Copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones with chiral sulfoxide-phosphine ligands

Article abstract of DOI:10.1016/j.tet.2015.12.062

The copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones was achieved with chiral sulfoxide-phosphine (SOP) ligands. This process showed good functional group tolerance and gave the 1, 4-adducts with excellent enantioselec

Full text of DOI:10.1016/j.tet.2015.12.062

Tetrahedron 72 (2016) 2707e2711
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper-catalyzed enantioselective conjugate addition of diethylzinc
to acyclic enones with chiral sulfoxideephosphine ligands
Tingting Yang , Yongling Zhang , Peng Cao , Min Wang , Li Li , Dong Li ,*,
Jian Liao
a
a
b
b
b
c
a,c
b,
*
College of Chemistry and Chemical Engineering, Hubei University of Technology, Wuhan 430068, PR China
Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China
Hubei Collaborative Innovation Center of Targeted Antitumor Drug, Jingchu University of Technology, Jingmen 448000, PR China
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
The copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones was achieved
with chiral sulfoxideephosphine (SOP) ligands. This process showed good functional group tolerance and
gave the 1, 4-adducts with excellent enantioselectivities (up to 96% ee).
Received 30 September 2015
Received in revised form 17 December 2015
Accepted 23 December 2015
Available online 29 December 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Copper catalysis
Conjugate addition
Acyclic enones
Chiral ligand
Sulfoxideephosphine
1. Introduction
selectivities and highly catalytic activities in a variety of asym-
metric reactions. However, the scope of developed reactions using
8
The catalytic enantioselective conjugate addition of various or-
ganometallic reagents to -unsaturated carbonyl compounds is
such ligands was mainly limited in Pd-catalyzed asymmetric allylic
alkylation and Rh-catalyzed conjugate addition of aryl boronic
acids to cyclic enones. Our group were focusing on exploring new
a, b
9
one of the most widely used methods for asymmetric CeC bond
1
formation in organic synthesis. In the past decades the copper-
reactions with this type ligands, and have found a series of Cu-
10
catalyzed enantioselective addition of diethylzinc to enones has
attracted great attention. A number of chiral auxiliaries and ligands
have been reported and provided high enantioselectivities in this
reaction.2 Among those, phosphorus ligands have played a domi-
nant role. The phosphates or phosphoramidites derived from
catalyzed asymmetric reactions using the SOP ligands. Herein,
we reported the application of our chiral SOP ligands for the
copper-catalyzed enantioselective conjugate addition of dieth-
ylzinc to acyclic enones.
BINOL,3 TADDOL,4 BIPOL and SPINOL were outstanding repre-
5
6
2. Results and discussion
7
sentations and have showed remarkable efficiency. Nevertheless,
in contrast to the excellent enantioselectivities (almost 100% ee) for
diethylzinc addition to cyclic enones, highly enantioselective con-
jugate addition to acyclic enones are more challenging.
In our group, we have developed a class of chiral sulfox-
ideephosphine (SOP) ligands based on the stereogeometry and
coordination properties of the tert-butylsulfinyl group, which can
be synthesized concisely and showed excellent enantio-
Initial investigation of the copper-catalyzed enantioselective
conjugated addition was carried out between diethylzinc and
chalcone (Table 1). Preliminary ligand screening was performed at
different temperatures using Cu(OTf) as the copper catalyst for its
2
high performance in this reaction (Table 1, entries 1e6). As shown
2
e7
in entry 2, 99% conversion of substrate and 88% ee of 1, 4-adduct
ꢁ
were obtained with ligand 2 after reacting in DCM at ꢀ30 C for
2
4 h. Heightening or lowering the temperature decrease both the
conversion and the enantioselectivity, and reaction almost cannot
ꢁ
proceed at ꢀ78 C. Other copper salts were inspected but didn’t
*
Corresponding authors. Tel.: þ86 27 59750460; fax: þ86 27 59750482 (D. L.);
2
show better activity than Cu(OTf) , although both Cu(I) and Cu(II)
salts produce good enantio-selectivities (Table 1, entry 7e10).
tel./fax: þ86 28 82890822 (J. L.); e-mail addresses: dongli@mail.hbut.edu.cn (D. Li),
jliao@cib.ac.cn (J. Liao).
http://dx.doi.org/10.1016/j.tet.2015.12.062
0
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

2708
T. Yang et al. / Tetrahedron 72 (2016) 2707e2711
Table 1
Cu-catalyzed enantioselective conjugate addition of diethylzinc to chalcone
a
Entry
Cu
Ligand
Solvent
T (oC)
Conv.b (%)
eec (%)
1
2
3
4
5
6
7
8
9
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OCOCF
Cu(OTf)
CuTC
2
2
2
2
2
2
L1
L2
L2
L2
L2
L3
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCE
ꢀ30
ꢀ30
0
50
99 (44)
51
68
Trace
56
90 (37)
99 (41)
67 (30)
52 (20)
99 (41)
56
44
99
95
31
35
Trace
53
88
62
73
e
ꢀ40
ꢀ78
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
ꢀ30
85
84
88
78
87
93 (R)
69
75
85
85
58
7
3
)
2
$xH
2
O
2 6 6
$C H
10
11
12
13
14
15
16
17
18
CuI
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
Cu(OTf)
2
2
2
2
2
2
2
2
Toluene
EtOAc
2
Et O
MTBE
DME
THF
Dioxane
e
a
b
c
Reaction conditions: 1a (1 mmol), Et
Isolated yield in parenthesis.
Determined by HPLC analysis.
2
Zn (1.1 mmol, 1.0 M in hexane), copper catalyst (1 mol %), ligand (1.2 mol %) in 3 mL solvent stirring for 24 h.
Solvent dependence was investigated subsequently (Table 1, entry
1e18). Comparing with polar solvents EtOAc, nonpolar solvent
such as DCE has shown to be excellent solvent for high enantio-
selectivity. Acyclic ethers such as Et O and MTBE gave good enan-
tioselectivities but cyclic ethers such as THF and dioxane gave poor
results. Taking one with another, the catalyst system might be af-
fected strongly by the coordination ability of the solvent.
this reaction since each of them was suitable for some substrates.
Good functional group compatibility such as Me, OMe, F and Cl on
each phenyl group of chalcone was demonstrated, affording the
corresponding products with good to excellent enantioselectivities
(Table 2, entry 1e5, 10e12). It was worth noting that the conjugate
addition was also suitable for alkyl substrates such as benzylide-
neacetone derivatives (Table 2, entry 6e9). Benzylideneacetone
seemed to be the most suitable substrate, the enantioselectivities of
whose reaction in DCE was up to 96% (Table 2, entry 6).
1
2
Using the conditions optimized above, the conjugate addition of
Et Zn to various acyclic enones has been carried out to extend the
2
range of substrates. The reactions of each substrate were examined
in both DCM and DCE, and the better results were summarized in
Table 2. These two solvents were both proved to be favorable for
We have noticed a confused but interesting fact in the substrates
extension that the yields of these reactions were low in contrast
with the high conversions. After investigation of the reaction
mixture, we found that parts of the substrates proceeded in-
termolecular tandem conjugate/conjugate addition to form a dimer
11
Table 2
Cu-catalyzed enantioselective conjugate addition of diethylzinc to various acyclic
2
product. In the conjugate addition of Et Zn to enones, the in-
termediate Zn-enolates 3 were trapped by another enone molecule
a
enones
and activated another conjugate addition (Scheme 1). The dimer
product
4 from chalcone was isolated in 27% yield and
characterized.
Entry
R
1
R
2
Solvent Conv. (%) Yieldb (%) eec (%)
1
2
3
4
5
6
7
8
9
4-CH
4-CH
2-CH
3
3
3
OC
6
H
4
4
Ph (1b)
Ph (1c)
Ph (1d)
Ph (1e)
Ph (1f)
Me (1g)
Et (1h)
Me (1i)
Me (1j)
4-MeOC
DCM
DCE
DCE
DCM
DCM
DCE
DCM
DCM
DCM
95
99
99
58
95
99
61
99
99
80
99
99
31 (2b)
38 (2c)
80 (2d)
18 (2e)
49 (2f)
54 (2g)
16 (2h)
61 (2i)
59 (2j)
10 (2k)
35 (2l)
35 (2m)
92 (R)
84 (ꢀ)
95 (þ)
89 (R)
93 (ꢀ)
96 (R)
92 (þ)
95 (þ)
90 (þ)
91 (þ)
78 (þ)
78 (þ)
6
C H
4
OC
6
H
4-ClC
H
6 4
4-FC
Ph
6
H
4
Ph
4-CH
3
OC
6
H
4
4-ClC
Ph
Ph
H
6 4
10
11
12
6
H
(1l)
4
(1k) DCE
4-ClC
4-BrC
6
H
4
DCE
DCE
Ph
6
H
4
(1m)
a
2 2
Reaction conditions: 1 (1 mmol), Et Zn (1.1 mmol, 1.0 M in hexane), Cu(OTf)
(
1 mol %), L2 (1.2 mol %) in 3 mL solvent stirring for 24 h.
Scheme 1. Intermolecular tandem conjugate addition/conjugate addition.
b
Isolated yield.
c
Determined by HPLC analysis.

T. Yang et al. / Tetrahedron 72 (2016) 2707e2711
2709
The property of this catalytic system inspired us to utilize it for
organic layers were washed with NaHCO
3
and brine then dried over
construction of complex compounds with consecutive stereo-
centers through asymmetric tandem reactions. Catalytic asym-
metric tandem transformations are an appealing strategy as it
involves a multi-step transformation that enables a rapid increase
in molecular complexity from readily available starting com-
pounds.12 In recent years, considerable efforts have been made to
develop catalytic asymmetric tandem transformations initiated by
conjugate additions.13 We attempted the synthesis of cyclic com-
pounds through intramolecular tandem conjugate addition/trap-
ping cyclization reaction of compound 5, which was only reported
Na SO . After filtration, the filtrate was concentrated under re-
2
4
duced pressure. The residue was purified by column chromatog-
raphy. The enantiomeric excess of the product was determined by
chiral HPLC.
4.3. Procedure for copper-catalyzed asymmetric tandem
conjugate addition/trapping cyclization reaction
A mixture of Cu(OTf)
0.04 mmol) in 2 mL CH
2
(7.2 mg, 0.02 mmol) and L2 (15.9 mg,
Cl were added to a Schlenk tube under
14
by Alexakis and co-workers. As anticipated, high yield of cyclic
product 6 was received with excellent diastereoselectivity and
moderate enantioselectivity (Scheme 2).
2
2
argon. After stirring at room temperature for 1 h, the solvent was
removed in vacuo and 2 mL toluene was added. After stirring for
ꢁ
5
(
(
min, the solution was cooled to ꢀ30 C, and 1.5 mmol diethylzinc
1.0 M solution in hexane) was added dropwise. Then the enone
1.0 mmol) in 1 mL toluene was added. After 24 h, the reaction was
4
quenched with saturated NH Cl aqueous solution. The reaction
mixture was treated just as the methods mentioned above in the
copper-catalyzed asymmetric conjugate addition. The enantio-
meric excess of the cyclic product was determined by chiral HPLC.
4
.4. Spectral characterization and analytical data of com-
Scheme 2. Asymmetric intramolecular tandem conjugate addition/trapping cycliza-
tion reaction.
pounds 2, 4 and 6
4
d
.4.1. 1,3-Diphenyl-1-pentanone (2a). 1H NMR (400 MHz, CDCl
7.90 (d, J¼7.60 Hz 2H), 7.55e7.51 (m, 1H), 7.44e7.40 (m, 2H),
.31e7.25 (m, 2H), 7.24e7.16 (m, 3H), 3.31e3.22 (m, 3H), 1.83e1.75
3
)
3
. Conclusions
7
In summary, we have demonstrated the Cu-catalyzed enantio-
13
(
m, 1H), 1.66e1.54 (m, 1H), 0.80 (t, J¼7.3 Hz, 3H); C NMR
selective conjugate addition of diethylzinc to acyclic enones using
chiral sulfoxideephosphine ligands. This process showed good
functional group tolerance and gave the 1, 4-adducts with excellent
enantioselectivities (up to 96% ee). A side-product resulted by
tandem conjugate/conjugate addition was identified, and pre-
liminary attempt to synthesize multi-chiral cyclic compounds was
carried out. Further study of this reaction and its application are
undertaking in our laboratory.
(100 MHz, CDCl 199.3, 144.7, 137.3, 132.9, 128.5, 128.4, 128.1,
3
) d
127.7, 126.3, 45.6, 43.0, 29.2, 12.1; HRMS-ESI (m/z): calcd for
þ
C
17
H
18O (MþNa ): 260.1250, found 260.1246. The enantiomeric
excess was determined by HPLC (Chiralpak AD-H, hexane/2-
propanol¼95/5, 1.0 mL/min, 254 nm). T ¼5.74 min (S), 6.89 min (R).
R
4
.4.2. 3-(4-Methoxyphenyl)-1-phenyl-pentanone (2b). 1
H
NMR
(
(
3
400 MHz, CDCl 7.90e7.88 (m, 2H),7.55e7.50 (m, 1H), 7.44e7.40
m, 2H), 7.15e7.12 (m, 2H), 6.84e6.81 (m, 2H), 3.77 (s, 3H),
.25e3.21 (m, 3H), 1.80e1.72 (m, 1H), 1.66e1.54 (m, 1H), 0.80 (t,
3
) d
4
4
. Experimental section
13
J¼7.3 Hz, 3H); C NMR (100 MHz, CDCl
3
) d 199.4, 158.0, 137.3, 136.7,
.1. General experimental
128.9, 128.5, 128.4, 128.0, 113.8, 55.2, 45.9, 42.3, 29.4, 12.1; HRMS-
þ
ESI (m/z): calcd for C18
The enantiomeric excess was determined by HPLC (Chiralpak AD-H,
H
20
O
2
(MþNa ): 291.1356, found 291.1356.
All experiments were carried out under an argon atmosphere.
All solvents were dried before use according to standard pro-
hexane/2-propanol¼95/5, 1.0 mL/min, 254 nm). T
R
¼7.76 min (S),
1
13
cedures. H NMR and C NMR spectra were acquired on a Bruker
00 spectrometer at 400 MHz and 100 MHz, respectively. Enan-
10.96 min (R).
4
tiomeric excess was determined by HPLC analysis on Chiralcel AD,
OD or OJ column (Daicel Chemical Industries, LTD). Unless other-
wise noted, materials were obtained from commercial suppliers
and used without further purification. Ligands L1ꢀ3 were prepared
(2c). 1
4
(
(
1
(
.4.3. 3-(4-Methylphenyl)-1-phenyl-pentanone
400 MHz, CDCl
m, 2H), 7.13e7.08 (m, 4H), 3.25e3.18 (m, 3H), 2.30 (s, 3H),
H
NMR
3
) d 7.91e7.89 (m, 2H),7.55e7.51 (m, 1H), 7.42e7.40
13
.80e1.72 (m,1H),1.65e1.57 (m,1H), 0.80 (t, J¼7.4 Hz, 3H); C NMR
7
by our previously reported method. Compound 5 was prepared
100 MHz, CDCl 199.3, 141.6, 137.3, 135.7, 132.9, 129.1, 128.5,
3
) d
1
4
according to literature procedure.
compounds.
All enones are known
1
C
28.1, 127.5, 45.7, 42.6, 29.2, 21.0, 12.1; HRMS-ESI (m/z): calcd for
þ
18
H
20O (MþNa ): 275.1406, found 275.1411. The enantiomeric
excess was determined by HPLC (Chiralpak AD-H, hexane/2-
4
.2. General procedure for copper-catalyzed asymmetric
propanol¼95/5, 1.0 mL/min, 254 nm). T ¼5.44 min, 7.05 min
R
conjugate addition
(major).
A mixture of Cu(OTf)
.012 mmol) in DCM or DCE (2 mL) was stirred at room tempera-
2
(3.6 mg, 0.01 mmol) and L2 (4.8 mg,
4.4.4. 3-(2-Methoxyphenyl)-1-phenyl-pentanone (2d). 1
(400 MHz, CDCl 7.94e7.92 (m, 2H),7.54e7.49 (m, 1H), 7.44e7.39
H
NMR
0
3
) d
ꢁ
ture for 1 h under argon. The mixture was cooled to ꢀ30 C and
(m, 2H), 7.19e7.14 (m, 2H), 6.92e6.88 (m, 1H), 6.85e6.82 (m, 1H),
3.77 (s, 3H), 3.67e3.60 (m, 1H), 3.33e3.27 (m, 1H), 3.23e3.16 (m,
diethylzinc (1.1 mmol, 1.1 mL of 1.0 M solution in hexane) wad
ꢁ
13
added dropwise. After stirring for 5 min at ꢀ30 C the enone
1H), 1.79e1.68 (m, 2H), 0.80 (t, J¼7.4 Hz, 3H); C NMR (100 MHz,
(
ꢀ
1.0 mmol) in 1 mL solvent was added. The reaction was lasted at
3
CDCl ) d 199.8, 157.5, 132.7, 128.4, 128.2, 128.1, 127.1, 120.6, 110.7,
ꢁ
30 C for 24 h then quenched with saturated NH
4
Cl aqueous so-
55.3, 44.6, 37.1, 27.3, 12.1; HRMS-ESI (m/z): calcd for C18
(MþNa ): 291.1356, found 291.1352. The enantiomeric excess was
H
20
O
2
þ
lution. The mixture was extracted with diethyl ether. The combined

2710
T. Yang et al. / Tetrahedron 72 (2016) 2707e2711
determined by HPLC (Chiralpak AD-H, hexane/2-propanol¼95/5,
.0 mL/min, 254 nm). T
¼6.03 min, 7.13 min (major).
d
197.8, 163.4,144.8,130.4,130.3,128.4,127.7,126.2,113.7, 55.5, 45.3,
þ
1
R
43.2, 29.2, 12.1; HRMS-ESI (m/z): calcd for C18
20
H O
2
(MþNa ):
2
91.1356, found 291.1352. The enantiomeric excess was determined
by HPLC (Chiralpak AD-H, hexane/2-propanol¼95/5, 1.0 mL/min,
254 nm). T
¼12.89 min, 20.21 min (major).
4.4.5. 3-(4-Chlorophenyl)-1-phenyl-pentanone
(2e). 1
H
NMR
(
7
400 MHz, CDCl 7.88 (d, J¼7.4 Hz 2H), 7.56e7.51 (m, 1H),
.45e7.40 (m, 2H), 7.26e7.23 (m, 2H), 7.17e7.14 (m, 2H), 3.26e3.20
m, 3H),1.82e1.73 (m, 1H), 1.65e1.58 (m, 1H), 0.80 (t, J¼7.3 Hz, 3H);
3
)
d
R
(
4.4.12. 1-(4-Chlorophenyl)-3-phenyl-1-pentanone (2l). 1
(400 MHz, CDCl 7.83e7.80 (m, 2H), 7.40e7.37 (m, 2H), 7.30e7.25
(m, 2H), 7.22e7.15 (m, 3H), 3.27e3.17 (m, 3H), 1.81e1.73 (m, 1H),
H
NMR
1
3
C NMR (100 MHz, CDCl
3
)
d
198.8, 143.2, 137.2, 133.0, 131.9, 129.0,
3
) d
1
C
28.6, 128.5, 128.0, 45.4, 42.4, 29.3, 12.0; HRMS-ESI (m/z): calcd for
þ
13
17
H17ClO (MþNa ): 295.0860, found 295.0854. The enantiomeric
1.68e1.60 (m, 1H), 0.80 (t, J¼7.4 Hz, 3H); C NMR (100 MHz, CDCl
3
)
excess was determined by HPLC (Chiralpak AD-H, hexane/2-
d
198.0, 144.4, 139.3, 135.6, 129.5, 128.8, 128.5, 127.6, 45.6, 43.1, 29.2,
þ
propanol¼95/5,1.0 mL/min, 254 nm). T
R
¼5.94 min (S), 8.08 min (R).
12.1; HRMS-ESI (m/z): calcd for C17
found 295.0850. The enantiomeric excess was determined by HPLC
H
17ClO (MþNa ): 295.0860,
4.4.6. 3-(4-Fluorophenyl)-1-phenyl-pentanone
(2f). 1
H
NMR
(Chiralpak AD-H, hexane/2-propanol¼95/5, 1.0 mL/min, 254 nm).
(
400 MHz, CDCl 7.90e7.87 (m, 2H),7.56e7.51 (m, 1H), 7.45e7.41
3
)
d
T
R
¼7.03 min, 8.74 min (major).
(
3
m, 2H), 7.20e7.15 (m, 2H), 6.99e6.93 (m, 2H), 3.28e3.20 (m,
13
4.4.13. 1-(4-Bromophenyl)-3-phenyl-1-pentanone (2m). 1
(400 MHz, CDCl 7.76e7.73 (m, 2H), 7.57e7.54 (m, 2H), 7.30e7.25
(m, 2H), 7.22e7.15 (m, 3H), 3.26e3.17 (m, 3H), 1.81e1.74 (m, 1H),
H),1.81e1.74 (m, 1H), 1.63e1.60 (m, 1H), 0.80 (t, J¼7.3 Hz, 3H);
C
H NMR
NMR (100 MHz, CDCl
3
)
d
199.1, 161.4 (J¼242.3 Hz), 140.3 (J¼3.2 Hz),
3
) d
1
4
2
37.2, 133.0, 129.0 (J¼7.7 Hz), 128.7, 128.0, 115.2 (J¼20.9 Hz), 45.7,
þ
13
2.3, 29.4, 12.0; HRMS-ESI (m/z): calcd for C17
H17FO (MþNa ):
1.68e1.60 (m, 1H), 0.81 (t, J¼7.3 Hz, 3H); C NMR (100 MHz, CDCl
3
)
79.1156, found 279.1156. The enantiomeric excess was determined
d
198.2,144.4,136.0,131.8, 129.6,128.5,128.1, 127.6, 126.4, 45.6, 43.1,
þ
by HPLC (Chiralpak AD-H, hexane/2-propanol¼95/5, 1.0 mL/min,
29.2, 12.1; HRMS-ESI (m/z): calcd for
339.0355, found 339.0350. The enantiomeric excess was de-
C
17
H
17BrO (MþNa ):
2
54 nm). T
R
¼6.18 min, 7.79 min (major).
termined by HPLC (Chiralpak AD-H, hexane/2-propanol¼95/5,
4
.4.7. 4-Phenyl-2-hexanone (2g). 1
H
NMR (400 MHz, CDCl
3
)
1.0 mL/min, 254 nm). T
R
¼7.56 min, 9.38 min (major);
d
7.33e7.28 (m, 3H), 7.23e7.19 (m, 2H), 3.09e3.02 (m, 1H), 2.75 (d,
J¼7.1 Hz, 2H), 2.04 (s, 3H), 1.74e1.55 (m, 2H), 0.80 (t, J¼7.3 Hz, 3H);
4.4.14. 1,3,5-Triphenyl-2-(1-phenylpropyl)pentane-1,5-dione (4). 1
NMR (300 MHz, CDCl 7.76e7.73 (m, 2H), 7.65e7.62 (m, 2H),
7.47e7.35 (m, 1H), 7.35e7.26 (m, 10H), 7.09e7.07 (m, 3H),
6.92e6.90 (m, 2H), 4.54e4.49 (m, 1H), 3.81e3.79 (m, 1H),
3.32e3.24 (m, 1H), 3.14e3.12 (m, 1H), 3.08e3.00 (m, 1H), 1.69e1.65
H
1
3
C NMR (100 MHz, CDCl
3
)
d
208.1, 144.3, 128.5, 127.6, 126.4, 50.6,
3
) d
þ
4
1
3.0, 30.7, 29.4, 12.0; HRMS-ESI (m/z): calcd for C12
99.1093, found 199.1094. The enantiomeric excess was de-
H16O (MþNa ):
termined by HPLC (Chiralcel OJ-H, hexane/2-propanol¼95/5,
13
0
.8 mL/min, 254 nm). T
R
¼10.75 min (S), 11.94 min (R).
(m, 1H), 1.56e1.52 (m, 1H), 0.61 (t, J¼7.3 Hz, 3H); C NMR (75 MHz,
CDCl 203.5, 198.6, 142.2, 141.0, 139.8, 136.8, 132.8, 132.5, 129.0,
3
) d
4
.4.8. 5-Phenyl-3-heptanone (2h). 1
H
NMR (400 MHz, CDCl
3
)
128.4, 128.33, 128.31, 127.9, 127.7, 126.5, 54.2, 48.5, 42.5, 41.6, 27.1,
11.9; HRMS-ESI (m/z): calcd for C32
found 469.2139.
þ
d
7.31e7.29 (m, 3H), 7.20e7.18 (m, 2H), 3.11e3.03 (m,1H), 2.73e2.71
H
30
O
2
(MþNa ): 469.2138,
(
0
1
m, 2H), 2.40e2.19 (m, 2H), 1.73e1.55 (m, 2H), 0.97 (t, J¼7.3 Hz, 3H),
13
.80 (t, J¼7.3 Hz, 3H); C NMR (100 MHz, CDCl
3
) d 210.7, 144.5,
28.4, 127.6, 126.3, 49.4, 43.0, 36.7, 29.3, 12.0, 7.6; HRMS-ESI (m/z):
4.4.15. 2-(2-Benzoyl-3-ethylcyclohexyl)-1-phenylethanone (6). 1
NMR (300 MHz, CDCl 8.05e8.01 (m, 2H), 7.78e7.77 (m, 2H),
H
þ
calcd for C13
H
18O (MþNa ): 213.1250, found213.1251. The enan-
3
) d
tiomeric excess was determined by HPLC (Chiralpak AD-H, hexane/
7.57e7.26 (m, 6H), 3.19 (t, J¼5.1 Hz, 1H), 2.89e2.85 (q, 1H),
2
6
-propanol¼95/5, 1.0 mL/min, 254 nm). T ¼5.75 min (major),
R
2.48e2.44 (m, 2H), 1.79e1.74 (m, 1H), 1.73e1.62 (m, 3H), 1.27e1.22
13
.57 min.
(m, 4H), 1.05e0.99 (m, 2H), 0.77 (t, J¼7.4 Hz, 3H), C NMR
100 MHz, CDCl 206.6, 199.4, 139.4, 136.8, 133.3, 132.9, 128.8,
(
3
) d
4
CDCl
3
1
CDCl
.4.9. 4-(4-Methoxyphenyl)-2-hexanone (2i). 1H NMR (400 MHz,
7.12e7.10 (m, 2H), 6.86e6.84 (m, 2H), 3.80 (s, 3H),
.03e2.96 (m, 1H), 2.72e2.70 (m, 2H), 2.03 (s, 3H), 1.69e1.63 (m,
128.6, 128.2, 128.1, 44.2, 43.3, 38.8, 31.7, 30.5, 29.7, 27.7, 25.2, 11.2;
HRMS-ESI (m/z): calcd for C23
357.1815. The enantiomeric excess was determined by HPLC
þ
3
)
d
H
26
O
2
(MþNa ): 357.1825, found
13
H), 1.58e1.50 (m, 1H), 0.80 (t, J¼7.4 Hz, 3H); C NMR (100 MHz,
(Chiralpak AD-H, hexane/2-propanol¼95/5, 1.0 mL/min, 254 nm).
3
)
d
208.4, 158.0, 136.3, 128.4, 113.8, 55.2, 50.8, 42.3, 30.7, 29.5,
T
R
¼9.80 min (major), 10.53 min.
þ
12.0; HRMS-ESI (m/z): calcd for C13
H
18
O
2
(MþNa ): 229.1199,
found 229.1194. The enantiomeric excess was determined by HPLC
Chiralpak AD-H, hexane/2-propanol¼95/5, 1.0 mL/min, 254 nm).
¼6.05 min (major), 6.60 min.
Acknowledgements
(
T
R
We are grateful to the support of National Natural Science
Foundation of China (No. 21472184, 21572218, 21272226 and
2
of Technology (D. Li) and Western-Light Foundation of Chinese
Academy of Sciences (J. Liao).
4
.4.10. 4-(4-Chlorophenyl)-2-hexanone (2j). 1H NMR (300 MHz,
CDCl 7.30e7.26 (m, 2H), 7.15e7.10 (m, 2H), 3.07e3.02 (m, 1H),
.74e2.71 (m, 2H), 2.05 (s, 3H), 1.71e1.54 (m, 2H), 0.79 (t, J¼7.4 Hz,
1402186), the Hundred-Talent Program Fund of Hubei University
3
) d
2
3
5
13
3
H); C NMR (100 MHz, CDCl ) d 207.6, 142.8, 131.9, 128.9, 128.6,
0.4, 42.2, 30.7, 29.3, 11.9; HRMS-ESI (m/z): calcd for C12
H15ClO
Supplementary data
þ
(
MþNa ): 233.0704, found 233.0709. The enantiomeric excess was
determined by HPLC (Chiralpak AD-H, hexane/2-propanol¼95/5,
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.12.062.
1
.0 mL/min, 254 nm). T
R
¼5.13 min (major), 5.50 min.
4
(
(
.4.11. 1-(4-Methoxyphenyl)-3-phenyl-1-pentanone (2k). 1H NMR
400 MHz, CDCl 7.90e7.88 (m, 2H), 7.26e7.15 (m, 5H), 6.90e9.88
m, 2H), 3.85 (s, 3H), 3.24e3.17 (m, 3H), 1.80e1.73 (m, 1H),
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