal. Calc. for C29H26MoNO5P (597.06) Calcd: C, 58.49; H,
4.40; N, 2.35. Found: C, 58.59; H, 4.31; N, 2.16.
(6) (a) Lowenthal, R. E.; Abiko, A.; Masamune, S. Tetrahedron Lett.
1990, 31, 6005. (b) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.;
Faul, M. M. J. Am. Chem. Soc. 1991, 113, 726. (c) Lo, M. M.-C.; Fu, G.
C. J. Am. Chem. Soc. 1998, 120, 10270.
(7) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336.
(8) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151.
(9) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Comprehensive
Asymmetric Catalysis; Springer-Verlag: Berlin, 1999.
29.5
Complex 8 (0.28 g, 80.3%): [α]D = −212.7 (c 0.1525, CHCl3);
(10) Crabtree, R. H. The Organometallic Chemistry of the Transition
Metals, 4th ed.; John Wiley & Sons: Hoboken, NJ, 2005; p 546.
(11) Kundig, E. P. Transition Metal Arene π-Complexes in Organic
Synthesis and Catalysis; Springer GmbH: Berlin, Germany, 2004; p 232.
(12) (a) Burg, A. B. Acc. Chem. Res. 1969, 2, 353. (b) Phillips, I. G.;
Ball, R. G.; Cavell, R. G. Inorg. Chem. 1988, 27, 4038. (c) Ernst, M. F.;
Roddick, D. M. Inorg. Chem. 1989, 28, 1624. (d) Adams, J. J.; Lau, A.;
Arulsamy, N.; Roddick, D. M. Inorg. Chem. 2007, 46, 11328.
(e) Brookhart, M.; Chandler, W. A.; Pfister, A. C.; Santini, C. C.;
White, P. S. Organometallics 1992, 11, 1263. (f) Kundig, E. P.; Dupre,
C.; Bourdin, b.; Cunningham, A.; Pons, D. Helv. Chim. Acta 1994, 77,
421. (g) Field, L. D.; Wilkinson, M. P. Organometallics 1997, 16, 1841.
(h) Fernandez, A. L.; Wilson, M. R.; Prock, A.; Giering, W. P.
1
IR vmax solid 2961.3, 2921.0, 2869.8, 2027.4, 1922.0, 1871.3 cm−1; H
NMR (CDCl3, 400 MHz) δ 1H NMR (400 MHz, CDCl3) δ 0.64 (d, J
= 6.8 Hz, 3 H), 0.94 (d, J = 6.8 Hz, 3 H), 2.69 (dq, J = 6.8, 3.2 Hz, 1
H), 4.16 (m, 1 H), 4.30 (m, 2 H), 6.55 (d, J = 8.8 Hz, 1 H), 7.06 (t, J =
7.6 Hz, 1 H), 7.16 (m, 4 H), 7.33 (m, 4 H), 7.57 (d, J = 8.8 Hz, 1 H),
7.71 (d, J = 8.8 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.89 (d, J = 8.0 Hz,
1 H), 8.00 (dd, J = 9.2 Hz, 1 H),8.04 (dd, J = 4.4, 7.6 Hz, 1 H) ppm;
13C NMR (100 MHz, CDCl3) δ 13.1, 19.3, 29.8, 66.9, 81.0 (d, J = 209
Hz), 122.5, 123.5 (d, J = 2.3 Hz), 123.9 (d, J = 3.7 Hz, ArC), 125.8 (d,
J = 3.0 Hz), 126.8, 126.9, 127.7, 127.9, 128.7, 128.8 (d, J = 1.5 Hz),
128.97, 129.0, 129.2, 129.23, 129.3, 130.3, 131.5, 131.7, 131.8 (d, J =
3.8 Hz, ArC), 131.9, 132. 5, 132.6 (d, J = 1.5 Hz), 133.37 (d, J = 1.5
Hz, ArC), 133.4 (d, J = 2.3 Hz, ArC), 148.9 (d, J = 3.2 Hz, ArC), 149.7
(d, J = 11.1 Hz, ArC), 164.5 (d, J = 3.0 Hz, CN), 205.4 (d, J = 13.4
Hz, CO), 206.9 (d, J = 10.4 Hz, CO), 214.4 (d, J = 51.3 Hz, CO),
217.1 (d, J = 11.9 Hz, CO) ppm; 31P{1H} NMR (162 MHz) δ 199.9
ppm. Anal. Calc. for C36H26MoNO7P (713.05) Calcd: C, 60.77; H,
3.68; N, 1.97. Found: C, 60.72; H, 3.83; N, 1.56.
̂
Organometallics 2001, 20, 3429. (i) Tworowska, I.; DaIbkowski, W.;
Michalski, J. Angew. Chem., Int. Ed. 2001, 40, 2898. (j) Eisenberger, P.;
Kieltsch, I.; Armanino, N.; Togni, A. Chem. Commun. 2008, 1575.
(k) Armanino, N.; Koller, R.; Togni, A. Organometallics 2010, 29,
1771. (l) Murphy-Jolly, M. B.; Lewis, L. C.; Caffyn, A. J. M. Chem.
Commun. 2005, 4479. (m) Velazco, E. J.; Caffyn, A. J. M.; Le Goff, X.
F.; Ricard, L. Organometallics 2008, 27, 2402. (n) Buergler, J. F.;
Togni, A. Chem. Commun. 2011, 47, 1896. (o) Sondenecker, A.;
Cvengros, J.; Aardoom, R.; Togni, A. Eur. J. Org. Chem. 2011, 2011,
78. (p) Eisenberger, P.; Kieltsch, I.; Armanino, N.; Togni, A. Chem.
Commun. 2008, 1575.
ASSOCIATED CONTENT
■
S
* Supporting Information
Proton and carbon NMR spectra of novel reported compounds
3a−h, 6a−h, 10a−m, CIF files of single crystals 6c, 8, and 14
as well as HPLC spectra for 10a−m. This material is available
free of charge via the Internet at http://pubs.acs.org.
(13) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339.
(14) (a) Blankenstein, J.; Pfaltz, A. Angew. Chem., Int. Ed. 2001, 40,
4445. (b) Knobel, A. K. H.; Escher, I. H.; Pfaltz, A. 1997, 1429.
̈
(c) Seebach, D. Helv. Chim. Acta 1999, 82, 1096. (d) Escher, I. H.;
Pfaltz, A. Tetrahedron 2000, 56, 2879. (e) Hahn, B. T.; Tewes, F.;
AUTHOR INFORMATION
■
Frohlich, R.; Glorius, F. Angew. Chem., Int. Ed. 2009, 49, 1143.
̈
Corresponding Author
*E-mail: shenql@mail.sioc.ac.cn.
(15) (a) Kundig, E. P.; Bourdin, B.; Bernardinelli, G. Angew. Chem.,
̈
Int. Ed. 1994, 33, 1856. (b) Viton, F.; Bernardinelli, G.; Kundig, E. P. J.
Am. Chem. Soc. 2002, 124, 4968. (c) Alezra, V.; Bernardinelli, G.;
̈
Notes
Corminboeuf, C.; Frey, U.; Kundig, E. P.; Merbach, A. E.; Saudan, C.
̈
The authors declare no competing financial interest.
M.; Viton, F.; Weber, J. J. Am. Chem. Soc. 2004, 126, 4843.
(16) (a) Wolfsberger, W.; Schmidbaur, H. Synth. React. Inorg. Met.-
Org. Chem. 1974, 4, 149. (b) Keller, J.; Schlierf, C.; Nolte, C.; Mayer,
P.; Straub, B. F. Synthesis 2006, 354. (c) Eisenberger, P.; Gischig, S.;
Togni, A. Chem.Eur. J. 2006, 12, 2579.
ACKNOWLEDGMENTS
■
We thank Mr. Kai Zhao and Chuan Qin for conducting some
experiments. We also acknowledge the National Natural
Science Foundation of China (21172245), National Basic
Research Program of China (2012CB821600), the Key
Program of the National Natural Science Foundation of
China (21032006), the Shanghai Pujiang program
(11PJ1412200), and the SIOC startup fund for financial
support.
(17) (a) Gallup, D. L.; Morse, L. G. J. Organomet. Chem. 1978, 159,
477. (b) Philips, I. G.; Ball, R. G.; Cavell, R. G. Inorg. Chem. 1988, 27,
4038. (c) Hoge, B.; Thosen, C.; Pantenburg, I. Chem.Eur. J. 2006,
̈
12, 9019. (d) Cook, R. L.; Morse, J. G. Inorg. Chem. 1989, 23, 2332.
(e) Chatt, J.; Watson, H. R. J. Chem. Soc. 1961, 4980.
(18) (a) Pfaltz, A.; Lautens, M. In Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
New York, 1999; Vol. 2, p 833. (b) Trost, B. M.; Crawley, M. L. Chem.
Rev. 2003, 103, 2921. (c) Lu, Z.; Ma, S. M. Angew. Chem., Int. Ed.
2008, 47, 258.
(19) (a) Hayashi, T.; Kawatsura, M.; Uozumi, Y. Chem. Commun.
1997, 561. (b) Hayashi, T.; Kawatsura, M.; Uozumi, Y. J. Am. Chem.
Soc. 1998, 120, 1681. (c) You, S.-L.; Zhu, X.-Z.; Luo, Y.-M.; Hou, X.-
L.; Dai, L.-X. J. Am. Chem. Soc. 2001, 123, 7471. (d) Pretot, R.; Pfaltz,
A. Angew. Chem., Int. Ed. 1998, 37, 323. (e) Hilgraf, R.; Pfaltz, A.
Synlett 1999, 1814.
(20) Selected examples for other transition metal-catalyzed alkylation
of monosubstituted allyl substrates. Mo-catalyzed allylic alkylation:
(a) Belda, O.; Moberg, C. Acc. Chem. Res. 2004, 37, 159. (b) Trost, B.
M.; Dogra, K.; Franzini, M. J. Am. Chem. Soc. 2004, 126, 1944.
(c) Malkov, A. V.; Gouriou, L.; Lloyd-Jones, G. C.; Stary, I.; Langer,
REFERENCES
■
(1) (a) Bhaduri, S.; Mukesh, D. Homogeneous Catalysis: Mechanisms
and Industrial Applications; John Wiley & Sons, Inc.: New York, 2000;
p 239. (b) Blaser, H.-U.; Indolese, A.; Schnyder, A. Curr. Sci. 2000, 78,
1336. (c) Larsen, R. D. Organometallics in Process Chemistry; Springer:
Berlin, 2004.
(2) Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691.
(3) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.;
Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932.
(4) (a) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029. (b) Berthod,
M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem. Rev. 2005, 105,
1801. (c) Xie, J.-H.; Zhou, Q.-L. Acc. Chem. Res. 2008, 41, 581.
(5) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, f.; Landert, H.;
Tijanit, A. J. Am. Chem. Soc. 1994, 116, 4062.
V.; Spoor, P.; Vinader, V.; Kocovsky, P. Chem.Eur. J. 2006, 12, 6910.
̈
7966
dx.doi.org/10.1021/jo3011717 | J. Org. Chem. 2012, 77, 7957−7967

The Journal of Organic Chemistry
Article
Ir-catalyzed allylic alkylation: (d) Bartels, B.; Helmchen, G. Chem.
Commun. 1999, 741. (e) Lipowsky, G.; Miller, N.; Helmchen, G.
Angew. Chem., Int. Ed. 2004, 43, 4595. (f) Kanayama, T.; Yoshida, K.;
Miyabe, H.; Kimachi, T.; Takemoto, Y. J. Org. Chem. 2003, 68, 6197.
(g) Graening, T.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 17192.
Rh-catalyzed allylic alkylation: (h) Hayashi, T.; Okada, A.; Suzuka, T.;
Kawatsura, M. Org. Lett. 2003, 5, 1713. (i) Menard, F.; Chapman, T.
M.; Dochendorff, C.; Lautens, M. Org. Lett. 2006, 8, 4569. Ru-
catalyzed allylic alkylation: (j) Matsushima, Y.; Onitsuka, K.; Kondo,
T.; Mitsudo, T.; Takahashi, S. J. Am. Chem. Soc. 2001, 123, 10405.
(l) Selvakumar, K.; Valentini, M.; Pregosin, P. S.; Albinati, A.
Organometallics 1999, 18, 4591.
(21) (a) Steinhagen, H.; Reggelin, M.; Helmchen, G. Angew. Chem.,
Int. Ed. 1997, 36, 2108. (b) Junker, J.; Bernd Reif, B.; Steinhagen, H.;
Junker, B.; Felli, I. C.; Reggelin, M.; Griesinger, C. Chem.Eur. J.
2000, 6, 3281.
(22) Wawrzyniak, P.; Slawin, A. M. Z.; Woollins, J. D.; Kilian, P.
Dalton Trans. 2010, 39, 85−92.
(23) Trost, B. M.; Hung, M. H. J. Am. Chem. Soc. 1983, 105, 7757.
(24) Alexakis, A.; Polet, D. Org. Lett. 2004, 6, 3529.
(25) (a) Kollmar, M.; Steinhagen, H.; Janssen, J. P.; Goldfuss, B.;
Malinovskaya, S. A.; Vaz
́
quez, J.; Rominger, F.; Helmchen, G. Chem.
Eur. J. 2002, 8, 3103. (b) Faller, J. W.; Wilt, J. C. Organometallics 2005,
24, 5076. (c) Faller, J. W.; Wilt, J. C.; Parr, J. Org. Lett. 2004, 6, 1301.
(26) (a) Li, J.; Lutz, M.; Spek, A. L.; van Klink, G. P. M.; van Koten,
G.; Klein Gebbink, R. J. M. J. Organomet. Chem. 2010, 695, 2618.
̀
(b) Francio, G.; Drommi, D.; Graiff, C.; Faraone, F.; Tiripicchio, A.
Inorg. Chim. Acta 2002, 338, 59.
NOTE ADDED AFTER ASAP PUBLICATION
■
Figure 5 contained errors in the version published ASAP
September 4, 2012; the correct version reposted September 10,
2012.
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