Supporting Information

Supporting Information for

Highly Enantioselective Alkylation Reaction of Enamides by Brnsted-Acid

Catalysis

Qi-Xiang Guo, * Yun-Gui Peng, Jin-Wei Zhang, Liu Song, Zhang Feng, Liu-Zhu Gong*

School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China, Hefei National
Laboratory for Physical Sciences at the Microscale and Department of Chemistry, UniVersity of Science and
Technology of China, Hefei 230026, China
E-mail: [email protected]; [email protected]

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Supporting Information

General data...............................................................................................................S2
I.

Preparation of Acidified Chiral phosphoric acid 5a....S2

II.

Optimization of reaction conditions............................................................. S3

III.

Preparation of diaryl methanols and the corresponding NMR data....S3-S7

IV.

Procedure for the asymmetric alkylation reaction and the analytic data for
the corresponding compounds..............................................................S7-S16

V.

Copies of HPLC and NMR spectra......................................................S17-S80

General data: NMR spectra were recorded on a Brucker-400 MHz spectrometer. Optical rotations
were determined at 589 nm (sodium D line) by using a Perkin-Elmer-343 polarimeter. HRMS
(Micromass GCT-MS) spectra were recorded on P-SIMS-Gly of Bruker Daltonics Inc. Infrared
spectra were recorded on a Nicolet MX-1E FT-IR spectromter. HPLC analysis was performed on
Waters-Breeze (2487 Dual Absorbance Detector and 1525 Binary HPLC Pump, UV detection
monitored at 254nm). Chiralpak AD-H, AS-H, Chromasil CHI-TBB columns were purchased from
Daicel Chemical Industries, LTD. CH2Cl2 was dried over CaH2 and distilled prior to use. Petroluem
ether and ethyl acetate for the column chromatography were distilled before use.
Materials: All the catalysts were synthesized according to the literature1-5. All starting materials
were purchased from Alfa and Aldrich and used directly. Absolute configuration of the major
isomer was assigned by comparison with the literature6 value of optical rotation.
I. Preparation of Acidified Chiral phosphoric acid 5a.
Ph

Ph
O
P
O

2M HCl

OH

CH 2 Cl2

O
P
O

O
OH

Ph

Ph

5a

5a'

A 100 ml round flask was charged with unacidified phosphoric acid 5a (762mg, 1.5mmol),
CH2Cl2 (40ml) was added to dissolved the compound. Then 2M HCl aqueous (40ml) was added.
The solution was stirred for 3hs. The organic layer was separated and the aqueous was extracted by
CH2Cl2 (15ml) for 3 times. The organic phase was combined and dried by Na2SO4. Removed the
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Supporting Information

solid by filtration, and evaporated the solvent to afford the active phosphoric acid 5a (740mg, 97%
yield).
II. Table S1. Solvent screeninga
O
HN

OH

5 mol % 4a
solvent, 0oC

HN

1a

2a

NH

3a

entry

solvent

Time(h)

Yield(%)b

Ee(%)c

CH2Cl2

12

78

56

Cl(CH2)2Cl

18

89

55

CCl4

18

61

38

CHCl3

18

71

48

Et2O

18

68

57

The reaction was carried out with 1a (0.2mmol), 2a (0.1mmol), 5% mol 4a in solvent (2ml) at 0oC.

isolated yield. c The ee value was determined by HPLC on a AS-H column.

III. General procedure for the preparation of the (1H-3-indolyl)(aryl)methanols:

O
R

Ar

N
H

20% mol TMG

OH

Ar

H 2O, rt

HN

A 10ml tube was charged with indole (702mg, 6mmol), benzaldehyde (212mg, 2mmol), and
Tetramethylguanidine (TMG, 46mg, 0.4mmol). Then the solvent H2O (2ml) was added to the
mixture and the resultant was stirred for 24hs. The EtOAc (10ml) and H2O (10ml) were added to
the solution. Separated the organic layer and the water phase was extracted by EtOAc (10ml*3).
The

organic

phase

was

combined

and

dried

by

Na2SO4.

The

product

(1H-3-indolyl)(phenyl)methanol (320mg, yield: 71%) was obtained by flash chromatography

(petroleum: AcOEt 5:1).

OH

(1H-indol-3-yl)(phenyl)methanol:1H NMR (400 MHz, DMSO) 10.85

(s, 1H), 7.51 7.39 (m, 3H), 7.31 (ddd, J = 16.6, 11.6, 4.1, 3H), 7.19 (dd,

HN

J = 10.9, 3.7, 1H), 7.09 (d, J = 2.3, 1H), 7.02 (t, J = 7.5, 1H), 6.89 (dd, J =
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Supporting Information

7.8, 7.1, 1H), 5.95 (d, J = 4.4, 1H), 5.55 (d, J = 4.4, 1H); 13C NMR (101 MHz, DMSO) 146.74,
137.44, 128.64, 127.26, 127.20, 126.54, 123.47, 121.80, 120.52, 120.43, 119.15, 112.23, 69.79.

(1H-indol-3-yl)(p-tolyl)methanol: 1H NMR (400 MHz, DMSO-d6)

OH

(ppm) 11.20 10.51 (m, 1H), 7.47 7.38 (m, 1H), 7.35 7.27 (m, 3H),
HN

7.12 7.05 (m, 3H), 7.05 6.97 (m, 1H), 6.91 6.83 (m, 1H), 5.94
5.81 (m, 1H), 5.50 5.43 (m, 1H), 2.26 (s, 3H);

13

C NMR (101 MHz,

DMSO-d6) (ppm) 143.77, 137.44, 136.15, 129.19, 127.17, 126.55, 123.39, 121.75, 120.66, 120.45,
119.08, 112.19, 69.61, 21.55.

(1H-indol-3-yl)(3-nitrophenyl)methanol:

OH
NO2
HN

H NMR (400 MHz,

DMSO-d6) (ppm) 10.99 (s, 1H), 8.33 (t, J = 1.8, 1H), 8.12 8.04
(m, 1H), 7.92 7.85 (m, 1H), 7.60 (t, J = 7.9, 1H), 7.47 (d, J = 7.6,
1H), 7.35 (d, J = 8.2, 1H), 7.21 (d, J = 2.4, 1H), 7.05 (ddd, J = 8.1,

7.1, 1.1, 1H), 6.96 6.87 (m, 1H), 6.12 (d, J = 4.4, 1H), 5.96 (d, J = 4.4, 1H); 13C NMR (101 MHz,
DMSO-d6) (ppm) 148.83, 148.16, 137.12, 133.53, 129.95, 125.89, 123.70, 121.99, 121.71, 121.12,
119.87, 119.10, 119.02, 112.06, 68.37.

4-(hydroxy(1H-indol-3-yl)methyl)benzonitrile: 1H NMR (400 MHz,

OH

DMSO-d6) (ppm) 10.95 (s, 1H), 7.78 7.73 (m, 2H), 7.66 (d, J =
HN

CN

8.1, 2H), 7.48 (d, J = 8.0, 1H), 7.34 (dt, J = 8.1, 0.8, 1H), 7.16 (d, J =
2.4, 1H), 7.08 7.02 (m, 1H), 6.92 (ddd, J = 8.0, 7.0, 1.0, 1H), 6.05

(d, J = 4.3, 1H), 5.85 (d, J = 4.4, 1H). 13C NMR (101 MHz, DMSO-d6) (ppm) 152.43, 137.44,
132.76, 128.00, 126.28, 123.91, 122.01, 120.25, 119.93, 119.39, 119.35, 112.37, 109.98, 69.18.

(1H-indol-3-yl)(4-(trifluoromethyl)phenyl)methanol:

OH

H-NMR

(DMSO-d6, 400MHz) (ppm) 10.9 (s, 1H), 7.70-7.64 (m, 4H), 7.47
HN

CF3

(d, J = Hz, 1H), 7.33 (d, J = Hz, 1H), 7.17 (s, 1H), 6.93-6.91 (t, J =
Hz, 1H), 6.91-6.89 (t, J = Hz, 1H), 6.06 (d, J = Hz, 1H), 5.83 (d, J =

Hz, 1H); 13C-NMR (DMSO-d6, 101MHz) (ppm) 150.6, 136.6, 127.2, 126.9, 125.4, 124.7, 124.7,
122.9, 121.1, 119.4, 118.8, 118.5, 111.5, 68.3.
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Supporting Information

(4-bromophenyl)(1H-indol-3-yl)methanol: 1H NMR (400 MHz,

OH

DMSO-d6) (ppm) 10.89 (s, 1H), 7.44 (dt, J = 15.7, 8.4, 6H), 7.33 (d,
HN

Br

J = 8.1, 1H), 7.12 (d, J = 2.1, 1H), 7.03 (t, J = 7.3, 1H), 6.90 (t, J = 7.4,
1H), 5.94 (d, J = 4.3, 1H), 5.66 (d, J = 4.4, 1H). 13C NMR (101 MHz,

DMSO-d6) (ppm) 146.18, 137.45, 131.52, 129.42, 126.37, 123.65, 121.89, 120.32, 120.20, 119.93,
119.25, 112.29, 69.07.

(4-chlorophenyl)(1H-indol-3-yl)methanol: 1H NMR (400 MHz,

OH

DMSO-d6) (ppm) 10.89 (s, 1H), 7.50 7.42 (m, 3H), 7.38 7.30 (m,
HN

Cl

3H), 7.12 (d, J = 2.4, 1H), 7.04 (ddd, J = 8.2, 7.1, 1.1, 1H), 6.90 (ddd,
J = 8.0, 7.0, 1.0, 1H), 5.96 (d, J = 4.4, 1H), 5.67 (d, J = 4.4, 1H). 13C

NMR (101 MHz, DMSO-d6) (ppm) 145.75, 137.47, 131.72, 129.03, 128.61, 126.40, 123.65,
121.90, 120.34, 120.01, 119.26, 112.30, 69.05.

(3-chloro-4-fluorophenyl)(1H-indol-3-yl)methanol:

OH

HN

H-NMR

Cl

(DMSO-d6, 400MHz) (ppm) 10.95 (s, 1H), 7.62-7.60 (d, J = Hz, 1H),

7.47-7.41 (m, 2H), 7.30 (m, 2H), 7.15 (d, J = Hz, 1H), 6.94-6.92 (m,
1H), 6.92-6.90 (m, 1H), 5.98 (d, J = Hz, 1H), 5.80 (d, J = Hz, 1H);

(DMSO-d6, 101MHz) (ppm) 157.0, 154.6, 143.8, 143.8, 136.6, 128.1, 126.8, 126.7, 125.4, 122.9,
121.1, 118.5, 116.3, 116.1, 111.5, 67.7.

(3,4-difluorophenyl)(1H-indol-3-yl)methanol: 1H NMR (400 MHz,

OH

HN

DMSO-d6) (ppm) 10.93 (s, 1H), 7.46 (ddd, J = 9.9, 7.9, 2.7, 2H), 7.40

7.22 (m, 3H), 7.15 (d, J = 2.3, 1H), 7.05 (t, J = 7.5, 1H), 6.92 (t, J =
7.5, 1H), 5.97 (d, J = 4.4, 1H), 5.77 (d, J = 4.5, 1H). 13C NMR (101

MHz, DMSO-d6) (ppm) 151.25, 151.12, 150.18, 150.05, 148.82, 148.69, 147.76, 147.63, 144.69,
137.46, 126.34, 123.76, 123.72, 123.69, 123.66, 121.95, 120.29, 119.71, 119.34, 117.68, 117.52,
115.96, 115.79, 112.33, 68.64.

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Supporting Information

(1H-indol-3-yl)(naphthalen-2-yl)methanol: 1H-NMR (DMSO-d6,

OH

400MHz) (ppm) 10.91 (s, 1H), 8.03, (s, 1H), 7.91-7.89 (m, 1H),
HN

7.83 (m, 1H), 7.81-7.79 (m, 1H), 7.55-7.52 (dd, J = 1.6 Hz, 8.4 Hz,
1H), 7.47-7.42 (m, 3H), 7.33-7.31 (dd, J = 0.8 Hz, 7.3 Hz, 1H),

7.18-7.17 (d, J = 2.3 Hz, 1H), 7.03-6.99 (m, 1H), 6.89-6.85 (m, 1H), 6.13-6.12 (d, J = 4.2 Hz, 1H),
5.74-5.73 (d, J = 4.2 Hz, 1H); 13C-NMR (DMSO-d6, 101MHz) (ppm) 143.1, 136.3, 132.5, 131.8,
127.5, 127.2, 127.0, 125.6, 125.4, 125.2, 125.1, 123.7, 122.5, 120.7, 119.2, 119.1, 118.0, 111.1,
68.7.

4-(hydroxy(5-methyl-1H-indol-3-yl)methyl)benzonitrile: 1H NMR
OH

(400 MHz, DMSO-d6) (ppm) 10.98 10.53 (m, 1H), 7.79 7.72 (m,
2H), 7.64 (d, J = 8.1, 2H), 7.27 (d, J = 0.7, 1H), 7.21 (d, J = 8.2, 1H),

HN

CN

7.07 (d, J = 2.4, 1H), 6.87 (dd, J = 8.3, 1.5, 1H), 6.00 (d, J = 4.4, 1H),
5.79 (d, J = 4.4, 1H), 2.31 (s, 3H); 13C NMR (101 MHz, DMSO-d6)
(ppm) 152.49, 135.78, 132.75, 127.99, 127.73, 126.56, 123.94, 123.61, 119.94, 119.79, 118.82,
112.05, 109.93, 69.15, 22.14.

4-((5-bromo-1H-indol-3-yl)(hydroxy)methyl)benzonitrile:

Br
OH

H-NMR (DMSO-d6, 400MHz) (ppm) 11.1 (s, 1H), 7.80-7.78 (d, J

= 8.0 Hz, 2H), 7.65-7.63 (d, J = 8.0 Hz, 2H), 7.31-7.29 (m, 1H),

HN

CN

7.22-7.21 (d, J = 4.0 Hz, 1H), 7.18-7.15 (dd, J = 4.0, 8.0 Hz, 1H),

6.04-6.03 (d, J = 4.0 Hz, 1H), 5.96-5.94 (d, J = 4.0 Hz, 1H); 13C-NMR (DMSO-d6, 101MHz) (ppm)
151.7, 135.7, 132.5, 127.7, 127.5, 125.2, 124.1, 122.1, 119.5, 118.8, 114.1, 109.7, 68.4.

4-((5-chloro-1H-indol-3-yl)(hydroxy)methyl)benzonitrile:

Cl
OH

HN

NMR (400 MHz, DMSO-d6) (ppm) 11.16 (d, J = 0.5, 1H), 7.78 (d,
J = 8.2, 2H), 7.65 (d, J = 8.1, 2H), 7.53 7.46 (m, 1H), 7.36 (dd, J =
CN

8.6, 0.4, 1H), 7.23 (d, J = 2.4, 1H), 7.05 (dd, J = 8.6, 2.1, 1H), 6.03
(d, J = 4.4, 1H), 5.92 (d, J = 4.4, 1H);

13

C NMR (101 MHz,

DMSO-d6) (ppm) 152.06, 135.87, 132.87, 127.93, 127.36, 125.71, 124.01, 121.96, 119.88, 119.41,
119.26, 113.95, 110.12, 68.80.
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Supporting Information

4-(hydroxy(5-methoxy-1H-indol-3-yl)methyl)benzonitrile:

MeO
OH

NMR (400 MHz, DMSO-d6) (ppm) 10.79 (d, J = 1.5, 1H), 7.77
(d, J = 8.4, 2H), 7.66 (d, J = 8.1, 2H), 7.23 (dd, J = 8.7, 0.4, 1H),

HN

CN

7.07 (d, J = 2.5, 1H), 6.96 (d, J = 2.5, 1H), 6.71 (dd, J = 8.8, 2.4,
1H), 6.02 (d, J = 4.5, 1H), 5.80 (d, J = 4.5, 1H), 3.69 (s, 3H); 13C

NMR (101 MHz, DMSO-d6) (ppm) 153.79, 152.41, 132.74, 128.46, 127.98, 126.71, 124.58,
119.95, 119.09, 112.96, 111.94, 109.94, 102.24, 69.07, 56.16.

(3-fluorophenyl)(1H-indol-3-yl)methanol: 1H NMR (400 MHz,

OH
F
HN

DMSO-d6) (ppm) 10.90 (s, 1H), 7.48 (d, J = 8.1, 1H), 7.36 7.21 (m,
4H), 7.14 (d, J = 2.4, 1H), 7.08 6.96 (m, 2H), 6.91 (ddd, J = 8.0, 7.1,
1.0, 1H), 5.98 (d, J = 4.4, 1H), 5.71 (d, J = 4.5, 1H);

13

C NMR (101

MHz, DMSO-d6) (ppm) 164.16, 161.75, 149.98, 149.92, 137.43, 130.58, 130.50, 126.40, 123.69,
123.20, 123.18, 121.91, 120.34, 119.88, 119.28, 114.01, 113.80, 113.78, 113.56, 112.30, 69.11.

3-(hydroxy(1H-indol-3-yl)methyl)benzonitrile: 1H NMR (400 MHz,

OH
CN
HN

DMSO-d6) (ppm) 11.01 (s, 1H), 7.88 (d, J = 1.6, 1H), 7.78 (d, J =
7.9, 1H), 7.70 7.63 (m, 1H), 7.57 7.43 (m, 2H), 7.35 (d, J = 8.1,
1H), 7.17 (d, J = 2.4, 1H), 7.08 7.00 (m, 1H), 6.96 6.88 (m, 1H),

6.03 (d, J = 4.3, 1H), 5.86 (d, J = 4.4, 1H); 13C NMR (101 MHz, DMSO-d6) (ppm) 148.0, 137.0,
131.7, 130.8, 130.1, 129.7, 125.9, 123.5, 121.6, 119.8, 119.6, 119.1, 119.0, 112.0, 111.3, 68.5.
IV. General Procedure for the asymmetric alkylation reaction of enamides:
HN

Bz

HO

Ar

R'

Ar

10% mol 5a
R

R'
1

N
H

CH2Cl2, -30oC

R
3

NH

A 10ml dried tube was charged with enamide 1a (44.6mg, 0.2mmol), alcohol 2a (22.3mg, 0.1mmol)
and catalyst 5a (5.1mg, 0.01mmol) at -30oC. The solvent CH2Cl2 (3ml) was added and the solution
was stirred for 51hs. Then two drop of Et3N was added to quench the reaction. Removed the solvent
and the pure product 3a (23.7mg, 73%yield and 92%ee) was obtained through siligel
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Supporting Information

chromatograph column separation (eluent: petroleum/ ethyl acetate = 6/1, Rf = 0.2).

(R)-3-(1H-indol-3-yl)-1,3-diphenylpropan-1-one (3a):
yield: 73%; ee: 92%; []D20 = -32.5 (c=0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 7.96-7.91 (m, 3H),
7.54-7.51 (m, 1H), 7.42-7.40 (m, 3H), 7.36-7.30 (m, 3H), 7.25-7.23 (m, 2H), 7.15-7.12 (m, 2H),
7.02-6.98 (m, 2H), 5.08-5.04 (t, J = 7.2Hz, 1H), 3.84-3.69 (m, 2H); 13C-NMR (CDCl3, 101 MHz)
(ppm) 199.0, 144.6, 137.5, 137.0, 133.4, 129.0, 128.8, 128.5, 128.2, 127.0, 126.7, 122.5, 121.8,
119.9, 119.8, 119.7, 111.5, 45.6, 38.6; IR (KBr) (cm-1) 3412, 3051, 2913, 1678, 1505, 1457, 1338,
1104, 741; HRMS(EI) calcd. for 325.1467, found: 325.1471; The enantiomeric excess of 92%ee
was determined by HPLC (Daicel Chirapak AS-H, hexane/isopropanol = 85/15, flow rate 1.0
mL/min, T = 30oC, 254 nm, tR (major)14.052 min, tR(minor) 16.168 min);
3-(1H-indol-3-yl)-1-phenyl-3-p-tolylpropan-1-one (3b):
Yield: 80; ee: 92; []D20 = -22.0 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether / ethyl acetate = 6:1); 1H-NMR (CDCl3, 400 MHz) (ppm) 7.93-7.90 (m, 3H),
7.53-7.49 (m, 1H), 7.44-7.38 (m, 3H), 7.28-7.26 (d, J = 8.16Hz, 1H), 7.23-7.21 (m, 2H), 7.14-7.10
(m, 1H), 7.05-7.03 (d, J = 8.04Hz, 2H), 7.01-6.98 (m, 1H), 6.94 (d, J = 2.4Hz, 1H), 5.03-5.00 (t, J =
7.24Hz, 1H), 3.81-3.65 (m, 2H), 2.26 (s, 3H); 13C-NMR (CDCl3, 101 MHz) (ppm) 199.11, 141.6,
137.6, 137.0, 136.1, 133.3, 129.5, 128.9, 128.5, 128.0, 127.0, 122.5, 121.8, 119.9, 119.9, 119.7,
111.5, 45.7, 38.2, 21.4; IR: (cm-1) 3413, 3054, 2923, 1678, 1514, 1456, 1338, 1099, 742;
HRMS(EI) calcd for 339.1623, found: 339.1621; The enantiomeric excess of 92% was determined
by HPLC (AS-H column, Hexane/ propan-2-ol = 90/10; flow rate 1 mL/ min, T = 30oC, 254 nm;
tR(major) 17.311min, tR(minor) 20.538 min).
3-(4-chlorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (3c):
Yield: 74%; ee: 91%; []D20 = -24.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H NMR (400 MHz, CDCl3) (ppm) 7.99 (br, 1H), 7.93 7.91
(m, 2H), 7.57 7.52 (m, 1H), 7.46 7.37 (m, 3H), 7.34-7.32 (dt, J = 8.9, 0.8, 1H), 7.29 7.24 (m,
2H), 7.20 7.18 (m, 2H), 7.16-7.14 (m, 1H), 7.04-7.00 (m, 1H), 6.99-6.98 (dd, J = 2.4, 0.9, 1H),
5.06-5.02 (m, 1H), 3.83-3.66 (m, 2H); 13C NMR (101 MHz, CDCl3) (ppm) 199.59, 144.11, 138.37,
138.02, 134.55, 130.63, 130.03, 129.95, 129.47, 127.81, 124.97, 123.73, 123.47, 122.72, 120.95,
120.80, 112.58, 46.34, 38.95; IR: (cm-1) 3399, 3054, 2906, 1681, 1537, 1457, 1335, 746;
HRMS(EI) calcd for 359.1077, found: 359.1075The enantiomeric excess of 91% was determined
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Supporting Information

by HPLC (AD-H column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/ min; T = 30oC, 254 nm; tR
(major) 17.440 min and tR (minor) 19.844 min).
3-(4-bromophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (3d):
Yield: 72%; ee: 92%; []D20 = -8.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H NMR (DMSO-d6, 400 MHz) (ppm) 10.89 (d, J = 0.6, 1H),
8.02-8.00 (dd, J = 4.4, 3.7, 2H), 7.64 7.60 (m, 1H), 7.52-7.49 (t, J = 7.8, 2H), 7.41 7.35 (m, 6H),
7.31-7.29 (m, 1H), 7.04-7.00 (t, J = 7.2, 1H), 6.91-6.87 (m, 1H), 4.86 4.83 (m, 1H), 3.93 3.80
(m, 2H); 13C NMR (DMSO-d6, 101 MHz) 197.9, 144.5, 136.5, 136.0, 132.9, 130.6, 129.8, 128.4,
127.7, 125.9, 121.7, 120.7, 118.4, 118.3, 118.0, 117.2, 111.1, 43.6, 36.7; IR: (cm-1) 3398, 3039,
2920, 1682, 1483, 1445, 709, 747; HRMS(EI) calcd for 403.0572found: 403.0578The
enantiomeric excess of 92% was determined by HPLC (AD-H column, Hexane/ propan-2-ol= 80/20;
flow rate 1 mL/ min; T = 30oC, 254 nm; tR (major) 13.256 min and tR (minor) 14.965 min).
4-(1-(1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (3e):
Yield: 80%; ee: 94%; []D20 = -3.5, (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 4/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.07 (s, 1H), 7.94-7.91
(m, 2H), 7.58-7.52 (m, 3H), 7.47-7.43 (m, 4H), 7.36-7.34 (m, 2H), 7.20-7.16 (m, 1H), 7.06-7.02 (m,
2H), 5.14-5.10 (m, 1H), 3.87-3.71 (m, 2H);

13

C-NMR (CDCl3, 101 MHz) (ppm) 199.0, 151.3,

138.1, 138.0, 134.7, 133.7, 130.1, 130.1, 129.4, 127.6, 123.9, 122.8, 121.1, 120.5, 120.3, 119.4,
112.7, 111.5, 45.8, 39.5; IR: (cm-1) 3398, 3048, 2917, 2226, 1682, 1529, 1457, 1313, 1263, 747;
HRMS(EI) calcd for 350.1419, found: 350.1411; The enantiomeric excess of 94% was determined
by HPLC (AS-H column, Hexane/propan-2-ol= 70/30; flow rate 1 mL/ min; T = 30oC, 254 nm; tR
(major) 14.048 min and tR (minor) 16.941 min).
3-(1H-indol-3-yl)-1-phenyl-3-(4-(trifluoromethyl)phenyl)propan-1-one (3f):
Yield: 96%; ee: 90%; []D20 = -33.0 (c=0.12, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.01 (s, 1H), 7.94-7.92
(m, 2H), 7.57-7.40 (m, 8H), 7.35-7.33 (d, J = 8.1Hz, 1H), 7.19-7.15 (t, J = 7.2Hz, 1H), 7.06-7.00
(m, 2H), 5.16-5.12 (t, J = 7.1Hz, 1H), 3.87-3.72 (m, 2H);

13

C-NMR (CDCl3, 101 MHz) (ppm)

198.1, 155.2, 148.5, 137.0, 136.7, 133.2, 128.7, 128.3, 128.1, 126.4, 125.6, 125.5, 122.5, 121.5,
119.7, 119.3, 118.6, 111.3, 44.8, 38.0; IR: (cm-1) 3398, 3064, 2959, 2925, 1680, 1614, 1458, 1425,
1324, 1113, 740; HRMS(EI) calcd for 393.1340found: 393.1335The enantiomeric excess of 90%
was determined by HPLC (AS-H column, Hexane/propan-2-ol= 90/10; flow rate 1 mL/ min; T =
S9

Supporting Information

30oC, 254 nm; tR (major) 12.133 min and tR (minor) 13.332 min).
3-(3-fluorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (3g):
Yield: 78%; ee: 90%; []D20 = -47.5 (c= 0.08, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H NMR (DMSO-d6, 400 MHz) (ppm) 10.84 (s, 1H), 7.97
7.95 (m, 2H), 7.59-7.54 (m, 1H), 7.47-3.99 (m, 3H), 7.32 (d, J = 2.0, 1H), 7.25-7.16 (m, 4H),
6.99-6.95 (m, 1H), 6.88-6.82 (m, 2H), 4.85-4.82 (t, J = 7.3Hz, 1H), 3.91-3.76 (m, 2H);

13

C-NMR

(DMSO-d6, 101 MHz) (ppm) 199.0, 164.1, 161.7, 149.3, 149.2, 137.6, 137.1, 134.0, 130.7, 130.6,
129.5, 128.9, 127.1, 124.8, 124.7, 122.8, 121.9, 119.4, 119.2, 118.3, 115.3, 115.1, 113.5, 113.3,
112.2, 44.7, 38.1; IR: (cm-1) 3398, 3053, 2959, 2914, 1669, 1585, 1486, 1458, 1274, 1202, 768,
740; HRMS(EI) calcd for 343.1372found: 343.1366The enantiomeric excess of 90% was
o

determined by HPLC (AS-H column, Hexane/propan-2-ol = 85/15; flow rate 1 mL/ min; T = 30 C,
254 nm; tR (major) 11.839 min and tR (minor) 13.180 min).
3-(1H-indol-3-yl)-3-(3-nitrophenyl)-1-phenylpropan-1-one (3h):
Yield: 85%; ee: 90%; []D20 = -11.0 (c=0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 5/1); 1H-NMR (DMSO-d6, 400 MHz) (ppm) 10.97 (d, J = 0.6Hz,
1H), 8.25 (s, 1H), 8.05-8.03 (d, J = 7.4Hz, 2H), 7.99-7.94 (m, 2H), 7.65-7.61 (t, J = 7.4Hz, 1H),
7.55-7.46 (m, 5H), 7.33-7.31 (d, J = 8.1Hz, 1H), 7.05-7.02 (t, J = 7.6Hz, 1H), 6.93-6.89 (t, J =
7.8Hz, 1H), 5.05-5.02 (m, 1H), 4.07-3.93 (m, 2H); 13C-NMR (DMSO-d6, 101 MHz) (ppm) 198.8,
148.6, 148.6, 137.5, 137.1, 135.7, 134.1, 130.4, 129.5, 128.9, 126.9, 123.1, 122.0. 121.9. 121.8.
119.3. 119.2. 117.9. 112.3. 44.6. 77.9; IR: (cm-1) 3398, 3058, 2920, 2848, 1680, 1519, 1452, 1346,
1107, 979, 735, 685; HRMS(EI) calcd for 343.1372, found: 343.1366; The enantiomeric excess of
90% was determined by HPLC (column, Hexane/propan-2-ol = 70/30; flow rate 1 mL/ min; T =
30oC, 254 nm; tR (major) 10.766 min and tR (minor) 12.330 min).
3-(1-(1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (3i):
Yield: 74%; ee: 91%; []D20 = -28.7 (c=0.08, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 4/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.07 (s, 1H) 7.95-7.92
(m, 2H), 7.64-7.62 (m, 2H), 7.56-7.54 (m, 1H), 7.47-7.43 (m, 3H), 7.37-7.33 (m, 3H), 7.20-7.16 (m,
2H), 7.06-7.02 (m, 2H), 5.12-5.08 (m, 1H), 3.86-3.69 (m, 2H);

13

C-NMR (CDCl3, 101 MHz)

(ppm) 198.1, 146.2, 137.1, 137.0, 133.7, 133.1, 131.8, 130.5, 129.6, 129.1, 128.4, 126.6, 122.9,
122.7, 121.7, 120.1, 119.5, 118.5, 112.8, 111.7, 45.0, 38.0; IR: (cm-1) 3410, 3057, 2926, 2227,
1677, 1505, 1456, 1336, 1103, 748; HRMS(EI) calcd for 350.1419, found: 350.1416; The
S10

Supporting Information

enantiomeric excess of 91% was determined by HPLC (AS-H column, Hexane/propan-2-ol = 70/30;
flow rate 1 mL/ min; T = 30oC, 254 nm; tR (major) 12.956 min and tR (minor) 14.759 min).
3-(3,4-difluorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (3j):
Yield: 89%; ee: 94%; []D20 = -41.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.07 (br, 1H), 7.95-7.92
(m, 2H), 7.58-7.54 (m, 1H), 7.47-7.32 (m, 4H), 7.20-6.99 (m, 6H), 5.06-5.02 (m, 1H), 3.82-3.65 (m,
1H); 13C-NMR (CDCl3, 101 MHz) (ppm) 199.4, 152.9, 152.7, 151.5, 151.4, 150.4, 150.3, 149.1,
148.9, 142.8, 142.7, 138.2, 138.0, 134.6, 130.0, 129.4, 125.1, 125.1, 125.1, 125.0, 123.8, 122.6,
121.0, 120.6, 118.4, 118.3, 118.1, 118.0, 112.6, 46.3, 38.8; IR: (cm-1) 3401, 3054, 2901, 1683,
1520, 1312, 1274, 824, 744; HRMS(EI) calcd for 361.1278, found: 361.1276; The enantiomeric
excess of 94% was determined by HPLC (AD-H column, Hexane/propan-2-ol = 85/15; flow rate 1
mL/ min; T = 30oC, 254 nm; tR (major) 13.435 min and tR (minor) 15.685 min).
3-(3-chloro-4-fluorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (3k):
Yield: 90%; ee: 92%; []D20 = -32.0 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.07 (br, 1H), 7.96-7.93
(m, 2H), 7.59-7.54 (m, 1H), 7.47-7.32 (m, 5H), 7.25-7.16 (m, 2H), 7.07-6.98 (m, 3H)5.06-5.02 (m,
1H), 3.84-3.65 (m, 2H);

13

C-NMR (CDCl3, 101 MHz) (ppm) 199.4, 159.2, 159.2, 156.8, 142.8,

142.7, 138.2, 138.0, 134.6, 131.2, 130.0, 129.4, 129.0, 128.9, 123.8, 122.7, 121.0, 120.6, 117.8,
117.6, 112.6, 46.3, 38.6; IR: (cm-1) 3398, 3058, 2914, 1682, 1533, 1495, 1246, 1154, 979, 911,
767, 748; HRMS(EI) calcd for 377.0983, found: 377.0981; The enantiomeric excess of 92% was
determined by HPLC (Chromasil CHI-TBB column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/
min; T = 30oC, 254 nm; tR (minor) 11.523 min and tR (major) 13.449 min).
3-(1H-indol-3-yl)-3-(naphthalen-2-yl)-1-phenylpropan-1-one (3l):
Yield: 90%; ee: 90%; []D20 = -8.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 7.98 (br, 1H), 7.95-7.93
(d, J = 7.72Hz, 2H), 7.80 (s, 1H), 7.77-7.72 (m, 3H), 7.55-7.37 (m, 7H), 7.33-7.31 (d, J = 8.16Hz,
1H), 7.15-7.11 (t, J = 7.20Hz, 1H), 7.03-7.02 ( d, J = 2.32Hz, 1H), 7.00-6.97 (t, J = 7.92Hz, 1H,
5.26-5.23 (m, 1H), 3.93-3.80 (m, 2H); 13C-NMR (CDCl3, 101 MHz) (ppm) 198.7, 141.8, 137.3,
136.7, 133.6, 133.0, 132.4, 128.6, 128.2, 127.8, 127.6, 126.8, 126.7, 126.0, 125.9, 125.7, 125.4,
122.3, 121.6, 119.6, 119.5, 119.3, 111.1, 45.1, 38.4; IR: (cm-1) 3403, 3058, 2920, 1680, 1596,
1458, 4330, 1269, 746, 679; HRMS(EI) calcd for 375.1623, found: 375.1620; The enantiomeric
S11

Supporting Information

excess of 90% was determined by HPLC (Chromasil CHI-TBB column, Hexane/propan-2-ol=

85/15; flow rate 1 mL/ min; T = 30oC, 254 nm; tR (minor) 12.310 min and tR (major) 14.377 min).
4-(1-(5-chloro-1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (3m):
Yield: 80%; ee: 88%; []D20 = +24.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.10 (br, 1H), 7.93-7.91
(m, 2H), 7.59-7.54 (m, 3H), 7.47-7.43 (m, 4H), 7.31 (m, 1H), 2.27-2.24 (m, 1H), 7.13-7.11 (dd, J =
1.96Hz, 8.64Hz, 1H), 7.05 (d, J = 1.96Hz, 1H), 5.05 (m, 1H), 3.82-3.69 (m, 2H); 13C-NMR (CDCl3,
101 MHz) (ppm) 197.8, 149.8, 137.0, 135.3, 133.8, 132.8, 129.1, 129.0, 128.4, 127.7, 125.9,
123.3, 123.2, 119.3, 118.9, 118.1, 112.7, 110.7, 44.8, 38.3; IR: (cm-1) 3400, 3134, 2913, 2229,
1683, 1537, 1463, 805, 759; HRMS(EI) calcd for 384.1029, found: 384.1034; The enantiomeric
excess of 88 % was determined by HPLC (AS-H column, Hexane/propan-2-ol= 70/30; flow rate 1
mL/ min; T = 30oC, 254 nm; tR (major) 10.872 min and tR (minor) 12.814 min).
4-(1-(5-bromo-1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (3n):
Yield: 79%; ee: 85%; []D20 = +27.1 (c= 0.12, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 5/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.13 (br, 1H), 7.93-7.91
(m, 2H), 7.59-7.54 (m, 3H), 7.48-7.42 (m, 5H), 7.26-7.19 (m, 2H), 7.02 (d, J = 2.36Hz, 1H).
5.07-5.04 (m, 1H), 3.82-3.67 (m, 2H);

13

C-NMR (CDCl3, 101 MHz) (ppm) 197.8, 149.3, 137.0,

135.6, 133.8, 132.8, 129.2, 129.1, 129.0, 128.4, 125.9, 123.0, 122.0, 119.2, 118.0, 113,4, 113.2,
110.8, 44.9, 38.3; IR: (cm-1) 3398, 3051, 2926, 2228, 1683, 1537, 1448, 759; HRMS(EI) calcd for
428.0524, found: 428.0526; The enantiomeric excess of 85% was determined by HPLC (AS-H
column, Hexane/propan-2-ol= 70/30; flow rate 1 mL/ min; T = 30oC, 254 nm; tR (major) 11.221
min and tR (minor) 13.355 min).
4-(1-(5-methyl-1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (3o):
Yield: 70%; ee: 95%; []D20 = +14.5 (c=0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 5/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 7.97 (s, 1H), 7.93-7.91
(m, 2H), 7.57-7.52 (m, 3H), 7.46-7.42 (m, 4H), 7.25-7.22 (m, 1H), 7.15 (s, 1H), 7.01-6.95 (m, 2H),
5.10-5.07 (m, 1H), 3.84-3.69 (m, 2H), 2.37 (m, 3H);

13

C-NMR (CDCl3, 101 MHz) (ppm)

13

NMR (101 MHz, CDCl3) (ppm) 197.8, 150.5, 144.7, 137.0, 134.6, 132.7, 129.8, 129.1, 128.6,
126.6, 122.8, 121.9, 120.0, 119.5, 119.4, 118.3, 111.8, 110.4, 44.7, 38.6, 22.0; IR: (cm-1) 3392,
3034, 2913, 2228, 1685, 1605, 1532, 1209, 806, 758; HRMS(EI) calcd for 364.1576, found:
364.1584; The enantiomeric excess of 95% was determined by HPLC (AS-H column, Hexane/
S12

Supporting Information

propan-2-ol= 70/30; flow rate 1 mL/ min; T = 30oC, 254 nm; tR (major) 10.035 min and tR (minor)
12.009 min).
4-(1-(5-methoxy-1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (3p):
Yield: 69%; ee: 94%; []D20 = +25.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 5/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 7.93-7.91 (m, 3H),
7.58-7.53 (m, 3H), 7.47-7.43 (m, 4H), 7.25-7.22 (m, 1H), 6.99 (d, J = 2.56Hz, 1H), 6.85-6.82 (dd, J
= 2.4Hz, 8.8Hz, 1H), 6.77 (d, J = 2.3Hz, 1H), 5.09 (t, J = 7.8Hz, 1H), 3.84-3.68 (m, 5H); 13C-NMR
(CDCl3, 101 MHz) (ppm) 13C NMR (101 MHz, CDCl3) (ppm) 198.19, 154.47, 150.32, 137.19,
133.78, 132.71, 132.18, 129.15, 129.13, 128.46, 127.11, 122.62, 119.37, 118.09, 112.83, 112.44,
110.55, 101.66, 56.28, 44.87, 38.52; IR: (cm-1) 3397, 3154, 2926, 2225, 1680, 1520, 1482, 1383,
1213, 797; HRMS(EI) calcd for 380.1525, found: 380.1519; The enantiomeric excess of 94% was
determined by HPLC (AS-H column, Hexane/ propan-2-ol= 70/30; flow rate 1 mL/ min; T = 30oC,
254 nm; tR (major) 13.638 min and tR (minor) 17.528 min).
4-(3-(4-chlorophenyl)-1-(1H-indol-3-yl)-3-oxopropyl)benzonitrile (3q):
Yield: 78%; ee: 96%; []D20 = -6.0 (c=0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 5/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.17 (br, 1H), 7.88-7.84
(m, 2H), 7.55-7.52 (m, 2H), 7.46-7.37 (m, 4H), 7.36-7.33 (m, 2H), 7.20-7.16 (m, 1H), 7.06-7.02 (m,
1H), 6.99 (d, J = 2.4Hz, 1H), 5.12-5.08 (m, 1H), 3.84-3.66 (m, 2H); 13C NMR (101 MHz, CDCl3)
197.0, 150.1, 140.3, 137.0, 135.4, 132.7, 129.8, 129.4, 129.1, 126.5, 122.9, 121.9, 120.1, 119.4,
119.4, 118.1, 111.8, 110.5, 44.8, 38.5; IR: (cm-1) 3407, 3058, 2913, 2227, 1683, 1532, 1400, 1338,
1092, 822, 746; HRMS(EI) calcd for 384.1029, found: 384.1034; The enantiomeric excess of 96%
was determined by HPLC (AS-H column, Hexane/propan-2-ol= 70/30; flow rate 1 mL/ min; T =
30oC, 254 nm; tR (major) 15.671 min and tR (minor) 18.948 min).
3-(3-chloro-4-fluorophenyl)-1-(4-chlorophenyl)-3-(1H-indol-3-yl)propan-1-one (3r):
Yield: 83%; ee: 96%; []D20 = -39.6 (c=0.14, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.07 (br, 1H), 7.87-7.84
(m, 2H), 7.42-7.39 (m, 3H), 7.36-7.32 (m, 2H), 7.22-7.16 (m, 2H), 7.07-6.99 (m, 2H), 6.97 (m, 1H),
5.03-3.99 (m, 1H), 3.80-3.60 (m, 2H); 13C-NMR (CDCl3, 101 MHz) (ppm) 13C NMR (101 MHz,
CDCl3) 198.2, 159.3, 156.8, 142.6, 142.5, 141.1, 138.0, 136.5, 131.2, 130.8, 130.4, 128.9, 128.9,
127.6, 123.9, 122.6, 121.1, 120.6, 119.7, 117.9, 117.7, 112.7, 46.2, 38.6.; IR: (cm-1) 3408, 3058,
2913, 1682, 1533, 1497, 1381, 1246, 1093, 820, 744; HRMS(EI) calcd for 411.0593, found:
S13

Supporting Information

411.0599; The enantiomeric excess of 96% was determined by HPLC (Chromasil CHI-TBB
column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/ min; T = 30oC, 254 nm; tR (minor) 13.145
min and tR (major) 15.760 min).
1-(4-chlorophenyl)-3-(3,4-difluorophenyl)-3-(1H-indol-3-yl)propan-1-one (3s):
Yield: 85%; ee: 96%; []D20 = -49.0 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.06 (br, 1H), 7.88-7.84
(m, 2H), 7.42-7.38 (m, 3H), 7.35-7.33 (m, 1H), 7.20-7.16 (m, 1H), 7.14-7.02 (m, 4H), 7.00-6.97 (m,
1H), 5.04-5.00 (m, 1H), 3.79-3.61 (m, 2H);

13

C-NMR (CDCl3, 101 MHz) (ppm) 198.3, 152.9,

152.8, 151.6, 151.4, 150.4, 150.3, 149.1, 149.0, 142.6, 142.5, 141.1, 138.0, 136.5, 130.8, 130.4,
127.6, 125.1, 125.1, 125.0, 125.0, 123.9, 122.6, 121.1, 120.6, 119.7, 118.5, 118.3, 118.1, 117.9,
112.7, 46.2, 38.8; IR: (cm-1) 3401, 3045, 2920, 1683, 1516, 1470, 1376, 1093, 744; HRMS (EI)
calcd for 395.0888, found: 395.0883; The enantiomeric excess of 96% was determined by HPLC
(Chromasil CHI-TBB column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/ min; T = 30oC, 254 nm;
tR (minor) 13.074 min and tR (major) 15.682 min).
1-(4-chlorophenyl)-3-(1H-indol-3-yl)-3-(naphthalen-2-yl)propan-1-one (3t):
Yield: 75%; ee: 94%; []D20 = -5.0 (c=0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.02 (br, 1H), 7.88-7.84
(m, 2H), 7.79-7.72 (m, 4H), 7.48-7.45 (m, 2H), 7.42-7.37 (m, 4H), 7.32-7.30 (d, J = 8.2Hz, 1H),
7.16-7.12 (m, 1H), 7.02-6.98 (m, 2H), 5.24-5.20 (m, 1H), 3.89-3.76 (m, 2H);

13

C-NMR (CDCl3,

101 MHz) (ppm) 202.2, 146.3, 144.3, 141.5, 140.2, 138.3, 137.1, 134.4, 131.4, 133.7, 133.0,
132.6, 132.4, 130.8, 130.7, 130.3, 127.1, 126.4, 124.3, 124.3, 123.8, 116.0, 49.8, 43.2; IR: (cm-1)
3416, 3054, 2920, 1682, 1537, 1400, 1269, 1092, 743; HRMS(EI) calcd for 409.1233, found:
409.1234; The enantiomeric excess of 94% was determined by HPLC (Chromasil CHI-TBB
column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/ min; T = 30oC, 254 nm; tR (minor) 10.920
and tR (major) 13.072 min).
1-(4-chlorophenyl)-3-(1H-indol-3-yl)-3-p-tolylpropan-1-one (3u):
Yield: 84%; ee: 92%; []D20 = -17.5 (c=0.08, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 7/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.01 (br, 1H), 7.86-7.83
(m, 2H), 7.47-7.45 (m, 2H), 7.41-7.37 (m, 2H), 7.31-7.28 (m, 1H), 7.25-7.23 (d, J = 8.08Hz, 2H),
7.17-7.13 (m, 1H), 7.09-7.07 (d, J = 7.84Hz, 2H), 7.05-7.01 (m, 1H), 6.94-6.93 (m, 1H), 5.03-5.00
(t, J = 7.28Hz, 1H), 3.79-3.64 (m, 2H), 2.29 (s, 3H); 13C-NMR (CDCl3, 101 MHz) (ppm) 198.0,
S14

Supporting Information

141.3, 139.8, 137.0, 136.2, 135.8, 131.9, 129.9, 129.6, 129.3, 128.0, 122.5, 121.8, 119.9, 119.8,
119.6, 111.6, 45.6, 38.3, 21.4; IR: (cm-1) 3419, 3291, 3137, 2915, 1754, 1642, 1500, 1455, 1265,
1099, 884, 828, 740; HRMS(EI) calcd for 373.1233, found: 373.1227; The enantiomeric excess of
92% was determined by HPLC (Chromasil CHI-TBB column, Hexane/propan-2-ol= 85/15; flow
rate 1 mL/ min; T = 30oC, 254 nm; tR (minor) 8.684 min and tR (major) 10.144 min).
4-(1-(1H-indol-3-yl)-3-oxo-3-p-tolylpropyl)benzonitrile (3v):
Yield: 91%; ee: 93%; []D20 = -8.0 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 5/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.18 (s, 1H), 7.83-7.81
(d, J = 8.20Hz, 2H), 7.51-7.49 (m, 2H), 7.44-7.42 (d, J = 8.32Hz, 2H), 7.35-7.30 (m, 2H), 7.23-7.21
(d, J = 7.96Hz, 2H), 7.17-7.13 (m, 1H), 7.04-6.97 (m, 2H), 5.11-5.08 (m, 1H), 3.82-3.66 (m, 2H),
2.38 (s, 3H); 13C-NMR (CDCl3, 101 MHz) (ppm) 197.8, 150.5, 144.7, 137.0, 134.6, 132.7, 129.8,
129.1, 128.6, 126.6, 122.8, 121.9, 120.0, 119.5, 119.4, 118.3, 111.8, 110.4, 44.7, 38.6, 22.0; IR:
(cm-1) 3401, 3051, 2922, 2227, 1608, 1535, 1457, 1187, 819, 743; HRMS(EI) calcd for 364.1576,
found: 364.1573; The enantiomeric excess of

93% was determined by HPLC (Chromasil

CHI-TBB column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/ min; T = 30oC, 254 nm; tR (minor)
14.797 min and tR (major) 18.059 min).
3-(3,4-difluorophenyl)-3-(1H-indol-3-yl)-1-p-tolylpropan-1-one (3w):
Yield: 90%; ee: 94%; []D20 = -60.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.07 (s, 1H), 7.84-7.82
(d, J = 7.9 Hz, 2H), 7.38-7.36 (d, J= 7.9Hz, 1H), 7.32-7.30 (d, J = 8.2Hz, 1H), 7.24-7.22 (d, J =
7.8Hz, 2H), 7.17-6.97 (m, 6H), 5.03-5.00 (t, J = 7.2Hz, 1H), 3.77-3.60 (m, 2H), 2.39 (s, 3H);
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C-NMR (CDCl3, 101 MHz) (ppm) 202.6, 156.3, 156.2, 155.0, 154.8, 153.9, 152.5, 152.4, 149.0,

146.3, 141.5, 139.2, 134.2, 133.0, 131.2, 128.6, 128.5, 127.2, 126.1, 124.4, 124.1, 123.4, 121.9,
121.7, 121.6, 121.4, 116.1, 49.6, 42.3, 26.5; IR: (cm-1) 3402, 3033, 2924, 1681, 1603, 1512, 1276,
810, 743; HRMS(EI) calcd for 375.1435, found: 375.1428; The enantiomeric excess of 94% was
determined by HPLC (Chromasil CHI-TBB column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/
min; T = 30oC, 254 nm; tR (minor) 10.400 min and tR (major) 12.066 min).
3-(3-chloro-4-fluorophenyl)-3-(1H-indol-3-yl)-1-p-tolylpropan-1-one (3x):
Yield: 87%; ee: 92%; []D20 = -44.5(c=0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 6/1 ); 1H-NMR (CDCl3, 400 MHz) (ppm) 8.05 (br, 1H), 7.85 (d, J
= 8.24Hz, 2H), 7.41-7.39 (d, J = 7.84Hz, 1H), 7.37-7.35 (dd, J = 7.04, 2.2Hz, 1H), 7.33-7.31 (d, J =
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8.16Hz, 1H), 7.25-7.15 (m, 4H), 7.06-6.97 (m, 3H), 5.05-5.01 (t, J = 7.20Hz, 1H), 3.80-3.61 (m,
2H); 2.41 (s, 3H); 13C-NMR (CDCl3, 101 MHz) (ppm) 198.0, 158.2, 155.8, 144.5, 141.9, 141.9,
137.0, 134.8, 130.2, 129.7, 128.6, 128.0, 127.9, 126.7, 122.8, 121.7, 120.0, 119.6, 118.9, 116.8,
116.6, 111.7, 45.2, 37.7, 22.0; IR: (cm-1) 3403, 3051, 2923, 1675, 1609, 1502, 1246, 809, 744;
HRMS(EI) calcd for 391.1139, found: 391.1131; The enantiomeric excess of 92% was determined
by HPLC (Chromasil CHI-TBB column, Hexane/propan-2-ol= 85/15; flow rate 1 mL/ min; T =
30oC, 254 nm; tR (minor) 10.504 min and tR (major) 12.199 min).
3-(1H-indol-3-yl)-1,3-dip-tolylpropan-1-one (3y):
Yield: 85%; ee: 90%; []D20 = -34.5 (c= 0.1, CHCl3); (Flash column chromatography eluent,
petroleum ether/ethyl acetate = 7/1); 1H-NMR (CDCl3, 400 MHz) (ppm) 7.96 (br, 1H), 7.83-7.81
(m, 2H), 7.43-7.41 (d, J =7.92 Hz, 1H), 7.26-7.25 (m, 1H), 7.22-7.18 (m, 4H), 7.12-7.08 (m, 1H),
7.04-7.02 (d, J = 7.80Hz, 2H), 6.98-6.94 (m, 1H), 6.90-6.89 (m, 1H), 5.02-4.99 (t, J = 7.20Hz, 1H),
2.78-3.61 (m, 2H), 2.35 (s, 3H), 2.25 (s, 3H); 13C-NMR (CDCl3, 101 MHz) (ppm) 198.8, 144.2,
141.7, 137.0, 136.0, 135.1, 129.7, 129.5, 129.0, 128.7, 128.1, 127.1, 122.4, 121.8, 119.9, 119.8,
119.7, 111.5, 45.6, 38.3, 22.0, 21.4; IR: (cm-1) 3413, 3101, 2919, 1738, 1674, 1531, 1456, 1181,
887, 812, 740; HRMS(EI) calcd for 353.1780, found: 353.1782; The enantiomeric excess of 90%
was determined by HPLC (Chromasil CHI-TBB column, Hexane/propan-2-ol= 85/15; flow rate 1
mL/ min; T = 30oC, 254 nm; tR (minor) 7.664 min and tR (major) 8.839 min).

References:
(1) Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356.
(2) Akiyama, T.; Morita, H.; Itoh, J.; Fuchibe, K. Org. Lett. 2005, 7, 2583.
(3) Storer, R. I.; Carrera, D. E.; Ni, Y.; MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, 84.
(4) Guo, Q.-X.; Liu, H.; Guo, C.; Luo, S.-W.; Gu, Yi.; Gong, L.-Z. J. Am. Chem. Soc. 2007 129, 3790.
(5) Chen, X.-H.; Zhang, W.-Q.; Gong, L.-Z. J. Am. Chem. Soc. 2008 130, 5652.
(6) Tang, H.-Y.; Lu, A.-D.; Zhou, Z.-H.; Zhao, G.-F.; He, L.-N.; Tang, C.-C.; Eur. J. Org. Chem. 2008, 1406.

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