Supporting Information Metal-Free, Intermolecular Carbopyridylation of Alkenes via Visible-Light

116 Pages·2017·12.77 MB·English

Electronic Supplementary Material (ESI) for Chemical Science.
This journal is © The Royal Society of Chemistry 2018
Supporting Information

Metal-Free, Intermolecular Carbopyridylation of Alkenes
via Visible-Light-Induced Reductive Radical Coupling

Dan Chen, Lei Xu, Tianyu Long, Shengqing Zhu, Jun Yang,
and Lingling Chu*

S1
Table of Contents

1. General Information……………………………………...…………S3
2. Substrate Preparations and Characterizations…………………..…..S4
3. Experimental Procedure and Characterization of Products………....S6
4. Mechanistic Studies .........................................................................S34
5. Spectral Data………………………………………….……...……S45

S2
1. General Information
Commercial reagents were purchased from Aldrich, TCI, Energy Chemical and J&K
chemical, and were used as received. Solvents were purchased from Sinopharm
Chemical Reagent Co., Ltd, and used as received. All reactions were carried out under
an atmosphere of nitrogen unless otherwise noted. Chromatographic purification of
products was accomplished by flash chromatography using silica gel. Thin-layer
chromatography (TLC) was performed on Silicycle 250 mm silica gel F-254 plates.1H,
19F NMR, and 13C NMR spectra were recorded on Bruker 400 (400, 376, and 100 MHz)
and Bruker 600 (600, 564, and 150 MHz), and are internally referenced to residual
solvent signals (for CDCl , d 7.26 and 77.0 ppm). Data for 1H NMR and 19F NMR are
3
reported as follows: chemical shift (d ppm), multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, br = broad), integration, coupling constant (Hz). 13C
spectra were reported as chemical shifts in ppm and multiplicity where appropriate.
High resolution mass spectra were obtained at Shanghai Institute of Organic Chemistry
mass spectrometry facilities. All alkenes were used from commercial suppliers or
prepared using standard literature procedures.

S3
2. Substrate preparations and characterizations

S1 was prepared according to a literature procedure1: The solution of (4-Vinylphenyl)
methanol (1 mmol, 134 mg), 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-
yl)acetic acid (1 mmol), dicyclohexylmethanediimine (DCC) (1.2 mmol, 247 mg) and
N,N-dimethylpyridin-4-amine (DMAP) (1.2 mmol, 146 mg) in DCM (10 mL) was
stirred at room temperature for overnight. The reaction mixture was diluted with
dichloromethane, and then washed with water. The organic layer was dried over
anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by
column chromatograph (PE: EA= 5:1) to afford the product as a white solid (203.0 mg,
42%).
4-Vinylbenzyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate：
1H NMR (400 MHz, CDCl ) δ 7.60 (d, J = 8.5 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.34
3
(d, J = 8.1 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 6.88 (dd, J = 12.1, 5.4 Hz, 2H), 6.72 –
6.63(m, 2H), 5.72 (d, J = 17.6 Hz, 1H), 5.24 (d, J = 10.9 Hz, 1H), 5.09 (s, 2H), 3.72 (s,
3H), 3.68 (s, 2H), 2.33 (s, 3H).; 13C NMR (100 MHz, CDCl ) δ 170.54, 168.17, 155.97,
3
139.13, 137.56, 136.18, 135.81, 135.13, 133.82, 131.08, 130.71, 130.48, 129.02,
128.39, 126.26, 114.89, 114.37, 112.41, 111.76, 101.10, 66.45, 55.51, 30.34, 13.33.
HRMS (ESI+): calcd for C H ClNO + (M+H) 474.1467, found: 474.1465.
28 25 4

1 A. Deb.; S. Manna.; A. Modak.; T. Patra.; S. Maity.; D. Maiti. Angew. Chem. Int. Ed.
2013, 52, 9747-9750.
S4
S2: To a solution of 4-((3R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl) -3-
hydroxypropyl)-4-oxoazetidin-2-yl)phenyl trifluoromethanesulfonate (510 mg, 0.94
mmol) and potassium vinyltrifluoroborate (251.8 mg, 1.88 mmol), NaHCO (317 mg,
3
3.76 mmol) in DMF (7.2 mL) and water (0.72 mL) was added PdCl (PPh ) (32 mg, 5
2 3 2
mol%). The reaction mixture was degassed by N2 sparging for 15 min, and then stirred
at 70 ℃ for 20 h under N . The reaction was cooled down to room temperature and
2
diluted with ethyl acetate. The organic layer was washed with water and brine. The
organic layer was dried over anhydrous magnesium sulfate, and concentrated in vacuo.
The crude material was purified by flash chromatography to afford the product (319
mg, 81%).
(3R)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-
vinylphenyl) azetidin-2-one: 1H NMR (400 MHz, CDCl ) δ 7.39 (d, J = 8.1 Hz, 2H),
3
7.28 – 7.25 (m, 4H), 7.22 – 7.19 (m, 2H), 6.98 (t, J = 8.7 Hz, 2H), 6.90 (t, J = 8.7 Hz,
2H), 6.69 (dd, J = 17.6, 10.9 Hz, 1H), 5.74 (d, J = 17.6 Hz, 1H), 5.26 (d, J = 10.9 Hz,
1H), 4.67 (t, J = 5.9 Hz, 1H), 4.60 (d, J = 2.1 Hz, 1H), 3.06 (dd, J = 10.3, 4.3 Hz, 1H),
2.87 (d, J = 32.3 Hz, 1H), 1.97 – 1.85 (m, 4H); 13C NMR (150 MHz, CDCl ) δ 167.42,
3
162.17 (d, J = 245.7 Hz), 158.99 (d, J = 243.4 Hz), 139.99 (d, J = 3.2 Hz), 138.04,
136.91, 135.96, 133.78 (d, J = 2.6 Hz), 127.36 (d, J = 8.0 Hz), 127.03, 126.04, 118.33
(d, J = 7.8 Hz), 115.83 (d, J = 22.7 Hz), 115.34 (d, J = 21.4 Hz), 114.72, 77.21, 77.00,
76.79, 73.07, 61.20, 60.30, 36.59, 25.04. HRMS (ESI+): calcd for C H F NO + (M+H)
26 24 2 2
420.1697, found: 420.1692.

3. Experimental procedure and characterization of products
S5
A 8 mL vial equipped with a magnetic stir bar was charged with 1, 4-diazabicyclo
[2.2.2]octane (DABCO, 0.3 mmol, 1.5 equiv.), HE (0.3 mmol, 1.5 equiv.),
cyanopyridines (0.4 mmol, 2.0 equiv.), and Togni reagent (0.3 mmol, 1.5 equiv.). The
vial was capped. After evacuated and backfilled nitrogen three times, methyl tert-butyl
ether (MTBE) [0.05 M] was added via a syringe, followed by the addition of alkene
(0.2 mmol, 1.0 equiv.). The reaction mixture was irritated with a 90 W blue LED, with
cooling from a fan. After 24h, the reaction was quenched with H O, extracted with ethyl
2
acetate. The combined organic layers were dried with MgSO , filtered, and
4
concentrated in vacuo. The crude material was purified by flash chromatography to
afford the products.

F C
3
N
AcO
4-(3,3,3-Trifluoro-1-(pyridin-4-yl)propyl)phenyl acetate (5): According to the
general procedure, 4-vinylphenyl acetate (30.6 µL, 0.2 mmol, 1.0 equiv.), DABCO
(33.6 mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and
isonicotinonitrile (41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol,
1.5 equiv.) in MTBE (4 mL) were used. After 24 h, the product was isolated by flash
chromatography (PE: EA= 3:1) as a pale-yellow oil (53.1 mg, 86%).
1H NMR (600 MHz, CDCl ) δ 8.53 (d, J = 3.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.17
3
(d, J = 4.8 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 4.29 (t, J = 7.3 Hz, 1H), 2.95 - 2.80 (m,
2H), 2.27 (s, 3H). 19F NMR (565 MHz, CDCl ) δ -63.69 (t, J = 10.2 Hz, 3F). 13C NMR
3
(150 MHz, CDCl ) δ 168.97, 150.82, 149.68, 149.52, 138.16, 128.14, 127.75 (q, J =
3
276.0 Hz), 122.49, 121.79, 43.61, 38.39 (q, J = 27.0 Hz), 20.66. HRMS (EI): calcd for
C H F NO 309.0977, found 309.0983.
16 14 3 2

S6
4-(3,3,3-Trifluoro-1-(p-tolyl)propyl)pyridine (9): According to the general
procedure, 1-methyl-4-vinylbenzene (26.4 µL, 0.2 mmol, 1.0 equiv.), DABCO (33.6
mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and isonicotinonitrile
(41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol, 1.5 equiv.) in
MTBE (4 mL) were used. After 24 h, the product was isolated by flash chromatography
(PE: Acetone= 8:1) as a pale-yellow oil (39.8 mg, 75%).
1H NMR (600 MHz, CDCl ) δ 8.52 (s, 2H), 7.17 (s, 2H), 7.12 (d, J = 8.1 Hz,4H), 4.26
3
(s, 1H), 2.89-2.87 (m, 2H), 2.31 (s, 3H).19F NMR (565 MHz, CDCl ) δ -63.69 (t, J =
3
10.2 Hz, 3F).13C NMR (150 MHz, CDCl ) δ 151.57, 150.04, 137.94, 137.11, 129.61,
3
127.21, 126.05 (q, J = 276.0 Hz,) 122.64, 44.09, 38.80 (q, J = 28.50 Hz,) 20.91. HRMS
(EI): calcd for C H F N265.1078, found 265.1079.
15 14 3

F C
3
N
tBu
4-(1-(4-(tert-Butyl)phenyl)-3,3,3-trifluoropropyl)pyridine (10)：According to the
general procedure, 4-tert-Butylstyrene (37.0 µL, 0.2 mmol, 1.0 equiv.), DABCO (33.6
mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and isonicotinonitrile
(41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol, 1.5 equiv.) in
MTBE (4 mL) were used. After 24 h, the product was isolated by flash chromatography
(PE: Acetone= 5:1) as a pale-yellow oil (44 mg, 71%).
1H NMR (600 MHz, CDCl ) δ 8.54 (s, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.20 (s, 2H), 7.14
3
(d, J = 8.1 Hz, 2H), 4.26 (t, J = 7.2 Hz, 1H), 2.91- 2.86 (m, 2H), 1.29 (s, 9H). 19F NMR
(377 MHz, CDCl ) δ -63.76 (t, J = 10.3 Hz, 3F). 13C NMR (100 MHz, CDCl ) δ 151.69,
3 3
150.40, 149.97, 137.92, 126.99, 126.91 (q, J = 276.0 Hz,), 125.92, 122.91, 44.14,
38.96(q, J = 28.0 Hz,), 34.46, 31.26. HRMS (EI): calcd for C H F N 307.1548, found
18 20 3
307.1555.

S7
4-(3,3,3-Trifluoro-1-(4-methoxyphenyl)propyl)pyridine (11)：According to the
general procedure, 1-methoxy-4-vinylbenzene (26.6 µL, 0.2 mmol, 1.0 equiv.),
DABCO (33.6 mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and
isonicotinonitrile (41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol,
1.5 equiv.) in MTBE (4 mL) were used. After 24 h, the product was isolated by flash
chromatography (PE: Et O= 1:1) as a pale-yellow oil (45.0 mg, 80%).
2
1H NMR (600 MHz, CDCl ) δ 8.52 (d, J = 6.0 Hz, 2H), 7.15 (d, J = 6.0 Hz, 2H), 7.13
3
(d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.24 (t, J = 7.4 Hz, 1H), 3.77 (s, 3H), 2.91
– 2.81 (m, 2H).19F NMR (565 MHz, CDCl ) δ -63.67 (t, J = 10.2 Hz, 3F);13C NMR
3
(150 MHz, CDCl ) δ 158.75, 151.68, 149.83, 132.90, 128.59, 128.42, 126.05 (q, J =
3
276.0 Hz), 114.31, 55.20, 43.74, 38.92 (q, J = 27.0 Hz). HRMS (EI): calcd for
C H F NO 281.1027, found 281.1031.
15 14 3

12
4-(1-([1,1'-Biphenyl]-4-yl)-3,3,3-trifluoropropyl)pyridine (12): According to the
general procedure, 4-vinyl-1,1'-biphenyl (36.00 mg, 0.2 mmol, 1.0 equiv.), DABCO
(33.6 mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and
isonicotinonitrile (41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol,
1.5 equiv.) in MTBE (4 mL) were used. After 24 h, the product was isolated by flash
chromatography (PE: EA= 2:1) as a pale-yellow oil (55.6 mg, 85%).
1H NMR (600 MHz, CDCl ) δ 8.56 (d, J = 5.7 Hz, 2H), 7.56 (d, J = 7.9 Hz, 4H), 7.43
3
(t, J = 7.6 Hz, 2H), 7.35 (t, J = 7.3 Hz, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 5.7
S8
Hz, 2H), 4.35 (t, J = 7.3 Hz, 1H), 2.98 – 2.90 (m, 2H). 19F NMR (565 MHz, CDCl ) δ
3
-63.61 (t, J = 10.2 Hz, 3F).13C NMR (150 MHz, CDCl ) δ 151.21, 150.15, 140.33,
3
140.22, 139.89, 128.75, 127.79, 127.62, 127.43, 126.94, 126.03 (q, J = 276.0 Hz),
122.70, 44.17, 38.80 (q, J = 27.0 Hz). HRMS (EI): calcd for C H F N 327.1235,
20 16 3
found 327.1239.

4-(3,3,3-Trifluoro-1-(4-fluorophenyl)propyl)pyridine (13): According to the general
procedure, 1-fluoro-4-vinylbenzene (24.0 µL, 0.2 mmol, 1.0 equiv.), DABCO (33.6 mg,
0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and isonicotinonitrile (41.6
mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol, 1.5 equiv.) in MTBE (4
mL) were used. After 24 h, the product was isolated by flash chromatography (PE: EA=
2:1) as a pale-yellow oil (37.6 mg, 70%).
1H NMR (600 MHz, CDCl ) δ 8.56 (s, 2H), 7.19 –7.17(m, 2H), 7.15 (d, J = 3.9 Hz,
3
2H), 7.02 (t, J = 8.5 Hz, 2H), 4.28 (t, J = 7.3 Hz, 1H), 2.94—2.82 (m, 2H). 19F NMR
(565 MHz, CDCl ) δ -63.67 (t, J = 10.2 Hz, 3F), -114.74-- -114.78 (m, 1F); 13C NMR
3
(150 MHz, CDCl ) δ 161.92 (d, J = 246.0Hz), 151.04, 150.23, 136.65 (d, J = 4.5 Hz),
3
129.03 (d, J = 9.0 Hz), 125.92 (q, J = 276.0 Hz), 122.62, 115.92 (d, J = 22.5 Hz), 43.76,
38.95 (q, J = 28.5 Hz). HRMS (EI): calcd for C H F N 269.0828, found 269.0833.
14 11 4

CF
3
N
Cl
1-Chloro-4-(3,3,3-trifluoro-1-phenylpropyl)benzene (14): According to the general
procedure, 1-chloro-4-vinylbenzene (24.0 µL, 0.2 mmol, 1.0 equiv.), DABCO (33.6
mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3 mmol, 1.5 equiv.), and isonicotinonitrile
(41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent (99.0 mg, 0.3 mmol, 1.5 equiv.) in
S9
MTBE (4 mL) were used. After 24 h, the product was isolated by flash chromatography
(PE: EA= 2:1) as a pale-yellow oil (42.2 mg, 74%).
1H NMR (600 MHz, CDCl ) δ 8.55 (d, J = 4.4 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 7.15
3
(m, 4H), 4.28 (t, J = 7.3 Hz, 1H), 2.92—2.82 (m, 2H); 19F NMR (565 MHz, CDCl ) δ
3
-63.65 (t, J = 10.1 Hz, 3F); 13C NMR (150 MHz, CDCl ) δ 150.78, 150.25, 139.32,
3
133.38, 129.17, 128.80, 125.87 (q, J = 276.0 Hz), 122.57, 43.87, 38.73 (q, J = 27.0 Hz).
HRMS (EI): calcd for C H F N 284.0580, found 284.0586.
14 11 4

4-(1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-3,3,3-trifluoropropyl)pyridine (15):
According to the general procedure, 6-vinyl-2,3-dihydrobenzo[b][1,4]dioxine (32.4
mg, 0.2 mmol, 1.0 equiv.), DABCO (33.6 mg, 0.3 mmol, 1.5 equiv.), HE (76 mg, 0.3
mmol, 1.5 equiv.), and isonicotinonitrile (41.6 mg, 0.4 mmol, 2.0 equiv.), Togni reagent
(99.0 mg, 0.3 mmol, 1.5 equiv.) in MTBE (4 mL) were used. After 24 h, the product
was isolated by flash chromatography (PE: EA= 2:1) as a pale-yellow oil (43.3 mg,
70%).
1H NMR (600 MHz, CDCl ) δ 8.52 (d, J = 5.1 Hz, 2H), 7.15 (d, J = 5.9 Hz, 2H), 6.80
3
(d, J = 8.3 Hz, 1H), 6.71 – 6.67 (m, 2H), 4.23 (s, 4H), 4.17 (t, J = 7.3 Hz, 1H), 2.88 –
2.80 (m, 2H).19F NMR (565 MHz, CDCl ) δ -63.75 (t, J = 10.2 Hz, 3F).13C NMR (150
3
MHz, CDCl ) δ 150.49, 150.15, 143.71, 142.83, 134.26, 126.06 (q, J = 276.0 Hz),
3
122.66, 120.31, 117.69, 116.18, 64.37, 64.28, 43.85, 38.94 (q, J =28.5 Hz,). HRMS
(EI): calcd for C H F NO 309.0977, found 309.0984.
16 14 3 2

S10