Synthesis and application of axially chiral biscarbolines with functional N-O and sulfone for 1,2-transfer hydrogenations of ketimines

Article abstract of DOI:10.1016/j.tet.2019.130495

A series of axially chiral biscarboline-based sulfones were synthesized from L-tryptophane and applied for enantioselective 1,2-transfer hydrogenations of ketimines using trichlorosilane. The catalyst 4e, which had a tertiary butyl group, exhibited a good conversion and high enantioselectivities up to 96%ee in the series of reactions.

Full text of DOI:10.1016/j.tet.2019.130495

Journal Pre-proof
Synthesis and application of axially chiral biscarbolines with functional N-O and
sulfone for 1,2-transfer hydrogenations of ketimines
Yongfei Xing, Shijie Wu, Mengxian Dong, Jie Wang, Li Liu, Huajie Zhu
PII:
S0040-4020(19)30822-1
https://doi.org/10.1016/j.tet.2019.130495
TET 130495
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 May 2019
Revised Date: 28 July 2019
Accepted Date: 31 July 2019
Please cite this article as: Xing Y, Wu S, Dong M, Wang J, Liu L, Zhu H, Synthesis and application of
axially chiral biscarbolines with functional N-O and sulfone for 1,2-transfer hydrogenations of ketimines,
Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.130495.
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2019 Published by Elsevier Ltd.

Synthesis and Application of Axially Chiral Biscarbolines
with Functional N-O and Sulfone for 1,2-Transfer
Hydrogenations of Ketimines
a
a
a
a
Yongfei Xing, Shijie Wu, Mengxian Dong, Jie Wang,
b
a
Li Liu,* Huajie Zhu*

Synthesis and Application of Axially Chiral Biscarbolines with Functional
N-O and Sulfone for 1,2-Transfer Hydrogenations of Ketimines
a
a
a
a
b
a
Yongfei Xing, Shijie Wu, Mengxian Dong, Jie Wang, Li Liu,* Huajie Zhu*
a
b
College of Pharmacy, Hebei University, Baoding, 071002, China. College of Medicine,
Hebei University, Baoding, 071002, China
Abstract A series of axially chiral biscarboline-based sulfones were synthesized from
L-tryptophane and applied for enantioselective 1,2-transfer hydrogenations of
ketimines using trichlorosilane. The catalyst 4e, which had a tertiary butyl group,
exhibited a good conversion and high enantioselectivities up to 96%ee in the series
of reactions.
Keywords functional N-O and sulfone, axially chiral biscarboline-based, transfer
hydrogenation, trichlorosilane, ketimine
Introduction
Hundreds of useful chiral catalysts, such as the analogues of BINOL, BINAP and
1-2
3-5
their phosphoric acids, have been reported in various asymmetric reactions.
These catalysts widely used in enantioselective reactions, including chiral amine
synthesis. In practice, chiral amine moieties are the key active groups in bioactive
components in many compounds which widely exist in nature or in medicine
6
structures.
For example, calcimimetic NPS R-568, an effective drug against
6
c-6d
hyperparathyroidism, has had successfully reported in different research groups.
Asymmetric synthesis is one of the important and effective methods by using
7
ketimines as the starting materials catalyzed by chiral catalysts. Recently, the
catalytic procedure without any metallic ions has attracted many researchers’
7
-10
11
attention. One of the typical representatives is the N-O moiety in chiral ligands.
This N-O structure has a strong polarity that could be good electrons donors in
1
2
various chemical reactions.
In our investigations of axially chiral biscarboline
catalysts used in the transfer hydrogenations of ketimines or allylations, these chiral
1
1,13
ligands exhibited good enantioselectivities.
In this study, the biscarboline
structures with functional N-O and sulfone were constructed and synthesized. A
chiral catalyst with higher catalytic activity is obtained. We report new axially chiral
biacarboline with sulfones as the catalysts used in enantioselective 1,2-transfer
hydrogenations with high up to 96%ee and over 90% yields.
Results and Discussion
Chiral catalysts 4a to 4j were synthesized from L-tryptophane via series of
1
3a
reactions as illustrated in Scheme 1.
After the isolation of the (aR)-4 and (aS)-4,
their optical rotations were measured and compared with the reported results. It is
1

1
3a
identified that (+)-4 should have (aR)-configuration.
Scheme 1 The reaction route towards the chiral catalysts 4a to 4j with functional
N-O and sulfone groups
These axis catalysts with sulfone moiety could selectively reduce the ketimines
to the corresponding chiral amines with a moderate conversion and
enantioselectivity at the first examination using N-(1-(4-nitrophenyl)ethylidene)-
aniline. Among the ten axis chiral catalysts, it looks like that 4e, which afforded at
6
5
5%ee, had the best enantioselectivity under the reaction conditions (Table 1, entry
).
The effect of the reaction temperatures on enantioselectivity was investigated.
o
The temperatures of 10, 0, -10, -15, and -20 C were selected in the reactions,
respectively. The results are summarized in Table 1 (entries 11- 14). It is found that
o
when the reaction temperature was -10 C, the yields could reach to 87% and the
enantioselectivity was 77%ee (Table 1, entry 12). The optimized temperature is -10
o
C. Solvents like DCM, THF, CHCl , CH CN and DMF were used in the reactions to
3
3
investigate the effect of solvents on the enantioselectivity. It showed that DCM is the
suitable solvent for the 1,2-transfer hydrogenations (Table 1, entry 12). The quantity
of the catalysts on the %ee values was also studied. When the mole percentages of
4
e increased from 1% to 15%, the %ee values increased from 39% to 81%. However,
if 20% of 4e was used, the %ee decreased a little (79%ee). The 10% mole of 4e is
suitable for the reactions Table 1, entry 20).
(
Table 1 Effects of solvents, temperatures and mol quantities of catalysts on the %ee
values in enantioselective 1,2-transfer hydrogenation using chiral catalysts (+)-4a to
(+)-4j.
o
b
c
Entry
Cat.*(mol%)
T( C)
Solvent
Yield (%)
Ee (%)
2

1
2
3
4
5
6
7
8
9
4a (5%)
4b (5%)
4c (5%)
4d (5%)
4e (5%)
4f (5%)
4g (5%)
4h (5%)
4i (5%)
0
0
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
81
79
77
81
80
78
60
63
40
74
90
87
61
55
60
63
59
65
47
46
29
5
0
0
0
0
0
0
0
1
0
1
2
3
4
5
6
7
8
9
0
1
2
4j (5%)
0
53
51
77
52
-
1
1
1
1
1
1
1
1
1
2
2
2
4e (5%)
4e (5%)
4e (5%)
4e (5%)
4e (5%)
4e (5%)
4e (5%)
4e (5%)
4e (1%)
4e (10%)
4e (15%)
4e (20%)
10
-10
-15
-20
-10
-10
-10
-10
-10
-10
-10
-10
d
-
62
76
43
70
77
88
76
70
64
50
31
0
CHCl3
CH CN
3
DMF
DCM
DCM
DCM
DCM
39
80
81
79
a
b
c
All reactions were performed using catalyst 4 and HSiCl (2 equiv.) for 16 h.
3
Isolated yield.
Determined by HPLC.
d
The reaction cannot run at this temperatures.
The optimized reaction conditions were summarized here: 10% of mole 4e
o
should be used in the reactions in DCM at -10 C. The reaction conditions were then
applied for various substrates hydrogenations of other 13 ketimines. The results are
summarized in Table 2. The catalyst 4e could catalyze the transfer hydrogenations
with high up to 96%ee and 95% yields.
Table 2 Enantioselectivities in the 1,2-transfer hydrogenations using 13 ketimines
with trichlorosilane catalyzed by (+)-(aR)-4e.
a
b
c
Entry R , R , R
3
Yield (%)
Ee (%)
93
Config
1
2
1
2
3
4
Ph, Me, Ph (a)
91
83
89
92
R
R
R
S
4-Me-Ph, Me, Ph (b)
Ph, Et, Ph (c)
72
82
4-NO -Ph, Me, Ph (d)
80
2
3

5
6
7
8
9
1
1
4-F-Ph, Me, Ph (e)
4-Cl-Ph, Me, Ph (f)
4-Br-Ph, Me, Ph (g)
Ph, Me, 4-Br-Ph (h)
Ph, Me, 4-Me-Ph (i)
Ph, Me, 4- Et-Ph (j)
Ph, Me, 4-MeO-Ph (k)
Ph, Me, 4-EtO-Ph (l)
89
87
90
87
88
90
93
95
91
82
85
87
83
89
91
96
R
S
R
R
R
S
0
1
2
R
S
1
a
Isolated yield.
b
c
Determined by HPLC.
The configuration was determined by comparing the sign of specific optical rotation value with the
reported value.
It was found that the %ee reached the highest value up to 96%ee in the series of
substrates when the substrate R was 4-EtO. Other substituent just led to 72-93%ee.
3
An interesting discovery is that the experimental %ee was over 85% when the
analine (R ) had an electron-donor group at C-4 of phenyl ring. In contrast, the %ee
3
decreased to 72% if the electron-donor group at C-4 on phenyl ring (R1).
The possible catalytic mechanism is suggested (Fig. 1). One molecular Cl SiH
3
chelated with O atom of N-O. This O atom could afford more electrons to Si and this
lead to the hydride on this Si is more active than the one on the Si in another
molecule of Cl SiH which chelated with O of sulfone. Thus, this hydride attacked the
3
carbonyl carbon of C=N via a six-membered-ring transition state to finish the transfer
hydrogenation. Partial TS structure is illustrated in Figure 1.
Figure 1 The (+)-(aR)-4 structure and the possible partial transition state structure (for clarity) for
the catalytic procedure.
Summary A new series of axial biscarboline-based sulfones were synthesized and
used in the 1,2-transfer hydrogenations. The high up to 96%ee has been achieved in
the enantioselective transfer hydrogenations. The effect of the substituent of chiral
catalyst on the %ee values was investigated. It is found that the catalyst with a
tertiary butyl can promote the reaction with a highest enantioselectivity.
Experimental section
1
. Synthesis of compound 2
Compound 1 (100 mg, 0.24 mmol) dissolved in anhydrous DCM. SOCl (0.5
2
mmol) was then added into the DCM solution under ice-bath. Pyridine was used a
base in the reaction to neutralize the acid formed in the reaction. The reaction was
4

stirred for 2 h at room temperature. After the reaction finished by TLC examination,
the saturated NaHCO aqueous solution was added into the reaction to quench it.
3
DCM (15 × 3 mL) was used to extract the products. The combined organic layers were
dried over anhydrous Na SO . After removing the organic solvent, the residue was
2
4
purified by column chromatography using silica and eluted with a mixture of
DCM/MeOH (100/1, v/v) to afford the product 2 with 87% yield.
3
,3'-bis(chloromethyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole 2, yellow
+
amorphous powder (yield 87%). MS-ESI, m/z 481.09 [M+ Na] . HR-MS-EI m/z calcd
+
1
for C H Cl N [M+ H] 459.1138, found 459.1143. H NMR (600 MHz, CDCl ) δ 8.30
2
6
21
2
4
3
(
s, 1 H), 8.26 (d, J = 7.9 Hz, 1 H), 7.65 (t, J = 7.6 Hz, 1 H), 7.44 (d, J = 8.2 Hz, 1 H), 7.37
1
3
(t, J = 7.5 Hz, 1 H), 5.00 (d, J = 22.4 Hz, 2 H), 3.39 (s, 3 H). C NMR (151 MHz, CDCl ) δ
3
1
1
2
44.37, 143.09, 139.95, 135.44, 131.28, 129.00, 121.68, 120.84, 120.16, 114.56,
09.83, 47.97, 32.20.
. Synthesis of compound 3
The corresponding thiol (200 mg) dissolved in anhydrous DMF, the NaH (1.2
equiv.) was added into the thiol solution under ice-bath. After compound 2 (1.0
equiv.) was added into the solution, it was stirred for 2 h. After reaction finished
examined by TLC, the reaction was quenched by ice-water. Ethyl acetate (15 × 3 ml)
was used to extract the reactants. The combined organic layers were dried over
Na SO . The organic solvents was removed under the reduced pressure to afford the
2
4
residue which was isolated and purified by column chromatography using the
mixture of ethyl acetate/petroleum (8/1, v/v) to give compound 3.
3
,3'-bis((butylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole
3a,
yellow amorphous powder (yield 97%). MS-ESI, m/z 589.24 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+ H]⁺ 567.2601, found: 567.2571 . H NMR (600 MHz, CDCl ) δ
3
4
38 4 2
3
8
7
1
.13 (d, J = 7.9 Hz, 1 H), 8.11 (s, 1 H), 7.50 (t, J = 7.7 Hz, 1 H), 7.28 (d, J = 8.3 Hz, 1 H),
.22 (t, J = 7.5 Hz, 1 H), 4.05 (d, J = 15.1 Hz, 2 H), 3.22 (s, 3 H), 2.50 (t, J = 6.2 Hz, 2 H),
13
.57 – 1.51 (m, 2 H), 1.34 – 1.28 (m, 2 H), 0.79 (t, J = 7.4 Hz, 3 H). C NMR (151 MHz,
CDCl ) δ 145.34, 142.03, 139.00, 134.09, 130.12, 127.52, 120.65, 119.93, 118.71,
3
1
12.75, 108.56, 37.64, 30.93, 30.45, 21.03, 12.65.
3
,3'-bis((isopropylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole 3b,
yellow amorphous powder (yield 95%). MS-ESI, m/z 561.21 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+ H]⁺ 539.2263, found: 539.2258. H NMR (600 MHz, CDCl ) δ
3
4
38 4 2
3
8
7
.22 (s, 1 H), 8.21 (d, J = 3.4 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.37 (d, J = 8.3 Hz, 1 H),
.30 (t, J = 7.5 Hz, 1 H), 4.18 (d, J = 13.1 Hz, 2 H), 3.30 (s, 3 H), 2.99 (dt, J = 13.4, 6.7
1
3
Hz, 1 H), 1.32 (d, J = 2.9 Hz, 6 H). C NMR (151 MHz, CDCl ) δ 146.36, 143.04, 140.03,
3
1
2
3
35.09, 131.16, 128.66, 121.71, 120.91, 119.71, 113.86, 109.60, 37.47, 35.14, 31.89,
3.42.
,3'-bis((isobutylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole 3c,
yellow amorphous powder (yield 94%). MS-ESI, m/z 589.24 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+ H]⁺ 567.2602, found: 567.2571. H NMR (600 MHz, CDCl ) δ
3
4
38 4 2
3
8
7
1
.14 (d, J = 7.9 Hz, 1 H), 8.12 (s, 1 H), 7.51 (t, J = 7.7 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 1 H),
.23 (t, J = 7.5 Hz, 1 H), 4.05 (d, J = 19.5 Hz, 2 H), 3.23 (s, 3 H), 2.40 (t, J = 7.4 Hz, 2 H),
1
3
.78 (td, J = 13.4, 6.7 Hz, 1 H), 0.90 (d, J = 6.6 Hz, 6 H). C NMR (151 MHz, CDCl ) δ
3
5

1
1
3
46.38, 143.06, 140.12, 135.11, 131.10, 128.66, 121.60, 120.96, 119.65, 113.80,
09.59, 41.37, 39.12, 31.90, 28.43, 22.13.
,3'-bis((isopentylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole 3d,
yellow amorphous powder (yield 97%). MS-ESI, m/z 617.27 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+ H]⁺ 594.2877, found 594.2851. H NMR (600 MHz, CDCl ) δ
3
4
38 4 2
3
8
7
1
.14 (d, J = 7.9 Hz, 1 H), 8.12 (s, 1 H), 7.52 (t, J = 7.6 Hz, 1 H), 7.30 (d, J = 8.2 Hz, 1 H),
.23 (t, J = 7.5 Hz, 1 H), 4.06 (d, J = 14.5 Hz, 2 H), 3.23 (s, 3 H), 2.51 (t, J = 7.2 Hz, 2 H),
1
3
.58 (dt, J = 13.2, 6.6 Hz, 1 H), 1.48 – 1.42 (m, 2 H), 0.78 (d, J = 6.6 Hz, 6 H).
C
NMR (151 MHz, CDCl ) δ 145.27, 142.01, 139.06, 134.07, 130.10, 127.64, 120.65,
3
1
19.90, 118.71, 112.77, 108.57, 37.55, 37.39, 30.87, 29.13, 26.49, 21.28.
3
,3'-bis((tert-butylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole 3e,
yellow amorphous powder (yield 98%). MS-ESI, m/z 589.24 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+H]⁺ 567.2599, found 567.2571. H NMR (600 MHz, CDCl ) δ
34
38 4 2
3
8
7
.18 (s, 1 H), 8.14 (d, J = 7.8 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 1 H),
1
3
.22 (t, J = 7.5 Hz, 1 H), 4.14 (d, J = 15.3 Hz, 2 H), 3.21 (s, 3 H), 1.34 (s, 9 H). C NMR
(
151 MHz, CDCl ) δ 145.19, 141.99, 138.81, 134.06, 130.18, 127.55, 120.72, 119.89,
3
1
18.61, 113.20, 108.53, 42.04, 34.56, 30.96, 30.07.
3
,3'-bis((cyclohexylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole 3f,
yellow amorphous powder (yield 91%). MS-ESI, m/z 641.27 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+ H]⁺ 619.2901, found 619.2884. H NMR (600 MHz, CDCl ) δ
3
8
42 4 2
3
8
7
2
9
1
2
3
3
.23 (s, 1 H), 8.21 (s, 1 H), 7.59 (t, J = 7.7 Hz, 1 H), 7.37 (d, J = 8.3 Hz, 1 H), 7.30 (t, J =
.5 Hz, 1 H), 4.18 (d, J = 7.8 Hz, 2 H), 3.30 (s, 3 H), 2.77 – 2.72 (m, 1 H), 2.02 (dd, J =
8.4, 9.0 Hz, 2 H), 1.76 – 1.72 (m, 2 H), 1.39 (dd, J = 19.8, 10.1 Hz, 2 H), 1.25 (d, J =
1
3
.7 Hz, 4 H). C NMR (151 MHz, CDCl ) δ 146.63, 143.04, 140.00, 135.08, 131.18,
3
28.64, 121.72, 120.96, 119.70, 113.81, 109.58, 43.72, 36.95, 33.62, 31.90, 25.97,
5.81.
,3'-bis((cyclopentylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole
g, yellow amorphous powder (yield 94%). MS-ESI, m/z 613.24 [M+ Na]⁺. HR-MS-ESI
1
m/z calcd for C H N S [M+ H]⁺ 591.2581, found 591.2571. H NMR (600 MHz,
3
6 38 4 2
CDCl ) δ 8.22 (s, 1 H), 8.21 (s, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), 7.37 (d, J = 8.3 Hz, 1 H),
3
7
.30 (t, J = 7.5 Hz, 1 H), 4.18 (d, J = 15.5 Hz, 2 H), 3.31 (s, 3 H), 3.14 (dd, J = 13.8, 6.9
Hz, 1 H), 1.99 (d, J = 4.7 Hz, 2 H), 1.77 – 1.71 (m, 2 H), 1.58 (dd, J = 27.6, 19.8 Hz, 4 H).
1
3
C NMR (151 MHz, CDCl ) δ 146.42, 143.04, 140.12, 135.09, 131.12, 128.62, 121.70,
3
1
20.95, 119.69, 113.85, 109.59, 43.98, 38.74, 33.79, 31.92, 24.90.
9
,9'-dimethyl-3,3'-bis((naphthalen-2-ylthio)methyl)-9H,9'H-1,1'-bipyrido[3,4-b]indo
le 3h
, brown amorphous powder (yield 91%). MS-ESI, m/z 729.21 [M+ Na]⁺.
1
HR-MS-ESI m/z calcd for C H N S [M+ H]⁺ 707.2267, found 707.2258. H NMR (600
3
6 38 4 2
MHz, CDCl ) δ 8.16 (s, 1 H), 8.04 (d, J = 7.9 Hz, 1 H), 7.81 (s, 1 H), 7.63 (d, J = 8.1 Hz, 1
3
H), 7.58 (d, J = 8.5 Hz, 1 H), 7.45 (m, 2 H), 7.41 (d, J = 8.5 Hz, 1 H), 7.28 (t, J = 7.4 Hz, 1
H), 7.21 (t, J = 7.5 Hz, 1 H), 7.18 (t, J = 7.5 Hz, 1 H), 7.04 (d, J = 8.2 Hz, 1 H), 4.65 (d, J =
1
3
1
1
1
1
3.7 Hz, 1 H), 4.51 (d, J = 13.6 Hz, 1 H), 2.82 (s, 3 H). C NMR (151 MHz, CDCl ) δ
3
45.34, 142.94, 139.78, 135.15, 134.00, 133.78, 131.79, 131.20, 128.68, 128.29,
27.63, 127.51, 127.18,127.07, 126.46, 125.62, 121.68, 120.82, 119.78, 114.23,
09.61, 40.46, 31.44.
6

3
,3'-bis(((2,6-dimethylphenyl)thio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b
]
indole 3i, brown amorphous powder (yield 90%). MS-ESI, m/z 685.24 [M+ Na]⁺.
1
HR-MS-ESI m/z calcd for C H N S [M+ H]⁺ 663.2588, found 663.2571. H NMR
4
2 38 4 2
(
600 MHz, CDCl ) δ 8.08 (d, J = 7.9 Hz, 1 H), 7.77 (s, 1 H), 7.59 (t, J = 7.7 Hz, 1 H), 7.36
3
(
d, J = 8.2 Hz, 1 H), 7.28 (t, J = 7.5 Hz, 1 H), 7.15 – 7.12 (m, 1 H), 7.08 (d, J = 7.4 Hz, 2
1
3
H), 4.23 (d, J = 53.3 Hz, 2 H), 3.29 (s, 3 H), 2.47 (s, 6 H). C NMR (151 MHz, CDCl ) δ
3
1
1
3
46.02, 143.38, 143.02, 139.98, 135.15, 133.82, 131.03, 128.61, 128.40, 128.16,
21.59, 120.97, 119.68, 113.85, 109.59, 42.17, 32.14, 22.16.
,3'-bis((benzylthio)methyl)-9,9'-dimethyl-9H,9'H-1,1'-bipyrido[3,4-b]indole
3j,
yellow amorphous powder (yield 92%). MS-ESI, m/z 657.21 [M+ Na]⁺. HR-MS-ESI m/z
1
calcd for C H N S [M+ H]⁺ 635.2276,found 635.2258. H NMR (600 MHz, CDCl ) δ
40
34 4 2
3
8
7
3
1
1
3
.19 (d, J = 7.9 Hz, 1 H), 8.07 (s, 1 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.37 (d, J = 8.3 Hz, 1 H),
.32 (t, J = 8.5 Hz, 3 H), 7.27 (t, J = 7.5 Hz, 2 H), 7.21 (t, J = 7.2 Hz, 1 H), 4.06 (d, J =
1
3
6.6 Hz, 2 H), 3.78 (s, 2 H), 3.32 (s, 3 H). C NMR (151 MHz, CDCl ) δ 145.81, 143.05,
3
40.28, 138.29, 135.10, 131.09, 129.09, 128.70, 128.52, 127.00, 121.67, 120.94,
19.79, 113.99, 109.66, 38.16, 36.57, 32.03.
. Synthesis of compound 4
m-CPBA (8 equiv.) was added into the solution of compound 3 (100 mg)
dissolved in anhydrous DCM at room temperature for 10 h. After reaction finished
checked by TLC, the reaction was quenched using saturated NaHCO aqueous
3
solution. DCM (15 × 3 mL) was used to extract the organic compounds. The
combined organic layers was then dried over Na SO , and removed. The residue was
2
4
isolated and purified by column chromatography using the mixture of DCM/MeOH
60/1, v/v) to afford pure compound 4.
(
3
2
,3'-bis((butylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indole]
,2'-dioxide 4a, white amorphous powder (yield 81%). MS-ESI, m/z 685.21 [M+ Na]⁺.
1
HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 663.229, found: 663.2266. H NMR
3
4 38 4 6 2
(
600 MHz, CDCl ) δ 8.27 (s, 1 H), 8.03 (d, J = 7.9 Hz, 1 H), 7.50 (t, J = 7.7 Hz, 1 H), 7.29
3
(t, J = 7.6 Hz, 1 H), 7.26 (d, J = 8.3 Hz, 1 H), 5.22 (d, J = 14.2 Hz, 1 H), 4.54 (d, J = 14.2
Hz, 1 H), 3.25 (m, 1 H), 3.19 (s, 3 H), 3.16 (m, 1 H), 1.81 (dd, J = 15.3, 7.7 Hz, 2 H), 1.34
1
3
(
dd, J = 15.0, 7.5 Hz, 2 H), 0.81 (t, J = 7.4 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 143.54,
3
1
5
38.03, 131.90, 128.61, 125.45, 121.61, 121.56, 121.24, 120.81, 120.24, 109.74,
5.67, 55.28, 29.83, 23.91, 21.70, 13.53. HPLC resolution with a Chiralpak ID column
(
THF:EtOH = 70:30, 2 mL/min), [α] -35.1 (c 0.31, CHCl ).
D 3
3
2
,3'-bis((isopropylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indole]
,2'-dioxide 4b, white amorphous powder (yield 85%). MS-ESI, m/z 657.18 [M+ Na]⁺.
1
HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 635.1961,found 635.1953. H NMR
3
2 34 4 6 2
(
600 MHz, CDCl ) δ 8.39 (s, 1 H), 8.09 (d, J = 7.9 Hz, 1 H), 7.54 (t, J = 7.7 Hz, 1 H), 7.34
3
(t, J = 7.6 Hz, 1 H), 7.30 (d, J = 8.3 Hz, 1 H), 5.45 (d, J = 14.1 Hz, 1 H), 4.54 (d, J = 14.1
Hz, 1 H), 3.54 (dt, J = 13.7, 6.8 Hz, 1 H), 3.25 (s, 3 H), 1.47 (d, J = 6.8 Hz, 3 H), 1.42 (d, J
1
3
=
1
2
6.9 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 143.58, 137.91, 131.83, 128.58, 125.50,
3
21.82, 121.46, 121.27, 120.75, 120.34, 109.72, 55.89, 51.78, 29.74, 16.10, 14.77.
3.91, 21.70, 13.53. HPLC resolution with a Chiralpak ID column (THF:EtOH = 70:30, 2
mL/min), [α] -45.8 (c 0.35, CHCl ).
D
3
7

3
2
,3'-bis((isobutylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indole]
,2'-dioxide 4c, white amorphous powder (yield 86%). MS-ESI, m/z 685.21 [M+ Na]⁺.
1
HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 663.2291, found: 663.2266. H NMR
3
4 38 4 6 2
(
600 MHz, CDCl ) δ 8.26 (s, 1 H), 8.01 (d, J = 7.9 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 1 H), 7.28
3
(t, J = 7.5 Hz, 1 H), 7.25 (d, J = 8.1 Hz, 1 H), 5.21 (d, J = 13.0 Hz, 1 H), 4.56 (d, J = 13.8
Hz, 1 H), 3.19 (s, 3 H), 3.14 (t, J = 7.0 Hz, 2 H), 2.35 (dt, J = 13.2, 6.6 Hz, 1 H), 1.00 (d, J
1
3
=
1
2
6.2 Hz, 6 H). C NMR (151 MHz, CDCl ) δ 142.55, 137.00, 131.28, 130.93, 127.62,
3
24.45, 120.55, 120.26, 119.79, 119.21, 108.70, 61.99, 55.43, 28.85, 22.77, 21.87,
1.75. HPLC resolution with a Chiralpak ID column (THF:EtOH = 70:30, 2 mL/min),
[
α] -43.2 (c 0.27, CHCl ).
D 3
3
2
,3'-bis((isopentylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indole]
,2'-dioxide 4d, white amorphous powder (yield 82%). MS-ESI, m/z 714.25 [M+ Na]⁺.
1
HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 691.2583, found: 691.2579. H NMR
3
4 38 4 6 2
(
600 MHz, CDCl ) δ 8.25 (s, 1 H), 8.01 (d, J = 7.9 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.28
3
(t, J = 7.6 Hz, 1 H), 7.25 (d, J = 8.3 Hz, 1 H), 5.22 (d, J = 14.1 Hz, 1 H), 4.52 (d, J = 14.1
Hz, 1 H), 3.24 (m, 1 H), 3.20 (s, 3 H), 3.16 (m, 1 H), 1.71 (dd, J = 15.8, 7.5 Hz, 2 H), 1.57
1
3
(
dt, J = 13.4, 6.7 Hz, 1 H), 0.78 (d, J = 6.6 Hz, 6 H). C NMR (151 MHz, CDCl ) δ 143.48,
3
1
3
7
3
38.08, 131.81, 128.51, 125.48, 121.45, 121.20, 120.84, 120.19, 109.70, 55.24, 54.36,
0.20, 29.83, 27.31, 22.08 . HPLC resolution with a Chiralpak ID column (THF:EtOH =
0:30, 2 mL/min), [α] -38.3 (c 0.34, CHCl ).
D
3
,3'-bis((tert-butylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indol
e] 2,2'-dioxide 4e, white amorphous powder (yield 87%). MS-ESI, m/z 685.21 [M+
1
Na]⁺. HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 663.2289, found 663.2266. H
3
4 38 4 6 2
NMR (600 MHz, CDCl ) δ 8.37 (s, 1 H), 8.01 (d, J = 7.9 Hz, 1 H), 7.45 (t, J = 7.7 Hz, 1 H),
3
7
1
1
2
.26 (t, J = 7.5 Hz, 1 H), 7.22 (d, J = 8.3 Hz, 1 H), 5.61 (d, J = 13.4 Hz, 1 H), 4.39 (d, J =
1
3
3.5 Hz, 1 H), 3.21 (s, 3 H), 1.44 (s, 9 H). C NMR (151 MHz, CDCl ) δ 143.57, 138.03,
3
30.71, 128.29, 125.95, 121.38, 121.14, 120.91, 119.85, 109.69, 60.50, 47.19, 29.80,
3.47 . HPLC resolution with a Chiralpak ID column (THF:EtOH = 70:30, 2 mL/min),
[
α] -46.7 (c 0.45, CHCl ).
D 3
3
,3'-bis((cyclohexylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indol
e] 2,2'-dioxide 4f, white amorphous powder (yield 76%). MS-ESI, m/z 738.25 [M+
1
Na]⁺. HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 715.2582, found: 715.2579. H
3
8 42 4 6 2
NMR (600 MHz, CDCl ) δ 8.30 (s, 1 H), 7.99 (d, J = 7.6 Hz, 1 H), 7.79 (s, 1 H), 7.73 (d, J
3
=
5
7.0 Hz, 1 H), 7.47 (d, J = 6.9 Hz, 1 H), 7.26 (t, J = 7.5 Hz, 1 H), 7.22 (d, J = 7.3 Hz, 1 H),
.43 (d, J = 11.7 Hz, 1 H), 4.43 (d, J = 13.5 Hz, 1 H), 3.19 (s, 3 H), 2.19 (s, 2 H), 1.76 (d,
1
3
J = 0.5 Hz, 2 H), 1.48 (d, J = 11.3 Hz, 1 H), 1.13 (dd, J = 37.4, 16.8 Hz, 6 H). C NMR
151 MHz, CDCl ) δ 143.79, 137.83, 134.39, 133.11, 129.58, 121.59, 121.44, 120.60,
(
3
1
20.25, 109.81, 107.63, 63.32, 51.63, 29.98, 25.76, 25.18, 25.06, 24.95, 24.51 . HPLC
resolution with a Chiralpak ID column (THF:EtOH = 70:30, 2 mL/min), [α] -53.9 (c
D
0
.21, CHCl3).
3
,3'-bis((cyclopentylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indo
le] 2,2'-dioxide 4g, white amorphous powder (yield 77%). MS-ESI, m/z 710.22 [M+
1
Na]⁺. HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 687.2271, found 687.2266. H
3
6 38 4 6 2
NMR (600 MHz, CDCl ) δ 8.28 (s, 1 H), 8.02 (d, J = 7.9 Hz, 1 H), 7.48 (t, J = 7.7 Hz, 1 H),
3
8

7
1
1
.28 (t, J = 7.5 Hz, 1 H), 7.24 (d, J = 8.3 Hz, 1 H), 5.29 (d, J = 14.1 Hz, 1 H), 4.51 (d, J =
4.1 Hz, 1 H), 3.76 (s, 1 H), 3.18 (s, 3 H), 2.12 (dt, J = 13.8, 6.9 Hz, 1 H), 2.03 (m, 2 H),
1
3
.94 (s, 2 H), 1.70 (td, J = 13.0, 6.3 Hz, 2 H), 1.53 (td, J = 12.6, 6.0 Hz, 2 H). C NMR
(
151 MHz, CDCl ) δ 143.59, 137.99, 131.94, 128.50, 125.59, 121.44, 121.20, 120.84,
3
1
20.10, 109.74, 107.61, 64.20, 53.92, 29.76, 27.55, 26.42, 26.13, 26.07. HPLC
resolution with a Chiralpak ID column (THF:EtOH = 70:30, 2 mL/min), [α] -52.8 (c
D
0
.15, CHCl3).
9
,9'-dimethyl-3,3'-bis((naphthalen-2-ylsulfonyl)methyl)-9H,9'H-[1,1'-bipyrido[3,4-b
]indole] 2,2'-dioxide 4h, buff amorphous powder (yield 70%). MS-ESI, m/z 826.18
[
1
M+ Na]⁺. HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 803.1967, found 803.1953.
4
6 34 4 6 2
H NMR (600 MHz, CDCl ) δ 8.36 (d, J = 56.8 Hz, 2 H), 7.91 (dd, J = 38.9, 0.7 Hz, 2 H),
3
7
5
.78 (s, 3 H), 7.59 – 7.40 (m, 5 H), 7.24 (d, J = 0.5 Hz, 1 H), 7.01 (d, J = 0.6 Hz, 1 H),
1
3
.80 (d, J = 11.0 Hz, 1 H), 4.52 (d, J = 6.1 Hz, 1 H), 2.81 (s, 3 H). C NMR (151 MHz,
CDCl ) δ 143.47, 137.87, 136.49, 135.42, 133.91, 132.16, 131.98, 130.00, 130.00 –
3
1
1
2
3
3
7
7
=
=
6
1
2
29.22, 129.18, 128.53, 127.93, 127.52, 125.71, 122.95, 121.46, 120.65, 119.79,
09.67, 56.17, 29.70. HPLC resolution with a Chiralpak ID column (THF:EtOH = 70:30,
mL/min), [α] -175.8 (c 0.25, CHCl ).
D
3
,3'-bis(((2,6-dimethylphenyl)sulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[
,4-b]indole] 2,2'-dioxide 4i, buff amorphous powder (yield 72%). MS-ESI, m/z
82.22 [M+Na]⁺. HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 759.2271, found:
4
2 38 4 6 2
1
59.2266. H NMR (600 MHz, CDCl ) δ 8.34 (s, 1 H), 8.03 (d, J = 7.9 Hz, 1 H), 7.48 (t, J
3
7.7 Hz, 1 H), 7.28 (t, J = 7.6 Hz, 1 H), 7.24 (d, J = 3.5 Hz, 1 H), 7.23 (s, 1 H), 7.05 (d, J
7.5 Hz, 2 H), 5.84 (d, J = 13.8 Hz, 1 H), 4.35 (d, J = 13.9 Hz, 1 H), 3.13 (s, 3 H), 2.67 (s,
1
3
H). C NMR (151 MHz, CDCl ) δ 171.18, 143.49, 140.74, 138.19, 136.64, 132.94,
3
31.53, 128.26, 125.91, 121.26, 121.11, 120.91, 119.90, 109.69, 107.65, 60.41, 29.50,
3.06. HPLC resolution with a Chiralpak ID column (THF:EtOH = 70:30, 2 mL/min),
[
α] -91.4 (c 0.23, CHCl ).
D 3
3
2
,3'-bis((benzylsulfonyl)methyl)-9,9'-dimethyl-9H,9'H-[1,1'-bipyrido[3,4-b]indole]
,2'-dioxide 4j, yellow amorphous powder (yield 83%). MS-ESI, m/z 754.18 [M + Na]⁺.
1
HR-MS-ESI m/z calcd for C H N O S [M+ H]⁺ 731.1601, found: 731.1593. H NMR
4
0 34 4 6 2
(
600 MHz, CDCl ) δ 8.29 (s, 1 H), 8.24 (d, J = 7.9 Hz, 1 H), 7.66 (t, J = 7.7 Hz, 1 H), 7.43
3
(d, J = 8.3 Hz, 1 H), 7.36 (dd, J = 7.7, 2.2 Hz, 3 H), 7.29 (s, 1 H), 7.21 (t, J = 7.5 Hz, 2 H),
4
=
1
1
7
4
.61 (d, J = 14.0 Hz, 1 H), 4.54 (d, J = 14.0 Hz, 1 H), 4.36 (d, J = 13.7 Hz, 1 H), 4.31 (d, J
1
3
8.2 Hz, 1 H), 3.35 (s, 3 H). C NMR (151 MHz, CDCl ) δ 142.66, 136.94, 133.21,
3
31.08, 130.29, 128.43, 127.63, 126.57, 124.45, 120.65, 120.33, 119.60, 119.41,
08.84, 59.40, 20.01, 13.18. HPLC resolution with a Chiralpak ID column (THF:EtOH =
0:30, 2 mL/min), [α] -50.3 (c 0.21, CHCl ).
D
3
.General procedure for 1,2-transfer hydrogenations
Ketimine 5 (20 mg) was dissolved in anhydrous DCM, the catalyst 4e (10% mol)
was added into the solution. HSiCl (2 equiv.) was then added into the solution at -10
3
o
C. The reaction was stirred for 12 h until the reaction finished by checking with TLC.
Saturated aqueous NaHCO solution was used to quench the reaction. DCM (15 × 3
3
mL) was used to extract the organic components. The combined organic layers were
dried over the Na SO . By removing the organic solvents, the residue was purified by
2
4
9

column chromatagraphy using the mixture of petroleum ether (PE)/isopropyl alcohol
(
(
[
IPA) (30/1, v/v) to afford the compound 6.
R)-N-(1-phenylethyl)aniline 6a, yellow viscous oil (yield 91%). MS-ESI, m/z 220.11
1
M+Na]⁺. HR-MS-ESI m/z calcd for C H N [M+ H]⁺ 197.121, found: 197.1204. H
14 15
NMR (600 MHz, CDCl ) δ 7.29 (d, J = 7.5 Hz, 2 H), 7.24 (t, J = 7.4 Hz, 2 H), 7.15 (t, J =
3
7
4
1
.1 Hz, 1 H), 7.01 (t, J = 7.3 Hz, 2 H), 6.56 (t, J = 7.1 Hz, 1 H), 6.44 (d, J = 7.7 Hz, 2 H),
1
3
.41 (q, J = 6.7 Hz, 1 H), 1.45 (d, J = 6.6 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 146.32,
3
44.25, 128.09, 127.62, 125.85, 124.85, 116.26, 112.33, 52.48, 23.95. Enantiomeric
excess was determined by HPLC with a Chiralpak ID column (PE/IPA = 95/5, 2
mL/min), t (minor)= 9.383 min (S); t (major)= 11.072 min (R), 93% ee. [α] +14.3 (c
R
R
D
0
.46, CHCl3).
(
R)-N-(1-(p-tolyl)ethyl)aniline 6b, colorless oil (yield 83%). MS-ESI, m/z 234.13 [M+
1
Na]⁺. HR-MS-ESI m/z calcd for C H N [M+ H]⁺ 211.1366, found: 211.1361. H NMR
1
5 17
(
600 MHz, CDCl ) δ 7.15 (dd, J = 7.9, 3.2 Hz, 2 H), 7.03 (dd, J = 7.7, 2.9 Hz, 2 H), 7.01 –
3
6
.96 (m, 2 H), 6.56 – 6.52 (m, 1 H), 6.44 – 6.40 (m, 2 H), 4.38 – 4.34 (m, 1 H), 2.22 (d,
13
J = 3.3 Hz, 3 H), 1.39 (dd, J = 6.7, 3.1 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 147.45,
3
1
42.31, 136.45, 129.39, 129.16, 125.84, 117.24, 113.37, 53.21, 25.07, 21.13.
Enantiomeric excess was determined by HPLC with a Chiralpak IB column (PE/IPA =
5/5, 2 mL/min), t (minor)= 11.432 min (S); t (major)= 12.675 min (R), %ee = 72%.
9
R
R
[
α] +13.3 (c 0.46, CHCl ).
D 3
(
R)-N-(1-phenylpropyl)aniline 6c, yellow oil (yield 89%). MS-ESI, m/z 234.13 [M+
1
Na]⁺. HR-MS-ESI m/z calcd for C H N [M+ H]⁺ 211.1368, found: 211.1361. H NMR
1
5 17
(
600 MHz, CDCl ) δ 7.25 (dt, J = 15.0, 7.5 Hz, 4 H), 7.14 (t, J = 7.1 Hz, 1 H), 7.00 (t, J =
3
7
1
1
.9 Hz, 2 H), 6.55 (t, J = 7.3 Hz, 1 H), 6.44 (d, J = 7.8 Hz, 2 H), 4.15 (t, J = 6.7 Hz, 1 H),
1
3
.82 – 1.72 (m, 2 H), 0.88 (t, J = 7.4 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 146.51,
3
42.91, 128.05, 127.47, 125.85, 125.46, 116.10, 112.22, 58.71, 30.64, 9.79.
Enantiomeric excess was determined by HPLC with a Chiralpak ID column (PE/IPA =
9
+
5/5, 2mL/min), t (minor)= 11.107min (S); t (major)= 12.007min (R), 82%ee. [α]
R
R
D
49.9 (c 0.46, CHCl3).
(
R)-N-(1-(4-nitrophenyl)ethyl)aniline 6d, yellow oil (yield 92%). MS-ESI, m/z 265.09
1
[
M+ Na]⁺. HR-MS-ESI m/z calcd for C H N O [M+ H]⁺ 243.1062, found 243.1055. H
1
4 14 2 2
NMR (600 MHz, CDCl ) δ 7.22 (dd, J = 9.0, 5.2 Hz, 4 H), 7.13 (dt, J = 5.8, 2.5 Hz, 1 H),
3
7
6
1
.05 (d, J = 8.8 Hz, 2 H), 6.27 (d, J = 8.8 Hz, 2 H), 4.33 (q, J = 6.7 Hz, 1 H), 1.40 (d, J =
1
3
.7 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 145.19, 143.60, 130.75, 127.69, 126.01,
3
24.73, 113.90, 107.86, 52.48, 23.85. Enantiomeric excess was determined by HPLC
with a Chiralpak ID column (PE/IPA = 95/5, 2 mL/min), t (major)= 21.340 min (S); tR
R
(
minor)= 22.255 min (R), 80%ee. [α] -18.5 (c 0.46, CHCl ).
D 3
(R)-N-(1-(4-fluorophenyl)ethyl)aniline 6e, yellow oil (yield 89%). MS-ESI, m/z
2
2
6
1
1
38.10 [M+ Na]⁺. HR-MS-ESI m/z calcd for C H FN [M+ H]⁺ 1216.1115, found
14 14
1
16.1110. H NMR (600 MHz, CDCl ) δ 7.26 – 7.21 (m, 2 H), 7.01 (t, J = 7.8 Hz, 2 H),
3
.91 (t, J = 8.6 Hz, 2 H), 6.56 (s, 1 H), 6.40 (d, J = 8.0 Hz, 2 H), 4.38 (q, J = 6.7 Hz, 1 H),
1
3
.40 (d, J = 6.7 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 162.61, 160.99, 147.14, 140.93,
3
29.15, 127.35, 117.48, 115.51, 115.37, 113.38, 52.93, 25.13. Enantiomeric excess
1
0

was determined by HPLC with a Chiralpak ID column (PE/IPA = 95/5, 2 mL/min), tR
(
minor)= 9.942 min (S); t (major)= 10.062 min (R), 91%ee. [α] +19.0 (c 0.46, CHCl ).
R D 3
(S)-N-(1-(4-chlorophenyl)ethyl)aniline 6f, yellow oil (yield 87%). MS-ESI, m/z
2
2
6
54.07 [M+ Na]⁺. HR-MS-ESI m/z calcd for C H ClN [M+ H]⁺ 232.0820, found
14 14
1
32.0815. H NMR (600 MHz, CDCl ) δ 7.22 – 7.12 (m, 4 H), 6.99 (t, J = 7.8 Hz, 2 H),
3
.56 (t, J = 7.3 Hz, 1 H), 6.37 (d, J = 7.8 Hz, 2 H), 4.36 – 4.29 (m, 1 H), 1.36 (d, J = 7.9
1
3
Hz, 3 H). C NMR (151 MHz, CDCl ) δ 147.08, 143.93, 132.47, 129.23, 128.87, 127.34,
3
1
17.60, 113.42, 53.04, 25.12. Enantiomeric excess was determined by HPLC with a
Chiralpak IB column (PE/IPA = 95/5, 2 mL/min), t (major)= 9.685 min (S); t (minor)=
R
R
9
.942 min (R), 82% ee. [α] -13.6 (c 0.46, CHCl ).
D 3
(
R)-N-(1-(4-bromophenyl)ethyl)aniline 6g, yellow oil (yield 90%). MS-ESI, m/z 298.02
1
[
M+ Na]⁺. HR-MS-ESI m/z calcd for C H BrN [M+ H]⁺ 276.0316, found: 276.0310. H
1
4 14
NMR (600 MHz, CDCl ) δ 7.43 (d, J = 8.4 Hz, 2 H), 7.24 (d, J = 8.6 Hz, 2 H), 7.09 (t, J =
3
7
1
1
.9 Hz, 2 H), 6.65 (t, J = 7.3 Hz, 1 H), 6.47 (d, J = 7.7 Hz, 2 H), 4.43 (q, J = 6.7 Hz, 1 H),
1
3
.48 (d, J = 6.7 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 146.96, 144.38, 131.75, 129.15,
3
27.64, 120.49, 117.55, 113.32, 53.06, 25.05. Enantiomeric excess was determined
by HPLC with a Chiralpak IB column (PE/IPA = 95/5, 2 mL/min), t (minor)= 16.987
R
min (S); t (major)= 20.810 min (R), 85% ee. [α] +18.2 (c 0.46, CHCl ).
R
D
3
(
R)-4-bromo-N-(1-phenylethyl)aniline 6h, yellow oil (yield 87%). MS-ESI, m/z 298.02
1
[
M+ Na]⁺. HR-MS-ESI m/z calcd for C H BrN [M+ H]⁺ 276.0313, found: 276.0310. H
1
4 14
NMR (600 MHz, CDCl ) δ 7.22 (dd, J = 8.1, 5.2 Hz, 4 H), 7.14 (dt, J = 8.5, 2.9 Hz, 1 H),
3
7
6
1
.06 (d, J = 8.8 Hz, 2 H), 6.28 (d, J = 8.8 Hz, 2 H), 4.33 (q, J = 6.7 Hz, 1 H), 1.41 (d, J =
1
3
.7 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 145.15, 143.57, 130.73, 127.68, 126.00,
3
24.71, 113.87, 107.82, 52.45, 23.88. Enantiomeric excess was determined by HPLC
with a Chiralpak IB column (PE/IPA = 95/5, 2 mL/min), t (major)= 14.353 min (R); tR
R
(
(
[
minor)= 16.155 min (S), 87%ee. [α] +30.9 (c 0.46, CHCl ).
D 3
R)-4-methyl-N-(1-phenylethyl)aniline 6i, yellow oil (yield 88%). MS-ESI, m/z 234.16
1
M+ Na]⁺. HR-MS-ESI m/z calcd for C H N [M+ H]⁺ 212.1364, found: 2112.1361. H
1
5 17
NMR (600 MHz, CDCl ) δ 7.28 (d, J = 7.4 Hz, 2 H), 7.23 (t, J = 7.6 Hz, 2 H), 7.13 (t, J =
3
7
2
1
.3 Hz, 1 H), 6.82 (d, J = 8.1 Hz, 2 H), 6.35 (d, J = 8.3 Hz, 2 H), 4.37 (q, J = 6.7 Hz, 1 H),
1
3
.10 (s, 3 H), 1.42 (d, J = 6.7 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 144.40, 144.00,
3
28.56, 127.57, 125.76, 125.36, 124.84, 112.43, 52.67, 23.98, 19.30. Enantiomeric
excess was determined by HPLC with a Chiralpak IB column (PE/IPA = 95/5, 2
mL/min), t (minor)= 12.283 min (S); t (major)= 13.207 min (R), 83%ee. [α] +11.3 (c
R
R
D
0
.46, CHCl3).
(
S)-4-ethyl-N-(1-phenylethyl)aniline 6j, yellow oil (yield 90%). MS-ESI, m/z 248.14
1
[
M+Na]⁺. HR-MS-ESI m/z calcd for C H N [M+ H]⁺ 226.1521, found: 226.1517. H
1
6 19
NMR (600 MHz, CDCl ) δ 7.26 (d, J = 7.6 Hz, 2 H), 7.20 (t, J = 7.5 Hz, 2 H), 7.11 (t, J =
3
7
2
.2 Hz, 1 H), 6.83 (d, J = 8.2 Hz, 2 H), 6.36 (d, J = 8.3 Hz, 2 H), 4.35 (q, J = 6.7 Hz, 1 H),
13
.39 (q, J = 7.6 Hz, 2 H), 1.39 (d, J = 6.7 Hz, 3 H), 1.05 (t, J = 7.6 Hz, 3 H). C NMR (151
MHz, CDCl ) δ 144.48, 144.27, 131.98, 127.56, 127.37, 125.76, 124.85, 112.40, 52.70,
3
2
6.84, 23.96, 14.79. Enantiomeric excess was determined by HPLC with a Chiralpak
IB column (PE/IPA = 95/5, 2 mL/min), t (minor) = 11.027 min (R); t (major) = 11.390
R
R
min (S), 89%ee. [α] -10.0 (c 0.46, CHCl ).
D
3
1
1

(R)-4-methoxy-N-(1-phenylethyl)aniline 6k, colorless oil (yield 93%). MS-ESI, m/z
2
2
7
6
1
50.12 [M+ Na]⁺. HR-MS-ESI m/z calcd for C H NO [M+ H]⁺ 228.1316, found:
15 17
1
28.1310. H NMR (600 MHz, CDCl ) δ 7.28 (d, J = 7.6 Hz, 2 H), 7.23 (t, J = 7.5 Hz, 2 H),
3
.14 (t, J = 7.2 Hz, 1 H), 6.61 (d, J = 8.8 Hz, 2 H), 6.39 (d, J = 8.8 Hz, 2 H), 4.33 (q, J =
1
3
.7 Hz, 1 H), 3.61 (s, 3 H), 1.42 (d, J = 6.7 Hz, 3 H). C NMR (151 MHz, CDCl ) δ 151.01,
3
44.44, 140.52, 127.58, 125.81, 124.90, 113.80, 113.65, 54.74, 53.33, 24.01.
Enantiomeric excess was determined by HPLC with a Chiralpak IB column (PE/IPA =
9
+
5/5, 2 mL/min), t (major)= 19.642 min (R); t (minor)= 20.710 min (S), 91% ee. [α]
R
R
D
13.4 (c 0.46, CHCl3).
(
S)-4-ethoxy-N-(1-phenylethyl)aniline 6l, yellow oil (yield 95%). MS-ESI, m/z 264.14
1
[
M+ Na]⁺. HR-MS-ESI m/z calcd for C H NO [M+ H]⁺ 242.1474, found: 242.1467. H
1
6 19
NMR (600 MHz, CDCl ) δ 7.29 (d, J = 7.6 Hz, 2 H), 7.23 (t, J = 7.6 Hz, 2 H), 7.14 (t, J =
3
7
3
.3 Hz, 1 H), 6.61 (d, J = 8.9 Hz, 2 H), 6.45 (d, J = 8.5 Hz, 2 H), 4.34 (q, J = 6.7 Hz, 1 H),
1
3
.83 (q, J = 7.0 Hz, 2 H), 3.03 (q, J = 6.9 Hz, 3 H), 1.46 (d, J = 6.7Hz, 3 H). C NMR (151
MHz, CDCl ) δ 128.58, 126.95, 126.12, 115.62, 64.04, 45.86, 14.96, 8.61.
3
Enantiomeric excess was determined by HPLC with a Chiralpak IB column (PE/IPA =
9
5/5, 2 mL/min), t (minor)= 11.673 min (R); t (major)= 12.458 min (S), 96% ee. [α]
R R D
-
20.6 (c 0.46, CHCl3).
Acknowledgements The NSFC is thanked for their financial supports (21877025,
1606174), including the Scientific Research Foundation of Hebei Educational
4
Committee (QN2016177, QN2017021).
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-
9
1
4

Highlight
Axial biscarboline N-O-containing catalysts with solfone moiety afforded high
enantioselectivity up to 96%ee in 1,2-transfer hydrogenations of ketimines using
trichlorosilane.