Chiral sulfinyl-based olefin ligands for rhodium-catalysed asymmetric conjugate addition of arylboronic acids to cyanoalkenes

Article abstract of DOI:10.3184/174751918X15287224792440

A rhodium/sulfinyl-based olefin ligand-catalysed asymmetric conjugate addition of arylboronic acids to cyanoalkenes without activation groups has been developed, where p-tolylsulfinyl-functionalised olefin ligands have been shown to be effective and with moderate enantioselectivities. This is the first example of applying chiral sulfinyl-based olefin ligands in the catalytic asymmetric addition to cyanoalkenes.

Full text of DOI:10.3184/174751918X15287224792440

300 RESEARCH PAPER
VOL. 42 JUNE, 300–304
JOURNAL OF CHEMICAL RESEARCH 2018
Chiral sulfinyl-based olefin ligands for rhodium-catalysed asymmetric
conjugate addition of arylboronic acids to cyanoalkenes
Feng Xue, Yong Zhu and Xiaolei Qi
Key Laboratory of Functional Organic Molecules of Xinxiang City, Henan Province, College of Chemistry and Chemical Engineering, Henan Institute of Science
and Technology, Xinxiang Henan 453002, P.R. China
A rhodium/sulfinyl-based olefin ligand-catalysed asymmetric conjugate addition of arylboronic acids to cyanoalkenes without activation
groups has been developed, where p-tolylsulfinyl-functionalised olefin ligands have been shown to be effective and with moderate
enantioselectivities. This is the first example of applying chiral sulfinyl-based olefin ligands in the catalytic asymmetric addition to
cyanoalkenes.
Keywords: chiral sulfinyl-based olefin ligands, cyanoalkenes, conjugate addition, asymmetric catalysis
The chiral 3,3-disubstituted propionitriles, which can be readily
transformed into other useful functionalities, such as amine,
aldehyde and carboxylic acid groups, are versatile synthetic
intermediates in many biologically active compounds and
pharmaceutical agents, such as ar-turmerone,1 tolterodine,2
indatraline,3 vabicaserin4 and florhydral.5
development of another enantioselective preparation method for
such compounds remains highly desirable.
In recent years, the Rh-catalysed asymmetric conjugate
addition of organoboronic acids to electron-deficient olefins,
pioneered by Carreira, Hayashi and co-workers, has been
established as one of the most powerful and convenient
tools for the enantioselective synthesis of β-substituted
functionalised compounds with chiral olefin ligands.14–16
Therefore, the most direct and attractive method for obtaining
chiral 3,3-diarylpropanenitriles would utilise the asymmetric
1,4-addition reaction of cyanoalkenes and arylboronic acids.
So far, however, there have been only two examples involving
asymmetric conjugate addition of α,β-unsaturated nitriles,
where only chiral diene and N-heterocyclic carbene (NHC)
ligands were applied.17,18 Moreover, high enantioselectivities
could only be achieved for substrates with activation groups as an
assistant coordinating group, such as an ester group attached to
the C=C bond. There have been no reports so far of other ligands
applied in the asymmetric addition of α,β-unsaturated nitriles,
especially for substrates without activation groups. In recent
years, chiral sulfinyl-based olefin ligands (SOLs) have been
successfully explored and applied in a range of Rh-catalysed
asymmetric transformations, which have obvious advantages
over some conventional chiral ligands in terms of activity and
Due to their importance in chemical synthesis, great attention
has been drawn to the development of enantioselective synthetic
protocols. A predominant route would be the enantioselective
hydrogenation of α,β-unsaturated nitriles. However, because of
the linear geometry of the nitrile group and the strong binding
affinity of the nitrile group to transition metal complexes, reports
of efficient catalyst systems for the asymmetric hydrogenation
of α,β-unsaturated nitriles remained very limited.6–8 Moreover,
α,β-unsaturated nitriles were restricted to β-alkyl-β-aryl
substituted alkenyl nitriles only.9,10 It was demonstrated that it
was more difficult for β,β-diaryl-substituted alkenyl substrates
to undergo asymmetric reductions than for other alkenyl
substrates, mainly because low enantioselectivity is generally
expected from the small steric difference between two aryl
substituents and because steric congestion of the aryl groups
influences the activity of the catalysts. Thus, until now, there
have been only a few reports of the enantioselective conjugate
reduction of 3,3-diaryl-substituted propionitriles,11–13 and so the
Previous work
:
N
C
N
C
[H]
R
R1
R1
*
R
N
N
C
ROOC
R
C
N
ROOC
R
C
NaCN,LiI
DMF
Rh/(R,R)-Ph-bod*
R1B(OH)2
+
R1
R
R1
*
*
H
This work
R
:
N
C
*
Rh
L
/SO
N
C
R1B(OH)2
+
*
R
R1
SOL* sulfinyl-based olefin ligands
:
Scheme 1 Synthesis of 3,3-diarylpropanenitriles.
* Correspondent. E-mail: fxuehist@sina.com

JOURNAL OF CHEMICAL RESEARCH 2018 301
selectivity.19–23 In spite of recent significant advances, there has
still been no report of the use of chiral SOLs in the asymmetric
conjugate addition of α,β-unsaturated nitriles. Thus, herein we
report on our explorations of these rhodium/SOL complexes in
the asymmetric addition of arylboronic acids to cyanoalkenes
without activation groups (Scheme 1).
increase in reactivity or enantioselectivity was observed (entry
11). Moreover, a further screen of other solvents also showed no
better results (entries 12–15).
With the p-tolylsulfiny moiety established, ligands L1e–j with
alkene moieties containing substituents with different steric
and electronic natures were further synthesised and explored
(Scheme 2). When ligand L1e was employed, which possessed
an electron-donating p-methoxy group on the terminal benzene
ring, both the catalytic reactivity and the enantioselectivity
increased (43% yield and 50% ee, respectively). The use of
ligand 1f with two methoxy groups on its terminal benzene ring
gave a higher ee value (58% ee), whereas the 2,4,6-trimethoxy
analogue 1g gave a lower ee value (40% ee). When ligands
1h–j with electron-withdrawing groups were screened on
the para-position of the benzene ring, lower reactivities and
enantioselectivities were obtained.
Next, we examined the substrate scope under the optimised
conditions (Table 2). A range of arylboronic acids with varying
electronic and steric demands were reacted smoothly with
cyanoalkenes to give the corresponding addition products
with moderate enantioselectivities. In general, the electronic
properties of the substituent on the substrates did not
significantly affect the reaction stereoselectivity significantly.
However, the steric hindrance of the substituents on the
aromatic ring had an impact on the activity, as in the reaction of
1-naphthylboronic acid and 2-naphthylboronic acid (entries 6,7
Results and discussion
We began with the Rh-catalysed conjugate addition of trans-
cinnamonitrile 1a with p-anisylboronic acid 2a in the presence
of SOLs L1–3 (Table 1). Initially, the reaction proceeded in the
presence of 1.5 mol% [RhCl(C2H4)2]2 and 3.3 mol% L1a, L2 or
L3 bearing the tert-butylsulfinyl moiety in Et3N/toluene, giving
a trace amount of desired product (entries 1–3). Next, ligands
L1b–d bearing different sulfinyl moieties were screened: ligand
L1b with the p-tolylsulfiny moiety gave a 35% isolated yield of
the expected product 3a with 40% ee (entry 4), whereas ligand
L1c bearing the p-methoxybenzenesulfinyl moiety and L1d
bearing the 2-methoxy-1-naphthylsulfinyl moiety gave 32% ee
(entry 5) and 37% ee (entry 6), respectively. When the reaction
proceeded in aqueous 0.75 M KOH/toluene, ligand L1b gave a
higher enantioselectivity of 46% ee (entry 7). A survey of other
inorganic bases, such as KF, K2CO3 and K3PO4,did not improve
the enantioselectivity of the reaction (entries 8–10). When
the reaction was conducted in aqueous KHF2/toluene, where
potassium aryltrifluoroborate can be generated in situ, no
Table 1 Screening of ligands, solvents and bases in the conjugate addition reactiona
N
C
[RhCl(C2H4)2]2 (1.5 mol %)
B(OH)2
L*(3.3 mol %)
*
+
N
C
Ph
,
solvent base
MeO
OMe
1a
3a
2a
O
S
O
O
S
N
S
1
N
H
a
R
: R = t-Bu
2
b
: R = p-Tol
3
c
: R = p-MeOC6H4
4
Ph
L1
d:
L
3
Ph
R = 2-MeO-1-naphthyl
L2
Ph
Entry
1
2
3
4
5
6
7
8
Ligand
L1a
L2
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
Base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
KOH (0.75 M)
KF (1.5 M)
K2CO3 (1.5 M)
K3PO4 (1.5 M)
KHF2 (1.5 M)
KOH (0.75 M)
KOH (0.75 M)
KOH (0.75 M)
KOH (0.75 M)
Yieldb (%)
Trace
Trace
Trace
35
30
34
40
35
41
36
33
35
43
41
Trace
eec (%)
n.d.d
n.d.d
n.d.d
40
L3
L1b
L1c
L1d
L1b
L1b
L1b
L1b
L1b
L1b
L1b
L1b
L1b
32
37
46
40
35
41
42
41
9
10
11
12
13
14
15
Dioxane
CH2Cl2
CH3OH
34
40
n.d.d
aThe reaction was carried out with trans-cinnamonitrile (0.30 mmol), p-anisylboronic acid (0.60 mmol), [RhCl(C2H4)2]2 (0.0045 mmol), ligand (0.0099 mmol, 1.1 equiv. to Rh) and 0.75 M
aqueous KOH (0.20 mL) in toluene (2.0 mL) at 80 °C for 12 h.
bYield based on trans-cinnamonitrile.
cDetermined by HPLC analysis.
dNot determined.

302 JOURNAL OF CHEMICAL RESEARCH 2018
N
C
[RhCl(C2H4)2]2 (1.5 mol %)
L*(3.3 mol %)
B(OH)2
*
+
N
C
Ph
.
,
toluene 0 75 M KOH
MeO
OMe
1a
3a
2a
O
S
L1e
: Ar =4-MeOC6H4, 43%, 50% ee
-
L1f
: Ar =3,4-(MeO)2C6H3, 45%, 58% ee
o
p T l
L1g
L1h
: Ar =2,4,6-(MeO)3C6H2, 30%, 40% ee
: Ar =4-FC6H4, 43%, 25% ee
L1i
: Ar =4-ClC6H4, 42%, 29% ee
L1
Ar
L1j:
Ar =4-CF3C6H4, 45%, 35% ee
Scheme 2 Further ligand screen.
Table 2 Substrate scope in the conjugate addition reactiona
[RhCl(C2H4)2]2 (1.5 mol %)
Ar2
1f
L *(3.3 mol %)
Ar2B(OH)2
N
C
+
Ar1
N
C
Ar1
*
toluene, 0.75 M KOH
1
2
3
Entry
1
2
3
4
5
6
7
8
Ar1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ar2
Yieldb (%)
eec (%)
58(S)
45(S)
46(S)
46(S)
48(S)
59(S)
56(S)
43(S)
47(S)
46(S)
50
4-MeOC6H4
2-MeOC6H4
3-MeOC6H4
2-MeC6H4
3-MeC6H4
1-Naphthyl
2-Naphthyl
4-FC6H4
45 (3a)
43 (3b)
44 (3c)
48 (3d)
51 (3e)
45 (3f)
53 (3g)
54 (3h)
57 (3i)
55 (3j)
42 (3k)
44 (3l)
44 (3m)
52 (3n)
9
4-ClC6H4
10
11
12
13
14
4-CF3C6H4
2-MeOC6H4
2-MeC6H4
1-Naphthyl
2-Naphthyl
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
57
52
59
aThe reaction was carried out with cyanoalkenes (0.30 mmol), arylboronic acid (0.60 mmol), [RhCl(C2H4)2]2 (0.0045 mmol), ligand 1f (0.0099 mmol, 1.1 equiv. to Rh) and 0.75 M aqueous
KOH (0.20 mL) in toluene (2.0 mL) at 80 °C for 12 h.
bYield based on cyanoalkenes.
cDetermined by HPLC analysis.
Experimental
and entries 13,14). Moreover, in the case of arylboronic acids
with electron-withdrawing groups, higher reactivities were
obtained (entries 8–10).
All reactions were carried out under an atmosphere of nitrogen using
standard Schlenk techniques, unless otherwise noted. Melting points
were determined on a Mettler FP5 apparatus and are uncorrected. NMR
spectra were recorded on a Bruker DRX 400 MHz spectrometer. Optical
rotations were measured with a JASCO P-1020 automatic polarimeter.
High resolution mass spectra (HRMS) were recorded on an Applied
Biosystems Mariner System 5303. 1H NMR chemical shifts were recorded
in parts per million (ppm) downfield from tetramethylsilane (TMS)
as internal standard. 13C NMR chemical shifts were recorded in ppm
downfield using the central peak of deuterochloroform (CDCl3, 77.2 ppm)
as internal standard. Coupling constants (J) are reported in hertz (Hz) and
refer to apparent peak multiplications. Flash column chromatography was
performed on silica gel (300–400 mesh). Thin-layer chromatographic
(TLC) analysis was performed using glass-backed plates coated with
0.2 mm silica. Commercially available reagents were used throughout
without further purification, other than those procedures detailed below.
THF, Et2O and toluene were distilled over sodium benzophenone ketyl
under nitrogen. Methylene chloride (CH2Cl2) was distilled over calcium
hydride. Arylboronic acids were recrystallised from water.
Conclusions
In summary, we have developed a catalytic system for
the rhodium-catalysed addition of arylboronic acids to
cyanoalkenes without activation groups, in which chiral
sulfinyl-based olefin ligands were applied to give moderate
yields and moderate enantioselectivities. Ligands bearing the
p-tolylsulfinyl group were shown to be more effective than
those bearing tert-butylsulfinyl, p-methoxybenzenesulfinyl or
2-methoxy-1-naphthylsulfinyl groups. Moreover, ligands with
electron-donating groups positioned on the terminal benzene
ring of the alkene moiety were more beneficial. This study sets
the stage for further exploration of these recently developed
ligands in other asymmetric transformations and for the
development of other kinds of unique olefin ligands. Further
studies are underway and will be reported in due course.

JOURNAL OF CHEMICAL RESEARCH 2018 303
Preparation of ligands L1–3; general procedure
1H), 7.53–7.49 (m, 1H), 7.48–7.43 (m, 4H), 7.39 (d, J = 8.5 Hz, 2H),
7.34 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 16.0 Hz,
1H), 2.30 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 143.1, 142.1,
141.6, 135.8, 134.2, 131.3, 130.0, 128.8, 128.1, 126.2, 125.4, 124.9,
123.8, 21.4; HRMS (ESI, m/z): Calcd for C21H17ClOSNa [M+Na]+:
375.0586; found: 375.0591.
Ligands L1–3 were prepared according to literature procedures;22 the
analytical data for L1a–d and L1h were identical in all respects to
those previously reported.22
(S,E) -2-Methyl-N- {2-[(E) -styryl]benzylidene}propane-2-
sulfinamide L2
(S,E)-1-(p-Tolylsulfinyl)-2-(4-(trifluoromethyl)styryl)benzene L1j:
White solid; 62% yield; m.p. 91–93 °C; [α]2ꢀ0 = −152.3 (c = 1.0,
A solution of (E)-2-styrylbenzaldehyde (624 mg, 3 mmol), (S)-tert-
butanesulfinamide (399 mg, 3.3 mmol) and Ti(OEt)4 (1.2 mL, 6 mmol)
was refluxed in tetrahydrofuran (THF) for 5 h. The resulting mixture
was quenched with cold saturated aqueous NH4Cl solution. After
extracting with CH2Cl2, the organic layer was washed with brine, dried
over Na2SO4 and concentrated in vacuo. Purification by
chromatography gave L2 as a white solid; 89% yield; m.p. 104–105 °C;
1
CHCl3); H NMR (500 MHz, CDCl3): δ (ppm) 8.02–8.00 (m, 1H),
7.66–7.62 (m, 4H), 7.56 (d, J = 8.0 Hz, 2H), 7.49–7.44 (m, 4H), 7.18 (d,
J = 8.0 Hz, 2H), 6.98 (d, J = 16.0 Hz, 1H), 2.30 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ (ppm) 143.4, 142.0, 141.7, 140.2, 135.5, 131.4,
130.9, 129.9 (q, JC,F = 32.6 Hz), 129.3, 127.0, 126.4, 125.9 (q, JC,F
=
3.5 Hz), 125.7, 125.4, 125.1, 125.0, 123.1, 21.5; HRMS (ESI, m/z):
Calcd for C22H17F3OSNa [M+Na]+: 409.0850; found: 409.0855.
1
[α]2ꢀ0 = −75.3 (c = 1.0, CHCl3); H NMR (400 MHz, CDCl3): δ (ppm)
8.97 (s, 1H), 7.94 (dd, J = 7.8, 1.1 Hz, 1H), 7.86 (d, J = 16.1 Hz, 1H),
7.70 (d, J = 7.8 Hz, 1H), 7.56–7.48 (m, 3H), 7.37 (dd, J = 13.9, 7.0 Hz,
3H), 7.32–7.26 (m, 1H), 7.03 (d, J = 16.1 Hz, 1H), 1.28 (s, 9H);
13C NMR (100 MHz, CDCl3): δ (ppm) 161.8, 139.3, 137.0, 133.4, 132.3,
131.2, 130.3, 128.8, 128.3, 127.8, 127.3, 127.0, 125.3, 57.9, 22.8; HRMS
(ESI, m/z): Calcd for C19H21NOSNa [M+Na]+: 334.1242; found:
334.1238.
Asymmetric conjugate addition of arylboronic acids to cyanoalkenes:
general procedure
Under a nitrogen atmosphere, a mixture of [RhCl(C2H4)2]2 (1.8 mg,
0.0045 mmol) and ligand L1f (3.7 mg, 0.0099 mmol) in toluene
(1 mL) was stirred at r.t. for 15 min, at which time arylboronic acid
(0.60 mmol) was added, followed by cyanoalkenes (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 80 °C for 12 h, after which the
reaction mixture was concentrated in vacuo and purified by silica gel
flash column chromatography (petroleum ether/ethyl acetate as eluent)
to give the product.
(S,E)-2-Methyl-N-(2-styrylbenzyl)propane-2-sulfinamide L3
NaBH4 (304 mg, 8 mmol) was slowly added to a solution of compound
L2 (933 mg, 3 mmol) in MeOH (10 mL) and continuously stirred at r.t.
for 2 h, then cold saturated aqueous NH4Cl solution was added and the
mixture extracted with CH2Cl2. The organic layer was washed with
brine, dried over Na2SO4 and concentrated in vacuo. The residue was
purified by chromatography to give L3 as a white solid; 91% yield;
3-(4-Methoxyphenyl)-3-phenylpropanenitrile 3a17: Light yellow
liquid; 45% yield, 58% ee; [α]2ꢀ0 = −3.2 (c = 1.0, CHCl3); Chiracel
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (80/20), flow =
m.p.112–114 °C; [α]2ꢀ0 = −53.0 (c = 1.0, CHCl3); H NMR (400 MHz,
1
1
1.0 mL min−1, tR = 19.5 min (major) and 20.5 min (minor); H NMR
CDCl3): δ (ppm) 7.67 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.4 Hz, 2H),
7.52–7.33 (m, 5H), 7.29–7.25 (m, 2H), 7.03 (d, J = 16.1 Hz, 1H),
4.50–4.36 (m, 2H), 3.43 (dd, J = 8.5, 3.6 Hz, 1H), 1.20 (s, 9H);
13C NMR (100 MHz, CDCl3): δ (ppm) 137.4, 137.0, 135.4, 131.3, 129.9,
128.9, 128.6, 128.0, 127.9, 126.8, 126.2, 125.6, 56.0, 47.6, 22.8; HRMS
(ESI, m/z): Calcd for C19H23NOSNa [M+Na]+: 336.1398; found:
336.1395.
(400 MHz, CDCl3): δ (ppm) 7.32–7.29 (m, 2H), 7.28–7.18 (m, 3H),
7.18–7.10 (m, 2H), 6.86–6.82 (m, 2H), 4.30 (t, J = 7.7 Hz, 1H), 3.74 (s,
3H), 2.95 (d, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm)
158.8, 141.7, 133.4, 128.9, 128.6, 127.5, 127.3, 118.6, 114.2, 55.3, 46.4,
24.4.
3-(2-Methoxyphenyl)-3-phenylpropanenitrile 3b17: Light yellow liquid;
43% yield, 45% ee; [α]2ꢀ0 = −22.2 (c = 0.8, CHCl3); Chiracel OD-H
(S,E)-1-(4-Methoxystyryl)-2-(p-tolylsulfinyl)benzene L1e: Light
yellow sticky oil; 57% yield; [α]2ꢁꢀ = −163.4 (c = 0.6, CHCl3);1H NMR
(400 MHz, CDCl3): δ (ppm) 7.89–7.87 (m, 1H), 7.48–7.46 (m, 1H), 7.37
(d, J = 7.6 Hz, 1H), 7.36–7.26 (m, 5H), 7.03 (d, J = 7.6 Hz, 2H),
6.85–6.78 (m, 3H), 3.69 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ (ppm) 159.8, 142.5, 142.1, 141.3, 136.2, 131.9, 131.0, 129.9,
129.3, 128.1, 125.7, 125.2, 124.4, 120.6, 114.3, 113.5, 55.1, 21.3; HRMS
(ESI, m/z): Calcd for C22H20O2SNa [M+Na]+: 371.1082; found:
371.1078.
(S,E)-1,2-Dimethoxy-4-(2-(p-tolylsulfinyl)styryl)benzene L1f: Light
yellow sticky oil; 61% yield; [α]2ꢁꢀ = −142.6 (c = 0.6, CHCl3); 1H NMR
(400 MHz, acetone-d6): δ (ppm) 8.01–7.97 (m, 1H), 7.80–7.74 (m, 1H),
7.55 (d, J = 7.6 Hz, 1H), 7.52–7.45 (m, 3H), 7.26 (d, J = 8.0 Hz, 1H), 7.21
(s, 1H), 7.15–7.11 (m, 4H), 6.97 (d, J = 8.0 Hz, 1H), 3.90 (s, 3H), 3.84 (s,
3H), 2.29 (s, 3H);13C NMR (100 MHz, acetone-d6): δ (ppm) 151.1, 150.7,
144.5, 144.3, 142.5, 137.0, 130.9, 130.6, 128.9, 125.2, 121.5, 121.3, 112.8,
110.6, 56.2, 21.3; HRMS (ESI, m/z): Calcd for C23H22O3SNa [M+Na]+:
401.1187; found: 401.1182.
(S,E)-1,3,5-Trimethoxy-2-(2-(p-tolylsulfinyl)styryl)benzene L1g:
White solid; 50% yield; m.p. 123–125 °C; [α]2ꢀ0 = −195.7 (c = 1.0,
CHCl3); 1H NMR (400 MHz, CDCl3): δ (ppm) 7.99–7.84 (m, 2H), 7.68
(d, J = 7.6 Hz, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.41–7.33 (m, 3H), 7.16 (d,
J = 8.0 Hz, 2H), 6.17 (s, 2H), 3.88 (s, 6H), 3.84 (s, 3H), 2.29 (s, 3H);
13C NMR (100 MHz, CDCl3): δ (ppm) 160.9, 159.9, 158.4, 142.7, 142.3,
141.1, 138.1, 130.8, 127.7, 125.4, 125.2, 124.4, 123.7, 123.1, 107.6, 90.8,
90.4, 55.9, 55.4, 55.0, 21.4; HRMS (ESI, m/z): Calcd for C24H24O4SNa
[M+Na]+: 431.1293; found: 431.1299.
Column, 210 nm, 25 °C, n-hexane/i-propanol (80/20), flow
=
1.0 mL min−1, tR = 7.8 min (major) and 9.7 min; H NMR (400 MHz,
CDCl3): δ (ppm)7.36–7.27 (m, 3H), 7.27–7.20 (m, 3H), 7.05 (d, J = 7.5 Hz,
1H), 6.93–6.87 (m, 2H), 4.78 (t, J = 7.6 Hz, 1H), 3.81 (s, 3H), 3.11–2.96 (m,
2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 156.8, 140.9, 129.8, 128.7,
128.6, 128.1, 127.8, 127.1, 120.9, 119.0, 111.0, 55.6, 40.9, 22.8.
1
3-(3-Methoxyphenyl)-3-phenylpropanenitrile 3c17: Light yellow
liquid; 44% yield, 46% ee; [α]2ꢀ0 = −1.9 (c = 0.6, CHCl3); Chiracel
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (70/30), flow =
1.0 mL min−1, tR = 22.4 min (major) and 25.0 min; 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.38–7.30 (m, 2H), 7.29–7.20 (m, 4H), 6.82–6.75 (m,
3H), 4.32 (t, J = 7.6 Hz, 1H), 3.75 (s, 3H), 2.99 (d, J = 7.7, 2H);
13C NMR (100 MHz, CDCl3): δ (ppm) 159.9, 142.9, 141.2, 130.0, 128.9,
127.6, 127.5, 119.8, 118.5, 113.9, 112.4, 55.3, 47.2, 24.2.
3-Phenyl-3-(o-tolyl)propanenitrile 3d17: Light yellow liquid; 48%
yield, 46% ee; [α]2ꢀ0 = +34.3 (c = 1.2, CHCl ); Chiracel OD-H Column,
3
210 nm, 25 °C, n-hexane/i-propanol (80/20), flow = 1.0 mL min−1,
tR = 15.1 min (major) and 16.4 min (minor); 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.31–7.27 (m, 2H), 7.23–7.14 (m, 7H), 4.53 (t,
J = 7.7 Hz, 1H), 2.97 (d, J = 7.7 Hz, 2H), 2.23 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ (ppm) 141.0, 139.0, 136.3, 131.1, 128.9, 127.9,
127.4, 127.3, 126.5, 125.9, 118.7, 43.4, 24.4, 19.8.
3-Phenyl-3-(m-tolyl)propanenitrile 3e12: Light yellow liquid; 51%
yield, 48% ee; [α]2ꢀ0 = +1.7 (c = 0.5, CHCl3); Chiracel OD-H Column,
210 nm, 25 °C, n-hexane/i-propanol (90/10), flow = 1.0 mL min−1,
tR = 16.6 min (major) and 17.5 min (minor); 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.32–7.29 (m, 2H), 7.27–7.18 (m, 4H), 7.06–7.00 (m,
3H), 4.30 (t, J = 7.7 Hz, 1H), 2.97 (d, J = 7.7 Hz, 2H), 2.30 (s, 3H);
13C NMR (100 MHz, CDCl3): δ (ppm) 141.4, 141.2, 138.6, 128.9, 128.7,
128.4, 128.2, 127.6, 127.4, 124.5, 118.6, 47.1, 24.2, 21.5.
(S,E)-1-(4-Chlorostyryl)-2-(p-tolylsulfinyl)benzene L1i: White
solid; 60% yield; m.p. 100–103 °C; [α]2ꢀ0 = −125.6 (c = 1.0, CHCl3);
1H NMR (500 MHz, CDCl3): δ (ppm) 8.00–7.98 (m, 1H), 7.62–7.60 (m,

304 JOURNAL OF CHEMICAL RESEARCH 2018
3-(Naphthalen-1-yl)-3-phenylpropanenitrile 3f: Light yellow liquid;
45% yield, 59% ee; [α]2ꢀ0 = −17.3 (c = 0.7, CHCl3); Chiracel OD-H
3-(4-Methoxyphenyl)-3-(naphthalen-1-yl)propanenitrile 3m: Light
yellow liquid; 44% yield, 52% ee; [α]2ꢀ0 = −12.6 (c = 1.0, CHCl ): Chiracel
3
Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50), flow
=
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50), flow =
1.0 mL min−1, tR = 19.3 min (major) and 29.1 min (minor); 1H NMR
(600 MHz, CDCl3): δ (ppm) 7.95–7.94 (m, 1H), 7.90–7.79 (m, 1H),
7.60–7.35 (m, 1H), 7.19 (d, J = 8.4 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H), 5.10 (t,
J = 7.2 Hz, 1H), 3.75 (s, 3H), 3.15–3.07 (m, 2H); 13C NMR (150 MHz,
CDCl3): δ (ppm) 158.9, 136.8, 134.3, 133.5, 131.3, 129.2, 128.9, 128.4,
126.7, 125.9, 125.4, 124.0, 123.4, 118.8, 114.5, 55.4, 42.5, 24.9; HRMS
(ESI, m/z): Calcd for C20H17NONa [M+Na]+: 310.1208; found: 310.1212.
3-(4-Methoxyphenyl)-3-(naphthalen-2-yl)propanenitrile 3n: Light
yellow liquid; 52% yield, 59% ee; [α]2ꢀ0 = −15.9 (c = 0.6, CHCl3);
Chiracel OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50),
flow = 1.0 mL min−1, tR = 17.3 min (minor) and 29.3 min (major);
1H NMR (600 MHz, CDCl3): δ (ppm) 7.82–7.78 (m, 3H), 7.69 (s, 1H),
7.49–7.45 (m, 2H), 7.27 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H),
6.87 (d, J = 8.4 Hz, 2H), 4.49 (t, J = 7.5 Hz, 1H), 3.78 (s, 3H), 3.14 –
3.06 (m, 2H); 13C NMR (150 MHz, CDCl3): δ (ppm) 158.9, 139.1, 133.4
(d, J = 14.1 Hz), 132.7, 128.9 (d, J = 5.1 Hz), 128.0, 127.8, 126.6, 126.3,
126.0, 125.8, 118.7, 114.4, 55.4, 46.6, 24.5; HRMS (ESI, m/z): Calcd for
C20H17NONa [M+Na]+: 310.1208; found: 310.1203.
1.0 mL min−1, tR = 16.1 min (major) and 27.7 min; 1H NMR (400 MHz,
CDCl3): δ (ppm) 8.04–7.90 (m, 1H), 7.89–7.75 (m, 2H), 7.56–7.35 (m,
4H), 7.35–7.17 (m, 5H), 5.13 (t, J = 7.5 Hz, 1H), 3.24–3.01 (m, 2H);
13C NMR (100 MHz, CDCl3): δ (ppm) 141.4, 136.5, 134.2, 131.3, 129.2,
129.0, 128.5, 127.8, 127.6, 126.7, 125.9, 125.4, 124.2, 123.2, 118.7, 43.1,
24.6; HRMS (ESI, m/z): Calcd for C19H15NNa [M+Na]+: 280.1102,
found 280.1095.
3-(Naphthalen-2-yl)-3-phenylpropanenitrile 3g12: Light yellow
liquid; 53% yield, 56% ee, [α]2ꢀ0 = +20.6 (c = 0.5, CHCl3); Chiracel
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50), flow =
1
1.0 mL min−1, tR = 16.0 min (minor) and 26.8 min (major); H NMR
(400 MHz, CDCl3): δ (ppm) 7.82–7.77 (m, 3H), 7.71 (s, 1H), 7.54–7.43
(m, 2H), 7.38–7.30 (m, 2H), 7.31–7.20 (m, 4H), 4.53 (t, J = 7.6 Hz, 1H),
3.12 (d, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 141.3,
138.7, 133.5, 132.7, 129.1, 128.9, 128.0, 127.8, 127.7, 126.6, 126.3, 126.0,
118.6, 47.3, 24.2.
3-(4-Fluorophenyl)-3-phenylpropanenitrile 3h12: Light yellow
liquid; 54% yield, 43% ee; [α]2ꢀ0 = +0.6 (c = 1.0, CHCl3); Chiracel
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50), flow =
1
1.0 mL min−1, tR = 8.5 min (major) and 10.6 min; H NMR (400 MHz,
Acknowledgement
CDCl3): δ (ppm) 7.54 (d, J = 7.1 Hz, 1H), 7.52–7.43 (m, 3H), 7.40–7.33
(m, 2H), 7.33–7.27 (m, 1H), 7.25–7.21 (m, 2H), 4.45 (t, J = 7.7 Hz, 1H),
3.07 (d, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) 142.3,
140.4, 131.6, 131.3, 131.1, 129.6, 129.3, 128.0, 127.6, 124.6–124.4 (m),
118.0, 47.1, 24.3; HRMS (ESI, m/z): Calcd for C15H12FNNa [M+Na]+:
248.0851; found: 248.0857.
This work was supported by a Grant-in-Aid for Scientific
Research from the Education Department of Henan Province
(14B150054).
Received 25 March 2018; accepted 25 May 2018
Paper 1805342
https://doi.org/10.3184/174751918X15287224792440
Published online: 19 June 2018
3-(4-Chlorophenyl)-3-phenylpropanenitrile 3i12: Light yellow
liquid; 57% yield, 47% ee; [α]2ꢀ0 = +3.2 (c = 1.0, CHCl3); Chiracel
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50), flow =
1
1.0 mL min−1, tR = 9.4 min (major) and 10.7 min (minor); H NMR
References
(400 MHz, CDCl3): δ (ppm) 7.36–7.31 (m, 3H), 7.30–7.25 (m, 2H),
7.21–7.16 (m, 4H), 4.36 (t, J = 7.6 Hz, 1H), 3.01 (d, J = 7.6 Hz, 2H);
13C NMR (100 MHz, CDCl3): δ (ppm) 140.81, 139.8, 133.5, 129.2,
129.1, 129.0, 127.8, 127.5, 118.3, 46.6, 24.3.
1
2
H. Rupe and A. Gassmann, Helv. Chim. Acta, 1936, 19, 569.
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3-Phenyl-3-(4-(trifluoromethyl)phenyl)propanenitrile 3j12: Light
yellow liquid; 55% yield, 46% ee; [α]2ꢀ0 = +2.3 (c = 0.8, CHCl3);
Chiracel OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (50/50),
flow = 1.0 mL min−1, tR = 8.1 min (major) and 9.6 min (minor);
1H NMR (400 MHz, CDCl3): δ (ppm) 7.60 (d, J = 8.2 Hz, 2H), 7.36 (t,
J = 7.4 Hz, 4H), 7.32–7.26 (m, 1H), 7.25–7.21 (m, 2H), 4.45 (t,
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δ (ppm) 145.2, 140.4, 130.0, 129.7, 129.2, 128.2, 127.9, 127.6, 126.0 (q,
J = 3.8 Hz), 125.4, 122.7, 118.1, 47.0, 24.1; HRMS (ESI, m/z): Calcd for
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K. Mori, Tetrahedron: Asymmetry, 2005, 16, 685.
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M.A. Müller and A. Pfaltz, Angew. Chem., Int. Ed., 2014, 53, 8668.
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M.J. Burk, P.D. De Koning, T.M. Grote, M.S. Hoekstra, G. Hoge, R.A.
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3-(2-Methoxyphenyl)-3-(4-methoxyphenyl)propanenitrile 3k: Light
yellow liquid; 42% yield, 50% ee; [α]2ꢀ0 = −1.0 (c = 1.0, CHCl3);
Chiracel OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (80/20),
flow = 1.0 mL min−1, tR = 10.3 min (major) and 13.4 min (minor);
1H NMR (600 MHz, CDCl3): δ (ppm) 7.27–7.17 (m, 3H), 7.04 (d,
J = 7.5 Hz, 1H), 6.99–6.81 (m, 4H), 4.73 (t, J = 7.6 Hz, 1H), 3.82 (s,
3H), 3.78 (s, 3H), 3.07–2.94 (m, 2H); 13C NMR (150 MHz, CDCl3): δ
(ppm) 158.7, 156.8, 133.0, 130.2, 129.0, 128.6, 128.1, 120.9, 119.1,
114.2, 111.0, 55.6, 55.4, 40.3, 23.1; HRMS (ESI, m/z): Calcd for
C17H17NO2Na [M+Na]+: 290.1157; found: 290.1162.
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3-(4-Methoxyphenyl)-3-(o-tolyl)propanenitrile 3l: Light yellow
liquid; 44% yield, 57% ee; [α]2ꢀ0 = +32.6 (c = 0.6, CHCl3); Chiracel
OD-H Column, 210 nm, 25 °C, n-hexane/i-propanol (80/20), flow =
1
1.0 mL min−1, tR = 18.9 min (major) and 20.5 min (minor); H NMR
(600 MHz, CDCl3): δ (ppm) 7.26–7.21 (m, 2H), 7.20–7.13 (m, 2H), 7.09
(d, J = 8.4 Hz, 2H), 6.83 (d, J = 7.8 Hz, 2H), 4.49 (t, J = 7.6 Hz, 1H),
3.76 (s, 3H), 2.97 (d, J = 7.2 Hz, 2H), 2.23 (s, 3H);13C NMR (150 MHz,
CDCl3): δ (ppm) 158.8, 139.4, 136.3, 133.1, 131.2, 128.9, 127.4, 126.5,
125.8, 118.8, 114.3, 55.4, 42.8, 24.6, 19.8; HRMS (ESI, m/z): Calcd for
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