Direct sp3 C-H amination of nitrogen-containing benzoheterocycles mediated by visible-light-photoredox catalysts

Article abstract of DOI:10.1002/chem.201203066

Visible-light-mediated direct sp³ C-H amination of benzocyclic amines via α-aminoalkyl radicals by using photoredox catalysts is described here. The obtained N,N-acetals were also successfully applied for carbon-carbon bond forming reactions with carbon nucleophiles. The procedure is suitable for a late-stage modification of C-H bonds to C-C bonds. Amination sees the light: Visible-light-mediated direct sp³ C-H amination of benzocyclic amines via α-aminoalkyl radicals by using photoredox catalysts is described here (see scheme). The obtained N,N-acetals were also successfully applied for carbon-carbon bond-forming reactions with carbon nucleophiles. The procedure is suitable for a late-stage modification of C-H bonds to C-C bonds.

Full text of DOI:10.1002/chem.201203066

FULL PAPER
DOI: 10.1002/chem.201203066
3
À
Direct sp C H Amination of Nitrogen-Containing Benzohetero
Mediated by Visible-Light-Photoredox Catalysts
ACHTUNGTRNEcNUNG ycles
Yoshihiro Miyake, Kazunari Nakajima, and Yoshiaki Nishibayashi*[a]
3
À
Abstract: Visible-light-mediated direct sp C H amination of benzocyclic amines
via a-aminoalkyl radicals by using photoredox catalysts is described here. The ob-
tained N,N-acetals were also successfully applied for carbon–carbon bond forming
reactions with carbon nucleophiles. The procedure is suitable for a late-stage modi-
Keywords: amination · heterocy-
cles · photocatalysts · redox chemis-
try
À
À
fication of C H bonds to C C bonds.
Introduction
Recently, we reported visible-light-mediated direct a-alky-
lation of amines[8] in which the formation of a-aminoalkyl
radicals meditated by photoredox catalysts is a key step,[9–13]
Nitrogen-containing benzoheterocycles, such as 1,2,3,4-tetra-
hydroquinolines and indolines, are common and important
structural motifs in biologically active natural compounds
and pharmaceutical products,[1] and thus the development of
efficient synthetic strategies to construct these skeletons is
À
and this C H functionalization via a-aminoalkyl radicals
provides an alternative approach to routes via iminium ions.
It is also worth noting that this reaction system is applicable
to the a-alkylation of indolines.[8] As an extension of our
study, we have now envisaged visible-light-mediated addi-
tion of a-aminoalkyl radicals to azodicarboxylate esters to
highly important. Direct functionalization of an sp3 C H
À
bond adjacent to the nitrogen atom is expected to be a suit-
able route for a late-stage modification of nitrogen-contain-
ing benzoheterocycles. Consequently, the oxidation of
amines to iminium ions and the subsequent addition of nu-
cleophiles are extensively studied as an efficient method for
À
give C N bond formation at the a-position. In fact, we have
À
succeeded in the direct a-C H amination of 1,2,3,4-tetrahy-
droquinolines and indolines to give N,N-acetals, which were
applied to further transformations to give functionalized
benzocyclic amines (Scheme 2). To the best of our knowl-
[2,3]
À
C H functionalization (Scheme 1).
In most of the report-
ed systems that proceed via iminium ions,[2a] reactions of
1,2,3,4-tetrahydroisoquinolines, methylamines, and glycine
derivatives that form non-enolizable iminium ions have
been developed so far, but successful transformations of
1,2,3,4-tetrahydroquinolines and indolines are quite limit-
ed[4,5] because undesirable reactions such as tautomerization
of iminium ions into enamines[6] and aromatization in the
presence of stoichiometric oxidants[7] are considered to in-
hibit the reaction of iminium ions with nucleophiles.
Scheme 2. Photochemical sp3 C H amination of benzocyclic amines with
À
azodicarboxylate esters (this work).
À
edge, there is no report of direct a-C H amination of
1,2,3,4-tetrahydroquinolines and indolines, although the for-
Scheme 1. sp3 C H functionalization of benzocyclic amines by oxidation
into an iminium ion.
À
À
À
mation of C C and C O bonds at the a-position of these
structures has been reported.[4,5] For decades it has been
known that heating tertiary amines with azodicarboxylate
esters gives a-aminated products via triazine intermediates,
but applicable substrates are still limited and there is no
report for diarylamines, including N-aryl-1,2,3,4-tetrahydro-
quinolines and N-arylindolines.[6b,14,15] Preliminary results
are described herein.
[a] Dr. Y. Miyake, K. Nakajima, Assoc. Prof. Dr. Y. Nishibayashi
Institute of Engineering Innovation
School of Engineering
The University of Tokyo
Yayoi, Bunkyo-ku, Tokyo, 113-8656 (Japan)
E-mail: ynishiba@sogo.t.u-tokyo.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203066.
Chem. Eur. J. 2012, 18, 16473 – 16477
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16473

Table 2. Photochemical reactions of amines (1a) with di-tert-butyl azodi-
carboxylate (2a).[a]
Results and Discussion
First, we investigated the reaction of N-phenyl-1,2,3,4-tetra-
hydroquinoline (1a) with di-tert-butyl azodicarboxylate
(2a). When a solution of 1a and two equivalents of 2a in
the presence of 1 mol% of [4a]ACHTNUGRTENUNG[BF4] in N-methylpyrroli-
done (NMP) was illuminated with a 14 W white LED at
258C for 18 h, N-phenyl-2-(1,2-di-tert-butoxycarbonylhydra-
zino)-1,2,3,4-tetrahydroquinoline (3a) was obtained in 45%
yield (Table 1, entry 1). Use of a larger amount of 2a in-
Table 1. Photochemical reactions of N-phenyl-1,2,3,4-tetrahydroquinoline
(1a) with di-tert-butyl azodicarboxylate (2a).[a]
Entry
2a [equiv]
Photocatalyst
[4a][BF4]
[4a][BF4]
[4a][BF4]
[4b][BF4]
[4c][BF4]
[Ru(bpy)3]
Yield of 3a [%]
1
2
3
4
5
6
7
8
2
3
4
4
4
4
4
4
4
4
G
N
45
72
85
79
72
66
24
0
E
E
T
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
G
ACHTUNGRTEN[NUNG BF4]
DCA
none
9[b]
10[b,c]
A
R
0
28
[a] All reactions of 1a (0.25 mmol) with 2a (4 equiv) were carried out in
the presence of photocatalyst) 0.0025 mmol) in NMP (2.5 mL) at 258C
and under illumination with a 14 W white LED for 18 h. [b] 3 equiv of 2a
was used. [c] 5 equiv of 2a was used.
[a] All reactions of 1a (0.25 mmol) with 2a were carried out in the pres-
ence of photocatalyst (0.0025 mmol) in NMP (2.5 mL) with 14 W white
LED illumination at 258C for 18 h. [b] In the absence of light. [c] At
808C.
good yields. Reactions of other six-membered benzocyclic
amines, such as 1,2,3,4-tetrahydroquinoxaline, 3,4-dihydro-
2H-1,4-benzoxazine, and 3,4-dihydro-2H-benzo-1,4-thiazine
derivatives, proceeded smoothly to give 3n–p in moderate
yields. When seven-membered benzocyclic amine was used
as a substrate, 3q was also obtained in 39% yield. Unfortu-
nately, reactions of acyclic amines were sluggish and the
yields of 3r and 3s were relatively low.[16] On the other
hand, in reactions of dialkyl amines, such as N-phenyl-
1,2,3,4-tetrahydroisoquinoline, N-phenylmorphorine, and N-
isopropyl-1,2,3,4-tetrahydroquinoline, only trace amounts of
a-aminated products were observed. These results are in
sharp contrast to reactions of dialkyl and trialkyl amines
with azodicarboxylate esters under thermal conditions,[6b,15]
and thus the photochemical reaction described here is con-
sidered to be a complementary method to the reported ther-
mal reactions.
creased the yield of 3a, and the best result (85% yield) was
obtained when four equivalents of 2a was used (Table 1, en-
tries 2 and 3). When other photocatalysts, such as [4b]
[4c][BF4], and [Ru(bpy)3][BF4], were used in place of [4a]-
ACHTUNGTRENNUNG[BF4], 3a was obtained in slightly lower yields (Table 1, en-
ACHTUNGTNER[NUGN BF4],
A
R
ACHTUNGTRENNUNG
tries 4–6), whereas the use of 9,10-dicyanoanthracene
(DCA) dramatically decreased the yield of 3a (Table 1,
entry 7). The reaction did not proceed at all in the absence
of photocatalyst or in the absence of light (Table 1, entries 8
and 9). Separately, we confirmed that the use of heating
conditions (at 808C)[6b,15] was not effective for the reaction
of 1a with 2a (Table 1, entry 10).
Next we investigated reactions of various amines (1) with
2a (Table 2). The introduction of a variety of functional
groups at the para-position in the benzene ring of N-phenyl-
1,2,3,4-tetrahydroquinoline was successful and the corre-
sponding aminated products (3b–h) were obtained in good
to high yields. A variety of indolines were also applicable to
this reaction system, giving a-aminated indolines (3i–m) in
Considering the redox potential of amines[17] and azodi-
carboxylate esters,[18] both oxidation of amines and reduc-
tion of azodicarboxylate esters by excited photocatalyst[19]
are possible. To obtain mechanistic insight into the electron-
transfer process, we investigated fluorescence quenching
studies of 4a in the presence of 1a or 2a in NMP. The rate
16474
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 16473 – 16477

Amination of Benzoheterocycles
FULL PAPER
constants for 1a and 2a were estimated to be 9.07ꢁ
108 mÀ1 sÀ1 and 6.35ꢁ108 mÀ1 sÀ1, respectively, by using the
Stern–Volmer plot. These results indicate that both elec-
tron-transfer processes certainly occur and the oxidation of
amines is slightly faster than the reduction of azodicarboxy-
late esters. Additionally, the quantum yield in the reaction
of 1a with 2a was estimated to be 0.27, which is less than 1
and is within the usual range of molecular transformations
by photoinduced electron transfer mediated by transition-
metal polypyridyl complexes.[8,20]
Scheme 5. Reaction of 3c with indole.
yields (Scheme 4a). The reaction of indoline derivative 3k
with allylmagnesium bromide was also successful to give 6
in 59% yield (Scheme 4b). It is worth noting that Grignard
reagents were successfully applied as nucleophiles because
Grignard reagents are usually difficult to use under oxida-
tive reaction conditions. Interestingly, reaction of 3c with
indole in the presence of a catalytic amount of TsOH also
proceeded smoothly to give 7 in 77% yield (Scheme 5). On
the other hand, when the reaction of N-(4-tert-butylphenyl)-
1,2,3,4-tetrahydroquinoline (1c) with indole in the presence
of a catalytic amount of CuBr was carried out under oxida-
tive reaction conditions, unidentified products were ob-
served without the formation of 7.[24] This result is in sharp
contrast to the reported reactions of tetrahydroisoquino-
lines, which form non-enolizable iminium ions with indoles
to give the coupling products in high yields under similar
conditions.[25] From these results, we believe that the ob-
tained N,N-acetals from our procedure are useful building
Accordingly, a plausible reaction pathway is shown in
Scheme 3. First, oxidation of amine (1) by the excited pho-
Scheme 3. A plausible reaction pathway.
blocks for the synthesis of a-functionalized amines. In addi-
3
À
tion, the combination of photochemical sp C H amination
tocatalyst (*cat) and deprotonation occur to give the re-
duced form of photocatalyst (catÀ) and a-aminoalkyl radical
(A). Subsequent reduction of the azodicarboxylate ester
(2a) by catÀ affords radical anion (B). After the radical–rad-
ical coupling of A with B to give C,[10,21] protonation of C
leads to the a-aminated product (3). On the other hand, the
reaction pathway involving the direct addition of A to
2a[15a,22] and subsequent reduction into C, similar to that de-
scribed in our previous reports,[8] is also possible.
of 1 (Tables 1 and 2) and the substitution reactions of 3 with
carbon-centered nucleophiles (Schemes 4 and 5) is consid-
3
À
ered to be a formal transformation of the sp C H bond of
À
amines into a C C bond, and is an alternative method for
oxidative transformations of amines via iminium ions
(Scheme 1).
Conclusion
N,N-Acetals are useful building blocks for nitrogen-con-
taining compounds because of their high reactivity toward
nucleophilic substitution reactions at the a-position.[14,23] We
applied the obtained N,N-acetals 3 for nucleophilic substitu-
tion reactions with various carbon-centered nucleophiles
(Schemes 4 and 5). A variety of Grignard reagents were ap-
plicable as nucleophiles (Scheme 4). The use of allyl-,
benzyl-, phenyl- and ethynyl-magnesium bromides as sp3-,
sp2-, and sp-carbon-centered nucleophiles gave 5a–d in high
In summary, we have developed a visible-light-mediated
3
À
direct sp C H amination of benzocyclic amines via a-ami-
noalkyl radicals, which is still a challenging task in synthetic
3
organic chemistry.[26] The procedure of sp C H amination
À
and nucleophilic substitution described in this article is suit-
able for a late-stage modification of nitrogen-containing het-
erocycles. Further applications of the method to the synthe-
sis of nitrogen-containing organic compounds are now under
investigation.
Experimental Section
General method: 1H NMR (270 MHz) and 13C NMR (67.8 MHz) spectra
were recorded in a suitable solvent by using a JEOL Excalibur 270 spec-
trometer. Mass spectra were measured on a JEOL JMS-700 mass spec-
trometer. Absorption and emission spectra were recorded by using Shi-
madzu MultiSpec-1500 and Shimadzu RF-5300PC spectrometers, respec-
tively. Excited-state lifetimes were measured by using a Hamamatsu
Quantaurus-Tau C11367 instrument. All reactions were carried out under
a dry nitrogen atmosphere. Solvents were dried by using general methods
Scheme 4. Reactions of 3c and 3k with Grignard reagents.
Chem. Eur. J. 2012, 18, 16473 – 16477
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16475

Y. Nishibayashi et al.
and degassed before use. Photoirradiation was carried out by using 14 W
white LED. Amines (1) were prepared from the reaction of correspond-
ing secondary amines with aryl halides.[27] Photocatalysts (4a–c) were pre-
pared according to reported procedures.[8b] Note that only observed sig-
nals are described for 13C NMR spectroscopic data because several sig-
nals are not observed due to significant broadening even at elevated tem-
perature.
2.18–2.06 (brm, 1H), 1.36 (s, 9H), 1.31 ppm (s, 9H); 13C NMR (C6D6,
508C): d=128.2, 127.0, 103.8, 80.5, 65.2, 28.2, 28.1 ppm; HRMS (FAB):
m/z calcd for C28H37N3O6: 511.2682 [M]; found: 511.2663.
Data for 3h: White solid (yield: 60%). M.p.: 178.68C (decomp.);
1H NMR (C6D6, 708C): d=7.16–7.08 (brm, 4H), 6.94–6.89 (brm, 1H),
6.73–6.69 (brm, 2H), 6.61–6.58 (brm, 1H), 6.09 (brs, 1H), 6.87 (brs,
1H), 2.70 (brs, 1H), 2.60–2.43 (brm, 2H), 2.21–2.11 (brm, 1H), 2.13 (s,
3H), 1.36 (s, 9H), 1.33 ppm (s, 9H); 13C NMR (C6D6, 508C): d=28.2,
28.1, 20.5 ppm; HRMS (FAB): m/z calcd for C26H36N3O4: 454.2706 [M+
H]; found: 454.2689.
General procedure for photocatalytic reactions of amines (1) with azodi-
carboxylate esters (2a): A typical experimental procedure for the reac-
tion of N-phenyl-1,2,3,4-tetrahydroquinoline (1a) with di-tert-butyl azodi-
Data for 3i: Viscous oil (yield: 36%). 1H NMR (C6D6, 708C): d=7.24–
7.15 (brm, 2H), 6.98–6.95 (brm, 2H), 6.93–6.66 (brm, 4H), 6.47 (brs,
1H), 5.91 (brs, 1H), 3.52–3.35 (brm, 1H), 3.38 (s, 3H), 3.21–3.11 (brm,
1H), 1.33 (s, 9H), 1.32 ppm (s, 9H); 13C NMR (C6D6, 508C): d=124.6,
119.0, 115.2, 107.9, 55.1, 28.13, 28.07 ppm; HRMS (FAB): m/z calcd for
C25H33N3O5: 455.2420 [M]; found: 455.2437.
Data for 3j: Viscous oil (yield: 57%). 1H NMR (C6D6, 708C): d=7.22–
7.16 (brm, 2H), 6.98–6.93 (brm, 4H), 6.83–6.80 (brm, 1H), 6.71–6.66
(brm, 1H), 6.50 (brs, 1H), 5.82 (brs, 1H), 3.52–3.45 (brm, 1H), 3.18–
3.08 (brm, 1H), 2.13 (s, 3H), 1.34 (s, 9H), 1.30 ppm (s, 9H); 13C NMR
(C6D6, 508C): d=130.2, 124.6, 119.3, 28.1, 20.8 ppm; HRMS (FAB): m/z
calcd for C25H34N3O4: 440.2549 [M+H]; found: 440.2550.
Data for 3k: Viscous oil (yield: 74%). 1H NMR (C6D6, 708C): d=7.31–
7.28 (brm, 2H), 7.18–7.12 (brm, 2H), 6.96–6.83 (brm, 4H), 6.72–6.66
(brm, 1H), 6.50 (brs, 1H), 5.78 (brs, 1H), 3.43 (brs, 1H), 3.16–3.06
(brm, 1H), 1.34 (s, 9H), 1.29 ppm (s, 9H); 13C NMR (C6D6, 508C): d=
129.6, 127.2, 124.7, 119.6, 108.6, 28.11, 28.10 ppm; HRMS (FAB): m/z
calcd for C24H32N3O4: 426.2393 [M+H]; found: 426.2414.
Data for 3l: Viscous oil (yield: 71%). 1H NMR (C6D6, 708C): d=7.16–
6.91 (brm, 6H), 6.75–6.66 (brm, 2H), 6.36 (brs, 1H), 5.70 (brs, 1H), 3.36
(brs, 1H), 3.11–3.01 (brm, 1H), 1.33 (s, 9H), 1.28 ppm (s, 9H); 13C NMR
(C6D6, 508C): d=129.6, 124.7, 119.9, 28.1 ppm; HRMS (FAB): m/z calcd
for C24H31N3O4Cl: 460.2003 [M+H]; found: 460.1995.
Data for 3m: Viscous oil (yield: 52%). 1H NMR (C6D6, 708C): d=7.16–
6.99 (brm, 4H), 6.78–6.72 (brm, 3H), 6.37 (brs, 1H), 5.70 (brs, 1H), 3.36
(brs, 1H), 3.12–3.02 (brm, 1H), 2.14 (s, 3H), 1.36 (s, 9H), 1.28 ppm (s,
9H); 13C NMR (C6D6, 508C): d=129.6, 129.1, 125.7, 28.11, 28.07 ppm;
HRMS (FAB): m/z calcd for C25H32N3O4Cl: 473.2081 [M]; found:
473.2099.
Data for 3n: Viscous oil (yield: 55%). 1H NMR (C6D6, 708C): d=7.20–
7.11 (brm, 5H), 7.01–6.96 (brm, 1H), 6.77–6.71 (brm, 1H), 6.64–6.59
(brm, 2H), 6.14 (brs, 1H), 6.05 (brs, 1H), 4.42 (brs, 1H), 3.71 (brs, 1H),
2.1 (s, 3H), 1.34 (s, 9H), 1.26 ppm (s, 9H); 13C NMR (C6D6, 508C): d=
129.9, 28.2, 28.0 ppm; HRMS (FAB): m/z calcd for C26H35N4O5: 483.2607
[M+H]; found: 483.2603.
Data for 3o: White solid (yield: 51%). M.p.: 110.9–112.38C; 1H NMR
(C6D6, 708C): d=7.20–7.08 (brm, 4H), 6.99–6.91 (brm, 2H), 6.70–6.61
(brm, 3H), 5.93 (brs, 2H), 4.48 (brs, 1H), 4.01 (brs, 1H), 1.35 (s, 9H),
1.31 ppm (s, 9H); 13C NMR (C6D6, 508C): d=129.8, 121.8, 112.0, 117.1,
28.2, 28.0 ppm; HRMS (FAB): m/z calcd for C24H31N3O5: 441.2264 [M];
found: 441.2260.
Data for 3p: White solid (yield: 49%). M.p.: 130.1–131.88C; 1H NMR
(C6D6, 708C): d=7.16–7.05 (brm, 5H), 6.93–6.87 (brm, 1H), 6.77–6.72
(brm, 2H), 6.64–6.58 (brm, 1H), 6.27 (brs, 1H), 6.11 (brs, 1H), 3.27
(brs, 1H), 3.01 (brs, 1H), 1.35 (s, 9H), 1.32 ppm (s, 9H); 13C NMR
(C6D6, 508C): d=129.8, 126.3, 125.6, 124.9, 120.6, 81.3, 28.2, 28.1 ppm;
HRMS (FAB): m/z calcd for C24H32N3O4S: 458.2114 [M+H]; found:
458.2124.
carboxylate (2a) is described below. A mixture of [4a]ACTHNUTRGNE[UNG BF4] (2.1 mg,
0.0025 mmol), 2a (229.8 mg, 0.998 mmol), and N-methylpyrrolidone
(2.5 mL) was placed in a 20 mL Schlenk flask (diameter: 2.5 cm) under
N2, and then 1a (52.2 mg, 0.249 mmol) was added. The reaction flask was
placed in a water bath (258C) and illuminated by using a 14 W white
LED (approximately 2 cm from the light source) for 18 h. The resulting
mixture was purified by using column chromatography (SiO2) with
hexane/ethyl acetate (20:1 to 10:1) as the eluent to give N-phenyl-2-(1,2-
di-tert-butoxycarbonylhydrazino)-1,2,3,4-tetrahydroquinoline
(3a;
93.1 mg, 0.212 mmol, 85% isolated yield).
Data for 3a: White solid. M.p.: 127.6–129.18C; 1H NMR (C6D6, 708C):
d=7.13–7.07 (m, 4H), 6.97–6.83 (m, 3H), 6.73–6.67 (m, 1H), 6.60–6.57
(m, 1H), 6.07 (brs, 1H), 5.90 (brs, 1H), 2.79 (brs, 1H), 2.64–2.54 (brm,
1H), 2.42 (brs, 1H), 2.18–2.06 (brm, 1H), 1.37 (s, 9H), 1.30 ppm (s, 9H);
13C NMR (C6D6, 508C): d=154.2, 129.8, 128.6, 126.9, 119.3, 80.8, 80.6,
28.2, 28.1, 25.3 ppm; HRMS (FAB): m/z calcd for C25H34N3O4: 440.2549
[M+H]; found: 440.2546.
Data for 3b: White solid (yield: 85%). M.p.: 141.8–142.48C; 1H NMR
(C6D6, 708C): d=7.03–7.00 (m, 2H), 6.94–6.86 (m, 2H), 6.75–6.65 (m,
3H), 6.49–6.46 (m, 1H), 6.01 (brs, 2H), 3.37 (s, 3H), 2.92–2.81 (brm,
1H), 2.74–2.63 (brm, 1H), 2.54–2.45 (brm, 1H), 2.20–2.08 (brm, 1H),
1.41 (s, 9H), 1.27 ppm (s, 9H); 13C NMR (C6D6, 508C): d=154.3, 128.7,
127.0, 118.5, 115.5, 80.8, 80.6, 55.0, 28.3, 28.1, 27.7 ppm; elemental analy-
sis calcd (%) for C26H35N3O5: C 66.50, H 7.51, N 8.95; found: C 66.30, H
7.64, N 8.74.
Data for 3c: White solid (yield: 80%). M.p.: 180.68C (decomp.);
1H NMR (CD2Cl2, 258C): d=7.44–7.41 (m, 2H), 7.17–7.14 (m, 2H), 7.03–
7.00 (m, 1H), 6.90–6.85 (m, 1H), 6.68–6.63 (m, 1H), 6.36–5.70 (brm,
3H), 2.85 (brs, 2H), 2.38–2.01 (brm, 2H), 1.44 (s, 9H), 1.33 (s, 9H),
1.23 ppm (s, 9H); 13C NMR (CD2Cl2, 258C): d=128.0, 126.4, 126.2, 34.1,
30.8, 27.6, 27.4, 22.3 ppm; HRMS (FAB): m/z calcd for C29H41N3O4:
495.3097 [M]; found: 495.3078.
Data for 3d: White solid (yield: 90%). M.p.: 129.3–131.28C; 1H NMR
(C6D6, 708C): d=7.05–7.02 (brm, 2H), 6.94–6.84 (brm, 4H), 6.72–6.66
(m, 1H), 6.57–6.54 (brm, 1H), 6.05 (brs, 1H), 5.94 (brs, 1H), 2.89–2.78
(brm, 1H), 2.69–2.58 (brm, 1H), 2.50–2.43 (brm, 1H), 2.19–2.06 (brm,
1H), 2.11 (s, 3H), 1.38 (s, 9H), 1.28 ppm (s, 9H); 13C NMR (C6D6, 508C):
d=154.2, 130.6, 128.7, 126.9, 118.9, 80.6, 28.2, 28.1, 20.8 ppm; HRMS
(FAB); m/z calcd for C26H35N3O4: 453.2628 [M]; found: 453.2645.
Data for 3e: White solid (yield 60%). M.p. 138.2–139.58C; 1H NMR
(C6D6, 708C): d=7.08–7.04 (m, 2H), 6.94–6.85 (brm, 4H), 6.74–6.68 (m,
1H), 6.53–6.51 (brm, 1H), 5.94 (brs, 1H), 5.81 (brs, 1H), 2.68 (brs, 1H),
2.57–2.27 (brm, 1H), 2.33 (brs, 1H), 2.13–2.00 (brm, 1H), 1.35 (s, 9H),
1.30 ppm (s, 9H); 13C NMR (C6D6, 508C): d=154.1, 129.9, 128.6, 127.0,
81.1, 80.7, 28.2, 28.1, 25.2 ppm; HRMS (FAB): m/z calcd for
C25H32N3O4Cl: 473.2081 [M]; found: 473.2100.
Data for 3 f: Viscous oil (yield: 44%). 1H NMR (C6D6, 708C): d=8.07–
8.04 (brm, 2H), 7.20 (brs, 2H), 6.93–6.89 (brm, 3H), 6.80–6.74 (brm,
1H), 6.09 (brs, 1H), 5.77 (brs, 1H), 2.53 (brs, 1H), 2.42–2.06 (brm, 3H),
1.50 (s, 9H), 1.37 (s, 9H), 1.30 ppm (s, 9H); 13C NMR (C6D6, 508C): d=
165.4, 155.5, 154.1, 131.3, 126.9, 121.5, 81.3, 80.5, 80.0, 28.3, 28.17, 28.16,
25.1 ppm; HRMS (FAB): m/z calcd for C30H42N3O6: 540.3074 [M+H];
found: 540.3065.
Data for 3q: Viscous oil (yield: 39%). 1H NMR (C6D6, 408C): d=7.16–
6.74 (brm, 9H), 6.10 (brs, 1H), 5.76 (brs, 1H), 2.44 (brs, 1H), 2.24 (brs,
1H), 2.07 (brs, 1H), 1.62–1.27 ppm (brm, 21H); 13C NMR (C6D6, 408C):
d=28.4, 28.2 ppm; HRMS (FAB): m/z calcd for C26H35N3O4: 453.2628
[M]; found: 453.2619.
Data for 3r: White solid (yield: 49%). M.p.: 141.1–143.18C; 1H NMR
(C6D6, 708C): d=7.14–7.06 (m, 8H), 6.88–6.81 (m, 2H), 5.87 (brs, 1H),
5.43 (brs, 2H), 1.38 (s, 9H), 1.32 ppm (s, 9H); 13C NMR (C6D6, 508C):
Data for 3g: Viscous oil (yield: 79%). 1H NMR (C6D6, 708C): d=7.47–
7.42 (m, 2H), 7.17–7.15 (brm, 2H), 6.93–6.83 (m, 2H), 6.74–6.60 (brm,
2H), 6.06 (brs, 1H), 5.94 (brs, 1H), 5.74 (s, 1H), 3.75–3.63 (m, 2H),
3.59–3.51 (m, 2H), 2.73 (brs, 1H), 2.61–2.51 (brm, 1H), 2.39 (brs, 1H),
16476
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 16473 – 16477

Amination of Benzoheterocycles
FULL PAPER
d=147.7, 129.5, 122.3, 121.9, 28.2 ppm; elemental analysis calcd (%) for
C23H31N3O4: C 66.81, H 7.56, N 10.16; found: C 66.69, H 7.73, N 9.96.
[11] a) S. Kamijo, T. Hoshikawa, M. Inoue, Org. Lett. 2011, 13, 5928;
b) T. Kamon, Y. Irifune, T. Tanaka, T. Yoshimitsu, Org. Lett. 2011,
13, 2674; c) S. Angioni, D. Ravelli, D. Emma, D. Dondi, M. Fagnoni,
A. Albini, Adv. Synth. Catal. 2008, 350, 2209; d) D. Harakat, J.
Data for 3s: Viscous oil (yield: 25%). 1H NMR (C6D6, 708C): d=7.15–
7.07 (m, 4H), 7.00–6.94 (brm, 4H), 6.90–6.84 (m, 2H), 6.47 (brs, 1H),
5.60 (brs, 1H), 1.45–1.27 ppm (brm, 21H); 13C NMR (C6D6, 508C): d=
129.4, 123.7, 122.8, 28.3, 28.2 ppm; HRMS (FAB): m/z calcd for
C24H33N3O4: 427.2471 [M]; found: 427.2461.
´
Pesch, S. Marinkovic, N. Hoffmann, Org. Biomol. Chem. 2006, 4,
1202; e) A. Bauer, F. Westkꢅmper, S. Grimme, T. Bach, Nature 2005,
436, 1139.
[12] a) L. Shi, W. Xia, Chem. Soc. Rev. DOI: 10.1039/c2cs35203f; b) S.
Maity, N. Zheng, Synlett 2012, 23, 1851; c) J. Xuan, W.-J. Xiao,
Angew. Chem. Int. Ed. 2012, 51, 6828; d) A. E. Allen, D. W. C. Mac-
Millan, Chem. Sci. 2012, 3, 633; e) J. W. Tucker, C. R. J. Stephenson,
J. Org. Chem. 2012, 77, 1617; f) M. A. Ischay, T. P. Yoon, Eur. J.
Org. Chem. 2012, 3359; g) J. M. R. Narayanam, C. R. J. Stephenson,
Acknowledgements
This work was supported by the Funding Program for Next Generation
World-Leading Researchers (GR025) and a Grant-in-Aid for Scientific
Research on Innovative Areas “Advanced Molecular Transformations by
Organocatalysts” from MEXT, Japan. K.N. is a recipient of the JSPS Pre-
doctoral Fellowships for Young Scientists and acknowledges the Global
COE program for Chemistry Innovation. We thank to Prof. Dr. Atsushi
Wakamiya and Prof. Dr. Yasujiro Murata at Kyoto University for meas-
urements of excited-state lifetimes. We also thank the Research Hub for
Advanced Nano Characterization at The University of Tokyo for X-ray
analysis.
´
Chem. Soc. Rev. 2011, 40, 102; h) F. Teply, Collect. Czech. Chem.
Commun. 2011, 76, 859; i) A. Inagaki, M. Akita, Coord. Chem. Rev.
2010, 254, 1220; j) T. P. Yoon, M. A. Ischay, J. Du, Nat. Chem. 2010,
2, 527; k) K. Zeitler, Angew. Chem. 2009, 121, 9969; Angew. Chem.
Int. Ed. 2009, 48, 9785.
[13] Under thermal conditions: a) M. Nishino, K. Hirano, T. Satoh, M.
Miura, J. Org. Chem. 2011, 76, 6447; b) T. Yoshimitsu, K. Matsuda,
H. Nagaoka, K. Tsukamoto, T. Tanaka, Org. Lett. 2007, 9, 5115;
c) T. Yoshimitsu, Y. Arano, H. Nagaoka, J. Am. Chem. Soc. 2005,
127, 11610.
[14] a) X. Xu, X. Li, Org. Lett. 2009, 11, 1027; b) X. Xu, X. Li, L. Ma, N.
Ye, B. Weng, J. Am. Chem. Soc. 2008, 130, 14048.
[15] a) R. Huisgen, F. Jakob, Justus Liebigs Ann. Chem. 1954, 590, 37;
b) G. W. Kenner, R. J. Stedman, J. Chem. Soc. 1952, 2089; c) O.
Diels, E. Fischer, Ber. Dtsch. Chem. Ges. 1914, 47, 2043; d) O. Diels,
M. Paquin, Ber. Dtsch. Chem. Ges. 1913, 46, 2000.
[16] Reaction of diphenyl(trimethylsilylmethyl)amine with 2a under sim-
ilar conditions afforded 3r in 47% yield.[8a] See the Supporting In-
formation for experimental details.
[17] E. T. Seo, R. F. Nelson, J. M. Fritsch, L. S. Marcoux, D. W. Leedy,
R. N. Adams, J. Am. Chem. Soc. 1966, 88, 3498.
[1] a) D.-S. Wang, Q.-A. Chen, S.-M. Lu, Y.-G. Zhou, Chem. Rev. 2012,
112, 2557; b) V. Sridharan, P. A. Suryavanshi, J. C. Menꢂndez, Chem.
Rev. 2011, 111, 7157.
[2] a) K. M. Jones, M. Klussmann, Synlett 2012, 159; b) C. S. Yeung,
V. M. Dong, Chem. Rev. 2011, 111, 1215; c) C. J. Scheuermann,
Chem. Asian J. 2010, 5, 436; d) C.-J. Li, Acc. Chem. Res. 2009, 42,
335; e) S.-I. Murahashi, D. Zhang, Chem. Soc. Rev. 2008, 37, 1490.
[3] For selected examples of photoredox catalysis, see: a) D. A. DiRoc-
co, T. Rovis, J. Am. Chem. Soc. 2012, 134, 8094; b) M. Rueping,
R. M. Koenigs, K. Poscharny, D. C. Fabry, D. Leonori, C. Vila,
Chem. Eur. J. 2012, 18, 5170; c) Q. Liu, Y.-N. Li, H.-H. Zhang, B.
Chen, C.-H. Tung, L.-Z. Wu, Chem. Eur. J. 2012, 18, 620; d) C.
Wang, Z. Xie, K. E. deKrafft, W. Lin, J. Am. Chem. Soc. 2011, 133,
13445; e) Y.-Q. Zou, L.-Q. Lu, L. Fu, N.-J. Chang, J. Rong, J.-R.
Chen, W.-J. Xiao, Angew. Chem. 2011, 123, 7309; Angew. Chem. Int.
Ed. 2011, 50, 7171; f) D. P. Hari, B. Kçnig, Org. Lett. 2011, 13, 3852;
g) A. G. Condie, J. C. Gonzꢃlez-Gꢄmez, C. R. J. Stephenson, J. Am.
Chem. Soc. 2010, 132, 1464.
[18] L. Eberson, O. Persson, J. O. Svensson, Acta Chim. Scand. 1998, 52,
1293.
[19] M. S. Lowry, J. I. Goldsmith, J. D. Slinker, R. Rohl, R. A. Pascal Jr.,
G. G. Malliaras, S. Bernhard, Chem. Mater. 2005, 17, 5712.
[20] For selected examples, see: a) S. Fukuzumi, T. Kishi, H. Kotani, Y.-
M. Lee, W. Nam, Nat. Chem. 2011, 3, 38; b) H. Takeda, K. Koike,
H. Inoue, O. Ishitani, J. Am. Chem. Soc. 2008, 130, 2023; c) E. D.
Cline, S. E. Adamson, S. Bernhard, Inorg. Chem. 2008, 47, 10378;
d) B. Gholamkhass, H. Mametsuka, K. Koike, T. Tanabe, M. Furue,
O. Ishitani, Inorg. Chem. 2005, 44, 2326; e) H. Cano-Yelo, A. Der-
onzier, Tetrahedron Lett. 1984, 25, 5517; f) P. J. DeLaive, T. K. Fore-
man, C. Giannotti, D. G. Whitten, J. Am. Chem. Soc. 1980, 102,
5627.
[21] a) F. D. Lewis, Acc. Chem. Res. 1986, 19, 401; b) F. D. Lewis, T.-I.
Ho, J. T. Simpson, J. Am. Chem. Soc. 1982, 104, 1924.
[22] a) M. Ohno, K. Ishizaki, S. Eguchi, J. Org. Chem. 1988, 53, 1285;
b) B. M. Jacobson, G. M. Arvanitis, C. A. Eliasen, R. Mitelman, J.
Org. Chem. 1985, 50, 194.
À
[4] For C C bond formation, see: a) G. Kumaraswamy, A. N. Murthy,
A. Pitchaiah, J. Org. Chem. 2010, 75, 3916; b) S. Shahane, F. Louafi,
J. Moreau, J.-P. Hurvois, J.-L. Renaud, P. van de Weghe, T. Roisnel,
Eur. J. Org. Chem. 2008, 4622; c) R. Malassene, L. Sanchez-Bajo, L.
Toupet, J.-P. Hurvois, C. Moinet, Synlett 2002, 1500; d) E. Le Gall,
T. Renaud, J.-P. Hurvois, A. Tallec, C. Moinet, Synlett 1998, 513;
e) A. Konno, T. Fuchigami, Y. Fujita, T. Nonaka, J. Org. Chem.
1990, 55, 1952.
À
[5] For C O bond formation, see: a) M. Okimoto, T. Yoshida, M.
Hoshi, K. Hattori, M. Komata, K. Numata, K. Tomozawa, Aust. J.
Chem. 2007, 60, 236; b) M. Okimoto, T. Yoshida, M. Hoshi, K. Hat-
tori, M. Komata, K. Numata, K. Tomozawa, Heterocycles 2006, 68,
2563.
[23] C. Kibayashi, N. Yamazaki in Science of Synthesis, Vol. 30 (Ed.: J.
Otera), Thieme, Stuttgart, 2007, pp. 639–648.
[24] See the Supporting Information for experimental details.
[25] Z. Li, C.-J. Li, J. Am. Chem. Soc. 2005, 127, 6968.
[26] a) J. L. Roizen, M. E. Harvey, J. Du Bois, Acc. Chem. Res. 2012, 45,
911; b) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147; c) F.
Collet, R. H. Dodd, P. Dauban, Chem. Commun. 2009, 5061; d) V.
Nair, A. T. Biju, S. C. Mathew, B. P. Babu, Chem. Asian J. 2008, 3,
810.
[27] a) B. R. Buckley, S. D. R. Christie, M. R. J. Elsegood, C. M. Gillings,
P. C. B. Page, W. J. M. Pardoe, Synlett 2010, 939; b) X. Xie, T. Y.
Zhang, Z. Zhang, J. Org. Chem. 2006, 71, 6522; c) M. H. Ali, S. L.
Buchwald, J. Org. Chem. 2001, 66, 2560.
[6] a) S. Minakata, Y. Ohshima, A. Takemiya, I. Ryu, M. Komatsu, Y.
Ohshiro, Chem. Lett. 1997, 311; b) G. H. Kerr, O. Meth-Cohn, E. B.
Mullock, H. Suschitzky, J. Chem. Soc. Perkin Trans. 1 1974, 1614.
[7] a) A. T. Soldatenkov, K. B. Polyanskii, N. M. Kolyadina, S. A. Solda-
tova, Chem. Heterocycl. Compd. 2009, 45, 633; b) T. Izumi, K.
Kohei, S. Murakami, J. Heterocycl. Chem. 1993, 30, 1133; c) S.-I.
Murahashi, T. Oda, T. Sugahara, Y. Masui, J. Org. Chem. 1990, 55,
1744.
[8] a) Y. Miyake, Y. Ashida, K. Nakajima, Y. Nishibayashi, Chem.
Commun. 2012, 48, 6966; b) Y. Miyake, K. Nakajima, Y. Nishibaya-
shi, J. Am. Chem. Soc. 2012, 134, 3338.
[9] P. Kohls, D. Jadhav, G. Pandey, O. Reiser, Org. Lett. 2012, 14, 672.
[10] A. McNally, C. K. Prier, D. W. C. MacMillan, Science 2011, 334,
1114.
Received: August 29, 2012
Published online: November 13, 2012
Chem. Eur. J. 2012, 18, 16473 – 16477
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16477