Supporting Information

(1)

S-1

Supporting Information

= quartet, sext = sextet, sept = septet, p = pseudo, b = broad, m = multiplet, dm = double multiplet), coupling constants (Hz). ¹³C-NMR spectra were recorded on a Varian 400 (100 MHz) spectrometer with complete proton decoupling. Chemical shifts are reported in ppm from TMS with the solvent as the internal standard (deuterochloroform: 77.0 ppm).

GC-MS spectra were taken by EI ionization at 70 eV on a Hewlett-Packard 5971 with GC injection.

They are reported as: m/z (rel. intensity). LC-electrospray ionization mass spectra were obtained with an Agilent Technologies MSD1100 (nebulizer: 15.0 PSI, dry Gas: 5.0 L/min, dry temperature:

325 °C, capillary voltage positive scan: 4000 mA, capillary voltage negative scan: 3500 mA) single- quadrupole mass spectrometer. Chromatographic purification was done with 240-400 mesh silica gel. Anhydrous solvents were supplied by Sigma Aldrich in Sureseal® bottles and used without any further purification. Commercially available chemicals were purchased from Sigma Aldrich, Stream, TCI, Alfa Aeser and Fluorochem and used without any further purification. Melting points were determined with Bibby Stuart Scientific Melting Point Apparatus SMP 3 and are not corrected.

Indole 1a was purchased from Merck-Aldrich and Fluorochem and used as received. Indoles 1h and 1i were purchased from Alfa Aeser and used as received.

Graphene oxide was purchased from Graphenea as powder and as water dispersion (4 mg/mL). The latter was dried before use.

FT-IR spectra were recorded on Brucker Alpha System spectrometer.

XPS spectra were acquired by using a Phoibos 100 hemispherical energy analyzer (Specs) using Mg Kα radiation (ħω =1253.6 eV). The X-ray power was 125 W. The spectra were recorded in the constant analyser energy (CAE) mode with analyser pass energies of 10 eV for the high-resolution spectra. Charging effects were corrected by energy calibration on C 1s at 285.0 eV. Overall resolution of 0.9 eV was determined on Ag 3d5/2. The base pressure in the analysis chamber during analysis was 1×10⁻⁹ mbar. High resolution XPS spectra of C 1s were analysed by CasaXPS (Casa software, Ltd), the curve fitting was carried out using Gaussian/Lorentzian curves shape (GL(30)) for C-O groups with a full width half-maximum of 1.4 eV and an asymmetric Voigt for the C-C sp². The C 1s peak revealed the relative amounts of functional groups:^[1] aromatic carbon (C−C sp², 284.4 eV), aliphatic carbon (C−C sp³, 285.0 eV), hydroxyl (C−OH, 285.7 eV), epoxy (C−O−C, 286.7 eV), carbonyl (C=O, 288.0 eV), carboxyl (O−C=O, 289.1 eV) and aromatic carbons near vacancies (C-C* sp², 283.5).^[2]

More detail on consistency of the fitting procedure are reported in our previous work on C 1s fit.^[1]

GO was measured as a dry powder in solid tablet form

(3)

S-3 Table S1. Optimization reaction conditions

Run^[a] Additive Solvent T (°C) Time (h) Yield (%) 3aa^[b]

1^[c] GO (25 % wt, flakes) CH3Cl 105 5 37

2^[c] GO (50 % wt, flakes) Toluene 105 8 traces

3^[c][d] GO (50 % wt, flakes) DMF 105 2 --

4^[c][e] GO (25 % wt, flakes) EtOH 105 2 --

5^[f] GO (50 % wt, flakes) Toluene : H2O (7:3) 105 Overnight traces

6^[f] GO (25 % wt, flakes) CH3Cl : H2O (1:4) 55 5 67

7^[f] GO (25 % wt, flakes) Dioxane : H2O (4:1) 55 5 66

8^[f] GO (25 % wt, flakes) THF : H2O (4:1) 55 5 30

9 GO (10 % wt, powder) CH3CN : H2O (4:1) 55 6 68

10[f] Grafite (25 % wt) CH3CN : H2O (4:1) 55 6 traces

11^[f] p-TsOH(pH = 4) CH3CN : H2O (4:1) 55 6 traces

12^[f] Styrene oxide (1 eq) CH3CN : H2O (4:1) 55 6 --

13 Styrene oxide (1 eq), AcOH (pH

= 4) CH3CN : H2O (4:1) 55 6 27

14 Used GO (10 % wt, powder) CH3CN : H2O (4:1) 55 36 12

15 Regenerated GO (10 % wt,

powder) CH3CN : H2O (4:1) 55 36 63

[a] All the reactions were carried out with reagent grade solvents, unless otherwise specified (1a/2a = 1/2 on 0.15 mmol of 1a, 0.1 M). [b] Determined after flash chromatography. [c] 1a/2a = 1/1.5. [d] Decomposition of indole 1a was observed.

[e] Alcohol 2a decomposed. [f] 1a/2a = 1/3.

NH

Me OH

+

N Me Additive

Solvent, T Me

Me

MeO OMe

1a (+/-)-2a (+/-)-3aa

(4)

S-4

General procedure for the synthesis of allylic alcohols 2a-p and propargylic alcohols 4a-c.

All alcohols were synthetized via addition of vinyl- or ethynylmagnesium bromide to the corresponding carbonyl compound according to literature procedures.^[3a,3e]

In a flame-dried three-necked round bottom flask, equipped with a dropping funnel, were added anhydrous THF (2.5 mL, 0.8 M) and carbonyl compound (2 mmol, 1 eq) under N2 atmosphere and the mixture was cooled to 0 °C. Then vinylmagnesium bromide (1 M in THF, 2.4 mL, 2.4 mmol, 1.2 eq) or ethynylmagnesium bromide (0.5 M in THF, 4.8 mL, 2.4 mmol, 1.2 eq) was added dropwise.

After the addition the ice bath was removed, and the mixture was allowed to warm at room temperature and stirred for 1-5 h. The reaction was quenched with a saturated aqueous NH4Cl solution, extracted with EtOAc and the combined organic phases were washed with brine and then dried over Na2SO4. Solvent was removed by rotary evaporation and the crude was purified by column chromatography to give the desired product.

2a. Pale yellow oil; yield = 88% (289 mg, cHex:EtOAc 3:1).^[3a]

2b. White solid; yield = 67% (322 mg, cHex:EtOAc 4:1).^[3b]

2c. Yellow oil; yield = 50% (264 mg, cHex:EtOAc 8:1). ¹H NMR (400 MHz, CDCl3) δ 7.23 – 7.18 (m, 2H), 6.82 – 6.77 (m, 2H), 6.03 (ddd, J = 17.1, 10.3, 5.7 Hz, 1H), 5.31 (d, J = 17.1 Hz, 1H), 5.17 (d, J = 10.3 Hz, 1H), 5.13 (d, J = 5.7 Hz, 1H), 1.92 (brs, 1H), 0.97 (s, 9H), 0.18 (s, 6H). ¹³C NMR (100 MHz, CDCl3) δ 155.27, 140.34, 135.35, 127.57, 120.06, 114.71, 74.89, 25.65 (9C), 18.17 -4.45 (6C). LC-MS (m/z): [M-OH]⁺= 247.0. Anal. Calc. for (C15H24O2Si: 264.44): C, 68.13; H, 9.15; found: C, 68.31; H, 9.26.

2d. Colourless oil; yield = 80% (215 mg, cHex:AcOEt = 4:1).^[3c]

2e. Pale yellow solid; yield = 83% (314 mg, cHex:EtOAc = 4:1).

1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.00 (ddd, J = 17.1, 10.3, 5.9 Hz, 1H), 5.31 (d, J = 17.1 Hz, 1H), 5.17 (d, J = 10.3 Hz, 1H), 5.13 (d, J = 5.9 Hz, 1H), 2.46 (s, 3H), 2.14 (brs, 1H). ¹³C NMR (100 MHz, CDCl3) δ 140.07, 139.48, 137.83, 126.86, 126.73, 115.17, 74.88, 15.89 (3C). LC- Ar

O R

Ar OH

R Ar

OH R

BrMg or BrMg or

THF, 0°C to rt

2 4

OH

MeO

OH

BnO

OH

TBDMSO

OH

H

OH

MeS

(5)

S-5

MS (m/z): [M-OH]⁺= 163.0; [M+OH]⁺= 197.0; [M+K]⁺= 219.0.

Anal. Calc. for (C10H12OS: 180.27): C, 66.63; H, 6.71; found: C, 66.55; H, 6.81.

2f. Pale yellow oil; yield = 65% (349 mg, cHex:EtOAc = 4:1).^[3a]

2g. Colourless oil; yield = 68% (223 mg, cHex:EtOAc = 4:1).^[3b]

2h. White solid; yield = 69% (268 mg, cHex:EtOAc = 2.5:1).^[3b]

2i. Pale yellow solid; yield = 80% (359 mg, cHex:EtOAc = 1.5:1).

1H NMR (400 MHz, CDCl3) δ 6.85 (s, 1H), 6.51 (s, 1H), 6.07 (ddd, J = 17.1, 10.4, 5.4 Hz, 1H), 5.38 (dddd, J = 17.2, 5.5 Hz, 1.5 Hz, 1,5 Hz, 1H), 5.29 (ddd, J = 17.2, 1.5 Hz, 1,5 Hz, 1H), 5.14 (ddd, J

= 10.4, 1.5 Hz, 1.5 Hz, 1H), 3.86 (s, 3H), 3.82 (s, 6H), 2.58 (d, J = 5.5 Hz, 1H).¹³C NMR (100 MHz, CDCl3) δ 150.80, 148.92, 143.13, 139.72, 122.47, 114.10, 111.28, 97.68, 70.27, 56.48 (3C), 56.31 (3C), 56.12 (3C). LC-MS (m/z): 207.0 [M-OH]⁺, 247.0 [M+Na]⁺, 471.0 [2M+Na]⁺. Anal. Calc. for (C12H16O4: 224.26): C, 64.27; H, 7.19; found: C, 64.16; H, 7.25.

2j. Yellow oil; yield = 70% (250 mg, nHex:EtOAc 4:1). Spectral data match those reported in the literature.^[3b]

2k. Yellow oil; yield = 51 % (143 mg, cHex:EtOAc = 6:1). Spectral data match those reported in the literature.^[3c]

2l. Yellow oil; yield = 65% (247 mg, cHex:EtOAc = 4:1). ¹H NMR (400 MHz, CDCl3)) δ 7.92 – 7.87 (m, 1H), 7.87 – 7.82 (m, 1H), 7.47 – 7.30 (m, 3H), 6.18 (ddd, J = 17.2, 10.3, 5.7 Hz, 1H), 5.53 (d, J = 5.7 Hz, 1H), 5.45 (d, J = 17.2 Hz, 1H), 5.28 (d, J = 10.3 Hz, 1H), 2.30 (s, 1H). ¹³C NMR (100 MHz, CDCl3) δ 138.38, 136.07, 134.88, 134.63, 121.91, 121.49, 120.68, 120.29, 120.00, 113.53, 68.10. LC-MS (m/z): [M-OH]⁺= 173.0. Anal. Calc. for (C11H10OS: 190.26): C, 69.44; H, 5.30; found: C, 69.21; H, 5.18.

2m. Red oil; yield = 60% (291 mg, nHex:EtOAc = 6:1). ¹H NMR (400 MHz, CDCl3) δ 6.07 (ddd, J = 17.1, 10.4, 5.9 Hz, 1H), 5.31 (d, J = 17.1 Hz, 1H), 5.16 (d, J = 10.4 Hz, 1H), 4.84 (dd, J = 5.9 Hz, 5.1 Hz, 1H), 4.21 – 4.14 (m, 9H), 1.91 (d, J = 5.1 Hz, 1H).¹³C NMR (100 MHz, CDCl3) δ 139.59, 114.99, 91.80, 70.65, 68.41 (5C), 68.19, 68.15, 66.69, 66.47. LC-MS (m/z): [M]⁺= 242.0.

OH

O N₃

OH

OMe OH

MeO OMe

OH

MeO

OMe OMe

OH

O O

OH

S

OH

S

Fe OH

(6)

S-6

Anal. Calc. for (C13H14FeO: 242.10): C, 64.50; H, 5.83; found: C, 64.31; H, 5.58.

2n. Pale yellow oil; yield = 88% (314 mg, cHex:EtOAc = 25:1).

Spectral data match those reported in the literature.^[3d]

2o. Colourless oil; yield = 60% (264 mg, cHex:EtOAc = 20:1). ¹H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.9 Hz, 1H), 6.86 (d, J = 8.9 Hz, 1H), 6.16 (dd, J = 17.2, 10.7 Hz, 1H), 5.26 (dd, J = 17.2, 1.0 Hz, 1H), 5.12 (dd, J = 10.7, 1.0 Hz, 1H), 3.78 (s, 3H), 1.94 – 1.80 (m, 2H), 1.78 (s, 1H), 1.33 – 1.03 (m, 4H), 0.85 (t, J = 7.1 Hz, 3H).

13C NMR (100 MHz, CDCl3) δ 158.33, 144.47, 137.87, 126.57, 113.44, 112.17, 55.20, 41.81, 25.78, 22.99, 14.00. LC-MS (m/z):

[M-OH]⁺= 203.0. Anal. Calc. for (C14H20O2: 220.31): C, 76.33; H, 9.15; found: C, 76.18; H, 9.01.

2p. Pale yellow solid; yield = 70% (336 mg, cHex:EtOAc = 6:1).

1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 7.8, 1.2 Hz, 2H), 7.39 (dd, J = 7.6, 1.1 Hz, 2H), 7.31 (ddd, J = 7.6, 7.6, 1.4 Hz, 2H), 7.24 (ddd, J = 7.5, 7.5,1.5 Hz, 2H), 5.91 (dd, J = 17.1, 10.2 Hz, 1H), 5.03 (dd, J = 10.2, 0.8 Hz, 1H), 4.79 (dd, J = 17.1, 0.8 Hz, 1H), 2.73 (brs, 1H).¹³C NMR (100 MHz, CDCl3) δ 138.53, 138.24, 130.64, 127.49, 126.65, 126.18, 125.74, 114.45, 75.42. LC-MS (m/z): 223.0 [M-OH]⁺. Anal. Calc. for (C15H12OS: 240.32): C, 74.97; H, 5.03; found: C, 74.79; H, 5.21.

4a. Pale yellow oil which solidifies on standing; yield = 90%

(291 mg, cHex:EtOAc = 3.4:1). Spectral data match those reported in the literature.^[3e]

4b. White solid; yield = 75% (333 mg, cHex:EtOAc = 1.5:1). ¹H NMR (400 MHz, CDCl3) δ 7.13 (s, 1H), 6.52 (s, 1H), 5.67 (dd, J = 5.9, 2.2 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H), 2.81 (d, J = 5.9 Hz, 1H), 2.60 (d, J = 2.3 Hz, 1H).¹³C NMR (100 MHz, CDCl3) δ 151.05, 149.92, 143.09, 119.87, 111.77, 97.59, 83.37, 73.92, 60.32, 56.54, 56.44, 56.19. GC-MS (m/z): 222 (100) [M]⁺, 205 (58) [M-OH]⁺, 191 (31) [M-OMe]⁺. Anal. Calc. for (C12H14O4: 222.24): C, 64.85; H, 6.35; found: C, 64.71; H, 6.20.

4c. Pale yellow solid; yield = 36% (127 mg, cHex:EtOAc = 4:1).

Spectral data match those reported in the literature.^[3f]

OH

Me MeO

n-Bu OH

MeO

HO

S

OH

MeO

OMe OMeOH

HO

MeO

Me

(7)

S-7

4e. White solid; yield = 68% (324 mg, cHex:EtOAc = 5:1). ¹H NMR (400 MHz, CDCl3) δ 7.49 – 7.44 (m, 2H), 7.44 – 7.35 (m, 4H), 7.35 – 7.29 (m, 1H), 7.01 – 6.93 (m, 2H), 5.40 (dd, J = 5.7, 1.9 Hz, 1H), 5.07 (s, 2H), 2.65 (d, J = 2.2 Hz, 1H), 2.21 (d, J = 5.9 Hz, 1H).¹³C NMR (100 MHz, CDCl3) δ 158.97, 136.79, 132.60, 128.58 (2C), 128.07 (2C), 127.99, 127.40 (2C), 114.96 (2C), 83.64, 74.64, 70.05, 64.01.GC-MS (m/z): 238 (6) [M]⁺, 91 (100), 65 (13). Anal. Calc. for (C16H14O2: 238.29): C, 80.65; H, 5.92;

found: C, 80.33; H, 5.68.

Procedure for the synthesis of aldehyde precursors and propagylic alcohol 4d.

Alcohol 2b: This compound was synthetized from 4-hydroxybenzaldehyde according to literature procedure.^[4^a]

Alcohol 2f: This compound was synthetized from 4-hydroxybenzaldehyde according to know literature procedures.^[3a]

Alcohol 2f: This compound was synthetized by oxidation of piperonol using IBX.

In a flame-dried two-necked round bottom flask were added anhydrous CH3CN (7.5 mL, 0.4 M), piperonol (475 mg, 3 mmol, 1 eq) and IBX (1.68 g, 6mmol, 2 eq) under N2 atmosphere. The mixture was refluxed overnight. The reaction mixture was filtered on a pad of Celite and the solvent was removed under vacuum. The crude was then dissolved in CH2Cl2 and washed with a saturated NaHCO3 aqueous solution, then with a Na2S2O3 aqueous solution (1 M) and dried over Na2SO4. Solvent was removed by rotary evaporation and the crude was purified by column chromatography.

BnO

OH

O

HO

O

BnO K₂CO₃ , BnBr

DMF, 60°C

HO

O

Br ⁵

O

N₃ ⁵ K₂CO_3, Br(CH₂)₅Br

DMF, r.t. DMF, reflux

NaN₃

O O

OH

O O

O IBX

CH₃CN, reflux

(8)

S-8

Yellow oil; yield = 86% (387 mg, nHex:EtOAc = 6:1). Spectral data match those reported in the literature.^[4b]

Alcohol 2o: This compound was synthetized from 4-methoxybenzoyl chloride according to know literature procedures.^[4c]

Alcohol 4d: This compound was synthetized from 4-methoxyacetophenone and hex-1-yne according to a general known procedure.^[4d]

In a flame-dried three-necked round bottom flask were added anhydrous THF (4 mL) and hex-1-yne (0.49 mL, 4.4 mmol, 2.2 eq). n-BuLi (2.5 M in Hex, 1.6 mL, 4 mmol, 2 eq) was added dropwise at - 78°C and the mixture was stirred at -78°C for 1 hour. Then a solution of 4-methoxyacetophenone (300 mg, 2 mmol, 1 eq) in THF (2.5 mL) was added dropwise at -78°C. After the addition the mixture was allowed to warm to room temperature and stirred overnight. The reaction was quenched with a saturated aqueous NH4Cl solution, extracted with EtOAc and the combined organic phases were washed with brine and then dried over Na2SO4. Solvent was removed by rotary evaporation and the crude was purified by column chromatography to give the desired product.

4d. Pale yellow oil; yield = 51% (238 mg, nHex:EtOAc = 6:1). ¹H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 2.26 (t, J = 7.0 Hz, 2H), 2.22 (s, 1H), 1.72 (s, 3H), 1.57 – 1.38 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H).¹³C NMR (100 MHz, CDCl3) δ 158.94, 138.45, 126.22, 113.42, 85.48, 83.85, 69.66, 55.27, 33.41, 30.72, 21.96, 18.39, 13.56. GC- MS (m/z): 214 (100) [M-H2O]⁺, 172 (36), 128 (56). Anal. Calc. for (C15H20O2: 232.32): C, 77.55; H, 8.68; found: C, 77.21; H, 8.57.

Cl O

O

n-Bu O

O 1. DIBAL-H, morfoline

2. n-BuLi THF, 0°C

HO

MeO

Me

MeO n-Bu

O

Me n-Bu

n-BuLi THF, -78°C to rt

4d O

O

HO

MeO

Me

n-Bu

(9)

S-9

General procedure for the synthesis of 2,3-disubstituted indoles 1b-c, 1e-g e 1j-o.

Indoles were synthetized from aryl hydrazines and ketones using Fischer’s indole synthesis. All commercially available carbonyl compounds were used without further purification.

A Schenk tube was charged with aryl hydrazine hydrochloride (3 mmol, 1.5 eq), ketone (2mmol, 1 eq) and reagent grade ethanol (4 mL, 0.5 M). The reaction mixture was stirred at refluxed until complete consumption of the ketone.

After cooling, the solvent was removed under vacuum, the crude was dissolved in ethyl acetate and washed with 2M aqueous HCl, saturated aqueous NaHCO3, deionized water, brine and dried over Na2SO4. Solvent was removed by rotary evaporation and (when necessary) the crude was purified by column chromatography to give the desired indole.

Compound Conditions Ref.

Pale brown solid, yield = 46% (147 mg, nHex:Acetone =

16:1). ^[5a]

Yellow oil, yield = 49% (184 mg, nHex:Acetone = 10:1) ^[5b]

Pale orange solid, yield = 50% (221 mg, cHex:AcOEt = 4:1) ^[5a]

Yellow oil, yield = 48% (209 mg, nHex:Acetone = 3.5:1). ^[5c]

Yellow oil, yield = 52% (166 mg, nHex:Acetone = 16:1). ^[5a]

Pale brown solid, yield = 64% (281 mg, nHex:Acetone =

10:1). ^[5d]

NHNH2

.

HCl

R² O

R¹

X EtOH, reflux X

NH R²

R¹

NH Et

Me 1b

NH Bu

Me 1c

NH Bn

Me 1d

NH

CH₂CO₂Et Me 1e

NH Me

Et 1f

NH 1g

(10)

S-10

Pale brown solid, yield = 59 % (193 mg, cHex:AcOEt = 12:1). ^[5e]

White solid, yield = 54% (194 mg, cHex:AcOEt = 8:1). ^[5f]

Orange solid, yield = 67% (300 mg, No purification) ^[5f]

Brown solid, yield = 93% (296 mg, No purification) ^[5f]

Pale brown solid, yield = 44% (154 mg, nHex:Acetone = 8:1) ^[5f]

Pale brown solid, yield = 30% (135 mg, nHex:AcOEt = 10:1). ^[5f]

NH Me

Me 1j F

NH Me

Me 1k Cl

NH Me

Me 1i Br

NH Me

Me 1m Me

NH Me

Me 1n MeO

NH Me

Me Br 1o

(11)

S-11 General procedure for the synthesis of aryl hydrazines

Aryl hydrazines were synthetized the from corresponding commercially available anilines that were used without further purification.^[6]

A one neck round-bottom flask is charged with aniline (1 eq) then HCl (37%) is added dropwise at 0

°C (for hydrazine 4f at -15 °C). An aqueous solution of NaNO2 (1.5 eq, 2 M) is added dropwise and the solution is stirred for 1h at 0°C (for hydrazine 4f at -15 °C). Then a solution of SnCl4 (3 eq, 1 M) in aqueous conc. HCl (37%) is added in one portion and the mixture is stirred for another 3 hours at 0 °C. The solution is then filtered and the solid is washed with a small amount of deionized water (0

°C) and then Et2O to yield the hydrochloride salt of the desired aryl hydrazine. The obtained hydrochloride salts were employed in the synthesis of the indoles without further purifications.

NH₂ X

HCl aq. (37%), 0 °C 1. NaNO₂, 1h

2. SnCl_4, 3h NHNH₂

.

^HCl

X

(12)

S-12

General procedure for the allylic dearomatization of indoles

A screw-capped vial is charged with CH3CN (1.2 mL), allylic alcohol 2 (0.3 mmol, 2 eq), indole 1 (0.15 mmol, 1 eq), GO dried flakes (10 wt% with respect to indole) and deionized water (0.3 mL). The reaction mixture was stirred at 55 °C (unless otherwise noted) until complete consumption of indole (vide infra for reaction times). The mixture was then filtered on a Gooch funnel and the GO washed with EtOAc. The collected organic layers were dried over Na2SO4 and evaporated to dryness under vacuum. The crude was purified by column chromatography to give the desired product 3.

3aa. Yellow oil, yield = 70% (31 mg, 6 h, nHex:Et2O = 1:1.8). ¹H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 1H), 7.33 – 7.25 (m, 2H), 7.18 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 8.6 Hz, 2H), 6.75 (d, J = 8.6 Hz, 2H), 6.25 (d, J

= 15.7 Hz, 1H), 5.47 (ddd, J = 15.7, 8.0, 6.7 Hz, 1H), 3.74 (s, 3H), 2.72 (dd, J = 13.9, 6.7 Hz, 1H), 2.48 (dd, J = 13.9, 8.0 Hz, 1H), 2.28 (s, 3H), 1.33 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.67, 158.95, 154.09, 143.47, 132.53, 129.78, 127.72, 127.23, 124.99, 121.91, 121.87, 119.85, 113.81, 57.74, 55.22, 40.34, 21.61, 16.00. LC-MS (m/z): 147.2 [C10H11O]⁺, 314.2 [M+Na]⁺. Anal. Calc. for (C20H21NO: 291.39): C, 82.44; H, 7.26; found: C, 82.31; H, 7.31.

3ba. Pale yellow oil, yield = 68% (31 mg, 16 h, nHex:Et2O = 1:2). ¹H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.6 Hz, 1H), 7.29 (dt, J = 7.6, 1.4 Hz, 1H), 7.25-7.21 (m, 1H), 7.18 (dt, J = 7.5, 0.8 Hz, 1H), 7.09 – 7.00 (m, 2H), 6.77 – 6.68 (m, 2H), 6.23 (d, J = 15.6 Hz, 1H), 5.41 (ddd, J = 15.6, 8.0, 6.6 Hz, 1H), 3.73 (s, 3H), 2.75 (ddd, J = 13.9, 6.6, 1.4 Hz, 1H), 2.49 (ddd, J = 13.9, 8.0, 0.8 Hz, 1H), 2.24 (s, 3H), 2.01 (dq, J = 15.0, 7.4 Hz, 1H), 1.84 (dq, J = 15.0, 7.4 Hz, 1H), 0.37 (t, J = 7.4 Hz, 3H).¹³C NMR (100 MHz, CDCl3) δ 185.54, 158.89, 155.24, 141.38, 132.29, 129.84, 127.68, 127.19, 124.88, 122.01, 121.87, 119.71, 113.77, 62.99, 55.21, 40.01, 28.85, 16.30, 8.12. LC-MS (m/z): 147.2 [C10H11O]⁺, 328.2 [M+Na]⁺. Anal. Calc. for (C21H23NO: 305.42): C, 82.58; H, 7.59; found: C, 82.36; H, 7.69.

3ca. Yellow oil, yield = 61% (31 mg, overnight, Hex:Et2O = 1:1). ¹H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.6 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.24 (d, J = 7.3Hz, 1H), 7.18 (t, J = 7.3 Hz, 1H), 7.05 (d, J = 8.5 Hz, 2H), 6.73 (d, J = 8.6 Hz, 2H), 6.22 (d, J = 15.7 Hz, 1H), 5.40 (ddd, J = 15.7, 8.1, 6.6 Hz, 1H), 3.73 (s, 3H), 2.74 (dd, J = 13.9, 6.6 Hz, 1H), 2.48 (dd, J = 13.9, 8.1 Hz, 1H), 1.95 (td, J = 12.9, 4.6 Hz, 1H), 1.78 (td, J = 12.8, 4.6 Hz, 1H), 1.21 – 1.06 (m, 2H), 0.80 – 0-63 (m, 4H), 0.63 – 0.49 (m, 1H). ¹³C NMR (100 MHz, CDCl3) δ 185.80, 158.89, 155.04, 141.81, 132.31, 129.84, 127.64, 127.20, 124.87, 121.98, 121.81, 119.71, 113.77, 62.42, 55.21, 40.29, 35.70, 25.80, 22.81, 16.35, 13.73.

LC-MS (m/z): 147.0 [C10H11O]⁺, 356.2 [M+Na]⁺. Anal. Calc. for (C23H27NO: 333.48): C, 82.84; H, 8.16;

found: C, 82.65; H, 8.02.

CH3CN : H2O (4:1) 55 °C X

NH R²

R¹ _Ar

OH GO (10 %wt)

N R²

R¹

Ar

X

1 2 3

R³

N Me

Me

OMe

N Et

Me

OMe

N n-Bu

Me

OMe

(13)

S-13

3da. Pale yellow oil, yield = 47% (26 mg, 7h, nHex:Et2O = 1:1.1, then nHex:Acetone 4:1). ¹H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.6 Hz, 1H), 7.25 (ddd, 8.4, 7.7, 3.7 Hz, 1H), 7.19 – 7.12 (m, 2H), 7.10 – 6.99 (m, 5H), 6.79 – 6.68 (m, 4H), 6.27 (d, J = 15.7 Hz, 1H), 5.34 (ddd, J = 15.7, 8.1, 6.5 Hz, 1H), 3.73 (s, 3H), 3.28 (d, J = 13.6 Hz, 1H), 2.95 (d, J = 13.6 Hz, 1H), 2.89 (dd, J = 14.0, 6.5 Hz, 1H), 2.68 (dd, J = 14.0, 8.1 Hz, 1H), 2.34 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 184.60, 158.94, 154.97, 140.90, 135.79, 132.57, 129.73, 129.30, 127.85, 127.75, 127.23, 126.65, 124.61, 122.92, 121.51, 119.82, 113.77, 63.03, 55.22, 42.01, 39.70, 16.96. LC-MS (m/z): 147.0 [C10H11O]⁺, 390.0 [M+Na]⁺. Anal. Calc. for (C26H25NO: 367.49): C, 84.98; H, 6.86; found: C, 84.71; H, 6.71.

3ea. Yellow oil, yield = 57% (31 mg, nHex:Et2O = 1:3). ¹H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.6 Hz, 1H), 7.30 (m, 2H), 7.17 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 8.6 Hz, 2H), 6.75 (d, J = 8.6 Hz, 2H), 6.25 (d, J = 15.7 Hz, 1H), 5.45 (ddd, J = 15.7, 7.7, 6.7 Hz, 1H), 3.81 (q, J = 7.1 Hz, 2H), 3.74 (s, 3H), 2.95 (d, J = 14.5 Hz, 1H), 2.81-2.72 (m, 2H), 2.46 (dd, J = 13.8, 7.7 Hz, 1H), 2.34 (s, 3H), 0.88 (t, J = 7.1 Hz, 3H).¹³C NMR (100 MHz, CDCl3) δ 184.30, 169.22, 159.06, 154.78, 140.15, 133.37, 129.55, 128.24, 127.30, 124.94, 122.50, 120.66, 119.98, 113.83, 60.46, 59.39, 55.23, 39.83, 39.82, 16.42, 13.66. LC- MS (m/z): 147.0 [C10H11O]⁺, 386.0 [M+Na]⁺, 749.2 [2M+Na]⁺. Anal. Calc. for (C23H25NO3: 363.46): C, 76.01; H, 6.93; found: C, 75.85; H, 6.81.

3fa. Pale yellow oil, yield = 68% (31 mg, 16 h, nHex:Acetone = 3.5:1).

1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.7 Hz, 1H), 7.29 (dt, J = 7.5, 1.4 Hz, 1H), 7.26 – 7.21 (m, 1H), 7.18 (ddd, J = 7.5, 7.5, 0.9 Hz, 1H), 7.05 (d, J = 8.7 Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 6.23 (d, J = 15.7 Hz, 1H), 5.41 (ddd, J = 15.6, 8.0, 6.7 Hz, 1H), 2.75 (ddd, J = 13.9, 6.6, 1.3 Hz, 1H), 2.49 (ddd, J = 14.0, 8.1, 0.9 Hz, 1H), 2.24 (s, 3H), 2.00 (dq, J = 14.9, 7.5 Hz, 1H), 1.84 (dq, J = 14.5, 7.3 Hz, 1H), 0.37 (t, J = 7.4 Hz, 3H).

13C NMR (100 MHz, CDCl3) δ 185.54, 158.90, 155.21, 141.37, 132.30, 129.84, 127.67, 127.19, 124.88, 122.01, 121.87, 119.71, 113.78, 62.99, 55.21, 40.00, 28.84, 16.28, 8.11. LC-MS (m/z): 147.0 [C10H11O]⁺, 328.2 [M+Na]⁺. Anal. Calc. for (C21H23NO: 305.42): C, 82.58; H, 7.59; found: C, 82.31; H, 7.71.

3ga. White solid, yield = 35% (19 mg, nHex:Acetone = 6.5:1). M.p. = 51.2-53.5 °C.

1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 7.7 Hz, 1H), 7.21 (t, J = 7.4 Hz, 1H), 7.46 – 7.28 (m, 5H), 7.14 (d, J = 8.6 Hz, 2H), 6.79 (d, J = 8.6 Hz, 2H), 6.18 (d, J = 15.7 Hz, 1H), 5.81 (ddd, J = 15.7, 7.6, 7.3 Hz, 1H), 3.35 (ddd, J = 18.0, 12.5, 5.7 Hz, 1H), 3.00 (dd, J = 17.9, 5.9 Hz, 1H), 2.73 (dd, J = 13.7, 7.6 Hz, 1H), 2.58 (dd, J = 13.5, 5.3 Hz, 1H), 2.24 (dd, J = 13.7, 7.3 Hz, 1H), 1.75 (ddd, J = 13.2, 12.5, 6.1 Hz, 1H).¹³C NMR (100 MHz, CDCl3) δ 180.31, 156.39, 153.20, 140.81, 137.16, 130.43, 128.51, 127.46, 127.39, 126.41, 125.55, 124.67, 124.28, 123.55, 122.33, 119.92, 119.24, 118.28, 111.30, 53.11, 52.69, 33.55, 27.05, 23.17. LC-MS (m/z): 147.0 [C10H11O]⁺, 218 [C16H11N]⁺,388.0 [M+Na]⁺, 404.3 [M+K]⁺. Anal. Calc. for (C26H23NO: 365.48): C, 85.45; H, 6.34; found: C, 85.21; H, 6.23.

N Bn

Me

OMe

N Me

OMe EtO

O

N Me

Et

OMe

N OMe

(14)

S-14

3ha. White solid, yield = 75% (36 mg, 6 h, nHex:Et2O = 1:1.5). M.p. = 124.5-125.3 °C.

1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.1 Hz, 1H), 7.34 – 7.26 (m, 2H), 7.17 (dt, J = 7.1, 0.5 Hz 1H), 7.08 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 6.25 (d, J = 15.7 Hz, 1H), 5.49 (ddd, 15.6, 7.4, 6.5 Hz, 1H), 3.74 (s, 3H), 2.88 (brs d, J = 8.7 Hz, 1H), 2.77 (ddd, J = 13.6, 6.5, 0.8 Hz, 1H), 2.66 – 2.50 (m, 2H), 2.41 (dd, J = 13.3, 1.8 Hz, 1H), 2.20 (brs d, J = 13.1 Hz, 1H), 1.86 (tq, 13.6, 3.6 Hz 1H), 1.69 (brs, 1H), 1.43 (tq, 13.6, 3.6 Hz 1H), 1.16 (td, J = 13.5, 4.0 Hz, 1H).¹³C NMR (100 MHz, CDCl3) ) δ 188.85, 158.91, 154.84, 144.70, 132.48, 129.87, 127.61, 127.21, 124.60, 122.00, 121.61, 120.18, 113.80, 57.88, 55.22, 36.62, 36.57, 30.17, 28.80, 21.08. LC-MS (m/z): 147.0 [C10H11O]⁺, 340.2 [M+Na]⁺. Anal. Calc. for (C22H23NO: 317.43): C, 83.24; H, 7.30; found: C, 83.03; H, 7.41.

3ia. Pale yellow oil, yield = 58% (29 mg, overnight, nHex:Acetone = 4.5:1). ¹H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.6 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.23 (d, J = 7.1 Hz, 1H), 7.16 (t, J = 7.3 Hz, 1H), 7.08 (d, J = 8.5 Hz, 2H), 6.75 (d, J = 8.5 Hz, 2H), 6.21 (d, J = 15.7 Hz, 1H), 5.54 (ddd, 15.7, 7.9, 6.9 Hz, 1H), 3.75 (s, 3H), 2.93 (ddd, J = 13.2, 5.7, 4.1 Hz, 1H), 2.72 (dd, J = 13.6, 6.9 Hz, 1H), 2.63 (ddd, 14.0, 10.8, 3.6 Hz, 1H), 2.47 (dd, J = 13.6, 7.9 Hz, 1H), 2.18 – 1.97 (m, 2H), 1.91 – 1.78 (m, 2H), 1.79 – 1.69 (m, 1H), 1.68 – 1.53 (m, 1H), 1.52 – 1.40 (m, 1H), 0.73 (dt, J = 14.5, 10.7 Hz, 1H).¹³C NMR (100 MHz, CDCl3) δ 190.71, 158.89, 154.89, 143.80, 132.49, 129.93, 127.68, 127.21, 124.81, 121.92, 121.89, 119.74, 113.80, 62.40, 55.22, 40.74, 34.74, 31.59, 30.49, 28.64, 24.63. LC-MS (m/z): 147.0 [C10H11O]⁺, 354.2 [M+Na]⁺. Anal. Calc. for (C23H25NO:

331.46): C, 83.34; H, 7.60; found: C, 83.55; H, 7.51.

3ja. Pale yellow oil, yield = 92% (43 mg, 7 h, nHex:Et2O = 1:2.3). ¹H NMR (400 MHz, CDCl3) δ 7.42 (dd, JH-F = 9.1, JH-H 4.6 Hz, 1H), 7.07 (d, J = 8.7 Hz, 2H), 7.02 – 6.91 (m, 2H), 6.75 (d, J = 8.7 Hz, 2H), 6.25 (d, J = 15.7 Hz, 1H), 5.42 (ddd, J = 15.5, 7.8, 6.9 Hz, 1H), 3.74 (s, 3H), 2.68 (ddd, J = 14.1, 6.9, 1.2 Hz, 1H), 2.49 (dd, J = 14.0, 7.9 Hz, 1H), 1.32 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.31 (d, JC-F = 3.7 Hz, 1C), 161.02 (d, JC-F = 243.5 Hz, 1C), 159.03, 150.18, 145.52 (d, JC-F = 8.5 Hz, 1C), 132.85, 129.61, 127.25, 121.25, 120.43 (d, JC-F = 8.9 Hz, 1C), 114.26 (d, JC-F = 23.6 Hz, 1C), 113.83, 109.59(d, JC-F = 24.4 Hz, 1C), 58.34, 55.21, 40.26, 21.58, 15.98. ¹⁹F NMR (377 MHz, CDCl3) -117.62 (td, JF-H = 9.2, 5.2 Hz). LC-MS (m/z): 147.0 [C10H11O]⁺, 332.2 [M+Na]⁺. Anal. Calc. for (C20H20FNO: 309.38): C, 77.64; H, 6.52; found: C, 77.42; H, 6.71.

3ka. Pale yellow oil, yield = 77% (38 mg, 4 h, nHex:Et2O = 1:1.8).

1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.0 Hz, 1H), 7.29 – 7.20 (m, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 6.25 (d, J

= 15.7 Hz, 1H), 5.39 (ddd, J = 15.6, 7.9, 6.8 Hz, 1H), 3.74 (s, 3H), 2.70 (ddd, J = 14.0, 6.7, 1.3 Hz, 1H), 2.50 (ddd, J = 14.1, 8.0, 0.9 Hz, 1H), 2.26 (s, 3H), 1.32 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 187.06, 159.04, 152.79, 145.37, 132.91, 130.81, 129.57, 127.90, 127.27, 122.39, 121.18, 120.71, 113.84, 58.30, 55.22, 40.25, 21.59, 16.04 LC-MS (m/z): 147.0 [C10H11O]⁺. Anal. Calc. for (C20H20ClNO: 325.84): C, 73.72; H, 6.19; found: C, 73.51; H, 6.01.

3la. Yellow oil, yield = 75% (42 mg, 4 h, nHex:Et2O = 1:1.8). ¹H NMR (400 MHz, CDCl3) δ 7.41 (m, 2H), 7.36 (d, J = 8.0 Hz, 1H), 7.07 (d, J

= 8.7 Hz, 2H), 6.75 (d, J = 8.8 Hz, 2H), 6.25 (d, J = 15.7 Hz, 1H), 5.39 (ddd, J = 15.5, 8.0, 6.7 Hz, 1H), 3.74 (s, 3H), 2.70 (ddd, J = 14.0, 6.7,

N OMe

N Me

Me F OMe

N Me

Me Cl OMe

N Me

Me Br OMe

(15)

S-15

1.4 Hz, 1H), 2.50 (ddd, J = 14.1, 8.0, 1.0 Hz, 1H), 2.25 (s, 3H), 1.32 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 187.07, 159.05, 153.27, 145.78, 132.92, 130.81, 129.57, 127.28, 125.26, 121.23, 121.17, 118.75, 113.84, 58.36, 55.23, 40.25, 21.59, 16.06. LC-MS (m/z): 147.0 [C10H11O]⁺, 392.0/394.0 [M+Na]⁺. Anal.

Calc. for (C20H20BrNO: 370.29): C, 64.87; H, 5.44; found: C, 64.71; H, 5.31.

3ma. Yellow oil, yield = 60% (28 mg, 7 h, nHex:Et2O = 1:1.1). ¹H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 7.6 Hz, 1H), 7.14 – 7.04 (m, 4H), 6.75 (d, J = 8.6 Hz, 2H), 6.26 (d, J = 15.7 Hz, 1H), 5.44 (ddd, J

= 15.7, 8.1, 6.3 Hz, 1H), 3.74 (s, 3H), 2.70 (dd, J = 14.0, 6.3 Hz, 1H), 2.48 (dd, J = 14.0, 8.1 Hz, 1H), 2.38 (s, 3H), 2.24 (s, 3H), 1.31 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 185.54, 158.91, 152.08, 143.67, 134.62, 132.32, 129.86, 128.28, 127.22, 122.65, 122.15, 119.37, 113.79, 57.53, 55.22, 40.41, 21.81, 21.48, 15.98. LC-MS (m/z): 147.0 [C10H11O]⁺, 328.0 [M+Na]⁺. Anal.

Calc. for (C21H23NO: 305.42): C, 82.58; H, 7.59; found: C, 82.31; H, 7.41.

3na. Pale yellow oil, yield = 70% (39 mg, 4h, nHex:Et2O = 1:1.3, then Hex:Acetone 4:1). ¹H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 1.5 Hz, 1H), 7.31 (dd, J = 7.9, 1.6 Hz, 1H), 7.13 (d, J = 7.9 Hz, 1H), 7.08 (d, J = 8.7 Hz, 2H), 6.76 (d, J = 8.7 Hz, 2H), 6.24 (d, J = 15.7 Hz, 1H), 5.43 (ddd, J = 15.7, 8.0, 6.6 Hz, 1H), 3.75 (s, 3H), 2.70 (ddd, J = 13.9, 6.6, 0.9 Hz, 1H), 2.46 (dd, J = 13.9, 8.0 Hz, 1H), 2.27 (s, 3H), 1.31 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 188.45, 159.06, 155.73, 142.46, 132.88, 129.55, 127.78, 127.27, 123.29, 123.08, 121.25, 121.06, 113.86, 57.79, 55.24, 40.17, 21.48, 16.11. LC-MS (m/z): 147.0 [C10H11O]⁺, 392.0/394.0 [M+Na]⁺. Anal. Calc. for (C20H20BrNO: 370.29): C, 64.87; H, 5.44; found: C, 64.88; H, 5.37.

3ab. Pale yellow oil, yield = 65% (36 mg, 16 h, nHex:Et2O = 1:1.8). ¹H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.6 Hz, 1H), 7.43 – 7.25 (m, 7H), 7.19 (t, J = 7.4 Hz, 1H), 7.08 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 6.24 (d, J = 15.8 Hz, 1H), 5.48 (ddd, J = 15.8, 8.1, 6.7 Hz, 1H), 5.01 (s, 2H), 2.73 (ddd, J = 13.9, 6.7, 1.1 Hz, 1H), 2.48 (dd, J = 14.1, 8.1 Hz, 1H), 2.28 (s, 3H), 1.34 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.57, 158.15, 154.27, 143.52, 136.91, 132.48, 130.06, 128.54, 127.91, 127.72, 127.38, 127.25, 124.95, 122.08, 121.90, 119.89, 114.79, 69.97, 57.74, 40.35, 21.64, 16.04.

LC-MS (m/z): 91.0 [Bn]⁺, 145.0 [C10H11N]⁺, 223.2 [C16H15O]⁺, 390.2 [M+Na]⁺, 406.0 [2M+Na]⁺. Anal.

3ac. Yellow oil, yield = 66% (39 mg, 36h, nHex:Et2O = 1.2:1). ¹H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 1H), 7.32 – 7.26 (m, 2H), 7.18 (t, J = 7.4 Hz, 1H), 7.01 (d, J = 8.5 Hz, 1H), 6.68 (d, J = 8.5 Hz, 1H), 6.25 (d, J = 15.7 Hz, 1H), 5.45 (ddd, J = 15.7, 8.1, 6.6 Hz, 1H), 2.72 (ddd, J = 14.0, 6.6, 1.3 Hz, 1H), 2.47 (ddd, J = 14.0, 8.1, 0.7 Hz, 1H), 2.27 (s, 1H), 1.33 (s, 1H), 0.95 (s, 9H), 0.15 (s, 6H).¹³C NMR (100 MHz, CDCl3) δ 186.62, 155.06, 154.24, 143.52, 132.60, 130.32, 127.70, 127.17, 124.96, 122.02, 121.88, 119.98, 119.87, 77.32, 77.00, 76.69, 57.73, 40.35, 25.64, 21.66, 18.17, 16.03, -4.46. LC-MS (m/z): 247.0 [C15H23Si]⁺, 414.0 [M+Na]⁺. Anal. Calc. for (C25H33NOSi: 391.63): C, 76.67; H, 8.49; found: C, 76.65; H, 8.41.

N Me

Me Me OMe

N Me

Me

OMe

Br

N Me

Me

OBn

N Me

Me

OTBDMS

(16)

S-16

3ae. Yellow oil, yield = 51% (24 mg, 70°C, 36h, nHex:Et2O = 1:1.8). ¹H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.6 Hz, 1H), 7.32 – 7.23 (m, 2H), 7.21 – 7.14 (m, 1H), 7.10 (d, J = 8.5 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.24 (d, J = 15.7 Hz, 1H), 5.55 (ddd, J = 15.7, 8.2, 6.8 Hz, 1H), 2.73 (dd, J = 14.0, 6.8 Hz, 1H), 2.49 (dd, J = 14.2, 8.2 Hz, 1H), 2.42 (s, 3H), 2.27 (s, 3H), 1.33 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.43, 154.22, 143.38, 137.34, 133.96, 132.46, 127.76, 126.63, 126.50, 125.00, 123.65, 121.87, 119.91, 57.69, 40.33, 21.65, 16.00, 15.89. LC-MS (m/z): 163.0 [C10H11S]⁺, 330.0 [M+Na]⁺, 346.0 [M+K]⁺. Anal. Calc. for (C20H21NS: 307.46): C, 78.13; H, 6.88; found: C, 78.01; H, 6.93.

3af. Orange oil which solidifies on standing, yield = 76% (44 mg, 4 h, nHex:Et2O = 1:1.8). ¹H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.6 Hz, 1H), 7.33 – 7.22 (m, 2H), 7.18 (dt, J = 7.4, 0.8 Hz, 1H), 7.06 (d, J = 8.7 Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 6.24 (d, J = 15.7 Hz, 1H), 5.46 (ddd, J = 15.7, 8.0, 6.7 Hz, 1H), 3.90 (t, J = 6.3 Hz, 2H), 3.27 (t, J = 6.8 Hz, 2H), 2.72 (ddd, J = 13.9, 6.7, 1.3 Hz, 1H), 2.47 (ddd, J = 14.0, 8.0, 0.9 Hz, 1H), 2.27 (s, 3H), 1.81 – 1.71 (m, 2H), 1.68 – 1.59 (m, 2H), 1.57 – 1.46 (m, 2H), 1.33 (s, 3H). ¹³C NMR (100 MHz, CDCl3 δ 186.60, 158.33, 154.24, 143.51, 132.50, 129.75, 127.69, 127.23, 124.94, 121.90, 121.87, 119.86, 114.37, 67.53, 57.74, 51.30, 40.35, 28.74, 28.60, 23.33, 21.64, 16.03. LC-MS (m/z): 244.0 [C14H18N3O]⁺, 411.0 [M+Na]⁺. Anal. Calc. for (C24H28N4O: 388.52): C, 74.20; H, 7.26; found: C, 74.11; H, 7.39.

3ag. Yellow oil, yield = 40% 17.5 mg, nHex:Et2O = 1:1.4). M.p. = 132.5- 135.5 °C. ¹H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.8 Hz, 1H), 7.29 (t, J = 6.9 Hz, 2H), 7.22 – 7.07 (m, 3H), 6.84 – 6.74 (m, 2H), 6.63 (d, J = 15.9 Hz, 1H), 5.58 (ddd, J = 15.9, 8.0, 6.7 Hz, 1H), 3.76 (s, 3H), 2.76 (dd, J = 13.9, 6.7 Hz, 1H), 2.52 (dd, J = 13.9, 8.0 Hz, 1H), 2.28 (s, 3H), 1.34 (s, 3H). ¹³C NMR (100 MHz, CDCl3) δ 184.13, 153.76, 151.68, 141.00, 125.69, 125.41, 125.08, 124.16, 123.63, 122.36, 122.35, 119.37, 117.98, 117.25, 108.17, 55.19, 52.84, 38.14, 19.05, 13.48. LC-MS (m/z): 147.0 [C10H11O]⁺, 292.2 [M+H]⁺. Anal. Calc. for (C20H21NO: 291.39): C, 82.44; H, 7.26; found: C, 82.24; H, 7.51.

3ah. Pale yellow oil, yield = 76% (37 mg, overnight, nHex:Et2O = 1:6).

1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.6 Hz, 1H), 7.32 – 7.22 (m, 1H), 7.17 (t, J = 7.4 Hz, 1H), 6.74 – 6.65 (m, 2H), 6.64 (s, 1H), 6.23 (d, J = 15.7 Hz, 1H), 5.44 (ddd, J = 15.7, 7.9, 6.7 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 2.72 (ddd, J = 13.9, 6.7, 1.0 Hz, 1H), 2.48 (ddd, J = 13.9, 7.9, 0.6 Hz, 1H), 2.27 (s, 3H), 1.33 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.52, 154.24, 148.85, 148.56, 143.47, 132.77, 130.15, 127.70, 124.96, 122.24, 121.90, 119.84, 118.98, 111.06, 108.95, 57.74, 55.87, 55.77, 40.30, 21.63, 16.02. LC-MS (m/z): 177.0 [C11H13O2]⁺, 344.0 [M+Na]⁺, 665.2 [2M+Na]⁺. Anal. Calc. for (C21H15NO2: 321.42): C, 78.47; H, 7.21; found: C, 78.62; H, 7.33.

3ai. White oil, yield = 81% (43 mg, 2 h, 25 °C, nHex:AcOEt = 1:2). ¹H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.6 Hz, 1H), 7.31 – 7.25 (m, 2H), 7.17 (t, J = 7.4 Hz, 1H), 6.57 (s, 1H), 6.53 (d, J = 15.8 Hz, 1H), 6.40 (s, 1H), 5.41 (ddd, J = 15.8, 8.0, 6.7 Hz, 1H), 3.82 (s, 3H), 3.73 (s, 3H), 3.70 (s, 3H), 2.73 (dd, J = 13.8, 6.7 Hz, 1H), 2.51 (dd, J = 13.8, 8.0 Hz, 1H), 2.27 (s, 3H), 1.33 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.75, 154.22, 151.02, 149.21, 143.60, 143.28,

N Me

Me

SMe

N Me

Me O N₃

5

N Me

Me MeO

N Me

Me

OMe

N Me

Me OMe

OMe MeO

(17)

S-17

127.61, 127.47, 124.95, 122.82, 121.96, 119.70, 118.26, 110.32, 98.02, 57.89, 56.75, 56.51, 56.05, 40.71, 21.58, 16.02. LC-MS (m/z): 207.2 [C12H15O3]⁺, 374.4 [M+Na]⁺. Anal. Calc. for (C22H25NO3: 351.45): C, 75.19; H, 7.17; found: C, 75.08; H, 7.31.

3aj. Yellow oil, yield = 66% (30 mg, 16 h, nHex:Et2O = 1:2.4). ¹H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.6 Hz, 1H), 7.34 – 7.23 (m, 2H), 7.18 (td, J = 7.4, 0.7 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H), 6.65 (d, J = 1.5 Hz, 1H), 6.58 (dd, J = 8.0, 1.5 Hz, 1H), 6.21 (d, J = 15.7 Hz, 1H), 5.88 (s, 2H), 5.42 (ddd, J = 15.7, 8.1, 6.7 Hz, 1H), 2.71 (ddd, J = 13.9, 6.7, 1.3 Hz, 1H), 2.46 (ddd, J = 13.9, 8.1, 0.9 Hz, 1H), 2.27 (s, 3H), 1.33 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.47, 154.23, 147.80, 146.90, 143.41, 132.63, 131.45, 127.75, 124.97, 122.37, 121.85, 120.57, 119.90, 108.09, 105.49, 100.92, 57.71, 40.24, 21.62, 16.01. LC-MS (m/z): 144.2 [C10H10N]⁺, 161.0 [C10H19O2]⁺, 328.0 [M+Na]⁺. Anal. Calc. for (C20H9NO2: 305.38): C, 78.66; H, 6.27; found: C, 78.41; H, 6.42.

3ak. Pale yellow oil, yield = 63% (25 mg, 36h, nHex:Et2O = 1:1.7). ¹H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 1H), 7.28 (m, 2H), 7.18 (t, J = 7.4 Hz, 1H), 7.04 (d, J = 4.7 Hz, 1H), 6.85 (dd, J = 4.7, 3.3 Hz, 1H), 6.77 (d, J = 3.3 Hz, 1H), 6.42 (d, J = 15.5 Hz, 1H), 5.52 (ddd, J = 15.5, 8.1, 6.9 Hz, 1H), 2.69 (dd, J = 13.9, 6.9 Hz, 1H), 2.43 (dd, J = 13.9, 8.1 Hz, 1H), 2.27 (s, 3H), 1.33 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.31, 154.19, 143.28, 141.93, 127.79, 127.16, 126.23, 125.01, 124.92, 123.95, 123.76, 121.94, 119.95, 57.57, 40.13, 21.47, 16.00. LC-MS (m/z): 123.0 [C7H7S]⁺, 268.0 [M+H]⁺. Anal. Calc. for (C17H17NS: 267.39): C, 76.36; H, 6.41; found: C, 76.24; H, 6.19.

3al. Yellow oil, yield = 53% (25 mg, 70 °C, 36 h, nHex:Et2O = 1:1.6). ¹H NMR (400 MHz, CDCl3) δ 7.78 (m, 1H), 7.59 – 7.51 (m, 2H), 7.36 – 7.26 (m, 4H), 7.20 (t, J = 7.1 Hz, 1H), 7.12 (s, 1H), 6.51 (d, J = 15.8 Hz, 1H), 5.61 (ddd, J = 15.8, 8.0, 6.7 Hz, 1H), 2.82 (ddd, J = 13.9, 6.7, 1.2 Hz, 1H), 2.59 (ddd, J = 13.9, 8.0, 0.8 Hz, 1H), 2.32 (s, 3H), 1.38 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.36, 154.29, 143.34, 140.23, 137.52, 133.70, 127.84, 126.32, 125.42, 125.09, 124.29, 124.10, 122.74, 121.90, 121.82, 121.59, 119.96, 57.80, 40.63, 21.68, 16.03. LC-MS (m/z): 173.0 [C11H9S]⁺, 318.0 [M+H]⁺, 340.2 [M+Na]⁺. Anal. Calc. for (C21H19NS: 317.45):

C, 73.46 H, 6.03; found: C, 73.61; H, 5.89.

3am. Red oil which solidifies on standing, yield = 61% (34 mg, 1 h, 25 °C, nHex:Et2O = 1.2:1, then nHex:Acetone 5:1). ¹H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 1H), 7.33 – 7.27 (m, 2H), 7.21 (t, J = 7.3 Hz, 1H), 5.96 (d, J = 15.5 Hz, 1H), 5.15 (ddd, J = 15.5, 7.6, 7.2 Hz, 1H), 4.12 – 4.01 (m, 4H), 3.88 (s, 5H), 2.61 (dd, J = 13.9, 7.6 Hz, 1H), 2.44 (dd, J = 13.8, 7.2 Hz, 1H), 2.31 (s, 3H), 1.32 (s, 3H).

13C NMR (100 MHz, CDCl3) δ 186.36, 154.39, 143.66, 130.30, 127.77, 124.94, 121.80, 121.01, 119.88, 82.78, 69.02 (5C), 68.35, 68.25, 66.73, 65.96, 57.89, 40.50, 21.95, 16.02. LC-MS (m/z): 225.0 [C13H13Fe]⁺, 369.0 [M]⁺. Anal. Calc. for (C23H23FeN: 369.29): 74.81; H, 6.28; found: C, 74.66; H, 6.15.

3an. Pale yellow oil, yield = 72% (33 mg, 6 h, nHex:Et2O = 1:1.5). ¹H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 7.6 Hz, 1H), 7.28 (m, 2H), 7.16 (t, J = 7.4 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H), 5.01 (ddd, J = 7.6, 7.0, 1.1 Hz, 1H), 3.74 (s, 3H), 2.74 (dd, J = 14.7, 7.0 Hz, 1H), 2.54 (dd, J = 14.7, 7.6 Hz, 1H), 2.29 (s, 3H), 1.88 (s, 3H), 1.36 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.90, 158.61, 154.06, 143.64, 136.92, 135.96, 127.72, 126.72, 125.04, 121.80, 120.19, 119.74,

N Me

Me

O O

N Me

Me S

N Me

Me S

N Me

Me Fe

N Me

Me OMe

Me

(18)

S-18

113.45, 57.77, 55.21, 35.80, 21.68, 16.31, 15.82. LC-MS (m/z): 161.2 [C1H13O]⁺, 344.2 [M+K]⁺. Anal.

3ao. Yellow solid, yield = 80% (42 mg, 5 h, cHex:AcOEt = 3:1). M.p. = 162.7-163.6 °C. ¹H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 1H), 7.27 (m, 2H), 7.15 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 6.73 (d, J = 8.8 Hz, 2H), 4.85 (t, J = 7.1 Hz, 1H), 3.74 (s, 2H), 2.73 (dd, J = 14.9, 7.0 Hz, 1H), 2.53 (dd, J = 14.9, 7.3 Hz, 1H), 2.36 – 2.28 (m, 2H), 2.27 (s, 3H), 1.35 (s, 3H), 1.29 – 1.18 (m, 2H), 1.18 – 1.07 (m, 2H), 0.82 (t, J = 7.2 Hz, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.72, 158.49, 154.36, 143.70, 142.41, 135.25, 127.67, 127.31, 124.96, 121.81, 120.57, 119.79, 113.43, 57.66, 55.17, 35.48, 30.64, 29.85, 22.76, 21.79, 15.92, 13.93. LC-MS (m/z): 203.2 [C14H19O]⁺, 370.2 [M+Na]⁺. Anal. Calc.

for (C24H29NO: 347.50): C, 82.95; H, 8.41; found: C, 82.76; H, 8.21.

3ap. White solid, yield = 84% (46 mg, 5 h, 25 °C, nHex:AcOEt = 2:1). M.p. = 61.8-62.6 °C. ¹H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.6 Hz, 1H), 7.45 – 7.40 (m, 1H), 7.29 (m, 3H), 7.26 – 7.20 (m, 3H), 7.18 (dd, J = 7.3, 0.8 Hz, 1H), 7.16 – 7.08 (m, 3H), 5.07 (dd, J = 8.6, 5.9 Hz, 1H), 3.02 (dd, J = 15.2, 5.9 Hz, 1H), 2.86 (dd, J = 15.2, 8.6 Hz, 1H), 2.05 (s, 3H), 1.28 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 186.46, 154.44, 143.18, 138.19, 138.17, 134.17, 133.40, 131.74, 128.52, 127.87, 127.14, 126.89, 126.82, 126.74, 125.77, 125.73, 125.37, 125.25, 125.14, 121.63, 119.93, 77.33, 77.02, 76.70, 57.86, 36.15, 22.22, 15.70. LC-MS (m/z): 223.0 [C15H11S]⁺, 390.0 [M+Na]⁺, 757.2 [2M+Na]⁺. Anal.

Calc. for (C25H21NS: 367.51): C, 81.71; H, 5.76; found: C, 81.91; H, 5.65.

N Me

Me OMe

n-Bu

N Me

Me S

(19)

S-19

General procedure for the allenylic dearomatization of indoles

A screw-capped vial is charged with CH3CN (0.8 mL), propargylic alcohol 4 (0.3 mmol, 3 eq), indole 1 (0.10 mmol, 1 eq), GO dried flakes (10 wt% with respect to indole) and deionized water (0.2 mL).

The reaction mixture was stirred at 55 °C (unless otherwise noted) until complete consumption of indole (vide infra for reaction times). The mixture was then filtered on a Gooch funnel and the GO washed with EtOAc. The collected organic layers were dried over Na2SO4 and evaporated to dryness under vacuum. The crude was purified by column chromatography to give the desired product as a mixture of two diastereomers 5’ and 5’’.

5aa’ + 5aa’’. Yellow oil, yield = 54% (15.6 mg, 48 h, nHex:Acetone = 6:1), d.r. = 58:42. ¹H NMR (400 MHz, CDCl3) δ 7.57 – 7.50 (m, 1H), 7.39 – 7.27 (m, 2H), 7.27 – 7.14 (m, 3H), 6.93 – 6.82 (m, 2H), 6.41 – 6.33 (m, 1H), 5.35 – 5.29 (m, 1H), 3.84 – 3.76 (m, 3H), 2.38 – 2.28 (m, 3H), 1.42 – 1.38 (m, 3H). ¹³C NMR (100 MHz, CDCl3) δ 204.99, 204.87, 185.73, 185.50, 159.11, 159.08, 154.12, 154.08, 144.07, 143.91, 128.09, 128.05, 127.85, 127.82, 125.98, 125.94, 125.45, 125.38, 122.42, 122.24, 120.01, 119.96, 114.29, 97.97, 97.01, 96.79, 58.02, 55.30, 20.51, 20.22, 15.97, 15.89. GC-MS (m/z): 289 (28) [M]⁺, 274. (4) [M-Me]⁺, 145 (100) [M-C10H10N]⁺. Anal. Calc. for (C20H19NO: 289.38): C, 83.01; H, 6.62; found: C, 82.82; H, 6.46.

5ab’ + 5ab’’. Orange oil, yield = 78% (27.8 mg, 3 h, nHex:AcOEt = 1:1).

d.r. = 77:23. ¹H NMR (400 MHz, CDCl3) δ 7.55 – 7.49 (m, 1H), 7.34 – 7.27 (m, 2H), 7.21 – 7.15 (m, 1H), 6.81 – 6.73 (m, 2H), 6.50 – 6.48 (m, 1H), 5.40 – 5.32 (m, 1H), 3.89 – 3.86 (m, 3H), 3.84 – 3.79 (m, 3H), 3.72 (s, 3H), 2.38 – 2.30 (m, 3H), 1.41 (s, 3H).¹³C NMR (100 MHz, CDCl3) δ 205.09, 185.51, 154.03, 150.68, 149.32, 144.33, 143.53, 128.06, 127.97, 125.40, 125.31, 122.26, 122.18, 120.02, 119.97, 113.54, 110.15, 97.97, 96.52, 92.36, 58.03, 57.93, 56.78, 56.14, 56.12, 20.54, 20.37, 15.96. GC-MS (m/z): 349 (22) [M]⁺, 205 (100) [M-C10H10N]⁺, 144 (94) [C10H10N]⁺. Anal. Calc. for (C22H23NO3: 349.43): C, 75.62; H, 6.63; found: C, 75.46; H, 6.29.

NH R²

R¹ X

OH R³

R⁴

Ar

N R²

R¹ X

Ar

R³ R⁴

N R²

R¹ X

Ar

R³ R⁴ GO (10 %wt)

CH₃CN : H₂O (4:1) 55 °C

1 4

5’

5’’

N Me

Me H

OMe

N Me

Me H

OMe

OMe MeO

(20)

S-20

5ac’ + 5ac’’. Orange oil, yield = 94% (28.4 mg, 12 h, nHex:AcOEt = 2.8:1), d.r. = 80:20 ¹H NMR (400 MHz, CDCl3) δ 7.56 – 7.50 (m, 1H), 7.36 – 7.25 (m, 4H), 7.23 – 7.16 (m, 1H), 6.92 – 6.84 (m, 2H), 5.22 – 5.16 (m, 1H), 3.82 – 3.79 (m, 3H), 2.35 – 2.30 (m, 3H), 2.18 – 2.11 (m, 3H), 1.39 – 1.36 (m, 3H).¹³C NMR (100 MHz, CDCl3) δ 204.11, 204.10, 185.95, 158.81, 158.79, 154.11, 154.05, 144.29, 144.22, 128.67, 128.62, 127.99, 127.93, 126.79, 126.73, 125.36, 125.33, 122.28, 119.93, 119.90, 113.90, 104.37, 104.30, 94.85, 94.67, 58.49, 58.41, 55.29, 20.43, 20.22, 17.67, 17.52, 16.02, 15.78. GC-MS (m/z): 303 (15) [M]⁺, 288 (8) [M-Me]⁺, 159 (100) [M- C10H10N]⁺. Anal. Calc. for (C21H21NO: 303.41): C, 83.13; H, 6.98; found: C, 83.01; H, 6.75.

5ad’ + 5ad’’. Orange oil, yield = 74% (26.6 mg, 6 h, nHex:AcOEt = 4:1), d.r. = 56:44. ¹H NMR (400 MHz, CDCl3) δ 7.60 – 7.51 (m, 1H), 7.47 – 7.36 (m, 2H), 7.36 – 7.16 (m, 3H), 6.97 – 6.85 (m, 2H), 3.86 – 3.77 (m, 3H), 2.34 – 2.24 (m, 3H), 2.25 – 2.19 (m, 3H), 1.46 – 1.38 (m, 1H), 1.32 – 1.23 (m, 4H), 1.23 – 1.13 (m, 2H), 1.13 – 0.99 (m, 2H), 0.71 – 0.63 (m, 3H).

13C NMR (100 MHz, CDCl3) δ 202.20, 202.12, 186.62, 158.64, 158.60, 154.80, 154.74, 144.01, 143.90, 129.78, 129.70, 127.90, 127.88, 126.57, 126.51, 125.38, 125.35, 122.10, 122.03, 119.94, 119.88, 113.94, 113.90, 107.85, 107.65, 104.95, 104.85, 61.91, 61.82, 55.33, 55.31, 29.78, 27.77, 27.70, 22.28, 22.19, 20.73, 20.68, 18.20, 17.75, 16.16, 15.71, 13.82, 13.79. GC- MS (m/z): 359 (10) [M]⁺, 344 (2) [M-Me]⁺, 215 (100) [M-C10H10N]⁺. Anal. Calc. for (C25H29NO: 359.22):

C, 83.52; H, 8.13; found: C, 83.31; H, 8.01.

5be’ + 5be’’. Pale yellow oil, yield = 40% (16.1 mg, 4 days, nHex:Et2O

= 1:1.8), d.r. = 72:28. ¹H NMR (400 MHz, CDCl3) δ 7.47 – 7.35 (m, 5H), 7.35 – 7.25 (m, 3H), 7.25 – 7.19 (m, 2H), 6.99 – 6.92 (m, 2H), 6.39 (d, J = 6.3 Hz, 1H), 5.33 – 5.27 (m, 1H), 5.09 – 5.05 (m, 2H), 2.37 – 2.27 (m, 3H), 1.39 (s, 3H). ¹³C NMR (100 MHz, CDCl3) δ 205.14, 204.94, 186.24, 186.08, 158.42, 158.37, 152.65, 152.60, 145.83, 145.74, 136.80, 131.23, 128.58, 128.26, 128.22, 127.98, 127.91, 127.89, 127.41, 127.39, 125.94, 125.87, 123.00, 122.85, 120.86, 120.80, 115.32, 115.30, 98.35, 98.26, 96.37, 96.21, 70.07, 58.37, 20.26, 20.22, 15.99, 15.89. LC-MS (m/z):

221.2 [C16H13O]⁺, 400.2/402.2 [M+H]⁺. Anal. Calc. for (C26H22ClNO: 399.92): C, 78.09; H, 5.55; found:

C, 77.35; H, 5.42.

N Me

Me Me

OMe n-Bu

N Me

MeH

OBn

Cl N Me

MeMe

OMe

Supporting Information

Supporting Information

Table of Contents

.

.