A class of benzene backbone-based olefin-sulfoxide ligands for Rh-catalyzed enantioselective addition of arylboronic acids to enones

Article abstract of DOI:10.1021/jo2011472

A class of readily available and easily tunable benzene backbone-based olefin-sulfoxide ligands was developed for the rhodium-catalyzed asymmetric conjugate addition reaction of arylboronic acids to enones with up to 97% yield and 97% ee.

Full text of DOI:10.1021/jo2011472

NOTE
pubs.acs.org/joc
A Class of Benzene Backbone-Based OlefinÀSulfoxide Ligands for
Rh-Catalyzed Enantioselective Addition of Arylboronic Acids to Enones
Feng Xue, Xincheng Li, and Boshun Wan*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
S Supporting Information
b
ABSTRACT: A class of readily available and easily tunable
benzene backbone-based olefinÀsulfoxide ligands was devel-
oped for the rhodium-catalyzed asymmetric conjugate addition
reaction of arylboronic acids to enones with up to 97% yield and
97% ee.
n the past few years, significant efforts have been made on the
development of the highly efficient chiral ligands in Rh-
I
catalyzed asymmetric 1,4-addition of organoboron reagents, which
has rapidly developed into a powerful tool for the stereoselective
formation of carbonÀcarbon bonds.1À6 Pioneered by the groups
of Hayashi and Carreira, chiral olefins as a new class of promising
ligands have attracted great attention in recent years,7À9 and
many excellent olefin-based ligands such as diene ligands,10À23
olefinÀphosphine ligands,24À30 and olefinÀnitrogen ligands31,32
have been successfully developed in the HayashiÀMiyaura asym-
metric reactions. Meanwhile, except for a chiral auxiliary in numer-
ous asymmetric transformations, the application of sulfoxides33
as ligands, especially the chiral bis-sulfoxides,34À38 has most
recently been appealing in the HayashiÀMiyaura reaction.
In view of ready availability, air and moisture stability, and fine
chiral environment of sulfoxides, as well as the relatively good
coordination ability of alkenes and sulfoxides to transition metals,
we envisioned that the combination of alkenes and sulfoxides
would allow the advantages of each class to be united which
provided good opportunities to find highly efficient hybrid ligands.
However, examples on the combination of alkenes with inherent
chiral sulfoxides into chiral olefinÀsulfoxide hybrid ligands were
very few;39À43 the sulfoxides were mainly limited to tert-butyl-
sulfinyl groups, and the incorporation of alkenes with different
sulfinyl groups was still absent (Figure 1). Herein, we present our
efforts on the development of a class of readily available and easily
tunable benzene backbone-based olefinÀsulfoxide ligands for
the rhodium-catalyzed asymmetric addition reaction.
Figure 1. Very recent examples of olefinÀsulfoxide ligands.
ligands on the reactivity and enantioselectivity of the Rh-catalyzed
HayashiÀMiyaura reaction, the ligands bearing different sulfinyl
moieties were also examined, and thus the highly modular and
easily tunable olefinÀsulfoxide ligands were formed (Scheme 1).
Subsequently, a series of electronically and sterically varied
benzene backbone-based olefinÀsulfoxide ligands (Figure 2)
were prepared in a facile two-step synthesis.
As an illustrative example, the synthesis of ligand 6c bear-
ing a (R)-tert-butylsulfinyl group was discussed (Scheme 2).
HornerÀWadsworthÀEmmons reaction of commercially avail-
able diethyl 2-bromobenzylphosphonate 944 with 4-fluoroben-
zaldehyde provided (E)-1-bromo-2-(4-fluorostyryl)benzene 10c
in good yield. After standard bromo-lithium exchange of bromo-
arene derivative with n-BuLi at low temperature, the commer-
cially available (R)-thiosulfinate was subsequently added and the
desired product (R,E)-6c was obtained in 54% overall yield. It
was worth noting that the HornerÀWadsworthÀEmmons reac-
tion of 3,4-dimethoxybenzaldehyde and 2,4,6-trimethoxybenzal-
dehyde selectively gave Z-isomers. Thus, the addition of (R)-
thiosulfinate could finally afford (R,Z)-7a and (R,Z)-7b ligands.
Inspired by recent success of olefinÀoxazoline32 and bis-sulfoxide36
ligands based on benzene backbone in asymmetric catalysis, a
benzene ring was chosen as an internal ring skeleton to strengthen
the coordination ability of alkenes to transition metals. Olefin
and sulfoxide frameworks attached to the benzene ring in a 1,2-
fashion would be helpful for the coordination of olefins and
sulfoxides to transition metals. We reasoned that the combina-
tion of η2-binding olefins with η1-binding sulfoxide would allow
new coordination geometries and possibilities in the class of
hybrid ligands. Moreover, to further examine the influence of
electronic and steric modulations at the olefinÀsulfoxide hybrid
Received: June 8, 2011
Published: July 27, 2011
r
2011 American Chemical Society
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NOTE
Scheme 1. Modular OlefinÀSulfoxide Ligand Assembly, Retrosynthetic Procedure
Table 1. Screening Reaction Conditions of the Addition of
Phenylboronic Acid to Cyclohexenonea
entry
ligand
solvent
yieldb (%)
eec,d (%)
1
2
6a
6b
7a
7b
6c
6d
6e
6f
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCM
94
76 (S)
41 (S)
8 (S)
91 (S)
92 (S)
87 (S)
90 (S)
ndh
89
Figure 2. OlefinÀsulfoxide ligands in this work.
3
94
4
78
Scheme 2. Synthesis of OlefinÀSulfoxide Ligand 6ca
5
94
6
96
7
92
8
trace
94
9
8a
8b
8c
8d
6c
6c
6c
6c
6c
6c
6c
6c
87 (R)
21 (R)
48 (S)
20 (R)
83 (S)
91 (S)
82 (S)
89 (S)
82 (S)
nd
10
11
12
13e
14f
15g
16
17
18
19
20
89
79
92
a Reagents and conditions: (a) NaH, THF, 0 °C to rt, 1 h; then
4-fluorobenzaldehyde, THF, 0 °C to rt, overnight, 87% yield; (b) n-
BuLi, THF, À78 °C; then (R)-thiosulfinate, THF, À78 °C to rt,
overnight, 62% yield.
93
94
91
93
dioxane
THF
56
To further enrich the electronical and sterical effect of olefinÀ
sulfoxide ligands, ligands 8aÀ8d (Figure 2) bearing different
sulfinyl moieties were synthesized by similar procedures.
trace
trace
trace
CH3CN
nd
DMF
nd
With the ligands in hand, the rhodium-catalyzed addition of
phenylboronic acid to cyclohexenone was used as the model
reaction to test the catalytic efficiency of this new series of ligands
(Table 1). The reaction proceeded smoothly and afforded the
desired product in 90% yield with 74% ee when using ligand 6a
(entry 1). Contrary to our anticipation, when ligand 6b was
employed which possesses an electron-donating para-methoxy
group on the terminal benzene ring, both the catalytic reactivity
and enantioselectivity decreased (89% yield and 41% ee, entry 2).
The use of ligand 7a with two methoxy groups on its terminal
benzene ring gave a much lower ee value (8% ee, entry 3),
whereas the 2,4,6-trimethoxy analogue afforded high ee value
(91% ee, entry 4). When electron-withdrawing groups were
screened on the para-position of the benzene ring, higher reactivities
and enantioselectivities were obtained (entries 5À7). However,
when a tert-butyl group was used as the terminal group instead of
the aromatic group (ligand 6f), no desired product was observed
a The reaction was carried out with 2-cyclohexenone (0.30 mmol),
arylboronic acid (0.45 mmol), [RhCl(C2H4)2]2 (0.003 mmol), ligand
(0.0066 mmol, 1.1 equiv of Rh), and 0.75 M aq KOH (0.20 mL) in
toluene (2.0 mL) at 40 °C for 0.5À3 h monitored by TLC unless
otherwise stated. b Isolated yield based on 2-cyclohexenone. c Deter-
mined by HPLC analysis. d The configuration was determined by
comparing the optical rotation with the reported one. e Reaction run
f
with 2 mol % of catalyst at rt for 1 h. Reaction run with 2 mol % of
catalyst at 60 °C for 0.25 h. g Reaction run with 1 mol % catalyst at 40 °C
for 0.5 h. h Not determined.
(entry 8). In addition to the influence of the alkene moiety with
different substituents on the yield and selectivity, the change of
chiral sulfinyl groups of sulfoxide moieties also obviously affected
the outcome of the reaction. Compared with ligand 6c, ligand 8a
bearing (S)-tert-butylsulfinyl groups showed decreased enantio-
selectivity (87% ee) with the retention of yield (94%, entry 9),
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NOTE
Table 2. Substrate Scope in the Addition Reaction Using 6c Liganda
entry
enone (11)
boronic acid (12)
product (13)
yieldb (%)
eec,d (%)
1
2
11a
11a
11a
11a
11a
11a
11a
11a
11a
11a
11a
11a
11a
11a
11b
11c
11d
Ph (12a)
13aa
13ab
13ac
13ad
13ae
13af
13ag
13ah
13ai
94
91
84
89
85
89
90
97
84
96
97
91
86
83
91
89
95
92 (S)
95 (S)
96 (S)
97 (S)
90 (S)
91 (S)
84 (S)
88 (S)
95 (S)
96 (S)
90 (S)
83 (S)
91 (S)
86 (S)
93 (S)
65 (S)
91 (S)
2-MeOC6H4 (12b)
3-MeOC6H4 (12c)
4-MeOC6H4 (12d)
2-MeC6H4 (12e)
4-MeC6H4 (12f)
4-CF3C6H4 (12g)
3-CF3C6H4 (12h)
2-FC6H4 (12i)
4-FC6H4 (12j)
4-ClC6H4 (12k)
4-t-BuC6H4 (12l)
1-naphthyl (12m)
2-naphthyl (12n)
Ph (12a)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
13aj
13ak
13al
13am
13an
13ba
13ca
13da
Ph (12a)
Ph (12a)
a The reaction was carried out with enone (0.30 mmol), arylboronic acid (0.45 mmol), [RhCl(C2H4)2]2 (0.003 mmol), ligand 6c (0.0066 mmol, 1.1
equiv of Rh), and 0.75 M aq KOH (0.20 mL) in toluene (2.0 mL) at 40 °C for 0.5À3 h. b Isolated yield was based on enone. c Determined by HPLC
analysis. d The configuration was determined by comparing the optical rotation with the reported one.
Table 3. Other Arylboronic Reagents in the Addition
Reaction Using 6c Liganda
whereas the ligands with other aryl sulfinyl groups resulted in a
drastic decrease in ee value (entries 10À12). When 2 mol % of
catalyst derived from the optimal ligand 6c was employed,
product 13aa was obtained with high reactivity (94% yield, entry 5)
and enantioselectivity (92% ee) at 40 °C. Increasing or decreas-
ing the reaction temperature resulted in a slight decrease in
enantioselectivities (entries 13 and 14). Decreasing the catalyst
loading to 1 mol % also led to a loss in yield and enantioselectivity
(entry 15). Furthermore, the reaction worked well in CH2Cl2 or
dioxane, albeit with slightly lower yields and ee values (entries 16
and 17). However, when the reaction was conducted in THF,
CH3CN, or DMF, no desired product was found (entries
18À20). Finally, a single sulfoxide ligand (R)-tert-butylsulfinyl-
benzene was employed in the model reaction, but no reaction
took place. This verified the fact that the alkene moiety was
indispensable in our olefinÀsulfoxide ligands.
enone
arylboronic
reagents
product yieldb
eec,d,e
(%)
entry
(11)
(13)
(%)
1
2
11a
11a
11b
11c
11d
11a
11b
11c
11d
11a
PhBF3K (14a)
13aa
13ad
13ba
13ca
13da
13aa
13ba
13ca
13da
13aa
92
90
91 (S)
94 (S)
90 (S)
68 (S)
90 (S)
44 (S)
75 (S)
5 (S)
4-MeOC6H4BF3K (14b)
PhBF3K (14a)
PhBF3K (14a)
PhBF3K (14a)
(PhBO)3 (15)
(PhBO)3 (15)
(PhBO)3 (15)
(PhBO)3 (15)
Ph4BNa (16)
3
90
4
90
5
89
6
92
7
89
8
56
9
87
77 (S)
ndf
10
trace
a General procedure: see Table 2. b Isolated yield was based on enone.
c Determined by HPLC analysis. d The configuration was determined by
comparing the optical rotation with the reported one. e See the Support-
ing Information for details. f Not determined.
With the optimized reaction conditions in hand, we tested the
scope of the reaction using representative enones and boronic
acids, and the results are summarized in Table 2. To our delight,
both electron-rich and electron-deficient arylboronic acids re-
acted efficiently to produce the desired products in good yields
(83À97%) and high enantioselectivities (83À97% ee). It was
worth noting that the position of the substituent on the phenyl
ring had little influence on the enantioselectivities (entries 2À10).
When five-membered cyclicenone 11b (entry 15) and R,β-
unsaturated cyclic ester 11d (entry 17) were subjected to this
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NOTE
reaction, good enantioselectivities were also obtained. Unfortu-
nately, lower ee was observed for the seven-membered cyclic-
enone 11c (65% ee, entry 16).
(E)-1-Bromo-2-(4-chlorostyryl)benzene (10d): following general
procedure with 4-chlorobenzaldehyde, white solid, 93% yield, mp
67À70 °C; 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 7.8 Hz, 1H),
7.58 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 13.1 Hz, 3H), 7.31 (dd, J = 15.2, 8.0
Hz, 3H), 7.16À7.09 (m, 1H), 6.97 (d, J = 16.2 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 136.9, 135.7, 133.8, 133.3, 130.2, 129.1 (d, J = 10.5 Hz),
128.1, 127.7, 126.8, 124.3; HRMS (EI, m/z) calcd for C14H10BrCl [M]+
291.9654, found 291.9665.
(E)-1-Bromo-2-(4-(trifluoromethyl)styryl)benzene (10e): following
general procedure with 4-(trifluoromethyl)benzaldehyde, white solid,
85% yield, mp 44À46 °C; 1H NMR (400 MHz, CDCl3) δ 7.66 (t, J = 6.3
Hz, 1H), 7.63À7.58 (m, 5H), 7.54 (d, J = 16.2 Hz, 1H), 7.32 (t, J = 7.5
Hz, 1H), 7.15 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 16.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 140.6, 136.6, 133.3, 130.1 (d, J = 10.8 Hz), 129.6,
127.8, 127.0 (d, J = 6.0 Hz), 125.8 (d, J = 2.8 Hz), 124.5, 122.9; 19F NMR
(377 MHz, CDCl3) δ À63.07 (s, 3F); HRMS (EI, m/z) calcd for
C15H10BrF3 [M]+ 325.9918, found 325.9910.
(E)-1-Bromo-2-(3,3-dimethylbut-1-enyl)benzene (10f): following
general procedure with pivalaldehyde, colorless oil, 78% yield; 1H
NMR (400 MHz, CDCl3) δ 7.49 (dd, J = 12.0, 7.9 Hz, 2H), 7.22 (t,
J = 7.5 Hz, 1H), 7.13À6.95 (m, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.17 (d,
J = 16.0 Hz, 1H), 1.14 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 144.7,
137.9, 132.8, 128.1, 127.4, 126.9, 124.1, 123.7, 33.8, 29.6; HRMS (EI,
m/z) calcd for C12H15Br [M]+ 238.0357, found 238.0353.
To further examine the reactivity of this catalyst, the reaction
of different cyclic enones (11) with trifluoroborate salts (14),
boronate ester (15), and tetraarylborate salts (16) were studied
under the optimal reaction conditions (Table 3). To our delight,
moderate to good yields and enantioselectivities were also
obtained by the reaction of cyclic enones with potassium
trifluoroborate salts (89À92% yield, 68À94% ee, entries 1À5).
However, drastic decrease of the enantioselectivity was observed
when phenyl boronate ester was employed (5À77% ee, entries
6À9), and sodium tetraarylborate (16) only gave a trace amount
of product (entry 10).
In conclusion, a class of simple and readily available benzene
backbone-based chiral olefinÀsulfoxide ligands was developed
and successfully applied in the rhodium-catalyzed asymmetric
conjugate addition reaction of arylboronic acids to enones with
high yields and great enantioselectivities. Such a kind of ligands
with both modularity and versatility can be easily varied on its
steric and electronic properties over a wide range, thus making
these types of ligands attractive and promising for asymmetric
catalysis.
(Z)-4-(2-Bromostyryl)-1,2-dimethoxybenzene (10g): following gen-
eral procedure with 3,4-dimethoxybenzaldehyde, white solid, 80% yield,
mp 98À101 °C; 1H NMR (400 MHz, acetone) δ 7.84À7.72 (m, 1H),
7.62 (d, J = 8.0 Hz, 1H), 7.37 (dd, J = 15.9, 9.4 Hz, 2H), 7.26À7.14 (m,
4H), 6.97 (d, J = 8.3 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H); 13C NMR (100
MHz, acetone) δ 150.9, 150.1, 133.9, 132.9, 129.7, 128.9, 127.7, 125.6,
121.2, 112.9, 110.9, 56.2; HRMS (ESI, m/z) calcd for C16H15BrO2Na
[M + Na]+ 341.0153, found 341.0160.
’ EXPERIMENTAL SECTION
General Considerations. All reactions were carried out under
nitrogen using standard Schlenk techniques. Commercially available
reagents were used without further purification. Solvents were dried
according to the standard procedure.
General Procedure for the Synthesis of 10. To a suspension
of NaH (60% in oil, 0.44 mg, 11.0 mmol) in THF (5 mL) at 0 °C was
slowly added diethyl 2-bromobenzylphosphonate 944 (3.07 g, 10.0 mmol).
The resulting suspension was stirred for an additional 1 h at room temperature.
The reaction mixture was cooled to 0 °C, and then a solution of aldehyde
(10.0 mmol) in THF (5 mL) was added dropwise and slowly warmed to
room temperature. After stirring overnight, the reaction was quenched
with ice water and the aqueous phase was extracted with Et2O. The
combined organic layers were washed with brine and dried over Na2SO4.
After concentration in vacuo, the residue was purified by silica gel flash
column chromatography to give product 10.
(E)-1-Bromo-2-styrylbenzene (10a) (ref 45): following general pro-
cedure with benzaldehyde, colorless oil, 89% yield; 1H NMR (400 MHz,
acetone) δ 7.80 (d, J = 7.8 Hz, 1H), 7.62 (dd, J = 7.8, 2.5 Hz, 3H), 7.51
(d, J = 16.3 Hz, 1H), 7.39 (q, J = 7.2 Hz, 3H), 7.31 (t, J = 7.3 Hz, 1H),
7.25À7.15 (m, 2H); 13C NMR (100 MHz, acetone) δ 137.2 (d, J = 6.2
Hz), 133.2, 131.9, 129.4, 128.9, 128.4, 128.1, 127.1, 126.9, 123.8.
(E)-1-Bromo-2-(4-methoxystyryl)benzene (10b) (ref 46): following
general procedure with 4-methoxybenzaldehyde, white solid, 88% yield,
mp 65À67 °C; 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.8 Hz, 1H),
7.55 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.36À7.22 (m, 2H),
7.07 (t, J = 7.6 Hz, 1H), 6.98 (d, J = 16.2 Hz, 1H), 6.90 (d, J = 8.3 Hz,
2H), 3.81 (s, 3H) 13C NMR (100 MHz, CDCl3) δ 159.8, 137.5, 133.2,
131.1, 129.9, 128.5, 128.2, 127.6, 126.6, 125.4, 124.1, 114.3, 55.5.
(E)-1-Bromo-2-(4-fluorostyryl)benzene (10c): following general pro-
cedure with 4-fluorobenzaldehyde, white solid, 87% yield, mp 55À57 °C;
1H NMR (400 MHz, CDCl3) δ7.62 (d, J = 7.8 Hz, 1H), 7.57 (d, J=8.0 Hz,
1H), 7.50 (dd, J = 8.2, 5.6 Hz, 2H), 7.36 (d, J = 16.2 Hz, 1H), 7.29 (t, J = 7.5
Hz, 1H), 7.08 (dt, J = 17.2, 8.0 Hz, 3H), 6.97 (d, J = 16.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 163.9, 161.5,137.1, 133.2, 130.4, 128.9, 128.5
(d, J = 7.4 Hz), 127.9, 127.5 (d, J = 35.2 Hz), 126.8, 124.2, 115.85 (d, J =
21.7 Hz); 19F NMR (377 MHz, CDCl3) δ À113.98 (s, 1F); HRMS (EI,
m/z) calcd for C14H10BrF [M]+ 275.9950, found 275.9944.
(Z)-2-(2-Bromostyryl)-1,3,5-trimethoxybenzene (10h): following
general procedure with 2,4,6-trimethoxybenzaldehyde, light yellow
1
solid, 78% yield, mp 104À107 °C; H NMR (400 MHz, CDCl3) δ
7.83 (d, J = 16.5 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 8.0 Hz,
1H), 7.37À7.24 (m, 2H), 7.04 (t, J = 7.6 Hz, 1H), 6.17 (s, 2H), 3.90 (s,
6H), 3.84 (s, 3H); 13C NMR (100 MHz, acetone) δ160.9, 133.9, 128.9
(d, J = 16.3 Hz), 128.5, 126.9, 124.3, 123.7, 91.9, 56.4, 55.8; HRMS (ESI,
m/z) calcd for C17H17BrO3Na [M + Na]+ 371.0259, found 371.0252.
Representative Procedure for the Synthesis of Chiral OlefinÀ
Sulfoxide Ligand 6c. At À78 °C, n-BuLi (5.25 mmol) was added
dropwise to a solution of (E)-1-bromo-2-(4-fluorostyryl)benzene 10c
(1.38 g, 5.0 mmol) in THF (15 mL). The resulting mixture was stirred
for 1 h at À78 °C, and a solution of (R)-tert-butyl tert-butanethiosulfi-
nate (1.02 g, 5.25 mmol) in THF (10 mL) was slowly added. After
stirring for an additional 1 h at À78 °C, the solution was allowed to warm
to room temperature and stirred for another 1 h, then quenched with
cold saturated aqueous NH4Cl solution. The aqueous layer was ex-
tracted with CH2Cl2. The organic layer was washed with brine and dried
over Na2SO4. After concentration in vacuo, the residue was purified by
flash chromatography to afford (R,E)-6c as a white solid: 0.94 g, 62% yield.
(R,E)-1-(tert-Butylsulfinyl)-2-styrylbenzene (6a): white solid, 62%
1
yield, mp 77À80 °C; [R]20 = 209.4 (c = 1.1, CHCl3); H NMR
D
(500 MHz, CDCl3) δ 7.92 (d, J = 7.1 Hz, 1H), 7.71 (dd, J = 7.5, 1.0 Hz,
1H), 7.54À7.45 (m, 5H), 7.39 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.3 Hz,
1H), 7.06 (d, J = 16.1 Hz, 1H), 1.18 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 137.9, 136.9, 131., 131.3, 129.0, 128.5, 127.8, 126.9, 126.7,
125.6, 124.4, 64.7, 23.5; HRMS (ESI, m/z) calcd for C18H20OSNa [M +
Na]+ 307.1133, found 307.1133.
(R,E)-1-(tert-Butylsulfinyl)-2-(4-methoxystyryl)benzene (6b): color-
less oil, 66% yield, [R]20D = 186.5 (c = 2.1, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 7.90 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.52À7.39
(m, 4H), 7.36 (d, J = 16.1 Hz, 1H), 7.01 (d, J = 16.1 Hz, 1H), 6.92 (d, J =
7259
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NOTE
8.5 Hz, 2H), 3.83 (s, 3H), 1.18 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
159.9, 138.1 (d, J = 7.1 Hz), 131.3 (d, J = 15.3 Hz), 131.0, 130.1, 129.6,
128.1, 127.3, 126.5, 125.2, 122.1, 114.4, 58.3, 55.4, 23.4; HRMS (ESI,
m/z) calcd for C19H22O2SNa [M + Na]+ 337.1238, found 337.1241.
(R,E)-1-(tert-Butylsulfinyl)-2-(4-fluorostyryl)benzene (6c): white so-
lid, 62% yield, mp 87À90 °C; [R]20D = 237.4 (c = 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.91 (dd, J = 7.6, 1.5 Hz, 1H), 7.71À7.66 (m, 1H),
7.52À7.45 (m, 4H), 7.42 (d, J = 16.1 Hz, 1H), 7.08 (t, J = 8.6 Hz, 2H),
7.02 (d, J = 16.1 Hz, 1H), 1.18 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
163.8, 161.9, 138.5, 137.8, 133.1, 131.3, 130.3, 128.4 (d, J = 8.0 Hz),
127.8, 126.7, 125.5, 124.2, 116.1, 115.9, 58.4, 23.4; 19F NMR (377 MHz,
CDCl3) δ À113.53 (s, 1F); HRMS (ESI, m/z) calcd for C18H19FOSNa
[M + Na]+ 325.1038, found 325.1044.
(R,E)-1-(tert-Butylsulfinyl)-2-(4-chlorostyryl)benzene (6d): white so-
lid, 60% yield, mp 113À116 °C; [R]20D = 220.5 (c = 1.0, CDCl3) 1H
NMR (400 MHz, acetone) δ 7.88 (dd, J = 10.2, 8.0 Hz, 2H), 7.67À7.62
(m, 3H), 7.61À7.52 (m, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 16.2
Hz, 1H), 1.14 (s, 9H); 13C NMR (100 MHz, acetone) δ 140.5, 138.4,
136.9, 134.3,132.1, 130.9, 129.9, 129.4, 128.7, 127.5, 126.4, 125.8, 58.5,
23.5; HRMS (ESI, m/z) calcd for C18H19ClOSNa [M + Na]+ 341.0743,
found 341.0737.
(R,E)-1-(tert-Butylsulfinyl)-2-(4-(trifluoromethyl)styryl)benzene (6e):
white solid, 61% yield, mp 77À79 °C; [R]20D = 183.9 (c = 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.97À7.91 (m, 1H), 7.75À7.70 (m, 1H),
7.68À7.57 (m, 5H), 7.51 (p, J = 7.3 Hz, 2H), 7.08 (d, J = 16.1 Hz, 1H),
1.18 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 140.3 138.9 137.3 131.4
130.2, 129.9 (q, JC,F = 32.6 Hz), 128.3, 126.9, 125.9 (q, JC,F = 3.5 Hz),
125.7, 123.2, 58.5 23.4; 19F NMR (377 MHz, CDCl3) δ À63.15 (s, 3F);
HRMS (ESI, m/z) calcd for C19H19F3OSNa [M + Na]+ 375.1006, found
375.1009.
163.9 161.9 138.6, 137.8, 133.1, 131.3 130.3 128.4 (d, J = 8.1 Hz), 127.8,
126.8 125.5, 124.3 116.1, 115.9, 58.4, 23.5; 19F NMR (377 MHz,
CDCl3) δ À113.53 (s, 1F); HRMS (ESI, m/z) calcd for C18H19FOSNa
[M + Na]+ 325.1038, found 325.1039.
(S,E)-1-(4-Fluorostyryl)-2-(p-tolylsulfinyl)benzene (8b): following
the general procedure with (1S,2R,5S)-(+)-menthyl-(S)-p-Tol-sulfinate
in place of (R)-tert-butyl tert-butanethiosulfinate, white solid, 55% yield,
mp 82À85 °C; [R]20D = À115.9 (c = 1.0, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 8.01À7.96 (m, 1H), 7.61 (dd, J = 5.9, 3.1 Hz, 1H), 7.51 (d, J =
8.2 Hz, 1H), 7.47À7.43 (m, 7H), 7.24 (d, J = 8.1 Hz, 1H), 7.18 (d, J = 8.1
Hz, 2H), 7.07 (t, J = 8.6 Hz, 2H), 6.94 (d, J = 16.1 Hz, 1H), 2.31 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 163.9, 161.9, 143.1, 142.2,141.5,136.1,
132.9, 131.3 (d, J = 13.1 Hz), 130.1, 128.7, 128.5 (d, J = 8.1 Hz), 126.1,
125.4, 124.9 (d, J = 9.6 Hz), 123.0, 115.9 (d, J = 21.8 Hz), 21.5; 19F NMR
(377 MHz, CDCl3) δ À113.31 (s, 1F); HRMS (ESI, m/z) calcd for
C21H17FOSNa [M + Na]+ 359.0882, found 359.0890.
(R,E)-1-(2-(4-Fluorostyryl)phenylsulfinyl)-2-methoxynaphthalene
(8c): following the general procedure with (S)-L-menthyl 2-methoxy-
1-naphthalensulfinate47 in place of (R)-tert-butyl tert-butanethiosulfi-
nate, white solid, 50% yield, mp 95À97 °C; [R]20D = À162.2 (c = 0.6,
CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.81 (dd, J = 8.7, 0.7 Hz, 1H),
8.36 (dd, J = 8.0, 1.2 Hz, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.74 (dd, J = 8.2,
0.5 Hz, 1H), 7.57À7.50 (m, 2H), 7.47 (d, J = 7.2 Hz, 1H), 7.42À7.36
(m, 2H), 7.07 (d, J = 9.1 Hz, 1H), 6.96À6.83 (m, 5H), 6.63 (d, J = 15.9
Hz, 1H), 3.71 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 163.4, 161.4,
157.6, 141.7, 135.1, 134.6, 132.8, 132.4, 130.1, 129.9, 129.2, 128.9,
128.5, 128.23, 127.3, 126.6, 125.6, 124.4, 123.7, 123.0, 122.6, 115.4,
115.3, 113.4, 56.5; 19F NMR (377 MHz, CDCl3) δ À114.09 (s, 1F);
HRMS (ESI, m/z) calcd for C25H19FO2SNa [M + Na]+ 425.0987,
found 425.0977.
(R,E)-1-(tert-Butylsulfinyl)-2-(3,3-dimethylbut-1-enyl)benzene (6f):
white solid, 57% yield, mp 47À50 °C; [R]20D = 138.1 (c = 1.1, CHCl3);
1H NMR (400 MHz, acetone) δ 7.81 (d, J = 9.1 Hz, 1H), 7.65 (d, J = 7.4
Hz, 1H), 7.53À7.43 (m, 2H), 6.77 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0
Hz, 1H), 1.14 (s, 9H), 1.13 (s, 9H); 13C NMR (100 MHz, acetone)
δ145.3 139.3 131.9, 127.8, 127.2 126.5 122.2 58.7, 34.5, 23.6; HRMS
(ESI, m/z) calcd for C16H24OSNa [M + Na]+ 287.1446, found
287.1448.
(S,E)-1-(4-Fluorostyryl)-2-(4-methoxyphenylsulfinyl)benzene (8d):
following the general procedure for the preparation with (S)-L-menthyl
p-methoxybenzenesulfinate48 instead of (R)-tert-butyl tert-butanethio-
sulfinate, white solid, 63% yield, mp 80À82 °C; [R]20D = À291.1 (c =
1
0.7, CHCl3); H NMR (500 MHz, CDCl3) δ 8.06À8.01 (m, 1H),
7.59À7.53 (m, 1H), 7.51À7.40 (m, 6H), 7.37 (d, J = 16.0 Hz, 1H),
7.10À7.04 (m, 2H), 6.91 (d, J = 16.0 Hz, 1H), 6.89À6.85 (m, 2H), 3.76
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 163.8, 161.8, 142.9, 136.3,
135.7, 132.9, 131.2, 131.0, 128.6, 128.36 (d, J = 8.1 Hz), 127.48 (s),
126.1, 124.5, 122.8, 115.9, 115.8, 114.76, 55.5; 19F NMR (377 MHz,
CDCl3) δ À113.38 (s, 1F); HRMS (ESI, m/z) calcd for C21H17FO2SNa
[M + Na]+ 375.0831, found 375.0839.
Asymmetric 1,4-Addition of Arylboronic Acids to Enones.
Under nitrogen atmosphere, a mixture of [RhCl(C2H4)2]2 (1.2 mg,
0.003 mmol) and 6c (2.0 mg, 0.0066 mmol) in 1 mL toluene was stirred
at room temperature for 1 h, at which time arylboronic acid (0.45 mmol)
was added, followed by enone (0.30 mmol), aqueous KOH (0.75 M in
H2O, 0.20 mL, 0.15 mmol), and toluene (1 mL). The reaction was
stirred at 40 °C and monitored by TLC. When the reaction was over, the
reaction mixture was concentrated in vacuo and purified by silica gel
flash column chromatography to afford the product.
(R,Z)-4-(2-(tert-Butylsulfinyl)styryl)-1,2-dimethoxybenzene (7a):
light yellow oil, 82% yield; [R]20 = 124.2 (c = 2.0, CHCl3); 1H
D
NMR (400 MHz, acetone) δ 7.85 (d, J = 7.8 Hz, 2H), 7.58À7.49 (m,
2H), 7.46 (d, J = 16.0 Hz, 1H), 7.22 (dd, J = 9.0, 7.0 Hz, 2H), 7.17 (dd,
J = 8.3, 1.8 Hz, 1H), 6.98 (d, J = 8.3 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H),
1.14 (s, 9H); 13C NMR (100 MHz, acetone) δ 151.1 150.7, 139.9,
139.1132.3 132.0, 131.1 127.9, 127.3, 126.1 122.8, 121.1 112.9, 111.1
56.3 30.6 23.6; HRMS (ESI, m/z) calcd for C20H24O3SNa [M + Na]+
367.1344, found 367.1344.
(R,Z)-2-(2-(tert-Butylsulfinyl)styryl)-1,3,5-trimethoxybenzene (7b):
light yellow solid, 89% yield, mp 110À113 °C; [R]20 = 224.7 (c =
D
1.1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 16.4 Hz, 1H),
7.87 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.45 (t, J = 7.5 Hz, 1H),
7.40 (d, J = 9.7 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 6.16 (s, 2H), 3.89 (s,
6H), 3.83 (s, 3H), 1.20 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
61.26,158.6 139.7 138.1 130.9, 129.8127.5, 126.9, 126.6 126.0 (t, J = 18.7
Hz), 125.3, 124.7 123.2 122.1, 107.4 90.9 90.6 58.3 55.9, 55.4, 55.3, 23.5;
HRMS (ESI, m/z) calcd for C21H26O4SNa [M + Na]+ 397.1450, found
397.1437.
3-Phenylcyclohexanone (13aa) (ref 16): colorless oil, 94% yield,
92% ee, [R]20 = À12.6 (c = 1.0, CHCl3); Chiracel AD-H column,
D
210 nm, n-hexane/i-propanol = 97/3, flow = 0.8 mL/min, tR = 9.9 and
11.8 min; 1H NMR (500 MHz, CDCl3) δ 7.39À7.28 (m, 2H),
7.26À7.19 (m, 3H), 3.01 (tt, J = 11.8, 3.9 Hz, 1H), 2.62À2.34 (m,
4H), 2.18À2.05 (m, 2H), 1.90À1.72 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 211.1, 144.5, 128.8, 126.7, 49.0, 44.9, 41.3, 32.9, 25.6.
3-(2-Methoxyphenyl)cyclohexanone (13ab) (ref 16): colorless oil,
(S,E)-1-(tert-Butylsulfinyl)-2-(4-fluorostyryl)benzene (8a): following
the general procedure with (S)-tert-butyl tert-butanethiosulfinate in
place of (R)-tert-butyl tert-butanethiosulfinate, gray-white solid, 63%
yield, mp 66À68 °C; [R]20D = À199.7 (c = 0.8, CHCl3); 1H NMR (500
MHz, CDCl3) δ 7.92 (dd, J = 7.3, 1.9 Hz, 1H), 7.68 (dd, J = 7.5, 1.5 Hz,
1H), 7.50À7.45 (m, 4H), 7.43 (d, J = 16.1 Hz, 1H), 7.13À7.06 (m, 2H),
7.02 (d, J = 16.1 Hz, 1H), 1.18 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
91% yield, 95% ee, [R]20 = À31.3 (c = 1.0, CHCl3); Chiracel OJ-H
D
column, 210 nm, n-hexane/i-propanol = 98/2, flow = 1.0 mL/min, tR =
13.4 and 14.3 min; 1H NMR (400 MHz, CDCl3) δ 7.28À7.13 (m, 2H),
6.94 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 3.81 (s, 3H), 3.49À3.36
(m, 1H), 2.65À2.31 (m, 4H), 2.20À1.97 (m, 2H), 1.92À1.73 (m, 2H);
7260
dx.doi.org/10.1021/jo2011472 |J. Org. Chem. 2011, 76, 7256–7262

The Journal of Organic Chemistry
NOTE
13C NMR (100 MHz, CDCl3) δ 211.9, 156.8, 138.2, 132.2,127.6, 126.6,
120.7, 110.8, 55.3, 47.7, 41.5, 38.0, 31.1, 25.7.
3-(4-Chlorophenyl)cyclohexanone(13ak) (ref 49): colorless oil, 97%
yield, 90% ee, [R]20D = À7.3 (c = 1.1, CHCl3); Chiracel AD-H column,
210 nm, n-hexane/i-propanol = 95/5, flow = 0.8 mL/min, tR = 9.8 and
10.7 min; 1H NMR (500 MHz, CDCl3) δ 7.36À7.24 (m, 2H),
7.20À7.07 (m, 2H), 3.09À2.92 (m, 1H), 2.69À2.30 (m, 4H),
2.26À2.00 (m, 2H), 1.85À1.72 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 210.5, 142.9, 132.5, 128.9, 128.1, 48.9, 44.2, 41.2, 32.8, 25.5.
3-(3-Methoxyphenyl)cyclohexanone (13ac) (ref 16): colorless oil,
84% yield, 96% ee, [R]20D = À10.4 (c = 0.8, CHCl3); Chiracel AD-H
column, 210 nm, n-hexane/i-propanol = 95/5, flow = 0.6 mL/min, tR =
16.6 and 18.1 min; 1H NMR (400 MHz, CDCl3) δ 7.24 (t, J = 7.6 Hz,
1H), 6.79 (dd, J = 14.9, 7.4 Hz, 3H), 3.80 (s, 3H), 3.09À2.88 (m, 1H),
2.66À2.27 (m, 4H), 2.22À1.99 (m, 2H), 1.94À1.67 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 211.0, 159.9, 146.1, 129.7, 118.9, 112.8, 111.7,
55.2, 48.9, 44.8, 41.2, 32.7, 25.6.
3-(4-tert-Butylphenyl)cyclohexanone (13al) (ref 49): white solid,
91% yield, 83% ee, [R]20 = À9.9 (c = 0.9, CHCl3); Chiracel AS-H
D
column, 210 nm, n-hexane/i-propanol = 98/2, flow = 0.6 mL/min, tR =
21.4 and 24.3 min; 1H NMR (500 MHz, CDCl3) δ 7.41À7.33 (m, 2H),
7.20À7.12 (m, 2H), 3.03À2.95 (m, 1H), 2.66À2.30 (m, 4H),
2.19À2.05 (m, 2H), 1.86À1.73 (m, 2H), 1.31 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 211.3, 149.6, 141.4, 126.3, 125.6, 49.1, 44.4, 41.3,
34.5, 32.9, 31.5, 25.7.
3-(4-Methoxyphenyl)cyclohexanone (13ad) (ref 49): white solid,
89% yield, 97% ee, [R]20 = À14.3 (c = 1.0, CHCl3); Chiracel OJ-H
D
column, 210 nm, n-hexane/i-propanol = 98/2, flow =1.0 mL/min, tR =
33.8 and 40.3 min; 1H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 8.5 Hz,
2H), 6.86 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 3.09À2.82 (m, 1H),
2.66À2.22 (m, 4H), 2.17À1.94 (m, 2H), 1.78 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 211.3, 158.5, 136.6, 127.6, 114.1, 55.3, 49.3, 44.0, 41.2,
33.1, 25.6.
3-(Naphthalen-1-yl)cyclohexanone (13am) (ref 16): white solid,
86% yield, 91% ee, [R]20D = À48.4 (c = 0.8, CHCl3); Chiracel AD-H
column, 210 nm, n-hexane/i-propanol = 98/2, flow = 0.6 mL/min, tR =
19.2 and 21.5 min; 1H NMR (500 MHz, CDCl3) δ 8.04 (d, J = 11.1 Hz,
1H), 7.86 (d, J = 7.9 Hz, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.59À7.38 (m, 4H),
3.85À3.80 (m, 1H), 2.78À2.40 (m, 4H), 2.26À2.13 (m, 2H), 2.03À1.86
(m, 2H); 13C NMR (125 MHz, CDCl3) δ 211.2, 140.2, 134.1, 131.0,
129.2, 127.4, 126.3, 125.7, 122.8, 122.6, 48.7, 41.5, 39.5, 32.4, 25.7.
3-(Naphthalen-2-yl)cyclohexanone (13an) (ref 49): white solid,
3-o-Tolylcyclohexanone (13ae) (ref 49): colorless oil, 85% yield,
90% ee, [R]20 = À32.6 (c = 1.0, CHCl3); Chiracel AD-H column,
D
210 nm, n-hexane/i-propanol = 95/5, flow = 0.6 mL/min, tR = 10.0 and
11.8 min; 1H NMR (500 MHz, CDCl3) δ 7.26À7.18 (m, 2H),
7.17À7.10 (m, 2H), 3.28À3.15 (m, 1H), 2.54À2.41 (m, 4H), 2.32 (s,
3H), 2.17 (m,1H), 2.04À1.97 (m, 1H), 1.86À1.75 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 211.2, 142.4, 135.2, 130.8, 126.52, 125.2, 48.4,
41.4, 40.4, 32.1, 25.9, 19.4.
83% yield, 86% ee, [R]20 = À6.3 (c = 1.0, CHCl3); Chiracel AD-H
D
column, 210 nm, n-hexane/i-propanol = 98/2, flow = 0.6 mL/min, tR =
20.8 and 23.1 min; 1H NMR (500 MHz, CDCl3) δ 7.87À7.76 (m, 3H),
7.64 (dd, J = 5.8, 5.4 Hz, 1H), 7.52À7.33 (m, 3H), 3.27À3.11 (m, 1H),
2.75À2.58 (m, 2H), 2.54À2.35 (m, 2H), 2.24À2.11 (m, 2H), 2.02À
1.76 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 210.9, 141.9, 133.7,
132.5, 128.5, 127.8, 126.3, 125.8, 125.4, 124.9, 48.9, 44.9, 41.4, 32.9, 25.7.
3-Phenylcyclopentanone (13ba) (ref 16): colorless oil, 91% yield,
3-p-Tolylcyclohexanone (13af) (ref 16): white solid, 89% yield, 91%
ee, [R]20D = À12.6 (c = 1.0, CHCl3); Chiracel AD-H column, 210 nm,
n-hexane/i-propanol = 95/5, flow = 0.6 mL/min, tR = 9.9 and 11.1 min;
1H NMR (500 MHz, CDCl3) δ 7.14À7.09 (m, 4H), 3.07À2.87 (m,
1H), 2.60À2.33 (m, 4H), 2.32 (s, 3H), 2.13À2.01 (m, 2H), 1.87À1.72
(m, 2H); 13C NMR (125 MHz, CDCl3) δ 211.1, 141.5, 136.3, 129.4,
126.5, 49.1, 44.5, 41.3, 32.9, 25.6, 21.0.
3-(4-(Trifluoromethyl)phenyl)cyclohexanone (13ag) (ref 16): white
solid, 90% yield, 84% ee, [R]20D = À8.1 (c = 1.0, CHCl3); Chiracel AS-H
column, 210 nm, n-hexane/i-propanol = 90/10, flow = 0.7 mL/min, tR =
12.6 and 13.9 min; 1H NMR (500 MHz, CDCl3) δ 7.59 (d, J = 8.1 Hz,
2H), 7.34 (d, J = 8.3 Hz, 2H), 3.08 (m, 1H), 2.68À2.32 (m, 4H),
2.25À2.03 (m, 2H), 1.96À1.72 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 210.2, 148.4, 129.2 (q, JC,F = 32.1 Hz), 127.1, 125.8 (q, J = 3.7 Hz),
124.3 (d, JC,F = 271.4 Hz), 48.6, 44.6, 41.2, 32.6, 25.5.
3-(3-(Trifluoromethyl)phenyl)cyclohexanone (13ah) (ref 34): color-
less oil, 97% yield, 88% ee, [R]20D = À9.5 (c = 1.0, CHCl3); Chiracel OJ-
H column, 210 nm, n-hexane/i-propanol = 99.5/0.5, flow = 0.5 mL/min,
tR = 41.7 and 45.4 min; 1H NMR (500 MHz, CDCl3) δ 7.61À7.35 (m,
4H), 3.08 (tt, J = 12.0, 3.9 Hz, 1H), 2.69À2.35 (m, 4H), 2.23À2.06 (m,
2H), 1.96À1.73 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 210.2, 145.3,
131.2 (q, JC,F = 31.7 Hz), 130.2, 129.3, 124.2 (d, JC,F = 270.7 Hz), 123.7
(q, JC,F = 3.75 Hz), 123.4 (q, JC,F = 3.64 Hz), 48.8, 44.6, 41.2, 32.7, 25.5.
3-(2-Fluorophenyl)cyclohexanone (13ai) (ref 34): colorless oil, 84%
yield, 95% ee, [R]20D = À8.8 (c = 1.0, CHCl3); Chiracel AD-H column,
210 nm, n-hexane/i-propanol = 95/5, flow = 0.8 mL/min, tR = 8.8 and
10.3 min; 1H NMR (500 MHz, CDCl3) δ 7.34À7.16 (m, 2H), 7.16À
6.99 (m, 2H), 3.42À3.24 (m, 1H), 2.65À2.32 (m, 4H), 2.20À2.00 (m,
2H), 1.97À1.74 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 210.6, 161.6,
159.7, 131.1 (d, J = 14.0 Hz), 128.3 (d, J = 8.4 Hz), 127.7 (d, J = 4.7 Hz),
124.4 (d, J = 3.4 Hz), 115.9, 115.7, 47.3, 41.3, 38.2, 31.3, 25.5.
3-(4-Fluorophenyl)cyclohexanone (13aj) (ref 34): colorless oil, 96%
yield, 96% ee, [R]20D = À12.6 (c = 0.9, CHCl3); Chiracel AD-H column,
210 nm, n-hexane/i-propanol = 95/5, flow = 0.8 mL/min, tR = 9.5 and
11.7 min; 1H NMR (500 MHz, CDCl3) δ 7.23À7.10 (m, 2H),
7.07À6.94 (m, 2H), 3.00 (m, 1H), 2.67À2.30 (m, 4H), 2.23À2.02
(m, 2H), 1.88À1.66 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 210.7,
162.7, 160.8, 140.2, 128.1, 115.6, 115.5, 49.2, 44.1, 41.2, 33.0, 25.5.
93% ee, [R]20 = À78.8 (c = 0.9, CHCl3); Chiracel GC (β-DEX-
D
GAMA-225, 1.0 mL H2/min, 120 °C isotherm); tR = 19.8 and 20.8 min;
1H NMR (400 MHz, CDCl3) δ 7.36À7.22 (m, 5H), 3.46À3.37
(m, 1H), 2.67 (m, 1H), 2.54À2.22 (m, 4H), 2.09À1.91 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 218.5, 143.2, 128.8, 126.8, 45.9, 42.3,
38.9, 31.3.
3-Phenylcycloheptanone (13ca) (ref 49): colorless oil, 89% yield,
65% ee, [R]20 = À19.9 (c = 0.9, CHCl3); Chiracel OD-H column,
D
210 nm, n-hexane/i-propanol = 98/2, flow =1.0 mL/min, tR = 11.7 and
13.3 min; 1H NMR (400 MHz, CDCl3) δ 7.36À7.12 (m, 5H),
3.01À2.85 (m, 2H), 2.70À2.55 (m, 3H), 2.09À1.95 (m, 3H),
1.86À1.73 (m, 2H), 1.56À1.46 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 213.6, 147.0, 128.8, 126.5, 126.5, 51.4, 44.1, 42.9, 39.3, 29.4, 24.3.
4-Phenyltetrahydro-2H-pyran-2-one (13da) (ref 49): colorless oil,
95% yield, 91% ee, [R]20 = 17.8 (c = 0.9, CHCl3); Chiracel AS-H
D
column, 210 nm, n-hexane/i-propanol = 70/30, flow = 0.6 mL/min, tR =
29.4 and 33.0 min; 1H NMR (400 MHz, CDCl3) δ 7.50À7.15 (m, 5H),
4.53À4.35 (m, 2H), 3.24 (m, 1H), 2.92 (dd, J = 17.6, 5.9 Hz, 1H), 2.63
(dd, J = 17.6, 10.7 Hz, 1H), 2.25À2.04 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 170.8, 142.9, 138.2, 129.1, 127.3, 126.6, 68.9, 37.6, 30.4.
’ ASSOCIATED CONTENT
S
Supporting Information. Copies of NMR, HRMS,
b
HPLC for racemic and chiral compound spectra for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: bswan@dicp.ac.cn.
7261
dx.doi.org/10.1021/jo2011472 |J. Org. Chem. 2011, 76, 7256–7262

The Journal of Organic Chemistry
NOTE
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2010, 16, 14335.
Financial support from the National Basic Research Program
of China (2010CB833300) is gratefully acknowledged.
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