Chiral bis(imidazolinyl)phenyl NCN pincer rhodium(III) Catalysts for enantioselective allylation of aldehydes and carbonyl-ene reaction of trifluoropyruvates

Article abstract of DOI:10.1021/jo4014194

Chiral NCN pincer rhodium(III) complexes with bis(imidazolinyl)phenyl ligands were found to be effective catalysts for the allylation of a variety of electronically and structurally diverse aldehydes with allyltributyltin, giving the corresponding optical

Full text of DOI:10.1021/jo4014194

Article
pubs.acs.org/joc
Chiral Bis(imidazolinyl)phenyl NCN Pincer Rhodium(III) Catalysts for
Enantioselective Allylation of Aldehydes and Carbonyl−Ene Reaction
of Trifluoropyruvates
Tao Wang, Xin-Qi Hao, Juan-Juan Huang, Jun-Long Niu, Jun-Fang Gong,* and Mao-Ping Song*
Henan Key Laboratory of Chemical Biology and Organic Chemistry, The College of Chemistry and Molecular Engineering,
Zhengzhou University, Zhengzhou 450052, People’s Republic of China
S
* Supporting Information
ABSTRACT: Chiral NCN pincer rhodium(III) complexes
with bis(imidazolinyl)phenyl ligands were found to be effective
catalysts for the allylation of a variety of electronically and
structurally diverse aldehydes with allyltributyltin, giving the
corresponding optically active homoallylic alcohols in high
yields with enantioselectivities of up to 97% ee. These
complexes were also applied in the carbonyl−ene reaction of
ethyl or methyl trifluoropyruvate with various 2-arylpropenes.
With the aid of silver trifluoromethanesulfonate, the pincer
rhodium(III) catalysts could catalyze the reaction to provide
the corresponding chiral α-hydroxy-α-trifluoromethyl esters in good yields with high stereoselectivities (up to 95% ee).
used in asymmetric catalysis, with most of the work being
reported by Nishiyama.13 Among them, the Rh−Phebox
complexes have attracted much attention and displayed high
stereoselectivities in various catalytic asymmetric reactions such
as conjugate reductions (up to 99% ee),10g,h reductive aldol
reactions (up to 98% ee),10d,e β-boration of α,β-unsaturated
carbonyl compounds (up to 97% ee),10i and alkynylation of α-
keto esters (up to >99% ee).10f On the other hand, we have
reported C2-symmetric NCN pincer Pd(II),14 Pt(II),15 and
Ni(II)16 complexes with chiral 1,3-bis(2′-imidazolinyl)phenyl
(Phebim) ligands, which are structural analogues of Phebox
ligands. Compared with Phebox ligands, Phebim ligands have
the advantage of further tunability of the electron density and
steric bulkiness of the ligands by appropriate choice of the
substituent on the additional nitrogen atom.17 The preliminary
attempt using a Pd−Phebim complex with a (4S)-phenyl
substituent as the catalyst for the asymmetric addition of
diphenylphosphine to chalcone gave the expected adduct in
84% yield with 85% ee.14b Also, a cationic Pt−Phebim complex
activated the asymmetric Friedel−Crafts alkylation of indoles
with nitroalkenes with up to 83% ee.15b During our study,
Nakamura and co-workers18 also explored the applications of
Pd−Phebim complexes in asymmetric catalysis. They corrobo-
rated that the Pd complexes are highly enantioselective catalysts
for the reaction of benzyl nitriles with imines (up to 92% ee),
the aza-Morita−Baylis−Hillman reaction of acrylonitrile with
imines (up to 98% ee), the decarboxylative Mannich-type
reaction of cyanoacetic acids with imines (up to 90% ee), and
allylation of ketimines (up to 95% ee). Furthermore, it was
INTRODUCTION
■
The uniquely intramolecular, terdentate coordination of pincer
ligands to metal centers in a meridional fashion through σ and/
or dative bonds results in transition-metal pincer complexes
that exhibit generally high stabilities toward heat, air, and
moisture. Since the independent pioneering work of Shaw1 and
van Koten and Noltes2 in the 1970s, a wide variety of chemical
motifs and various transition metals have been introduced into
pincer skeletons. By systematic ligand modifications and/or
variation of the metal center, it has been possible to readily
control the reactivities, stabilities, and other important
properties of the pincer metal complexes. Consequently, such
complexes have been widely utilized in organic synthesis,
organometallic catalysis, materials science, and the related
areas.3 Although these species have been found to be
particularly useful as catalysts in a number of metal-mediated
organic transformations, the development of known or new
chiral pincer metal complexes with excellent catalytic activities
and stereoselectivities still constitutes one of the most
challenging and formidable endeavors in the field of pincer
chemistry. Baratta and co-workers4 demonstrated that a series
of chiral CNN pincer Ru(II) and Os(II) complexes show high
enantioselectivities in ketone hydrogenation (up to 99% ee) and
transfer hydrogenation (up to 99% ee). Recently, Duan and co-
workers5 extended the enantioselective hydrophosphination of
several kinds of electron-deficient alkenes with secondary
phosphines using the known bisphosphine PCP pincer Pd(II)
catalysts, giving chiral phosphine derivatives with excellent
enantioselectivities. In addition, it is worth mentioning that
chiral NCN pincer metal complexes (e.g., M = Pd,6 Pt,7 Ni,8
Ru,9 Rh,10 Ir10d,11 and Fe12) with tridentate bis(oxazolinyl)-
phenyl (Phebox) ligands have been extensively investigated and
Received: July 3, 2013
© XXXX American Chemical Society
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found that the related bis(imidazolidine) NCN pincer Pd(II)
complexes exhibited high performance in the asymmetric
reaction of nitroalkenes with malononitriles (up to 93% ee).19
Very recently, we reported the first synthesis of NCN pincer
Rh(III) complexes with bis(imidazolinyl)phenyl ligands,
including (Phebim)RhCl2(H2O) complexes 1a−e (Scheme 1)
and carbonyl−ene reaction of trifluoropyruvates using these
complexes as the catalysts are described in this report.
RESULTS AND DISCUSSION
■
Allylation of Aldehydes. Catalytic asymmetric allylation of
aldehydes with allyltributyltin can provide direct, efficient
access to potentially useful chiral homoallylic alcohols as
important building blocks for the construction of various
biologically active compounds. Therefore, there has been
intense research activity in this area in recent years, leading
to the development of a large and diverse array of chiral ligands
attached to metals such as Ti,22 In,23 and Bi.24 Although a lot of
achiral pincer complexes, particularly pincer Pd(II) complexes
with structural diversity,3n,25 have been successfully applied in
the allylation of aldehydes and exhibited high catalytic activity,
the chiral ones in the asymmetric allylation have not afforded
impressive enantioselectivitities.10a,b,26 The highest enantiose-
lectivity was only 62% ee26a when chiral pincer Pd(II)
complexes were utilized as the catalysts for this transformation.
Better enantioselectivities were obtained with 5 mol % pincer
Rh−Phebox catalysts, albeit with a limited substrate scope
(eight examples, 35−80% ee).10a,b Moreover, excellent
enantioselectivities (up to 99% ee) have been achieved by
using methallyltributyltin instead of allyltributyltin as the allyl
source.10c It was believed that these Rh(III) complexes acted as
traditional Lewis acid catalysts in the above allylation reactions.
Overall, there is still much room for improvement in the chiral
pincer complex-catalyzed enantioselective allylation of alde-
hydes with allyltributyltin. Also, literature results revealed that
the chiral Rh−Phebox complexes were rather promising in this
reaction. Therefore, it seemed to be necessary to investigate the
potential of our previously reported structurally very related
pincer Rh−Phebim complexes in the asymmetric allylation. The
current experiment began with the allylation of benzaldehyde
with allyltributyltin in the presence of 5 mol % pincer Rh−
Phebim complex at room temperature in CH2Cl2 as the model
Scheme 1. Chiral C2-Symmetric NCN Pincer Rhodium(III)
Complexes with Bis(imidazolinyl)phenyl Ligands
as well as the corresponding (Phebim)Rh(OAc)2(H2O)
complexes. The potential of these complexes in the catalytic
asymmetric alkynylation of trifluoropyruvates with terminal
alkynes was evaluated.20 The results of the studies indicated
that in the presence of 3.0 mol % (Phebim)Rh(OAc)2(H2O)
complex, excellent enantioselectivities (21 examples, 94−99%
ee) could be obtained in the alkynylation of ethyl or methyl
trifluoropyruvate with a range of terminal alkynes, including
aromatic and heteroaromatic alkynes and conjugated enynes.
Moreover, the C2-symmetric Rh−Phebim complexes consis-
tently provided better enantioselectivities than the related C2-
or C1-symmetric Rh−Phebox complexes10f in the addition of
aromatic terminal alkynes to ethyl trifluoropyruvate under
similar reaction conditions. Encouraged by the above results
and also in continuation of our investigations of the pincer
metal complexes,21 we decided to further determine the activity
and stereocontrolling potential of the chiral pincer Rh−Phebim
complexes. The highly enantioselective allylation of aldehydes
Table 1. Optimization of Reaction Conditions for the Asymmetric Allylation of Benzaldehyde with Allyltributyltin Using the
a
Pincer Rh−Phebim Complexes 1 as Catalysts
b
cd
,
entry
cat.
solvent
CH2Cl2
yield (%)
ee (%)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
52
71
41
46
35
40
92
83
57
46
91
67
41
30
77
40
42
45
50
90
86
83
77
90
69
47
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
e
7
1b
1b
1b
1b
1b
1b
1b
ef
,
8
9
eg
,
e
10
11
12
13
e
e
e
ClCH2CH2Cl
toluene
THF
a
b
Reaction conditions: benzaldehyde (0.20 mmol), allyltributyltin (0.30 mmol), cat. 1 (5 mol %), solvent (2 mL), rt, 6 h. Isolated yields.
c
d
Determined by chiral HPLC. The absolute configuration of the product was assigned to be S by comparison of optical rotation with that in ref
e
f
g
10a,b. In the presence of 4 Å molecular sieves (250 mg). Cat. 1b (4 mol %). Cat. 1b (2 mol %), 12 h.
B
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a
Table 2. Asymmetric Allylation of Aldehydes with Allyltributyltin Using the Pincer Rh−Phebim Complex 1b as the Catalyst
a
Reaction conditions: aldehyde (0.20 mmol), allyltributyltin (0.30 mmol), cat. 1b (5 mol %), CH2Cl2 (2 mL), 4 Å molecular sieves (250 mg), rt, 6 h.
b
c
d
Isolated yields. Determined by chiral HPLC. The absolute configurations of the products were assigned to be S by comparison of optical rotations
e
f
with those in ref 10a,b or by analogy. Literature results from ref 10a,b with Rh−Phebox catalysts are given in parentheses. The absolute
configuration of the product was assigned to be R by comparison of the optical rotation with that in ref 10a,b.
reaction. It was found that complex 1b with the (4S)-benzyl
substituent gave the best results among the six Rh−Phebim
complexes, producing the expected homoallylic alcohol 4a in
71% yield with 77% ee (Table 1, entries 1−6). Gratifyingly,
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both the yield and enantioselectivity were significantly
improved by the addition of 4 Å molecular sieves (92% yield
with 90% ee; entry 7). When the catalyst loading was reduced
from 5 mol % to 4 or 2 mol %, a decrease in both the yield and
enantioselectivity was observed, although good enantioselectiv-
ities could still be obtained (entries 8 and 9). In addition,
CH2Cl2 was found to be the most appropriate solvent for the
reaction among the tested solvents, including CH2Cl2, CHCl3,
ClCH2CH2Cl, toluene, and THF (entry 7 vs entries 10−13).
Under the above optimized reaction conditions, various
aldehydes reacted smoothly with allyltributyltin to give the
corresponding chiral homoallylic alcohols in high chemical
yields and enantioselectivities (Table 2). Both electron-
donating and electron-withdrawing groups in the substituted
benzaldehydes were tolerated, and good to excellent
enantioselectivities were obtained (80−97% ee; entries 1−15).
Roughly, the electron-withdrawing group showed some
beneficial effect on the yield of the catalysis product while
the electron-donating group was beneficial for the enantiose-
lectivity compared with benzaldehyde. The position of the
group on the aryl ring also had some influence on the yield
and/or enantioselectivity. For example, the reactions of 2-, 3-,
and 4-methoxybenzaldehyde with allyltributyltin afforded the
expected adducts in 82, 80, 85% yield, respectively, with 93, 92,
and 88% ee, respectively (entries 9−11). For 1- and 2-
naphthaldehyde, excellent enantioselectivities were achieved
(94 and 92% ee, respectively; entries 16 and 17). Particularly,
when heteroaromatic aldehydes such as thiophene- and furan-2-
carboxaldehyde were used as substrates, excellent stereocontrol
of the alcohol products was always observed (90−95% ee;
entries 18−21). These aldehydes are somewhat special since
they bear ligating atoms that may deactivate the catalyst. In fact,
in the case of pyridine-2-carboxaldehyde, no allylation occurred
under the present reaction conditions (data not shown in Table
2). Besides aromatic and heteroaromatic aldehydes, allylations
of several aliphatic aldehydes were also examined. It was found
that trans-β-phenylacrolein, which is an enal, afforded high
enantioselectivity (86% ee; entry 22), while for 3-phenyl-
propanal, a rather low enantiomeric excess was obtained (37%
ee; entry 23). Nonetheless, the use of α-benzyloxyacetaldehyde
as the substrate gave the corresponding chiral homoallylic
alcohol with good stereocontrol (85% ee; entry 24). The above
results confirm that the Rh−Phebim complexes are highly
enantioselective catalysts for the asymmetric allylation of
aldehydes with allyltributyltin. It is worth pointing out that in
the allylation of six specific aldehydes, the Rh−Phebim
complexes invariably provided much better enantioselectivities
than the related Rh−Phebox complexes10a,b under similar
reaction conditions (entries 1, 7, 11, 18, 22, and 24).
Furthermore, to the best of our knowledge, Rh−Phebim
catalysts are the most effective among the pincer catalysts for
the studied allylation in regard to the scope of aldehyde
substrate and the product enantioselectivity.
interest to further explore their performance in the Lewis acid-
catalyzed carbonyl−ene reaction. To the best of our knowledge,
there is no report on the use of pincer catalysts in this reaction.
The addition of 2-phenylpropene to ethyl trifluoropyruvate was
selected as the model reaction, and a brief optimization of
reaction conditions is summarized in Table 3. No reaction
Table 3. Optimization of the Reaction Conditions for the
Asymmetric Carbonyl−Ene Reaction of Ethyl
Trifluoropyruvate Using the Pincer Rh−Phebim Complexes
a
1 as Catalysts
b
cd
,
entry
cat.
solvent
additive
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
1a
1a
1b
1c
1d
1e
1f
1f
1f
1f
1f
1f
1f
1f
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CH2Cl2
−
0
21
31
51
10
15
82
74
89
<5
<5
88
49
41
−
33
8
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgBF4
0
0
9
54
39
93
AgOTf
AgOTf
Me3SiOTf
AgOTf
AgOTf
AgOTf
e
f
10
n.d.
f
11
12
13
14
n.d.
89
53
40
CHCl3
toluene
a
Reaction conditions: ethyl trifluoropyruvate (0.20 mmol), 2-phenyl-
propene (0.24 mmol), Rh complex 1 (3 mol %), additive (6 mol %),
b
c
solvent (2 mL), rt, 16 h. Isolated yields. Determined by chiral
d
HPLC. The absolute configuration of the product was assigned to be
S by comparison of optical rotation with that in ref 27c. 3 mol %
e
f
AgOTf. Not determined.
occurred in the presence of Rh−Phebim complex 1a containing
the (4S)-phenyl substituent as the catalyst (entry 1). When 2
equiv of AgSbF6 relative to complex 1a was added to the
reaction mixture to enhance the Lewis acidity of the Rh(III)
catalyst, the expected product could be isolated, albeit in rather
modest yield and enantioselectivity (21% yield with 33% ee;
entry 2). When the other five Rh−Phebim complexes 1b−f
were examined in the presence of AgSbF6 (entries 3−7), it was
found that both the reactivity and selectivity of the reaction
were greatly influenced by the ligand structure of the Rh−
Phebim complex. Although complex 1b with the (4S)-benzyl
substituent gave the best results in the allylation, it afforded
only 8% ee in the carbonyl−ene reaction (entry 3). Pleasingly,
complex 1f with the (4S)-tert-butyl substituent provided
hopeful results (82% yield with 54% ee; entry 7). Further
studies revealed that the anion of the Ag(I) salt played a key
role for effective stereocontrol of the reaction (entries 7−9).
When AgOTf instead of AgSbF6 was used to abstract the
chloride in complex 1f, the enantioselectivity of the reaction
was significantly improved to 93% ee (entry 9). It was found
that the amount of AgOTf was also crucial for the reaction.
With 1 equiv of AgOTf relative to complex 1f, only a trace
amount of the expected alcohol product was isolated (<5%
yield; entry 10). When the reaction of ethyl trifluoropyruvate
with 2-phenylpropene was carried out in the presence of 6 mol
Carbonyl−Ene Reaction. The chiral Lewis acid- or
Brønsted acid-catalyzed enantioselective carbonyl−ene reaction
of trifluoropyruvates,27 which can construct a tetrasubstituted
stereogenic center, continues to receive considerable attention
in asymmetric synthesis because the obtained α-CF3-
substituted optically active homoallylic alcohols are important
intermediates for drug molecules. On the basis of the successful
application of the Rh−Phebim complexes in the aforemen-
tioned asymmetric allylation, where they may act as Lewis acid
catalysts similar to the Rh−Phebox complexes,10a−c it was of
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% AgOTf without the pincer Rh−Phebim complex, the
expected product was not detected after stirring at room
temperature in 1,2-dichloroethane (DCE) for 16 h (data not
shown in Table 3). In addition, the use of Me3SiOTf as an
additive to activate the neutral pincer Rh−Phebim complex 1f
proved to be ineffective (entry 11). Finally, a quick survey of
different solvents, including DCE, CH2Cl2, CHCl3, and toluene
indicated that DCE was the most appropriate solvent (entry 9
vs entries 12−14). Thus, the optimized conditions include
using complex 1f in the presence of 2 equiv of AgOTf as the
catalyst and DCE as the solvent.
trifluoropyruvate with several representative alkenes was also
studied. Although good results (60−82% yield with 65−77%
ee) could still be obtained, the yields and ee values were
obviously inferior to those in the corresponding reactions of
ethyl trifluoropyruvate (entries 13−17). In these reactions, an
electron-withdrawing group on the phenyl ring of the 2-
arylpropene had a detrimental effect on the stereoselectivity
instead.
In the enantioselective allylation of aldehydes with allyltin
reagents catalyzed by pincer Rh−Phebox complexes, a detailed
mechanistic study by Nishiyama and coauthors10b revealed that
the (Phebox)RhCl2 fragment generated by release of H2O from
the neutral pincer (Phebox)RhCl2(H2O) complex was the
catalytically active species. This fragment activates the carbonyl
group of the aldehyde through coordination of the carbonyl
oxygen to the rhodium center. The allyltin then attacks the
activated aldehyde to give the homoallylic alcohol product.
Thus, the allylation proceeds via a Lewis acid-catalyzed
mechanism. In view of the high structural similarity between
Rh−Phebim and Rh−Phebox complexes, it seems to be
reasonable to deduce that the neutral (Phebim)RhCl2(H2O)
complexes 1 also act as traditional Lewis acid catalysts in the
allylation. In fact, there is some evidence that the coordinated
H2O molecule in the (Phebim)RhCl2(H2O) complex disso-
ciates easily and that the carbonyl compound can coordinate to
the Rh(III) center of the (Phebim)RhCl2 fragment. In our
previous studies, crystals of the corresponding acetone- or
dichloromethane-coordinated complexes were always obtained
when we performed recrystallization in acetone or dichloro-
methane to get crystals of (Phebim)RhCl2(H2O) complexes.20
This phenomenon means that in the allylation the (Phebim)-
RhCl2(H2O) complex can also release H2O to give the
(Phebim)RhCl2 fragment, which can activate the aldehyde
just as the (Phebox)RhCl2 fragment does. In contrast to
allylation, the Lewis acid-catalyzed carbonyl−ene reaction of
trifluoropyruvate did not occur in the presence of (Phebim)-
RhCl2(H2O) complexes 1. It seemed that the electrophilicity of
the metal center in these neutral complexes was not high
enough to activate trifluoropyruvate. Fortunately, the Lewis
acidity of the complexes could be enhanced by abstraction of
chloride from the Rh(III) center to form the corresponding
cationic species. Not unexpectedly, the carbonyl−ene reaction
proceeded in the presence of Ag(I) salts, particularly AgOTf.
Since 2 equiv of AgOTf relative to Rh−Phebim complex 1 was
essential for smooth reaction, an in situ-generated dicationic
Rh(III) species, [(Phebim)Rh(H2O)][OTf]2, is considered to
be the active catalyst, which can activate trifluoropyruvate
through chelate coordination of both carbonyl oxygen atoms to
the rhodium center. A catalytic cycle for the carbonyl−ene
reaction is proposed in Scheme S1 in the Supporting
Information.
With the optimal conditions established, the scope of the
reaction with respect to various alkenes was investigated (Table
4). A broad range of 2-arylpropenes (5a−l) underwent the
Table 4. Substrate Scope for the Catalytic Asymmetric
Carbonyl−Ene Reaction of Trifluoropyruvates Using the
a
Pincer Rh−Phebim Complex 1f as the Catalyst
b
cd
,
entry
Ar
R
product
yield (%)
ee (%)
1
Ph
Et
7a
7b
7c
7d
7e
7f
89
85
85
87
87
80
88
80
85
80
81
87
82
81
62
80
60
93
77
89
74
74
91
95
94
94
93
75
81
77
70
65
71
74
2
4-MeC6H4
3-MeC6H4
4-EtC6H4
4-tBuC6H4
4-FC6H4
4-ClC6H4
3-ClC6H4
4-BrC6H4
3-BrC6H4
1-naphthyl
2-naphthyl
Ph
Et
3
Et
4
Et
5
Et
6
Et
7
Et
7g
7h
7i
8
Et
9
Et
10
11
12
13
14
15
16
17
Et
7j
Et
7k
7l
Et
Me
Me
Me
Me
Me
7m
7n
7o
7p
7q
4-ClC6H4
3-ClC6H4
4-BrC6H4
3-BrC6H4
a
Reaction conditions: trifluoropyruvate (0.20 mmol), alkene (0.24
mmol), Rh complex 1f (3 mol %), AgOTf (6 mol %), ClCH2CH2Cl
b
c
d
(2 mL), rt, 16 h. Isolated yields. Determined by chiral HPLC. The
absolute configurations of the products were assigned to be S by
comparison of optical rotations with those in ref 27c or by analogy.
desired reaction with trifluoropyruvates to provide the
corresponding α-hydroxy-α- trifluoromethyl esters (7a−q) in
high yields with good to excellent enantioselectivities. In the
reaction of ethyl trifluoropyruvate, an evident electronic effect
on the enantioselectivy was observed. In comparison with 2-
phenylproene (93% ee; entry 1), 2-arylpropenes containing an
electron-donating group such as alkyl on the phenyl group
provided obviously lower stereoselectivities (74−89% ee;
entries 2−5), while those with an electron-withdrawing group
such as 4-F, 4-Cl, 4-Br, 3-Cl, or 3-Br on the phenyl ring gave
comparable or slightly higher enantioselectivities (91−95% ee;
entries 6−10). Similarly, 2-naphthylpropenes, which are more
electron-rich than 2-phenylpropene, also afforded lower
stereoselectivities (75 and 81% ee; entries 11 and 12). In
addition, the asymmetric carbonyl−ene reaction of methyl
CONCLUSIONS
■
In conclusion, we have shown that chiral NCN pincer Rh−
Phebim complexes are highly enantioselective catalysts for the
allylation of aldehydes with allyltributyltin, giving the
corresponding catalysis products in high yields with enantio-
selectivities of up to 97% ee. The current process tolerates a
range of aldehyde substrates under mild conditions, and the
Rh−Phebim catalysts were found to be much superior to the
closely related Rh−Phebox catalysts with respect to substrate
scope and enantioselectivity. In addition, in the presence of
AgOTf, the aforementioned Rh−Phebim complexes gave
E
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rate = 1.0 mL/min, and detection at a UV wavelength of 220 nm.
effective catalysts with high stereoselectivities (up to 95% ee)
for the asymmetric carbonyl−ene reaction of trifluoropyruvates
with 2-arylpropenes, a reaction which was catalyzed for the first
time by pincer metal complexes. The scope of the alkene
substrates are relatively broad. Further experiments to study the
applications of the Rh−Phebim catalysts to other reactions are
in progress.
Retention times: 15.6 min (major), 16.9 min, 86% ee. [α]2D0 = −45.3 (c
1
0.524, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.59 (d, J = 8.2 Hz,
2H), 7.46 (d, J = 8.1 Hz, 2H), 5.83−5.73 (m, 1H), 5.19−5.15 (m,
2H), 4.78 (dd, J = 4.9, 7.8 Hz, 1H), 2.56−2.41 (m, 2H), 2.29 (br s,
1H, OH).
(S)-1-(4-Chlorophenyl)but-3-en-1-ol (4e).23,24,30,31a,b Pale-yellow
oil (33.6 mg, 92%). The enantiomeric excess was determined on a
Daicel Chiralcel OJ-H column with hexane/2-propanol = 100/2, flow
rate = 0.5 mL/min, and detection at a UV wavelength of 254 nm.
Retention times: 29.1 min (major), 31.5 min, 86% ee. [α]2D0 = −43.6 (c
0.520, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.32−7.26 (m, 4H),
5.82−5.72 (m, 1H), 5.17−5.13 (m, 2H), 4.70 (dd, J = 5.2, 7.6 Hz,
1H), 2.53−2.40 (m, 2H), 2.19 (br s, 1H, OH).
EXPERIMENTAL SECTION
■
General. Solvents were dried with standard methods and freshly
distilled prior to use if needed. The 2-arylpropenes were synthesized
according to the literature methods.28 All other chemicals were used as
purchased. NMR spectra were recorded with CDCl3 as the solvent and
TMS as an internal standard. HRMS data were acquired on a Q-Tof
Micro MS/MS ESI mass spectrometer.
(S)-1-(2,4-Dichlorophenyl)but-3-en-1-ol (4f).32 Pale-yellow oil
(42.1 mg, 97%). The enantiomeric excess was determined on a Daicel
Chiralcel OJ-H column with hexane/2-propanol = 99/1, flow rate =
1.0 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 11.8 min, 13.7 min (major), 84% ee. [α]2D0 = −81.9 (c 0.764,
Synthesis of the NCN Pincer (Phebim)RhCl2(H2O) Complexes
1a−f. The ligands and the corresponding NCN pincer (Phebim)-
RhCl2(H2O) complexes 1a−f were prepared according to the
procedure reported previously by us.20 The analytical data of the
new complex 1f is given in the next paragraph.
(2,6-Bis((S)-4-tert-butyl-1-p-tolyl-4,5-dihydro-1H-imidazol-2-yl)-
phenyl)RhCl2(H2O) (1f). Yellow solid (149.9 mg, 43%); mp 180−182
°C. [α]2D0 = +885 (c 0.156, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ
7.23 (d, J = 8.6 Hz, 4H, ArH), 7.20 (d, J = 8.4 Hz, 4H, ArH), 6.63 (dd,
J = 6.7, 8.7 Hz, 1H, ArH), 6.56−6.54 (m, 2H, ArH), 4.29 (app t, J =
11.8 Hz, 2H, NCH), 4.18 (dd, J = 9.2, 10.8 Hz, 2H, NCHH), 3.82 (dd,
J = 9.2, 12.6 Hz, 2H, NCHH), 2.40 (s, 6H, CH3), 1.62 (br s, 2H,
OH2), 1.32 (s, 18H, C(CH3)3). 13C NMR (100 MHz, CDCl3): δ
165.7, 138.4, 137.9, 134.8, 130.3, 128.2, 126.3, 121.8, 72.1, 56.9, 33.7,
26.9, 21.2. Anal. Found: C, 58.09; H, 6.01; N, 7.91. Calcd for
C34H43Cl2N4ORh: C, 58.54; H, 6.21; N, 8.03.
General Procedure for the Asymmetric Allylation of
Aldehydes with Allyltributyltin by the NCN Pincer (Phebim)-
RhCl2(H2O) Complexes 1. Under an argon atmosphere, to a
suspension of 4 Å molecular sieves (250 mg) in CH2Cl2 (2 mL) was
added the NCN pincer (Phebim)RhCl2(H2O) complex 1 (0.01 mmol,
5.0 mol %), aldehyde (0.20 mmol), and allyltributyltin (0.30 mmol,
93.0 μL) at room temperature. After the resulting solution mixture was
stirred at that temperature for 6 h, the residue was purified by
preparative TLC on silica gel plates eluting with CH2Cl2 to afford the
homoallylic alcohol.
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 1H),
7.33 (d, J = 2.1 Hz, 1H), 7.26 (dd, J = 2.0, 8.4 Hz, 1H), 5.88−5.78 (m,
1H), 5.19−5.15 (m, 2H), 5.08 (dd, J = 3.5, 8.0 Hz, 1H), 2.62−2.56
(m, 1H), 2.36−2.29 (m, 2H).
(S)-1-(4-Bromophenyl)but-3-en-1-ol (4g).10a,b,29 Pale-yellow oil
(43.1 mg, 95%). The enantiomeric excess was determined on a Daicel
Chiralcel OJ-H column with hexane/2-propanol = 100/1, flow rate =
1.0 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 31.3 min (major), 34.9 min, 88% ee. [α]2D0 = −42.5 (c 0.720,
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 8.4 Hz, 2H),
7.21 (d, J = 8.4 Hz, 2H), 5.81−5.71 (m, 1H), 5.17−5.12 (m, 2H), 4.67
(dd, J = 5.3, 7.5 Hz, 1H), 2.52−2.39 (m, 2H), 2.26 (br s, 1H, OH).
(S)-1-(3-Bromophenyl)but-3-en-1-ol (4h).33 Pale-yellow oil (41.8
mg, 92%). The enantiomeric excess was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 99/1, flow rate =
1.0 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 24.9 min, 26.9 min (major), 90% ee. [α]2D0 = −39.5 (c 0.626,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.52 (s, 1H), 7.41−7.39 (m,
1H), 7.27 (d, J = 7.4 Hz, 1H), 7.21 (t, J = 7.7 Hz, 1H), 5.84−5.73 (m,
1H), 5.19−5.15 (m, 2H), 4.71−4.68 (m, 1H), 2.55−2.41 (m, 2H),
2.16 (br s, 1H, OH).
(S)-1-(2-Methoxyphenyl)but-3-en-1-ol (4i).24,30 Pale-yellow oil
(29.2 mg, 82%). The enantiomeric excess was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 99.5/0.5, flow rate
= 1.0 mL/min, and detection at a UV wavelength of 220 nm.
Retention times: 24.9 min (major), 29.4 min, 93% ee. [α]2D0 = −51.2 (c
0.364, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.33 (dd, J = 1.5, 7.5
Hz, 1H), 7.27−7.22 (m, 1H), 6.98−6.94 (m, 1H), 6.88 (d, J = 8.2 Hz,
1H), 5.90−5.80 (m, 1H), 5.16−5.09 (m, 2H), 4.96 (t, J = 3.7 Hz, 1H),
3.85 (s, 3H, OCH3), 2.62−2.47 (m, 3H).
(S)-1-Phenylbut-3-en-1-ol (4a).10a,b,22−24,29,30 Pale-yellow oil (27.2
mg, 92%). The enantiomeric excess was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 100/5, flow rate =
0.5 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 15.3 min, 17.5 min (major), 90% ee. [α]2D0 = −52.0 (c 0.840,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.35−7.25 (m, 5H), 5.85−
5.75 (m, 1H), 5.18−5.12 (m, 2H), 4.72 (dd, J = 5.5, 7.4 Hz, 1H),
2.55−2.46 (m, 2H), 2.17 (br s, 1H, OH).
(S)-1-(3-Methoxyphenyl)but-3-en-1-ol (4j).30,31a,b Pale-yellow oil
(28.5 mg, 80%). The enantiomeric excess was determined on a Daicel
Chiralcel OJ-H column with hexane/2-propanol = 99.5/0.5, flow rate
= 1.0 mL/min, and detection at a UV wavelength of 220 nm.
Retention times: 42.6 min (major), 46.9 min, 92% ee. [α]2D0 = −48.0 (c
0.340, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.28−7.24 (m, 1H),
6.94−6.93 (m, 2H), 6.83−6.80 (m, 1H), 5.87−5.76 (m, 1H), 5.19−
5.13 (m, 2H), 4.72 (t, J = 6.2 Hz, 1H), 3.82 (s, 3H, OCH3), 2.57−2.45
(m, 2H), 2.07 (br s, 1H, OH).
(S)-1-(4-Nitrophenyl)but-3-en-1-ol (4b).22b,29,31a Pale-yellow oil
(38.3 mg, 99%). The enantiomeric excess was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 98/2, flow rate =
1.0 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 48.9 min, 52.5 min (major), 80% ee. [α]2D0 = −45.5 (c 1.000,
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 8.8 Hz, 2H),
7.53 (d, J = 8.6 Hz, 2H), 5.84−5.74 (m, 1H), 5.20−5.15 (m, 2H), 4.86
(dd, J = 4.7, 7.9 Hz, 1H), 2.59−2.53 (m, 1H), 2.50−2.42 (m, 2H).
(S)-1-(3-Nitrophenyl)but-3-en-1-ol (4c).29,31a Pale-yellow oil (33.2
mg, 86%). The enantiomeric excess was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 98/2, flow rate =
1.0 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 41.8 min, 46.0 min (major), 85% ee. [α]2D0 = −48.2 (c 0.388,
(S)-1-(4-Methoxyphenyl)but-3-en-1-ol (4k).10a,b,24,30,31a,b Pale-yel-
low oil (30.3 mg, 85%). The enantiomeric excess was determined on a
Daicel Chiralcel OD-H column with hexane/2-propanol = 90/3, flow
rate = 0.5 mL/min, and detection at a UV wavelength of 254 nm.
Retention times: 28.1 min, 30.6 min (major), 88% ee. [α]2D0 = −49.8 (c
1
1
0.550, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.28 (d, J = 8.6 Hz,
CH2Cl2). H NMR (400 MHz, CDCl3): δ 8.24 (t, J = 1.8 Hz, 1H),
2H), 6.88 (d, J = 8.7 Hz, 2H), 5.85−5.74 (m, 1H), 5.17−5.11 (m,
2H), 4.69 (t, J = 6.5 Hz, 1H), 3.80 (s, 3H, OCH3), 2.49 (t, J = 6.8 Hz,
2H), 2.04 (br s, 1H, OH).
8.14−8.12 (m, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.53 (t, J = 7.9 Hz, 1H),
5.85−5.75 (m, 1H), 5.22−5.17 (m, 2H), 4.87 (dd, J = 4.8, 7.8 Hz,
1H), 2.61−2.44 (m, 2H), 2.37 (br s, 1H, OH).
(S)-1-(4-(Trifluoromethyl)phenyl)but-3-en-1-ol (4d).30,31b Pale-yel-
low oil (42.8 mg, 99%). The enantiomeric excess was determined on a
Daicel Chiralcel OJ-H column with hexane/2-propanol = 99/1, flow
(S)-1-(4-Methylphenyl)but-3-en-1-ol (4l).23b,24,29,30,31a Pale-yellow
oil (29.9 mg, 92%). The enantiomeric excess was determined on a
Daicel Chiralcel OB-H column with hexane/2-propanol = 99/1, flow
F
dx.doi.org/10.1021/jo4014194 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
rate = 1.0 mL/min, and detection at a UV wavelength of 220 nm.
0.5 mL/min, and detection at a UV wavelength of 220 nm. Retention
Retention times: 27.1 min (major), 35.5 min, 97% ee. [α]2D0 = −59.6 (c
times: 20.2 min (major), 23.0 min, 95% ee. [α]2D0 = −31.0 (c 0.280,
1
1
0.826, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.23 (d, J = 8.0 Hz,
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.25 (dd, J = 1.6, 4.8 Hz,
2H), 7.15 (d, J = 8.0 Hz, 2H), 5.84−5.74 (m, 1H), 5.17−5.10 (m,
2H), 4.68 (t, J = 6.5 Hz, 1H), 2.51−2.47 (m, 2H), 2.34 (s, 3H, CH3),
2.10 (br s, 1H, OH).
1H), 6.99−6.96 (m, 2H), 5.88−5.78 (m, 1H), 5.22−5.15 (m, 2H),
4.98 (t, J = 6.4 Hz, 1H), 2.64−2.60 (m, 2H), 2.24 (br s, 1H, OH).
(S)-1-(5-Methylthiophen-2-yl)but-3-en-1-ol (4u). Pale-yellow oil
(26.9 mg, 80%). The enantiomeric excess was determined on a Daicel
Chiralcel OJ-H column with hexane/2-propanol = 100/2, flow rate =
0.8 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 19.3 min (major), 21.0 min, 92% ee. [α]2D0 = −21.1 (c 0.408,
(S)-1-(3-Methylphenyl)but-3-en-1-ol (4m).29,31b Pale-yellow oil
(25.9 mg, 80%). The enantiomeric excess was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 99/1, flow rate =
1.0 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 18.7 min, 19.7 min (major), 87% ee. [α]2D0 = −48.0 (c 0.100,
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 6.75 (d, J = 3.4 Hz, 1H),
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.23 (t, J = 7.2 Hz, 1H),
6.59 (dd, J = 0.9, 3.3 Hz, 1H), 5.88−5.77 (m, 1H), 5.20−5.13 (m,
2H), 4.87 (t, J = 6.4 Hz, 1H), 2.60−2.57 (m, 2H), 2.46 (s, 3H, CH3),
2.18 (br s, 1H, OH). 13C NMR (100 MHz, CDCl3): δ 145.3, 139.3,
134.0, 124.6, 123.8, 118.6, 69.5, 43.6, 15.4. HRMS (positive ESI): [M
+ H]+ calcd for C9H13OS: 169.0687. Found: 169.0684.
7.15 (t, J = 8.7 Hz, 2H), 7.09 (d, J = 7.4 Hz, 1H), 5.86−5.76 (m, 1H),
5.19−5.13 (m, 2H), 4.70 (dd, J = 5.3, 7.6 Hz, 1H), 2.56−2.44 (m,
2H), 2.36 (s, 3H, CH3), 2.03 (br s, 1H, OH).
(S)-1-(4-Cyanophenyl)but-3-en-1-ol (4n).30,31c Pale-yellow oil
(27.7 mg, 80%). The enantiomeric excess was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 98/2, flow rate =
1.0 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 46.7 min, 48.9 min (major), 80% ee. [α]2D0 = −59.7 (c 0.378,
(S)-(E)-1-Phenyl-1,5-hexadien-3-ol (4v).10a,b,31a Pale-yellow oil
(33.1 mg, 95%). The enantiomeric excess was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 90/10, flow rate =
0.5 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 14.6 min, 20.3 min (major), 86% ee. [α]2D0 = −20.7 (c 0.760,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.39−7.37 (m, 2H), 7.33−
7.29 (m, 2H), 7.25−7.21 (m, 1H), 6.60 (d, J = 15.9 Hz, 1H), 6.23 (dd,
J = 6.3, 15.9 Hz, 1H), 5.91−5.80 (m, 1H), 5.20−5.15 (m, 2H), 4.38−
4.33 (m, 1H), 2.47−2.34 (m, 2H), 1.90 (br s, 1H, OH).
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.3 Hz, 2H),
7.47 (d, J = 8.2 Hz, 2H), 5.82−5.72 (m, 1H), 5.19−5.14 (m, 2H), 4.80
(dd, J = 4.7, 7.9 Hz, 1H), 2.57−2.40 (m, 2H), 2.37 (br s, 1H, OH).
(S)-1-(4-(Dimethylamino)phenyl)but-3-en-1-ol (4o).34 Pale-yellow
oil (32.2 mg, 84%). The enantiomeric excess was determined on a
Daicel Chiralpak AD-H column with hexane/2-propanol = 100/0.5,
flow rate = 1.0 mL/min, and detection at a UV wavelength of 220 nm.
Retention times: 104.8 min (major), 115.6 min, 92% ee. [α]2D0 = −61.0
(R)-1-Phenyl-5-hexen-3-ol (4w).10a,b,31a Pale-yellow oil (28.2 mg,
80%). The enantiomeric excess was determined on a Daicel Chiralcel
OD-H column with hexane/2-propanol = 90/10, flow rate = 0.5 mL/
min, and detection at a UV wavelength of 254 nm. Retention times:
15.0 min (major), 20.0 min, 37% ee. [α]2D0 = +14.6 (c 0.506, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.30−7.24 (m, 2H), 7.21−7.16 (m,
1
(c 0.112, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.24 (d, J = 8.7
Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 5.87−5.76 (m, 1H), 5.18−5.10 (m,
2H), 4.64 (t, J = 6.3 Hz, 1H), 2.94 (s, 6H, CH3), 2.53−2.49 (m, 2H).
(S)-1-(Naphthalen-1-yl)but-3-en-1-ol (4p).23b,24,31a Pale-yellow oil
(34.9 mg, 88%). The enantiomeric excess was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 95/5, flow rate =
0.8 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 15.1 min (major), 18.7 min, 94% ee. [α]2D0 = −90.9 (c 0.492,
3H), 5.87−5.76 (m, 1H), 5.16−5.12 (m, 2H), 3.70−3.64 (m, 1H),
2.84−2.77 (m, 1H), 2.72−2.64 (m, 1H), 2.35−2.29 (m, 1H), 2.22−
2.14 (m, 1H), 1.81−1.75 (m, 2H), 1.74 (br s, 1H, OH).
(S)-1-Benzyloxy-4-penten-2-ol (4x).10b,31d Pale-yellow oil (30.7
mg, 80%). The enantiomeric excess was determined on a Daicel
Chiralcel OB-H column with hexane/2-propanol = 90/10, flow rate =
0.5 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 21.3 min (major), 24.9 min, 85% ee. [α]2D0 = +3.7 (c 0.920,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.37−7.24 (m, 5H), 5.87−
5.76 (m, 1H), 5.13−5.07 (m, 2H), 4.54 (s, 2H), 3.86 (s, 1H), 3.50
(dd, J = 3.4, 9.5 Hz, 1H), 3.37 (dd, J = 7.4, 9.5 Hz, 1H), 2.49 (br s, 1H,
OH), 2.25 (t, J = 6.7 Hz, 2H).
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.0 Hz, 1H),
7.86 (d, J = 7.4 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.65 (d, J = 7.1 Hz,
1H), 7.52−7.45 (m, 3H), 5.97−5.86 (m, 1H), 5.51 (dd, J = 4.0, 8.3
Hz, 1H), 5.23−5.16 (m, 2H), 2.78−2.72 (m, 1H), 2.63−2.55 (m, 1H),
2.24 (br s, 1H, OH).
(S)-1-(Naphthalen-2-yl)but-3-en-1-ol (4q).23,24,31a,b Pale-yellow oil
(35.7 mg, 90%). The enantiomeric excess was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 95/5, flow rate =
0.8 mL/min, and detection at a UV wavelength of 254 nm. Retention
times: 17.9 min (major), 21.0 min, 92% ee. [α]2D0 = −57.9 (c 0.550,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.82−7.78 (m, 4H), 7.49−
7.43 (m, 3H), 5.86−5.76 (m, 1H), 5.19−5.12 (m, 2H), 4.87 (dd, J =
5.6, 7.2 Hz, 1H), 2.62−2.52 (m, 2H), 2.25 (br s, 1H, OH).
(S)-1-(Furan-2-yl)but-3-en-1-ol (4r).10a,b,31b Pale-yellow oil (22.6
mg, 82%). The enantiomeric excess was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 99.5/0.5, flow rate
= 0.5 mL/min, and detection at a UV wavelength of 220 nm.
Retention times: 70.6 min (major), 77.7 min, 90% ee. [α]2D0 = −14.0 (c
General Procedure for the Asymmetric Catalytic Carbonyl−
Ene Reaction by the NCN Pincer (Phebim)RhCl2(H2O) Com-
plexes 1. Under an argon atmosphere, the NCN Pincer (Phebim)-
RhCl2(H2O) complex 1 (0.006 mmol, 3.0 mol %) was dissolved in 2
mL of ClCH2CH2Cl, and AgOTf (0.012 mmol, 6.0 mol %) was added.
The resulting mixture was stirred at room temperature for 10 min.
Ethyl trifluoropyruvate or methyl trifluoropyruvate (0.20 mmol) was
added, followed by alkene (0.24 mmol), and then the resulting
solution mixture was stirred at room temperature for 16 h. The residue
was purified by preparative TLC on silica gel plates eluted with
CH2Cl2/petroleum ether to afford the desired product.
(S)-Ethyl 2-Hydroxy-4-phenyl-2-(trifluoromethyl)pent-4-enoate
(7a).27c Colorless oil (51.3 mg, 89%). The enantiomeric excess was
determined on a Daicel Chiralcel OJ-H column with hexane/2-
propanol = 100/1, flow rate = 1.0 mL/min, and detection at a UV
wavelength of 220 nm. Retention times: 12.9 min (major), 17.6 min,
93% ee. [α]2D0 = −60.3 (c 0.992, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ 7.34−7.26 (m, 5H), 5.39 (s, 1H), 5.28 (s, 1H), 4.07−3.99
(m, 1H), 3.78 (s, 1H), 3.67−3.58 (m, 1H), 3.28 (d, J = 14.0 Hz, 1H),
3.03 (d, J = 14.0 Hz, 1H), 1.11 (t, J = 7.2 Hz, 3H).
1
0.100, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.38 (d, J = 0.9 Hz,
1H), 6.33 (dd, J = 1.9, 3.0 Hz, 1H), 6.25 (d, J = 3.2 Hz, 1H), 5.86−
5.76 (m, 1H), 5.17 (t, J = 11.2 Hz, 2H), 4.75 (t, J = 6.4 Hz, 1H), 2.68−
2.57 (m, 2H), 2.11 (br s, 1H, OH).
(S)-1-(5-Methylfuran-2-yl)but-3-en-1-ol (4s).23a Pale-yellow oil
(23.7 mg, 78%). The enantiomeric excess was determined on a Daicel
Chiralpak AD-H column with hexane/2-propanol = 300/1, flow rate =
1.0 mL/min, and detection at a UV wavelength of 220 nm. Retention
times: 55.1 min (major), 64.4 min, 93% ee. [α]2D0 = −25.0 (c 0.226,
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 6.12 (d, J = 3.0 Hz, 1H),
(S)-Ethyl 2-Hydroxy-4-(p-tolyl)-2-(trifluoromethyl)pent-4-enoate
(7b).27c Colorless oil (51.4 mg, 85%). The enantiomeric excess was
determined on a Daicel Chiralcel OJ-H column with hexane/2-
propanol = 100/1, flow rate = 1.0 mL/min, and detection at a UV
wavelength of 220 nm. Retention times: 11.3 min (major), 15.2 min,
77% ee. [α]2D0 = −20.1 (c 0.996, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ 7.22 (d, J = 8.2 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 5.35 (s,
5.90 (dd, J = 0.9, 3.0 Hz, 1H), 5.87−5.77 (m, 1H), 5.21−5.13 (m,
2H), 4.68 (t, J = 6.6 Hz, 1H), 2.63−2.59 (m, 2H), 2.28 (s, 3H, CH3),
2.04 (br s, 1H, OH).
(S)-1-(Thiophen-2-yl)but-3-en-1-ol (4t).24,31a,b Pale-yellow oil
(25.9 mg, 84%). The enantiomeric excess was determined on a Daicel
Chiralcel OJ-H column with hexane/2-propanol = 100/5, flow rate =
G
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1H), 5.22 (s, 1H), 4.09−4.01 (m, 1H), 3.76 (s, 1H), 3.72−3.64 (m,
1H), 3.25 (d, J = 14.0 Hz, 1H), 3.02 (d, J = 14.0 Hz, 1H), 2.33 (s, 3H),
1.13 (t, J = 7.1 Hz, 3H).
3.76 (s, 1H), 3.21 (d, J = 14.1 Hz, 1H), 3.03 (d, J = 14.0 Hz, 1H), 1.17
(t, J = 7.2 Hz, 3H).
(S)-Ethyl 4-(3-Bromophenyl)-2-hydroxy-2-(trifluoromethyl)pent-
4-enoate (7j). Colorless oil (58.7 mg, 80%). The enantiomeric excess
was determined on a Daicel Chiralpak AS-H column with hexane/2-
propanol = 100/1, flow rate = 0.5 mL/min, and detection at a UV
wavelength of 254 nm. Retention times: 12.0 min, 14.8 min (major),
93% ee. [α]2D0 = −78.9 (c 0.528, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ 7.46 (t, J = 1.7 Hz, 1H), 7.42−7.39 (m, 1H), 7.27−7.25 (m,
1H), 7.18 (t, J = 7.8 Hz, 1H), 5.39 (s, 1H), 5.31 (s, 1H), 4.15−4.07
(m, 1H), 3.80−3.72 (m, 1H), 3.78 (s, 1H), 3.22 (d, J = 14.1 Hz, 1H),
3.01 (d, J = 14.0 Hz, 1H), 1.17 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 168.9, 143.2, 139.9, 130.7, 129.8, 129.7, 125.6, 123.3
(q, JC−F = 285 Hz), 122.3, 120.6, 77.2 (q, JC−F = 29 Hz), 63.7, 36.8,
13.6. 19F NMR (376 MHz, CDCl3): δ −78.5. HRMS (positive ESI):
[M + Na]+ calcd for C14H14O3F3BrNa: 388.9976. Found: 388.9964.
(S)-Ethyl 2-Hydroxy-4-(naphthalen-1-yl)-2-(trifluoromethyl)pent-
4-enoate (7k). Colorless oil (54.8 mg, 81%). The enantiomeric excess
was determined on a Daicel Chiralpak AS-H column with hexane/2-
propanol = 100/1, flow rate = 1.2 mL/min, and detection at a UV
wavelength of 254 nm. Retention times: 4.9 min, 5.6 min (major),
75% ee. [α]2D0 = −76.8 (c 0.718, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ 7.85−7.75 (m, 4H), 7.51−7.45 (m, 3H), 5.52 (s, 1H), 5.38
(s, 1H), 3.97−3.89 (m, 1H), 3.80 (s, 1H), 3.55−3.46 (m, 1H), 3.40 (d,
J = 14.0 Hz, 1H), 3.14 (d, J = 14.0 Hz, 1H), 1.00 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 169.0, 140.5, 139.4, 133.6, 131.0,
(S)-Ethyl 2-Hydroxy-4-(m-tolyl)-2-(trifluoromethyl)pent-4-enoate
(7c).27a,d Colorless oil (51.3 mg, 85%). The enantiomeric excess was
determined on a Daicel Chiralpak AS-H column with hexane/2-
propanol = 100/1, flow rate = 0.5 mL/min, and detection at a UV
wavelength of 254 nm. Retention times: 9.6 min, 11.1 min (major),
89% ee. [α]2D0 = −69.7 (c 0.690, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ 7.19 (t, J = 7.5 Hz, 1H), 7.13−7.07 (m, 3H), 5.36 (s, 1H),
5.25 (s, 1H), 4.07−3.99 (m, 1H), 3.78 (s, 1H), 3.68−3.60 (m, 1H),
3.27 (d, J = 14.0 Hz, 1H), 3.01 (d, J = 14.0 Hz, 1H), 2.35 (s, 3H), 1.11
(t, J = 7.2 Hz, 3H).
(S)-Ethyl 4-(4-Ethylphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-
enoate (7d).27a,d Colorless oil (55.0 mg, 87%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 300/1, flow rate = 1.0 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 6.9 min, 7.4 min
1
(major), 74% ee. [α]D20 = −95.3 (c 0.770, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.25 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.2 Hz, 2H),
5.36 (s, 1H), 5.23 (s, 1H), 4.06−3.98 (m, 1H), 3.78 (s, 1H), 3.66−
3.58 (m, 1H), 3.26 (d, J = 14.0 Hz, 1H), 3.01 (d, J = 14.0 Hz, 1H),
2.63 (q, J = 7.6 Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H), 1.10 (t, J = 7.2 Hz,
3H).
(S)-Ethyl 4-(4-(tert-Butyl)phenyl)-2-hydroxy-2-(trifluoromethyl)-
pent-4-enoate (7e).27a,d Colorless oil (59.9 mg, 87%). The
enantiomeric excess was determined on a Daicel Chiralcel OJ-H
column with hexane/2-propanol = 300/1, flow rate = 1.0 mL/min, and
detection at a UV wavelength of 254 nm. Retention times: 10.1 min,
12.8 min (major), 74% ee. [α]2D0 = −59.0 (c 0.927, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ 7.33 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz,
2H), 5.37 (s, 1H), 5.24 (s, 1H), 4.02−3.94 (m, 1H), 3.80 (s, 1H),
3.57−3.49 (m, 1H), 3.27 (d, J = 13.9 Hz, 1H), 3.00 (d, J = 13.8 Hz,
1H), 1.30 (s, 9H), 1.07 (t, J = 7.2 Hz, 3H).
128.4, 127.9, 126.1, 126.0, 125.8, 125.5, 125.1, 123.4 (q, JC−F = 285
Hz), 122.6, 76.7 (q, JC−F = 28 Hz), 63.4, 39.3, 13.1. 19F NMR (376
MHz, CDCl3): δ −78.9. HRMS (positive ESI): [M + Na]+ calcd for
C18H17O3F3Na: 361.1027. Found: 361.1027.
(S)-Ethyl 2-Hydroxy-4-(naphthalen-2-yl)-2-(trifluoromethyl)pent-
4-enoate (7l).27a,d Colorless oil (58.9 mg, 87%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 100/1, flow rate = 0.5 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 13.7 min, 15.6 min
(S)-Ethyl 4-(4-Fluorophenyl)-2-hydroxy-2-(trifluoromethyl)pent-
4-enoate (7f).27c Colorless oil (49.0 mg, 80%). The enantiomeric
excess was determined on a Daicel Chiralcel OJ-H column with
hexane/2-propanol = 100/1, flow rate = 0.5 mL/min, and detection at
a UV wavelength of 220 nm. Retention times: 18.2 min (major), 19.7
(major), 81% ee. [α]D20 = −59.1 (c 0.770, CH2Cl2). H NMR (400
1
MHz, CDCl3): δ 7.83−7.76 (m, 4H), 7.48−7.42 (m, 3H), 5.52 (s,
1H), 5.37 (s, 1H), 3.96−3.88 (m, 1H), 3.81 (s, 1H), 3.54−3.46 (m,
1H), 3.40 (d, J = 14.0 Hz, 1H), 3.14 (d, J = 14.0 Hz, 1H), 0.99 (t, J =
7.2 Hz, 3H).
min, 91% ee. [α]2D0 = −71.1 (c 0.604, CH2Cl2). H NMR (400 MHz,
1
CDCl3): δ 7.32−7.28 (m, 2H), 7.02−6.98 (m, 2H), 5.34 (s, 1H), 5.25
(s, 1H), 4.13−4.05 (m, 1H), 3.79−3.71 (m, 1H), 3.77 (s, 1H), 3.23 (d,
J = 14.1 Hz, 1H), 3.02 (d, J = 14.0 Hz, 1H), 1.16 (t, J = 7.2 Hz, 3H).
(S)-Ethyl 4-(4-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)pent-
4-enoate (7g).27c Colorless oil (56.8 mg, 88%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 100/1, flow rate = 0.5 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 12.5 min, 14.2 min
(S)-Methyl 2-Hydroxy-4-phenyl-2-(trifluoromethyl)pent-4-enoate
(7m).27b Colorless oil (45.0 mg, 82%). The enantiomeric excess was
determined on a Daicel Chiralcel OJ-H column with hexane/2-
propanol = 100/1, flow rate = 1.0 mL/min, and detection at a UV
wavelength of 220 nm. Retention times: 14.9 min (major), 16.8 min,
77% ee. [α]2D0 = −86.3 (c 0.488, CH2Cl2). 1H NMR (400 MHz,
CDCl3): δ 7.32−7.25 (m, 5H), 5.39 (s, 1H), 5.27 (s, 1H), 3.76 (s,
1H), 3.37 (s, 3H), 3.29 (d, J = 13.9 Hz, 1H), 3.02 (d, J = 14.0 Hz, 1H).
(S)-Methyl 4-(4-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)-
pent-4-enoate (7n).27b Colorless oil (50.0 mg, 81%). The
enantiomeric excess was determined on a Daicel Chiralpak AS-H
column with hexane/2-propanol = 300/1, flow rate = 1.0 mL/min, and
detection at a UV wavelength of 254 nm. Retention times: 13.3 min,
14.9 min (major), 70% ee. [α]2D0 = −14.4 (c 0.458, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ 7.30−7.25 (m, 4H), 5.38 (s, 1H), 5.27 (s, 1H),
3.73 (s, 1H), 3.49 (s, 3H), 3.23 (d, J = 14.0 Hz, 1H), 3.02 (d, J = 14.0
Hz, 1H).
(major), 95% ee. [α]D20 = −65.0 (c 0.824, CH2Cl2). H NMR (400
1
MHz, CDCl3): δ 7.30−7.25 (m, 4H), 5.38 (s, 1H), 5.28 (s, 1H), 4.15−
4.07 (m, 1H), 3.82−3.74 (m, 1H), 3.77 (s, 1H), 3.21 (d, J = 14.1 Hz,
1H), 3.03 (d, J = 14.1 Hz, 1H), 1.16 (t, J = 7.2 Hz, 3H).
(S)-Ethyl 4-(3-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)pent-
4-enoate (7h).27c Colorless oil (51.6 mg, 80%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 100/1, flow rate = 0.5 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 11.3 min, 13.8 min
(major), 94% ee. [α]D20 = −19.2 (c 0.476, CH2Cl2). H NMR (400
1
(S)-Methyl 4-(3-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)-
pent-4-enoate (7o). Colorless oil (38.3 mg, 62%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 300/1, flow rate = 1.0 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 10.6 min, 13.8 min
MHz, CDCl3): δ 7.32−7.31 (m, 1H), 7.26−7.20 (m, 3H), 5.40 (s,
1H), 5.32 (s, 1H), 4.15−4.07 (m, 1H), 3.80−3.72 (m, 1H), 3.78 (s,
1H), 3.23 (d, J = 14.1 Hz, 1H), 3.02 (d, J = 14.1 Hz, 1H), 1.17 (t, J =
7.2 Hz, 3H).
(major), 65% ee. [α]D20 = −80.6 (c 0.428, CH2Cl2). H NMR (400
1
(S)-Ethyl 4-(4-Bromophenyl)-2-hydroxy-2-(trifluoromethyl)pent-
4-enoate (7i).27c Colorless oil (62.4 mg, 85%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 100/1, flow rate = 0.5 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 13.4 min, 15.0 min
MHz, CDCl3): δ 7.31−7.30 (m, 1H), 7.26−7.25 (m, 2H), 7.23−7.19
(m, 1H), 5.41 (s, 1H), 5.30 (s, 1H), 3.74 (s, 1H), 3.51 (s, 3H), 3.24
(d, J = 14.0 Hz, 1H), 3.01 (d, J = 14.0 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 169.4, 142.7, 139.9, 134.1, 129.5, 127.8, 126.8, 125.1, 123.2
(q, JC−F = 285 Hz), 120.6, 77.2 (q, JC−F = 29 Hz), 53.7, 37.1. 19F NMR
(376 MHz, CDCl3): δ −78.4. HRMS (positive ESI): [M + Na]+ calcd
for C13H12O3F3ClNa: 331.0325. Found: 331.0321.
(major), 94% ee. [α]D20 = −47.8 (c 1.000, CH2Cl2). H NMR (400
1
MHz, CDCl3): δ 7.44 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.5 Hz, 2H),
5.38 (s, 1H), 5.28 (s, 1H), 4.15−4.07 (m, 1H), 3.83−3.73 (m, 1H),
H
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(S)-Methyl 4-(4-Bromophenyl)-2-hydroxy-2-(trifluoromethyl)-
pent-4-enoate (7p).27b Colorless oil (56.5 mg, 80%). The
enantiomeric excess was determined on a Daicel Chiralpak AS-H
column with hexane/2-propanol = 300/1, flow rate = 1.0 mL/min, and
detection at a UV wavelength of 254 nm. Retention times: 15.0 min,
16.5 min (major), 71% ee. [α]2D0 = −115.6 (c 0.463, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ 7.44 (d, J = 8.6 Hz, 2H), 7.20 (d, J = 8.6 Hz,
2H), 5.39 (s, 1H), 5.27 (s, 1H), 3.73 (s, 1H), 3.50 (s, 3H), 3.22 (d, J =
14.0 Hz, 1H), 3.02 (d, J = 14.0 Hz, 1H).
(c) Baratta, W.; Benedetti, F.; Zotto, A. D.; Fanfoni, L.; Felluga, F.;
Magnolia, S.; Putignano, E.; Rigo, P. Organometallics 2010, 29, 3563.
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2010, 132, 5562. (b) Huang, M.; Li, C.; Huang, J.; Duan, W.-L.; Xu, S.
Chem. Commun. 2012, 48, 11148.
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Nishiyama, H. Chem. Lett. 1997, 951. (b) Stark, M. A.; Jones, G.;
Richards, C. J. Organometallics 2000, 19, 1282. (c) Bugarin, A.;
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Uozumi, Y. Organometallics 2008, 27, 5159. (e) Bugarin, A.; Connell,
B. T. Chem. Commun. 2011, 47, 7218.
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Nishiyama, H. Organometallics 1999, 18, 3584. (b) Motoyama, Y.;
Kawakami, H.; Shimozono, K.; Aoki, K.; Nishiyama, H. Organo-
metallics 2002, 21, 3408. (c) Fossey, J. S.; Richards, C. J.
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Commun. 1999, 131. (b) Motoyama, Y.; Okano, M.; Narusawa, H.;
Makihara, N.; Aoki, K.; Nishiyama, H. Organometallics 2001, 20, 1580.
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(S)-Methyl 4-(3-Bromophenyl)-2-hydroxy-2-(trifluoromethyl)-
pent-4-enoate (7q). Colorless oil (42.4 mg, 60%). The enantiomeric
excess was determined on a Daicel Chiralpak AS-H column with
hexane/2-propanol = 300/1, flow rate = 1.0 mL/min, and detection at
a UV wavelength of 254 nm. Retention times: 11.5 min, 14.9 min
(major), 74% ee. [α]D20 = −68.7 (c 0.440, CH2Cl2). H NMR (400
1
MHz, CDCl3): δ 7.46 (t, J = 1.8 Hz, 1H), 7.42−7.39 (m, 1H), 7.27−
7.24 (m, 1H), 7.19 (t, J = 7.8 Hz, 1H), 5.40 (s, 1H), 5.30 (s, 1H), 3.75
(s, 1H), 3.51 (s, 3H), 3.23 (d, J = 14.1 Hz, 1H), 3.01 (d, J = 14.0 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 169.4, 142.9, 139.8, 130.7,
129.8, 129.7, 125.5, 123.2 (q, JC−F = 285 Hz), 122.3, 120.7, 77.1 (q,
JC−F = 29 Hz), 53.7, 37.1. 19F NMR (376 MHz, CDCl3): δ −78.4.
HRMS (positive ESI): [M + Na]+ calcd for C13H12O3F3BrNa:
374.9820. Found: 374.9822.
ASSOCIATED CONTENT
* Supporting Information
■
S
Additional catalytic results, a proposed reaction cycle for the
asymmetric carbonyl−ene reaction, H NMR and 13C NMR
1
spectra of complex 1f, and NMR spectra and chiral HPLC
traces for all of the catalysis products. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*Tel./Fax: (+86)-371-6778-3012. E-mail: mpsong@zzu.edu.cn.
*E-mail: gongjf@zzu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21272217) for financial support of this work.
REFERENCES
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