Chiral N-aryl tert-butanesulfinamide-olefin ligands for rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to cyclic enones

Article abstract of DOI:10.24820/ark.5550190.p009.977

Chiral N-aryl sulfinamide-olefins which are readily synthesized via C-N coupling and nucleophilic substitution have been used as chiral ligands, which demonstrate moderate to excellent asymmetric catalytic performance in the rhodium-catalyzed asymmetric 1

Full text of DOI:10.24820/ark.5550190.p009.977

The Free Internet Journal
for Organic Chemistry
Paper
Archive for
Organic Chemistry
Arkivoc 2017, part v, 32-42
Chiral N-aryl tert-butanesulfinamide-olefin ligands for rhodium-catalyzed
asymmetric 1,4-addition of aryl boronic acids to cyclic enones
Shuai Yuan, Qingle Zeng,* Jiajun Wang, and Lihong Zhou
State Key Laboratory of Geohazard Prevention and Geoenvironment Protection (Chengdu University of
Technology), College of Materials, Chemistry & Chemical Engineering, Chengdu University of Technology, 1#,
Dongsanlu, Erxianqiao, Chengdu 610059, Sichuan, P. R. China.
Email: qinglezeng@hotmail.com; qlzeng@cdut.edu.cn
Received 12-03-2016
Accepted 04-16-2017
Published on line 06-28-2017
Abstract
Chiral N-aryl sulfinamide-olefins which are readily synthesized via C-N coupling and nucleophilic substitution
have been used as chiral ligands, which demonstrate moderate to excellent asymmetric catalytic performance
in the rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to cyclic enones. The chiral ligands are
readily synthesized via C-N coupling reaction and nucleophilic substitution. Given that chiral ligands with
97%ee produced 1,4-addition products up to 95%ee, N-aryl tert-butanesulfinamide-olefin ligands
demonstrates fairly high chiral induction ability in the rhodium-catalyzed asymmetric 1,4-addition.
O
S
N
O
n
O
n
ArB(OH)2
+
[RhCl(C2H4)2]2
K3PO4, dioxane, 40 oC, 3 h
Ar
70-97% yield
55-95%ee
Keywords: Enantioselective catalysis; N-aryl sulfinamide-olefin; 1,4-addition reaction; rhodium; chiral ligands
DOI: https://doi.org/10.24820/ark.5550190.p009.977
Page 32
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
Introduction
Chiral sulfinyl chemistry has developed fast in the recent several decades.1-3 Chiral sulfinyl compounds have
found more and more applications in organic synthesis, pharmaceuticals, agricultural chemicals and
materials.1-3 Esomeprazole, garlicin, sparsomycin and so on are the clinic chiral sulfinyl drugs, and more
sulfinyl drugs are in developing.1-4
Chiral sulfinyl compounds are used in organic synthesis. They are extensively used as chiral intermediates
and auxiliaries, chiral ligands and catalysts.5-6 para-Toluenesulfinyl imines, tert-butanesulfinamide, tert-
butanesulfinyl imines are the common chiral intermediates for organic synthesis and drug synthesis.1-3
Chiral sulfinyl ligands and catalysts now has entered rapid developing period after a long slow development.1-3
In 1976, James, McMillan and Reimer reported the first asymmetric catalytic reaction with chiral sulfoxides as
chiral ligands, namely ruthenium catalyzed asymmetric hydrogenation.7 In 2009 the bis-sulfoxide ligands
reported by Dorta group8-9 and Liao group10 accelerate the development of chiral sulfoxide ligands.
Not only sulfoxides are used as ligands and catalysts, sulfinamide derivatives are developed as chiral ligands
pioneered by Ellman in 2001.11 Recently chiral sulfoxide- and sulfinamide-olefins are developing as new types
of chiral ligands.12-13 Knochel,14 Xu,15-17 Du,18-19 Liao,20-21 Wan,22 Chen,23 Zeng24 and so on have developed a
series of chiral sulfoxide-olefin and sulfinamide-olefin ligands. Some typical chiral ligands are shown in Figure
1.
O
S
S O
S O
O
S
R2
S
HN
HN
R1
Du 2011
O
R
N
R1
H
R1
R2
R
MeO
Xu 2011
Xu 2011
Xu 2011
Knochel 2011
R1
O
S
N
S O
R2
S O
N
S
R
F
O
Ar
R1
Wan 2011
Liao 2011
Chen & Xia 2013
Zeng 2016
S O
R
N
R'
This work
Figure 1. Some representative chiral sulfoxide/sulfinamide-olefin ligands and our designed N-aryl tert-
butanesulfinamide-olefin ligands
We noticed that chiral sulfoxide-olefin ligands commonly possessed one or two aromatic rings, which often
directly connect with sulfinyl groups. The reason probably is that the aromatic rings act as “chiral fences”, as
afford excellent chiral induction circumstances. To the best of our knowledge, there is no chiral sulfinamide-
olefin ligand with an aryl group directly connected to the nitrogen atom of the sulfinamide block. Therefore
we wonder what reactivity and enantioselectivity of catalytic reactions will be if an aromatic ring was
introduced on the nitrogen atom of the sulfinamide-olefin ligands (Figure 1).
Page 33
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
Our group has done a series of researches on chiral organic sulfur chemistry,24-27 especially we have
reported synthesis of a sulfinamide-olefin compound, namely, N-allyl-N-phenyl-tert-butanesulfinamide, via C-
N coupling reaction and SN2 nucleophilic substitution.28 As we know, sulfinamide-olefin compounds are
recently used as chiral ligand in highly enantioselective rhodium-catalyzed asymmetric 1,4-addition reaction of
arylboronic acids to ,-unsaturated carbonyl compounds,29-30 which has extensive applications in medicinal
synthesis and natural synthesis,31 and has achieved great progress.32-39 Furthermore, the C-N coupling reaction
products are seldom directly used as chiral ligands.40-41 Therefore we would like to explore the application of
the C-N coupling products chiral N-aryl tert-butanesulfinamide-olefin ligands in rhodium-catalyzed asymmetric
1,4-addition reaction of arylboronic acids to cyclic enones (Scheme 1).
O
S
N
Ar
R
O
n
O
n
L1-L4
ArB(OH)2
+
[RhCl(C2H4)2]2
Ar
K3PO4, dioxane, 40 oC, 3 h
1a, n=2
1b, n=1
3
2
Scheme 1. Rhodium-catalyzed asymmetric addition with N-aryl tert-butanesulfinamide-olefin ligands as chiral
ligands
Results and Discussion
We started our research by preparing chiral sulfinamide-olefin ligands (Scheme 2). Firstly, (R)-N-aryl-tert-
butanesulfinamides are prepared according to our group’s C-N coupling protocol (Scheme 2).28 It is a little pity
that slight racemization occurred during the C-N coupling reaction and N-phenyl-tert-butanesulfinamide with
97%ee was obtained.28 And then chiral N-allyl and N-cinnamyl N-aryl-tert-butanesulfinamides were
synthesized via SN2 nucleophilic substitution of N-aryl-tert-butanesulfinamide with allyl or cinnamyl bromide
(Scheme 2). To our delight, no any racemization occurred during the substitution.
Br
O
S
R'
Br
O
S O
Pd2(dba)3, tBuXPhos
S
NH
+
H2N
N
R'
NaOH, H2O, 90 oC, 20 h
N
a
H
, D
M
F
R
R
R
R = H, R' = H, L1
R = H, R' = Ph, L2
R = p-Ph, R' = H, L3
R = p-Ph, R' = Ph, L4
Scheme 2. Synthesis of chiral sulfinamide-olefin ligands N-allyl and N-cinnamyl-N-aryl-tert-butanesulfinamides
L1-L4.
With chiral N-allyl and N-cinnamyl N-aryl-tert-butanesulfinamides in hand, we chose Rh-catalyzed 1,4-
addition of phenylboronic acid to cyclohexenone as the model reaction to evaluate their catalytic performance
(Table 1).
Page 34
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
First of all, (R)-N-allyl-N-phenyl-tert-butanesulfinamide was used as the chiral ligand to examine the
reaction (Table 1). To our delight, moderate enantioselectivity (63%ee) was obtained for the ligand (Entry 1),
but it is much better than that (only 5%ee) of the reported ligand N-allyl-tert-butanesulfinamide without the
N-phenyl group.17 This result encouraged us to study further.
When allyl group was placed with cinnamyl group and thus (R)-N-cinnamyl-N-phenyl-tert-
butanesulfinamide (L2) was used as ligand, enantioselectivity and yield increased obviously (Entry 2). Ligands
(L3 and L4) with another phenyl substitution at the para-position of N-phenyl of ligands L1 and L2, but no
better results were obtained (Entries 3 and 4).
Table 1. Evaluation of chiral ligands L1 to L4 in Rh-catalyzed asymmetric 1,4-addition
O
B(OH)2
S O
O
N
R'
[RhCl(C2H4)2]2, ligand
K3PO4, dioxane, 40 oC
R
+
R = H, R' = H, L1
R = H, R' = Ph, L2
R = p-Ph, R' = H, L3
R = p-Ph, R' = Ph, L4
Tol
1a
2a
3a
Entry
Ligand
Yield (%)
ee (%)
63
89
59
83
1
2
3
4
L1
L2
L3
L4
75
96
66
64
All the reactions were carried out with 2-cyclohexenone (1.00 mmol), p-tolylboronic acid
(1.5 mmol), K3PO4 (0.5 mmol), [RhCl(C2H4)2]2 (0.015 mmol), 97%ee chiral ligand (0.035
o
mmol) in 1,4-dioxane (3.0 mL) at 40 C under argon for 3 h. The ee values were
determined by chiral HPLC.
Next, we examined bases and solvents in Rh-catalyzed 1,4-addition of phenylboronic acid to cyclohexenone
with L2 as chiral ligand (Table 2). The results shows that all of the tested solvents may carried out the addition
reaction, and 1,4-dioxane was the best one (Entries 1-4). The evaluation of the bases confirmed that K3PO4 is
the preferred base (Entries 4-10).
With the optimized conditions in hand, we examined various arylboronic acids to react with cyclohexenone
in the presence of [RhCl(C2H4)2]2 and chiral ligand L2 (Table 3). All of the reactions gave moderate to very high
yields (Entries 1-13).
Except that 4-fluorophenylboronic acid gave lower ee value (Entry 13), arylboronic acids all afforded
moderate to high enantioselectivities (Entries 1-12). Compared with phenylboronic acid (Entry 1), para-alkyl
substitution favored the addition reaction (Entries 2 and 5), and para-tert-butylphenylboronic acid afforded
the highest enantioselectivity of 93%ee (Entry 5). In view of the chiral ligand L2 only with 97%ee, this is an
excellent enantioselectivity. Among methyl-substituted arylboronic acids, para-methyl one gave the highest ee
value, and meta-methyl one achieved the lowest.
However, for chloro-substituted arylboronic acids, para-chlorophenylboronic acid exhibited poorer
enantioselectivity than the meta- and ortho-phenylboronic acids (Entries 9 vs 10-11). It seems that arylboronic
acids with para-electron-donating groups, such as alkyl, methoxyl, were more beneficial to enantioselectivity
Page 35
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
than that with para-electron-withdrawing groups, such as chloro, bromo, fluoro (Entries 2, 5, 8 vs. 9, 12, 13).
To our delight, halo and vinyl groups are compatible for this reaction (Entries 6 and 9-13).
Table 2. Screening of bases and solvents of Rh-catalyzed 1,4-addition of phenylboronic acid to cyclohexanone
O
B(OH)2
O
[Rh(C2H4)2Cl]2, L2
+
solvent, base, 40 oC, 3 h
1a
2b
3b
Entry
solvent
EtOH
DCE
base
K3PO4
K3PO4
K3PO4
K3PO4
KF
Yield (%)
43
46
41
90
Ee (%)b
70
71
55
93
1
2
3
4
5
6
THF
dioxane
dioxane
dioxane
75
71
68
67
KOH
All the reactions were carried out with cyclohexenone (1.00 mmol), phenylboronic acid (1.5
mmol), base (0.5 mmol), [RhCl(C2H4)2]2 (0.015 mmol), 97%ee L2 as chiral ligand (0.035 mmol) in
solvent (3.0 mL) at 40 oC under argon for 3 h. The ee was determined by chiral HPLC.
Table 3. Asymmetric 1,4-addition reaction of various arylboronic acids and cyclohexenone in the presence of
rhodium and chiral ligand L2
O
O
[RhCl(C2H4)2]2, L2
ArB(OH)2
+
K3PO4, dioxane, 40 oC
Ar
1a
2
3
Entry
1
2
Ar
Ph
4-MeC6H4
Product
3b
3a
Yield (%)
93
96
Ee (%)
83
89
3
3-MeC6H4
3c
90
75
4
5
2-MeC6H4
4-(CH3)3CC6H4
3d
3e
91
89
81
93
6
7
8
9
4-(CH2=CH)C6H4
2-naphthyl
4-MeOC6H4
4-ClC6H4
3f
3g
3h
3i
81
90
97
88
85
79
85
73
10
11
12
13
3-ClC6H4
2-ClC6H4
4-BrC6H4
4-FC6H4
3j
3k
3l
3m
81
83
83
70
83
83
83
55
All the reactions were carried out with cyclohexenone (1.00 mmol), arylboronic acid (1.5 mmol), base
(0.5 mmol), [RhCl(C2H4)2]2 (0.015 mmol), 97% ee L2 as chiral ligand (0.035 mmol) in solvent (3.0 mL)
at 40 oC under argon for 3 h. The ee was determined by chiral HPLC.
Page 36
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
After evaluation of cyclohexenone, we continued to investigate cyclopentenone to react with several
arylboronic acids in the presence of [RhCl(C2H4)2]2 and chiral ligand L2 (Table 4). Phenylboronic acid afforded
good yield and high enantioselectivity of 93%ee (Entry 1). Moreover, ortho-methylphenylboronic acid even
gave better result with 95%ee (Entry 3), which is a very high enantioselectivity in consideration of 97%ee L2 as
chiral ligand. Except 4-tert-butylphenylboronic acid with much poorer result, arylboronic acids with electron-
donating groups afforded good to high enantioselectivities (Entries 1-5). For 2-naphthylboronic acid,
cyclopentenone gave poorer result cyclohexenone (Table 4, entry 6 vs. Table 3, entry 7).
Table 4. Asymmetric 1,4-addition reaction of various arylboronic acids and cyclopentenone in the presence of
rhodium and chiral ligand L2
O
O
[RhCl(C2H4)2]2, L2
ArB(OH)2
+
Ar
K3PO4, dioxane, 40 oC
1b
2
3
Entry
Ar
Ph
Product
3n
3o
3p
3q
Yield (%)
82
90
86
77
Ee (%)
93
83
95
55
1
2
3
4
5
6
4-MeC6H4
2-MeC6H4
4-(CH3)3CC6H4
4-MeOC6H4
2-Naphthyl
3r
3s
89
80
83
55
All the reactions were carried out with cyclopentenone (1.00 mmol), arylboronic acid (1.5 mmol),
base (0.5 mmol), [RhCl(C2H4)2]2 (0.015 mmol), 97%ee L2 as chiral ligand (0.035 mmol) in solvent (3.0
mL) at 40 oC under argon for 3 h. The ee was determined by chiral HPLC.
According to the structure of (R)-N-cinnamyl-N-phenyl-tert-butanesulfinamide (L2) and the former study on
the rhodium-catalyzed 1,4-addition mechanism,33,38-39 we propose a Rh-catalyzed enantioselective 1,4-
addition model during the transition state. There will exist a most stable conformation with Si face selectivity,
which produce S form addition product (S)-3-phenylcyclohexanone (Figure 2). While there is large repulsion
between cinnamyl’s phenyl group and cyclohexenone perpendicular coordination to rhodium in the Re face
transition state, so (R) form product is the minor component (Figure 2). The model well explains high S form
enantioselectivity when (R)-L2 is used.
Page 37
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
N
O
O
S
(S)
Rh
O
(major)
Si face (favorable)
O
N
O
S
(R)
Rh
O
(minor)
Re face (unfavorable)
Figure 2. Enantioselective model for the addition to 2-cyclohexenone (1a) catalyzed by the Rh(I)/(R)-L2
complex.
Conclusions
We have developed a new type of chiral N-aryl tert-butanesulfinamide-olefin ligand as chiral ligands in
rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to cyclic enones. The chiral ligands are readily
synthesized via C-N coupling reaction and nucleophilic substitution, but only 97%ee chiral ligands were
obtained due to the slight racemization during the C-N coupling reaction. Given that chiral ligands with 97%ee
produced 1,4-addition products up to 95%ee, N-aryl tert-butanesulfinamide-olefin ligands demonstrates fairly
high chiral induction ability in the rhodium-catalyzed asymmetric 1,4-addition.
Experimental Section
General. All chemicals were purchased from Aldrich, Aladdin, Alfa Aesar, Adamas, and Kelong Chemical
Company and used as received. Petroleum ether (PE) refers to the fraction boiling in the 60–90 °C range. All
o
reactions were carried out under argon atmosphere. All glassware used was dried in electric oven at 120 C.
1
All new compounds were characterized by H NMR, 13C NMR, HR-MS and IR spectroscopy, unless otherwise
mentioned. Nuclear magnetic resonance spectra were recorded on a 300MHz instrument or 400 MHz
1
instrument. All H NMR experiments are reported in δ units, parts per million (ppm), and were measured
relative to the signals for residual chloroform (7.26 ppm), DMSO (2.50 ppm) or acetone (2.05 ppm) in the
deuterated solvent, unless otherwise stated. All 13C NMR spectra are reported in ppm relative to
deuterochloroform (77.2 ppm), DMSO-d6 (39.5 ppm) or acetone-d6 (206.7 ppm for C=O) unless otherwise
stated, and all were obtained with 1H decoupling. All IR spectra were taken on an infrared spectrometer. High-
resolution mass spectra are recorded on an LCMS-IT-TOF instrument. Chiral HPLC analyses were performed on
Page 38
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
a Shimadzu liquid chromatography with a Chiralcel OD-H, AD-H, AS-H chiral column (4.6 mm × 250 mm × 5
μm). All rotation data are recorded on an auto rotation (Na D line, cell long 10 cm, λ 589 nm).
Procedure for synthesis of chiral ligands L1 to L4. An oven-dried round-bottom flask with a magnetic stir bar
and fitted with a rubber septum, was charged with (R)-tert-butanesulfinamide (13.0 mmol), Pd2(dba)3 (0.26
mmol), tBu-XPhos (0.45 mmol), NaOH (26 mmol), bromobenzene (10.0 mmol), toluene (20 mL), and degassed
water (3.0 mL).The vessel was evacuated and backfilled with argon for three times. The solution was stirred at
o
90 C for 20 h. when cooled to room temperature, quenched by water, and extracted with ethyl acetate (35
mL) for three times. The combined organic layer was dried over anhydrous MgSO4. The filtrate was condensed
under vacuum. The resulting residual was purified with silica gel column chromatography with a solution of
petroleum ether and ethyl acetate (5:1 (v:v)) as an eluent to afford N-aryl tert-butanesulfinamide.
To an oven-dry round-bottom flask with a magnetic stir bar was added N-phenyl (R)-tert-butanesulfinamide
(4.0 mmol), 60% NaH (8 mmol), and THF (15 mL). The vessel was evacuated and backfilled with argon for three
times. Then the mixture was stirred in an ice water bath for 1 h, and then added cinnamyl bromide (1.2 mmol)
by syringe to the flask. The reaction mixture was stirred overnight. Then quenched by saturated NH4Cl
solution, the reaction mixture was extracted with ethyl acetate (20 mL) three times. The combined organic
layer was washed with saturated NaCl solution and then dried over anhydrous MgSO4. The filtrate was
condensed under vacuum. The residual was purified with a silica gel column chromatography with a mixed
solution of petroleum ether and ethyl acetate (5:1(v:v)) as an eluent to afford (R)-N-cinnamyl-2-methyl-N-
phenylpropane-2-sulfinamide (L2).
The same synthetic method as L2 was adopted for synthesis of chiral ligands L1, L3, L4.
(R)-N-cinnamyl-2-methyl-N-phenylpropane-2-sulfinamide (L2). White solid. Yield: 25.3 mg (81%). mp 94-97
oC. []D20.5 +105°(c 0.21, CH2Cl2). 1H NMR (400 MHz, DMSO-d6) δ 7.43 – 7.39 (m, 2H), 7.35 – 7.21 (m, 4H), 7.07
(dd, J 16.2, 8.0 Hz, 2H), 6.58 (dt, J 14.4, 7.6 Hz, 4H), 6.36 (dt, J 16.0, 5.6 Hz, 1H), 3.89 – 3.81 (m, 2H), 1.05 (s,
7H). 13C NMR (101 MHz, DMSO): δ 137.19 (s), 136.68 (s), 132.66 (s), 130.63 (s), 129.43 (d, J 17.0 Hz), 129.08
(s), 128.42 (s), 128.07 (s), 127.78 (s), 126.60 (d, J 6.9 Hz), 126.34 (s), 123.67 (s), 121.68 (s), 59.99 (s), 55.73 (s),
23.44 (s), 21.51 (s). IR (KBr), ν (cm-1): 3056, 3025, 2936, 2593, 2154, 1927, 1702, 1655, 1592, 1472, 1363, 1298,
+
1246, 1176, 1075, 968, 852, 781. ESI-MS (positive mode), m/z 336 [M + Na] . HR-MS (ESI-TOF) m/z calcd for
C19H23NNaOS [M+Na+] 336.1393; found 336.1379. Chiral HPLC: Chiralcel OD-H Column (Particle Size: 5 μm,
dimensions: 4.6 mm×250 mm); detected at 254 nm; n-hexane: 2-propanol 95:5; flow rate: 0.7 ml/min;
retention time: 12.7 min (minor), 15.2 min (major). Measured ee value 97 %.
(R)-N-([1,1'-biphenyl]-4-yl)-N-allyl-2-methylpropane-2-sulfinamide (L3). White solid. Yield: 21.0 mg (80%). mp
72-75 oC. []D21.0 +88.98° (c 0.12, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.59 – 7.51 (m, 4H), 7.45 – 7.40 (m, 2H),
7.32 (ddt, J 9.5, 8.2, 4.1 Hz, 1H), 7.25 – 7.21 (m, 2H), 5.88 – 5.76 (m, 1H), 5.25 – 5.12 (m, 2H), 4.38 – 4.25 (m,
1H), 4.14 – 4.00 (m, 1H), 1.26 (d, J 11.7 Hz, 9H). 13C NMR (101 MHz, DMSO): δ 141.01 (s), 129.29 (d, J 18.4 Hz),
127.60 (s), 126.74 (s), 126.22 (s), 125.89 (s), 113.35 (s), 60.09 (s), 55.73 (s), 23.32 (s), 21.50 (s). IR (KBr), ν (cm-
1): 3417, 3050, 2959, 1601, 1519, 1484, 1450, 1364, 1295, 1251, 1204, 1142, 1091, 1055, 995, 918, 827, 757,
692. ESI-MS (positive mode), m/z 336 [M + Na] +. HR-MS (ESI-TOF) m/z calcd for C19H23NOS [M+Na+] 336.1393;
found 336.1405. Chiral HPLC: Chiralcel OD-H Column (Particle Size: 5 μm, dimensions: 4.6 mm×250 mm);
detected at 254 nm; n-hexane: 2-propanol 95:5; flow rate: 0.7 ml/min; retention time: 5.5 min (minor), 10.6
min (major).
(R)-N-([1,1'-biphenyl]-4-yl)-N-cinnamyl-2-methylpropane-2-sulfinamide (L4). Yellow solid. Yield: 23.3 mg
(81%). mp 116-119 oC. []D21.2 +116.20° (c 0.14, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.59 – 7.49 (m, 4H), 7.44
– 7.38 (m, 2H), 7.30 (ddd, J 8.8, 7.4, 2.0 Hz, 6H), 7.21 (ddd, J 6.8, 3.8, 1.6 Hz, 1H), 6.51 (d, J 16.0 Hz, 1H), 6.19
Page 39
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
(dt, J 16.0, 5.9 Hz, 1H), 4.45 (ddd, J 16.8, 6.2, 1.5 Hz, 1H), 4.24 (ddd, J 16.8, 5.6, 1.5 Hz, 1H), 1.28 (d, J 11.9 Hz,
8H). 13C NMR (101 MHz, DMSO): δ 144.88 (s), 139.88 (s), 137.18 (s), 136.66 (s), 135.07 (s), 132.66 (s), 130.58
(s), 129.46 – 128.95 (m), 128.42 (s), 128.09 (s), 127.66 (t, J 13.6 Hz), 126.86 – 126.49 (m), 126.27 (d, J 18.1 Hz),
125.86 (s), 121.46 (s), 113.17 (s), 60.17 (s), 55.73 (s), 23.44 (s), 21.51 (s). IR (KBr), ν (cm-1): 3432, 3041, 2938,
1602, 1519, 1486, 1364, 1305, 1254, 1203, 1083, 1050, 962, 845, 733, 694. ESI-MS (positive mode), m/z 412
([M + Li]+). HR-MS (ESI-TOF) m/z calcd for C25H27NNaOS [M+Na+] 412.1706; found 412.1715. Chiral HPLC:
Chiralcel OD-H Column (Particle Size: 5 μm, dimensions: 4.6 mm×250 mm); detected at 254 nm; n-hexane: 2-
propanol 95:5; flow rate: 0.7 ml/min; retention time: 15.3 min (minor), 20.3 min (major).
Procedure of rhodium-catalyzed 1,4-addition reaction. To an oven-dry test tube with a ground joint neck with
a magnetic stir bar were added enone (1.00 mmol), arylboronic acid (1.5 mmol), [RhCl(C2H4)2]2 (0.015 mmol,
1.32 mg), Ligand (0.035 mmol) in 1,4-dioxane (3.0 mL). The vessel was evacuated and backfilled with argon for
o
three times. The solution was stirred at 40 C for 30 min, and then aqueous K3PO4 (0.5 mmol, 106 mg) was
o
added by syringe to the flask. After being stirred at 40 C for 3 h, the reaction mixture was then cooled to
room temperature, quenched by water, and extracted with ethyl acetate (15 mL) for three times. The
combined organic layer was dried over anhydrous MgSO4. The filtrate was condensed in vacuum. The residual
was purified with silica gel column chromatography with a solution of petroleum ether and ethyl acetate as an
eluent to afford the product. The ee value was determined by chiral HPLC.
Acknowledgements
We thank the Ministry of Science and Technology of the People’s Republic of China (No. 2013DFA21690), the
National Natural Science Foundation of China (No. 21372034), the Department of Science and Technology of
Sichuan Province (No. 2016HH0074), the Education Department of Sichuan Province (No. 16ZA0084), Chengdu
Science and Technology Bureau (No. 2015-HM01-00362-SF) and the State Key Laboratory of Geohazard
Prevention and Geoenvironment Protection Independent Research Project (No. SKLGP2016Z004).
Supplementary Material
Full experimental details, 1H and 13C NMR spectra.
References
1.
2.
3.
4.
5.
Robak, M. T.; Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600-3740.
http://dx.doi.org/10.1021/cr900382t
Trost, B. M.; Rao, M. Angew Chem. Int. Ed. 2015, 54, 5026–5043.
http://dx.doi.org/10.1002/anie.201411073
Zeng, Q. Prog. Chem. 2007, 19, 745-750.
http://www.progchem.ac.cn/EN/Y2007/V19/I05/745
Zeng, Q.; Gao, S.; Chelashaw, A. K. Mini-Rev. Org. Chem. 2013, 10, 198-206.
http://dx.doi.org/10.2174/1570193X11310020008v
Ferreira, F.; Botuha, C. Chemla F.; Pérez-Luna, A. Chem. Soc. Rev. 2009, 38, 1162-1186.
Page 40
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
http://dx.doi.org/10.1039/B809772K
Carreńo, M. C.; Hernández-Torres, G.; Ribagorda, M.; Urbano, A. Chem. Commun. 2009, 6129-6144.
http://dx.doi.org/10.1039/B908043K
James, B. R.; McMillan, R. S.; Reimer, K. J. J. Mol. Catal. 1976, 1, 439-441.
http://dx.doi.org/10.1016/0304-5102(76)85006-7
Mariz, R.; Luan, X. J.; Gatti, M.; Linden, A.; Dorta, R. J. Am. Chem. Soc. 2008, 130, 2172-2173.
http://dx.doi.org/10.1021/ja710665q
6.
7.
8.
9.
Bürgi, J.; Mariz, R.; Gatti, M.; Drinkel, E.; Luan, X. J.; Blumentritt, S.; Linden, A.; Dorta, R. Angew. Chem.,
Int. Ed. 2009, 48, 2768-2771.
http://dx.doi.org/10.1002/anie.200900429
10. Chen, J.; Chen, J. M.; Lang, F.; Zhang, X. Y.; Cun, L. F.; Zhu, J.; Deng, J. G.; Liao, J. J. Am. Chem. Soc. 2010,
132, 4552-4553.
http://dx.doi.org/10.1021/ja1005477
11. Owens, T. D.; Hollander, F. J.; Oliver, A. G.; Ellman, J. A. J. Am. Chem. Soc. 2001, 123, 1539-1540.
http://dx.doi.org/10.1021/ja005635c
12. Li, Y.; Xu, M.-H. Chem. Commun. 2014, 50, 3771-3782.
http://dx.doi.org/10.1039/C3CC49431D
13. Revu, O.; Uphade, M. B.; Prasad, K. R. Tetrahedron 2016, 72, 5355-5362.
http://dx.doi.org/10.1016/j.tet.2016.07.024
14. Thaler, T.; Guo, L.-N.; Steib, A. K.; Raducan, M.; Karaghiosoff, K.; Mayer, P.; Knochel, P. Org. Lett. 2011,
13, 3182-3185.
http://dx.doi.org/10.1021/ol200841x
15. Wang, H.; Jiang, T.; Xu, M. H. J. Am. Chem. Soc. 2013, 135, 971-974.
http://dx.doi.org/10.1021/ja3110818
16. Jin, S. S.; Wang, H.; Xu, M. H. Chem. Commun. 2011, 47, 7230-7232.
http://dx.doi.org/10.1039/C1CC12322J
17. Jin, S. S.; Wang, H.; Zhu, T. S.; Xu, M. H. Org. Biomol. Chem. 2012, 10, 1764-1768.
http://dx.doi.org/10.1039/c2ob06723d
18. Feng, X.; Wang, Y.; Wei, B.; Yang, J.; Du, H. Org. Lett. 2011, 13, 3300-3303.
http://dx.doi.org/10.1021/ol2009494
19. Feng, X. Q.; Nie, Y. Z.; Yang, J.; Du, H. F. Org. Lett. 2012, 14, 624-627.
http://dx.doi.org/10.1021/ol203238j
20. Chen, G.; Gui, J.; Li, L.; Liao, J. Angew. Chem., Int. Ed. 2011, 50, 7681-7685.
http://dx.doi.org/10.1002/anie.201102586
21. Du, L.; Cao, P.; Xing, J. W.; Lou, Y. Z.; Jiang, L. Y.; Li, L. C.; Liao, J. Angew. Chem., Int. Ed. 2013, 52, 4207-
4211.
http://dx.doi.org/10.1002/anie.201209485
22. Xue, F.; Li, X.; Wan, B. J. Org. Chem. 2011, 76, 7256-7262.
http://dx.doi.org/10.1021/jo2011472
23. Chen, Q.; Chen, C.; Guo, F.; Xia, W. Chem. Commun. 2013, 49, 6433-6435.
http://dx.doi.org/10.1039/c3cc42673d
24. Wen, Q.; Zhang, L.; Xiong, J.; Zeng, Q. Eur. J. Org. Chem. 2016, 2016, 5360-5364.
http://dx.doi.org/10.1002/ejoc.201601206
25. Zeng, Q.; Wang, H.; Wang, T.; Cai, Y.; Weng, W.; Zhao, Y. Adv. Synth. Catal. 2005, 347, 1933-1936.
Page 41
©ARKAT USA, Inc

Arkivoc 2017, v, 32-42
Yuan, S. et al.
http://dx.doi.org/10.1002/adsc.200505259
26. Zeng, Q.; Wang, H.; Weng, W.; Lin, W.; Gao, Y.; Huang, X.; Zhao, Y. New J. Chem. 2005, 29, 1125-1127.
http://dx.doi.org/10.1039/B505237H
27. Zeng, Q.-L.; Tang, H.-Y.; Zhang, S.; Liu, J.-C. Chin. J. Chem. 2008, 26, 1435-1439.
http://dx.doi.org/10.1002/cjoc.200890261
28. Sun, X.; Tu, X.; Dai, C.; Zhang, X.; Zhang, B.; Zeng, Q. J. Org. Chem. 2012, 77, 4454–4459.
http://dx.doi.org/10.1021/jo3003584
29. Heravi, M. M.; Dehghani, M.; Zadsirjanm V. Tetrahedron: Asymm. 2016, 27, 513–588.
http://dx.doi.org/10.1016/j.tetasy.2016.05.004
30. Gandia, V. R.; Lua, Y.; Hayashia, T. Tetrahedron: Asymm. 2015, 26, 679–682.
http://dx.doi.org/10.1016/j.tetasy.2016.05.004
31. Jean, M.; Casanova, B.; Gnoatto, S.; van de Weghe, P. Org. Biomol. Chem. 2015, 13, 9168-9175.
http://dx.doi.org/10.1039/c5ob01402f
32. Heravi, M. M.; Dehghani, M.; Zadsirjan, V. Tetrahedron: Asymm. 2016, 27, 513–588.
http://dx.doi.org/10.1016/j.tetasy.2016.05.004
33. Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829-2844.
http://dx.doi.org/10.1021/cr020022z
34. Holder, J. C.; Goodman, E. D.; Kikushima, K.; Gatti, M.; Marziale, A. N.; Stoltz, B. M. Tetrahedron 2015,
71, 5781-5792.
http://dx.doi.org/10.1016/j.tet.2014.11.048
35. Qin, H.-L.; Chen, X.-Q.; Huang, Y.-Z.; Kantchev, E. A. B. Chem. Eur. J. 2014, 20, 12982-12987.
http://dx.doi.org/10.1002/chem.201402451
36. Wang, F.; Chen, F.; Qu, M.; Li, T.; Liu, Y.; Shi, M. Chem. Comm. 2013, 49, 3360-3362.
http://dx.doi.org/10.1039/C3CC00295K
37. Yamamoto, Y.; Kurihara, K.; Takahashi, Y.; Miyaura, N. Molecules 2013, 18, 14-26.
http://dx.doi.org/10.3390/molecules18010014
38. Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052-5058.
http://dx.doi.org/10.1021/ja012711i
39. Hayashi, T.; K. Ueyama, N. Tokunaga, K. Yoshida, J. Am. Chem. Soc. 2003, 125, 11508-11509.
http://dx.doi.org/10.1021/ja037367z
40. Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27–50.
http://dx.doi.org/10.1039/C0SC00331J
41. Hartwig, J. F. Nature, 2008, 455, 318-322.
http://dx.doi.org/10.1038/nature07369
Page 42
©ARKAT USA, Inc