Asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by Pd(II)-SunPhos complex

Article abstract of DOI:10.1016/j.tet.2017.10.044

An efficient asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by chiral Pd(II)/(S)-SunPhos complex was developed. A series of optically active homoallylic alcohols containing a CF₃ group were obtained with high yields and excellent ee under mild conditions. Particularly, the reaction of isobutylene and trifluoropyruvate gave the desired product (90% yield, 98% ee) with catalyst loading as low as 0.01 mol% in dichloroethane/toluene.

Full text of DOI:10.1016/j.tet.2017.10.044

Tetrahedron xxx (2017) 1e5
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Asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by
Pd(II)-SunPhos complex
, b, *
Lili Jiang a, Bei Hu a, Xiaomin Xie a, Zhaoguo Zhang a
a School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
b Shanghai Institute of Organic Chemistry, 345 Lingling Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by chiral Pd(II)/(S)-SunPhos
complex was developed. A series of optically active homoallylic alcohols containing a CF3 group were
obtained with high yields and excellent ee under mild conditions. Particularly, the reaction of isobutylene
and trifluoropyruvate gave the desired product (90% yield, 98% ee) with catalyst loading as low as
0.01 mol% in dichloroethane/toluene.
Received 22 August 2017
Received in revised form
15 October 2017
Accepted 17 October 2017
Available online xxx
© 2017 Published by Elsevier Ltd.
Keywords:
Asymmetric catalysis
Carbonyl-ene reaction
Cationic palladium complexes
Low catalyst loading
1. Introduction
high enantioselectivities were generally obtained in these catalytic
systems, the catalyst loadings were always 5e10 mol%. Therefore,
The chiral Lewis acid-catalyzed enantioselective carbonyl-ene
reactions have gained considerable attention in asymmetric syn-
thesis as an atom-economical way to synthesize optically pure
homoallylic alcohols,1 especially for the chiral alcohols containing a
CF3 group, which are important building blocks for some natural
products and pharmaceuticals (Scheme 1).2
Many Lewis acid catalysts have been developed for the
carbonyl-ene reactions, among them are Ti-BINOL,3 Cu-Box,4 In-
PyBox,5 Ni(Ⅱ)-N,N0-dioxides,6 Rh(Ⅲ)-Phebim,7 other transition
metal catalyst8 and organocatalysts.9 Since 2000, cationic ‘coordi-
nately unsaturated’ metal complexes [M(diphosphine)]2þ (M ¼ Pt,
Pd) with a chiral diphosphine ligand, formed in situ by the reaction
of M(diphosphine)Cl2 with silver salts, had served as catalysts for
carbonyl-ene reactions to afford homoallylic alcohols with good ee
values.10 Many C4-bridged and C2-bridged chiral diphosphine li-
gands, such as SEGPHOS,10b,10c BINAP,10f,10a NUPHOS,11,10d CAT-
PHOS.10f BINAPHANE,10e BINAPINE,10e TANGPHOS,10e DUPHOS10e
were also developed to incorporate with Pd(II) for the carbonyl-
ene reactions of ethyl trifluoropyruvate and alkenes. Although
the development of efficient asymmetric catalytic systems using
lower catalyst/ligand loading is highly desirable.8f,5b,6a
The geometric, steric and electronic properties of chiral ligands
have a significant effect on enantioselectivity and reactivity of the
catalysts. Herein, we report the cationic palladium catalyzed
enantioselective carbonyl-ene reactions of ethyl trifluoropyruvate
and alkenes with finely-tunable SunPhos ligands12 (Scheme 2).
2. Results and discussion
We initiated our investigation by examining the reaction of
methylenecyclohexane and ethyl trifluoropyruvate with 0.1 mol% of
PdCl2[(S)-SunPhos)] (I) as pre-catalyst, AgBF4 as additive, and
dichloroethane as solvent at room temperature. The reaction
occurred in 40% conversion and the objective alcohol 3a was ob-
tained in 35% isolated yield and 65% ee (Table 1, entry 1). Because
the counter ion of cationic metal complexes has an important effect
on the enantioselectivity and catalytic activity of the catalytic sys-
tem,13,11,5c,5d the additives with ‘noncoordinating’ or weak coordi-
nating anion, such as AgPF4, AgSbF4, and AgOTf were examined
(Table 1, entries 2e4). When AgPF4 was used, the yield and ee of 3a
were improved (Table 1, entry 2). The enantioselectivity was
increased to 82% in the case of AgSbF4 as additive (Table 1, entry 3).
While AgOTf was worst for the reaction (Table 1, entry 4).13 With
* Corresponding author. School of Chemistry and Chemical Engineering,
Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
E-mail address: zhaoguo@sjtu.edu.cn (Z. Zhang).
https://doi.org/10.1016/j.tet.2017.10.044
0040-4020/© 2017 Published by Elsevier Ltd.
Please cite this article in press as: Jiang L, et al., Asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by Pd(II)-SunPhos complex,
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2
L. Jiang et al. / Tetrahedron xxx (2017) 1e5
Table 1
The optimization of the reaction conditions.a
Entry
catalyst
additive
solvent
yield (%)b
ee (%)c
1
2
3
4
5
6
7
I
I
I
I
I
I
I
AgBF4
AgPF6
DCE
DCE
DCE
DCE
35
52
65
5
0
60
80
65
79
82
12
N/A
92
84
Scheme 1. Glucocorticoid receptor agonists containing a chiral CF3 group.
AgSbF6
AgOTf
AgSbF6
AgSbF6
AgSbF6
THF
Toluene
DCE/Toluene,
1/2
8
I
AgSbF6
AgSbF6
AgSbF6
AgSbF6
No
DCE/Toluene,
1/10
DCE/Toluene,
1/30
DCE/Toluene,
1/50
DCM/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
DCE/Toluene,
1/30
92
93
96
96
96
N/A
N/A
97
0
9
I
93
10
11
12
13
14d
15e
16
17
18
19
20
I
91
I
92
I
trace
trace
92
Scheme 2. Structures of PdCl2(SunPhos) complexes.
No
I
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF4 as additive, the effect of solvent was explored. Moreover,
solvent showed important influence on the efficiency and enan-
tioselectivity of the catalytic system.5b The reaction failed in THF
(Table 1, entry 5), which may resulted from the coordination of THF
with Pd(II)-complex. When the reaction was carried out in toluene
which was considered as an unsuitable solvent owing to the low
solubility for the catalyst, the reaction afforded the alcohol 3a in
92% ee and moderate yield (Table 1, entry 6). In view of good sol-
ubility of cationic catalyst in chlorinated solvent, the mixed solvent
of DCE/toluene at 1/2 (in volume) ratio was used, and the yield was
increased to 80%, but ee value decreased slightly (Table 1, entry 7).
Increasing the amount of toluene led to higher yield and ee (Table 1,
entry 8). Finally, the best result was presented when the ratio of the
solvents was 1/30 (Table 1, entry 9). When the ratio reached to 1/50
by increasing the amount of toluene, the yield and ee were not
improved (Table 1, entry 10). Replacing DCE with DCM, the high
yield and ee were almost retained (Table 1, entry 11). The reaction
did not occur without catalyst or additive (Table 1, entries 12 and
13). These result furthermore confirmed that cationic Pd(Sun-
Phos)(SbF6)2 was the most active catalyst.12 In addition, the loading
of additive was also crucial for the enantioselectivity. When 0.1 mol
% of AgSbF6 (1 eq. to palladium catalyst) was added to the system,
the alcohol 3a was obtained in 52% yield and 0% ee (Table 1, entry
15). While the excess of AgSbF6 had no obvious effect on the re-
action (Table 1, entry 14).
Next, the effect of ligand was investigated. The substituents on
the diarylphosphino group of the ligands affected inconspicuously
on the catalytic activity. The yields of the alcohol 3a were about 90%
in all the cases when L2, L3, and L4 were used as ligands. However,
the substituents on the diarylphosphine group influenced the
enantioselectivity remarkably (Table 1, entries 16e18). Introducing
a methyl group to the diarylphosphine group of the ligand
decreased the ee value of 3a slightly (Table 1, entry 17). When
sterically even bulkier L3 and L4 with 3,5-dimethyl group or 3,5-
dimethyl and 4-methoxyl group were used, the enantioselectivity
dropped dramatically (Table 1, entries 17, 18). Under our standard
reaction conditions, SEGPHOS and BINAP (see Scheme 3) also gave
good activity and enantioselectivity for the reaction, in contrast to
I
52
Ⅱ
Ⅲ
Ⅳ
Ⅴ
Ⅵ
90
96
49
51
96
97
89
93
96
DCE/Toluene,
1/30
93
a
The reactions were carried out with the catalyst (0.1 mol%), additive (0.22 mol%),
methylenecyclohexane (96.2 mg, 1.0 mmol), and ethyl trifluoropyruvate (225.1 mg,
1.5 mmol, 1.5 eq) in solvent (18.6 mL) at room temperature for 12 h. N/A ¼ not
determined.
b
Isolated yield.
c
Determined by chiral GC using Beta Dex™120 Capillary Column.
AgSbF6 (0.3 mol%) was added.
AgSbF6 (0.1 mol%) was added.
d
e
the previous report (Table 1, entries 19, 20).11,10b,10c
The substrates scope of cationic Pd[(S)-SunPhos)] complexes
catalyzed carbonyl-ene reactions was probed under the optimized
conditions. As shown in Table 2, the symmetric 1,1-dialkyl
substituted olefins (1a-1c) were reacted with ethyl tri-
fluoropyruvate to give the corresponding alcohol (3a) in excellent
yields and enantioselectivities (Table 2, entries 1e3), as a result, the
reaction of isobutylene (1c) at ꢀ20 ~ ꢀ15 ꢁC afforded the corre-
sponding product in 89% yield and 97% ee even with as low as
0.01 mol% of catalyst loading (Table 2, entry 3)2c; When unsym-
metric 1,1-dialkyl substituted olefin, 2,4,4-trimethylpent-1-ene
(1d), was subjected to the reaction, the catalytic system showed
high regioselectivity and only one product was observed, giving 3d
in 89% yield and 97% ee (Table 2, entry 4). Apparently, the steric
hindrance plays an important role in achieving perfect regiose-
lectivity in the reaction.10e In the reaction of allylbenzene (1e) and
ethyl trifluoropyruvate, the catalytic system also showed good
regioselectivity and enantioselectivity. Under the identical
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L. Jiang et al. / Tetrahedron xxx (2017) 1e5
3
Table 3
Substrate scope of styrene derivatives for the catalytic asymmetric carbonyl-ene
reaction.a
Scheme 3. Structures of PdCl2(SEGPHOS) and PdCl2(BINAP).
Entry
1f-1n
R
time (t/h)
yield (%)b
ee (%)c
Table 2
1
2
3
4
5
6
7
8
9
1f
H
0.5
0.5
0.5
0.5
1
95
94
96
94
96
93
97
93
61
83
54
66
85
89
89
85
91
90
Substrate scope of alkyl substituted olefins for the catalytic asymmetric carbonyl-
1g
1h
1i
1j
1k
1l
p-OMe
p-Me
p-F
p-Cl
p-Br
o-Me
o-Cl
o-Br
ene reaction.a
1
12
12
12
1m
1n
a
The reactions were carried out with PdCl2[(S)-Sunphos] (1 mol%), AgSbF6
(2.2 mol%), styrene derivative (0.5 mmol), and ethyl trifluoropyruvate (0.75 mmol)
in DCE/Toluene (0.3 mL/9 mL, 1/30) at r.t. for 12 h.
Entry
1
1a-1e
3a-3e
Yieldb (%)
95%
eec (%)
95%
b
Isolated yield.
Determined by chiral HPLC column.
c
2
92%
90%
91%
98%
the contrary, the existence of an electron-withdrawing group at p-
position decreased the reactivity of the alkene, and a longer reac-
tion time was required to complete the reaction (Table 3, entries
4e6). The substituents at the o-position of the phenyl ring of the
aromatic alkene increased the enantioselectivities of the products
(Table 3, entries 7e9). As a result, 2-hydroxy-4-(p-tolyl)-2-(tri-
fluoromethyl) pent-4-enoate (3h) was obtained in 66% ee, while 2-
hydroxy-4-(o-tolyl)-2-(trifluoromethyl) pent-4-enoate (3l) was
generated in 85% ee. The electron nature of the substituents of the
styrene determined the reaction activation: an electron-donating
substituent increased the reaction rate while an electron-
withdrawing substituent decreased the reaction activation. When
ethyl trifluoropyruvate was replaced with other carbonyl ana-
logues, such as glyoxalate ester, ethyl benzoylformate and phe-
nylglyoxal, the catalytic system showed low activity. The reaction of
2-(3-bromophenyl)-2- oxoacetaldehyde (4) gave the object product
1-(3-bromophenyl)-3-(cyclohex-1-en-1-yl)-2-hydroxypropan-1-
one (5) in only 13% yield.
3d
4
89%
48%
97%
96%
5e
a
The reactions were carried out with the catalyst (0.1 mol%), AgSbF6 (0.22 mol%),
alkene (0.5 mmol), and ethyl trifluoropyruvate (0.75 mmol) in DCE/Toluene (0.3 mL/
9 mL, 1/30) at r.t. (25 ꢁC) for 12 h.
b
Isolated yields.
c
3. Conclusions
Determined by chiral GC using Beta Dex™120 Capillary Column.
d
Catalyst (0.01 mol%) was used, reaction temperature at ꢀ20 to ꢀ15 ꢁC.
e
Catalyst (5 mol%) was used and the conversion was 60% for 12 h.
In summary, a simple and efficient catalyst system of PdCl2[(S)-
SunPhos)]/AgSbF6 has been successfully developed for the asym-
metric carbonyl-ene reactions to construct homoallylic alcohols.
With 0.01e1 mol% of PdCl2[(S)-SunPhos] as catalyst, various of
aliphatic alkenes and styrenes were reacted smoothly with ethyl
trifluoropyruvate to generate the homoallylic alcohols containing a
conditions, only a small amount of product 3e in 96% ee was
detected, and increasing the catalyst loading from 0.1 mol% to 5 mol
% increased the yield to 48% yield (Table 2, entry 5).
Furthermore, the carbonyl-ene reaction of ethyl tri-
CF3 group in good yields and ee's in
a mixed solvent of
fluoropyruvate with a-methylstyrene and its derivatives were also
dichloroethane-toluene. This method represented an attractive and
economically viable protocol with great potential in practical
applications.
explored in our catalytic system. The results are summarized in
Table 3. Because styrene derivatives are weaker nucleophiles than
aliphatic alkenes, the catalyst loading was increased to 1 mol% in
the catalytic system. Reaction of a-methylstyrene with ethyl tri-
4. Experimental section
fluoropyruvate afforded the product (3f) in 95% yield and 83% ee
within 30 min (Table 3, entry 1). Significant electronic and steric
effects were observed in the reaction of aromatic alkenes. An
electron-donating group at p-position of the phenyl ring increased
the reactivity of alkenes. As a result, 4-methoxy-a-methylstyrene
(1g) gave the product in high yield (94%) but decreased ee (54%)
4.1. General experimental details
All reactions were carried out under an atmosphere of nitrogen
using standard Schlenk techniques or in a glove box unless other-
wise noted. Commercially available reagents (including tri-
fluoropyruvate, methylene cyclohexane, methylene cyclo-pentane,
2-methylprop-1-ene, allybenzene, and 2,4,4-trimethylpentene)
(Table 3, entry 2). Similar result was also obtained in the case of 4-
methyl-a-methyl styrene (1h) as the substrate (Table 3, entry 3). On
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L. Jiang et al. / Tetrahedron xxx (2017) 1e5
were used throughout without further purification other than
those detailed below. Anhydrous DCE and DCM were freshly
distilled from calcium hydride. Anhydrous toluene and THF were
freshly distilled from Sodium. 1H NMR, 13C NMR and 19F NMR
spectra were recorded on a 400 MHz spectrometer. The chemical
shifts for 1H NMR were recorded in ppm downfield from tetrame-
thylsilane (TMS) with the solvent resonance as the internal stan-
dard. The chemical shifts for 13C NMR were recorded in ppm
downfield using the central peak of deuterochloroform
(77.00 ppm) as the internal standard. Coupling constants (J) are
reported in Hz and refer to apparent peak multiplications. Analysis
of enantiomers was performed on a GC with FID detect or a LC with
UV detector. Flash column chromatography was performed on silica
116.05, 78.1 (q, JC,F ¼ 28.4 Hz), 77.3, 77.0, 76.7, 63.7, 38.8, 23.9, 13.8.
19F NMR (376 MHz, CDCl3)
¼ ꢀ79.0.
d
4.2.4. (R)-Ethyl 2-hydroxy-6,6-dimethyl-4-methylene-2-(trifluoro-
methyl)heptanoate (3d)
Colorless oil (125 mg, yield: 89%); [
NMR (400 MHz, CDCl3)
25
a]
¼ ꢀ5.6 (c 0.97, CHCl3). 1H
D
d
¼ 5.02 (s, 1H), 4.88e4.87 (m, 1H),
4.39e4.28 (m, 2H), 3.84 (d, J ¼ 0.8 Hz, 1H), 2.75 (d, J ¼ 14.0 Hz, 1H),
2.64 (dd, J ¼ 14.0 Hz, 1H), 2.10 (d, J ¼ 13.0 Hz, 1H), 1.88 (dd,
J ¼ 13.0 Hz, 1H), 1.35 (t, J ¼ 7.2 Hz, 3H), 0.91 (s, 9H). 13C NMR
(100 MHz, CDCl3)
d
¼ 169.5, 140.3, 123.3 (q, JC,F ¼ 285.1 Hz), 118.3,
78.3 (q, JC,F ¼ 28.4 Hz), 77.3, 77.0, 76.7, 63.6, 50.4, 38.4, 31.7, 29.7,
13.9. 19F NMR (376 MHz, CDCl3)
d
¼ ꢀ79.2. HRMS (ESI) calcd for
gel (300e400 mesh). [
a
]
D values are given in deg cm2 gꢀ1 and were
[C13H21F3NaO3]þ (M þ Naþ): 305.1340; found 305.1336.
recorded at the D line of sodium (589 nm) in a 0.05 dm cell.
4.2.5. (R,E)-Ethyl 2-hydroxy-5-phenyl-2-(trifluoro-methyl)pent-4-
4.2. General procedure for enantioselective carbonyl-ene reactions
between ethyl trifluoropyruvate and alkenes
enoate (3e)10c
Yellow oil (69 mg, yield:48%); [
NMR (400 MHz, CDCl3)
25
a
]
¼ þ39.3 (c 0.49, CHCl3). 1H
D
d
¼ 7.32e7.22 (m, 5H), 6.52 (d, J ¼ 16 Hz,
A flame-dried Schlenk tube was charged with AgSbF6 (3.8 mg,
0.011 mmol) in 1,2-dichloroethane (0.2 mL) and Pd(SunPhos)Cl2
(4.2 mg, 0.005 mmol) under a nitrogen atmosphere. The resulting
mixture was stirred for 30 min under a nitrogen atmosphere at
room temperature, giving the activated catalyst solution of
Pd(SunPhos)(SbF6)2. To the above prepared catalyst solution was
added a solution of ethyl trifluoropyruvate (0.75 mmol) in DME
(0.1 mL), which was stirred for 30 min and followed by the addition
of the desired alkene 1 (0.5 mmol) in toluene (9 mL). The resulting
mixture was stirred for 0.5 h-12 h at room temperature. Then the
reaction mixture was filtered through a short plug of silica with
petroleum ether (1.5 mL), and the filtration was concentrated to
give the crude product. The residue was loaded onto silica gel, and
eluted with a petroleum ether/ethyl acetate mixture to give the
corresponding compound 3. The isolated product was character-
ized with 1H NMR, 13C NMR and 19F NMR spectroscopy. The
enantiomeric excess was determined by HPLC or GC with a chiral
column.
1H), 6.13e6.05 (m, 1H), 4.37e4.29 (m, 2H), 3.96 (s, 1H), 2.89e2.81
(m, 2H), 1.30 (t, J ¼ 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 169.2,
136.6, 135.5, 128.5, 127.7, 126.3, 123.6 (q, JC,F ¼ 284.6 Hz), 120.4, 77.9
(q, JC,F ¼ 28.7 Hz), 77.3, 77.0, 76.7, 63.8, 35.5,14.0. 19F NMR (376 MHz,
CDCl3)
d
¼ ꢀ79.0.
4.2.6. (R)-Ethyl 2-hydroxy-4-phenyl-2-(trifluoro-methyl)pent-4-
enoate (3f)9a
25
Yellow oil (137 mg, yield: 95%); [
NMR (400 MHz, CDCl3)
a]
¼ þ26.9 (c 0.76, CHCl3). 1H
D
d
¼ 7.34e7.26 (m, 5H), 5.38 (d, J ¼ 1.2 Hz,
1H), 5.28 (d, J ¼ 0.8 Hz, 1H), 4.05e3.99 (m, 1H), 3.78 (s, 1H),
3.67e3.61 (m, 1H), 3.28 (d, J ¼ 13.6 Hz, 1H), 3.03 (dd, J1 ¼ 14.2 Hz,
J2 ¼ 0.6 Hz, 1H), 1.09 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
¼ 168.9, 141.0, 128.1, 127.7, 126.7, 123.4 (q, JC,F ¼ 284.4 Hz), 119.4,
77.3, 77.0, 76.7, 63.4, 37.0, 13.5. 19F NMR (376 MHz, CDCl3)
d
¼ ꢀ78.9.
4.2.7. (R)-Ethyl 2-hydroxy-4-(4-methoxyphenyl)-2-
(trifluoromethyl)pent-4-enoate (3g)9a
25
White solid (150 mg, yield: 94%), mp 59e62 ꢁC, [
a]
¼ þ19.4 (c
D
4.2.1. (R)-Ethyl 2-(cyclohex-1-en-1-ylmethyl)-3,3,3-trifluoro-2-
0.63, CHCl3).1H NMR (400 MHz, CDCl3)
d
¼ 7.30e7.26 (m, 2H),
hydroxypropanoate (3a)10c
6.86e6.82 (m, 2H), 5.32 (d, J ¼ 1.2 Hz, 1H), 5.18 (d, J ¼ 1.2 Hz, 1H),
4.12e4.04 (m, 1H), 3.80 (s, 3H), 3.76e3.74 (m, 1H), 3.24 (d,
25
Yellow oil (126 mg, yield: 95%); [
NMR (400 MHz, CDCl3)
a]
¼ þ19.3 (c 0.38, CHCl3). 1H
D
d
¼ 5.55 (s, 1H), 4.37e4.29 (m, 2H), 3.79 (d,
J ¼ 14.0 Hz, 1H), 3.01 (dd, J ¼ 14.0 Hz, 1H), 1.16 (t, J ¼ 7.2 Hz, 3H). 13
C
J ¼ 1.2 Hz, 1H), 2.66 (d, J ¼ 14.0 Hz, 1H), 2.50 (d, J ¼ 13.6 Hz, 1H),
NMR (100 MHz, CDCl3)
d
¼ 168.9, 159.3, 140.4, 133.3, 127.9, 123.4 (q,
2.12e1.85 (m, 4H), 1.59e1.50 (m, 4H), 1.34 (t, J ¼ 7.2 Hz, 3H). 13C
JC,F ¼ 284.4 Hz), 117.7, 113.4, 77.3, 77.0, 76.7, 63.4, 55.2, 37.0, 13.5. 19
F
NMR (100 MHz, CDCl3)
d
¼
169.7, 130.9, 127.6, 123.4 (q,
NMR (376 MHz, CDCl3)
d
¼ ꢀ78.9.
JC,F ¼ 284.7 Hz), 78.2 (q, JC,F ¼ 28.1 Hz), 77.3, 77.0, 76.7, 63.4, 39.6,
29.7, 25.3, 22.8, 21.9, 13.8. 19F NMR (376 MHz, CDCl3)
d
¼ ꢀ79.2.
4.2.8. (R)-Ethyl 2-hydroxy-4-(p-tolyl)-2-(trifluoro-methyl)pent-
4enoate(3h)9a
25
4.2.2. (R)-Ethyl 2-(cyclopent-1-en-1-ylmethyl)-3,3,3-trifluoro-2-
Yellow oil (145 mg, yield: 96%); [
NMR (400 MHz, CDCl3)
a]
¼ þ19.8 (c 0.28, CHCl3). 1H
D
hydroxypropanoate (3b)11
d
¼ 7.24e7.21 (m, 2H), 7.11 (d, J ¼ 8.0 Hz,
25
Yellow oil (116 mg, yield: 92%); [
NMR (400 MHz, CDCl3)
a]
¼ þ16.4 (c 1.98, CHCl3). 1H
2H), 5.35 (d, J ¼ 1.2 Hz, 1H), 5.22 (d, J ¼ 1.2 Hz, 1H), 4.07e4.03 (m,
1H), 3.75 (s, 1H), 3.72e3.67 (m, 1H), 3.25 (d, J ¼ 14.0 Hz, 1H), 3.02
(dd, J1 ¼14.0 Hz, J2 ¼ 1.2 Hz, 1H), 2.33 (s, 3H), 1.13 (t, J ¼ 7.2 Hz, 3H).
D
d
¼ 5.54 (s, 1H), 4.36e4.30 (m, 2H), 3.83 (s,
1H), 2.87 (d, J ¼ 13.6 Hz, 1H), 2.67 (d, J ¼ 13.6 Hz, 1H), 2.37e2.16 (m,
4H), 1.87e1.79 (m, 2H), 1.33 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz,
13C NMR (100 MHz, CDCl3)
d
¼ 168.9,140.9,138.1,137.5,128.8,126.6,
CDCl3)
d
¼ 169.7, 136.4, 130.1, 123.3 (q, JC,F ¼ 284.9 Hz), 77.7 (q,
123.4(q, JC,F ¼ 284.7 Hz), 118.4, 77.3, 77.0, 76.7, 63.4, 37.0, 21.0, 13.5.
JC,F ¼ 28.4 Hz), 77.3, 77.0, 76.7, 63.7, 36.0, 33.0, 32.4, 23.5, 13.9. 19
F
19F NMR (376 MHz, CDCl3)
d
¼ ꢀ78.9.
NMR (376 MHz, CDCl3)
d
¼ ꢀ79.27.
4.2.9. (R)-Ethyl 4-(4-fluorophenyl)-2-hydroxy-2-(trifluoromethyl)-
4.2.3. (R)-Ethyl 2-hydroxy-4-methyl-2-(trifluoro-me thyl)pent-4-
pent-4-enoate(3i)9a
enoate (3c)14
Yellow oil (102 mg, yield: 90%); [
NMR (400 MHz, CDCl3)
Colorless oil (144 mg, yield: 94%); [
a
]
¼ þ19.8 (c 0.29,
25
D
25
a]
¼ ꢀ6.7 (c 0.65, CHCl3). 1H
CHCl3).1H NMR (400 MHz, CDCl3)
d
¼ 7.32e7.29 (m, 2H), 7.02e6.98
D
d
¼ 4.93e4.91 (m, 1H), 4.83e4.82 (m, 1H),
(m, 2H), 5.35e5.25 (m, 2H), 4.14e4.06 (m, 1H), 3.80e3.72 (m, 2H),
3.23 (d, J ¼ 14.0 Hz, 1H), 3.03 (d, J ¼ 14.0 Hz, 1H), 1.16 (t, J ¼ 7.0 Hz,
4.41e4.27 (m, 2H), 3.86 (s, 1H), 2.76 (d, J ¼ 13.6 Hz, 1H), 2.59 (d,
J ¼ 14.0 Hz, 1H), 1.78 (t, J ¼ 1.2 Hz, 3H), 1.34 (t, J ¼ 7.2 Hz, 3H). 13
C
3H). 13C NMR (100 MHz, CDCl3)
d
¼ 168.9, 163.6, 161.2, 140.1, 137.1,
NMR (100 MHz, CDCl3)
d
¼ 169.5, 138.7, 123.3 (q, JC,F ¼ 284.8 Hz),
128.4, 128.4, 123.3 (q, JC,F ¼ 284.5 Hz), 119.3, 115.1, 114.8, 77.3, 77.0,
Please cite this article in press as: Jiang L, et al., Asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by Pd(II)-SunPhos complex,
Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.10.044

L. Jiang et al. / Tetrahedron xxx (2017) 1e5
5
76.7, 63.6, 37.1, 13.6. 19F NMR (376 MHz, CDCl3)
d
¼ ꢀ79.0, ꢀ115.1.
(20 mg, yield: 13%); 1H NMR (400 MHz, CDCl3)
d
¼ 8.05e8.04 (m,
1H), 7.84e7.81 (m, 1H), 7.75e7.72 (m, 1H), 7.38 (t, J ¼ 8.0 Hz, 1H),
5.46 (br, 1H), 5.14e5.10 (m, 1H), 3.50 (d, J ¼ 4.0 Hz, 1H), 2.48e2.43
(m, 1H), 2.18 (q, J ¼ 8.0 Hz, 1H), 2.02e1.97 (m, 4H), 1.66e1.52 (m,
4.2.10. (R)-Ethyl 4-(4-chlorophenyl)-2-hydroxy-2-(trifluoromethyl)
pent-4-enoate(3j)9a
Yellow oil (155 mg, yield: 96%); [
NMR (400 MHz, CDCl3)
25
a]
¼ þ27.6 (c 0.65, CHCl3). 1H
4H). 13C NMR (100 MHz, CDCl3)
d
¼ 200.9, 136.7, 135.9, 132.9, 131.6,
D
d
¼ 7.30e7.25 (m, 4H), 5.38 (d, J ¼ 1.2 Hz,
130.4, 127.1, 125.5123.2, 122.0, 77.4, 77.0, 76.7, 72.3, 44.4, 28.8, 25.3,
22.8, 22.1. HRMS (ESI) calcd for [C15H18BrO2]þ (M þ Hþ):
309.0490; found 309.0490.
1H), 5.28 (s, 1H), 4.15e4.06 (m, 1H), 3.83e3.75 (m, 2H), 3.21 (d,
J ¼ 14.0 Hz, 1H), 3.03 (d, J ¼ 14.0 Hz, 1H), 1.17 (t, J ¼ 7.0 Hz, 3H). 13
C
NMR (100 MHz, CDCl3)
d
¼ 168.9, 140.1, 139.5, 133.6, 128.3, 128.0,
123.3 (q, JC,F ¼ 284.5 Hz), 119.7, 77.3, 77.0, 76.7, 63.6, 36.8, 13.6. 19
F
Acknowledgments
NMR (376 MHz, CDCl3)
d
¼ ꢀ78.9.
We thank the National Natural Science Foundation of China (No.
21472124) for financial support.
4.2.11. (R)-Ethyl 4-(4-bromophenyl)-2-hydroxy-2-(trifluoromethyl)
pent-4-enoate (3k)9a
25
Colorless oil (171 mg, yield: 93%); [
a
]
D
¼ þ25.4 (c 0.82, CHCl3).
1H NMR (400 MHz, CDCl3)
d
¼ 7.45e7.42 (m, 2H), 7.22e7.19 (m, 2H),
Appendix A. Supplementary data
5.38 (d, J ¼ 1.2 Hz, 1H), 5.28 (d, J ¼ 0.8 Hz, 1H), 4.16e4.08 (m, 1H),
3.83e3.77 (m, 1H), 3.75 (d, J ¼ 0.4 Hz, 1H), 3.21 (d, J ¼ 14.0 Hz, 1H),
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2017.10.044
3.03 (dd, J1 ¼ 14.0 Hz, J2 ¼ 0.8 Hz, 1H), 1.17 (t, J ¼ 7.0 Hz, 3H). 13
C
NMR (100 MHz, CDCl3)
d
¼ 168.8, 140.1, 139.9, 131.2, 128.4, 123.3 (q,
JC,F ¼ 284.7 Hz), 121.7, 119.7, 77.3, 77.0, 76.7, 63.6, 36.8, 13.6. 19F NMR
References
(376 MHz, CDCl3)
d
¼ ꢀ78.9.
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Colorless oil (147 mg, yield: 97%); [
NMR (400 MHz, CDCl3)
a]
¼ þ44.6 (c 1.4, CHCl3). 1H
D
d
¼ 7.16e7.03 (m, 4H), 5.41 (s, 1H), 5.11 (d,
J ¼ 2.0 Hz, 1H), 4.02e3.94 (m, 1H), 3.80 (d, J ¼ 1.2 Hz, 1H), 3.55e3.47
(m, 1H), 3.20 (d, J ¼ 14.0 Hz, 1H), 2.96 (d, J ¼ 14.0 Hz, 1H), 2.30 (s,
3H), 1.07 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
¼ 169.0,
141.3,141.0, 135.1,130.2,128.9,127.4,125.4,123.4 (q, JC,F ¼ 285.0 Hz),
121.4, 77.3, 77.0, 76.7, 63.5, 38.7, 19.9, 13.4. 19F NMR (376 MHz,
CDCl3)
d
¼ ꢀ79.3.
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2002;43:3431;
4.2.13. (R)-Ethyl 4-(2-chlorophenyl)-2-hydroxy-2-(trifluoromethyl)
pent-4-enoate (3m)
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8712.
25
Light yellow oil (150 mg, yield: 93%); [
a
]
¼ þ20.2 (c 0.54,
D
CHCl3). 1H NMR (400 MHz, CDCl3)
d
¼ 7.35e7.32 (m, 1H), 7.23e7.18
(m, 2H), 7.13e7.10 (m, 1H), 5.45 (d, J ¼ 1.2 Hz, 1H), 5.23 (d, J ¼ 1.6 Hz,
1H), 4.09e4.01 (m, 1H), 3.78 (d, J ¼ 1.2 Hz, 1H), 3.68e3.60 (m, 1H),
3.40 (d, J ¼ 14.0 Hz, 1H), 3.05 (dd, J1 ¼ 14.0 Hz, J2 ¼ 0.8 Hz, 1H), 1.12
(t, J ¼ 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3)
¼ 169.0, 140.3, 132.2,
d
131.0, 129.4, 128.8, 126.6, 123.3 (q, JC,F ¼ 284.9 Hz), 123.0, 77.3, 77.0,
76.7, 63.6, 37.6, 13.5. 19FNMR (376 MHz, CDCl3)
d
¼ ꢀ79.18. HRMS
(ESI) calcd for [C14H14ClF3NaO3]þ (M þ Naþ): 345.0481; found
345.0487.
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2008;47:6798;
4.2.14. (R)-Ethyl 4-(2-bromophenyl)-2-hydroxy-2-(trifluoromethyl)
pent-4-enoate (3n)
Yellow oil (112 mg, yield: 61%); [
NMR (400 MHz, CDCl3)
a]
D
¼ þ14.3 (c 0.71, CHCl3). 1H
25
d
¼ 7.54 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.2 Hz, 1H),
7.27e7.23 (m, 1H), 7.15e7.10 (m, 2H), 5.45 (d, J ¼ 0.8 Hz,1H), 5.21 (d,
J ¼ 1.6 Hz, 1H), 4.09e4.01 (m, 1H), 3.79 (d, J ¼ 1.2 Hz, 1H), 3.69e3.61
(m, 1H), 3.42 (d, J ¼ 14.0 Hz, 1H), 3.04 (d, J ¼ 14.0 Hz, 1H), 1.13 (t,
(b) Rueping M, Bootwicha T, Kambutong S, Sugiono E. Chem Asian J. 2012;7:
1195;
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
¼ 169.0, 142.3, 141.6,
(c) Lv J, Zhang Q, Zhong X, Luo S. J Am Chem Soc. 2015;137:15576.
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3885;
132.6, 131.1, 128.9, 127.1, 123.3 (q, JC,F ¼ 285.1 Hz), 122.8, 122.0, 77.3,
77.0, 76.7, 63.6, 37.7, 13.5. 19F NMR (376 MHz, CDCl3)
d
¼ ꢀ79.2.
HRMS (ESI) calcd for [C14H14BrF3NaO3]þ (M þ Naþ): 388.9976;
(d) Doherty S, Knight JG, Smyth CH, Harrington RW, Clegg W. Organometallics.
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found 388.9983.
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9751.
4.2.15. 1-(3-bromophenyl)-3-(cyclohex-1-en-1-yl)-2-hydroxy-
propan-1-one(5)
The compound 5 was prepared in a similar procedure described
for the preparation of 3 except for the use of 2-(3-bromophenyl)-2-
oxoacetaldehyde instead of ethyl trifluoropyruvate. Colorless oil
12. Sun Y, Wan X, Guo M, et al. Tetrahedron Asymmetry. 2004;15:2185.
ꢀ
13. Koh JH, Larsen AO, Gagne MR. Org Lett. 2001;3:1233.
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Please cite this article in press as: Jiang L, et al., Asymmetric carbonyl-ene reaction of trifluoropyruvate catalyzed by Pd(II)-SunPhos complex,
Tetrahedron (2017), https://doi.org/10.1016/j.tet.2017.10.044