Catalytic amounts of triarylaminium salt initiated aerobic oxidative coupling of N-aryl tetrahydroisoquinolines

Article abstract of DOI:10.1039/c3ob42454e

A novel stable radical cation triarylaminium salt able to induce aerobic oxidative α-C-H functionalization of tertiary amines in catalytic amounts has been developed. The reaction is performed in the absence of any other additives under mild conditions an

Full text of DOI:10.1039/c3ob42454e

Organic &
Biomolecular Chemistry
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Catalytic amounts of triarylaminium salt initiated
aerobic oxidative coupling of N-aryl
tetrahydroisoquinolines†
Cite this: Org. Biomol. Chem., 2014,
12, 3123
Congde Huo,* Cheng Wang, Mingxia Wu, Xiaodong Jia, Xicun Wang, Yong Yuan
and Haisheng Xie
Received 9th December 2013,
Accepted 11th March 2014
A novel stable radical cation triarylaminium salt able to induce aerobic oxidative α-C–H functionalization
of tertiary amines in catalytic amounts has been developed. The reaction is performed in the absence of
any other additives under mild conditions and only requires atmosphere air as a sustainable co-oxidant.
DOI: 10.1039/c3ob42454e
www.rsc.org/obc
Introduction
Carbon–hydrogen (C–H) bonds are ubiquitous in organic
molecules, which are traditionally considered unreactive. The
activation of C–H bonds has become an significant area in
research on modern organic chemistry.1 The direct functionali-
zations of C–H bonds in the α-position to a nitrogen atom are
of special interest for both industry and academia.2–4 Among
these reactions, the oxidative coupling of secondary amines
such as glycine derivatives2 and tertiary amines such as N-aryl
tetrahydroisoquinolines3,4 with nucleophiles has gained a lot
of attention. Recently, various transition metal catalyzed oxi-
dative dehydrogenative coupling reactions of amines have
been reported.3 In addition, metal-free methods using a stoi-
chiometric amount of an oxidant, such as DDQ, PhI(OAc)2,
H2O2, tropylium ion, or the TEMPO Oxoammonium Salt, have
also been reported.4 However, the catalytic metal-free aerobic
oxidative dehydrogenative coupling of amines is still very rare.5
Our group has a long-standing interest in the stable triarylami-
nium salt initiated radical cation mediated transformations
and their synthetic potential.6 Very recently, we discovered that
triarylaminium salt could catalyze the reaction of glycine
derivatives with indoles in the absence of any other additives
and only required atmosphere air as a co-oxidant.7 An aerobic
double oxidative dehydrogenative Friedel–Crafts alkylation
cascade reaction occurred to deliver a series of bisindolyl-
methane (BIM) derivatives (Scheme 1). Jia et al. also reported
that triarylaminium salt/InCl3/O2 system could catalyze the
reaction of glycine esters with alkenes or alkynes in a one-pot
Scheme 1 Triarylaminium salt induced aerobic oxidative coupling of
amines.
dehydrogenative Povarov/oxidation tandem process to con-
struct substituted quinolines.8 These previous studies indi-
cated that the triarylaminium salt induced aerobic oxidative
coupling reaction is an interesting subject, whereas the appli-
cation of this catalytic system for oxidative coupling of tertiary
amines with various nucleophiles has not yet been developed.
Herein we describe a highly efficient oxidative C–C, C–P coup-
ling reaction of N-aryl tetrahydroisoquinolines initiated by
commercially available and bench-stable tris(4-bromophenyl)-
aminium hexachloro-antimonate (TBPA+•SbCl6−, 1).
Results and discussion
For the optimization studies, we chose N-phenyl tetrahydroiso-
quinoline (2a) and indole (3a) as model substrates.9 As shown
in Table 1, the best yield (89%) was achieved with 10 mol%
Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education,
College of Chemistry and Chemical Engineering, Northwest Normal University,
TBPA+•SbCl6 in THF at room temperature in 6 h. No appreci-
−
Lanzhou, Gansu 730070, China. E-mail: Huocongde1978@hotmail.com;
Fax: (+86)-931-7971989
†Electronic supplementary information (ESI) available: Characterization of pro-
ducts. See DOI: 10.1039/c3ob42454e
able differences of the transformation were observed when the
reaction time was prolonged from 6 h to 12 h or oxygen was
used instead of air. Under the optimized conditions (Table 1,
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Table 1 Screening of reaction conditionsa
Table 2 Scope of TBPA+•SbCl6− induced aerobic indolation of sp3 C–H
bondsb
Entry
Conditions
Yieldb (%)
1
2
3
4
5
6
7
8
20 mol% 1, CH2Cl2, air, rt, 6 h
20 mol% 1, CHCl3, air, rt, 6 h
20 mol% 1, (CH2Cl)2, air, rt, 6 h
20 mol% 1, MeCN, air, rt, 6 h
20 mol% 1, THF, air, rt, 6 h
20 mol% 1, EtOAc, air, rt, 6 h
20 mol% 1, Acetone, air, rt, 6 h
10 mol% 1, THF, air, rt, 6 h
5 mol% 1, THF, air, rt, 6 h
50
—
45
65
86
—
—
89
78
89
88
9
10
11
10 mol% 1, THF, air, rt, 12 h
10 mol% 1, THF, O2, rt, 6 h
a Reaction conditions: 2a (0.1 mmol), 3a (0.1 mmol), 1 (0.01 mmol),
solvent (1 mL), air (1 atm), rt, 6 h. b Yields were determined by NMR
spectroscopy.
entry 8), we probed the scope and generality of both indoles
and tetrahydroisoquinolines for the TBPA radical cation
induced aerobic α-arylation (Table 2). Initially, we investigated
different substituted indoles. N-Me and N-Bn protected
indoles gave the corresponding products in high yields
(Table 2, 4ab, 4ac). Indoles with electron-donating groups or
electron-withdrawing groups on C2, C4 and C5 all worked well
with N-phenyl tetrahydroisoquinoline under the present reac-
tion conditions (Table 2, 4aa–4ai). The steric hindrance did
not affect the yield of the reaction significantly (Table 2, 4ae).
An unprotected hydroxyl group was tolerated in this reaction
(Table 2, 4ag). The introduction of a halogen atom into this
system made this method more useful for further transform-
ation (Table 2, 4ai). Furthermore, we explored the variety of
a Standard reaction conditions: tetrahydroisoquinolines 2 (1.0 mmol),
indoles 3 (1.0 mmol), 1 (0.1 mmol), THF (10 mL), ambient air, rt,
6–12 h. b Isolated yields of the isolated products. c 40 °C.
tetrahydroisoquinolines. For both electron-donating and elec- ively). It indicated that this protocol not only is atom-efficient
tron-withdrawing groups, the desired products were achieved and environmentally benign but also could be conveniently
scaled up in industry.
in high yields (Table 2, 4ba–4da). The success of C–C bond for-
mation of tertiary amines by using triarylaminium salt 1
Extending the nucleophile scope further turned out to be
encouraged us to investigate C–P bond coupling reactions. rather difficult. In contrast to our expectations, the more
nucleophilic nitromethane and malonic acid esters hardly
α-Amino phosphoric derivatives are valuable precursors of a
number of biologically active molecules and have aroused a lot reacted under these conditions. It seems the reaction perform-
of synthetic interest.10 In this work, a variety of phosphites ance was not related to nucleophilicity. This may be due to the
oxidation step being the limiting factor and that it depends on
presence of 1 to give the desired products in high yields the nucleophile present. The exact reason for this pheno-
and phosphine oxides could react with tertiary amines in the
(Table 3).
It is worth noting that when diaryl phosphines were used
instead of diaryl phosphine oxides, the same products were
obtained in excellent yield (Scheme 2).
menon is not yet clear, and more detailed investigation of the
reaction conditions are currently ongoing in our laboratory.
Some control experiments were carried out in order to
reveal the mechanism of this transformation. Firstly, the reac-
tion of 2a with 3a or 5a in argon atmosphere (in the absence
To evaluate the practicability of our method, the reactions
of N-phenyl tetrahydroisoquinoline (2a) with indole (3a) or of molecular oxygen) furnished no product [Scheme 3, eqn (1)
diethyl phosphite (5a) have been performed on a 20 mmol and (3)], indicating that molecular oxygen is definitely crucial
for the reaction. Secondly, a stoichiometric amount of TEMPO
scale in a single batch. To our delight, no obvious loss of
yields were observed (isolated yield: 78% and 91% respect- was employed in the standard reaction as radical scavenger;
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−
Table 3 Scope of TBPA+•SbCl6 induced aerobic phosphonation of sp3
C–H bondsb
Scheme 3 Control experiments.
Scheme 4 Proposed reaction mechanism.
a Standard reaction conditions: tetrahydroisoquinolines 2 (1.0 mmol),
phosphorus reagents 5 (1.0 mmol), 1 (0.1 mmol), THF (15 mL),
ambient air, rt, 5–8 h. b Isolated yields of the isolated products.
stirring for 24 h, which implied that peroxides could not be
the terminal oxidant. More details of the mechanism are cur-
rently under investigation.
Experimental
General information
The starting materials, reagents and solvents, purchased from
commercial suppliers, were used without further purification.
Literature procedures were used for the preparation of N-aryl
tetrahydroisoquinoline. Analytical TLC was performed with
silica gel GF254 plates, and the products were visualized by UV
detection. Flash chromatography was carried out using silica
gel 200–300. 1HNMR (400 MHz) and 13CNMR (100 MHz)
spectra were measured with CDCl3 or acetone-d6 as solvent.
High-resolution electrospray ionization (HRESI) mass spectra
were recorded by a QTOF-2 Micromass spectrometer.
Scheme 2
a significant drop in yield was observed [Scheme 3, eqn (2)
and (4)]. This result suggested that the present reaction
includes a radical process. Consequently, based on experi-
mental observations, a plausible mechanism for this triaryla-
minium salt catalyzed aerobic transformation is illustrated in
Scheme 4. TBPA radical cation 1 couples with oxygen to gene-
rate a distonic11 peroxy radical cation A, which abstracts a
hydrogen atom from 2 to afford a free radical C. On the other
hand, after homolytic cleavage of the peroxide intermediate B,
a TBPA radical cation is regenerated and a peroxy radical (•O–
OH) is formed. Subsequent one-electron oxidation of C offers
an intermediate D, followed by nucleophilic addition leading
to the product 4 or 6. We also tried the reaction in the pres-
ence of a catalytic or even stoichiometric amount of H2O2 or
TBHP, but the starting materials remained unchanged after
−
Preparation of TBPA+•SbCl6
−
TBPA+•SbCl6 is a commercially available, inexpensive and
bench-stable reagent. It can also be synthesized according to
literature procedures and used as freshly prepared as follows:
Tris-(p-bromophenyl)amine (TBPA, 4.8 g) was dissolved in
DCM (20 mL) and a solution of SbCl5 (2 mL) in DCM (20 mL)
was added slowly. The reaction mixture was then poured into
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dry ether (50 mL). The obtained blue precipitate was washed 120.6, 120.4, 119.8, 114.9, 110.7, 57.1, 47.3, 28.4. HRMS (EI)
thoroughly with dry ether and dried.
for C24H22N2, calcd: 338.1783, found: 338.1785.
General procedure for TBPA+•SbCl6− induced aerobic
indolation of N-aryl tetrahydroisoquinolines
2-Phenyl-1-(2-phenyl-1H-indol-3-yl)-1,2,3,4-
tetrahydroisoquinoline (4ae)3b
N-Aryl tetrahydroisoquinolines (2, 1 mmol) and indoles (3, Pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H),
1 mmol) were dissolved in THF (10 mL) at ambient tempera- 7.46–6.98 (m, 15H), 6.93 (t, J = 7.4 Hz, 1H), 6.79 (m, 3H), 5.96
−
ture; TBPA+•SbCl6 (1, 0.1 mmol) was then added in one (s, 1H), 3.87–3.58 (m, 2H), 3.20–3.00 (m, 2H).
portion under stirring. The reactions were performed under an
air atmosphere (open flask) at room temperature and com-
pleted within 6–12 hours as monitored by TLC. The products
1-(5-Methoxy-1H-indol-3-yl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (4af)3b
were isolated by column chromatographic separation.
White solid. 1H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H),
7.40–7.10 (m, 6H), 7.02 (d, J = 8.7 Hz, 2H), 6.88 (s, 1H),
6.85–6.71 (m, 2H), 6.56 (s, 1H), 6.14 (s, 1H), 3.65 (s, 3H), 3.59
(dd, J = 7.8, 4.4 Hz, 2H), 3.07 (m, 1H), 2.81 (m, 1H).
General procedure for TBPA+•SbCl6− induced aerobic
phosphonation of N-aryl tetrahydroisoquinolines
N-Aryl tetrahydroisoquinolines (2, 1 mmol) and phosphorous
3-(2-Phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl)-1H-indol-4-ol
(4ag)
reagents (5, 1 mmol) were dissolved in THF (10 mL) at
ambient temperature; TBPA+•SbCl6 (1, 0.1 mmol) was then
−
1
added in one portion under stirring. The reactions were per- Pale brown solid. H NMR (400 MHz, CDCl3) δ 11.48 (s, 1H),
formed under an air atmosphere (open flask) at room temp- 7.96 (s, 1H), 7.38–7.01 (m, 11H), 6.83 (d, J = 8.1 Hz, 1H), 6.59
erature and completed within 6 hours as monitored by TLC. (d, J = 7.6 Hz, 1H), 6.46 (s, 1H), 5.83 (s, 1H), 3.94–3.53 (m, 2H),
The products were isolated by column chromatographic 3.04–2.67 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 151.7, 148.1,
separation.
139.0, 135.2, 134.0, 129.4, 129.3, 128.3, 127.0, 125.8, 124.3,
123.8, 123.3, 121.5, 118.4, 115.4, 105.2, 102.4, 58.0, 47.1, 25.1.
HRMS (EI) for C23H20N2O, calcd: 340.1576, found: 338.
340.1569.
1-(1H-Indol-3-yl)-2-phenyl-1,2,3,4-tetrahydroisoquinoline
(4aa)3b
1
White solid. H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.56 (d,
1-(5-Methyl-1H-indol-3-yl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (4ah)
J = 8.0 Hz, 1H), 7.39–7.10 (m, 8H), 7.10–6.96 (m, 3H), 6.77 (t,
J = 7.3 Hz, 1H), 6.63 (d, J = 1.3 Hz, 1H), 6.17 (s, 1H), 3.62 (dd,
J = 7.6, 4.6 Hz, 2H), 3.07 (m, 1H), 2.80 (m, 1H).
1
White solid. H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.56 (d,
J = 8.0 Hz, 1H), 7.39–7.10 (m, 8H), 7.10–6.96 (m, 3H), 6.77 (t,
J = 7.3 Hz, 1H), 6.63 (s, 1H), 6.17 (s, 1H), 3.62 (dd, J = 7.6,
4.6 Hz, 2H), 3.07 (m, 1H), 2.80 (m, 1H). 13C NMR (101 MHz,
1-(1-Methyl-1H-indol-3-yl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (4ab)3b
1
White solid. H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, CDCl3) δ 149.9, 137.6, 135.5, 134.9, 129.2, 128.8, 128.8, 128.1,
1H), 7.37–7.10 (m, 8H), 7.02 (ddd, J = 7.9, 4.9, 1.8 Hz, 3H), 6.76 126.7, 126.6, 125.7, 124.5, 123.7, 119.6, 118.7, 118.2, 116.1,
(t, J = 7.3 Hz, 1H), 6.50 (s, 1H), 6.17 (s, 1H), 3.77–3.50 (m, 5H), 110.8, 56.7, 42.3, 26.6, 21.6. HRMS (EI) for C24H22N2, calcd:
3.15–2.99 (m, 1H), 2.81 (m, 1H).
338.1783, found: 338.1773.
1-(1-Benzyl-1H-indol-3-yl)-2-phenyl-1,2,3,4-
1-(5-Bromo-1H-indol-3-yl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (4ac)
tetrahydroisoquinoline (4ai)
1
White oil. 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.1 Hz, 1H), White solid. H NMR (400 MHz, Acetone) δ 10.27 (s, 1H), 7.67
7.39–6.89 (m, 14H), 6.77 (t, J = 7.1 Hz, 1H), 6.63 (s, 1H), 6.21 (s, (d, J = 1.7 Hz, 1H), 7.36 (dd, J = 8.2, 5.6 Hz, 2H), 7.30–7.16 (m,
1H), 5.15 (s, 2H), 3.73–3.50 (m, 2H), 3.06 (m, 1H), 2.90–2.70 6H), 7.11 (d, J = 7.9 Hz, 2H), 6.83 (s, 1H), 6.75 (t, J = 7.2 Hz,
(m, 1H). 13C NMR (101 MHz, CDCl3) δ 150.0, 137.6, 137.5, 1H), 6.27 (s, 1H), 3.77–3.48 (m, 2H), 3.16–2.98 (m, 1H),
137.0, 135.6, 129.2, 128.9, 128.7, 128.5, 128.5, 128.1, 127.5, 2.92–2.77 (m, 2H). 13C NMR (101 MHz, Acetone) δ 149.9, 137.5,
127.3, 126.7, 126.4, 125.8, 121.9, 120.4, 119.4, 118.3, 118.2, 135.7, 135.3, 129.0, 128.7, 128.3, 128.0, 126.6, 126.2, 125.6,
116.2, 109.8, 56.9, 49.9, 42.5, 26.8. HRMS (EI) for C30H26N2, 124.0, 122.2, 118.2, 118.1, 115.9, 113.1, 111.8, 56.2, 42.1, 26.4.
calcd: 414.2096, found: 414.2091.
HRMS (EI) for C23H19BrN2, calcd: 402.0732, found: 402.0739.
1-(2-Methyl-1H-indol-3-yl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (4ad)
1-(1H-Indol-3-yl)-2-(4-methoxyphenyl)-1,2,3,4-
tetrahydroisoquinoline (4ba)3b
White solid. 1H NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), Pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H),
7.24–6.95 (m, 9H), 6.90 (t, J = 7.3 Hz, 1H), 6.84 (t, J = 7.3, 1H), 7.40(d, J = 3.0 Hz, 1H), 7.25–7.10(m, 6H), 6.98(t, J = 8.0, 1H),
5.96 (s, 1H), 3.80–3.47 (m, 2H), 3.16–2.90 (m, 2H), 2.01 (s, 3H). 6.93(d, J = 8.0 Hz, 2H), 6.78(d, J = 8.5 Hz, 2H), 6.50(s, 1H), 5.95
13C NMR (101 MHz, CDCl3) δ 150.7, 138.2, 137.1, 135.8, 135.3, (s, 1H), 3.73(s, 3H), 3.52(m, 1H), 3.45(m, 1H), 3.02(m, 1H),
133.0, 128.8, 128.5, 128.2, 128.1, 128.0, 126.2, 121.8, 120.9, 2.78(m, 1H).
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1-(1H-Indol-3-yl)-2-p-tolyl-1,2,3,4-tetrahydroisoquinoline (4ca)
1H), 6.80 (m, 3H), 6.66 (d, J = 7.8 Hz, 1H), 5.58 (d, J = 10.6 Hz,
1H), 4.05 (m, 1H), 3.59 (m, 1H), 2.99–2.58 (m, 2H).
1
Pale red solid. H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.59
(d, J = 7.9 Hz, 1H), 7.40–6.92 (m, 12H), 6.61 (s, 1H), 6.16 (s,
1H), 3.63 (m, 2H), 3.28–3.04 (m, 1H), 2.82 (d, J = 16.3 Hz, 1H),
2.32 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 147.8, 137.5, 136.6,
135.5, 129.7, 128.9, 128.1, 127.7, 126.6, 126.5, 125.6, 124.2,
122.0, 120.2, 119.6, 119.4, 116.6, 111.0, 56.9, 42.7, 26.5, 20.4.
HRMS (EI) for C24H22N2, calcd: 338.1783, found: 338.1790.
Diethyl 2-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-
1-ylphosphonate (6ba)10d
1
Colorless oil. H NMR (300 MHz, CDCl3) δ 7.38 (d, J = 6.6 Hz,
1H), 7.15 (m, 3H), 6.90 (m, 2H), 6.80 (m, 2H), 5.01 (d, J =
21.5 Hz, 1H), 4.25–3.86 (m, 5H), 3.74 (s, 3H), 3.60–3.41 (m,
1H), 2.90 (d, J = 7.8 Hz, 2H), 1.24 (t, J = 6.1 Hz, 3H), 1.15 (t, J =
7.1 Hz, 3H).
2-(4-Chlorophenyl)-1-(1H-indol-3-yl)-1,2,3,4-
tetrahydroisoquinoline (4da)
Diethyl 2-p-tolyl-1,2,3,4-tetrahydroisoquinolin-1-ylphosphonate
1
White solid. H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.59 (d,
(6ca)10d
J = 7.9 Hz, 1H), 7.41–7.17 (m, 8H), 7.13 (t, J = 8.0, 1H), 6.97 (d,
J = 7.9 Hz, 2H), 6.63 (s, 1H), 6.15 (s, 1H), 3.76–3.48 (m, 2H),
3.09 (m, 1H), 2.87 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 148.4,
137.1, 136.6, 135.3, 129.0, 128.8, 128.0, 126.8, 126.3, 125.8,
124.1, 122.9, 122.2, 119.9, 119.7, 118.8, 117.0, 111.1, 56.8, 42.6,
26.6. HRMS (EI) for C23H19ClN2, calcd: 358.1237, found:
358.1244.
Colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.34 (m, 1H),
7.19–7.08 (m, 3H), 7.02 (d, J = 8.3 Hz, 2H), 6.85 (d, J = 8.7 Hz,
2H), 5.09 (d, J = 20.8 Hz, 1H), 4.20–3.81 (m, 5H), 3.67–3.50 (m,
1H), 2.96 (m, 2H), 2.22 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.12
(t, J = 7.1 Hz, 3H).
Diethyl 2-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-
1-ylphosphonate (6da)10d
Colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.34 (m, 1H),
7.30–7.09 (m, 5H), 6.89 (d, J = 9.1 Hz, 2H), 5.10 (d, J = 19.2 Hz,
1H), 4.24–3.76 (m, 5H), 3.65–3.47 (m, 1H), 3.29–2.84 (m, 2H),
1.23 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H).
Diethyl 2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-
ylphosphonate (6aa)10a
White solid. 1H NMR (400 MHz, CDCl3) δ 7.49–7.31 (m, 1H),
7.31–7.07 (m, 5H), 6.98 (d, J = 8.3 Hz, 2H), 6.80 (t, J = 7.6 Hz,
1H), 5.19 (d, J = 20.0 Hz, 1H), 4.24–3.79 (m, 4H), 3.60 (m, 1H),
3.18–2.89 (m, 2H), 1.26 (t, J = 6.8 Hz, 3H), 1.16 (t, J = 6.8 Hz,
3H).
Diethyl 2-(3-nitrophenyl)-1,2,3,4-tetrahydroisoquinolin-
1-ylphosphonate (6ea)
1
Pale yellow oil. H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.62
Diisopropyl 2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-
ylphosphonate (6ab)10a
(m, 1H), 7.39 (m, 2H), 7.32–7.12 (m, 4H), 5.22 (d, J = 17.7 Hz,
1H), 4.13–3.79 (m, 5H), 3.68–3.55 (m, 1H), 3.47–3.31 (m, 1H),
3.12–2.92 (m, 1H), 1.24 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz,
3H). 13C NMR (101 MHz, CDCl3) δ 149.6, 149.6, 149.2,
136.2, 136.1, 130.1, 129.6, 128.5, 128.5, 128.2, 128.1,
128.0, 127.9, 126.2, 126.2, 119.34, 112.4, 108.0, 63.1, 63.0, 62.8,
62.7, 59.3, 57.8, 43.8, 27.3, 16.4, 16.3, 16.3. HRMS (ESI) exact
mass for C19H23N2O5P [M + H]+ calcd: 391.1423; found:
391.1419.
White solid. 1H NMR (400 MHz, CDCl3) δ 7.47–7.36 (m, 1H),
7.35–7.07 (m, 5H), 6.98 (d, J = 9.7 Hz, 2H), 6.80 (t, J = 7.6 Hz,
1H), 5.14 (d, J = 19.9 Hz, 1H), 4.76–4.48 (m, 2H), 4.16–3.95 (m,
1H), 3.64 (m, 1H), 3.18–2.82 (m, 2H), 1.30 (m, 6H), 1.17 (d, J =
4.6 Hz, 3H), 0.94 (d, J = 4.6 Hz, 3H).
Dibenzyl 2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-
ylphosphonate (6ac)10a
1
White solid. H NMR (400 MHz, CDCl3) δ 7.61–7.09 (m, 16H),
1-(Dip-tolylphosphoryl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (6af)
7.00 (d, J = 8.3 Hz, 2H), 6.85 (t, J = 7.6 Hz, 1H), 5.30 (d, J =
19.7 Hz, 1H), 5.13–4.71 (m, 4H), 4.05 (m, 1H), 3.74–3.55
(m, 1H), 3.23–2.88 (m, 2H).
White solid. 1H NMR (400 MHz, CDCl3) δ 7.69 (m, 2H), 7.59
(m, 2H), 7.42–7.05 (m, 8H), 7.05–6.91 (m, 1H), 6.77 (m, 4H),
5.51 (d, J = 10.5 Hz, 1H), 4.13–3.90 (m, 1H), 3.61 (m, 1H), 2.79
(m, 2H), 2.47 (s, 3H), 2.34 (s, 4H). 13C NMR (101 MHz, CDCl3)
δ 150.1, 150.0, 142.2, 141.9, 136.8, 132.3, 132.2, 131.7, 131.6,
130.2, 129.7, 129.2, 129.0, 128.9, 128.7, 127.9, 127.8, 127.2,
125.4, 119.3, 116.67, 62.4, 61.6, 44.9, 25.5, 21.6, 21.5. HRMS
(ESI) exact mass for C29H29NOP [M + H]+ calcd: 438.1987;
found: 438.1994.
Diphenyl 2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-
ylphosphonate (6ad)10b
1
White solid. H NMR (300 MHz, CDCl3) δ 7.46 (d, J = 6.7 Hz,
1H), 7.29–6.91 (m, 16H), 6.86–6.77 (m, 2H), 5.53 (d, J =
20.2 Hz, 1H), 4.13–3.97 (m, 1H), 3.68–3.55 (m, 1H), 3.00 (m,
2H).
1-(Diphenylphosphoryl)-2-phenyl-1,2,3,4-
tetrahydroisoquinoline (6ae)10d
White solid. 1H NMR (400 MHz, CDCl3) δ 7.96–7.78 (m, 2H),
Conclusions
7.78–7.66 (m, 2H), 7.55 (m, 1H), 7.51–7.42 (m, 3H), 7.35 (m, In summary, we have developed a highly efficient and scalable
2H), 7.20–7.12 (m, 3H), 7.09 (d, J = 7.5 Hz, 1H), 7.02–6.91 (m, triarylaminium salt induced aerobic oxidative C–H functionali-
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Paper
Organic & Biomolecular Chemistry
zation of N-aryl tetrahydroisoquinolines to form C–C and C–P
bonds. Simple organo-SET oxidant induced process and the
use of molecular oxygen as the oxidant make this transform-
ation practical and sustainable. TBPA+•SbCl6− 1 displays a high
activity in oxidative coupling reaction and this highlights the
potential of stable radical cation salts in promoting new reac-
tions via O2 involved C–H bond activation. Further exploration
of more sustainable and metal-free catalytic systems for
aerobic oxidative coupling is ongoing in our laboratory.
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Acknowledgements
We thank the National Natural Science Foundation of China
(21262029) and the Fok Ying Tong Education Foundation
(141116) for financially supporting this work.
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