Tris(trimethylsilyl)silane and Visible-Light Irradiation: A New Metal- and Additive-Free Photochemical Process for the Synthesis of Indoles

and Oxindoles**

Gustavo Piva da Silva, Akbar Ali, Rodrigo César da Silva, Hao Jiang, and Márcio W.

Paixão*

[a] Prof. Dr. M. W. Paixão, G. P. Silva, A. Ali, , Dr. R. C. Silva Departamento de Química, Universidade Federal de

São Carlos, São Carlos, 97105-900, SP, Brazil, [*] E-mail: mwpaixao@ufscar.br

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2015

1. General information:

All solvents were dried and distilled prior to use by standard procedures and

chemicals were either used as received or purified according to the procedures outlined

in Purification of Common Laboratory Chemicals1. Glassware used was dried in oven or

flame dried under vacuum and cooled under inert atmosphere. Reactions were

monitored by TLC and visualized by a dual shortwave/longwave UV lamp and stained

with an ethanolic solution of potassium permanganate or vanillin. Column flash

chromatography was performed using gel 60 (230−400 mesh), and analytical thin-layer

chromatography (TLC) was performed using silica gel aluminum sheets. Yields refer to

chromatographically and spectroscopically pure compounds, unless otherwise noted. 1H NMR and 13C NMR spectra were recorded at 400 MHz. for 1H and 100 MHz for 13C.

Chemical shifts (δ) are reported in parts per million relative to tetramethylsilane (TMS),

and coupling constants (J) are reported in hertz. All signals are reported in ppm with the

internal reference of 7.26 ppm or 77.0 ppm for chloroform. Data are presented as

follows: multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m =

multiplet, br = broad, dd = doublet of doublet, dt = doublet of triplet), coupling constant

(J/Hz) and integration.

1 Armarengo, W. L. F.; Perrin, D. D. In Purification of Laboratory Chemicals, 4th ed.; Butterworth Heinemann: Oxford, 1996

A. General Procedure for the Preparation of Starting Materials

Preparation of the N-tosyl-protected aniline 2

NH2

X TsCl, pyridine

rt NH

X

Ts

R1 R1

X= I, Br

In a round bottom flask containing a solution of 2-haloaniline (4.50 mmol, 1

equiv) in pyridine (10 mL), p-toluenesulfonyl chloride was added (4.70 mmol, 1.05

equiv). The reaction was stirred at room temperature for 1.5 h, then quenched by

addition of water (10 mL). The reaction mixture was extracted with CH2Cl2 (3 x 20 mL)

and the combined organic layers were washed with an aqueous CuSO4 solution (10%,

3 x 20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced

pressure. The crude mixture was purified by silica gel chromatography (hexane/EtOAc)

to afford the corresponding tosyl-protected aniline. All spectroscopic data are in

accordance with seminal literature.

Preparation of the N-tosyl-propargyl anilines 3

DMF, rtNH

X

Ts

R1 Cl+K2CO3

N

X

Ts

R1

X= I, Br

To a round bottom flask containing a solution of N-tosyl protected 2-haloaniline (1.0 mmol, 1 equiv) in DMF (5 mL), K2CO3 (3.0 mmol, 3 equiv) and propargyl chloride

(2.0 mmol, 2 equiv) were added. The reaction was stirred at room temperature for 3 h,

2 C. Bressy, D. Alberico, M. Lautens, J. Am. Chem. Soc. 2005, 127, 13148-13149.3 Q.L.Luo, L. Lv, Y. Li, P. Tan, W. Nan, Q. Hui, Eur. J. Org. Chem. 2011, 34, 6916-6922.

and then quenched by addition of water (5 mL). The aqueous layer was extracted with

diethyl ether (3 x 10mL) and the combined organic layers were dried over anhydrous

Na2SO4, filtered and concentrated. The crude residue was purified by silica gel

chromatography (hexane/EtOAc) to afford N-tosyl-propargyl aniline. All spectroscopic

data are in accordance with seminal literature.

Preparation of the N-acrylamides 4

NH2

XR1 +

NH

XR1

O

HOP(OMe)3, CH2Cl2

Et3N, I2O

X=I or Br

To a round bottom flask under N2 atmosphere containing a solution of P(OMe)3

(0.35 mL, 3.0 mmol) in dichloromethane (15 mL), precooled to 10 oC, was added I2 (760

mg, 3.0 mmol). After the solid iodine was completely dissolved, acrylic acid (204.7 µL,

3.0 mmol) and Et3N (0.70 mL, 5.0 mmol) were added in sequential order, and the

solution was stirred for 10 min in a cooling bath. The substituted aniline (2.0 mmol) was

then added and the mixture was stirred for 10 min. After removing the cooling bath, the

reaction mixture was stirred for additionally 3 h at room temperature (reaction monitored

by TLC), then diluted with saturated aqueous NaHCO3 and extracted with

dichloromethane (3 x 30 mL). The combined organic layer was sequentially washed

with water, 1N HCl and brine (3 x 20mL) dried over anhydrous Na2SO4, and then

purified by flash chromatography (hexane/EtOAc) to afford substituted N-acrylamide. All

spectroscopy data are accordance with seminal literature.

4 X. Liu, X. Ma, Y. Huang, Z. Gu, Organic Letters 2013, 15, 4814-4817.

Preparation of the N-benzyl-acrylamides 5

.

NH

X

R1O

Ph Br+N

X

R1O

Ph

NaHDMF

X=I or Br

In a round bottom flask, under N2 atmosphere, NaH (60 mg, 60% in mineral oil,

1.5 mmol, 1.5 equiv) was added in portions to a solution of substituted N-(2-halophenyl)

acrylamide (1.0 mmol, 1.0 equiv) in DMF (4.0 ml) at 0 °C. After stirring for 20 min, BnBr

(70 μl, 0.60 mmol, 1.2 equiv) was added dropwise and the reaction mixture was allowed

to warm to room temperature and stirred overnight. The reaction was quenched with

water and THF was removed by evaporation. The residue was extracted with ethyl

acetate twice, and the organic phase was washed with brine, dried over Na2SO4, filtered

and concentrated. The residue was purified by column chromatography (hexane/EtOAc)

to afford the desired product. All spectroscopy data are accordance with seminal

literature.

5 J. D. Nguyen, E. M. D. Amato, J. M. R. Narayaman, C. R. J. Stephenson, Nature Chemistry 2012, 4, 854-859.

B. Screening and Control Experiments

Table S1: Effect of the amount of TTMS a

I

NTs TTMSS (X equiv), MeCNTime, r.t.

15 W household bulb(compact fluorescent light)

NTs

TMSSi

TMS

TMS H

TTMSS

Entry (X equiv) Time (h) Yieldb (%)

1 1 24 58

2 1.5 24 76

3 2 2 994c 1 24 nr

5 0 24 nraReactions were carried out at 0,1 mmol scale of the aryl halide with varying amounts of TTMSS in 0.4 mL MeCN. bYield determined after column chromatography. cReaction was carry out in the absence of light.

Table S2: Solvent screening

I

NTs TTMSS, Solvent, Time, r.t.

15 W household bulb(compact fluorescent light)

NTs

Entrya Solvent Time (h) Yield (%)b

1 MeCN 2 992 DCM 24 57

3 Toluene 24 64

4 THF 24 53

5 DMSO 24 5

6 DMF 24 12

7 AcOEt 24 76

8 EtOH 4 88

9 EtOH 24 90

10 Acetone 6 89

11 H2O 24 nd

a Reactions were carried out at 0,1 mmol scale using 2 equiv of TTMSS. b Isolated yield.

Table S3: Protic Co-solvent Screening

X

NTs TTMSS, MeCN/ROH, 4h, r.t.

15 W household bulb(compact fluorescent light)

NTs

Entrya X Protic Source (X Equiv) Yieldb (%)

1 I EtOH 1 82

2 I EtOH 3,5 80

3 I EtOH 5 924 Br EtOH 5 85

5 I MeOH 5 75

6 I iPrOH 5 76

aReactions were carried out at 0.1 mmol scale using 1 equiv of TTMSS, 0.4 mL of MeCN. bIsolated yield.

Table S4: Effect of N protecting group I

NR TTMSS, MeCN/EtOHTime, r.t.

15 W household bulb(compact fluorescent light)

NR

Entrya R Time (h) Yieldb (%)

1 Tosyl 4 922 Acetyl 24 13

3 Isobutytyl 24 14

a Reactions were carried out at 0,1 mmol scale using 1 equiv of TTMSS, 0,4 mL of MeCN, and 5 equiv of

EtOH. b Isolated yield.

D. Mechanistic Insights

1. Reaction in the Presence of a Radical Scavenger - 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO)

I

NTs

NMeMe MeMe

O+ X

1.5 equiv

15 Whousehold buld(compact fluorescent light)

TTMSS, MeCN/EtOH, 24h, r.t

No product was observed

NTs

Comment: The reaction was completely inhibited when was performed using TEMPO as radical scavenger. This observation indicates that the indole formation is via

a radical pathway.

H

NTs

15 Whousehold buld(compact fluorescent light)

TTMSS, MeCN/EtOH, 24h, r.tNo product was observed

NTs

X

Comment: When the substrate used did not displayed a halogen atom attached to the aryl ring, the product formation was not observed. The presence of the halogen atom is

crucial for the generation of the aryl radical.

2. Reaction using Deuterated Methanol

I

NTs TTMSS, MeCN/MeOD, 4 h, r.t.

15 W household bulb(compact fluorescent light)

NTs

D

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.30

3.00

3.12

2.04

0.99

2.02

1.00

2.002.052.102.152.20f1 (ppm)

2.30

3.00

Figure S1: 1H spectra showing the integration of the methyl signal at 2.06 ppm.

Comment: When the reaction was performed using deuterated methanol as proton source, the insertion of deuterium at the last step on the indole synthesis has

been observed. The proportion of deuterium and hydrogen (D/H, 7:3) detected by

integration of signal in the 1H NMR experiment.

3. Kinetic Study using the model reaction

The kinetic study was performed using the GC-MS equipment, giving us the possibility

to build the calibration curves and, consequently, the kinetic curves using the kinetic

equation. Solutions at different concentration of 1a and TTMSS (obtained by diluting the original stock solution with MeCN) were prepared.

3.1. Calibration curves of the starting materials

0 0.05 0.1 0.15 0.2 0.25 0.30

10000000

20000000

30000000

40000000

50000000

60000000

70000000

80000000

90000000

100000000

Concentration (molL-1)

Are

a

I

NTs

Figure S2: Calibration curve for 2-iodo aniline.

0 0.05 0.1 0.15 0.2 0.25 0.30

10000000

20000000

30000000

40000000

50000000

60000000

Concetration (molL-1)

Are

a

Figure S3: Calibration curve for TTMSS.

3.2. Kinetic equations and curves

Reaction Order Rate law Integrated form equation

First to Single reagent – ARate = k[A]

or ln ([𝐴]0[𝐴] ) = 𝑘𝑡 [𝐴] = 𝐴0𝑒 - 𝑘𝑡

Second to Single reagent - ARate = k[A]2

𝑘𝑡 = (1𝐴) - ( 1𝐴0)Second to two reagents – A and B

Rate = k[A][B]𝑘𝑡 = ( 1[𝐵]0 - [𝐴]0)𝑙𝑛(

[𝐴]0[𝐵]

[𝐵]0[𝐴])

Each one of the expressions above provides a graph that can be used to

determine the order with respect to the reagents. Graphically, a straight line is

necessary to be achieved. Supported by this concept we started our studies to

investigate the kinetics of our photo mediated reaction.

First, the expression of first order for both reagents was applied, the following

graphs were obtained:

0 0.5 1 1.5 2 2.5 3

-1.4

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0Time (h)

ln(A

/A0) I

NTs

Figure S4: First order applied to 2-iodo aniline.

0 0.5 1 1.5 2 2.5 3

-3

-2.5

-2

-1.5

-1

-0.5

0Time (h)

ln [(

A)/(

A)0

]

TMSSi

TMS

TMS H

Figure S5: First order applied to TTMSS.

Next, we used the expression of second order for both reagents, and the graphs obtained are given as follows:

0 0.5 1 1.5 2 2.5 30

1

2

3

4

5

6

7

8

9

10

Time (h)

ln (1

/A –

1/A

0)

I

NTs

Figure S6: Second order applied to 2-iodo aniline.

730.5 731 731.5 732 732.5 733 733.5 734 734.5 735 735.50.042

0.0425

0.043

0.0435

0.044

0.0445

Time (h)

ln (1

/A -

1/A

0)

TMSSi

TMS

TMS H

Figure S7: Second order applied to TTMSS.

From there obtained results, it is possible to observed that both reagents

following first order kinetics is a better fit. Furthermore, we applied another expression

that relates both reagents in a single expression, i.e.:

𝑘𝑡 = ( 1[𝐵]0 ‒ [𝐴]0)𝑙𝑛([𝐴]0[𝐵]

[𝐵]0[𝐴])

Using the rate expression and analyzing the graph, we can conclude that this reaction is second order overall, being first order for each reagent.

0 0.5 1 1.5 2 2.5 3

-1.4

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

0.2 Time (h)

ln (A

/A0)

/(B/B

0))

I

NTs

TMSSi

TMS

TMS H

Figure S8: Second order overall – first order with respect to each reagent.

Comment: The kinetic study provided us a virtuous interpretation of this photo-mediated process. Since the best adjustment of the curve was using the last expression

that correlated both reagents by a single expression - the overall reaction order being

two, first order in regard to each reagent. Having made this observation, we can

conclude that both reagents are involved in the rate determining step.

4. Ultraviolet-Visible Experiment

We were interested to confirm that a complex between the starting material 1a and the silicon-based reagent (TTMSS) is responsible for the energy absorption. Thus,

all the spectra are recorded in MeCN using the same concentrations as in the reaction

conditions.

250 300 350 400 450 500 550 6000

0.5

1

1.5

2

2.5

3

TTMSS

1a

1a + TTMSS

Wavelenght (nm)

Abs

orpt

ion

Figure S9: Absorption spectra of the reagents of the model reaction: [TTMSS] = 0,25 molL-1, [1a] = 0,25 molL-1, and [1a + TTMSS] = 0,25 molL-1. The solutions were

prepared using 0,5 ml of MeCN and 1 cm cuvettes were used.

Upon mixing 1a and TTMSS, a new absorption band is observed (green line in Figure S9). Additionally, changes in visual color appearance is observed when the reagents are mixed, indicating the formation of a transient interaction between the

reagents (EDA Complex).

1a

1a + TTMSSwithout light

TTMSS

1a + TTMSS with light

Figure S10: Images showing the colors of the reagents separately and mixed, suggesting the formation of the EDA complex.

.

Colored EDA complexGround State

INS OO

SiTMS

TMSH

TMS

To complete the mechanistic study as well as emphasizing the requirement of

visible light irradiation, the reaction was performed using successive interval of

irradiation and dark periods for the model reaction. The obtained results are plotted in a

graph bellow.

I

NTs TTMSS, MeCN/EtOH, 4h, r.t.

15 W household bulb(compact fluorescent light)

NTs

Light

Dark Period

Dark Period

Dark Period

Light

Light

Light

Figure S11: Graph of converstion over time in successive intervals of irradiation and dark periods for the model reaction.

Comment: These experiments indicate the necessity of irradiation, which presumably promotes the reaction by generating the excited state of the EDA-complex.

E. General procedure for the photochemical intramolecular cyclization reaction

E1. Indole Synthesis

X

NTs TTMSS, MeCN/EtOH, 4h, r.t.

15 W household bulb(compact fluorescent light)

NTs

RR

To a 5 mL vial equipped with a Teflon-coated magnetic stirring bar was added

the N-tosyl-propargyl aniline (0.1 mmol, 1 equiv.), 0.4 mL acetonitrile (0.25 M), 29.2 µL (5 equiv) ethanol and TTMSS (0.1 mmol, 1 equiv). The reaction mixture was positioned

approximately 5 cm away from the light source, and stirred at room temperature. After

complete consumption of the starting material (followed by TLC), the reaction was

quenched with 2 mL water, then aqueous layer was extracted with DCM (3x10 mL) and

the combined organic layers were dried over Na2SO4. After vacuum removal of

solvents, the crude product was purified by silica gel column chromatography (SiO2, n-

Hexane/EtOAc (9:1).

Compound 2a: The title compound was synthesized according to the general procedure in 92% (26.2 mg) isolated yield as a yellow solid (m.p:

102-103 °C). 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.3 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 7.3 Hz, 1H), 7.23 – 7.00 (m, 5H), 2.19 (s, 3H), 2.11 (d, J =

1.2 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 144.6, 135.4, 135.2, 131.7, 129.7, 126.7, 124.5, 123.0, 122.9, 119.3, 118.5, 113.6, 21.5, 9.6. HRMS: calculated for C16H16NO2S (M-H)+ 286.0902; found 286.0892.

NTs

Compound 2d: The title compound was synthesized according to the general procedure in 53% (19.2 mg) isolated yield as a yellow viscous

oil. 1H NMR (400 MHz, CDCl3) ) δ 7.72 (d, J = 8.8 Hz, 1H), 7.62 – 7.55 (m, 2H), 7.46 – 7.42 (m, 1H), 7.29 – 7.24 (m, 1H), 7.17 (d, J = 1.2 Hz, 1H), 7.11 – 7.05

(m, 2H), 2.21 (s, 3H), 2.07 (d, J = 1.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 144.9, 135.1, 133.9, 133.5, 129.8, 127.4, 126.7, 124.2, 122.2, 117.9, 116.5, 115.1, 21.5, 9.5.

HRMS: calculated for C16H15BrNO2S (M-H)+ 364.0007; found 364.0013.

Compound 2e: The title compound was synthesized according to the general procedure in 62% (19.8 mg) isolated yield as a yellow solid

(m.p: 111-113 °C). 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.40 (m, 1H), 7.26 (m, 4H), 2.34 (s, 3H), 2.20 (d, J = 1.2

Hz, 3H). 13C NMR (100 MHz, CDCl3) 144.9, 135.1, 133.6, 133.0, 129.8, 128.9, 126.7, 124.7, 124.4, 119.2, 118.0, 114.7, 21.5, 9.5 ppm. HRMS: calculated for C16H15ClNO2S (M-H)+ 320.0512; found 320.0528.

Compound 2f: The title compound was synthesized according to the general procedure in 70% (22.3 mg) isolated yield as yellow solid (m.p:

168-170 °C). 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 1.6 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 1H), 7.11 – 6.98 (m, 4H), 2.16 (s, 3H), 2.02 (d, J

= 1.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 145.0, 135.5, 135.2, 130.6, 130.2, 129.9, 126.7, 123.6, 123.5, 120.2, 118.3, 113.8, 21.5, 9.6. HRMS: calculated for C16H15ClNO2S (M-H)+ 320.0512; found 320.0523.

Compound 2g: The title compound was synthesized according to the general procedure in 50% (15.2 mg) isolated yield as a yellow solid (m.p:

98-100 °C). 1H NMR (400 MHz, CDCl3) δ 7.76 – 7.69 (m, 1H), 7.56 – 7.49 (m, 2H), 7.17 – 7.12 (m, 1H), 7.05 – 6.99 (m, 2H), 6.93 – 6.80 (m, 2H), 2.15 (s,

3H), 2.01 (d, J = 1.3 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 144.8, 135.1, 129.8, 126.7,

NTs

Br

NTs

Cl

NTs

Cl

NTs

F

124.7, 118.4, 114.7, 114.6, 112.5, 112.3, 105.2, 104.9, 21.5, 9,6. HRMS: calculated for C16H15FNO2S (M-H)+ 304.0808; found 304.0802.

Compound 2h: The title compound was synthesized according to the general procedure in 51% (18.0 mg) isolated yield as a yellow solid

(m.p: 117-119 °C). 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.7 Hz, 1H), 7.59 – 7.51 (m, 3H), 7.36 (d, J = 8.7, 1H), 7.23 (d, J = 1.2 Hz, 1H), 7.10 – 7.00 (m,

2H), 2.16 (s, 3H), 2.09 (d, J = 1.3 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 145.8, 137.3, 135.7, 132.0, 130.5, 127.3, 125.2, 121.9, 121.9, 119.1, 117.6, 117.6, 114.4, 22.1, 10.1.

HRMS: calculated for C17H15F3NO2S (M + H)+ 354.0776; found 354.0767.

Compound 2i: The title compound was synthesized according to the general procedure in 52% (18.4 mg) isolated yield as a yellow solid

(m.p: 131-133 °C). 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.58 – 7.41 (m, 3H), 7.23 (d, J = 8.1 Hz, 2H), 2.34 (s, 3H), 2.26 (d, J =

1.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 145.2, 135.0, 134.4, 134.2, 130.0, 126.8, 125.5, 119.9, 119.8, 119.7, 118.2, 111.1, 111.0, 21.6, 9.6. HRMS: calculated for C17H15O2F3NS (M + H)+ 354.0776; found 354.0766.

Compound 2j: The title compound was synthesized according to the general procedure in 65% (23.2 mg) isolated yield as an off

brown solid (m.p: 115-117 °C). 1H NMR (400 MHz, CDCl3) δ 8.10 (t, J = 1.2 Hz, 1H), 7.95 – 7.89 (m, 2H), 7.66 (d, 8,6 Hz, 2H), 7.28

(q, J = 1.1 Hz, 1H), 7.12 (d, J = 8.6, 2H), 4.31 (q, J = 7.1 Hz, 2H), 2.24 (s, 3H), 2.19 (d, J

= 1.3 Hz, 3H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 166.8, 145.1, 137.7, 135.2, 131.6, 129.9, 126.7, 125.8, 125.4, 124.2, 121.7, 119.0, 113.3, 60.9, 21.6,

14.4, 9.6. HRMS: calculated for C19H20O4NS (M + H)+ 358.1113; found 358.1110.

Compound 2k: The title compound was synthesized according to the general procedure in 50% (16.3 mg) isolated yield as a yellow solid

(m.p: 143-145 °C). 1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J = 1.7, 0.6 Hz, 1H), 7.86 (dd, J = 8.7, 0.6 Hz, 1H), 7.77 (dd, J = 8.7, 1.7 Hz, 1H),

NTs

F3C

NTs

F3C

NTs

O

O

NTs

O

7.59 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 1.3 Hz, 1H), 7.06 (d, J = 8.5 Hz, 2H), 2.49 (s, 3H),

2.18 (s, 3H), 2.13 (d, J = 1.3 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 197.8, 145.2, 137.8, 135.1, 132.5, 131.7, 129.9, 126.8, 124.9, 124.4, 120.5, 119.2, 113.4, 26.8, 21.6, 9.6.

HRMS: calculated for C18H18O3NS. (M + H)+ 328.1007, found 328.0996.

Compound 2l: The title compound was synthesized according to the general procedure in 45% (14.1 mg) isolated yield as a yellow solid

(m.p: 138-140 °C). 1H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.93 (d, J = 1.0 Hz, 1H), 7.77 (dd, J = 8.6, 1.5 Hz,

1H), 7.69 (dd, J = 8.5, 1.9 Hz, 2H), 7.34 (d, J = 1.2 Hz, 1H), 7.18 ((d, J = 8.5 Hz, 2H)

2.28 (s, 3H), 2.23 (d, J = 1.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 191.9, 145.3, 138.6, 135.1, 131.9, 130.0, 127.0, 126.8, 125.7, 124.7, 122.4, 119.0, 113.9, 21.6, 9.6. HRMS: calculated for C17H16O3NS (M + H)+ 314.0851; found 314.0857.

Compound 2m: The title compound was synthesized according to the general procedure in 82% (25.8 mg) isolated yield as a yellow

solid (m.p: 60-62 °C). 1H NMR (400 MHz, CDCl3 δ 7.87 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 8.6, 2H), 7.38 – 7,37 (m, 1H), 7.25 – 7.20 (m, 2H), 7.11 (d, J = 8.6,

2H), 4.67 (s, 2H), 2.24 (s, 3H), 2.15 (d, J = 1.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 144.7, 135.8, 135.3, 134.8, 132.0, 129.8, 126.7, 123.9, 123.6, 118.6, 118.0, 113.8, 65.5,

21.5, 9.7. HRMS: calculated for C17H18NO3S (M+H)+ 316.1007; found 316.1002.

Compound 2n: The title compound was synthesized according to the general procedure in 52% (17.1 mg) isolated yield as a yellow solid

(m.p: 81-83 °C). 1H NMR (400 MHz, CDCl3) 1H NMR (400 MHz, CDCl3) δ 7.73 - 7.72 (m, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.45 – 7.41 (m,

1H), 7.38 (d, J = 8.0 Hz, 1H), 7.31 (s, 1H), 7.18 (d, J = 8.6, 2H), 7.05 – 7.00 (m, 1H),

6.81 (d, J = 8.6, 2H) ,4.95 (q, J = 6.5 Hz), 2.34 (s, 3H), 2.18 (d, J = 1.3 Hz, 3H), 1.49 (d,

J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 147.7, 145.0, 144.1, 131.9, 131.4, 128.9, 128.8, 128.4, 127.2, 126.4, 124.6, 122.4, 69.8, 25.5, 21.7, 21.4. HRMS: calculated for C18H20NO3S (M+H)+ 330.1164; found 330.1128.

NTs

O

H

NTs

HO

NTs

OH

Compound 2o: The title compound was synthesized according to the general procedure in 85% (25.4 mg) isolated yield as a yellow solid

(m.p: 64-66 °C). 1H NMR (400 MHz, CDCl3) 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.6 Hz, 2H), 7.07 – 7.02 (m, 2H), 6.99 (d, J = 8.6

Hz, 2H), 6.93 (dd, J = 8.4, 1.6 Hz, 1H), 2.22 (s, 3H), 2.12 (s, 3H), 2.01 (d, J = 1.3 Hz,

3H). 13C NMR (100 MHz, CDCl3) δ 145.1, 136.0, 134.1, 133.2, 132.6, 130.3, 127.3, 126.5, 123.8, 119.9, 119.1, 113.9, 22.1, 21.9, 10.2. HRMS: calculated for C17H18NO2S (M+H)+ 300.1058; found 300.1028.

Compound 2p: The title compound was synthesized according to the general procedure in 85% (26.8 mg) isolated yield as a white solid

(m.p: 111-113 °C). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.9 Hz, 1H), 7.63 (d, J = 8.3 Hz, 2H), 7.17 (s, 1H), 7.11 (d, J = 8.0 Hz, 2H), 6.88 – 6.74 (m, 2H),

3.75 (s, 3H), 2.25 (s, 3H), 2.12 (d, J = 1.1 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 156.4, 144.5, 135.4, 132.8, 129.9, 129.7, 126.7, 123.9, 118.7, 114.6, 113.4, 101.9, 55.7, 21.5,

9.8. HRMS: calculated for C17H18NO3S (M+H)+ 316.1007; found 316.0995.

Compound 2q: The title compound was synthesized according to the general procedure in 82% (27.0 mg) isolated yield as a white viscous

oil.1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.6 Hz, 2H), 7.49 (m, 1H), 7.20 (d, J = 8.6 Hz, 2H), 7.18 (m, 1H), 6.81 – 6.75 (m, 1H), 5.96 (s, 2H), 2.34 (s, 3H),

2.15 (d, J = 1.2 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 146.4, 144.9, 144.6, 135.3, 130.0, 129.8, 126.7, 126.1, 122.08, 118.8, 101.3, 98.3, 95.5, 21.6, 9.8. HRMS: calculated for C17H16NO4S (M+H)+ 330.0800; found 330.0791.

E2. Oxindole Synthesis

NTs

Me

NTs

MeO

NTs

O

O

X

N OR1

RN

O

R1

RTTMSS, MeCN, 10h, r.t.

15 W household bulb(compact fluorescent light)

To a 5 mL vial equipped with a Teflon-coated magnetic stirring bar was added

the N-benzyl-acrylamides (0.1 mmol, 1 equiv.), 0.4 ml acetonitrile (0.25 M) and TTMSS

(0.2 mmol, 2 equiv). The reaction mixture was positioned approximately 5 cm away from

the light source, and stirred at room temperature. After complete consumption of the

starting material (followed by TLC), the reaction was quenched with 2 mL water, then

aqueous layer was extracted with DCM (3x10 mL) and the combined organic layers

were dried over Na2SO4. After vacuum removal of solvents, the crude product was

purified by silica gel chromatography (SiO2, n-Hexane/EtOAc (9:1).

Compound 4a: The title compound was synthesized according to the general procedure in 80% (19.0 mg) isolated yield as viscous oil. 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.40 (m, 6H), 7.35 – 7.30 (m, 1H), 7.21 – 7.16 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 5.08 (s, 2H), 3.71 (q, J = 7.6 Hz,

1H), 1.71 (d, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 178.8, 143.1, 135.9, 130.6, 128.7, 127.8, 127.6, 127.3, 123.6, 122.4, 108.9, 43.7, 40.6, 15.6. HRMS: calculated for C16H16NO (M+H)+ 238.1232; found 238.1223.

Compound 4b: The title compound was synthesized according to the general procedure in 54% (8.7 mg) isolated yield as yellow oil.6 1H NMR (400 MHz, CDCl3) δ 7.16 – 7.07 (m, 2H), 6.94 – 6.89 (m, 1H), 6.68 (d, J =

7.8 Hz, 1H), 3.29 (q, J = 7.6 Hz, 1H), 3.06 (s, 3H), 1.33 (d, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 178.7, 127.9, 123.5, 123.2, 122.4, 108.5, 107.9, 40.6, 26.2, 15.3.

HRMS: calculated for C10H12NO (M+H)+ 162.0919; found 162.0863.

6 B. Li, Y. Park, S. Chang, J. Am. Chem. Soc. 2014, 136, 1125−1131

NO

Ph

NO

Me

Compound 4c: The title compound was synthesized according to the general procedure in 65% (17.6 mg) isolated yield as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.24 – 7.07 (m, 6H), 7.03 – 6.94 (m, 1H), 6.48 (d, J = 8.3 Hz, 1H), 4.76 (s, 2H), 3.41 (q, J = 7.6 Hz, 1H),

1.40 (d, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 178.2, 142.8, 141.6, 135.5, 132.3, 128.8, 127.9, 127.7, 127.2, 124.2, 109.9, 43.8, 40.6, 15.5. HRMS: calculated for C16H15ClNO (M+H)+ 272.0842; found 272.0867.

Compund 4d: The title compound was synthesized according to the general procedure in 45% (12.2 mg) isolated yield as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.25 – 7.12 (m, 5H), 7.02 (dd, J = 7.9, 0.9 Hz, 1H), 6.87 (dd, J = 7.9, 1.8 Hz, 1H), 6.58 (d, J = 1.8 Hz, 1H),

4.75 (s, 2H), 3.38 (q, J = 7.6 Hz, 1H), 1.40 (d, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3 δ 178.6, 144.2, 135.4, 133.5, 128.9, 128.5, 127.8, 127.2, 124.4, 122.3, 109.5,

43.7, 40.1, 15.5. HRMS: calculated for C16H15ClNO (M+H)+ 272.0842; found 272.0823.

Compund 4e: The title compound was synthesized according to the general procedure in 56% (14.3 mg) isolated yield as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.50 – 7.35 (m, 5H), 7.16 – 7.08 (m, 1H), 7.04 – 6.91 (m, 1H), 6.74 (dd, J = 8.5, 4.2 Hz, 1H), 5.01 (s, 2H), 3.67

(q, J = 7.7 Hz, 1H), 1.73 (s, 3H), 1.67 (d, J = 7.7 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 178.4, 158.0, 135.7, 128.8, 127.7, 127.2, 114.1, 113.8, 111.9, 111.6, 109.4, 43.8, 40.9,

15.5. HRMS: calculated for C16H15FNO (M+H)+ 256.1138; found 256.1107.

Compund 4f: The title compound was synthesized according to the general procedure in 51% (15.6 mg) isolated yield as oil. 1H NMR (400 MHz, CDCl3) δ 7.85 – 7.77 (m, 2H), 7.3 – 7.2 (m, 5H), 6.7 (d, J = 8.7 Hz, 1H), 4.8 (s, 2H), 4.25 (q, J = 7.1 Hz,

2H), 3.5 (q, J = 7.6 Hz, 1H), 1.5 (d, J = 7.6 Hz, 3H), 1.3 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 178.9, 166.4, 147.1, 135.4, 130.5, 130.5, 128.9, 128.9, 127.8,

NO

Ph

Cl

NO

Ph

Cl

NO

Ph

F

NO

Ph

O

O

127.2, 124.8, 108.4, 60.8, 43.8, 40.3, 15.5, 14.4. HRMS: calculated for C19H20NO3 (M+H)+ 310.1453; found 310.1447.

Compound 4g: The title compound was synthesized according to the general procedure in 70% (17.8 mg) isolated yield as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.49 – 7.36 (m, 5H), 7.22 (m, 1H), 7.13 – 7.06 (m, 1H), 6.75 (d, J = 7.9 Hz, 1H), 5.05 (s, 2H), 3.66 (q, J = 7.6

Hz, 1H), 2.46 (s, 3H), 1.68 (d, J = 7.6 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 178.8, 140.6, 136.1, 131.9, 130.7, 128.7, 127.9, 127.5, 127.2, 124.5, 108.7, 43.7, 40.6, 21.0,

15.7. HRMS: calculated for C17H18NO (M+H)+ 252.1388; found 252.1369.

Compound 4h: The title compound was synthesized according to the general procedure in 72% (19.2 mg) isolated yield as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.26 – 7.13 (m, 5H), 6.82 – 6.77 (m, 1H), 6.61 - 6.59 (m, 1H), 6.52 (d, J = 8.5 Hz, 1H), 4.81 (s, 2H), 3.68

(s, 3H), 3.45 (q, J = 7.6 Hz, 1H), 1.45 (d, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 178.4, 155.9, 136.5, 136.0, 132.0, 128.8, 127.5, 127.3, 111.9, 111.2, 109.3, 55.8, 43.7,

40.9, 15.7. HRMS: calculated for C17H18NO2 (M+H)+ 268.1338; found 268.1356.

Compound 4h: The title compound was synthesized according to the general procedure in 45% (12.6 mg) isolated yield as oil. 1H NMR (400 MHz, CDCl3) δ ) δ 7.30 – 7.12 (m, 5H), 6.68 (s, 1H), 6.22 (s,

1H), 5.82 (s, 2H), 4.79 (s, 2H), 3.39 (q, J = 7.5 Hz, 1H), 1.42 (d, J =

7.5 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 179.0, 146.9, 143.2, 137.1, 135.8, 128.8, 127.6, 127.2, 122.5, 105.3, 100.9, 93.0, 43.8, 40.8, 15.9. HRMS: calculated for C17H16NO3 (M+H)+ 282.1130; found 282.1138.

NO

Ph

Me

NO

Ph

O

NO

Ph

O

O

F. NMR Spectra

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.00

3.23

1.98

0.98

1.98

0.98

1H NMR of compound 2a (400 MHz, CDCl3)

0102030405060708090100110120130140150f1 (ppm)

9.68

21.5

3

113.

68

118.

5911

9.38

122.

9712

3.06

124.

5612

6.75

129.

7713

1.79

135.

2713

5.44

144.

64

13C NMR of compound 2a (100 MHz, CDCl3)

NTs

2a

NTs

2a

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.09

2.24

1.12

1.05

1.01

2.23

1.04

1

H NMR of compound 2d (400 MHz, CDCl3)

05101520253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

9.59

21.5

7

115.

1311

6.57

117.

96

122.

2912

4.29

126.

7212

7.42

129.

89

133.

5713

3.96

135.

11

144.

99

13C NMR of compound 2d (100 MHz, CDCl3)

NTs

Br

2d

NTs

Br

2d

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.01

3.03

2.01

1.97

0.99

1H NMR of compound 2e (400 MHz, CDCl3)

0102030405060708090100110120130140150f1 (ppm)

9.59

21.5

7

114.

7411

8.07

119.

21

124.

4412

4.76

126.

7212

8.95

129.

8813

3.08

133.

6013

5.13

144.

97

13C NMR of compound 2e (100 MHz, CDCl3)

NTs

Cl

2e

NTs

Cl

2e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.01

3.00

2.95

0.99

0.97

1.99

0.96

1H NMR of compound 2f (400 MHz, CDCl3)

0102030405060708090100110120130140150f1 (ppm)

9.61

21.5

8

113.

8311

8.32

120.

2112

3.58

123.

6512

6.76

129.

9513

0.26

130.

6513

5.19

135.

56

145.

01

13C NMR of compound 2f (100 MHz, CDCl3)

NTs

Cl

2f

NTs

Cl

2f

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.00

2.16

2.17

0.99

2.17

1.06

1H NMR of compound 2g (400 MHz, CDCl3)

05101520253035404550556065707580859095100105110115120125130135140145f1 (ppm)

9.66

21.5

6

104.

9710

5.21

112.

3311

2.59

114.

6911

4.78

118.

51

124.

7812

6.70

129.

82

135.

17

144.

84

13C NMR of compound 2g (100 MHz, CDCl3)

NTs

F

2g

NTs

F

2g

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.03

2.01

0.98

1.03

2.99

1.00

1H NMR of compound 2h (400 MHz, CDCl3)

5101520253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

10.1

5

22.1

8

114.

4911

7.60

117.

6411

9.15

121.

9212

1.95

125.

2712

7.38

130.

5913

2.07

135.

7113

7.29

145.

82

13C NMR of compound 2h (100 MHz, CDCl3)

NTs

F3C

2h

NTs

F3C

2h

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.00

3.06

2.04

3.12

2.06

1.01

1H NMR of compound 2i (400 MHz, CDCl3)

0102030405060708090100110120130140150f1 (ppm)

9.59

21.5

7

111.

0611

1.10

118.

2611

9.77

119.

8011

9.87

125.

5212

6.77

130.

01

134.

1613

4.37

135.

05

145.

22

13C NMR of compound 2i (100 MHz, CDCl3)

NTs

F3C

2i

NTs

F3C

2i

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.07

3.00

3.04

2.03

1.99

0.97

2.00

1.98

0.96

1H NMR of compound 2j (400 MHz, CDCl3)

0102030405060708090100110120130140150160170f1 (ppm)

9.64

14.4

0

21.5

5

60.9

7

113.

27

119.

0412

1.73

124.

1912

5.44

125.

8112

6.76

129.

9113

1.58

135.

1513

7.76

145.

08

166.

78

13C NMR of compound 2j (100 MHz, CDCl3)

NTs

O

O

2j

NTs

O

O

2j

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.03

3.00

2.10

0.97

2.03

0.99

0.99

0.97

1H NMR of compound 2k (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180190200f1 (ppm)

9.64

21.5

7

26.7

6

113.

41

119.

1612

0.50

124.

3812

4.90

126.

7712

9.96

131.

6713

2.49

135.

1313

7.81

145.

16

197.

76

13C NMR of compound 2k (100 MHz, CDCl3)

NTs

O

2k

NTs

O

2k

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)

3.02

3.00

1.94

1.02

2.19

1.13

1.02

1.06

1.02

1H NMR of compound 2l (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180190200f1 (ppm)

9.60

21.5

9

113.

99

119.

0012

2.42

124.

7012

5.74

126.

8112

7.06

130.

0213

1.90

135.

1013

8.59

145.

31

191.

89

13C NMR of compound 2l (100 MHz, CDCl3)

NTs

O

H

2l

NTs

O

H

2l

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

1.43

3.00

3.08

2.00

2.02

2.05

0.97

2.01

1.03

1

H NMR of compound 2m (400 MHz, CDCl3)

05101520253035404550556065707580859095100105110115120125130135140145f1 (ppm)

9.67

21.5

3

65.5

1

113.

77

118.

0511

8.66

123.

5912

3.98

126.

7112

9.78

132.

0513

4.82

135.

3313

5.77

144.

71

13C NMR of compound 2m (100 MHz, CDCl3)

NTs

HO

2m

NTs

HO

2m

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.97

0.83

3.05

2.92

1.00

1.90

1.01

2.28

0.97

0.96

0.95

1H NMR of compound 2n (400 MHz, CDCl3)

0102030405060708090100110120130140150f1 (ppm)

21.4

321

.73

25.5

2

69.7

5

122.

3512

4.57

126.

4212

7.21

128.

3712

8.88

128.

9113

1.37

131.

89

144.

1414

5.04

147.

73

13C NMR of compound 2n (100 MHz, CDCl3)

NTs

OH

2n

NTs

OH

2n

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

3.08

3.10

1.02

2.03

2.16

2.00

1.01

1H NMR of compound 2o (400 MHz, CDCl3)

5101520253035404550556065707580859095100105110115120125130135140145f1 (ppm)

10.2

7

21.9

222

.11

113.

98

119.

0711

9.91

123.

7812

6.51

127.

3013

0.31

132.

6413

3.21

134.

1213

6.04

145.

10

13C NMR of compound 2o (100 MHz, CDCl3)

NTs

Me

2o

NTs

Me

2o

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.04

3.05

3.00

1.95

1.98

1.41

1.96

1.01

1H NMR of compound 2p (400 MHz, CDCl3)

0102030405060708090100110120130140150160f1 (ppm)

9.75

21.5

2

55.6

8

101.

98

113.

3611

4.63

118.

70

123.

9312

6.68

129.

7112

9.97

132.

8313

5.35

144.

53

156.

36

13C NMR of compound 2p (100 MHz, CDCl3)

NTs

MeO

2p

NTs

MeO

2p

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

3.00

2.03

0.96

3.00

0.97

2.04

1H NMR of compound 2q (400 MHz, CDCl3)

05101520253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

9.82

21.5

5

95.4

798

.29

101.

27

118.

80

122.

08

126.

1312

6.72

129.

7813

0.05

135.

32

144.

6314

4.99

146.

41

13C NMR of compound 2q (100 MHz, CDCl3)

NTs

O

O

2q,

NTs

O

O

2q,

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.00

0.98

1.96

1.02

1.05

0.99

6.71

1H NMR of compound 4a (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180190f1 (ppm)

15.6

1

40.5

7

43.6

6

108.

98

122.

4312

3.58

127.

2812

7.57

127.

7912

8.76

130.

6513

5.99

143.

07

178.

79

13C NMR of compound 4a (100 MHz, CDCl3)

NO

Ph4a

NO

Ph4a

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

3.01

0.99

1.05

1.01

2.10

1

H NMR of compound 4b (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180f1 (ppm)

15.3

3

26.1

7

40.5

6

107.

9510

8.48

122.

4012

3.18

123.

5412

7.87

178.

74

13C NMR of compound 4b (100 MHz, CDCl3)

NO

Me

4b

NO

Me

4b

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

0.99

2.05

1.04

1.03

6.77

1H NMR of compound 4c (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180f1 (ppm)

15.5

0

40.6

2

43.7

6

109.

89

124.

1612

7.21

127.

7312

7.88

128.

8513

2.27

135.

52

141.

5714

2.83

178.

19

13C NMR of compound 4c(100 MHz, CDCl3)

NO

Ph

Cl

4c

NO

Ph

Cl

4c

0.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

3.00

0.99

1.96

0.97

0.98

1.10

3.15

2.30

1H NMR of compound 4d (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180f1 (ppm)

15.5

6

40.1

743

.76

109.

54

122.

3112

4.46

127.

2312

7.80

128.

5312

8.91

133.

5413

5.44

144.

26

178.

65

13C NMR of compound 4d (100 MHz, CDCl3)

NO

Ph

Cl

4d

NO

Ph

Cl

4d

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

1.02

1.96

1.02

1.01

0.98

5.97

1H NMR of compound 4e (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180f1 (ppm)

15.5

3

40.9

0

43.8

1

109.

3711

1.64

111.

8811

3.84

114.

08

127.

2312

7.69

128.

83

135.

68

158.

06

178.

36

13C NMR of compound 4e (100 MHz, CDCl3)

NO

Ph

F

4e

NO

Ph

F

4e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.20

3.07

0.96

2.18

1.90

1.00

5.46

1.80

1H NMR of compound 4f (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180190f1 (ppm)

14.3

715

.48

40.3

1

43.8

2

60.8

6

108.

45

124.

8412

7.24

127.

7912

8.88

128.

9513

0.46

130.

5013

5.46

147.

10

166.

39

178.

94

13C NMR of compound 4f (100 MHz, CDCl3)

NO

Ph

O

O

4f

NO

Ph

O

O

4f

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

3.00

1.07

1.97

1.00

0.99

0.99

5.42

1H NMR of compound 4g (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180f1 (ppm)

15.6

6

21.0

5

40.6

3

43.6

7

108.

71

124.

4812

7.24

127.

5112

7.97

128.

7313

0.72

131.

9813

6.08

140.

64

178.

76

13C NMR of compound 4g (100 MHz, CDCl3)

NO

Ph

Me

4g

NO

Ph

Me

4g

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

3.00

1.00

3.15

1.90

0.99

1.04

1.09

5.73

1H NMR of compound 4h (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180190f1 (ppm)

15.6

9

40.9

843

.74

55.7

8

109.

2711

1.23

111.

94

127.

2612

7.54

128.

7513

2.03

136.

0413

6.52

155.

96

178.

45

13

C NMR of compound 4h (100 MHz, CDCl3)

NO

Ph

O

4h

NO

Ph

O

4h

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

3.17

1.01

2.08

2.09

1.02

1.00

1.33

4.51

1H NMR of compound 4i (400 MHz, CDCl3)

0102030405060708090100110120130140150160170180f1 (ppm)

15.9

3

40.8

5

43.7

9

93.0

2

100.

96

105.

28

122.

47

127.

2012

7.63

128.

82

135.

8513

7.13

143.

15

146.

94

179.

03

1

3C NMR of compound 4i (100 MHz, CDCl3)

NO

Ph

O

O

4i

NO

Ph

O

O

4i