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Electronic Supplementary Information for:

Synthesis of 3-Substituted 3-Fluoro-2-Oxindoles by Deacylative Alkylation

Cynthia Molina,[a,b] Aitor Ortega-Martínez,[a,b] José M. Sansano,*[a,b] and Carmen Nájera*[a]

a Department of Organic Chemistry and Centro de Innovación en Química Avanzada (ORFEO-CINQA). Faculty of Sciences, University of Alicante, E-03080 Alicante, Spain. Fax: +34 965903549

b Instituto de Síntesis Orgánica, University of Alicante.

[email protected], [email protected]

Table of contents

1. General remarks S22. Synthesis of starting materials S2

2.1. Procedures2.2. Characterization of products

3. Synthesis of fluoro-1-methyl-2-oxindoles 3 S43.1. Procedures3.2. Characterization of products

4. Deacylative alkylation S4 2.1 Procedures2.2 Characterization of products

5. Deacylative allylation S14 3.1 Procedures3.2 Characterization of products

6. References S177. NMR Spectra S18

7.1. Starting materials 7.2. Synthesis of fluoro-1-methyl-2-oxindoles 37.3. Deacylative alkylation7.4. Deacylative allylation

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2018

mailto:[email protected]

mailto:[email protected]

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1. General remarksMelting points were determined with a Marienfeld melting point meter (MPM-H2) apparatus and are uncorrected. For flash chromatography, silica gel 60 (40-60 µm) was employed. 1H NMR (300, 400 MHz or 500 MHz) and 13C NMR (75, 101 or 126 MHz) spectra were recorded using Bruker AV300, Bruker AV400 and Bruker ADVANCE DRX500, respectively, with CDCl3 as solvent and TMS as internal standard and chemical shifts are given in ppm. Low-resolution electron impact (GC-EI) mass spectra were obtained at 70 eV using an Agilent 6890N Network GC system and Agilent 5973Network Mass Selective Detector. High-resolution mass spectra (GC-EI) were recorded using a QTOF Agilent 7200 instrument for the exact mass and Agilent 7890B for the GC. Analytical TLC was performed using ALUGRAM® Xtra SIL G/UV254 silica gel plates, and the spots were determined under UV light (λ=254 nm).

2. Synthesis of starting materials2.1. Procedures

Procedure for the synthesis of 3-acetyl-5-chloro-3-fluoro-1-methylindolin-2-one (1c).

A round-bottom flask containing a solution of 5-cloroisatin (3.63 g, 20 mmol) in anhydrous DMF (40 mL) was cooled to 0 °C, then sodium hydride (606 mg, 24 mmol) was added in one portion and the mixture was stirred for 5 min. Iodomethane was added (1.84 mL, 30 mmol) and the mixture was stirred at 0 °C for 30 min. The mixture was poured in saturated aqueous NH4Cl (20 mL) and extracted with dichloromethane (3 × 40 mL). The organic phase was washed with H2O (3 × 15 mL) and brine (20 mL), dried over MgSO4, and evaporated under vacuum. The dark-red solid was dissolved in hydrazine monohydrate (12 mL, 247 mmol) and heated at 130 °C for 3 h. After cooling the solution to r.t., H2O (40 mL) was added and the mixture was extracted with dichloromethane (3 × 40 mL). The organic phase was washed with saturated aqueous NaHCO3 (50 mL), brine (50 mL), and dried over MgSO4, filtered and concentrated.To the resulting residue, acetic anhydride (22.5 mL, 238 mmol) was added. Then, DMAP (73.3 mg, 0.6 mmol) was added and the mixture was heated at reflux (140 °C) for 5 h and then evaporated under reduced pressure. The residue was dissolved in MeOH (50 mL), then a solution of KOH (11 g, 196 mmol) in MeOH (70 mL) at 0 °C was added. The solution was stirred at r.t. for 22 h and then cooled in an ice-bath at 0 °C. A solution of 12 M aqueous HCl was added until pH 3. The organic solvent was evaporated and the residue was extracted with EtOAc (3 × 100 mL), washed with H2O (100 mL), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (hexane/EtOAc) to obtain pure compound 2c.

Procedure for the synthesis of compounds 2.

In a round-bottom flask that contains a solution of compounds 1 (8 mmol) and Mg(ClO4)2 (0.54 g, 2.4 mmol) in ethyl acetate (160 mL) was stirred for 5 min. Then, NFSI (2.77 g, 8.8 mmol) was added. The reaction was stirred overnight at room temperature and an extractive work-up was performed with (80 mL x 3) of EtOAc in 80 mL of H2O, drying the organic phases with MgSO4, filtering and concentrating. The resulting crude product was purified by flash chromatography (toluene/ethyl acetate) to obtain pure compounds 2.

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2.2. Characterization of productsCompounds 2 is known compounds and experimental data are consistent with reported data. The 1H NMR spectra will be shown afterwards:

2: 3-Acetyl-3-fluoro-1-methylindolin-2-one (354 mg, 85% yield)1

Following, characterization data of new compounds will be displayed:

3-Acetyl-3-fluoro-5-methoxy-1-methylindolin-2-one (2b)

Yield: 702 mg (74%); pale orange solid; mp 74–76 °C (hexane/EtOAc); Rf 0.15 (hexane:EtOAc, 8:2).

1H NMR (400 MHz): δ = 6.96 (ddd, J = 8.5, 2.5, 1.8 Hz, 1H), 6.90 (t, J = 2.2 Hz, 1H), 6.81 (dd, J = 8.5, 1.2 Hz, 1H), 3.79 (s, 3H), 3.20 (s, 3H), 2.39 (d, J = 3.8 Hz, 3H).

13C NMR (101 MHz): δ = 200.30 (d, J = 30.3 Hz), 168.99 (d, J = 21.4 Hz), 156.67 (d, J = 2.5 Hz), 138.48 (d, J = 5.1 Hz), 124.07 (d, J = 18.5 Hz), 116.83 (d, J = 2.6 Hz), 111.94 , 110.03 , 96.13 (d, J = 204.0 Hz), 56.00 , 26.82 , 26.09.

19F NMR (282 MHz): δ = -165.58 (dt, J = 4.1, 2.0 Hz).

LRMS (EI): m/z (%) = 237 (15) [M]+, 196 (12), 195 (100), 194 (11), 180 (21), 152 (22).

HRMS (EI): m/z calcd. for [C12H12FNO3] 237.0801; found: 237.0799.

3-Acetyl-5-chloro-3-fluoro-1-methylindolin-2-one (2c)

Yield: 800 mg (66%); purple solid; mp 108–110 °C (hexane/EtOAc); Rf 0.39 (PhMe:EtOAc, 9.5:0.5).

1H NMR (400 MHz): δ = 7.42 (dt, J = 8.3, 1.7 Hz, 1H), 7.28 (t, J = 1.9 Hz, 1H), 6.83 (d, J = 8.3 Hz, 1H), 3.21 (s, 3H), 2.46 (d, J = 4.1 Hz, 3H).

13C NMR (101 MHz): δ = 200.33 (d, J = 31.3 Hz), 168.82 (d, J = 21.1 Hz), 143.86 (d, J = 4.8 Hz), 132.23 (d, J = 2.3 Hz), 129.17 (d, J = 2.7 Hz), 125.48 , 124.64 (d, J = 18.7 Hz), 110.46 , 95.42 (d, J = 205.4 Hz), 26.92 , 26.32.

19F NMR (282 MHz): δ = -165.38 (dd, J = 3.9, 1.8 Hz).

LRMS (EI): m/z (%) = 241 (8) [M]+, 201 (34), 200 (13), 199 (100), 43 (18).

HRMS (EI): m/z calcd. for [C11H9ClFNO2] 241.0306; found: 241.0302.

3-Acetyl-1-benzyl-3-fluoro-5-methoxyindolin-2-one (2d)

Yield: 206 mg (73%); pale yellow oil; Rf 0.28 (hexane:EtOAc, 8:2).

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1H NMR (400 MHz): δ = 7.31 (m, 5H), 6.90 (t, J = 2.2 Hz, 1H), 6.85 – 6.79 (m, 1H), 6.64 (dd, J = 8.6, 1.2 Hz, 1H), 4.99 (d, J = 15.8 Hz, 1H), 4.77 (d, J = 15.8 Hz, 1H), 3.74 (s, 3H), 2.43 (d, J = 3.8 Hz, 3H).

13C NMR (101 MHz): δ = 200.43 (d, J = 30.6 Hz), 169.27 (d, J = 21.2 Hz), 156.62 (d, J = 2.5 Hz), 137.52 (d, J = 5.2 Hz), 134.71 , 129.09 , 128.09 , 127.30 , 124.21 (d, J = 18.6 Hz), 116.80 (d, J = 2.5 Hz), 111.86 , 111.18 , 96.26 (d, J = 204.8 Hz), 55.97 , 44.35 , 26.21.

19F NMR (282 MHz): δ = -165.69 – -165.79 (m).

LRMS (EI): m/z (%) = 313 (25) [M]+, 272 (19), 271 (99), 193 (18), 92 (12), 91 (100), 65 (11), 43 (11).


3. Synthesis of fluoro-1-methyl-2-oxindole 33.1.Procedure

Procedure for the synthesis of compounds 3.

In a round-bottom flask that contains a solution of compound 2 (0.5 mmol) in THF (3 mL) was degassed using freezing-pump technique. Then, Triton B (85 mg, 0.5 mmol) dissolved in THF (1 mL) was added slowly and the reaction was stirred at this temperature for 5 min. Then, acetic acid (0.5 mL) were added and the solvent was evaporated. 10 mL of H2O was added and this phase was extracted with EtOAc (10 mL x 3), the organic phase was dried (MgSO4), filtered and concentrated under vacuo. The resulting crude product was purified by flash chromatography (toluene/ethyl acetate) to obtain pure compound 3.

3.2.Characterization of productsCompounds 3a, 3b and 3c are known compounds and experimental data are consistent with reported data. The 1H NMR spectra will be shown afterwards:

3a: 3-Fluoro-1-methylindolin-2-one (45 mg, 50%)2

3b: 3-Fluoro-5-methoxy-1-methylindolin-2-one (31 mg, 53%)3

3c: 5-Chloro-3-fluoro-1-methylindolin-2-one (36 mg, 59%)4

4. Deacylative alkylation4.1.Procedure

General procedure for deacylative alkylation of compounds 2 with alkyl halides.

Oxindole 2 (0.3 mmol) and alkyl halide (0.42 mmol) were dissolved under argon atmosphere in anhydrous THF (3 mL). A benzyltrimethylammonium hydroxide solution (Triton B) in MeOH (40wt%, 0.136 mL, 0.3 mmol) was added dropwise and the reaction mixture was stirred at r.t. for

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18 hours. Afterwards, 10 mL of H2O were added and the mixture was extracted with EtOAc (3 × 10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated. After flash chromatography (hexane/EtOAc), pure 3-substituted 3-fluoro-1-methyl-2-oxindole derivatives 4a-m were obtained.

General procedure for the deacylative alkylation of compounds 2 with electrophilic alkenes

The compound 2 (0.3 mmol) and the electrophilic alkene (0.42 mmol) were dissolved in THF (3 mL). Then, three cycles of freezing-pump-thaw was made to the reaction mixture and after filling the flask with Ar, benzyltrimethylammonium hydroxide (Triton B) in MeOH (40% wt, 0.136 mL, 0.3 mmol) was added. The reaction was stirred overnight at room temperature and an extractive work-up was performed with (10 mL x 3) of EtOAc in 10 mL of H2O, drying the organic phases with MgSO4, filtering and concentrating. The resulting crude product was purified by flash chromatography (hexane/EtOAc) obtaining pure 5a-j compounds.

4.2.Characterization of productsCompounds 4a, 5d and are known compounds and experimental data are consistent with reported data. The 1H NMR spectra will be shown afterwards:

4a: 3-Fluoro-1,3-dimethylindolin-2-one (38 mg, 71% yield)5

5d: 3-Fluoro-1-methyl-3-(3-oxobutyl)indolin-2-one (31 mg, 70%)6

Following, characterization data of new compounds will be displayed:

3-Allyl-3-fluoro-1-methylindolin-2-one (4b)

Yield: 56 mg (91%); Red oil; Rf 0.35 (hexane:EtOAc, 9:1)

1H NMR (400 MHz): δ = 7.44–7.35 (m, 2H), 7.10 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 7.8 Hz, 1H), 5.60 (dddd, J = 16.6, 10.1, 8.2, 6.4 Hz, 1H), 5.15–5.10 (m, 2H), 3.18 (s, 3H), 3.02–2.94 (m, 1H), 2.79 (ddd, J = 18.7, 13.6, 8.2 Hz, 1H).

13C NMR (101 MHz): δ = 172.6 (d, J = 21.2 Hz), 144.0 (d, J = 5.2 Hz), 131.2 (d, J = 2.8 Hz), 129.0 (d, J = 8.3 Hz), 125.6 (d, J = 18.7 Hz), 125.0, 123.2 (d, J = 2.3 Hz), 121.1, 108.7, 92.4 (d, J = 189.0 Hz), 39.5 (d, J = 28.0 Hz), 26.3.

19F NMR (376 MHz): δ = -157.7 (dd, J = 18.6, 11.5 Hz).

LRMS (EI): m/z (%) = 205 (25) [M]+, 165 (11), 164 (100), 146 (14).

HRMS (EI): m/z calcd. for [C12H12FNO] 205.0903; found: 205.0885.

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3-(But-2-en-1-yl)-3-fluoro-1-methylindolin-2-one (4c) (mixture of diastereoisomers)

Yield: 52 mg (78%); Orange oil; Rf 0.35 (hexane:EtOAc, 9:1)

1H NMR (400 MHz): δ = 7.46 – 7.34 (m, 2.52H), 7.14 – 7.06 (m, 1.24H), 6.83 (d, J = 7.7 Hz, 1.21H), 5.64 – 5.48 (m, 1.22H), 5.27 – 5.16 (m, 1.24H), 3.18 (s, 0.76H), 3.18 (s, 3H), 2.96 – 2.85 (m, 1.46H), 2.77 – 2.63 (m, 1H), 1.60 (d, J = 6.5 Hz, 3H), 1.55 (d, J = 6.9 Hz, 0.73H).

13C NMR (101 MHz): δ = 172.88 (d, J = 21.3 Hz), 144.10 (d, J = 5.2 Hz), 131.92 , 131.08 (d, J = 2.7 Hz), 129.77 , 125.93 (d, J = 18.8 Hz), 125.04 , 124.85 , 123.11 (d, J = 2.3 Hz), 121.26 (d, J = 8.3 Hz), 120.43 (d, J = 8.1 Hz), 108.66 , 92.75 (d, J = 188.5 Hz), 38.35 (d, J = 27.9 Hz), 32.79 (d, J = 28.2 Hz), 26.28 , 18.13 , 13.13.

19F NMR (282 MHz): δ = -157.51 (dd, J = 17.9, 11.7 Hz), -157.86 (dd, J = 19.5, 11.2 Hz).

LRMS (EI): m/z (%) = 219 (15) [M]+, 166 (10), 165 (100), 164 (48).

HRMS (EI): m/z calcd. for C13H14FNO: 219.1059; found: 219.1064.

3-Fluoro-1-methyl-3-(3-methylbut-2-en-1-yl)indolin-2-one (4d)

Yield: 53 mg (75%); Orange oil; Rf 0.38 (hexane:EtOAc, 9:1)

1H NMR (400 MHz): δ = 7.42 – 7.33 (m, 2H), 7.08 (t, J = 7.6 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 4.95 (tdq, J = 6.5, 2.7, 1.3 Hz, 1H), 3.18 (s, 3H), 2.96 – 2.85 (m, 1H), 2.77 (ddd, J = 22.3, 14.2, 8.4 Hz, 1H), 1.64 (s, 3H), 1.54 (s, 3H).

13C NMR (101 MHz): δ = 173.06 (d, J = 21.4 Hz), 144.11 (d, J = 5.3 Hz), 137.65 , 131.02 (d, J = 2.7 Hz), 126.11 (d, J = 18.8 Hz), 124.90 , 123.09 (d, J = 2.4 Hz), 114.46 (d, J = 7.8 Hz), 108.60 , 92.90 (d, J = 188.3 Hz), 34.01 (d, J = 27.8 Hz), 26.12 (d, J = 30.0 Hz), 18.14.

19F NMR (282 MHz): δ = -157.74 (dd, J = 20.2, 11.0 Hz).

LRMS (EI): m/z (%) = 233 (12) [M]+, 166 (10), 165 (100), 69 (13).


3-(Cyclohex-2-en-1-yl)-3-fluoro-1-methylindolin-2-one (mixture of isomers) (4e)

Yield: 62 mg (84%); Pale orange solid; Rf 0.35 (hexane:EtOAc, 9:1).

1H NMR (300 MHz): δ = 7.45 – 7.34 (m, 3.8H), 7.13 – 7.03 (m, 1.9H), 6.83 (d, J = 7.8 Hz, 1.8H), 6.03 – 5.94 (m, 1.7H), 5.83 – 5.75 (m, 1H), 5.64 (dt, J = 10.3, 1.7 Hz, 1H), 3.24 – 3.06 (m, 7.5H), 2.05 – 1.28 (m, 11.6H), 0.89 – 0.70 (m, 1H).

13C NMR (101 MHz): δ = 172.9, 172.8, 172.7, 172.5, 144.6, 144.5, 144.4, 144.3, 131.6, 131.0, 131.0, 130.1, 125.8, 125.8, 125.6, 124.8, 124.7, 123.6, 123.6, 123.5, 123.1, 123.1, 123.1, 123.0,

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108.6, 108.4, 96.1, 96.0, 94.2, 94.1, 77.2, 42.2, 41.9, 41.1, 40.9, 26.3, 25.0, 25.0, 22.9, 22.9, 22.8, 22.8, 21.6, 20.9.

19F NMR (282 MHz) δ -161.15 (d, J = 10.7 Hz), -164.40 (d, J = 9.4 Hz).

LRMS (EI): m/z (%) = 245 (4) [M]+, 166 (11), 165 (100), 81 (21).


3-Cinnamyl-3-fluoro-1-methylindolin-2-one (4f)

Yield: 71 mg (85%); pale orange wax; Rf 0.27 (hexane:EtOAc, 9:1).

1H NMR (300 MHz): δ = 7.44–7.33 (m, 2H), 7.29–7.18 (m, 3H), 7.09 (t, J = 7.6 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.46 (d, J = 15.8 Hz, 1H), 6.02 (ddd, J = 15.8, 8.6, 6.3 Hz, 1H), 3.22–3.09 (m, 4H), 2.95–2.79 (m, 1H).

13C NMR (75 MHz): δ = 172.65 (d, J = 21.2 Hz), 144.04 (d, J = 5.3 Hz), 136.89, 135.77, 131.25 (d, J = 2.6 Hz), 128.61, 127.73, 126.38, 125.67 (d, J = 18.8 Hz), 125.16, 123.23 (d, J = 2.4 Hz), 120.34 (d, J = 7.9 Hz), 108.80, 92.61 (d, J = 189.3 Hz), 38.71 (d, J = 28.1 Hz), 26.34.

19F NMR (376 MHz): δ = -157.5 (dd, J = 20.7, 11.1 Hz).

LRMS (EI): m/z (%) = 281 (18) [M]+, 261 (21), 260 (15), 118 (11), 117 (100), 115 (24).


3-Benzyl-3-fluoro-1-methylindolin-2-one (4g)

Yield: 71 mg (92%); Pale red solid; mp 110–112 °C (hexane/EtOAc); Rf 0.3 (hexane:EtOAc, 9:1).

1H NMR (400 MHz): δ = 7.32–7.27 (m, 1H), 7.19–7.15 (m, 3H), 7.06–7.04 (m, 2H), 7.00–6.97 (m, 2H), 6.69 (d, J = 7.8 Hz, 1H), 3.57 (dd, J = 13.4, 10.4 Hz, 1H), 3.20 (dd, J = 22.5, 13.4 Hz, 1H), 3.05 (s, 3H).

13C NMR (101 MHz): δ = 172.8 (d, J = 21.2 Hz), 143.9 (d, J = 5.4 Hz), 132.8 (d, J = 7.0 Hz), 131.1 (d, J = 2.6 Hz), 130.6, 128.1, 127.3, 125.5, 125.2 (d, J = 19.1 Hz), 122.9 (d, J = 2.7 Hz), 108.6, 93.3 (d, J = 190.7 Hz), 41.3 (d, J = 27.7 Hz), 26.2.

19F NMR (376 MHz): δ = -157.1 (dd, J = 22.4, 10.4 Hz).

LRMS (EI): m/z (%) = 255 (24) [M]+, 164 (27), 146 (13), 91 (100), 65 (10).


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3-(3,5-Bis(trifluoromethyl)benzyl)-3-fluoro-1-methylindolin-2-one (4h)

Yield: 101 mg (86%); Pale orange solid; Rf 0.3 (hexane:EtOAc, 9:1).

1H NMR (300 MHz): δ = 7.74 (s, 1H), 7.52 (s, 2H), 7.36 (tt, J = 7.8, 1.6 Hz, 1H), 7.10 – 6.97 (m, 2H), 6.74 (d, J = 7.9 Hz, 1H), 3.65 (dd, J = 13.4, 10.6 Hz, 1H), 3.36 (dd, J = 20.2, 13.4 Hz, 1H), 3.08 (s, 3H).

13C NMR (101 MHz): δ = 172.01 (d, J = 20.9 Hz), 143.77 (d, J = 5.3 Hz), 135.57 (d, J = 7.2 Hz), 132.09 – 130.90 (m), 130.83 , 125.11 , 124.60 – 124.09 (m), 123.30 (d, J = 2.1 Hz), 121.85 , 121.41 (dt, J = 7.4, 3.7 Hz), 109.02 , 92.55 (d, J = 193.4 Hz), 41.14 (d, J = 28.9 Hz), 26.20.

19F NMR (282 MHz): δ = -63.77, -158.95 (dd, J = 20.1, 10.7 Hz).

LRMS (EI): m/z (%) = 391 (27) [M]+, 261 (21), 165 (10), 164 (100).

HRMS (EI): m/z calcd. for [C18H12F7NO] 391.0807; found: 391.0812.

3-Fluoro-1-methyl-3-(prop-2-yn-1-yl)indolin-2-one (343d) (4i)

Yield: 36 mg (59%); Pale brown solid; mp 84–85 ºC (hexane/EtOAc); Rf 0.23 (hexane:EtOAc, 9:1).

1H NMR (300 MHz): δ = 7.65 (dt, J = 7.4, 1.4 Hz, 1H), 7.43 (tt, J = 7.8, 1.5 Hz, 1H), 7.17 – 7.12 (m, 1H), 6.87 (d, J = 7.9 Hz, 1H), 3.23 – 3.14 (m, 4H), 2.87 (ddd, J = 20.5, 16.6, 2.7 Hz, 1H), 2.00 (t, J = 2.7 Hz, 1H).

13C NMR (75 MHz): δ = 171.7 (d, J = 20.9 Hz), 144.3 (d, J = 5.1 Hz), 131.7 (d, J = 2.8 Hz), 125.2, 124.9 (d, J = 18.6 Hz), 123.5 (d, J = 2.4 Hz), 108.8, 90.5 (d, J = 191.7 Hz), 76.2 (d, J = 11.3 Hz), 71.9 (d, J = 1.1 Hz), 26.4, 25.8 (d, J = 33.7 Hz)

19F NMR (376 MHz): δ = -157.9 (dd, J = 20.5, 8.2 Hz).

LRMS (EI): m/z (%) = 204 (15), 203 (100) [M]+, 183 (11), 165 (23), 164 (100), 154 (11), 136 (20), 109 (19).

HRMS (EI): m/z calcd. for [C12H10FNO] 203.0746; found: 203.0746.

Ethyl 2-((3-fluoro-1-methyl-2-oxoindolin-3-yl)methyl)acrylate (4j)

Yield: 69 mg (82%); Pale yellow oil; Rf 0.18 (hexane:EtOAc, 9:1)

1H NMR (300 MHz): δ = 7.36 (td, J = 7.7, 1.7 Hz, 2H), 7.05 (t, J = 7.6 Hz, 1H), 6.80 (d, J = 8.4 Hz, 1H), 6.26 (t, J = 1.2 Hz, 1H), 5.74 (s, 1H), 4.02 (q, J = 7.1 Hz, 2H), 3.44 – 3.31 (m, 1H), 3.20 – 3.02 (m, 4H), 1.15 (t, J = 7.1 Hz, 3H).

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13C NMR (75 MHz): δ = 172.45 (d, J = 21.3 Hz), 166.44 , 144.03 (d, J = 5.4 Hz), 133.22 (d, J = 6.9 Hz), 131.33 (d, J = 2.7 Hz), 130.08 , 125.61 , 124.91 (d, J = 18.8 Hz), 122.92 (d, J = 2.3 Hz), 108.69 , 92.39 (d, J = 190.7 Hz), 61.03 , 35.80 (d, J = 29.4 Hz), 26.28 , 14.14.

19F NMR (282 MHz): δ = -156.63 (t, J = 16.4 Hz).

LRMS (EI): m/z (%) = 277 (27) [M]+, 261 (21), 165 (11), 164 (100).


3-Benzyl-3-fluoro-5-methoxy-1-methylindolin-2-one (4k)

Yield: 34 mg (79 %); yellow solid; mp 112–114 °C (hexane/EtOAc); Rf 0.32 (hexane:EtOAc, 8:2).

1H NMR (400 MHz): δ = 7.23 – 7.18 (m, 3H), 7.09 (dd, J = 6.1, 2.7 Hz, 2H), 6.82 (ddd, J = 8.5, 2.6, 1.7 Hz, 1H), 6.61 (dd, J = 8.5, 1.1 Hz, 1H), 6.52 – 6.48 (m, 1H), 3.67 (s, 3H), 3.58 (dd, J = 13.5, 10.8 Hz, 1H), 3.14 (dd, J = 24.3, 13.5 Hz, 1H), 3.05 (s, 3H).

13C NMR (101 MHz): δ = 172.62 (d, J = 21.0 Hz), 155.98 (d, J = 2.6 Hz), 137.22 (d, J = 5.4 Hz), 132.89 (d, J = 6.2 Hz), 130.76 , 128.18 , 127.39 , 126.30 (d, J = 18.8 Hz), 115.89 (d, J = 2.3 Hz), 112.37 , 109.11 , 93.49 (d, J = 191.2 Hz), 55.83 , 41.35 (d, J = 27.4 Hz), 26.27.

19F NMR (282 MHz): δ = -157.51 (dd, J = 24.3, 10.8 Hz).

LRMS (EI): m/z (%) = 286 (22), 285 (100) [M]+, 195 (23), 194 (100), 179 (12), 151 (23), 91 (76).


3-Benzyl-5-chloro-3-fluoro-1-methylindolin-2-one (4l)

Yield: 67 mg (77 %); red oil; Rf 0.39 (hexane:EtOAc, 8:2).

1H NMR (400 MHz): δ = 7.33 – 7.25 (m, 1H), 7.21 (m, 3H), 7.05 (m, 2H), 6.95 (t, J = 1.9 Hz, 1H), 6.62 (dd, J = 8.3, 1.1 Hz, 1H), 3.54 (dd, J = 13.4, 10.5 Hz, 1H), 3.20 (dd, J = 22.1, 13.4 Hz, 1H), 3.05 (s, 3H).

13C NMR (101 MHz): δ = 172.35 (d, J = 21.1 Hz), 142.47 (d, J = 5.2 Hz), 132.23 (d, J = 7.0 Hz), 130.96 (d, J = 2.3 Hz), 130.59 , 128.31 , 127.59 , 126.81 (d, J = 19.1 Hz), 125.95 , 109.60 , 93.03 (d, J = 192.5 Hz), 41.25 (d, J = 27.5 Hz), 26.30.

19F NMR (282 MHz): δ = -157.56 (dd, J = 22.0, 10.5 Hz).

LRMS (EI): m/z (%) = 291 (16), 289 (47) [M]+, 198 (15), 92 (13), 91 (100).

HRMS (EI): m/z calcd. for [C16H13ClFNO] 289.0670; found: 289.0670.

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1,3-Dibenzyl-3-fluoro-5-methoxyindolin-2-one (4m)

Yield: 41 mg (76%); Brown solid; mp 122-123 °C; Rf 0.22 (hexane:EtOAc, 9:1)

1H NMR (300 MHz): δ = 7.28 – 7.12 (m, 6H), 7.06 (d, J = 7.1 Hz, 2H), 6.81 (t, J = 2.2 Hz, 1H), 6.79 – 6.73 (m, 2H), 6.69 (ddd, J = 8.6, 2.6, 1.8 Hz, 1H), 6.36 (dd, J = 8.5, 1.1 Hz, 1H), 5.00 (d, J = 15.9 Hz, 1H), 4.46 (d, J = 15.9 Hz, 1H), 3.71 (s, 3H), 3.61 (dd, J = 13.0, 8.6 Hz, 1H), 3.40 (dd, J = 18.4, 13.0 Hz, 1H).

13C NMR (75 MHz): δ = 172.48 (d, J = 21.1 Hz), 156.11 (d, J = 2.7 Hz), 136.59 (d, J = 5.4 Hz), 134.86 , 132.49 (d, J = 9.4 Hz), 130.87 , 128.81 , 128.42 , 127.49 (d, J = 11.9 Hz), 126.82 , 126.45 (d, J = 18.6 Hz), 115.85 (d, J = 2.6 Hz), 112.21 , 110.45 , 93.88 (d, J = 190.5 Hz), 55.88 , 43.87 , 41.31 (d, J = 28.4 Hz).

19F NMR (282 MHz): δ = -153.34 (dd, J = 18.3, 8.4 Hz).

LRMS (EI): m/z (%) = 362 (21), 361 (83) [M]+, 343 (10), 271 (12), 270 (66), 252 (11), 91 (100).

HRMS (EI): m/z calcd. for [C23H20FNO2] 361,1478; found: 361.1482.

tert-Butyl 3-(3-fluoro-1-methyl-2-oxoindolin-3-yl)propanoate (5a)

Yield: 36 mg (95%); Pale yelow oil; Rf 0.40 (hexane:EtOAc, 8:2).

1H NMR (300 MHz, CDCl3): δ = 7.45 – 7.35 (m, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 7.7 Hz, 1H), 3.19 (s, 3H), 2.52 – 2.28 (m, 4H), 1.40 (s, 9H).

13C NMR (101 MHz, CDCl3): δ = 172.62 (d, J = 21.7 Hz), 171.45, 144.00 (d, J = 5.2 Hz), 131.40 (d, J = 2.5 Hz), 125.73 (d, J = 18.7 Hz), 124.73, 123.43 (d, J = 2.3 Hz), 108.86, 92.46 (d, J = 187.8 Hz), 80.89, 30.50 (d, J = 28.6 Hz), 28.85 (d, J = 6.1 Hz), 28.13, 26.34.

19F NMR (376 MHz, CDCl3): δ = -161.82 (dd, J = 23.7, 12.2 Hz).

LRMS (EI): m/z (%) = 293 (49) [M]+, 237 (32), 220 (33), 217 (17), 200 (11), 172 (36), 166 (10), 165 (100), 164 (37), 159 (22), 158 (12), 144 (17), 57 (32), 55 (11).

HRMS (EI): m/z calcd. for [C16H20FNO3] 293,1427; found 293.1425.

3-(3-Fluoro-1-methyl-2-oxoindolin-3-yl)propanenitrile (5b)

Yield: 31 mg (75%); Yelow oil; Rf 0.15 (hexane:EtOAc, 8:2).

1H NMR (300 MHz, CDCl3): δ = 7.50 – 7.38 (m, 2H), 7.16 (t, J = 7.6 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 3.20 (s, 3H), 2.87 – 2.52 (m, 3H), 2.41 – 2.20 (m, 1H).

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13C NMR (101 MHz, CDCl3): δ = 171.63 (d, J = 21.7 Hz), 143.88 (d, J = 5.2 Hz), 132.07 (d, J = 2.8 Hz), 124.84, 124.55, 123.76 (d, J = 2.5 Hz), 118.65, 109.26, 90.79 (d, J = 190.0 Hz), 31.37 (d, J = 28.8 Hz), 26.44, 11.05 (d, J = 6.8 Hz).

19F NMR (376 MHz, CDCl3): δ = -159.63 (t, J = 16.0 Hz).

LRMS (EI): m/z (%) = 218 (100) [M]+, 219 (14), 165 (100), 164 (99), 158 (11), 150 (14), 148 (17), 136 (16), 130 (24), 109 (14).

HRMS (EI): m/z calcd. for [C12H11FN2O] 218.0855; found 218.0855.

3-(3-Fluoro-1-methyl-2-oxoindolin-3-yl)-N,N-dimethylpropanamide (5c)

Yield: 64 mg (81%); Yellow oil; Rf 0.25 (hexane:EtOAc, 2:8).

1H NMR (300 MHz, CDCl3): δ =7.45 – 7.35 (m, 2H), 7.12 (t, J = 7.2 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 3.19 (s, 3H), 3.00 (s, 3H), 2.92 (s, 3H), 2.69 – 2.49 (m, 3H), 2.47 – 2.24 (m, 1H).

13C NMR (101 MHz, CDCl3): δ =172.77 (d, J = 22.1 Hz), 171.53, 143.75 (d, J = 5.2 Hz), 131.31 (d, J = 2.7 Hz), 126.21 (d, J = 18.6 Hz), 124.54, 123.42 (d, J = 2.3 Hz), 108.78, 92.47 (d, J = 187.5 Hz), 36.44 (d, J = 168.3 Hz), 30.97 (d, J = 27.7 Hz), 26.30, 26.06 (d, J = 4.6 Hz).

19F NMR (376 MHz, CDCl3): δ = -161.04 – -161.20 (m).

LRMS (EI): m/z (%) = 264 (8) [M]+, 244 (11), 201 (38), 199 (16), 173 (12), 172 (61), 171 (21), 165 (11), 164 (13), 160 (16), 159 (85), 144 (39), 130 (19), 115 (16), 109 (10), 100 (22), 91 (12), 87 (20), 77 (11), 72 (100), 55 (37).

HRMS (EI): m/z calcd. for [C14H17FN2O2] 264.1274; found 264.1280.

3-Fluoro-1-methyl-3-(2-(phenylsulfonyl)ethyl)indolin-2-one (5e)

Yield: 49 mg (70%); Orange wax; Rf 0.10 (hexane:EtOAc, 8:2).

1H NMR (300 MHz, CDCl3): δ = 7.96 – 7.86 (m, 2H), 7.74 – 7.62 (m, 1H), 7.65 – 7.52 (m, 2H), 7.48 – 7.31 (m, 2H), 7.13 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 3.58 (ddd, J = 13.9, 12.6, 4.0 Hz, 1H), 3.38 (ddd, J = 13.9, 12.7, 4.3 Hz, 1H), 3.16 (s, 3H), 2.65 (dtd, J = 14.2, 12.9, 4.3 Hz, 1H), 2.32 (dddd, J = 25.1, 14.3, 12.7, 4.0 Hz, 1H).

13C NMR (101 MHz, CDCl3): δ = 171.64 (d, J = 21.9 Hz), 143.67 (d, J = 5.1 Hz), 138.78, 134.09, 131.91 (d, J = 2.6 Hz), 129.54, 128.16, 125.11 (d, J = 18.5 Hz), 124.45, 123.72 (d, J = 2.2 Hz), 109.15, 90.81 (d, J = 190.8 Hz), 49.73 (d, J = 3.8 Hz), 28.77 (d, J = 28.8 Hz), 26.39.


LRMS (EI): m/z (%) = 333 (100) [M]+, 334 (20), 192 (15), 172 (44), 171 (44), 165 (66), 164 (93), 162 (13), 158 (21), 144 (39), 143 (20), 115 (12) 109 (12) 77 (24).

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HRMS (EI): m/z calcd. for [C17H16FNO3S] 333.0835; found 333.0835.

Diethyl (2-(3-fluoro-1-methyl-2-oxoindolin-3-yl)ethyl)phosphonate (5f)

Yield: 60 mg (69%); Yellow oil; Rf 0.20 (hexane:EtOAc, 1:9).

1H NMR (300 MHz, CDCl3): δ = 7.41 (dtd, J = 6.9, 3.6, 2.9, 1.4 Hz, 2H), 7.13 (t, J = 7.6 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 4.16 – 4.02 (m, 4H), 3.20 (s, 3H), 2.52 – 2.21 (m, 2H), 2.02 – 1.75 (m, 2H), 1.31 (q, J = 7.1 Hz, 6H).

13C NMR (101 MHz, CDCl3): δ = 172.29 (d, J = 21.8 Hz), 143.95 (d, J = 5.1 Hz), 131.55 (d, J = 2.7 Hz), 125.42 (d, J = 18.8 Hz), 124.55, 123.52 (d, J = 2.3 Hz), 108.96, 92.21 (d, J = 210.2 Hz), 62.48 – 61.61 (m), 28.79 (dd, J = 29.2, 3.7 Hz), 26.35, 19.98 (d, J = 5.4 Hz), 18.08 (d, J = 5.4 Hz), 16.51 (m).

19F NMR (376 MHz, CDCl3): δ = -160.96 (t, J = 16.6 Hz).

LRMS (EI): m/z (%) = 329 (3) [M]+, 310 (18), 309 (100), 236 (16), 235 (24), 173 (63), 172 (52), 171 (28), 165 (11), 164 (26), 160 (12), 158 (43), 144 (45), 143 (82), 130 (25), 115 (13), 109 (20).

HRMS (EI): m/z calcd. for [C15H21FNO4P] 329.1192; found 329.1184.

3-(2,2-Bis(phenylsulfonyl)ethyl)-3-fluoro-1-methylindolin-2-one (5g)

Yield: 130 mg (92%); Yellow solid; mp 220 °C (dec.); Rf 0.10 (hexane:EtOAc, 8:2).

1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 7.4 Hz, 2H), 7.88 (d, J = 7.4 Hz, 2H), 7.66 (m, 2H), 7.55 (m, 4H), 7.44 (t, J = 7.8 Hz, 1H), 7.36 (d, J = 7.5 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 5.62 (t, J = 4.3 Hz, 1H), 3.34 – 3.14 (m, 4H), 3.13 – 2.89 (m, 1H).

13C NMR (101 MHz, CDCl3): δ = 171.77 (d, J = 23.0 Hz), 143.84, 138.72, 137.48, 134.77, 134.51, 132.13 (d, J = 2.2 Hz), 129.85, 129.70, 129.28, 129.16, 125.00 (d, J = 18.0 Hz), 124.40, 123.62 (d, J = 2.0 Hz), 109.38, 89.54 (d, J = 191.1 Hz), 30.53 (d, J = 30.5 Hz), 26.50.


LRMS (EI): m/z (%) = 473 (62) [M]+, 474 (16), 312 (14), 311 (29), 190 (12), 172 (16), 171 (63), 170 (16), 164 (100), 162 (21), 141 (15), 125 (27), 115 (14), 109, (12), 77 (45), 51 (10).

HRMS (EI): m/z calcd. for [C23H20FNO5S2] 473.0767; found 473.0765.

tert-Butyl 3-(3-fluoro-5-methoxy-1-methyl-2-oxoindolin-3-yl)propanoate (5h)

Yield: 36 mg (74 %); orange wax; Rf 0.28 (hexane:EtOAc, 8:2).

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1H NMR (400 MHz): δ = 7.02 (t, J = 2.2 Hz, 1H), 6.94 – 6.84 (m, 1H), 6.75 (dd, J = 8.5, 0.9 Hz, 1H), 3.81 (s, 3H), 3.17 (s, 3H), 2.49 – 2.25 (m, 4H), 1.40 (s, 9H).

13C NMR (101 MHz): δ = 172.35 (d, J = 21.7 Hz), 171.44 , 156.55 (d, J = 2.4 Hz), 137.22 (d, J = 5.3 Hz), 126.79 (d, J = 18.5 Hz), 115.74 (d, J = 2.3 Hz), 111.89 , 109.39 , 92.79 (d, J = 188.4 Hz), 80.91 , 56.00 , 30.56 (d, J = 28.6 Hz), 28.84 (d, J = 6.3 Hz), 28.13 , 26.43.

19F NMR (282 MHz): δ = -159.66 (t, J = 15.9 Hz).

LRMS (EI): m/z (%) = 323 (46) [M]+, 268 (15), 267 (100), 252 (21), 250 (31), 202 (16), 195 (23), 194 (26), 174 (11), 57 (10).


tert-Butyl 3-(5-chloro-3-fluoro-1-methyl-2-oxoindolin-3-yl)propanoate (5i)


1H NMR (400 MHz): δ = 7.45 – 7.32 (m, 0H), 6.83 – 6.68 (m, 0H), 3.18 (s, 0H), 2.49 – 2.29 (m, 0H), 1.41 (s, 1H).

13C NMR (101 MHz): δ = 172.13 (d, J = 21.6 Hz), 171.20 , 142.51 (d, J = 4.9 Hz), 131.28 (d, J = 2.3 Hz), 128.90 (d, J = 2.8 Hz), 127.24 (d, J = 18.8 Hz), 125.32 , 109.92 , 92.16 (d, J = 189.6 Hz), 81.09 , 30.42 (d, J = 28.3 Hz), 28.68 (d, J = 6.1 Hz), 28.13 , 26.50.

19F NMR (282 MHz): δ = -160.07 (t, J = 15.9 Hz).

LRMS (EI): m/z (%) = 329 (22), 328 (12), 327 (64) [M]+, 273 (26), 272 (11), 271 (78), 256 (13), 254 (41), 234 (10), 208 (13), 206 (39), 178 (15), 57 (40), 55 (16), 41 (12).

HRMS (EI): m/z calcd. for [C16H19ClFNO3] 327.1037; found: 327.1033.

tert-Butyl 3-(1-benzyl-3-fluoro-5-methoxy-2-oxoindolin-3-yl)propanoate (5j)

Yield: 39 mg (66%); Dark violet oil; Rf 0.19 (hexane:EtOAc, 9:1)

1H NMR (400 MHz): δ = 7.35 – 7.23 (m, 5H), 7.02 (t, J = 2.2 Hz, 1H), 6.77 (dt, J = 8.6, 2.1 Hz, 1H), 6.61 (dd, J = 8.6, 1.0 Hz, 1H), 4.90 (d, J = 15.7 Hz, 1H), 4.81 (d, J = 15.7 Hz, 1H), 3.76 (s, 3H), 2.60 – 2.26 (m, 4H), 1.41 (s, 9H).

13C NMR (101 MHz): δ = 172.52 (d, J = 21.5 Hz), 171.44, 156.48, 136.26 (d, J = 5.4 Hz), 135.24, 129.02, 127.95, 127.34, 126.80 (d, J = 18.4 Hz), 115.75, 111.91, 110.55, 92.80 (d, J = 188.3 Hz), 80.94, 55.95, 44.03, 30.66 (d, J = 28.5 Hz), 28.87 (d, J = 6.5 Hz), 28.14.

19F NMR (282 MHz): δ = -153.16 – -160.31 (m).

LRMS (EI): m/z (%) = 400 (11), 399 (43) [M]+, 343 (42), 326 (20), 265 (11), 264 (13), 207 (16), 204 (12), 91 (100), 41 (14).

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5. Deacylative allylation5.1.Procedures

General procedure for the Pd-catalyzed synthesis of 3-allyl-3-fluro-1-methylindolin-2-one through deacylative alkylation

To a mixture of Pd(OAc)2 (4.04 mg, 0.018 mmol) and 1.3-bis(diphenylphosphino)propane (7.42 mg, 0.018 mmol) was added dry toluene (1 mL) under Ar and stirring continued for 30 min. This mixture was added to a solution of 3-acetyl-3-fluoro-1-methylindolin-2-one (62.2 mg, 0.3 mmol) in dry toluene (0.5 mL). Finally, the alcohol (0.45 mmol) was added and the mixture was degassed by three cycles of freeze-pump-thaw and filled with Ar before the addition of tBuOLi (36 mg, 0.45 mmol). The solution was stirred overnight at room temperature and an extractive work-up was performed with (10 mL x 3) of EtOAc in 10 mL of H2O, drying the organic phases with MgSO4, filtering and concentrating. The resulting crude product was purified by flash chromatography (hexane/EtOAc) affording pure compounds 4b, 4c, 4c’, 3e and 4j-m.

5.2. Characterization of products

3-Allyl-3-fluoro-1-methylindolin-2-one (4b)

Yield: 52 mg (85%).

3-(But-2-en-1-yl)-3-fluoro-1-methylindolin-2-one (4c) and 3-(but-3-en-2-yl)-3-fluoro-1-methylindolin-2-one (4c’) (mixture of diasteroisomers):

Yield: 36 mg (55%); Pale yelow oil; Rf 0.51 (hexane:EtOAc, 8:2).

1H NMR (300 MHz, CDCl3): δ = δ 7.48 – 7.33 (m, 3.8H), 7.15 – 7.02 (m, 1.9H), 6.83 (m, 1.8H), 6.04 (ddd, J = 17.1, 10.5, 6.4 Hz, 0.5H, 3c’), 5.56 (dq, J = 14.4, 6.4 Hz, 1H, 3c), 5.45 – 5.31 (m, 0.4H, 3c’), 5.31 – 5.07 (m, 2.4H), 4.99 (dt, J = 10.2, 1.8 Hz, 0.4H, 3c’), 3.20 (s, 1.5H, 3c’), 3.18 (s, 3H, 3c), 3.16 (s, 1.4H, 3c’), 2.91 (m, 1H, 3c), 2.78 – 2.61 (m, 1H, 3c), 1.60 (d, J = 6.5 Hz, 3H, 3c), 1.26 (dd, J = 6.8, 0.8 Hz, 1.8H, 3c’), 0.86 (d, J = 6.9 Hz, 1.5H, 3c’).

13C NMR (101 MHz, CDCl3): δ = 173.04 (d, J = 6.6 Hz), 172.83 (d, J = 6.4 Hz), 144.51 (dd, J = 10.0, 5.8 Hz), 144.12 (d, J = 5.2 Hz), 135.57 (d, J = 7.2 Hz), 135.36 (d, J = 4.4 Hz), 131.94 , 131.11 (dd, J = 5.2, 2.6 Hz), 129.79 , 126.05 , 125.86 , 125.66 , 125.38 , 125.06 , 123.12 (d, J = 2.3 Hz), 123.07 – 122.92 (m), 121.27 (d, J = 8.3 Hz), 120.44 (d, J = 8.7 Hz), 118.41 (d, J = 12.6 Hz), 108.66, 108.57, 94.71 (d, J = 190.3 Hz), 92.76 (d, J = 188.7 Hz), 43.72 (d, J = 26.5 Hz), 41.86 (d, J = 24.9 Hz), 38.37 (d, J = 27.9 Hz), 32.80 (d, J = 28.3 Hz), 26.29, 26.15 (3c’) , 18.14, 13.38 (d, J = 4.0 Hz), 12.42 (d, J = 6.3 Hz).

19F NMR (282 MHz, CDCl3): δ = -157.91 (dd, J = 19.4, 11.2 Hz, 3c), -159.30 (d, J = 9.0 Hz, 3c’), -162.78 (d, J = 8.1 Hz, 3c’).

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LRMS (EI): m/z (%) = 219 (14) [M]+, 166 (10), 165 (100), 164 (48).

HRMS (EI): m/z calcd. for [C13H14FNO] 219.1059; found 219.1063.

3-(Cyclohex-2-en-1-yl)-3-fluoro-1-methylindolin-2-one (mixture of isomers) (4e)

Yield: 45 mg (61%).

Ethyl 2-((3-fluoro-1-methyl-2-oxoindolin-3-yl)methyl)acrylate (4j)

Yield: 47 mg (57%).

3-Fluoro-1-methyl-3-(2-methylallyl)indolin-2-one (4n)

Yield: 47 mg (82%); Red oil; Rf 0.28 (hexane:EtOAc; 9:1).

1H NMR (300 MHz, CDCl3): δ = 7.42 (dddd, J = 7.4, 2.1, 1.3, 0.6 Hz, 1H), 7.37 (ddd, J = 7.8, 1.9, 1.3 Hz, 1H), 7.09 (tt, J = 7.6, 0.9 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H), 4.83 (m, 1H), 4.66 (m, 1H), 3.18 (s, 3H), 2.95 (t, J = 12.5 Hz, 1H), 2.79 (ddd, J = 20.4, 13.4, 0.8 Hz, 1H), 1.62 (s, 3H).

13C NMR (101 MHz, CDCl3): δ = 172.85 (d, J = 21.3 Hz), 144.21 (d, J = 5.3 Hz), 137.86 (d, J = 7.3 Hz), 131.22 (d, J = 2.8 Hz), 125.72 (d, J = 18.5 Hz), 125.42, 123.03 (d, J = 2.5 Hz, CH), 116.86, 108.71, 93.03 (d, J = 188.5 Hz), 42.55 (d, J = 27.3 Hz), 26.29, 23.97 – 23.83 (m).


LRMS (EI): m/z (%) = 219 (33) [M]+, 165 (11), 164 (100).


(E)-3-Fluoro-3-(hex-2-en-1-yl)-1-methylindolin-2-one (4o)

Yield: 45.1 mg (60%); Orange oil; Rf 0.24 (hexane:EtOAc; 9:1).

1H NMR (300 MHz, CDCl3): δ = 7.45 – 7.34 (m, 1H), 7.39 – 7.31 (m, 1H), 7.16 – 7.04 (m, 1H), 6.82 (d, J = 7.8 Hz, 1H), 5.50 (dt, J = 14.4, 6.8 Hz, 1H), 5.22 – 5.04 (m, 1H), 3.17 (s, 3H), 3.00 – 2.83 (m, 1H), 2.73 (m, 1H), 1.88 (m, 2H), 1.35 – 1.16 (m, 2H), 0.76 (t, J = 7.4 Hz, 3H).

13C NMR (101 MHz, CDCl3): δ = 172.90 (d, J = 21.1 Hz), 144.18 (d, J = 5.4 Hz), 137.44, 131.09 (d, J = 2.6 Hz), 125.97 (d, J = 18.7 Hz), 125.04, 123.12 (d, J = 2.4 Hz), 120.24 (d, J = 8.7 Hz), 108.61, 92.92 (d, J = 189.1 Hz), 38.37 (d, J = 27.9 Hz), 34.65, 26.26, 22.36, 13.49.


LRMS (EI): m/z (%) = 247 (5) [M]+, 166 (11), 165 (100), 164 (18).


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(E)-3-Fluoro-1-methyl-3-(penta-2,4-dien-1-yl)indolin-2-one (4p) and isomer (4p’)

Yield: 41.5 mg (60%); Orange oil; Rf 0.50 (hexane:EtOAc; 8:2).

1H NMR (300 MHz, CDCl3): δ = 7.46 – 7.33 (m, 3.2H), 7.09 (q, J = 7.7 Hz, 1.6H), 6.90 – 6.76 (m, 1.6H), 6.33 – 6.00 (m, 2.5H), 5.55 – 5.42 (m, 1H), 5.37 – 4.99 (m, 4.9H), 3.77 – 3.67 (m, 0.5H), 3.18 (s, 3H), 3.16 (s, 1.5H), 3.12 – 2.94 (m, 1H), 2.76 (ddd, J = 20.8, 14.2, 9.0 Hz, 1H).

13C NMR (101 MHz, CDCl3): δ = 172.74 , 172.53 , 144.45 (d, J = 5.9 Hz), 144.07 (d, J = 5.0 Hz), 136.69 , 136.37 , 134.08 , 132.88 (d, J = 3.8 Hz), 131.86 (d, J = 7.1 Hz), 131.55 , 131.26 (t, J = 2.7 Hz), 125.99 – 125.46 (m), 125.28 – 124.86 (m), 124.40 – 124.05 (m), 123.23 (d, J = 2.3 Hz), 122.98 (d, J = 2.3 Hz), 120.81 , 119.61 , 117.37 , 108.77 , 108.60 , 93.48 (d, J = 194.8 Hz), 92.48 (d, J = 189.4 Hz), 52.45 (d, J = 25.9 Hz), 38.33 (d, J = 28.3 Hz), 26.34 , 26.19.

19F NMR (282 MHz, CDCl3): δ = -157.66 (dd, J = 19.9, 11.4 Hz), -159.85 (d, J = 8.4 Hz).

LRMS (EI): m/z (%) = 231 (27) [M]+, 165 (27), 164 (100), 67 (24).


3-Allyl-3-fluoro-5-methoxy-1-methylindolin-2-one (4q)

Yield: 57 mg (81 %); brown wax; Rf 0.31 (hexane:EtOAc, 8:2).

1H NMR (400 MHz): δ = 7.03 (t, J = 2.2 Hz, 1H), 6.90 (ddd, J = 8.5, 2.5, 1.8 Hz, 1H), 6.74 (dd, J = 8.5, 1.1 Hz, 1H), 5.61 (dddd, J = 16.6, 10.1, 8.2, 6.3 Hz, 1H), 5.24 – 5.03 (m, 2H), 3.80 (s, 3H), 3.16 (s, 3H), 3.02 – 2.91 (m, 1H), 2.77 (ddd, J = 18.8, 13.6, 8.2 Hz, 1H).

13C NMR (101 MHz): δ = 172.34 (d, J = 21.2 Hz), 156.34 , 137.33 (d, J = 5.2 Hz), 129.02 (d, J = 8.4 Hz), 126.78 (d, J = 18.5 Hz), 121.11 , 115.39 , 112.31 , 109.19 , 92.71 (d, J = 189.7 Hz), 55.96 , 39.53 (d, J = 28.0 Hz), 26.34.

19F NMR (282 MHz): δ = -157.83 (dd, J = 18.7, 11.5 Hz).

LRMS (EI): m/z (%) = 235 (45) [M]+, 195 (11), 194 (100), 151 (11).


3-Allyl-5-chloro-3-fluoro-1-methylindolin-2-one (4r)


1H NMR (400 MHz): δ = 7.40 (t, J = 2.0 Hz, 1H), 7.36 (dt, J = 8.3, 1.9 Hz, 1H), 6.77 (dd, J = 8.3, 1.3 Hz, 1H), 5.66 – 5.51 (m, 1H), 5.21 – 5.11 (m, 2H), 3.18 (s, 3H), 2.96 (dddt, J = 13.9, 11.4, 6.4, 1.3 Hz, 1H), 2.84 – 2.69 (m, 1H).

13C NMR (101 MHz): δ = 172.12 (d, J = 21.2 Hz), 142.61 (d, J = 5.1 Hz), 131.09 (d, J = 2.5 Hz), 128.57 (dd, J = 13.6, 5.6 Hz), 127.19 (d, J = 18.7 Hz), 125.54 , 121.62 , 109.77 , 92.11 (d, J = 190.8 Hz), 39.51 , 39.24 , 26.42.

S17

19F NMR (282 MHz): δ = -158.20 (dd, J = 19.0, 11.3 Hz).

LRMS (EI): m/z (%) = 242 (2) [M]+, 241 (19), 239 (56), 200 (55), 199 (18), 198 (100), 135 (11).

HRMS (EI): m/z calcd. for [C12H11ClFNO] 242.0748; found: 242.0758.

3-Allyl-1-benzyl-3-fluoro-5-methoxyindolin-2-one (4s)

Yield: 30 mg (64%); Pale orange oil; Rf 0.27 (hexane:EtOAc, 9:1)

1H NMR (400 MHz): δ = 7.34 – 7.23 (m, 5H), 7.04 (t, J = 2.2 Hz, 1H), 6.76 (ddd, J = 8.6, 2.5, 1.8 Hz, 1H), 6.58 (dd, J = 8.6, 1.1 Hz, 1H), 5.58 (dddd, J = 17.0, 10.1, 8.4, 6.2 Hz, 1H), 5.23 – 5.10 (m, 2H), 4.98 (d, J = 15.7 Hz, 1H), 4.73 (d, J = 15.7 Hz, 1H), 3.76 (s, 3H), 3.08 – 2.97 (m, 1H), 2.88 (ddd, J = 17.0, 13.4, 8.4 Hz, 1H).

13C NMR (101 MHz): δ = 172.52 (d, J = 21.3 Hz), 156.34 (d, J = 2.6 Hz), 136.47 (d, J = 5.2 Hz), 135.28, 129.04 (d, J = 9.0 Hz), 128.93 , 127.89, 127.38, 126.83 (d, J = 18.5 Hz), 121.42, 115.51, 112.24, 110.40, 92.81 (d, J = 189.8 Hz), 55.95, 44.05, 39.65 (d, J = 28.1 Hz).

19F NMR (282 MHz): δ = -156.35 (dd, J = 16.7, 11.2 Hz).

LRMS (EI): m/z (%) = 312 (21), 311 (100) [M]+, 271 (14), 270 (79), 252 (10), 91 (100).

HRMS (EI): m/z calcd. for C19H18FNO2: 311.1322; found: 311.1321.

6. References1 N. Liu, Q. P. Tian, Q. Yang, S. D. Yang, Synlett, 2016, 27, 2621–2625.

2 Q. Yang, G.-L. Dai, Y.-M. Yang, Z. Luo, Z.-Y Tang, J. Org. Chem., 2018, 83, 6762-6768.

3 Y. Jin, M. Chen, S. Ge and J. F. Hartwig, Org. Lett., 2017, 19, 1390–1393.

4 K. Dong, B. Yan, S. Chang, Y. Chi, L. Qiu and X. Xu, J. Org. Chem., 2016, 81, 6887–6892.

5 K. Dong, B. Yan, S. Chang, Y. Chi, L. Qiu, X. Xu, J. Org. Chem., 2016, 81, 6887–6892.

6 K. Balaraman, R. Ding, C. Wolf, Adv. Synth. Catal. 2017, 359, 4165 – 4169.

S18

7. NMR Spectra7.1. Starting materials

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

3.07

1.02

1.04

1.01

1.04

-0.0

0

2.41

2.42

3.22

6.89

6.91

7.11

7.12

7.14

7.27

7.30

7.32

7.43

7.45

7.47

N

O

F

O

2a

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

3.06

2.97

1.02

1.12

1.06

0.00

2.39

2.40

3.20

3.79

6.80

6.80

6.82

6.82

6.89

6.90

6.90

6.94

6.95

6.95

6.95

6.96

6.97

6.97

6.98

7.27

N

O

O

F

O

2b

S19

0102030405060708090100110120130140150160170180190200210220ppm

26.0

926

.82

56.0

0

77.1

6

95.1

297

.14

110.

0311

1.94

116.

8111

6.84

123.

9812

4.17

138.

4613

8.51

156.

6615

6.68

168.

8816

9.09

200.

1520

0.45

N

O

O

F

O

2b

-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-165

.60

-165

.59

-165

.58

-165

.58

-165

.57

-76.

55

N

O

O

F

O

2b

S20

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

3.02

0.96

0.93

1.10

-0.0

0

2.46

2.47

3.21

6.82

6.85

7.27

7.28

7.29

7.29

7.40

7.41

7.42

7.43

7.44

7.44

N

Cl

O

F

O

2c

0102030405060708090100110120130140150160170180190200210220ppm

26.3

226

.92

77.1

6

94.4

096

.44

110.

46

124.

5512

4.73

125.

4812

9.16

129.

1813

2.22

132.

24

143.

8414

3.88

168.

7216

8.93

200.

1820

0.49

N

Cl

O

F

O

2c

S21

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-165

.39

-165

.38

-165

.38

-165

.37

-76.

55

N

Cl

O

F

O

2c

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

2.93

1.03

1.07

1.02

1.04

0.99

5.50

-0.0

0

2.42

2.43

3.74

4.75

4.79

4.97

5.01

6.63

6.63

6.65

6.65

6.80

6.81

6.81

6.81

6.82

6.83

6.83

6.83

6.89

6.90

6.90

7.26

7.27

7.29

7.29

7.31

7.32

7.33

7.34

7.34

7.35

7.36

N

O

O

F

O

2d

S22

0102030405060708090100110120130140150160170180190200210220ppm

26.2

1

44.3

5

55.9

7

77.1

6

95.2

497

.27

111.

1811

1.86

116.

7911

6.82

124.

1212

4.30

127.

3012

8.09

129.

0913

4.71

137.

4913

7.54

156.

6115

6.63

169.

1716

9.38

200.

2820

0.58

N

O

O

F

O

2d

-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-165

.75

-165

.74

-165

.74

-165

.73

-76.

55

N

O

O

F

O

2d

S23

7.2.Synthesis of fluoro-1-methyl-2-oxindoles 3

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

1.08

1.02

1.08

2.15

-0.0

0

3.20

5.59

5.76

6.83

6.86

7.10

7.12

7.15

7.26

7.38

7.41

7.43

7.46

7.48

N

O

F

3a

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.02

3.03

1.01

1.00

1.03

1.00

-0.0

0

3.17

3.81

5.58

5.70

6.73

6.74

6.75

6.76

6.90

6.91

6.91

6.92

6.93

6.93

7.08

7.08

7.09

7.27

N

O

O

F

3b

S24

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.06

1.00

1.02

1.02

0.98

-0.0

0

3.19

5.59

5.72

6.77

6.77

6.79

6.79

7.27

7.37

7.37

7.38

7.39

7.39

7.40

7.45

N

O

F

Cl

3c

7.3.Deacylative alkylation

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.13

3.09

1.00

1.02

2.02

0.00

1.72

1.80

3.20

6.84

6.86

7.09

7.09

7.09

7.12

7.14

7.14

7.14

7.27

7.36

7.36

7.37

7.38

7.39

7.39

7.40

7.41

7.41

7.43

7.43

7.44

N

O

F

4a

S25

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

1.04

1.05

3.04

2.03

1.00

1.00

1.01

2.02

-0.0

0

2.73

2.76

2.77

2.78

2.79

2.80

2.82

2.84

2.94

2.94

2.94

2.95

2.96

2.96

2.97

2.97

2.97

2.98

2.98

2.99

2.99

3.00

3.01

3.02

3.02

3.02

3.18

5.10

5.11

5.12

5.12

5.12

5.15

5.55

5.56

5.57

5.57

5.59

5.59

5.59

5.61

5.61

5.62

5.63

5.63

5.64

5.65

6.83

6.85

7.08

7.10

7.12

7.27

7.36

7.36

7.37

7.38

7.38

7.38

7.40

7.40

7.41

7.42

7.43

7.43

N

O

F

4b

0102030405060708090100110120130140150160170180190200210f1 (ppm)

26.2

5

39.3

239

.59

77.1

6

91.4

793

.35

108.

71

121.

0512

3.15

123.

1712

4.97

125.

5212

5.70

128.

9812

9.07

131.

1913

1.22

144.

0114

4.06

172.

4817

2.69

N

O

F

4b

S26

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-157

.76

-157

.73

-157

.71

-157

.68

-76.

55

N

O

F

4b

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0.73

3.00

1.06

1.46

2.89

3.52

0.71

1.24

1.22

1.21

1.24

2.52

-0.0

01.

541.

561.

591.

602.

642.

662.

682.

702.

712.

722.

752.

872.

872.

882.

882.

892.

902.

902.

912.

912.

922.

922.

922.

932.

932.

932.

942.

952.

952.

953.

183.

185.

165.

175.

175.

185.

195.

195.

205.

215.

225.

235.

235.

245.

255.

25

5.51

5.53

5.54

5.56

5.58

5.60

5.62

5.62

6.82

6.84

7.07

7.08

7.08

7.09

7.10

7.11

7.12

7.27

7.35

7.36

7.36

7.38

7.38

7.40

7.40

7.43

7.44

N

O

F

4c

S27

0102030405060708090100110120130140150160170180190200210f1 (ppm)

13.1

3

18.1

3

26.2

8

32.6

532

.93

38.2

238

.49

77.1

6

91.8

193

.69

108.

66

120.

3912

0.47

121.

2212

1.30

123.

1012

3.12

124.

8512

5.04

125.

8412

6.03

129.

7713

1.06

131.

0913

1.92

144.

0714

4.12

172.

7717

2.98

N

O

F

4c

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-157

.91

-157

.87

-157

.84

-157

.80

-157

.56

-157

.52

-157

.50

-157

.46

-76.

55

N

O

F

4c

S28

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

2.99

3.00

1.04

1.03

3.08

0.99

0.99

1.00

2.03

-0.0

0

1.54

1.64

2.72

2.74

2.75

2.77

2.79

2.80

2.82

2.86

2.88

2.89

2.90

2.91

2.91

2.92

2.93

2.94

3.18

4.93

4.93

4.93

4.94

4.94

4.94

4.95

4.95

4.95

4.96

4.96

4.96

4.97

4.97

4.97

4.98

6.81

6.83

7.06

7.08

7.10

7.34

7.35

7.35

7.36

7.37

7.37

7.39

7.41

N

O

F

4d

0102030405060708090100110120130140150160170180190200210f1 (ppm)

18.1

4

25.9

726

.27

33.8

734

.14

77.1

6

91.9

793

.84

108.

60

114.

4211

4.50

123.

0812

3.11

124.

9012

6.02

126.

2013

1.01

131.

03

137.

65

144.

0814

4.14

172.

9617

3.17

N

O

F

4d

S29

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-157

.80

-157

.76

-157

.73

-157

.69

-76.

55

N

O

F

4d

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

1.01

11.6

2

7.53

1.00

1.02

1.68

1.84

1.89

3.82

0.00

0.72

0.73

0.76

0.76

0.79

0.80

0.83

0.84

1.33

1.34

1.38

1.41

1.42

1.45

1.47

1.49

1.51

1.52

1.54

1.55

1.56

1.58

1.59

1.67

1.69

1.71

1.73

1.76

1.77

1.82

1.83

1.85

1.87

1.89

1.94

1.95

1.98

2.01

3.07

3.08

3.09

3.10

3.10

3.11

3.13

3.14

3.15

3.17

3.19

3.20

3.21

5.62

5.62

5.63

5.65

5.66

5.66

5.77

5.78

5.79

5.80

5.81

5.94

5.98

6.82

6.85

7.03

7.03

7.04

7.06

7.07

7.07

7.07

7.08

7.08

7.09

7.09

7.12

7.12

7.12

7.35

7.38

7.40

7.40

7.42

7.43

N

O

F

4e

S30

0102030405060708090100110120130140150160170180190200210f1 (ppm)

20.9

121

.63

22.8

022

.84

22.8

622

.89

24.9

625

.02

26.2

6

40.9

141

.15

41.9

042

.15

77.1

6

94.0

994

.23

95.9

696

.12

108.

4210

8.62

123.

0412

3.06

123.

1112

3.13

123.

4812

3.56

123.

6112

4.67

124.

8212

5.58

125.

7612

5.85

130.

0913

1.02

131.

0413

1.64

144.

3514

4.40

144.

5514

4.61

172.

5417

2.69

172.

7617

2.90

N

O

F

4e

-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010f1 (ppm)

-164

.41

-164

.38

-161

.17

-161

.13

-76.

55

N

O

F

4e

S31

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

1.06

4.06

1.00

0.99

1.00

1.03

5.19

2.20

0.00

2.79

2.80

2.82

2.83

2.84

2.84

2.86

2.87

2.87

2.89

2.90

2.91

2.91

2.94

2.94

3.10

3.11

3.13

3.13

3.14

3.16

3.18

3.19

3.19

3.21

3.21

5.97

5.99

5.99

6.02

6.02

6.04

6.05

6.07

6.43

6.48

6.80

6.83

7.06

7.09

7.11

7.17

7.19

7.20

7.22

7.22

7.23

7.24

7.26

7.27

7.34

7.34

7.35

7.36

7.37

7.37

7.40

7.40

7.41

7.43

N

O

F

4f

0102030405060708090100110120130140150160170180190200210f1 (ppm)

26.3

4

38.5

238

.90

77.1

6

91.3

693

.87

108.

8012

0.29

120.

3912

3.22

123.

2512

5.16

125.

5412

5.79

126.

3812

7.73

128.

6113

1.23

131.

2713

5.77

136.

8914

4.00

144.

08

172.

5117

2.79

N

O

F

4f

S32

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-157

.58

-157

.55

-157

.53

-157

.50

-76.

55

N

O

F

4f

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.06

1.03

1.00

0.98

2.00

2.05

3.00

1.02

0.00

3.05

3.15

3.19

3.21

3.24

3.54

3.57

3.57

3.60

6.68

6.70

6.97

6.97

6.98

6.99

7.00

7.01

7.04

7.05

7.06

7.15

7.15

7.16

7.16

7.17

7.18

7.18

7.19

7.25

7.27

7.28

7.28

7.29

7.30

7.30

7.31

7.31

7.31

7.32

N

O

F

4g

S33

0102030405060708090100110120130140150160170180190200210f1 (ppm)

26.1

5

41.1

441

.41

77.1

6

92.3

694

.26

108.

57

122.

8812

2.91

125.

1412

5.33

125.

4612

7.31

128.

1413

0.64

131.

0813

1.11

132.

7613

2.82

143.

9214

3.97

172.

7017

2.91

N

O

F

4g

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-157

.15

-157

.12

-157

.09

-157

.07

-76.

55

N

O

F

4g

S34

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

2.84

1.00

0.98

0.97

1.97

0.99

1.89

0.97

0.00

3.08

3.31

3.35

3.37

3.42

3.61

3.64

3.65

3.69

6.72

6.75

6.98

7.01

7.04

7.06

7.09

7.33

7.33

7.34

7.35

7.36

7.36

7.38

7.38

7.39

7.52

7.74

N

O

F

FF

F F

FF

4h

0102030405060708090100110120130140150160170180190200210f1 (ppm)

26.2

0

41.0

041

.28

77.1

6

91.5

993

.52

109.

0212

1.34

121.

3812

1.41

121.

4512

1.49

121.

8512

3.29

123.

3112

4.23

124.

4312

4.56

125.

1113

0.83

131.

0013

1.33

131.

6613

1.78

131.

8113

1.99

135.

5313

5.61

143.

7514

3.80

171.

9017

2.11

N

O

F

FF

F F

FF

4h

S35

-220-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010f1 (ppm)

1.00

6.25

-159

.01

-158

.97

-158

.94

-158

.90

-76.

55

-63.

77

N

O

F

FF

F F

FF

4h

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0.96

1.04

4.08

1.00

1.02

1.05

1.00

-0.0

0

1.99

2.00

2.01

2.81

2.82

2.86

2.87

2.87

2.88

2.93

2.94

3.14

3.15

3.16

3.17

3.19

3.20

3.22

3.23

6.86

6.88

7.12

7.12

7.15

7.17

7.17

7.17

7.40

7.40

7.41

7.42

7.43

7.43

7.45

7.46

7.46

7.63

7.63

7.64

7.65

7.66

7.66

N

O

F

4i

S36

0102030405060708090100110120130140150160170180190200210f1 (ppm)

25.5

526

.00

26.4

3

71.8

871

.89

76.1

376

.28

77.1

6

89.2

491

.78

108.

80

123.

4512

3.48

124.

8212

5.06

125.

2313

1.70

131.

73

144.

2514

4.32

171.

5217

1.80

N

O

F

4i

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-157

.98

-157

.96

-157

.93

-157

.91

-76.

55

N

O

F

4i

S37

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.05

4.24

1.05

2.04

1.02

1.00

1.04

1.04

2.06

0.00

1.13

1.15

1.18

3.03

3.08

3.09

3.14

3.17

3.19

3.33

3.38

3.42

3.99

4.01

4.03

4.06

5.74

6.26

6.79

6.82

7.03

7.05

7.08

7.28

7.32

7.33

7.33

7.35

7.36

7.38

7.38

N

O

F

O

O

4j

-20-100102030405060708090100110120130140150160170180190200210220f1 (ppm)

14.1

4

26.2

8

35.6

035

.99

61.0

3

77.1

6

91.1

393

.66

108.

69

122.

9112

2.94

124.

7812

5.03

125.

6113

0.08

131.

3113

1.34

133.

1813

3.27

144.

0014

4.07

166.

44

172.

3117

2.59

N

O

F

O

O

4j

S38

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-156

.69

-156

.63

-156

.57

-76.

55

N

O

F

O

O

4j

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

2.98

1.06

1.04

3.00

0.98

1.00

0.99

1.99

2.96

0.00

3.05

3.09

3.13

3.15

3.19

3.55

3.58

3.58

3.61

3.67

6.50

6.51

6.51

6.60

6.60

6.62

6.62

6.81

6.81

6.81

6.82

6.83

6.83

6.83

6.84

7.08

7.09

7.10

7.10

7.20

7.21

7.22

7.26

N

O

O

F

4k

S39

0102030405060708090100110120130140150160170180190200210ppm

26.2

7

41.2

141

.48

55.8

3

77.1

6

92.5

494

.44

109.

1111

2.37

115.

8811

5.90

126.

2012

6.39

127.

3912

8.18

130.

7613

2.86

132.

9213

7.20

137.

25

155.

9715

6.00

172.

5217

2.72

N

O

O

F

4k

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-157

.57

-157

.53

-157

.49

-157

.45

-76.

55

N

O

O

F

4k

S40

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

1.05

1.02

0.99

0.97

2.03

2.98

1.16

0.00

3.05

3.16

3.19

3.22

3.25

3.51

3.54

3.55

3.57

6.61

6.61

6.63

6.63

6.94

6.95

6.95

7.04

7.05

7.06

7.06

7.18

7.19

7.20

7.21

7.22

7.22

7.26

7.27

7.27

7.28

7.29

7.29

N

Cl

O

F

4l

0102030405060708090100110120130140150160170180190200210ppm

26.3

0

41.1

241

.39

77.1

6

92.0

793

.99

109.

6012

5.95

126.

7212

6.91

127.

5912

8.31

130.

5913

0.95

130.

9713

2.20

132.

27

142.

4414

2.49

172.

2417

2.45

N

Cl

O

F

4l

S41

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-157

.61

-157

.58

-157

.53

-157

.50

-76.

55

N

Cl

O

F

4l

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

1.11

1.17

3.00

1.04

1.05

1.00

1.06

3.07

2.08

6.68

-0.0

0

3.35

3.39

3.41

3.45

3.57

3.60

3.61

3.64

3.71

4.44

4.49

4.97

5.03

6.35

6.35

6.38

6.38

6.67

6.68

6.68

6.69

6.70

6.71

6.71

6.71

6.75

6.75

6.77

6.78

6.80

6.81

6.81

7.05

7.07

7.14

7.16

7.16

7.18

7.18

7.20

7.20

7.22

7.22

7.23

7.24

7.25

7.25

N

O

F

O

4m

S42

0102030405060708090100110120130140150160170180190200f1 (ppm)

41.1

241

.50

43.8

7

55.8

8

77.1

6

92.6

295

.15

110.

4511

2.21

115.

8311

5.87

126.

3212

6.57

126.

8212

7.41

127.

5712

8.42

128.

8113

0.87

132.

4313

2.56

134.

8613

6.56

136.

63

156.

1015

6.13

172.

3417

2.62

N

O

F

O

4m

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-153

.39

-153

.36

-153

.32

-153

.29

-76.

55

N

O

F

O

4m

S43

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

9.00

4.23

3.06

1.03

1.05

2.11

0.00

1.40

2.33

2.33

2.34

2.35

2.36

2.37

2.37

2.37

2.38

2.38

2.39

2.39

2.40

2.41

2.41

2.42

2.43

2.44

2.44

2.45

2.45

2.47

3.19

6.83

6.86

7.09

7.09

7.09

7.11

7.12

7.12

7.12

7.13

7.14

7.14

7.14

7.27

7.36

7.37

7.37

7.37

7.39

7.39

7.39

7.40

7.40

7.41

7.41

7.41

7.41

7.42

7.42

7.42

7.43

7.43

7.43

7.43

N

O

FO

O

5a

0102030405060708090100110120130140150160170180190200210ppm

26.3

428

.13

28.8

228

.88

30.3

630

.65

77.1

6

80.8

9

91.5

293

.39

108.

86

123.

4212

3.44

124.

7312

5.63

125.

8213

1.39

131.

41

143.

9814

4.03

171.

4517

2.51

172.

72

N

O

FO

O

5a

S44

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-161

.86

-161

.83

-161

.80

-161

.77

-76.

55

N

O

FO

O

5a

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.29

3.29

3.00

1.00

1.03

2.04

0.00

2.22

2.25

2.27

2.30

2.31

2.33

2.34

2.36

2.38

2.40

2.53

2.55

2.57

2.59

2.62

2.63

2.65

2.67

2.69

2.70

2.72

2.74

2.77

2.78

2.80

2.82

2.86

3.20

6.87

6.90

7.13

7.16

7.18

7.39

7.39

7.40

7.41

7.42

7.42

7.44

7.44

7.45

7.46

7.47

7.48

N

O

F

N

5b

S45

0102030405060708090100110120130140150160170180190200ppm

11.0

011

.09

26.4

431

.18

31.5

6

77.1

6

89.5

492

.05

109.

26

118.

6512

3.74

123.

7712

4.55

124.

8413

2.05

132.

09

143.

8414

3.91

171.

4817

1.77

N

O

F

N

5b

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-159

.67

-159

.63

-159

.59

-76.

55

N

O

F

N

5b

S46

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.00

2.96

2.93

2.99

3.00

0.98

1.00

1.99

-0.0

0

2.26

2.28

2.30

2.31

2.31

2.33

2.33

2.35

2.36

2.36

2.39

2.39

2.41

2.41

2.43

2.46

2.50

2.52

2.52

2.53

2.54

2.54

2.55

2.55

2.56

2.57

2.58

2.58

2.59

2.59

2.59

2.60

2.61

2.63

2.64

2.66

2.92

3.00

3.19

6.84

6.86

7.09

7.12

7.14

7.36

7.36

7.37

7.38

7.39

7.39

7.40

7.40

7.41

7.42

7.42

7.43

N

O

FN

O

5c

0102030405060708090100110120130140150160170180190200210ppm

26.0

326

.08

26.3

029

.77

30.8

331

.10

35.6

137

.28

77.1

6

91.5

493

.40

108.

78

123.

4112

3.43

124.

5412

6.12

126.

3013

1.30

131.

33

143.

7214

3.78

171.

5317

2.66

172.

88

N

O

FN

O

5c

S47

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-161

.17

-161

.15

-161

.14

-161

.10

-161

.07

-76.

55

N

O

FN

O

5c

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

2.87

2.36

2.09

3.00

1.01

1.05

2.01

0.00

2.14

2.24

2.25

2.27

2.29

2.32

2.34

2.36

2.37

2.40

2.41

2.43

2.45

2.46

2.47

2.49

2.51

2.52

2.54

2.60

2.61

2.66

2.67

2.69

2.71

2.72

2.74

2.77

2.78

3.19

6.84

6.87

7.09

7.12

7.14

7.37

7.38

7.38

7.39

7.39

7.40

7.41

7.41

7.42

7.42

7.43

N

O

F

O

5d

S48

0102030405060708090100110120130140150160170180190200210220

26.3

529

.27

29.5

030

.05

36.3

436

.37

77.1

6

91.4

892

.97

108.

87

123.

4712

3.49

124.

5312

6.14

126.

2913

1.41

131.

43

143.

8714

3.91

172.

6217

2.80

206.

76

N

O

F

O

5d

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-160

.93

-160

.90

-160

.87

-160

.83

-76.

55

N

O

F

O

5d

S49

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.05

1.00

2.85

1.06

0.99

0.98

1.01

2.04

2.02

1.03

1.03

0.94

0.00

2.61

2.63

3.16

3.38

3.38

3.39

3.39

3.42

3.44

3.53

3.55

3.58

3.58

3.59

3.59

6.84

6.87

7.10

7.13

7.15

7.27

7.34

7.34

7.34

7.35

7.35

7.35

7.35

7.36

7.37

7.37

7.37

7.37

7.38

7.38

7.38

7.39

7.39

7.41

7.41

7.41

7.42

7.44

7.55

7.56

7.56

7.57

7.57

7.58

7.58

7.58

7.60

7.61

7.61

7.65

7.66

7.66

7.68

7.68

7.71

7.89

7.89

7.90

7.90

7.91

7.92

7.92

7.92

N

O

F

S

O

O

5e

0102030405060708090100110120130140150160170180190200210ppm

26.3

928

.63

28.9

2

49.7

249

.75

77.1

6

89.8

691

.75

109.

15

123.

7112

3.73

124.

4512

5.02

125.

2112

8.16

129.

5413

1.90

131.

9213

4.09

138.

7814

3.65

143.

70

171.

5317

1.75

N

O

F

S

O

O

5e

S50

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-161

.75

-161

.70

-161

.66

-161

.61

-76.

55

N

O

F

S

O

O

5e

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

6.41

1.98

2.45

3.00

4.19

0.98

1.01

2.00

-0.0

01.

281.

301.

331.

351.

821.

841.

851.

851.

861.

871.

881.

881.

891.

901.

921.

921.

921.

931.

941.

941.

962.

262.

272.

282.

292.

302.

302.

312.

312.

322.

322.

332.

332.

342.

352.

352.

362.

362.

362.

372.

372.

382.

392.

392.

392.

402.

402.

412.

412.

422.

422.

432.

442.

452.

473.

204.

024.

034.

054.

054.

074.

074.

084.

094.

104.

104.

124.

124.

144.

146.

856.

877.

107.

137.

157.

387.

387.

397.

397.

407.

417.

417.

427.

437.

437.

44

N

O

FP

O

O

O

5f

S51

0102030405060708090100110120130140150160170180190200210ppm

16.4

616

.48

16.5

316

.56

18.0

418

.11

19.9

520

.02

26.3

528

.57

28.6

228

.96

29.0

1

61.8

861

.96

62.0

4

77.1

6

90.8

293

.61

108.

96

123.

5012

3.53

124.

5512

5.30

125.

5513

1.54

131.

57

143.

9114

3.98

172.

1517

2.43

N

O

FP

O

O

O

5f

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-161

.01

-160

.96

-160

.92

-76.

55

N

O

FP

O

O

O

5f

S52

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.33

4.12

1.00

0.98

1.03

0.97

1.09

4.20

2.22

2.07

2.00

0.00

2.94

3.00

3.04

3.06

3.10

3.11

3.19

3.21

3.22

3.24

3.26

3.28

3.30

3.32

5.61

5.62

5.64

6.86

6.88

7.12

7.15

7.17

7.35

7.38

7.41

7.44

7.46

7.50

7.53

7.54

7.55

7.56

7.59

7.63

7.66

7.66

7.69

7.72

7.87

7.90

8.01

8.04

N

O

F

S

S

O O

O

O

5g

0102030405060708090100110120130140150160170180190200210

26.5

030

.37

30.6

8

76.7

677

.16

88.5

990

.49

109.

3812

3.61

123.

6312

4.40

124.

9112

5.08

129.

1612

9.28

129.

7012

9.85

132.

1213

2.14

134.

5113

4.77

137.

4813

8.72

143.

84

171.

6617

1.88

N

O

F

S

S

O O

O

O

5g

S53

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10

-159

.01

-158

.97

-158

.89

-158

.85

-76.

55

N

O

F

S

S

O O

O

O

5g

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

9.03

4.11

3.02

3.00

1.01

1.01

1.00

-0.0

0

1.40

2.29

2.32

2.32

2.34

2.35

2.37

2.38

2.39

2.41

2.42

2.43

2.44

2.47

3.17

3.81

6.74

6.74

6.76

6.76

6.89

6.89

6.89

6.90

6.91

6.91

6.91

6.92

7.02

7.02

7.03

7.27

N

O

O

FO

O

5h

S54

0102030405060708090100110120130140150160170180190200210ppm

26.4

328

.13

28.8

128

.87

29.8

230

.42

30.7

0

56.0

0

77.1

6

80.9

1

91.8

593

.72

109.

3911

1.89

115.

7311

5.75

126.

7012

6.89

137.

2013

7.25

156.

5415

6.56

171.

4417

2.24

172.

46N

O

O

FO

O

5h

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-159

.71

-159

.66

-159

.60

-76.

55

N

O

O

FO

O

5h

S55

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

9.00

4.15

3.00

1.04

2.06

-0.0

0

1.41

2.32

2.34

2.35

2.36

2.37

2.37

2.39

2.40

2.42

2.43

2.44

2.45

2.46

3.18

6.77

6.77

6.79

6.79

7.27

7.35

7.36

7.36

7.37

7.38

7.38

7.39

7.39

7.40

N

Cl

O

F O

O

5i

0102030405060708090100110120130140150160170180190200210ppm

26.5

028

.13

28.6

528

.71

30.2

830

.56

77.1

6

81.0

9

91.2

293

.10

109.

92

125.

3212

7.15

127.

3412

8.89

128.

9113

1.26

131.

29

142.

4814

2.53

171.

2017

2.02

172.

23

N

Cl

O

F O

O

5i

S56

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-160

.13

-160

.07

-160

.02

-76.

55

N

Cl

O

F O

O

5i

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

9.09

4.18

3.00

1.03

1.05

1.04

1.01

1.00

5.47

0.00

1.41

2.30

2.31

2.32

2.34

2.35

2.36

2.37

2.38

2.39

2.39

2.40

2.41

2.43

2.44

2.45

2.46

2.46

2.47

2.48

2.49

2.50

2.50

2.51

2.51

2.52

2.54

2.56

3.76

4.79

4.83

4.88

4.92

6.60

6.60

6.62

6.62

6.76

6.76

6.77

6.78

6.78

6.79

7.02

7.02

7.03

7.25

7.26

7.27

7.28

7.31

7.32

7.34

N

F

O

O

O

O

5j

S57

0102030405060708090100110120130140150160170180190200210f1 (ppm)

28.1

428

.84

28.9

030

.52

30.8

0

44.0

3

55.9

5

77.1

6

80.9

4

91.8

693

.73

110.

5511

1.91

115.

75

126.

7112

6.89

127.

3412

7.95

129.

0213

5.24

136.

2413

6.29

156.

48

171.

4417

2.42

172.

63

N

F

O

O

O

O

5j

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-158

.86

-158

.85

-158

.80

-158

.74

-76.

55

N

O

F

O

O

O

5j

S58

7.4.Deacylative allylation

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.08

1.08

3.00

2.07

1.03

1.03

1.05

2.10

-0.0

0

2.72

2.75

2.76

2.78

2.79

2.81

2.83

2.85

2.93

2.95

2.95

2.97

2.98

2.99

3.01

3.03

3.03

5.09

5.10

5.10

5.12

5.13

5.13

5.16

5.53

5.55

5.56

5.57

5.58

5.59

5.59

5.61

5.62

5.62

5.64

5.65

5.65

5.67

6.82

6.85

7.08

7.10

7.13

7.27

7.35

7.36

7.36

7.38

7.38

7.39

7.40

7.41

7.41

7.43

7.43

N

O

F

4b

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.54

1.93

3.05

1.00

1.18

0.40

2.38

0.42

1.01

0.47

1.83

1.94

3.78

-0.0

00.

850.

871.

251.

251.

271.

281.

541.

561.

571.

591.

612.

672.

692.

702.

732.

762.

882.

902.

902.

922.

922.

933.

163.

183.

204.

975.

015.

155.

155.

165.

195.

205.

215.

215.

225.

225.

235.

245.

245.

255.

275.

285.

285.

525.

545.

555.

575.

596.

046.

816.

826.

826.

826.

846.

846.

856.

857.

047.

077.

077.

087.

087.

097.

107.

107.

107.

117.

127.

127.

137.

137.

357.

357.

367.

377.

377.

387.

397.

397.

407.

407.

417.

437.

437.

457.

46

N

O

F

N

O

F

4c 4c'

S59

0102030405060708090100110120130140150160170180190200210ppm

12.3

912

.45

13.3

613

.40

18.1

4

26.1

526

.29

38.2

338

.50

41.7

441

.99

43.5

943

.85

77.1

691

.82

93.7

093

.77

95.6

610

8.57

108.

6611

8.35

118.

4712

0.40

120.

4912

1.23

121.

3112

2.97

123.

0012

3.03

123.

1112

3.14

125.

0612

5.38

125.

6612

5.86

126.

0512

9.79

131.

0713

1.10

131.

1213

1.15

131.

9413

5.34

135.

3913

5.53

135.

6014

4.09

144.

1414

4.43

144.

4914

4.53

144.

59

172.

7917

2.86

173.

0017

3.07

N

O

F

N

O

F

4c 4c'

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-162

.79

-162

.76

-159

.31

-159

.28

-157

.97

-157

.93

-157

.90

-157

.86

-76.

55

N

O

F

N

O

F

4c 4c'

S60

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

2.20

17.1

6

10.2

8

0.99

1.00

3.45

2.74

2.78

5.51

-0.0

0

1.33

1.38

1.42

1.44

1.47

1.49

1.51

1.52

1.54

1.56

1.58

1.59

1.67

1.77

1.84

1.85

1.87

1.89

1.94

1.96

1.98

2.00

3.19

3.20

5.62

5.65

5.66

5.66

5.76

5.77

5.78

5.80

5.81

5.94

5.98

5.98

6.02

6.82

6.84

7.04

7.06

7.09

7.10

7.12

7.26

7.34

7.35

7.35

7.37

7.37

7.38

7.40

7.40

7.42

7.43

N

O

F

4e

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.06

1.20

3.07

1.01

1.99

0.97

0.97

1.01

1.02

2.02

-0.0

0

1.13

1.15

1.18

3.03

3.08

3.09

3.14

3.17

3.33

3.38

3.42

3.99

4.01

4.03

4.06

5.74

6.26

6.26

6.27

6.79

6.82

7.02

7.05

7.07

7.27

7.32

7.33

7.33

7.35

7.36

7.38

7.38

N

O

F

O

O

4j

S61

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.12

1.08

1.08

3.06

0.99

1.00

1.02

1.04

2.08

-0.0

0

1.63

2.73

2.77

2.80

2.84

2.90

2.95

2.99

3.18

4.66

4.82

4.83

4.83

4.84

6.82

6.85

7.07

7.09

7.12

7.27

7.35

7.38

7.41

7.43

N

O

F

4n

0102030405060708090100110120130140150160170180190200210ppm

23.9

023

.91

26.2

9

42.4

242

.69

77.1

6

92.0

993

.97

108.

71

116.

8612

3.02

123.

0412

5.42

125.

6312

5.81

131.

2113

1.24

137.

8213

7.90

144.

1814

4.23

172.

7417

2.95

N

O

F

4n

S62

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10

-154

.67

-154

.63

-154

.60

-154

.56

-76.

55

N

O

F

4n

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

2.96

2.58

2.01

1.04

1.10

2.86

1.05

1.00

1.06

1.07

2.16

-0.0

0

0.74

0.76

0.79

1.19

1.22

1.24

1.26

1.29

1.31

1.85

1.87

1.89

1.92

3.17

5.08

5.10

5.11

5.13

5.15

5.16

5.18

5.46

5.48

5.50

5.53

5.55

6.81

6.83

7.07

7.10

7.13

7.27

7.34

7.35

7.35

7.37

7.39

7.39

7.41

7.41

N

O

F

4o

S63

0102030405060708090100110120130140150160170180190200210ppm

13.4

9

22.3

626

.26

34.6

538

.23

38.5

1

77.1

6

91.9

993

.86

108.

6112

0.20

120.

2812

3.11

123.

1312

5.04

125.

8812

6.06

131.

0713

1.10

137.

4414

4.15

144.

20

172.

8017

3.01

N

O

F

4o

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-157

.70

-157

.66

-157

.63

-157

.60

-76.

55

N

O

F

4o

S64

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.00

1.20

1.50

3.00

0.51

4.85

0.96

2.46

1.57

1.60

3.18

-0.0

0

2.69

2.72

2.74

2.76

2.77

2.79

2.81

2.83

2.97

3.00

3.02

3.04

3.06

3.08

3.16

3.18

3.68

3.70

3.71

3.73

3.74

3.76

5.01

5.04

5.09

5.12

5.14

5.15

5.17

5.18

5.19

5.22

5.23

5.25

5.27

5.31

5.34

5.44

5.46

5.47

5.49

5.51

5.54

6.07

6.08

6.10

6.12

6.14

6.15

6.17

6.19

6.20

6.23

6.24

6.26

6.30

6.81

6.82

6.85

7.05

7.08

7.10

7.13

7.36

7.38

7.38

7.40

7.41

7.42

7.44

N

O

F

N

O

F

4p 4p'

0102030405060708090100110120130140150160170180190200210

26.1

926

.34

38.1

938

.47

52.3

252

.58

77.1

691

.54

92.5

193

.42

94.4

510

8.60

108.

7711

7.37

119.

6112

0.81

122.

9712

2.99

123.

2212

3.25

124.

2112

4.29

125.

0712

5.61

125.

6812

5.80

131.

2313

1.26

131.

2913

1.55

131.

8313

1.90

132.

8613

2.90

134.

0813

6.37

136.

6914

4.04

144.

0914

4.42

144.

48

172.

5317

2.74

N

O

F

N

O

F

4p 4p'

S65

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10

-159

.87

-159

.84

-157

.72

-157

.68

-157

.65

-157

.61

-76.

55

N

O

F

N

O

F

4p 4p'

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.00

1.02

2.98

3.00

1.99

0.99

0.97

0.98

0.97

0.00

2.72

2.74

2.76

2.77

2.78

2.79

2.80

2.82

2.92

2.94

2.95

2.97

2.98

3.00

3.00

3.16

3.80

5.11

5.12

5.13

5.17

5.55

5.57

5.58

5.58

5.59

5.60

5.60

5.61

5.62

5.62

5.63

5.64

5.64

5.66

6.73

6.74

6.75

6.76

6.88

6.89

6.89

6.89

6.90

6.91

6.91

6.91

7.03

7.03

7.04

7.28

N

O

O

F

4q

S66

0102030405060708090100110120130140150160170180190200210ppm

26.3

4

39.4

039

.67

55.9

6

77.1

6

91.7

693

.65

109.

1911

2.31

115.

39

121.

11

126.

6912

6.88

128.

9812

9.06

137.

3013

7.35

156.

34

172.

2417

2.45

N

O

O

F

4q

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-157

.88

-157

.84

-157

.82

-157

.78

-76.

55

N

O

O

F

4q

S67

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.02

1.03

3.00

1.98

0.99

0.96

0.96

0.97

-0.0

0

2.72

2.74

2.75

2.77

2.77

2.79

2.80

2.82

2.92

2.94

2.95

2.97

2.99

3.00

3.18

5.14

5.16

5.18

5.54

5.56

5.58

5.60

5.62

5.64

6.76

6.76

6.78

6.79

7.27

7.34

7.35

7.35

7.36

7.37

7.37

7.39

7.40

7.40

N

Cl

O

F

4r

0102030405060708090100110120130140150160170180190200210ppm

26.4

2

39.2

439

.51

77.1

6

91.1

693

.06

109.

77

121.

6212

5.54

127.

0912

7.28

128.

4612

8.54

128.

6212

8.65

131.

0713

1.10

142.

5814

2.63

172.

0217

2.23

N

Cl

O

F

4r

S68

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10ppm

-158

.26

-158

.22

-158

.19

-158

.15

-76.

55

N

Cl

O

F

4r

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

1.04

1.01

2.94

1.00

1.01

2.03

1.00

0.98

0.99

0.99

5.37

-0.0

02.

842.

862.

872.

882.

892.

902.

912.

932.

982.

982.

982.

992.

993.

003.

003.

013.

013.

013.

023.

023.

033.

033.

033.

043.

043.

053.

063.

063.

764.

714.

754.

965.

005.

125.

155.

175.

215.

535.

545.

555.

555.

575.

575.

575.

575.

595.

595.

595.

605.

615.

615.

625.

636.

576.

576.

596.

606.

756.

756.

756.

766.

776.

776.

776.

787.

037.

047.

047.

247.

257.

267.

277.

277.

297.

307.

317.

327.

337.

33

N

O

F

O

4s

S69

0102030405060708090100110120130140150160170180190200210f1 (ppm)

39.5

139

.79

44.0

5

55.9

5

77.1

6

91.8

793

.75

110.

4011

2.24

115.

51

121.

4212

6.74

126.

9212

7.38

127.

8912

8.93

128.

9912

9.08

135.

2813

6.45

136.

50

156.

3315

6.36

172.

4217

2.63

N

O

F

O

4s

-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10f1 (ppm)

-156

.40

-156

.36

-156

.34

-156

.30

-76.

55

N

O

F

O

4s

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