Photochemical Intramolecular Amination for the Synthesis of Heterocycles.

72 Pages·2017·1.31 MB·English

Electronic Supplementary Material (ESI) for Green Chemistry.
This journal is © The Royal Society of Chemistry 2017
Photochemical Intramolecular Amination for
the Synthesis of Heterocycles.
Shawn Parisien-Collette, Corentin Cruché, Xavier Abel-Snape and Shawn K. Collins*
Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal, CP 6128
Station Downtown, Montréal, Québec, Canada H3C 3J7
SUPPORTING INFORMATION
TABLE OF CONTENTS:
GENERAL S2
SYNTHESIS OF PRECURSORS S3
SYNTHESIS OF CARBAZOLES S18
SYNTHESIS OF CARPROFEN METHYL ESTER S27
KINETIC ISOTOPE EFFECTS S31
BACKGROUND ON LIGHT SOURCES S34
ABSORPTION/EMISSION DATA S36
NMR DATA FOR ALL NEW COMPOUNDS S37
S1
General:
All reactions that were carried out under anhydrous conditions were performed under an
inert argon or nitrogen atmosphere in glassware that had previously been dried overnight
at 120 oC or had been flame dried and cooled under a stream of argon or nitrogen.1 All
chemical products were obtained from Sigma-Aldrich Chemical Company or Alfa Aesar
and were reagent quality. The following products were prepared according to their
respective literature procedures: Methyl (2Z,4E)-2-azido-5-phenylpenta-2,4-dienoate
Technical solvents were obtained from VWR International Co. Anhydrous solvents
(CH Cl , Et O, THF, DMF, toluene, and n-hexane) were dried and deoxygenated using a
2 2 2
GlassContour system (Irvine, CA). Isolated yields reflect the mass obtained following
flash column silica gel chromatography. Organic compounds were purified using the
method reported by W. C. Still2 and using silica gel obtained from Silicycle Chemical
division (40-63 nm; 230-240 mesh). Analytical thin-layer chromatography (TLC) was
performed on glass-backed silica gel 60 coated with a fluorescence indicator (Silicycle
Chemical division, 0.25 mm, F .). Visualization of TLC plate was performed by UV
254
(254 nm), KMnO or p-anisaldehyde stains. All mixed solvent eluents are reported as v/v
4
solutions. Concentration refers to removal of volatiles at low pressure on a rotary
evaporator. All reported compounds were homogeneous by thin layer chromatography
(TLC) and by 1H NMR. NMR spectra were taken in deuterated CDCl using Bruker AV-
3
300 and AV-400 instruments unless otherwise noted. Signals due to the solvent served as
the internal standard (CHCl : δ 7.27 for 1H, δ 77.0 for 13C). The acquisition parameters
3
are shown on all spectra. The 1H NMR chemical shifts and coupling constants were
determined assuming first-order behavior. Multiplicity is indicated by one or more of the
following: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad); the list
of couplings constants (J) corresponds to the order of the multiplicity assignment. High
resolution mass spectroscopy (HRMS) was done by the Centre régional de spectrométrie
de masse at the Département de Chimie, Université de Montréal from an Agilent LC-
MSD TOF system using ESI mode of ionization unless otherwise noted.
1 Shriver, D. F.; Drezdon, M. A. in The Manipulation of Air-Sensitive Compounds; Wiley-VCH: New York, 1986.
2 Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
S2
SYNTHESIS OF PRECURSORS
General Procedure for Suzuki Cross-Coupling (C): An oven-dried sealed tube was
charged with 2-iodoaniline (1 equiv.), arylboronic acid (1.2 equiv.), K CO (4 equiv.),
2 3
Pd(PPh ) Cl (2 mol %) and a mixture of dimethoxyethane/water (1:1 [0.25 M]) under a
3 2 2
nitrogen atmosphere. The mixture was stirred at 80 ºC for 18 h under nitrogen. Upon
cooling, the biphasic solution was diluted with ethyl acetate (20 mL) and the phases were
separated. The aqueous phase was extracted twice with EtOAc (20 mL) and the combined
organic phases were washed with brine (50 mL). The organic phases were dried over
Na SO , filtered and concentrated. The crude mixture was purified by silica gel column
2 4
chromatography (hexanes/ethyl acetate) to afford corresponding product.
General Procedure for Sandmeyer reaction (D): The corresponding 2-aminobiaryl (1.0
equiv.) was dissolved in a mixture of acetic acid / water (2:1, 0.1 M) and cooled to 0 ºC.
NaNO (1.4 equiv.) was added and the resulting was stirred at 0 ºC for one hour. NaN
2 3
(1.5 equiv.) was then added slowly, the resulting mixture was warmed to room
temperature and stirred for an additional hour. The solution was diluted with CH Cl (20
2 2
mL) and made basic by the slow addition of saturated aqueous K CO until bubbling
2 3
ceased. The phases were separated and the aqueous phase was extracted twice with
CH Cl (20 mL). The combined organic phases were washed with water (50 mL) and
2 2
brine (50 mL). The organic phases were dried over Na SO , filtered and concentrated.
2 4
The crude mixture was purified by silica gel column chromatography (hexanes/ethyl
acetate) to afford corresponding product.
S3
N
3
2-Azido-1,1’-biphenyl (1): Following the General Procedure D, starting from [1,1’-
biphenyl]-2-amine (1.0 g, 5.9 mmol), the crude mixture was purified by silica gel column
chromatography (100 % hexanes → 10 % ethyl acetate in hexanes), to afford the desired
product as a yellow solid (1.08 g, 94 % yield). NMR data was in accordance with what
was previously reported.3
NH
2
Cl
4’-Chloro-[1,1’-biphenyl]-2-amine (S1): Following the General Procedure C, starting
from 4-chlorophenylboronic acid (0.28 g, 1.8 mmol, 1.2 equiv.), the crude mixture was
purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in
hexanes), to afford the desired product as a brown oil (0.25 g, 81 % yield). NMR data
was in accordance with what was previously reported.4
N
3
Cl
2-Azido-4’-chloro-1,1’-biphenyl (2): Following the General Procedure D, starting from
4’-chloro-[1,1’-biphenyl]-2-amine S1 (0.25 g, 1.2 mmol), the crude mixture was purified
by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes),
to afford the desired product as a yellow solid (0.20 g, 74 % yield). NMR data was in
accordance with what was previously reported.5
3Stokes, B. J.; Jovanović, B.; Dong, H.; Richert, K. J.; Riell, R. D.; Driver, T. G. J. Org. Chem. 2009, 74, 3225-3228
4Liang, Z.; Feng, R.; Yin, H.; Zhang, Y. Org. Lett. 2013, 15, 4544-4547
5 Nagaki, A.; Ichinari, D.; Yoshida, J. J. Am. Chem. Soc. 2014, 136, 12245-12248
S4
NH
2
Br
4’-Bromo-[1,1’-biphenyl]-2-amine (S2): Following the General Procedure C, starting
from 4-bromophenylboronic acid (0.36 g, 1.8 mmol, 1.2 equiv.), the crude mixture was
purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in
hexanes), to afford the desired product as a yellow solid (0.25 g, 68 % yield). NMR data
was in accordance with what was previously reported.6
N
3
Br
2-Azido-4’-bromo-1,1’-biphenyl (3): Following the General Procedure D, starting from
4’-bromo-[1,1’-biphenyl]-2-amine S2 (0.25 g, 1.0 mmol), the crude mixture was purified
by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes),
to afford the desired product as a yellow solid (0.23 g, 84 % yield). 1H NMR (300 MHz,
CDCl ) δ = 7.55 (d, J = 8.5 Hz, 2H,), 7.44-7.38 (m, 1H), 7.34-7.29 (m, 3H), 7.26-7.18
3
(m, 2H); 13C NMR (100 MHz, CDCl ) δ = 137.1, 137.0, 132.4, 131.3, 131.0, 129.1,
3
125.0, 121.8, 118.8; HRMS (ESI) m/z calculated for C H BrN [M-N -H]+ 243.9751;
12 7 2
found 243.9762.
NH
2
F
4’-Fluoro-[1,1’-biphenyl]-2-amine (S3): Following the General Procedure C, starting
from 4-fluorophenylboronic acid (0.17 g, 1.2 mmol, 1.2 equiv.), the crude mixture was
purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in
hexanes), to afford the desired product as a brown solid (0.15 g, 83 % yield). NMR data
was in accordance with what was previously reported.3
6 Ohwada, A.; Nara, S.; Sakamoto, T.; Kikugawa, Y. J. Chem. Soc., Perkin Trans. I, 2001, 3064-3068
S5
N
3
F
2-Azido-4’-fluoro-1,1’-biphenyl (S4): Following the General Procedure D, starting from
4’-fluoro-[1,1’-biphenyl]-2-amine S3 (0.15 g, 0.8 mmol), the crude mixture was purified
by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in hexanes),
to afford the desired product as a white solid (0.15 g, 87 % yield). NMR data was in
accordance with what was previously reported.3
NH
2
N
2’-Amino-[1,1’-biphenyl]-4-carbonitrile (S5): Following the General Procedure C,
starting from 4-cyanophenylboronic acid (0.18 g, 1.2 mmol, 1.2 equiv.), the crude
mixture was purified by silica gel column chromatography (100 % hexanes → 30 % ethyl
acetate in hexanes), to afford the desired product as a yellow solid (0.18 g, 92 % yield).
NMR data was in accordance with what was previously reported.3
N
3
N
2’-Azido-[1,1’-biphenyl]-4-carbonitrile (S6): Following the General Procedure D,
starting from 2’-amino-[1,1’-biphenyl]-4-carbonitrile S5 (0.18 g, 0.9 mmol), the crude
mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl
acetate in hexanes), to afford the desired product as a yellow solid (0.08 g, 41 % yield).
NMR data was in accordance with what was previously reported.3
NH
2
O
O
Methyl 2’-amino-[1,1’-biphenyl]-4-carboxylate (S7): Following the General
Procedure C, starting from 4-methoxycarbonylphenylboronic acid (0.43 g, 2.4 mmol, 1.2
equiv.), the crude mixture was purified by silica gel column chromatography (100 %
hexanes → 15 % ethyl acetate in hexanes), to afford the desired product as a pale yellow
S6
solid (0.29 g, 65 % yield). 1H NMR (400 MHz, CDCl ) δ = 8.12 (d, J = 8.2 Hz, 2H), 7.56
3
(d, J = 8.4 Hz, 2H) 7.20 (ddd, J = 7.5, 7.5, 1.7 Hz, 1H), 7.14 (dd, J = 7.5, 1.3 Hz, 1H),
6.85 (ddd, J = 7.5, 7.5, 1.1 Hz, 1H), 6.79 (dd, J = 7.9, 0.9 Hz, 1H), 3.96 (s, 3H), 3.76
(brs, 2H); 13C NMR (100 MHz, CDCl ) δ = 166.7, 144.3, 143.3, 130.2, 129.9, 129.0,
3
128.9, 128.7, 126.1, 118.6, 115.7, 51.9; HRMS (ESI) m/z calculated for C H NO H
14 13 2
[M+H]+ 228.1015; found 228.1019.
N
3
O
O
Methyl 2’-azido-[1,1’-biphenyl]-4-carboxylate (S8): Following the General Procedure
D, starting from methyl 2’-amino-[1,1’-biphenyl]-4-carboxylate S7 (0.29 g, 1.3 mmol),
the crude mixture was purified by silica gel column chromatography (100 % hexanes →
10 % ethyl acetate in hexanes), to afford the desired product as a yellow solid (0.29 g, 88
% yield). 1H NMR (300 MHz, CDCl ) δ = 8.11 (d, J = 8.6 Hz, 2H), 7.54 (d, J = 8.6 Hz,
3
2H), 7.47-7.41 (m, 1H), 7.36 (dd, J = 7.6, 1.7 Hz, 1H), 7.30-7.21 (m, 2H), 3.95 (s, 3H);
13C NMR (75 MHz, CDCl ) δ = 166.9, 142.8, 137.2, 132.6, 131.1, 129.5, 129.4, 129.3,
3
129.1; 125.0, 118.8, 52.1; HRMS (ESI) m/z calculated for C H N O H [M+H]+
14 11 3 2
254.0921; found 254.0924.
NH
2
CF
3
4’-(Trifluoromethyl)-[1,1’-biphenyl]-2-amine (S9): Following the General
Procedure C, starting from 4-(trifluoromethyl)phenylboronic acid (0.23 g, 1.2 mmol, 1.2
equiv.), the crude mixture was purified by silica gel column chromatography (100 %
hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a tan oil (0.20
g, 83 % yield). NMR data was in accordance with what was previously reported.3
N
3
CF
3
2-Azido-4’-trifluoromethyl-1,1’-biphenyl (S10): Following the General Procedure D,
starting from 4’-(trifluoromethyl)-[1,1’-biphenyl]-2-amine S9 (0.20 g, 0.8 mmol), the
crude mixture was purified by silica gel column chromatography (100 % hexanes → 10
S7
% ethyl acetate in hexanes), to afford the desired product as a clear oil (0.16 g, 78 %
yield). NMR data was in accordance with what was previously reported.3
NH
2
NMe
2
N4’,N4’-Dimethyl-[1,1’-biphenyl]-2,4’-diamine (S11): Following the General
Procedure C, starting from 4-(dimethylamino)phenylboronic acid (0.20 g, 1.2 mmol, 1.2
equiv.), the crude mixture was purified by silica gel column chromatography (100 %
hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a red oil (0.19
g, 88 % yield). 1H NMR (400 MHz, CDCl ) δ = 7.36 (d, J = 8.6 Hz, 1H), 7.15-7.10 (m,
3
2H), 6.84-6.76 (m, 4H), 3.79 (brs, 2H), 3.01 (s, 6H); 13C NMR (100 MHz, CDCl ) δ =
3
149.5, 143.7, 130.3, 129.6, 127.7, 127.6, 127.2, 118.4, 115.3, 112.6, 40.4; HRMS (ESI)
m/z calculated for C H N H[M+H]+ 213.1377; found 213.1386.
14 16 2
N
3
NMe
2
2’-Azido-N,N-dimethyl-[1,1’-biphenyl]-4-amine (S12): Following the General
Procedure D, starting from N4’,N4’-dimethyl-[1,1’-biphenyl]-2,4’-diamine S11 (0.19 g,
0.9 mmol), the crude mixture was purified by silica gel column chromatography (100 %
hexanes → 10 % ethyl acetate in hexanes), to afford the desired product as a yellow solid
(0.19 g, 90 % yield). 1H NMR (400 MHz, CDCl ) δ = 7.38-7.32 (m, 4H), 7.25-7.17 (m,
3
2H), 6.80 (d, J = 8.7 Hz, 2H), 3.01 (s, 6H); 13C NMR (100 MHz, CDCl ) δ = 149.8,
3
136.8, 133.9, 190.9, 130.1, 127.6, 125.8, 124.8, 118.6, 111.9, 40.4; HRMS (ESI) m/z
calculated for C H N H[M+H]+ 239.1296; found 239.1291.
14 14 4
NH
2
OMe
4’-Methoxy-[1,1’-biphenyl]-2-amine (S13): Following the General Procedure C,
starting from 4-methoxyphenylboronic acid (0.18g, 1.2 mmol, 1.2 equiv.), the crude
mixture was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl
acetate in hexanes), to afford the desired product as a pale yellow oil (0.19 g, 97 % yield).
NMR data was in accordance with what was previously reported.3
S8
N
3
OMe
2-Azido-4’-methoxy-1,1’-biphenyl (S14): Following the General Procedure D, starting
from 4’-methoxy-[1,1’-biphenyl]-2-amine S13 (0.19 g, 0.97 mmol), the crude mixture
was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate
in hexanes), to afford the desired product as a yellow solid (0.19 g, 89 % yield). NMR
data was in accordance with what was previously reported.3
NH
2
SiMe
3
4’-(Trimethylsilyl)-[1,1’-biphenyl]-2-amine (S15): Following the General Procedure C,
starting from (4-(trimethylsilyl)phenyl)boronic acid (0.35 g, 1.8 mmol, 1.2 equiv.), the
crude mixture was purified by silica gel column chromatography (100 % hexanes → 5 %
ethyl acetate in hexanes), to afford the desired product as a yellow oil (0.31 g, 86 %
yield). 1H NMR (400 MHz, CDCl ) δ = 7.61 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H),
3
7.19-7.14 (m, 2 H), 6.83 (ddd, J = 7.4, 7.4, 1.2 Hz, 1H), 6.78 (dd, J = 8.0, 0.8 Hz, 1 H),
3.78 (brs, 2H), 0.32 (s, 9H); 13C NMR (100 MHz, CDCl ) δ = 143.5, 139.9, 139.2, 133.8,
3
130.4, 128.5, 128.3, 127.6, 118.6, 115.6, -1.1; HRMS (ESI) m/z calculated for
C H NSiH[M+H]+ 242.1356; found 242.1359.
15 19
N
3
SiMe
3
(2’-Azido-[1,1’-biphenyl]-4-yl)trimethylsilane (S16): Following the General
Procedure D, starting from 4’-(trimethylsilyl)-[1,1’-biphenyl]-2-amine S15 (0.31 g, 1.3
mmol), the crude mixture was purified by silica gel column chromatography (100 %
hexanes → 5 % ethyl acetate in hexanes), to afford the desired product as a pale yellow
solid (0.26 g, 74 % yield). 1H NMR (400 MHz, CDCl ) δ = 7.61 (d, J = 8.0 Hz, 2H), 7.46
3
(d, J = 8.0 Hz, 2H), 7.43-7.39 (m, 1H), 7.36 (dd, J = 7.6 Hz, J = 1.5 Hz, 1H), 7.29-7.27
1 2
(m, 1H), 7.25-7.21 (m, 1H), 0.32 (s, 9H) ; 13C NMR (100 MHz, CDCl ) δ = 139.5, 138.5,
3
137.1, 133.6, 133.1, 131.2, 128.7, 128.6, 124.9, 118.6, -1.1; HRMS (ESI) m/z calculated
for C H N SiNH [M+NH ]+ 285.1522; found 285.1530.
15 17 3 4 4
S9
NH
2
2’-Isopropyl-[1,1’-biphenyl]-2-amine (S17): Following the General Procedure C,
starting from 1-bromo-2-isopropylbenzene (0.17 mL, 1.1 mmol, 1.1 equiv.) and 2-
aminophenylboronic acid hydrochloride (0.17 g, 1.0 mmol, 1.0 equiv.), the crude mixture
was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate
in hexanes), to afford the desired product as a tan oil (0.22 g, 99 % yield). NMR data was
in accordance with what was previously reported.7
N
3
2-Azido-2’-isopropyl-1,1’-biphenyl (S18): Following the General Procedure D, starting
from 2’-isopropyl-[1,1’-biphenyl]-2-amine S17 (0.22 g, 1.0 mmol), the crude mixture
was purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate
in hexanes), to afford the desired product as a pale brown solid (0.15 g, 68 % yield).
NMR data was in accordance with what was previously reported.7
NH
2
Me
4’-Methyl-[1,1’-biphenyl]-2-amine (S19): Following the General Procedure C, starting
from 4-methylphenylboronic acid (0.16 g, 1.2 mmol, 1.2 equiv.), the crude mixture was
purified by silica gel column chromatography (100 % hexanes → 10 % ethyl acetate in
hexanes), to afford the desired product as a clear oil (0.15 g, 83 % yield). NMR data was
in accordance with what was previously reported.3
7 Intrieri, D.; Mariani, M.; Caselli, A.; Ragaini, F.; Gallo, E. Chem. Eur. J. 2012, 18, 10487-10490
S10