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Supporting Information
Visible-Light-Promoted Intramolecular C–H Amination in
Aqueous Solution: Synthesis of Carbazoles
Lizheng Yang,[a] Yipin Zhang,[a] Xiaodong Zou,[a] Hongjian Lu*[a] and
Guigen Li[a,b]
[email protected]
Table of Contents
Table of Contents ............................................................................................................................ S1
Ⅰ. General Information ............................................................................................................... S2
Ⅱ. Scheme 3 Mechanism Studies Results ............................................................................ S3
1. Scheme 3a ........................................................................................................................ S3
2. Scheme 3b ........................................................................................................................ S4
3. Scheme 3c ......................................................................................................................... S5
4. Scheme 3d………………………………………………………………………………………...S9
Ⅲ. Contents of Starting Materials ......................................................................................... S10
Ⅳ. General Procedures for Synthesis of Starting Materials and Spectroscopic Data
of Biaryl Azides ............................................................................................................................ S14
1. Preparation of biaryl azides 1a-h, 1j-u, 1w-z, 3a-d......................................... S14
2. Preparation of biaryl azides 1i, 3e .......................................................................... S26
3. Preparation of biaryl azide 1v .................................................................................. S29
4. Preparation of biaryl azide 1a-D ............................................................................. S31
5. Preparation of biaryl azide 1aa ................................................................................ S33
Ⅴ Experimental Procedure for for Synthesis of Carbazoles ..................................... S35
Ⅵ. Spectroscopic Data of Carbazoles Obtained in this Study .................................... S36
Ⅶ. References ............................................................................................................................... S47
Ⅷ. Spectral Copies of 1H, 13C NMR of All Compounds .................................................. S48
[a] Institute of Chemistry & BioMedical Sciences, Jiangsu Key Laboratory of Advanced Organic
Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, (China)
E-mail: [email protected] .
[b] Department of Chemistry and Biochemistry,Texas Tech University, Lubbock, TX 79409-1061
(USA)
Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2018
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Ⅰ. General Information
Unless otherwise mentioned, all commercial reagents and solvents were used without
further purification. Thin layer chromatography (TLC) was performed on pre-coated
silica gel GF254 plates. Visualization of TLC was achieved by the use of UV light (254
nm). Column chromatography was performed on silica gel (300-400 mesh) using a
proper eluent. 1H NMR was recorded on FT AM 400 (400 MHz). Chemical shifts were
reported in parts per million (ppm) referenced to the appropriate solvent peak or 0.0
ppm for tetramethylsilane or chloroform-d (CDCl3) at 7.26 ppm. The following
abbreviations were used to describe peak splitting patterns: brs = broad, s = singlet, d =
doublet, t = triplet, q = quartet, dd = doublet of doublet, td = triplet of doublet, ddd =
doublet of doublet of doublet, m = multiplet. Coupling constants, J, were reported in
hertz (Hz). The fully decoupled 13C NMR was recorded on FT AM 400 (100 MHz).
Chemical shifts were reported in ppm referenced to the center of a triplet at 77.36 ppm
of chloroform-d. Infrared (IR) spectra were recorded neat in KBr cell. Frequencies are
given in centimeter inverse (cm-1) and only selected absorbance is reported. High
resolution mass spectra were obtained by using the UHD Accurate-Mass Q-TOF.
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Ⅱ. Scheme 3 Mechanism Studies Results
1. Scheme 3a
Azides 1b (0.10 mmol, 22.5 mg), 1g (0.10 mmol, 26.7 mg), silica gel 15.0 mg, H2O
(1.5 ml) and Acetone (1.5 ml) were added to a 15 ml glass vial equipped with a stirring
bar. Then the solution was stirred at a distance of ~1 cm from a 23 w fluorescent lamp
at room temperature about 24 hours. The biphasic solution was diluted with 5 mL of
water and 5 mL of CH2Cl2 and separated. The aqueous phase was extracted with an
additional 3 × 5 mL of CH2Cl2, and the combined organic phases were washed 2 × 5
mL of water. The organic phase was dried over Na2SO4 and filtered. The solvents were
removed under reduced pressure, and the crude yield was measured by 1H NMR
spectroscopy using CH2Br2 as an internal standard. 1H NMR of reaction mixture:
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2. Scheme 3b
Azides 1p (0.10 mmol, 22.5 mg), 1u (0.10 mmol, 26.7 mg), silica gel 15.0 mg, H2O
(1.5 ml) and Acetone (1.5 ml) were added to a 15 ml glass vial equipped with a stirring
bar. Then the solution was stirred at a distance of ~1 cm from a 23 w fluorescent lamp
at room temperature about 24 hours. The biphasic solution was diluted with 5 mL of
water and 5 mL of CH2Cl2 and separated. The aqueous phase was extracted with an
additional 3 × 5 mL of CH2Cl2, and the combined organic phases were washed 2 × 5
mL of water. The organic phase was dried over Na2SO4 and filtered. The solvents were
removed under reduced pressure, and the crude yield was measured by 1H NMR
spectroscopy using CH2Br2 as an internal standard. 1H NMR of reaction mixture:
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3. Scheme3c
1a-D (0.10 mmol, 19.6 mg), silica gel 15.0 mg, H2O (1.5 ml) and Acetone (1.5 ml) were
added to a 15 ml glass vial equipped with a stirring bar. Then the solution was stirred
at a distance of ~1 cm from a 23 w fluorescent lamp at room temperature about 48 hours.
The biphasic solution was diluted with 5 mL of water and 5 mL of CH2Cl2 and separated.
The aqueous phase was extracted with an additional 3 × 10 mL of CH2Cl2, and the
combined organic phases were washed 2 × 5 mL of water. The crude product was
purified by flash chromatography on silica gel (petroleum ether : ethyl acetate gradient:
20:1-10:1) afforded the products (2a + 2a-D): 10.6 mg, 63%; white solid; TLC Rf =
0.36 (petroleum ether : ethyl acetate 10:1).
Kinetic Isotope Effect of Intramolecular was estimated by 1H NMR
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1H NMR (400 MHz, DMSO): Carbazole 2a-D
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Kinetic Isotope Effect of Intramolecular was estimated by GC-MS
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4. Scheme3d
1aa (0.20 mmol, 74.7 mg), silica gel 15.0 mg, H2O (1.5 ml) and Acetone (1.5 ml) were added to a
15 ml glass vial equipped with a stirring bar. Then the solution was stirred at a distance of ~1 cm
from a 23 w fluorescent lamp at room temperature about 24 hours. The biphasic solution was diluted
with 5 mL of water and 5 mL of CH2Cl2 and separated. The aqueous phase was extracted with an
additional 3 × 10 mL of CH2Cl2, and the combined organic phases were washed 2 × 5 mL of water.
The organic phase was dried over Na2SO4 and filtered. The crude product was purified by
chromatography on silica gel (petroleum ether : ethyl acetate gradient: 10:1-1:1) afforded the
mixture products 2aa +2aa′ (39.2 mg, 56%), Rf = 0.12 (petroleum ether : ethyl acetate 10:1). The
ratio of the two products was determined by mixture 1H NMR. Then the mixture was separated by
chromatography on silica gel (petroleum ether : acetone gradient 30:1-3:1) directly to give the
desired product.
Mixture 1H NMR of 2aa and 2aa′
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Ⅱ. Contents of Starting Materials
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Detailed information for Table 1
Entry[a] Solvent Time(h) Conversion Yield[%][b]
1 Toluene 18 40 70
2 Benzene 17 50 68
3 CCl4 18 49 75
4 MeOH 18 55 70
5 EtOH 24 64 50
6 Ethylene glycol 20 50 26
7 MeCN 18 53 80
8 Acetone 13 40 67
9 DME 20 70 70
10 1,4-dioxane 15 67 76
11 Et2O 14 58 69
12 THF 18 60 85
13 DMF 18 65 68
14 H2O 18 45 100
15 H2O 36 60 100
16[d] H2O 36 45 100
17 H2O / Acetone = 1 / 1 36 75 100
18[e] H2O / Acetone = 1 / 1 36 80(19)[c] 100
19[e] H2O / MeOH = 1 / 1 36 64 100
20[e] H2O / DMF = 1 / 1 36 60 100
21[e] H2O / DCM = 1 / 1 36 58 100
22[e] H2O / EtOH = 1 / 1 36 75 100
23[e] H2O / Acetone = 10 / 1 36 67 100
24[e] H2O / Acetone = 5 / 1 36 69 100
25[e] H2O / Acetone = 2 / 1 36 71 100
23[e] H2O / Acetone = 1 / 5 36 78 100
24[e] H2O / Acetone = 1 / 10 36 75 100
26[f] Acidic buffer solution 36 59 100
27[g] Alkaline buffer solution 36 61 100
28[h] H2O / Acetone = 1 / 1 36 0 0
[a] Reaction conditions: substrate (1a, 0.15 mmol), fluorescent lamp 23 W, solvent (2.0 mL), room temperature. [b]
Yield of 2a were determined by crude 1HNMR and the remaining percent of the starting material is shown in bracket.
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[c]. Isolated yield by column chromatography. [d].Fluorescent lamp 18 W. [e] Substrate (1a, 0.15 mmol), fluorescent
lamp 23 W, (1.5 / 1.5 mL), silca gel 15 mg, room temperature [f] Acidic buffer solution (NaAc-HAc, 2.0 mL PH =
4.0 ). [g] Alkaline buffer solution ( Glycine – NaOH, 2.0 mL PH = 8.6 ). [h] no light
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IV. General Procedures for Synthesis of Starting Materials
and Spectroscopic Data of Biaryl Azides
1. Preparation of biaryl azides 1a-h, 1j-u, 1w-z, 3a-d.
Unless otherwise noted, the biaryl azides were synthesized from the substituted 2-
bromoanilines and substituted phenylboronic acid using Suzuki reactions.[1] The
resulting biaryl amines were converted to corresponding biaryl azides without
purification using traditional diazotization reaction conditions. Yields were not
optimized.
In a 50 mL round bottom flask, Substituted phenylboronic acid (9 mmol, 3.0 equiv),
Na2CO3 (6 mmol, 2.0 equiv, 635.9 mg), and Pd(OAc)2 (0.06 mmol, 0.02 equiv, 13.5 mg)
were then dissolved in 9 mL of ethylene glycol, 9 mL of H2O. Substituted 2-
bromoaniline (3 mmol, 1.0 equiv) was added, and the resulting mixture was heated
to 80 ˚C for 24 hours. After cooling, the biphasic solution was diluted with 50 mL of
water and 30 mL of CH2Cl2 and separated. The aqueous phase was extracted with an
additional 3 × 30 mL of CH2Cl2, and the combined organic phases were washed 2 × 50
mL of water. The organic phase was dried over Na2SO4 and filtered. The filtrate was
concentrated in vacuo to afford oil. This crude mixture was used for the next step
without any further purification.
For 1l (synthesis of 5-bromo-[1,1'-biphenyl]-2-amine): In a 50mL of round bottom flask,
biphenyl amine (1.0 equiv, 5mmol, 0.85g) was dissolved in 20mL DMF and chilled in
an ice bath. N-Bromosuccinimide(1.2equvi, 6mmol, 1.05g dissolved in 10mL DMF)
was added dropwise. The system reacted for 2h and the solution was then diluted with
50 mL of water and extracted with DCM for 3 times. The organic phase was washed
with water and then dried over Na2SO4.The solution was concentrated in vacuo and
crude was purified by silica gel column using petroleum ether and ethyl acetate as
eluent. Yield: 0.88g, 71%.
For 1m (synthesis of 5-iodo-[1,1'-biphenyl]-2-amine) method was the same as
previous report.[23] Aryl biphenyl amine (0.85 g, 5 mmol, 1 equiv), NaHCO3 (0.63 g,
7.5 mmol, 1.5 equiv) and 15 mL water were added into a 50 mL round-bottom flask
under vigorous stirring, and iodine powder(1.14 g, 4.5 mmol, 0.9 equiv) was added with
several portions in 0.5 h. The reaction mixture was stirred for an additional hour at room
temperature until the color of iodine disappeared. The crude product was obtained by
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vacuum filtration and used for next step without purification.
In a 100 mL of round bottom flask, the crude biaryl amine (1.0 equiv) was dissolved in
HOAc and H2O (2:1 v/v, 0.2 M) and chilled in an ice bath. NaNO2 (1.4 equiv, 275.5
mg) was added slowly, and then the resulting mixture was stirred at 0 °C for 2 hours.
NaN3 (1.5 equiv, 310.5 mg) was then added slowly; the resulting mixture was warmed
up to ambient temperature, and stirred overnight. The solution was then diluted with 20
mL of water and 20 mL of CH2Cl2, and basified by slow addition of K2CO3 until the
pH of the mixture was 8. The phases were separated and the aqueous phase was
extracted with an additional 3 × 30 mL of CH2Cl2. The combined organic phase were
dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and crude was
purified by silica gel column using petroleum ether and ethyl acetate as eluent.
2-azido-1,1'-biphenyl (1a).[2] The general procedure was followed using 0.516 g of 2-
bromoaniline (3.0 mmol). Purification of the reaction mixture using column
chromatography (petroleum ether : ethyl acetate 30:1) afforded the product 1a (584.0
mg, 99%); TLC Rf = 0.69 (petroleum ether : ethyl acetate 20:1). 1H NMR (400 MHz,
CDCl3) δ = 7.64 – 7.57 (m, 4H), 7.56 – 7.45 (m, 3H), 7.42 – 7.30 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ 138.16, 137.09, 133.78, 131.25, 129.48, 128.70, 128.14, 127.53,
124.94, 118.78. IR (neat) v 2124, 1501, 1479, 1431, 1298 cm-1.
2-azido-5-methyl-1,1'-biphenyl (1b).[2] The general procedure was followed using
0.558 g of 2-bromo-4-methylaniline (3.0 mmol). Purification of the reaction mixture
using column chromatography(petroleum ether : ethyl acetate 30:1) afforded the
product 1b (565.0 mg, 90%), Rf = 0.72 (petroleum ether : ethyl acetate 20:1). 1H NMR
(400 MHz, CDCl3) δ = 7.60 –7.40 (m, 5H), 7.35–7.20 (m, 3H), 2.46 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 138.34, 134.68, 134.36, 133.59, 131.96, 129.48, 129.37, 128.15,
127.51, 118.73, 20.88. IR (neat) v 2117, 1486, 1299, 1157, 697 cm-1.
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4'-azido-1,1':3',1''-terphenyl (1c). The general procedure was followed using 0.744 g
of 3-bromo-[1,1'-biphenyl]-4-amine (3.0 mmol). Purification of the reaction mixture
using column chromatography (petroleum ether : ethyl acetate 30:1) afforded the
product 1c (732.0 mg, 90%), Rf = 0.56 (petroleum ether : ethyl acetate 20:1). 1H NMR
(400 MHz, CDCl3) δ = 7.73 – 7.62 (m, 4H), 7.60 – 7.31 (m, 9H). 13C NMR (100 MHz,
CDCl3) δ 140.04, 138.19, 138.06, 136.36, 134.13, 130.05, 129.58, 128.99, 128.30,
127.79, 127.58, 127.37, 127.00, 119.32. IR (neat) v 2110, 1478, 1295, 1270, 696 cm-1.
HRMS (ESI) ([M+H]+) Calcd. for C18H13N3 272.1182, found 272.1178.
2-azido-4-methoxy-1,1'-biphenyl (1d). The general procedure was followed using
0.606 g of 2-bromo-5-methoxyaniline (3.0 mmol). Purification of the reaction mixture
using column chromatography (petroleum ether : dichloromethane 20:1) afforded the
product 1d (648.0 mg, 96%), Rf = 0.24 (petroleum ether : dichloromethane 20:1). 1H
NMR (400 MHz, CDCl3) δ = 7.43 (d, J = 4.4, 4H), 7.36 (dd, J = 8.4, 4.4, 1H), 7.28 (d,
J = 8.4, 1H), 6.81 – 6.75 (m, 2H), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 160.09,
138.09, 138.06, 132.16, 129.59, 128.22, 127.27, 126.67, 110.69, 104.66, 55.66. IR (neat)
v 2110, 1511, 1486, 1300, 1227, 763 cm-1.
6-azido-[1,1'-biphenyl]-3-carbonitrile (1e). The general procedure was followed
using 0.591 g of ethyl 4-amino-3-bromobenzonitrile (3.0 mmol). Purification of the
reaction mixture using column chromatography (petroleum ether : ethyl acetate 20:1)
afforded the product 1e (346.0 mg, 52%), Rf = 0.32 (petroleum ether : ethyl acetate
20:1). 1H NMR (400 MHz, CDCl3) δ = 7.67 (dd, J = 8.4, 2.0, 1H), 7.59 (d, J = 1.6, 1H),
7.51 – 7.39 (m, 5H), 7.33 (d, J = 8.4, 1H). 13C NMR (100 MHz, CDCl3) δ 142.10,
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135.96, 134.93, 134.73, 133.88, 132.33, 129.32, 128.54, 128.50, 119.58, 108.46. IR
(neat) v 2227, 2119, 1482, 1300, 1159, 698 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for
C13H8N4 243.0641, found 243.0639.
ethyl 6-azido-[1,1'-biphenyl]-3-carboxylate (1f).[5] The general procedure was
followed using 0.732 g of ethyl 4-amino-3-bromobenzoate (3.0 mmol). Purification of
the reaction mixture using column chromatography (petroleum ether : ethyl acetate 30:1)
afforded the product 1f (681.0 mg, 85%), Rf = 0.66 (petroleum ether : ethyl acetate
20:1). 1H NMR (400 MHz, CDCl3) δ = 8.18 – 8.05 (m, 2H), 7.58 – 7.39 (m, 5H), 7.29
(d, J = 8.0, 1H), 4.42 (q, J = 7.2, 2H), 1.43 (t, J = 7.2, 3H). 13C NMR (100 MHz, CDCl3)
δ 165.75, 141.64, 137.26, 133.56, 132.60, 129.99, 129.44, 128.24, 127.92, 127.05,
118.63, 61.12, 14.36. IR (neat) v 2123, 1717, 1599, 1483, 1236, 1101, 698 cm-1.
1-(6-azido-[1,1'-biphenyl]-3-yl)ethanone (1g). The general procedure was followed
using 0.642 g of ethyl 1-(4-amino-3-bromophenyl)ethanone (3.0 mmol). Purification of
the reaction mixture using column chromatography (petroleum ether : ethyl acetate 10:1)
afforded the product 1g (702.0 mg, 67%), Rf = 0.23 (petroleum ether : ethyl acetate
25:1). 1H NMR (400 MHz, CDCl3) δ = 8.00 (d, J = 8.4, 1H), 7.95 (s, 1H), 7.50 – 7.37
(m, 5H), 7.32 (d, J = 8.4, 1H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 196.73,
142.05, 137.27, 133.81, 133.77, 131.68, 129.46, 128.88, 128.36, 128.08, 118.86, 26.61.
IR (neat) v 2114, 1681, 1594, 1356, 1296, 1323, 699 cm-1. HRMS (ESI) ([M+Na]+)
Calcd. for C14H11N3O 260.0794, found 260.0815.
6-azido-N-methyl-[1,1'-biphenyl]-3-carboxamide (1h).[6] The general procedure was
followed using 0.687 g of ethyl 4-amino-3-bromo-N-methylbenzamide (3.0 mmol).
Purification of the reaction mixture using column chromatography (petroleum ether :
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EtOAc gradient: 3:1-1:1) afforded the product 1h (454.0 mg, 60%), Rf = 0.35
(petroleum ether : ethyl acetate 1:1). 1H NMR (400 MHz, CDCl3) δ = 7.80 (dd, J = 8.4,
2.0, 1H), 7.76 (d, J = 2.0, 1H), 7.44–7.34 (m, 5H), 7.18 (d, J = 8.4, 1H), 7.12 (brs, 1H),
2.93 (d, J = 4.8, 3H). 13C NMR (100 MHz, CDCl3) δ 167.44, 140.08, 137.25, 133.51,
131.00, 130.01, 129.34, 128.20, 127.88, 127.53, 118.71, 26.88. IR (neat) v 3313, 2120,
1636, 1549, 1482, 1295, 698 cm-1. HRMS (ESI) ([M-H]-) Calcd. for C14H12N4O
251.0938, found 251.0933.
2-azido-5-fluoro-1,1'-biphenyl (1j).[2] The general procedure was followed using
0.570 g of 2-bromo-4-fluoroaniline (3.0 mmol). Purification of the reaction mixture
using column chromatography (petroleum ether : dichloromethane 40:1) afforded the
product 1j (186.0 mg, 29%), Rf = 0.51 (petroleum ether : dichloromethane 20:1). 1H
NMR (400 MHz, CDCl3) δ = 7.56 – 7.45 (m, 5H), 7.28 – 7.22 (m, 1H), 7.19 – 7.11 (m,
2H). 13C NMR (100 MHz, CDCl3) δ = 159.75 (d, JCF = 244.8), 137.11, 135.44 (d, JCF
= 7.6), 132.97 (d, JCF = 2.8), 129.34, 128.31, 128.07, 120.17 (d, JCF = 8.8), 117.94 (d,
JCF = 23.2), 115.42 (d, JCF = 23.2). 19F NMR (376 MHz, CDCl3) δ -117.53. IR (neat) v
2123, 1502, 1485, 1409, 1289, 1187, 697 cm-1.
2-azido-5-chloro-1,1'-biphenyl (1k).[3] The general procedure was followed using
0.619 g of 2-bromo-4-chloroaniline (3.0 mmol). Purification of the reaction mixture
using column chromatography(petroleum ether : ethyl acetate 30:1) afforded the
product 1k (523.0 mg, 76%), Rf = 0.78 (petroleum ether : ethyl acetate 20:1). 1H NMR
(400 MHz, CDCl3) δ = 7.56 – 7.43 (m, 5H), 7.43– 7.37 (m, 2H), 7.24 – 7.19 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 136.88, 135.80, 135.20, 131.08, 130.19, 129.34, 128.54,
128.30, 128.08, 120.06. IR (neat) v 2111, 1479, 1444, 1392, 1300, 697 cm-1.
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2-azido-5-bromo-1,1'-biphenyl (1l).[24] Purification of the reaction mixture using
column chromatography(petroleum ether : ethyl acetate 30:1) afforded the product 1l
(960.0 mg, 70%), Rf = 0.68 (petroleum ether : ethyl acetate 20:1). 1H NMR (400 MHz,
CDCl3) δ 7.54 – 7.39 (m, 7H), 7.15 (d, J = 8.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ
= 136.77, 136.40, 135.55, 133.97, 131.46, 129.31, 128.27, 128.07, 120.35, 117.76. IR
(neat) v 2104, 1477, 1445, 1387, 1298, 698 cm -1.
2-azido-5-iodo-1,1'-biphenyl (1m).[24] Purification of the reaction mixture using
column chromatography(petroleum ether : ethyl acetate 30:1) afforded the product 1l
(960.0 mg, 70%), Rf = 0.60 (petroleum ether : ethyl acetate 20:1). 1H NMR (400 MHz,
CDCl3) δ 7.70 – 7.64 (m, 2H), 7.46 – 7.37 (m, 5H), 7.00 (d, J = 8.2 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ = 139.87, 137.40, 137.23, 136.66, 135.85, 129.29, 128.25, 128.04,
120.63.
IR (neat) v 2098, 1474, 1444, 1380, 1296, 697 cm -1.
2-azido-1,1':4',1''-terphenyl (1n). The general procedure was followed using 0.516 g
of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using column
chromatography (petroleum ether : ethyl acetate 20:1) afforded the product 1n (447.0
mg, 55%), Rf = 0.58 (petroleum ether : ethyl acetate 20:1). 1H NMR (400 MHz, CDCl3)
δ = 7.78 – 7.64 (m, 4H), 7.58 (d, J = 7.6, 2H), 7.54 – 7.37 (m, 5H), 7.36 – 7.20 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 140.82, 140.51, 137.25, 137.20, 133.40, 131.33, 129.98,
128.91, 128.90, 127.50, 127.26, 127.01, 125.11, 118.88. IR (neat) v 2119, 1479, 1396,
1290, 835 cm-1. HRMS (ESI) ([M+H]+) Calcd. for C18H13N3 272.1182, found 272.1178.
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2-azido-4'-fluoro-1,1'-biphenyl (1o).[2] The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate 20:1) afforded the product 1o
(256.0 mg, 40%), Rf = 0.82 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz,
CDCl3) δ = 7.43 (ddd, J = 11.2, 7.2, 1.9, 3H), 7.33 (dd, J = 7.6, 1.6, 1H), 7.29 – 7.20
(m, 2H), 7.17 – 7.10 (m, 2H). 13C NMR (100 MHz, CDCl3) δ = 162.43 (d, JCF = 247.0),
137.23, 134.18 (d, JCF = 3.2), 132.80, 131.28 (d, JCF = 1.2), 131.19, 128.96, 125.10,
118.89, 115.20 (d, JCF = 21.6). 19F NMR (376 MHz, CDCl3) δ -114.77. IR (neat) v 2126,
1513, 1482, 1291, 1231, 1159, 752 cm-1.
2-azido-4'-methoxy-1,1'-biphenyl (1p).[2] The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate gradient: 20:1-10:1-3:1)
afforded the product 1p (608.0 mg, 90%), Rf = 0.58 (petroleum ether : ethyl acetate
20:1). 1H NMR (400 MHz, CDCl3) δ = 7.52 – 7.34 (m, 4H), 7.34 – 7.19 (m, 3H), 7.09
– 6.98 (m, 2H), 3.90 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.15, 137.07, 133.48,
131.19, 130.64, 130.54, 128.36, 124.98, 118.78, 113.66, 55.30. IR (neat) v 2124, 1611,
1516, 1483, 1245, 831 cm-1.
2-azido-2'-methoxy-1,1'-biphenyl (1q).[7] The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate 20:1) afforded the product 1q
(432.0 mg, 64%), Rf = 0.64 (petroleum ether : ethyl acetate 30:1). 1H NMR (400 MHz,
CDCl3) δ = 7.48 (td, J = 8.2, 1.6, 2H), 7.39 (dd, J = 7.6, 1.4, 1H), 7.36 – 7.27 (m, 3H),
7.17 – 7.06 (m, 2H), 3.88 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 156.83, 138.30,
131.88, 131.31, 130.91, 129.42, 128.69, 127.29, 124.59, 120.42, 118.64, 111.00, 55.64.
IR (neat) v 2121, 1479, 1296, 1232, 655 cm-1.
Page 21
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2-azido-3'-methoxy-1,1'-biphenyl (1r).[2] The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate 30:1) afforded the product 1r
(540.0 mg, 80%), Rf = 0.61 (petroleum ether : ethyl acetate 30:1). 1H NMR (400 MHz,
CDCl3) δ = 7.50 – 7.42 (m, 3H), 7.37 – 7.26 (m, 2H), 7.18 – 7.11 (m, 2H), 7.06 – 7.01
(m, 1H), 3.93 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.32, 139.50, 137.10, 133.63,
131.18, 129.11, 128.77, 124.89, 121.90, 118.79, 115.30, 112.96, 55.20. IR (neat) v 2122,
1475, 1419, 1293, 1210, 697 cm-1.
2-azido-3'-methyl-1,1'-biphenyl (1s).[2] The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate 40:1) afforded the product 1s
(421.0 mg, 67%), Rf = 0.72 (30:1petroleum ether : ethyl acetate). 1H NMR (400 MHz,
CDCl3) δ = 7.49 – 7.39 (m, 3H), 7.38 – 7.25 (m, 5H), 2.51 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 138.19, 137.78, 137.18, 134.04, 131.31, 130.21, 128.66, 128.39, 128.09,
126.62, 124.94, 118.78, 21.57. IR (neat) v 2123, 1496, 1477, 1296, 1148, 787, 701 cm-
1.
2-azido-3',5'-dimethyl-1,1'-biphenyl (1t). The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate 50:1) afforded the product 1t
(529.0 mg, 79%), Rf = 0.75 (petroleum ether : ethyl acetate 30:1). 1H NMR (400 MHz,
CDCl3) δ = 7.52 – 7.43 (m, 2H), 7.38 – 7.34 (m, 1H), 7.34 – 7.28 (m, 1H), 7.21 (s, 2H),
7.16 (s, 1H), 2.53 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 138.16, 137.63, 137.15,
134.18, 131.27, 129.31, 128.54, 127.31, 124.84, 118.69, 21.42. IR (neat) v 2923, 2122,
1602, 1574, 1484, 1295, 834 cm-1.
Page 22
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ethyl 2'-azido-[1,1'-biphenyl]-4-carboxylate (1u).[2] The general procedure was
followed using 0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction
mixture using column chromatography (petroleum ether : ethyl acetate 20:1) afforded
the product 1u (465.0 mg, 58%), Rf = 0.45 (petroleum ether : ethyl acetate 20:1). 1H
NMR (400 MHz, CDCl3) δ = 8.13 (d, J = 8.0, 2H), 7.54 (d, J = 8.0, 2H), 7.43 (t, J =
7.6, 1H), 7.35 (d, J = 7.6, 1H), 7.32 – 7.16 (m, 2H), 4.42 (q, J = 7.2, 2H), 1.43 (t, J =
7.2, 3H). 13C NMR (100 MHz, CDCl3) δ 166.38, 142.69, 137.21, 132.65, 131.11,
129.49, 129.37, 125.07, 118.88, 61.00, 14.40. IR (neat) v 2981, 2126, 1715, 1610,
1482,1276, 750 cm-1.
2-azido-2',4-dimethoxy-1,1'-biphenyl (1w). The general procedure was followed
using 0.606 g of ethyl2-bromo-5-methoxyaniline (3.0 mmol). Purification of the
reaction mixture using column chromatography (petroleum ether : ethyl acetate 40:1)
afforded the product 1w (203.0 mg, 30%), Rf = 0.35 (20:1petroleum ether : ethyl
acetate). 1H NMR (400 MHz, CDCl3) δ = 7.39 – 7.33 (m, 1H), 7.22 – 7.16 (m, 2H),
7.05 – 6.95 (m, 2H), 6.78 – 6.72 (m, 2H), 3.87 (s, 3H), 3.80 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 160.02, 157.06, 139.19, 132.67, 131.68, 129.28, 127.02, 123.39, 120.46,
111.01, 110.39, 104.58, 55.79, 55.60. IR (neat) v 2109, 1512, 1486, 1321, 1295, 1226
cm-1.
2'-azido-5'-methyl-1,1':3',1''-terphenyl (1x).[4] The general procedure was followed
Page 23
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using 0.794 g of 2,6-dibromo-4-methylaniline (3.0 mmol). Purification of the reaction
mixture using column chromatography (petroleum ether : dichloromethane 20:1)
afforded the product 1x (104.0 mg, 12%), Rf = 0.21 (petroleum ether : dichloromethane
20:1). 1H NMR (400 MHz, CDCl3) δ = 7.62 – 7.39 (m, 10H), 7.23 – 7.15 (m, 2H), 2.45
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 138.72, 136.51, 135.36, 132.07, 131.21, 129.48,
128.45, 127.72, 20.93. IR (neat) v 2923, 2114, 1457, 1420, 1300, 1242, 1158, 698 cm-
1.
2'-azido-4,4''-dimethoxy-1,1':3',1''-terphenyl (1y). The general procedure was
followed using 1.255 g of ethyl 2,6-dibromoaniline (5.0 mmol). Purification of the
reaction mixture using column chromatography (petroleum ether : ethyl acetate 20:1)
afforded the product 1y (222.0 mg, 14%), Rf = 0.45 (petroleum ether : ethyl acetate
10:1). 1H NMR (400 MHz, CDCl3) δ = 7.49 (d, J = 8.7, 4H), 7.34 – 7.27 (m, 3H), 7.04
(d, J = 8.7, 4H), 3.89 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 159.25, 136.28, 134.79,
130.97, 130.62, 130.19, 125.56, 113.89, 55.36. IR (neat) v 2121, 1564, 1488, 1261,
1031, 801, 667 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C20H17N3O2 354.1213, found
354.1230.
4-(2-azidophenyl)dibenzo[b,d]furan (1z). The general procedure was followed using
0.516 g of ethyl 2-bromoaniline (3.0 mmol). Purification of the reaction mixture using
column chromatography (petroleum ether : ethyl acetate 30:1) afforded the product 1z
(513.0 mg, 60%), Rf = 0.55 (petroleum ether : ethyl acetate 20:1). 1H NMR (400 MHz,
CDCl3) δ = 8.09 – 8.01 (m, 2H), 7.66 – 7.59 (m, 2H), 7.57 – 7.46 (m, 4H), 7.45 – 7.38
(m, 2H), 7.35 (td, J = 7.6, 0.9, 1H). 13C NMR (100 MHz, CDCl3) δ 156.29, 153.69,
138.35, 132.03, 129.52, 128.66, 128.55, 127.32, 124.93, 124.53, 124.35, 122.85,
122.67, 120.81, 120.38, 118.99, 111.92. IR (neat) v 2121, 1449, 1410, 1296, 1191, 667
cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C18H11N3O 308.0794, found 308.0806.
Page 24
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2-azido-2'-methoxy-5-methyl-1,1'-biphenyl (3a).[3] The general procedure was
followed using 0.558 g of 2-bromo-4-methylaniline (3.0 mmol). Purification of the
reaction mixture using column chromatography (petroleum ether : dichloromethane
gradient: 10:1-5:1) afforded the product 3a (480.0 mg, 67%), Rf = 0.12 (petroleum
ether : dichloromethane 10:1). 1H NMR (400 MHz, CDCl3) δ = 7.48 (t, J = 7.6, 1H),
7.33 – 7.18 (m, 4H), 7.17 – 7.04 (m, 2H), 3.90 (s, 3H), 2.47 (s, 3H). 13C NMR (100
MHz, CDCl3) δ = 156.78, 135.53, 134.27, 132.38, 131.23, 130.64, 129.38, 129.34,
127.37, 120.40, 118.50, 110.88, 55.64, 20.88. IR (neat) v 2923, 2119, 1501, 1486, 1298,
1283, 1236, 808 cm-1.
methyl 6-azido-4'-methoxy-[1,1'-biphenyl]-3-carboxylate (3b). The general
procedure was followed using 0.690 g of methyl 4-amino-3-bromobenzoate (3.0 mmol).
Purification of the reaction mixture using column chromatography (petroleum ether :
ethyl acetate 20:1) afforded the product 3b (399.0 mg, 47%), Rf = 0.28 (petroleum ether :
ethyl acetate 20:1). 1H NMR (400 MHz, CDCl3) δ = 8.05 – 7.98 (m, 2H), 7.40 (d, J =
8.8, 2H), 7.25 (d, J = 9.2, 1H), 6.98 (d, J = 8.8, 2H), 3.92 (s, 3H), 3.85 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 166.23, 159.36, 141.61, 133.23, 132.47, 130.56, 129.52,
129.43, 126.61, 118.60, 113.67, 55.23, 52.12. IR (neat) v 2119, 1719, 1515, 1435, 1294,
1242, 1121 cm-1. HRMS (ESI) ([M+H]+) Calcd. for C15H13N3O3 284.1030, found
284.1037.
Page 25
S25
methyl 6-azido-4-methoxy-[1,1'-biphenyl]-3-carboxylate (3c). The general
procedure was followed using 0.780 g of methyl 4-amino-5-bromo-2-methoxybenzoate
(3.0 mmol). Purification of the reaction mixture using column chromatography
(petroleum ether : ethyl acetate 20:1) afforded the product 3c (255.0 mg, 30%), Rf =
0.13 (petroleum ether : ethyl acetate 20:1). 1H NMR (400 MHz, CDCl3) δ = 7.88 (s,
1H), 7.47 – 7.32 (m, 5H), 6.77 (s, 1H), 3.97 (s, 3H), 3.88 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 165.54, 159.73, 141.89, 136.83, 134.90, 129.38, 128.16, 127.50, 125.84,
116.36, 102.29, 56.26, 52.00. IR (neat) v 2113, 1729, 1485, 1434, 1314, 1233 cm-1.
HRMS (ESI) ([M+H]+) Calcd. for C15H13N3O3 284.1030, found 284.1034.
methyl 6-azido-4,4'-dimethoxy-[1,1'-biphenyl]-3-carboxylate (3d). The general
procedure was followed using 0.780 g of methyl 4-amino-5-bromo-2-methoxybenzoate
(3.0 mmol). Purification of the reaction mixture using column chromatography
(petroleum ether : ethyl acetate gradient: 20:1-10:1-3:1) afforded the product 3d (273.0
mg, 29%), Rf = 0.13 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3)
δ = 7.83 (s, 1H), 7.38 – 7.29 (m, 2H), 6.96 – 6.89 (m, 2H), 6.74 (s, 1H), 3.96 (s, 3H),
3.87 (s, 3H), 3.82 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 165.62, 159.44, 159.04,
141.81, 134.73, 130.51, 129.17, 125.58, 116.35, 113.62, 102.30, 56.27, 55.23, 51.99.
IR (neat) v 2112, 1728, 1497, 1317, 1232, 832 cm-1. HRMS (ESI) ([M+H]+) Calcd. for
C16H15N3O4 314.1135, found 314.1132.
Page 26
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2. Preparation of biaryl azides 1i, 3e
Unless otherwise noted, the biaryl azides were synthesized from the 4-amino-3-
bromophenylmethanol[8] reduced from methyl 4-amino-3-bromobenzoate without
purification and substituted phenylboronic acid using Suzuki reactions.[1] The resulting
biaryl amines were converted to correspongding biaryl azides without purification
using traditional diazotization reaction conditions. After purification, the final azides
were obtained by oxidative process. Yields were not optimized.
A solution of 4-amino-3-bromo-benzoic acid methyl ester (3 mmol, 1.0 equiv 690.0 mg)
in THF (4 mL) was added slowly at –10 °C to a suspension of LiAlH4 (6 mmol, 2.0
equiv, 227.0 mg) in THF (6 mL). After warming to 0 °C and stirring for 24 hours at this
temperature the reaction mixture is quenched with aqueous Na2SO4, diluted with
dichloromethane (20 mL) and the aqueous phase was extracted with an additional 3 ×
30 mL of CH2Cl2, and the combined organic phases were washed 2 × 50 mL of water.
The organic phase was dried over Na2SO4 and filtered. The filtrate was concentrated in
vacuo to afford an oil. This crude mixture was used for the next step without any further
purification.
In a 50 mL round bottom flask, substituted phenylboronic acid (9 mmol, 3.0 equiv),
Na2CO3 (6 mmol, 2.0 equiv, 635.9 mg), and Pd(OAc)2 (0.06 mmol, 0.02 equiv, 13.5 mg)
were then dissolved in 9 mL of ethylene glycol, 9 mL of H2O. The amine made by last
step was added, and the resulting mixture was heated to 80 ˚C for 24 hours. After
cooling, the biphasic solution was diluted with 50 mL of water and 30 mL of CH2Cl2
and separated. The aqueous phase was extracted with an additional 3 × 30 mL of CH2Cl2,
and the combined organic phases were washed 2 × 50 mL of water. The organic phase
was dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford an
oil. This crude mixture was used for the next step without any further purification.
In a 100 mL of round bottom flask, the crude biaryl amine (1.0 equiv) was dissolved in
HOAc and H2O (2:1 v/v, 0.2 M) and chilled in an ice bath. NaNO2 (1.4 equiv, 289.8
mg) was added slowly, then the resulting mixture was stirred at 0 °C for 2 hour. NaN3
(1.5 equiv, 295.2 mg) was then added slowly, the resulting mixture was warmed up to
ambient temperature, and stirred overnight. The solution was then diluted with 20 mL
of water and 20 mL of CH2Cl2, and basified by slow addition of K2CO3 until the pH of
Page 27
S27
the mixture was 8. The phases were separated and the aqueous phase was extracted with
an additional 3 × 30 mL of CH2Cl2. The combined organic phase were dried over
Na2SO4 and filtered. The filtrate was concentrated in vacuo and crude was purified by
silica gel column using petroleum ether and ethyl acetate as eluent.
In an oven dried schlenk tube, the substituted (6-azido-[1,1'-biphenyl]-3-yl)methanol
(0.5 mmol, 1.0 equiv), 2-iodoxybenzoic acid(IBX) (1.2 equiv) and a stir bar were taken
and the ethyl acetate (2.0 ml) was added. The reaction mixture was heated to 80 ˚C for
24 hours. After cooling, the biphasic solution was filtered and the filtrate was
concentrated in vacuo and crude was purified by silica gel column using petroleum
ether and ethyl acetate as eluent.
(6-azido-[1,1'-biphenyl]-3-yl)methanol (1i′). The general procedure was followed
using 0.69 g of methyl 4-amino-3-bromobenzoate (3.0 mmol). Purification of the
reaction mixture using column chromatography (petroleum ether : ethyl acetate
gradient: 8:1-3:1) afforded the product 1i’ in yield 45%, Rf = 0.28 (petroleum ether :
ethyl acetate 3:1). 1H NMR (400 MHz, CDCl3) δ = 7.52 – 7.32 (m, 7H), 7.28 – 7.21 (m,
1H), 4.71 (s, 2H), 1.97 (brs, 1H). 13C NMR (100 MHz, CDCl3) δ 137.94, 137.59, 136.35,
133.74, 129.93, 129.41, 128.19, 127.68, 127.33, 118.93, 64.44. IR (neat) v 3319, 2119,
1485, 1296, 1013, 698 cm-1. HRMS (APCI) ([M-H]-) Calcd. for C13H11N3O 224.0829,
found 224.0837.
(6-azido-4'-methoxy-[1,1'-biphenyl]-3-yl)methanol (3e′).The general procedure was
followed using 0.69 g of methyl 4-amino-3-bromobenzoate (3.0 mmol). Purification of
the reaction mixture using column chromatography (petroleum ether : ethyl acetate
gradient: 10:1-3:1) afforded the product 3e’ in yield 12%, Rf = 0.26 (petroleum ether :
ethyl acetate 3:1). 1H NMR (400 MHz, CDCl3) δ = 7.43 – 7.27 (m, 4H), 7.20 (d, J =8.0,
1H), 7.00 – 6.94 (m, 2H), 4.66 (s, 2H), 3.85 (s, 3H), 2.40 (brs, 1H). 13C NMR (100 MHz,
CDCl3) δ 159.14, 137.64, 136.34, 133.45, 130.59, 130.34, 129.87, 127.00, 118.94,
113.68, 64.61, 55.36. IR (neat) v 3320, 2118, 1608, 1560, 1294, 1029, 831 cm-1. HRMS
(ESI) ([M+Na]+) Calcd. for C14H13N3O2 278.0900, found 278.0912.
Page 28
S28
6-azido-[1,1'-biphenyl]-3-carbaldehyde (1i). The general procedure was followed
using 0.11 g of methyl (6-azido-[1,1'-biphenyl]-3-yl)methanol (0.5 mmol). Purification
of the reaction mixture using column chromatography (petroleum ether : ethyl acetate
gradient: 20:1-10:1) afforded the product 1i in yield 89%, Rf = 0.28 (petroleum ether :
ethyl acetate 3:1). 1H NMR (400 MHz, CDCl3) δ = 7.52 – 7.32 (m, 7H), 7.28 – 7.21 (m,
1H), 4.71 (s, 2H), 1.97 (brs, 1H). 13C NMR (100 MHz, CDCl3) δ 137.94, 137.59, 136.35,
133.74, 129.93, 129.41, 128.19, 127.68, 127.33, 118.93, 64.44. IR (neat) v 2121, 1697,
1595, 1479, 1293, 1177, 698 cm-1. HRMS (APCI) ([M-H]-) Calcd. for C13H9N3O
222.0673, found 222.0688.
6-azido-4'-methoxy-[1,1'-biphenyl]-3-carbaldehyde (3e).The general procedure was
followed using 0.1 g of (6-azido-4'-methoxy-[1,1'-biphenyl]-3-yl)methanol (0.45
mmol). Purification of the reaction mixture using column chromatography (petroleum
ether : ethyl acetate gradient: 20:1-10:1) afforded the product 3e in yield 73%, Rf = 0.18
(petroleum ether: ethyl acetate 20:1). 1H NMR (400 MHz, CDCl3) δ = 9.98 (s, 1H), 7.92
– 7.82 (m, 2H), 7.46 – 7.35 (m, 3H), 7.04 – 6.94 (m, 2H), 3.87 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 190.94, 159.68, 143.41, 134.13, 133.29, 132.89, 130.71, 129.64, 129.22,
119.38, 113.94, 55.48. IR (neat) v 2118, 1689, 1594, 1488, 1179 cm-1. HRMS (ESI)
([M+Na]+) Calcd. for C14H11N3O2 276.0743, found 276.0734.
Page 29
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3. Preparation of biaryl azide 1v
Unless otherwise noted, the biaryl azide was synthesized from the 2-bromoanilines and
substituted phenylboronic acid using Suzuki reactions. The resulting biaryl amines after
reduced by LiAlH4 were converted to the biaryl azides without purification using
traditional diazotization reaction conditions. After purification, the final azides were
obtained by oxidative process. Yields were not optimized.
In a 50 mL round bottom flask, 4-(methoxycarbonyl)phenyl boronic acid (9 mmol, 3
equiv, 1.6920 g), Na2CO3 (6 mmol, 2.0 equiv, 635.9 mg), and Pd(OAc)2 (0.06 mmol,
0.02 equiv, 13.5 mg) were then dissolved in 9 mL of ethylene glycol, 9 mL of H2O. The
2-bromoanilines (3mmol, 1.0 equiv, 516.1 mg) was added, and the resulting mixture
was heated to 80 ˚C for 24 hours. After cooling, the biphasic solution was diluted with
50 mL of water and 30 mL of CH2Cl2 and separated. The aqueous phase was extracted
with an additional 3 × 30 mL of CH2Cl2, and the combined organic phases were washed
2 × 50 mL of water. The organic phase was dried over Na2SO4 and filtered. The filtrate
was concentrated in vacuo to afford an oil. This crude mixture was used for the next
step without any further purification.
A solution of the crude mixture made by last step in THF (4 mL) was added slowly at
–10 °C to a suspension of LiAlH4 (6 mmol, 2.0 equiv, 227.7 mg) in THF (6 mL). After
warming to 0 °C and stirring for 24 hours at this temperature the reaction mixture is
quenched with aqueous Na2SO4, diluted with dichloromethane (20 mL) and the aqueous
phase was extracted with an additional 3 × 30 mL of CH2Cl2, and the combined organic
phases were washed 2 × 50 mL of water. The organic phase was dried over Na2SO4 and
filtered. The filtrate was concentrated in vacuo to afford an oil. This crude mixture was
used for the next step without any further purification.
In a 100 mL of round bottom flask, the crude biaryl amine (1.0 equiv) was dissolved in
HOAc and H2O (2:1 v/v, 0.2 M) and chilled in an ice bath. NaNO2 (1.4 equiv, 289.8
mg) was added slowly, then the resulting mixture was stirred at 0 °C for 2 hours. NaN3
(1.5 equiv, 295.2 mg) was then added slowly, the resulting mixture was warmed up to
ambient temperature, and stirred overnight. The solution was then diluted with 20 mL
of water and 20 mL of CH2Cl2, and basified by slow addition of K2CO3 until the pH of
the mixture was 8. The phases were separated and the aqueous phase was extracted with
an additional 3 × 30 mL of CH2Cl2. The combined organic phase were dried over
Page 30
S30
Na2SO4 and filtered. The filtrate was concentrated in vacuo and crude was purified by
silica gel column using petroleum ether and ethyl acetate as eluent (petroleum ether :
ethyl acetate 5:1) directly to give the desired product 1v′ in 57% yield. Rf = 0.32
(petroleum ether : ethyl acetate 3:1). 1H NMR (400 MHz, CDCl3) δ = 7.54 – 7.33 (m,
6H), 7.32 – 7.19 (m, 2H), 4.75 (s, 2H), 2.45 (brs, 1H). 13C NMR (100 MHz, CDCl3) δ
140.24, 137.50, 137.14, 133.44, 131.24, 129.68, 128.81, 126.80, 125.01, 118.80, 65.00.
IR (neat) v 3319, 2123, 1483, 1442, 1293, 751 cm-1.
In an oven dried schlenk tube, the (2'-azido-[1,1'-biphenyl]-4-yl)methanol (0.7 mmol,
1.0 equiv), 2-iodoxybenzoic acid(IBX) (1.2 equiv, 235.2 mg) and a stir bar were taken
and the ethyl acetate (2.0 ml) was added. The reaction mixture was heated to 80 ˚C for
24 hours. After cooling, the biphasic solution was filtered and the filtrate was
concentrated in vacuo and crude was purified by silica gel column using petroleum
ether and ethyl acetate as eluent (petroleum ether : ethyl acetate 20:1) directly to give
the desired product 1v in 51% yield, Rf = 0.45 (petroleum ether : ethyl acetate 10:1).
1H NMR (400 MHz, CDCl3) δ = 10.07 (s, 1H), 7.95 (d, J = 8.4, 2H), 7.63 (d, J = 8.4,
2H), 7.46 (td, J = 8.0, 1.6, 1H), 7.36 (dd, J = 7.6, 1.4, 1H), 7.33 – 7.20 (m, 2H). 13C
NMR (100 MHz, CDCl3) δ 192.02, 144.51, 137.36, 135.40, 132.38, 131.19, 130.31,
129.78, 129.62, 125.24, 119.02. IR (neat) v 2125, 1701, 1481, 1296, 1233, 838, 735 cm-
1.
Page 31
S31
4. Preparation of biaryl azide 1a-D[9]
In a 50 mL round bottom flask, (2-bromophenyl)boronic acid (4 mmol, 3 equiv, 803.3
mg), Na2CO3 (16 mmol, 4.0 equiv, 1.6958 g), and Pd(OAc)2 (1.2 mmol, 0.2 equiv, 269.1
mg) were then dissolved in 9 mL of ethylene glycol, 9 mL of H2O. 2-iodoaniline (12
mmol, 3.0 equiv, 2.6282 g) was added, and the resulting mixture was heated to 90 ˚C
for 48 hours. After cooling, the biphasic solution was diluted with 50 mL of water and
30 mL of CH2Cl2 and separated. The aqueous phase was extracted with an additional 3
× 30 mL of CH2Cl2, and the combined organic phases were washed 2 × 50 mL of water.
The organic phase was dried over Na2SO4 and filtered. The filtrate was concentrated in
vacuo and crude was purified by silica gel column using column chromatography
(petroleum ether : ethyl acetate 20:1) afforded the product 1a-D′′ (0.248 g, 25%), TLC
Rf = 0.13 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 7.72
(d, J = 8.0, 1H), 7.44 – 7.33 (m, 2H), 7.31 – 7.18 (m, 2H), 7.06 (dd, J = 7.5, 1.4, 1H),
6.92 – 6.78 (m, 2H), 3.54 (brs, 2H). 13C NMR (100 MHz, CDCl3) δ 143.61, 140.06,
133.17, 131.88, 130.31, 129.32, 129.19, 127.92, 127.17, 124.33, 118.33, 115.59.
Aniline 1a-D′′ (0.65 mmol, 1.0 equiv, 161.3 mg) was dissolved in dry THF (10 mL)
and the solution was cooled to -78 °C under nitrogen. A solution of n-BuLi (2.5 M in
hexane, 1.56 mL, 3.9 mmol) was added dropwise to the reaction mixture. After one
hour at -78 °C, CD3OD (1.5 mL) was added and then quenched with demin. water. The
aqueous fraction was extracted twice with diethyl ether (10 mL). The organic phases
were dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford
the crude product. Purification by column chromatography on silica gel (petroleum
ether : ethyl acetate 10:1) afforded the corresponding product 1a-D′ (109.0 mg, 99%),
H NMR showed 60 % deuterium incorporation. Rf = 0.45 (petroleum ether : ethyl
acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 7.59 – 7.48 (m, 3H), 7.41 (t, J = 6.5, 1H),
7.27 – 7.16 (m, 2H), 6.95 – 6.77 (m, 2H), 3.91 (brs, 2H). IR (KBr) v 1614, 1541, 1434,
1261, 1008, 748, 667 cm-1. HRMS (ESI) ([M+H]+) Calcd. for C12H10DN 171.0721,
found 171.1023.
In a 100 mL of round bottom flask, the crude 4-amino-3-bromobenzoate (0.7 mmol)
was dissolved in HOAc and H2O (2:1 v/v, 0.2 M) and chilled in an ice bath. NaNO2
(1.4 equiv, 62.3 mg) was added slowly, then the resulting mixture was stirred at 0 °C
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for 2 hours. NaN3 (1.5 equiv, 68.9 mg) was then added slowly, the resulting mixture
was warmed up to ambient temperature, and stirred overnight. The solution was then
diluted with 20 mL of water and 20 mL of CH2Cl2, and basified by slow addition of
K2CO3 until the pH of the mixture was 8. The phases were separated and the aqueous
phase was extracted with an additional 3 × 30 mL of CH2Cl2. The combined organic
phase were dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and
crude was purified by silica gel column using column chromatography (petroleum
ether : ethyl acetate 30:1) afforded the product 1a-D (116.0 mg, 84%), Rf = 0.78
(petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 7.56 – 7.38 (m,
6H), 7.35 – 7.23 (m, 2H). IR (neat) v 2124, 1579, 1431, 1299, 1009, 750, 657 cm-1.
HRMS (ESI) ([M+H]+) Calcd. for C12H8DN3 197.0937, found 197.0954.
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5. Preparation of biaryl azide 1aa[3]
To a dry 100 mL round bottom flask equipped with a stir bar were added 2,6-
dibromoaniline (6 mmol, 1.0 equiv, 1.5054 g), (4-(ethoxycarbonyl)phenyl)boronic acid
(7.20 mmol, 1.2 equiv, 1.3967 g), K2CO3 (24 mmol, 4.0 equiv, 3.3170 g), and Pd(PPh3)4
(0.60 mmol, 0.1 equiv, 693.3 mg) under N2 atmosphere. Toluene (36 mL), 24 mL of
H2O, and 12 mL of EtOH were added and the resulting mixture was heated to 95 ˚C for
16 hours. After cooling, the biphasic solution was diluted with 100 mL of saturated
aqueous NH4Cl and 100 mL of CH2Cl2 and separated. The organic phase was washed
1 × 100 mL of water and 1 × 100 mL of saturated aqueous NaHCO3. The organic phase
was dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford a
brown oil. Purification of the reaction mixture using column chromatography
(petroleum ether : ethyl acetate 20:1) afforded the product 1aa′ (1.340 g, 70%), Rf =
0.42 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.15 – 8.07
(m, 2H), 7.58 – 7.47 (m, 2H), 7.43 (d, J = 8.0, 1H), 7.04 (d, J = 7.5, 1H), 6.68 (t, J =
7.8, 1H), 4.40 (q, J = 7.1, 2H), 4.21 (brs, 2H), 1.42 (t, J = 7.1, 3H). 13C NMR (100 MHz,
CDCl3) δ 166.28, 143.75, 141.31, 132.42, 130.26, 129.74, 129.43, 129.04, 127.50,
119.04, 110.06, 61.16, 14.45. IR (neat) v 1714, 1608, 1540, 1452, 1263, 1100, 667 cm-
1. HRMS (ESI) ([M+H]+) Calcd. for C15H14BrNO2 320.0281, found 320.0286.
In a 50 mL round bottom flask, (4-methoxyphenyl)boronic acid (4.5 mmol, 3 equiv,
873.0 mg), Na2CO3 (6 mmol, 2.0 equiv, 635.9 mg), and Pd(OAc)2 (0.06 mmol, 0.02
equiv, 13.5 mg) were then dissolved in 9 mL of ethylene glycol, 9 mL of H2O. Aniline
1aa′ (1.5 mmol, 1.0 equiv, 480.3 mg) was added, and the resulting mixture was heated
to 80 ˚C for 24 hours. After cooling, the biphasic solution was diluted with 50 mL of
water and 30 mL of CH2Cl2 and separated. The aqueous phase was extracted with an
additional 3 × 30 mL of CH2Cl2, and the combined organic phases were washed 2 × 50
mL of water. The organic phase was dried over Na2SO4 and filtered. The filtrate was
concentrated in vacuo to afford an oil. This crude mixture was used for the next step
without any further purification.
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In a 100 mL of round bottom flask, the crude biaryl amine (1.0 equiv) was dissolved in
HOAc and H2O (2:1 v/v, 0.2 M) and chilled in an ice bath. NaNO2 (1.4 equiv, 144.9
mg) was added slowly, then the resulting mixture was stirred at 0 °C for 2 hours. NaN3
(1.5 equiv, 147.6 mg) was then added slowly, the resulting mixture was warmed up to
ambient temperature, and stirred overnight. The solution was then diluted with 20 mL
of water and 20 mL of CH2Cl2, and basified by slow addition of K2CO3 until the pH of
the mixture was 8. The phases were separated and the aqueous phase was extracted with
an additional 3 × 30 mL of CH2Cl2. The combined organic phase were dried over
Na2SO4 and filtered. The filtrate was concentrated in vacuo and crude was purified by
silica gel column using column chromatography (petroleum ether : ethyl acetate 20:1)
afforded the product 1aa (222.0 mg, 14%), Rf = 0.45 (petroleum ether : ethyl acetate
10:1). 1H NMR (400 MHz, CDCl3) δ = 7.49 (d, J = 8.7, 4H), 7.34 – 7.27 (m, 3H), 7.04
(d, J = 8.7, 4H), 3.89 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 159.25, 136.28, 134.79,
130.97, 130.62, 130.19, 125.56, 113.89, 55.36. IR (neat) v 2121, 1564, 1488, 1261,
1031, 801, 667 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C20H17N3O2 354.1213, found
354.1230.
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Ⅱ Experimental Procedure for for Synthesis of Carbazoles
1, General procedure
Corresponding azide (0.15 mmol), silica gel 15.0 mg, H2O (1.5 ml) and Acetone (1.5
ml) were added to a 15 ml glass vial equipped with a stirring bar. Then the solution was
stirred at a distance of ~1 cm from a 23 w fluorescent lamp at room temperature about
48 hours or 4 days. The biphasic solution was diluted with 5 mL of water and 5 mL of
CH2Cl2 and separated. The aqueous phase was extracted with an additional 3 × 10 mL
of CH2Cl2, and the combined organic phases were washed 2 × 5 mL of water. The
organic phase was dried over Na2SO4 and filtered. The organic phase was dried over
Na2SO4 and filtered. The crude product was purified by flash chromatography on silica
gel (petroleum ether : ethyl acetate gradient: 30:1-3:1) directly to give the desired
product.
2, Large scale reaction
A spiral quartz tube (8 round, inner diameter: 8 mm) was made. A 40 W white LED
corn-light was hanged at the middle of the circle (the light is about 1.5 cm far to quartz
tubes). The whole facility was drove by an 8 W chemical pump.
0.585 g (3.0 mmol) of 2-azido biphenyl 1a, 0.3 g silica gel, 20 mL water and 20 mL of
acetone was added in a 150 mL conical flask, stir evenly and transform to the spiral
quartz tube. Additional 15 mL of water and 15 mL of acetone was used to wash the
flask and was then transformed to spiral quartz tube. The mixture was kept flowing for
72 hours with the light irradiation. The reaction mixture was extracted by 30 mL ethyl
acetate. The organic phase was washed by brine, dried over Na2SO4 and concentrated
in vacuo to afford yellow solid. The conversion of the reaction was 69% based on 1H
NMR of reaction mixture. The obtained solid was washed with 10 mL n-hexane for
three times. The remained solid was desired product 2a (320.6 mg, 64%, pure based on 1H NMR). The obtained n-hexane solution was concentrated in vacuo, 0.146 g
(containing 10% product 2a) of azide 1a was recycled (25% recovered) as a yellow
solid.
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Ⅵ. Spectroscopic Data of Carbazoles Obtained in this Study
Yield of (2a)[10]:20.1 mg, 80 %, white solid, M.p.=245℃, Rf = 0.36 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.27 (brs, 1H), 8.11 (d, J = 8.0,
2H), 7.48 (d, J = 8.0, 2H), 7.38 (t, J = 7.6, 2H), 7.15 (t, J = 7.6, 2H). 13C NMR (100
MHz, DMSO) δ 139.71, 125.52, 122.39, 120.18, 118.49, 110.94. HRMS (ESI) ([M+H]+)
Calcd. for C12H9N 168.0808, found 168.0804.
Yield of (2b)[11]:22.0 mg, 81%, white solid, M.p. = 208℃, Rf = 0.48 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.05 (d, J = 7.6, 1H), 7.94 (brs,
1H), 7.89 (s, 1H), 7.40 (d, J = 3.6, 2H), 7.32 (d, J = 8.0, 1H), 7.28 – 7.17 (m, 2H), 2.54
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 139.92, 137.82, 128.86, 127.30, 125.77, 123.63,
123.34, 120.38, 120.36, 119.33, 110.68, 110.37, 21.58. IR (neat) v 3404, 2921, 1459,
1333, 1217, 747, 728 cm-1. HRMS (ESI) ([M-H]-) Calcd. for C13H11N 180.0814, found
180.0822.
Yield of (2c): 27.4 mg, 75%, white solid, M.p. = 216℃, Rf = 0.41 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.34 (brs, 1H), 8.44 (d, J=0.8,
1H), 8.21 (d, J = 7.6, 1H), 7.77 (d, J = 7.6, 2H), 7.70 (dd, J = 8.4, 1.7, 1H), 7.56 (d, J =
8.4, 1H), 7.49 – 7.40 (m, 3H), 7.40 (t, J = 7.2, 1H), 7.32 (t, J = 7.2, 1H), 7.18 (t, J = 7.6,
1H). 13C NMR (100 MHz, DMSO) δ 141.34, 140.24, 139.29, 130.97, 128.88, 126.69,
126.37, 125.77, 124.64, 123.10, 122.61, 120.48, 118.67, 118.32, 111.32, 111.10. IR
(neat) v 3410, 2927, 1459, 1356, 1255, 750 cm-1. HRMS (ESI) ([M-H]-) Calcd. for
C18H13N 242.0975, found 242.0982.
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Yield of (2d): 24.6 mg, 83% (4 d), white solid, M.p. = 234℃, Rf = 0.28 (petroleum
ether : ethyl acetate 10:1). 1H NMR (400 MHz, Acetone) δ = 10.21 (brs, 1H), 7.98 (dd,
J = 10.8, 8.0, 2H), 7.44 (d, J = 8.0, 1H), 7.32 – 7.24 (m, 1H), 7.18 – 7.08 (m, 1H), 7.03
(d, J = 2.4, 1H), 6.80 (dd, J = 8.4, 2.4, 1H), 3.86 (s, 3H). 13C NMR (100 MHz, Acetone)
δ 160.04, 142.31, 140.96, 125.01, 124.19, 121.56, 119.97, 119.68, 117.68, 111.36,
108.76, 95.30, 55.68. IR (neat) v 3404, 2921, 1459, 1333, 1195, 747 cm-1. HRMS (ESI)
([M-H]-) Calcd. for C13H11NO 196.0768, found 196.0784.
Yield of (2e)[14]: 25.9 mg, 90% (4 d), white solid, M.p. = 184℃, Rf = 0.25 (petroleum
ether : ethyl acetate 5:1). 1H NMR (400 MHz, DMSO) δ = 11.89 (brs, 1H), 8.72 (s, 1H),
8.24 (d, J = 8.0, 1H), 7.75 (d, J = 8.4, 1H), 7.63 (d, J = 8.4, 1H), 7.57 (d, J = 8.0, 1H),
7.49 (t, J = 7.6, 1H), 7.26 (t, J = 7.6, 1H). 13C NMR (100 MHz, DMSO) δ 141.71,
140.28, 128.66, 127.06, 125.69, 122.67, 121.63, 121.03, 120.67, 119.93, 112.09,
111.64, 100.21. IR (neat) v 3293, 2923, 2222, 1465, 1326, 1242, 1127, 736 cm-1. HRMS
(ESI) ([M+Na]+ ) Calcd. for C13H8N2 215.0585, found 215.0575.
Yield of (2f)[13]: 33.0 mg, 92%, white solid, M.p. = 160℃, Rf = 0.48 (petroleum ether :
ethyl acetate 5:1). 1H NMR (400 MHz, CDCl3) δ = 8.83 (s, 1H), 8.40 (brs, 1H), 8.21 –
8.10 (m, 2H), 7.46 – 7.41 (m, 3H), 7.32 – 7.31 (m, 1H), 4.45 (q, J = 7.2, 2H), 1.46 (t, J
= 7.2, 3H). 13C NMR (100 MHz, CDCl3) δ 167.58, 142.36, 140.04, 127.59, 126.67,
123.47, 123.23, 122.98, 121.87, 120.80, 120.44, 111.02, 110.23, 60.91, 14.65. IR (neat)
v 3294, 2925, 1685, 1460, 1332, 1245, 745, 727 cm-1. HRMS (ESI) ([M+Na]+) Calcd.
for C15H13NO2 262.0838, found 262.0837.
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Yield of (2g)[12]: 26.1 mg, 83%, white solid, M.p. = 178℃, Rf = 0.28 (petroleum ether :
ethyl acetate 3:1). 1H NMR (400 MHz, CDCl3) δ = 8.74 (d, J=1.5, 1H), 8.59 (brs, 1H),
8.17 – 8.05 (m, 2H), 7.48 – 7.42m, 3H), 7.35 – 7.27 (m, 1H), 2.74 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 198.13, 142.57, 140.17, 129.41, 126.79, 126.69, 123.54, 123.23,
122.02, 120.70, 120.54, 111.19, 110.44, 26.85. IR (neat) v 3294, 2924, 1446, 1329,
1246, 736 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C14H11NO 2 232.0733, found
232.0729.
Yield of (2h): 28.6 mg, 85% (4 d), white solid, M.p. = 242℃, Rf = 0.18 (petroleum
ether : ethyl acetate 1:1). 1H NMR (400 MHz, DMSO) δ = 11.52 (brs, 1H), 8.65 (s, 1H),
8.41 – 8.39(m, 1H), 8.13 (d, J = 7.6, 1H), 7.91 (dd, J = 8.4, 1.6, 1H), 7.51 (t, J = 8.0,
2H), 7.46 – 7.37 (m, 1H), 7.21 (t, J = 7.2, 1H), 2.83 (d, J = 4.4, 3H). 13C NMR (100
MHz, DMSO) δ 167.33, 141.27, 140.31, 126.04, 125.13, 124.94, 122.54, 121.91,
120.20, 119.63, 119.17, 111.30, 110.33, 26.37. IR (neat) v 3295, 2925, 1603, 1495, 1330,
1245, 745 cm-1. HRMS (ESI) ([M+Na]+ ) Calcd. for C14H12N2O 247.0847, found
247.0857.
Yield of (2i): 17.6 mg, 60%; 22.0 mg, 75% (4 d), yellow solid, M.p. = 163℃, Rf =
0.36 (petroleum ether : ethyl acetate 3:1). 1H NMR (400 MHz, Acetone) δ = 10.90
(brs, 1H), 10.10 (s, 1H), 8.74 – 8.67 (m, 1H), 8.26 (d, J = 7.8, 1H), 8.05 – 7.93 (m,
1H), 7.63 (dd, J = 24.4, 8.4, 2H), 7.54 – 7.43 (m, 1H), 7.34 – 7.25 (m, 1H). 13C NMR
(100 MHz, Acetone) δ 192.05, 144.71, 141.70, 130.07, 127.60, 127.30, 124.90,
124.15, 124.04, 121.49, 121.06, 112.46, 112.26. IR (neat) v 3293, 2924, 1678, 1456,
1331, 1244, 745 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C13H9NO 218.0576, found
218.0572.
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Yield of (2j)[12]: 16.7 mg, 60% (34%); 19.4 mg, 70% (4d), white solid, M.p. = 208℃,
Rf = 0.32 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.04
– 8.02 (m, 2H), 7.73 (dd, J = 9.2, 2.4, 1H), 7.48 – 7.40 (m, 2H), 7.34 (dd, J = 8.8, 4.2,
1H), 7.28 – 7.21 (m, 1H), 7.16 (td, J = 9.2, 2.4, 1H). 13C NMR (100 MHz, CDCl3) δ =
157.61 (d, JCF = 235.6), 140.62, 135.85, 126.55, 123.99 (d, JCF = 9.6), 123.20 (d, JCF =
4.0), 120.68, 119.58, 113.75 (d, JCF = 25.6), 111.22 (d, JCF = 9.2), 110.98, 106.13 (d,
JCF = 23.6). 19F NMR (376 MHz, CDCl3) δ -124.44. HRMS (ESI) ([M-H]-) Calcd. for
C12H8FN 184.0568, found 184.0582.
Yield of (2k)[10]: 20.9 mg, 69%, white solid, M.p. = 198℃, Rf = 0.34 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.42 (brs, 1H), 8.28 – 8.06 (m,
2H), 7.58 – 7.28 (m, 4H), 7.19 – 7.15 (m, 1H). 13C NMR (100 MHz, DMSO) δ 140.31,
138.11, 126.34, 125.29, 123.74, 122.82, 121.57, 120.73, 119.81, 118.89, 112.41, 111.23.
IR (neat) v 3405, 2923, 1488, 1268, 1089, 747 cm-1. HRMS (ESI) ([M+H]+) Calcd. for
C12H8NCl 202.0418, found 202.0421.
Yield of (2l)[24]: 28.4 mg, 77%, yellow solid. M.p. = 198℃, R f = 0.34 (petroleum ether :
ethylacetate 10:1). 1H NMR (400 MHz, Acetone) δ 10.54 (s, 1H), 8.34 (s, 1H), 8.20 (d,
J = 7.9 Hz, 1H), 7.60 – 7.50 (m, 3H), 7.50 – 7.43 (m, 1H), 7.25 (t, J = 7.5 Hz, 1H). 13C
NMR (101 MHz, Acetone) δ(s) 140.53, 138.74, 128.03, 126.41, 125.01, 122.71, 122.05,
120.42 , 119.26 , 112.65 , 111.11, 111.07. IR (neat) v 3405, 2920, 1468, 1444, 1271,
747 cm -1 . HRMS (ESI) ([M-H]+) Calcd. for C12H8NBr 243.9762, found 243.9766.
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Yield of (2m)[24]: 31.9 mg, 73%, white solid. M.p. = 196℃, Rf = 0.39 (petroleum ether :
ethylacetate 10:1). 1H NMR (400 MHz, Acetone) δ 10.54 (s, 1H), 8.53 (d, J = 1.4 Hz,
1H), 8.20 (d, J = 7.9 Hz, 1H), 7.71 (dd, J = 8.5, 1.7 Hz, 1H), 7.57 (d, J = 8.2 Hz, 1H),
7.50 – 7.40 (m, 2H), 7.26 (dd, J = 11.1, 3.9 Hz, 1H). 13C NMR (101 MHz, Acetone) δ
(s) 140.16, 139.20, 133.68, 128.91, 126.37, 125.79, 121.78, 120.38, 119.32, 113.19,
111.04, 80.68. IR (neat) v 3403, 2919, 2849, 1468, 1443, 747 cm -1 . HRMS (ESI) ([M-
H]+) Calcd. for C12H8NI 291.9623, found 291.9626.
Yield of (2n)[10]: 29.2 mg, 80%, brown solid, M.p. = 241℃, Rf = 0.47 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.34 (brs, 1H), 8.16 (dd, J = 20.4,
8.0, 2H), 7.82 – 7.65 (m, 3H), 7.51 – 7.43 (m, 4H), 7.38 (q, J = 7.6, 2H), 7.17 (t, J =
7.6, 1H). 13C NMR (100 MHz, DMSO) δ 141.22, 140.36, 140.27, 137.84, 128.96,
127.09, 127.02, 125.64, 122.16, 121.81, 120.63, 120.28, 118.70, 117.84, 111.00, 108.87.
IR (neat) v 3404, 2923, 1459, 1434, 1273, 1126, 745, 728 cm-1. HRMS (ESI) ([M+H]+)
Calcd. for C18H13N 244.1121, found 244.1112.
Yield of (2o): 16.7 mg, 60%; 21.7 mg, 78%, white solid, M.p. = 230℃, Rf = 0.49
(petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.38 (brs, 1H),
8.15 – 8.05 (m, 2H), 7.49 (d, J = 8.1, 1H), 7.40 – 7.34 (m, 1H), 7.26 (dd, J = 10.1, 2.3,
1H), 7.20 – 7.11 (m, 1H), 6.98 (ddd, J = 9.8, 8.6, 2.4, 1H). 13C NMR (100 MHz, DMSO)
δ = 161.14 (d, JCF = 238.4), 140.31 (d, JCF = 9.2), 140.25, 125.21, 122.04, 121.42 (d,
JCF = 10.7), 119.93, 119.16, 118.96, 110.98, 106.45 (d, JCF = 24.1), 97.30 (d, JCF =
26.0).19F NMR (376 MHz, DMSO) δ -116.01. HRMS (ESI) ([M-H]-) Calcd. for
C12H8FN 184.0568, found 184.0584.
Yield of (2p): 18.6 mg, 63%, white solid, M.p. = 230℃, Rf = 0.23 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, Acetone) δ = 10.21 (brs, 1H), 7.98 (dd, J =
10.8, 8.2, 2H), 7.44 (d, J = 8.0, 1H), 7.35 – 7.25 (m, 1H), 7.20 – 7.10 (m, 1H), 7.03 (d,
J = 2.4, 1H), 6.80 (dd, J = 8.4, 2.4, 1H), 3.86 (s, 3H). 13C NMR (100 MHz, Acetone) δ
160.04, 142.31, 140.96, 125.02, 124.19, 121.56, 119.97, 119.68, 117.68, 111.36, 108.76,
95.31, 55.68. IR (neat) v 3187, 2925, 1456, 1266, 1158, 741 cm-1. HRMS (ESI) ([M-
H]-) Calcd. for C13H11NO 196.0768, found 196.0777.
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Yield of (2q)[12]: 27.8 mg, 94%, white solid, M.p. = 134℃, Rf = 0.23 (petroleum ether :
ethyl acetate 20:1). 1H NMR (400 MHz, CDCl3) δ = 8.35 (d, J = 7.6, 1H), 8.00 (brs,
1H), 7.43 – 7.32 (m, 3H), 7.27 (ddd, J = 8.0, 5.9, 2.1, 1H), 7.03 (d, J = 8.0, 1H), 6.70
(d, J = 8.0, 1H), 4.09 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 156.38, 140.98, 138.76,
126.79, 125.03, 123.16, 122.75, 119.73, 112.71, 110.05, 103.63, 100.48, 55.54. IR (neat)
v 3405, 2926, 1506, 1454, 1346, 1260, 1099, 751, 719 cm-1. HRMS (ESI) ([M-H]-)
Calcd. for C13H11NO 196.0768, found 196.0784.
Yield of (2r)[17]: 10.4 mg, 35 %; 13.3 mg, 45 % (4 d), white solid, M.p.= 70℃, Rf =
0.23 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.27 (brs,
1H), 8.07 (d, J = 8.0, 1H), 7.70 (d, J = 8.0, 1H), 7.48 – 7.40 (m, 2H), 7.29 – 7.12 (m,
2H), 6.92 (d, J = 8.0, 1H), 4.02 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 145.80, 139.29,
129.91, 125.82, 124.43, 123.78, 120.69, 119.87, 119.50, 112.98, 111.05, 106.02, 55.66.
IR (neat) v 3405, 2924, 1507, 1435, 1311, 1234, 742 cm-1. HRMS (ESI) ([M+Na]+ )
Calcd. for C13H11NO 220.0738, found 220.0738.
Yield of (2r′)[12]: 10.4 mg, 35%; 13.3 mg, 45% (4 d), white solid, M.p.= 140℃, Rf =
0.21 (petroleum ether : ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.04 (d, J
= 8.0, 1H), 7.92 (brs, 1H), 7.56 (d, J = 2.4, 1H), 7.41 (d, J = 3.6, 2H), 7.33 (d, J = 8.8,
1H), 7.21 (dt, J = 8.0, 4.1, 1H), 7.07 (dd, J = 8.8, 2.4, 1H), 3.94 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 153.99, 140.37, 134.46, 125.92, 123.89, 123.46, 120.38, 119.17, 115.19,
111.43, 110.87, 103.25, 56.20. IR (neat) v 3404, 2925, 1460, 1255, 1170, 746 cm-1.
HRMS (ESI) ([M+Na]+ ) Calcd. for C13H11NO 220.0738, found 220.0725.
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Yield of mixture (2s + 2s′)[18]: 17.9 mg, 66%; 22.0 mg, 81% (4 d) (1.5 : 1). Yellow solid.
Rf = 0.43 (petroleum ether : ethyl acetate 10:1). 2r: 1H NMR (400 MHz, CDCl3) δ =
8.09 (d, J = 7.9, 1H), 7.97 (brs, 1H), 7.95 (d, J = 7.8, 1H), 7.51 – 7.42 (m, 2H), 7.22 –
7.14 (m, 3H), 2.58 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 139.50, 138.95, 126.53,
125.75, 123.95, 122.93, 120.60, 119.84, 119.70, 119.60, 118.06, 110.81, 17.01. 2r′: 1H
NMR (400 MHz, CDCl3) δ = 8.05 (d, J = 7.6, 1H), 7.94 (brs, 1H), 7.89 (s, 1H), 7.40 (d,
J = 3.6, 2H), 7.32 (d, J = 8.0, 1H), 7.28 – 7.17 (m, 2H), 2.54 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 139.92, 137.82, 128.86, 127.30, 125.77, 123.63, 123.34, 120.38, 120.36,
119.33, 110.68, 110.37, 21.58. The mixture of IR (neat) v 3405, 2924, 1507, 1457, 1327,
1275, 746, 727cm-1. The mixture of HRMS (ESI) ([M+Na]+) Calcd. for C13H11N
204.0789, found 204.0798.
Yield of (2t)[13]: 25.5 mg, 87%, white solid, M.p. = 90℃, Rf = 0.49 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.05 (d, J = 7.6, 1H), 7.87 (brs,
1H), 7.75 (s, 1H), 7.46 – 7.38 (m, 2H), 7.27 – 7.20 (m, 1H), 7.09 (s, 1H), 2.53 (d, J =
4.4, 6H). 13C NMR (100 MHz, CDCl3) δ 139.93, 137.29, 129.09, 128.14, 125.67,
123.93, 123.23, 120.58, 119.57, 119.46, 117.97, 110.87, 21.59, 17.02. IR (neat) v 3432,
2921, 1452, 1305, 1229, 745 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C14H13N
218.0940, found 218.0951.
Yield of (2u)[15]: 32.3 mg, 90%, white solid, M.p.= 180℃ Rf = 0.45 (petroleum ether :
ethyl acetate 5:1). 1H NMR (400 MHz, DMSO) δ = 11.55 (brs, 1H), 8.22 (dd, J = 12.0,
8.0, 2H), 8.11 (d, J = 0.8, 1H), 7.78 (dd, J = 8.0, 1.4, 1H), 7.57 –7.42 (m, 2H), 7.21 (t,
J = 7.2, 1H), 4.36 (q, J = 7.2, 2H), 1.37 (t, J = 7.2, 3H). 13C NMR (100 MHz, DMSO)
δ 166.43, 141.07, 139.04, 127.06, 126.58, 126.15, 121.61, 121.13, 120.14, 119.24,
119.16, 112.29, 111.43, 60.63, 14.32. IR (neat) v 3312, 2924, 1690, 1445, 1344, 1272,
749 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C15H13NO2 262.0838, found 262.0845.
Yield of (2v)[16]: 14.6 mg, 50% (4 d), yellow solid, M.p.= 150℃ Rf = 0.36 (petroleum
ether : ethyl acetate 3:1). 1H NMR (400 MHz, CDCl3) δ = 10.13 (s, 1H), 8.45 (brs, 1H),
8.17 (dd, J = 23.6, 7.9, 2H), 7.99 (s, 1H), 7.77 (dd, J = 8.0, 1.2, 1H), 7.59 – 7.46 (m,
2H), 7.32 – 7.29 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.72, 141.37, 139.19,
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134.18, 128.76, 127.95, 122.50, 121.70, 121.51, 120.72, 120.35, 112.08, 111.24. IR
(neat) v 3403, 1497, 1440, 1348, 1242, 1140, 742 cm-1. HRMS (ESI) ([M+Na]+) Calcd.
for C13H9NO 218.0576, found 218.0574.
Yield of (2w): 22.5 mg, 66% (4 d), white solid, M.p. = 135℃ Rf = 0.39 (petroleum
ether : ethyl acetate 5:1). 1H NMR (400 MHz, CDCl3) δ = 8.19 (d, J = 8.8, 1H), 7.86
(brs, 1H), 7.30 – 7.23 (m, 1H), 6.96 (d, J = 8.0, 1H), 6.88 (dd, J = 8.8, 2.2, 1H), 6.80
(d, J = 2.4, 1H), 6.68 (d, J = 8.0, 1H), 4.06 (s, 3H), 3.87 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 158.42, 155.60, 140.98, 140.06, 125.55, 123.75, 116.66, 112.72, 108.27,
103.57, 100.68, 94.41, 55.68, 55.52. IR (neat) v 3405, 2926, 1446, 1333, 1266, 1157,
1100, 722 cm-1. HRMS (ESI) ([M+Na]+ ) Calcd. for C14H13NO2 250.0844, found
250.0823.
Yield of (2x): 35.9 mg, 93%, yellow oil, M.p.= 92℃ Rf = 0.51 (petroleum ether : ethyl
acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.22 (brs, 1H), 8.12 (d, J = 7.6, 1H),
7.92 (s, 1H), 7.77 – 7.68 (m, 2H), 7.59 (t, J = 7.6, 2H), 7.49 – 7.41 (m, 3H), 7.32 (s,
1H), 7.30 – 7.24 (m, 1H), 2.63 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 139.89, 139.27,
135.61, 129.33, 128.46, 127.58, 127.25, 125.89, 124.79, 124.03, 123.51, 120.50, 119.57,
119.44, 110.77, 77.48, 76.84, 21.58. IR (neat) v 3440, 2922, 1452, 1316, 1324, 1156,
747, 734 cm-1. HRMS (ESI) ([M+H]+ ) Calcd. for C19H15N 258.1283, found 258.1266.
Yield of (2y): 42.2 mg 93%, white solid, M.p.= 179℃ Rf = 0.31 (petroleum ether :
ethyl acetate 3:1). 1H NMR (400 MHz, DMSO) δ = 10.90 (brs, 1H), 8.28 – 7.86 (m,
2H), 7.63 (d, J=8.7, 2H), 7.31 – 7.17 (m, 2H), 7.13 (d, J=8.7, 2H), 7.05 (d, J=2.2, 1H),
6.79 (dd, J=8.6, 2.3, 1H), 3.85 (s, 3H), 3.83 (s, 3H). 13C NMR (100 MHz, DMSO) δ
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158.59, 158.41, 141.61, 136.92, 131.02, 129.47, 124.17, 123.97, 123.40, 120.80, 119.17,
117.98, 116.35, 114.40, 107.80, 95.04, 55.21, 55.13. IR (neat) v 3672, 2962, 1568, 1541,
1031, 802, 667 cm-1. HRMS (ESI) ([M-H]-) Calcd. for C20H17NO2 302.1186, found
302.1176.
Yield of (2z): 30.9 mg 80% (4 d), light brown solid, M.p. = 210℃, Rf = 0.24 (petroleum
ether : ethyl acetate 10:1). 1H NMR (400 MHz, Acetone) δ = 10.83 (brs, 1H), 8.42 (d,
J = 8.0, 1H), 8.15 – 8.03 (m, 2H), 7.78 (d, J = 8.0, 1H), 7.62 (dd, J = 18.8, 8.4, 2H),
7.53 – 7.31 (m, 4H). 13C NMR (100 MHz, Acetone) δ 156.73, 151.87, 141.66, 140.54,
126.43, 126.12, 126.05, 123.90, 122.81, 121.36, 120.53, 120.52, 118.81, 116.08, 112.26,
111.98, 108.93, 107.93. IR (neat) v 3403, 2925, 1456, 1324, 1243, 1141, 742 cm-1.
HRMS (ESI) ([M-H]-) Calcd. for C18H11NO 256.0768, found 256.0779.
Yield of (4a)[19]: 25.4 mg, 80%, white solid, M.p.= 155℃ Rf = 0.31 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, CDCl3) δ = 8.15 (s, 1H), 7.89 (brs, 1H), 7.33
(t, J = 8.0, 1H), 7.26 – 7.21 (m, 2H), 7.00 (d, J = 8.0, 1H), 6.68 (d, J = 8.0, 1H), 4.09
(s, 3H), 2.55 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 156.33, 141.30, 136.98, 128.99,
126.57, 126.31, 123.03, 122.90, 112.53, 109.71, 103.66, 100.25, 55.51, 21.59. IR (neat)
v 3405, 2928, 1506, 1458, 1346, 1260, 1100, 748 cm-1. HRMS (ESI) ([M+Na]+ ) Calcd.
for C14H13NO 234.0895, found 234.0893.
Yield of (4b)[20]: 31.4 mg, 82%; 36.0 mg, 94% (4 d), white solid, M.p. = 198℃, Rf =
0.65 (petroleum ether : ethyl acetate 1:1). 1H NMR (400 MHz, DMSO) δ = 11.59 (brs,
1H), 8.67 (d, J = 1.2, 1H), 8.11 (d, J = 8.4, 1H), 7.94 (dd, J = 8.4, 1.6, 1H), 7.50 (d, J =
8.4, 1H), 7.02 (d, J = 2.4, 1H), 6.83 (dd, J = 8.4, 2.2, 1H), 3.87 (s, 3H), 3.85 (s, 3H). 13C NMR (100 MHz, DMSO) δ 167.06, 159.07, 142.68, 141.84, 125.50, 122.56, 121.52,
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121.34, 119.90, 116.05, 110.46, 108.76, 94.87, 55.34, 51.74. IR (neat) v 3279, 1697,
1438, 1328, 1265, 1159, 742 cm-1. HRMS (ESI) ([M+Na]+ ) Calcd. for C15H13NO3
278.0793, found 278.0783.
Yield of (4c)[21]: 33.7 mg, 88% (4 d), white solid, M.p. = 172℃, Rf = 0.49 (petroleum
ether : ethyl acetate 1:1). 1H NMR (400 MHz, CDCl3) δ = 8.70 (brs, 1H), 8.62 (s, 1H),
7.99 (d, J = 7.6, 1H), 7.41 – 7.31 (m, 2H), 7.27 – 7.23 (m, 1H), 6.74 (s, 1H), 3.97 (s,
3H), 3.74 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 167.37, 159.21, 143.60, 140.11,
125.48, 124.94, 123.35, 120.33, 119.84, 116.42, 112.05, 110.87, 93.62, 56.08, 52.07.
IR (neat) v 3297, 2951, 1704, 1462, 1349, 1237, 1083, 765, 748, 727 cm-1. HRMS (ESI)
([M+Na]+ ) Calcd. for C15H13NO3 278.0793, found 278.0780.
Yield of (4d)[22]: 37.2 mg, 87% (4 d), white solid, M.p. = 186℃, Rf = 0.29 (petroleum
ether : ethyl acetate 3:1). 1H NMR (400 MHz, Acetone) δ = 10.39 (brs, 1H), 8.41 (s,
1H), 7.95 (d, J = 8.4, 1H), 7.11 (s, 1H), 7.03 (d, J = 2.4, 1H), 6.83 (dd, J = 8.4, 2.4, 1H),
3.90 (s, 3H), 3.84 (d, J = 9.6, 6H). 13C NMR (100 MHz, Acetone) δ 167.41, 159.70,
158.94, 144.66, 142.80, 123.88, 121.12, 117.73, 117.19, 113.49, 109.21, 95.95, 94.90,
56.40, 55.75, 51.66. IR (neat) v 3303, 2925, 1704, 1462, 1266, 1235, 1157, 747 cm-1.
HRMS (ESI) ([M+Na]+ ) Calcd. for C16H15NO4 308.0899, found 308.0881.
Yield of (4e): 25.3 mg, 75%, yellow solid, M.p. = 185℃, Rf = 0.12 (petroleum ether :
ethyl acetate 5:1). 1H NMR (400 MHz, DMSO) δ = 11.73 (brs, 1H), 10.01 (s, 1H), 8.60
(s, 1H), 8.11 (d, J = 8.4, 1H), 7.85 (dd, J = 8.4, 1.1, 1H), 7.57 (d, J = 8.4, 1H), 7.04 (d,
J = 2.0, 1H), 6.87 (dd, J = 8.4, 2.2, 1H), 3.86 (s, 3H). 13C NMR (100 MHz, DMSO) δ
192.03, 159.23, 143.65, 141.95, 128.30, 125.48, 123.02, 122.90, 121.61, 116.12, 111.09,
109.13, 95.09, 55.40. IR (neat) v 3286, 2925, 1673, 1456, 1321, 1266, 1158, 741 cm-1.
HRMS (ESI) ([M+Na]+ ) Calcd. for C14H11NO2 248.0687, found 248.0673.
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Yield of (2aa): 13.8 mg, 20 %, yellow solid, M.p. = 84℃, Rf = 0.12 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.07 (brs, 1H), 8.14 (d, J = 8.3,
2H), 8.04 (dd, J = 17.4, 8.1, 2H), 7.86 (d, J = 8.3, 2H), 7.38 (d, J = 6.7, 1H), 7.25 (t, J
= 7.6, 1H), 7.02 (d, J = 2.2, 1H), 6.81 (dd, J=8.6, 2.2, 1H), 4.38 (q, J = 7.1, 2H), 3.83
(s, 3H), 1.37 (t, J = 7.1, 3H). 13C NMR (100 MHz, DMSO) δ = 165.62, 158.60, 143.48,
141.68, 136.79, 129.78, 128.70, 128.50, 124.32, 123.76, 123.12, 121.00, 119.41,
119.30, 116.14, 108.13, 94.95, 60.76, 55.17, 14.23. IR (neat) v 3365, 2980, 1698, 1398,
1129, 769, 747 cm-1. HRMS (ESI) ([M+Na]+) Calcd. for C22H19NO3 368.1263, found
368.1262.
Yield of (2aa′): 12.4 mg, 18 %, white solid, M.p.= 129℃ Rf = 0.12 (petroleum ether :
ethyl acetate 10:1). 1H NMR (400 MHz, DMSO) δ = 11.33 (brs, 1H), 8.30 – 8.14 (m,
3H), 7.79 (d, J = 8.1, 1H), 7.66 (d, J = 7.9, 2H), 7.45 (d, J = 7.1, 1H), 7.30 (t, J = 7.5,
1H), 7.16 (d, J = 8.1, 2H), 4.35 (d, J = 7.0, 2H), 3.86 (s, 3H), 1.36 (t, J=6.9, 3H). 13C
NMR (100 MHz, DMSO) δ = 166.44, 158.85, 139.53, 138.39, 130.51, 129.58, 126.66,
126.24, 124.94, 122.38, 120.09, 119.81, 119.39, 114.55, 113.08, 99.54, 60.58, 55.30,
14.29. IR (neat) v 3368, 2932, 1696, 1515, 1300, 1243, 763 cm-1. HRMS (ESI)
([M+Na]+) Calcd. for C22H19NO3 368.1263, found 368.1257.
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VII. References
[1] Liu, L.; Zhang, Y.; Wang, Y. J. Org. Chem. 2005, 70, 6122–6125.
[2] Stokes, B. J.; Jovanovic´, B.; Dong, H.; Richert, K. J.; Riell, R. D. Driver, T. G. J.
Org. Chem. 2009, 74, 3225–3228.
[3] Gritsan, N.P.; Polshakov, D. A.; Tsaoa, M.; Platz, M. S. Photoch Photobio Sci, 2005,
4, 23–32.
[4] Stokes, B. J. ; K. Richert, J.; Driver , T. G. J. Org. Chem. 2009,74, 6442–6451.
[5] Liu, C.; Knochel, P. J. Org. Chem. 2007, 72, 7106–7115.
[6] Saneyoshi, H.; Ito, Y.; Abe, H. J. Am. Chem. Soc. 2013, 135, 13632–13635.
[7] Ullah, E.; McNulty, J.; Robertson, A. Eur. J. Org. Chem. 2012, 2127–2131.
[8] Manolikakes, G.; Schade, M. A.; Hernandez, C. M.; Mayr, H.; Knochel, P. Org.
Lett. 2008, 10, 2765–2768.
[9] Alt, I. T.; Plietker, B. Angew. Chem., Int. Ed. 2016, 55, 1519–1522.
[10] Takamatsu, K.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2014, 16, 2892–2895.
[11] Zhang, L.; Wang, W.; Fan, R. Org. Lett. 2013, 15, 2018–2021.
[12] Jiang, Q.; Mu, D.; Zhong, W.; Chen, H.; Yan, H. Chem. Eur. J. 2013, 19, 1903–
1907.
[13] Ackermann, L.; Althammer, A.; Mayer, P. Synthesis 2009, 20, 3493–3503.
[14] Guerra, W. D.; Rossi, R. A.; Pierini, A. B.; Barolo, S. M. J. Org. Chem. 2015, 80,
928−941.
[15] Sun, K.; Sachwani, R.; Richert, K. J. Driver, T. G. Org. Lett. 2009, 11, 3598–3601.
[16] Freeman, A. W.; Urvoy, M.; Criswell, M. E. J. Org. Chem. 2005, 70, 5014–5019.
[17] Bedford, R. B.; Betham, M. J. Org. Chem. 2006, 71, 9403–9410.
[18] Chakrabarty, S.; Chatterjee, I.; Tebben, L.; Studer, A. Angew. Chem. Int. Ed. 2013,
52, 2968–2971.
[19] Bautista, R.; P. Montoya, A.; Rebollar, A.; Burgueño, E.; Tamariz, J. Molecules
2013, 18, 10334–10351.
[20] Kuethea, J. T.; Childers, K. G. Adv. Synth. Catal. 2008, 350, 1577–1586.
[21] Rasheed, S.; Rao, D. N.; Reddy, K. R.; Aravinda, S.; Vishwakarma, R. A. RSC Adv.
2014, 4, 4960–4969.
[22] Krahl, M.; Kataeva, P. O.; Schmidt, A. W. H.; Knölker, J. Eur. J. Org. Chem. 2013,
1, 59–64.
[23] Huang, J.; Sun, N.; Chen, P.; Tang, R.; Li, Q.; Ma, D.; Li, Z. Chem. Commun.,
2014, 50, 2136-2138.
[24] Shou, W. G.; Li, J.; Guo, T.; Lin Z.; Jia, G. Organometallics, 2009, 28, 6847-6854.
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Ⅷ. Spectral Copies of 1H, 13C NMR of All Compounds
Compound 1a
Page 100
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Compound 1x
Page 101
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Compound 1x
Page 102
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Compound 1y
Page 103
S103
Compound 1y
Page 104
S104
Compound 1z
Page 105
S105
Compound 1z
Page 106
S106
Compound 1aa
Page 107
S107
Compound 1aa
Page 108
S108
Compound 3a
Page 109
S109
Compound 3a
Page 110
S110
Compound 3b
Page 111
S111
Compound 3b
Page 112
S112
Compound 3c
Page 113
S113
Compound 3c
Page 114
S114
Compound 3d
Page 115
S115
Compound 3d
Page 116
S116
Compound 3e
Page 117
S117
Compound 3e
Page 118
S118
Compound 3e′
Page 119
S119
Compound 3e′
Page 120
S120
Compound 1a-D′′
Page 121
S121
Compound 1a-D′′
Page 122
S122
Compound 1a-D′
Page 123
S123
Compound 1a-D
Page 126
S126
Compound 2b
Page 127
S127
Compound 2b
Page 128
S128
Compound 2c
Page 129
S129
Compound 2c
Page 130
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Compound 2d
Page 131
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Compound 2d
Page 132
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Compound 2e
Page 133
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Compound 2e
Page 134
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Compound 2f
Page 135
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Compound 2f
Page 136
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Compound 2g
Page 137
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Compound 2g
Page 138
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Compound 2h
Page 139
S139
Compound 2h
Page 140
S140
Compound 2i
Page 141
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Compound 2i
Page 142
S142
Compound 2j
Page 143
S143
Compound 2j
Page 144
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Compound 2j
Page 145
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Compound 2k
Page 146
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Compound 2k
Page 147
S147
Compound 2l
Page 148
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Compound 2l
Page 149
S149
Compound 2m
Page 150
S150
Compound 2m
Page 151
S151
Compound 2n
Page 152
S152
Compound 2n
Page 153
S153
Compound 2o
Page 154
S154
Compound 2o
Page 155
S155
Compound 2o
Page 156
S156
Compound 2p
Page 157
S157
Compound 2p
Page 158
S158
Compound 2q
Page 159
S159
Compound 2q
Page 160
S160
Compound 2r
Page 161
S161
Compound 2r
Page 162
S162
Compound 2r′
Page 163
S163
Compound 2r′
Page 164
S164
Compound 2s
Page 165
S165
Compounds 2s
Page 166
S166
Compound 2t
Page 167
S167
Compound 2t
Page 168
S168
Compound 2u
Page 169
S169
Compound 2u
Page 170
S170
Compound 2v
Page 171
S171
Compound 2v
Page 172
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Compound 2w
Page 173
S173
Compound 2w
Page 174
S174
Compound 2x
Page 175
S175
Compound 2x
Page 176
S176
Compound 2y
Page 177
S177
Compound 2y
Page 178
S178
Compound 2z
Page 179
S179
Compound 2z
Page 180
S180
Compound 4a
Page 181
S181
Compound 4a
Page 182
S182
Compound 4b
Page 183
S183
Compound 4b
Page 184
S184
Compound 4c
Page 185
S185
Compound 4c
Page 186
S186
Compound 4d
Page 187
S187
Compound 4d
Page 188
S188
Compound 4e
Page 189
S189
Compound 4e
Page 190
S190
Compound 2aa
Page 191
S191
Compound 2aa
Page 192
S192
Compound 2aa′
Page 193
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Compound 2aa′