Double-asymmetric hydrogenation strategy for the reduction of 1,1-diaryl olefins applied to an improved synthesis of CuIPhEt, a C2-symmetric N-heterocyclic carbenoid

Article abstract of DOI:10.1021/jo3026548

A library of iridium and rhodium phosphine catalysts have been screened for the double-asymmetric hydrogenation of 2,6-di-(1-phenylethenyl)-4-methylaniline to produce the C₂-symmetric aniline precursor of the N-heterocyclic carbenoid CuIPhEt. The best catalyst produced the desired enantiomer in 98.6% selectivity. This rare example of a highly selective hydrogenation of a 1,1-diaryl olefin enables a four-step asymmetric synthesis of the C ₂-symmetric phenylethyl imidazolium ion (IPhEt) from p-toluidine and phenylacetylene and its conversion to the hydrosilylation catalyst CuIPhEt.

Full text of DOI:10.1021/jo3026548

Note
pubs.acs.org/joc
Double-Asymmetric Hydrogenation Strategy for the Reduction of
1,1-Diaryl Olefins Applied to an Improved Synthesis of CuIPhEt, a
C2‑Symmetric N‑Heterocyclic Carbenoid
Elizabeth Spahn,† Abigail Albright,† Michael Shevlin,‡,* Larissa Pauli,§ Andreas Pfaltz,§,*
and Robert E. Gawley†,*
†Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States
‡Department of Process Chemistry, Merck and Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, United States
§Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland
S
* Supporting Information
ABSTRACT: A library of iridium and rhodium phosphine catalysts
have been screened for the double-asymmetric hydrogenation of 2,6-
di-(1-phenylethenyl)-4-methylaniline to produce the C2-symmetric
aniline precursor of the N-heterocyclic carbenoid CuIPhEt. The best
catalyst produced the desired enantiomer in 98.6% selectivity. This
rare example of a highly selective hydrogenation of a 1,1-diaryl olefin
enables a four-step asymmetric synthesis of the C2-symmetric
phenylethyl imidazolium ion (IPhEt) from p-toluidine and phenylacetylene and its conversion to the hydrosilylation catalyst
CuIPhEt.
N-Heterocyclic carbenes have risen to prominence in recent
years as ligands in transition-metal catalysis and as organic
catalysts.1−8 The versatility of the N,N′-bis(2,6-
diisopropylphenyl)imidazol-2-ylidine (IPr) ligand9 led us to
explore the synthesis and structure of several imidazolium
heterocycles having a stereocenter γ to the imidazolium
nitrogen.10 The Cu(I) complex of one of these ligands, which
we call CuIPhEt (I for imidazolium, PhEt for phenethyl, Figure
1), was shown to be extraordinarily selective in the hydro-
In our first synthesis of CuIPhEt (Scheme 1),10 we used
Sartori’s procedure12 to prepare aniline 1 by condensation of
Scheme 1
Figure 1. X-ray crystal structure of CuIPhEt.10
silylation of aryl alkyl and dialkyl ketones.11 To our knowledge,
there is no other asymmetric hydrosilylation or hydrogenation
catalyst that matches CuIPhEt in its enantioselectivity in the
reduction of dialkyl ketones. A typical CuIPhEt hydrosilylation
is performed at room temperature in THF for less than 60 min
with 2 mol % catalyst loading.11 Ten examples were reported
with good yields and excellent enantioselectivities. In the
presence of CuIPhEt, the hydrosilylation of acetophenone, the
benchmark test for catalysts in this category, gives a 99:1 er in
90% yield after 45 min at room temperature. Especially
noteworthy is the hydrosilylation of 2-butanone and 3-
heptanone, which proceeded in 98:2 and 95:5 er, respectively.
phenylacetylene with p-toluidine. Hydrogenation then afforded
a mixture of racemic and meso anilines 2, which were separated
by chiral stationary phase chromatography. The chiral
enantiomers were then separately condensed with glyoxal,
cyclized, deprotonated, and added to CuCl to give CuIPhEt in
65% yield over the three steps. X-ray crystallography revealed a
beautiful chiral pocket surrounding the copper atom (Figure 1).
Because of the excellent selectivity exhibited by CuIPhEt in
Received: December 5, 2012
© XXXX American Chemical Society
A
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The Journal of Organic Chemistry
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hydrosilylations and because of the potential for new
applications of the IPhEt ligand in both organocatalysis and
transition-metal catalysis, we investigated the possibility of an
asymmetric hydrogenation of 1 to S,S-2 and R,R-2. This
approach seemed attractive because of the statistical benefit of
two consecutive asymmetric reactions. Assuming that both
CC bonds were reduced under catalyst control, with little
influence of the stereogenic center formed in the first
hydrogenation step, high enantioselectivity could be expected
even if the facial selectivies of the individual steps were only
moderate.
Disubstituted terminal alkenes are a challenging substrate
class for asymmetric hydrogenation compared to the more
widely studied trisubstituted olefins.13−16 Although Marks and
co-workers reported the asymmetric hydrogenation of 2-
phenyl-1-butene in 98:2 er at −80 °C in 1992, the chiral
organosamarium complex they used did not find further
application due to the difficult preparation and high sensitivity
of this catalyst system.17,18 Iridium complexes based on chiral
P,N ligands provided a more practical solution in this case, as
they are less sensitive to air and moisture and are easy to
handle. It was found that the enantioselectivity in the
hydrogenation of 2-phenyl-1-butene strongly depended on
the hydrogen pressure with best results achieved at 1 atm of H2.
Under these conditions, a range of 2-aryl-1-butenes was
hydrogenated with high enantioselectivites of up to 97:3
er.19,20 Until recently, no examples of asymmetric hydro-
genation of diaryl-substituted terminal alkenes were known.
Scheme 3
which results in outstanding stereoselectivity for the formation
of one of the chiral stereoisomers.
The search for an effective catalyst for the asymmetric
hydrogenation of aniline 1 entailed screening of libraries of
both iridium- and rhodium-based catalysts (Table 1).
Table 1. Catalyst Library (See the Supporting Information
for Structures)
However, in a combined effort, the groups of Borner,
̈
́
Andersson, and Dieguez showed that excellent enantioselectiv-
ities can be obtained with substrates of this type using sterically
very demanding phosphite−oxazoline ligands (Scheme 2).21 In
view of these results, we decided to screen a library of iridium
complexes in the hydrogenation of diene 1 and the
corresponding N-acetyl derivative.
Scheme 2
Our search began using catalysts 3−7 made in situ from
commercially available chloro(1,5-cyclooctadiene)rhodium(I)
dimer and chiral diphosphine ligands (Table 2, entries 1−5).
The amino group in diene 1 was acylated for two reasons in
these studies: free amines can act as catalyst poisons to decrease
reactivity, and acyl groups can act as anchors for catalysts to
increase selectivity. In order to achieve complete conversion to
product at low H2 pressure, the reaction times were increased
from the standard procedure developed for Pd/C hydro-
genations (Scheme 1). None of these rhodium−phosphine
catalysts provided a selective hydrogenation of acetanilide 24
(Table 2, entries 1−5). Only low diastereoselectivity for the
unwanted meso isomer was achieved, and no enantioselectivity
within the C2 symmetric products was seen. This may have
been partly due to the chloride counterion, which is more
tightly associated with the cation than the tetrafluoroborate−
rhodium catalysts tested at high pressure (compare entries 5
and 8). We started to see encouraging diastereo- and
enantioselectivity with rhodium catalysts 14−20 at high
While iridium P,N ligand complexes are the catalysts of
choice for the asymmetric hydrogenation of olefins lacking any
coordinating substituents, rhodium− and ruthenium−diphos-
phine complexes perform best with functionalized olefins
bearing a coordinating group next to the CC bond: 2-
acetamidoacrylic acid derivatives are typical examples.22
A
recent example of phenol-directed rhodium-catalyzed asym-
metric hydrogenation of 1,1-diarylethenes was reported by
Wang and co-workers (Scheme 3).23 By analogy, because the
amino group of diene 1 or the acetamido group of the N-
acetylated substrate are both potential coordinating groups, we
included a series of rhodium−diphosphine catalysts in our
study.
Herein, we report the results of a survey of a library of
enantioselective hydrogenation catalysts, the most selective of
B
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Note
a
the diphosphine ligand (RC-SP)-DuanPhos developed by Zhang
et al.,24 provided the highest dr and er for S,S-2 of any system
tested.
Table 2. Catalysts Screened in Acetanilide 24 Reduction
If the two reductions proceed with similar facial selectivity,
statistical ratios of the product stereoisomers can be predicted.
For example, if each reduction proceeds with 99:1 selectivity for
the S enantiomer, the ratio of products would be
98.01:0.01:1.98 (S,S:R,R:meso).25 The Rh-DuanPhos reduction
produced only trace amounts of the R,R isomer and ∼1% of the
meso isomer, indicating that each step was ∼99:1 selective.
Upon identifying the Rh-DuanPhos catalyst 20 as the most
selective system, we optimized the reaction conditions. We
began by probing solvent options. On the basis of solvent
studies (Table 4), methanol and ethyl acetate proved to be
cat.
meso:RR:SS
solvent
1
3
56:22:22
60:20:20
56:22:22
66:17:17
60:20:20
70:15:15
5:1:94
EtOH
2
4
EtOH
3
5
EtOH
4
6
EtOH
5
7
EtOH
6
8
EtOH
7
14
15
16
17
18
19
20
MeTHF
MeTHF
MeTHF
MeTHF
MeOH
MeOH
MeOH
8
7:93:0
Table 4. Solvent Studies with 20 at 500 psi Overnight
9
6:1:93
10
11
12
13
13:0:87
22:4:74
24:74:2
26:3:72
solvent
meso
R,R
S,S
MeOH
EtOH
iPrOH
TFE
1.2
5.6
0.2
0.3
0.6
1.4
0.4
0.2
0.3
0.5
1.8
0.2
0.2
0.1
0.3
0.3
0.3
0.2
98.6
94.1
86.2
65.4
81.0
94.9
93.6
93.1
91.8
96.5
95.7
97.4
93.8
93.4
94.2
96.1
13.2
33.1
18.5
4.9
a
Key: entries 1−6, 100 psi, 40 h; entries 7−13, 500 psi, 40 h.
DCE
pressure (Table 2, entries 7−13). The diastereoselectivity was
best with catalysts 14−16 in 2-methyltetrahydrofuran, and the
enantioselectivity of 93−94% was especially encouraging
(Table 2, entries 7−9). Iridium catalyst 8 gave increased
diastereoselectivity for the meso stereoisomer compared to the
rhodium catalysts tested at low pressure, but no enantiose-
lectivity was achieved (Table 2, entry 6). None of the iridium
catalysts 9−13 provided any conversion of 24 to 25.
PhCF3
PhCl
6.1
CyH
6.4
PhMe
EtOAc
iPrOAc
MEK
6.5
3.3
4.0
2.5
THF
5.9
We also screened the reduction of aniline 1. Using iridium-
based catalysts 9−13, we continued our search for enantio- and
diastereoselectivity at 725 psi (Table 3, entries 1−5). Although
MeTHF
CPME
DME
6.3
5.5
3.8
a
Table 3. Catalysts Screened in Aniline 1 Reduction
viable candidates for the reaction. We chose to proceed with
methanol due to the ease of use and solubility of the catalyst. In
larger scale-ups, 10 vol % of methylene chloride was employed
as a cosolvent to enhance the solubility of diene 1 (see the
Experimental Section). To further optimize the system, catalyst
loading studies were performed on 0.1 M reactions (Table 5).
cat.
(meso:R,R:S,S)
solvent
Table 5. Loading Studies with 20 at 500 psi Overnight
1
2
3
4
5
6
7
8
9
10
9
46:38:16
46:37:17
46:52:2
65:1:34
91:3:6
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeOH
MeOH
MeOH
MeOH
MeOH
10
11
12
13
18
20
21
22
23
load (%)
% conversion
meso
R,R
S,S
5
100.0
100.0
100.0
100.0
99.7
1.2
3.6
4.8
3.6
3.1
3.7
2.5
2.5
0.2
0.3
0.5
0.1
0.1
0.1
0.4
1.4
98.6
96.2
94.7
96.3
96.8
96.2
97.0
96.1
2
1
3:3:94
0.5
0.3
0.2
0.1
0.05
1:0:99
6:0:94
99.3
20:74:6
31:61:8
23.1
9.3
a
Key: entries 1−5 at 725 psi, entries 6−10 at 500 psi.
the diastereoselectivity using catalyst 12 was low, the
enantioselectivity was about 34:1 in favor of (S,S)-2. Catalyst
13 provided good selectivity for the meso diastereomer.
In a final attempt to find conditions to provide both high
diastereo- and enantioselectivity, we turned to rhodium-based
catalysts (18−23) prepared in situ from bis(norbornadiene)-
rhodium(I) tetrafluoroborate and chiral ligands (Table 3,
entries 6−10). In general, the diastereoselectivity was better
when the amino group was not acylated. Catalyst 20, based on
Only 0.2% catalyst loading is needed to effectively reduce the
starting material in a reaction at 500 psi overnight. Smaller
loadings still exhibit high selectivity but conversion to product
is attenuated. In practice, a catalyst loading of 0.5% was
employed to ensure that potential catalyst poisons in the
substrate lot and reaction vessel would not be as likely to affect
the reaction.
The asymmetric hydrogenation of 1 has now been conducted
on a 5 g scale, with only small amounts of the meso
C
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The Journal of Organic Chemistry
Note
HPLC (Chiralpak AD-H, 0.5 mL/min, isocratic, 99:1 heptane/i-
PrOH).
diastereomer contaminating the enantiopure product (Figure
2). Aniline 2 can be carried on to the CuIPhEt catalyst using
Typical Procedure for High Pressure Rh-Catalyzed Hydro-
genation. In a glovebox with O2 < 5 ppm, a solution of 0.36 mg (0.95
μmol) of (NBD)2RhBF4 in 100 μL of 1,2-dichloroethane was added to
an 8 × 30 mm vial containing a magnetic stirbar and 0.38 mg (1.0
μmol) of (RC,SP)-DuanPhos. The catalyst mixture was stirred for 30
min, and the solvent was removed on a Genevac vacuum centrifuge. A
solution of aniline 1 (1.25 mg, 4 μmol) in 100 μL of dry MeOH was
then added to the vial. The vial was sealed in a pressure vessel,
removed from the glovebox, and pressurized to 500 psi H2. The vessel
was subjected to shaking at 500 rpm at room temperature for 18 h.
After this time, hydrogen was released and chiral stationary phase
HPLC (Chiralpak OJ-RH 150 × 4.6 mm, 5 μm, 1 mL/min, isocratic
80% CH3CN/20% 0.1% aq. H3PO4, 25 °C) indicated complete
conversion to a 98.6:0.2:1.2 mixture of S,S:R,R:meso product isomers.
Large-Scale Reduction Procedure. All large-scale reactions were
carried out in Parr 5500 compact mini bench top reactor with the
following modifications. The cooling loop was removed and replaced
on one side with a Swagelok ball valve with septum and on the other
side with a stainless steel plug. The original gas relief valve was
modified with Swagelok fittings to become a manifold with three
needle valves. The needle valves were designated as ports for N2,
vacuum, or vent. The lower guide bearing that formerly braced the
impeller shaft to the cooling loop was reconnected to the dip tube. A
1L Parr High Pressure Buret was connected to the reactor with a high
pressure hose. This buret was fitted with valves so that it can be sealed
off from both the hydrogen supply cylinder and the reactor. Reactions
were performed in a glass insert inside of the stainless steel reactor.
A 25 mL round-bottom flask containing bis(norbornadiene)-
rhodium(I) tetrafluoroborate (30 mg, 80 μmol; 0.5 mol % loading)
and (SC, RP)-DuanPhos (37 mg, 96 μmol) was sealed with a septum
and purged with anhydrous nitrogen. Dichloromethane distilled from
CaH2 (6 mL) was added, and the solution was allowed to stir for 15
min. Aniline diene 1 (5 g, 16 mmol) and methanol dried over MgSO4
(55 mL, ∼0.25 M solution) were stirred in a round bottomed flask
with stir bar to form a well-distributed slurry before addition to the
glass insert for the Parr reactor. The hydrogenation chamber was
assembled and then evacuated and flushed five times with nitrogen.
The catalyst solution was introduced to the reactor under slight
positive pressure of nitrogen via syringe through the ball valve. Upon
filling three times and venting the system with hydrogen, the system
was pressurized to 500 psi; the buret was closed to the hydrogen
cylinder to minimize hydrogen loss in the event of a leak. After
vigorously stirring overnight, the reactor was closed to the hydrogen
buret, then vented and disassembled. The reaction mixture was filtered
through a plug of silica gel (4 × 1.5 cm) and concentrated to yield 4.98
g (98%) as an orange solid. The product mixture was analyzed by
chiral stationary phase HPLC (Chiralpak OJ-RH 150 × 2.1 mm, 5 μm,
0.1 mL/min isocratic, 65% CH3CN/35% 0.1% aq H3PO4) indicating
complete conversion to a 98:0.2:1.8 mixture of R,R:S,S:meso products.
Figure 2. CSP-HPLC of 1: racemate/meso mixture and S,S
enantiomer obtained in gram scale reduction.
the published procedure (Scheme 1) without any chromatog-
raphy.10 The small amounts of undesired stereoisomers are
eliminated during condensation with glyoxal and subsequent
manipulations.
CONCLUSION
■
The asymmetric hydrogenation of 1,1-diaryl-substituted termi-
nal olefins is a challenge, and a highly selective double-
asymmetric hydrogenation of functionalized dienes of this type
is rare.23 We found that the Rh-DuanPhos catalyst is highly
selective in reducing 2,6-di(1-phenylethenyl)-4-methylaniline
(1) to provide a key intermediate in the synthesis of the NHC
carbenoid CuIPhEt. Through this discovery, CuIPhEt is now
attainable through a five-step synthesis in 56% overall yield.
EXPERIMENTAL SECTION
■
General Methods. All solvents used were reagent grade and were
used as received unless otherwise noted. Catalysts 1−7 and 14−23
were prepared in situ from the requisite ligands and either
[RhCl(COD)]2 or (NBD)2RhBF4, all of which are commercially
available and which were used as received. Iridium catalyst 8 was
purchased and used as received. Synthesis and characterization of the
following catalysts has previously been reported: 9 and 10,26 11,27
12,28 and 13,29 and 20.24,30
Typical Procedure for Low-Pressure Hydrogenation. The
cyclooctadiene rhodium chloride dimer (56.6 μmol) and chiral
diphosphine (56.6 μmol), or catalyst 8, were dissolved in anhydrous
ethanol under an inert atmosphere and stirred for 15 min. To the
resultant bright orange slurry was added the acetanilide (0.283 mmol).
The vessel was purged with hydrogen three times and then pressurized
to 100 psi. The solution was heated to 100 °C and shaken for 40 h.
The reaction mixture was filtered through a plug of silica and analyzed
by CSP-SFC (Chiracel OD-H column with absolute ethanol as
modifier).
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of S,S-2 and H 13C and 31P NMR
1
Typical Procedure for High-Pressure Ir-Catalyzed Hydro-
genation. Catalyst 11 (0.9 mg, 0.5 μmol, 1 mol %) was added to a
solution of aniline 1 (16.5 mg, 0.05 mmol) in dry CH2Cl2 (0.25 mL).
The reaction vial was equipped with a magnetic stirrer bar and placed
in an autoclave that was pressurized to 725 psi H2. The reaction
mixture was stirred for 24 h at room temperature, after this time,
hydrogen was released and the solvent removed under reduced
pressure. The mixture was filtered through a plug of silica gel (0.5 × 3
cm) using a mixture of hexane/MTBE (4:1, 2 mL). After evaporation
of the solvent, the hydrogenation product (12.8 mg, 0.04 mmol, 77%)
was obtained as a yellow oil, together with unreacted starting material.
The product ratio, 52:2:46 RR:SS:meso, was determined by CSP-
spectra of in situ prepared RhDuanPhos. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: bgawley@uark.edu, michael_shevlin@merck.com,
andreas.pfaltz@unibas.ch.
Notes
The authors declare no competing financial interest.
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Note
ACKNOWLEDGMENTS
■
Work in Fayetteville was supported by the National Science
Foundation (CHE1011788) and the Arkansas Biosciences
Institute; core facilities were supported by the NIH (P30
GM103450). The work in Basel was supported by the Swiss
National Science Foundation. We thank Dr. Chris Welch
(Merck and Co.) for helpful discussions.
REFERENCES
■
(1) N-Heterocyclic Carbenes in Transition Metal Catalysis; Glorius, F.,
Ed.; Springer-Verlag: Berlin, 2004; Vol. 21.
(2) N-Heterocyclic Carbenes in Synthesis; Nolan, S. P., Ed.; Wiley-
VCH: Weinheim, 2006.
(3) Díez-Gonzal
3612.
́
ez; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109,
(4) Droge, T.; Glorius, F. Angew. Chem., Int. Ed. 2010, 49, 6940.
̈
(5) N-Heterocyclic Carbenes in Transition Metal Catalysis; Glorius, F.,
Ed.; Springer: Berlin, 2007.
(6) N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient
Synthetic Tools; Diez-Gonzalez, S., Ed.; Royal Society of Chemistry:
London, 2010.
(7) Kuhl, O. Functionalized N-Heterocyclic Carbene Complexes; Wiley:
̈
New York, 2010.
(8) N-Heterocyclic Carbenes in Transition Metal Catalysis and
Organocatalysis; Cazin, C. S. J., Ed.; Springer: Berlin, 2011.
(9) Kaur, H.; Zinn, R. K.; Nolan, S. P. Organometallics 2004, 23,
1157.
(10) Albright, A.; Eddings, D.; Black, R.; Welch, C. J.; Gerasimchuk,
N. N.; Gawley, R. E. J. Org. Chem. 2011, 76, 7341.
(11) Albright, A.; Gawley, R. E. J. Am. Chem. Soc. 2011, 133, 19680.
(12) Arienti, A.; Bigi, F.; Maggi, R.; Marzi, E.; Moggi, P.; Rastelli, M.;
Sartori, G.; Tarantola, F. Tetrahedron 1997, 53, 3795.
(13) Cui, X.; Burgess, K. Chem. Rev. 2005, 105, 3272.
(14) Roseblade, S. J.; Pfaltz, A. Acc. Chem. Res. 2007, 40, 1402.
(15) Church, T. L.; Andersson, P. G. Coord. Chem. Rev. 2008, 252,
513.
(16) Woodmansee, D. H.; Pfaltz, A. Chem. Commun. 2011, 47, 7912.
(17) Conticello, V. P.; Brard, L.; Giardello, M. A.; Tsuji, Y.; Sabat,
M.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992, 114, 2761.
(18) Giardello, M. A.; Conticello, V. P.; Brard, L.; Gagne, M. R.;
Marks, T. J. J. Am. Chem. Soc. 1994, 116, 10241.
(19) Blankenstein, J.; Pfaltz, A. Angew. Chem., Int. Ed. 2001, 40, 4445.
(20) McIntyre, S.; Hormann, E.; Menges, F.; Smidt, S. P.; Pfaltz, A.
̈
Adv. Synth. Catal. 2005, 347, 282.
(21) Mazuela, J.; Verendel, J. J.; Coll, M.; Schaffner, B.; Borner, A.;
̈
̈
Andersson, P. G.; Pam
131, 12344.
̀ ́
ies, O.; Dieguez, M. J. Am. Chem. Soc. 2009,
(22) Knowles, W. S. Angew. Chem., Int. Ed. 2002, 41, 1998.
(23) Wang, X.; Guram, A.; Caille, S.; Hu, J.; Preston, J. P.; Ronk, M.;
Walker, S. Org. Lett. 2011, 13, 1881.
(24) Liu, D.; Zhang, X. Eur. J. Org. Chem. 2005, 2005, 646.
(25) (0.99)2:(0.01)2:2(0.99 × 0.01).
(26) Kaiser, S.; Smidt, S. P.; Pfaltz, A. Angew. Chem., Int. Ed. 2006, 45,
5194.
(27) Smidt, S. P.; Menges, F.; Pfaltz, A. Org. Lett. 2004, 6, 2023.
(28) Schrems, M. G.; Pfaltz, A. Chem. Commun. 2009, 0, 6210.
(29) Menges, F. University of Basel, 2004, http://edoc.unibas.ch/
diss/DissB_6766.
(30) Zigterman, J. L.; Woo, J. C. S.; Walker, S. D.; Tedrow, J. S.;
Borths, C. J.; Bunel, E. E.; Faul, M. M. J. Org. Chem. 2007, 72, 8870.
E
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