Addition-Versus-Oxygenative cleavage: Two contradictory reactivities in the reaction of N-Benzyl-4-Pentenylamine catalyzed by colloidal nanogold under aerobic conditions

Article abstract of DOI:10.1246/cl.2012.1328

Gold nanoclusters stabilized by a hydrophilic polymer, poly(N-vinyl-2- pyrrolidone), (Au:PVP) catalyze two contradictory types of the reaction from N-benzyl secondary amines with unactivated alkenes in EtOH under basic conditions. One is an intramolecular

Full text of DOI:10.1246/cl.2012.1328

doi:10.1246/cl.2012.1328
1328
Published on the web October 13, 2012
Addition-versus-Oxygenative Cleavage: Two Contradictory Reactivities in the Reaction
of N-Benzyl-4-pentenylamine Catalyzed by Colloidal Nanogold under Aerobic Conditions
Hiroaki Kitahara and Hidehiro Sakurai*
Research Center for Molecular Scale Nanoscience, Institute for Molecular Science,
Myodaiji, Okazaki, Aichi 444-8787
(Received May 14, 2012; CL-120611; E-mail: hsakurai@ims.ac.jp)
Previous work
Gold nanoclusters stabilized by a hydrophilic polymer,
poly(N-vinyl-2-pyrrolidone), (Au:PVP) catalyze two contra-
dictory types of the reaction from N-benzyl secondary amines
with unactivated alkenes in EtOH under basic conditions. One is
an intramolecular addition reaction that also starts from N-
sulfonylamine or primary amine as previously reported. The
other involves the oxygenative cleavage of alkene, giving the
corresponding £-lactam compound.
R
N
NHR
Ph
5 atom% Au:PVP
CH3
ð1Þ
air, 50 °C
Ph
Ph
Ph
1
2
300 mol% Cs2CO3, EtOH, 1 h, >99%
R=Ts
R=H 1000 mol% HCO2H, 500 mol% NH3
pH=4.01 buffer/EtOH, 4 h, 94%
This work
Bn
N
5 atom% Au:PVP
CH3
Our previous reports have demonstrated that colloidal
nanogold protected by a hydrophilic polymer, poly(N-vinyl-2-
pyrrolidone), (Au:PVP)1 exhibits not only an aerobic oxidation
activity but also a formal Lewis acid activity and promotes
intramolecular heterocyclization of £-hydroxyalkenes and £-
aminoalkenes.2 The choice of the sacrificial reductant as well
as the basicity of the reaction conditions are important for
successfully promoting the formal Lewis acid reaction, because
the redox reaction between O2 and the solvent occurs after
the main addition reaction. For example, in the reaction of
toluenesulfonamides, EtOH acts as a suitable sacrificial reduc-
tant under strong basic conditions,3 whereas formic acid needs to
be added as a reductant under slightly acidic conditions starting
from primary amines as reactants (eq 1).4
Herein, we report that two contradictory reactions proceeded
from N-benzyl secondary amines with 4-pentenyl group cata-
lyzed by Au:PVP in EtOH under basic conditions (eq 2). One is
hydroamination, same as in the case of the previous examples,
which occurred in the presence of Cs2CO3 as a base with up to
45% yield. The other is the formation of a £-lactam compound
that proceeded in the presence of CsOAc as a base with up to
46% yield (eq 2). The latter reaction might involve the oxidative
cleavage of carbon-carbon multiple bond, which has been
observed under ozonolysis conditions but is unknown under the
usual aerobic oxidation conditions in the presence of any type of
catalyst, including gold.
Table 1 shows the representative results for screening the
reaction conditions. First, the reaction was carried out under the
same conditions as hydroalkoxylation.5 Treatment of N-benzyl-
amine 1 with 10 atom % Au:PVP in the presence of 200 mol %
DBU as a base at 50 °C for 16 h in DMF/H2O mixed solvent
afforded N-benzylpyrrolidine 2 and N-benzylpyrrolidinone 3 in
26% and 17% yields, respectively (Entry 1). When the solvent
was changed to EtOH, which was a suitable hydrogen donor in
the case of toluenesulfonamides, the yields of both 2 and 3 were
slightly decreased (Entry 2). When the base was changed to
K2CO3 or Cs2CO3, the yield of 2 increased to 35% or 45%,
respectively. Note that 5 atom % of Au:PVP was sufficient to
complete the reaction and the reaction time of the reaction with
Cs2CO3 was slightly shorter (Entries 3 and 4).6
Ph
300 mol% Cs2CO3
EtOH, air
Ph
2
NHBn
50 °C, 10.5 h, 45%
ð2Þ
Ph
Ph
Bn
N
5 atom% Au:PVP
O
1
Ph
300 mol% CsOAc
EtOH, air
50 °C, 35 h, 46%
Ph
3
Indeed, the reaction time was markedly shortened when a more
stronger base such as CsOH was used (Entry 5). However, the
yield of 2 slightly decreased to 42%. On the other hand, the
oxidation reaction proceeded even in the absence of a base,
giving 12% of 2 and 32% of 3 after 26 h (Entry 6). Since the
yield of 3 increased under neutral conditions, next, we surveyed
additives ranging from weak base to weak acid. We found that
weak basic conditions such as those obtained by the addition of
Table 1. Optimization of the reaction conditions
Bn
Bn
NHBn
N
N
5 atom% Au:PVP
O
CH3
Ph
Ph
Ph
Ph
300 mol% base
solvent, 50 °C
Ph
2
Ph
3
1
Yield/%
Entry
Base
DBU
Solvent
Time/h
2
3
1a,b
2b
3
4
5
6
7
8
9
10c
11c
DMF/H2O
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
BuOH
EtOH
EtOH
16
12
12
10.5
3
26
35
17.5
12
23
23
26
22
35
45
42
12
14
17
16
17
7
13
7
16
32
46
31
21
DBU
K2CO3
Cs2CO3
CsOH
®
CsOAc
NaOAc
CsOAc
Cs2CO3
CsOAc
no reaction
no reaction
a10 atom % Au:PVP was used. b200 mol % DBU was used.
cWithout Au:PVP catalyst.
Chem. Lett. 2012, 41, 1328-1330
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1329
NHBn
CsOAc gave the best result, with the maximum yield of 3 of up
to 46%, along with 2 in 14% yield (Entry 7).7 Changing the base
to NaOAc or the solvent to BuOH did not improve the yield of 3
(Entries 8 and 9). It should be pointed out that no reaction
occurred in the absence of Au:PVP when either Cs2CO3 or
CsOAc was used (Entries 10 and 11).
Ph
Ph
1
Au:PVP
In order to elucidate the reaction mechanism, the following
two reactions were examined. The reaction of ¤-methyl-
substituted alkene 4 afforded an addition product 5 almost
quantitatively when Cs2CO3 was used, whereas when CsOAc
was used, 5 was obtained only in 28% yield and no oxygenated
product was obtained; instead, the aldehyde 6, which might be
obtained by the oxidation of amine, was obtained in 22% yield
(eq 3). Further, from the 4-pentynyl derivative 7, 3 was obtained
as a major product when Cs2CO3 or CsOAc was used. When the
reaction was carried out using Cs2CO3, 3 was obtained as a sole
product in 21% yield. The use of CsOAc gave 3 and the addition
product 8 in 48% and 20% yields, respectively (eq 4). These
results suggested that hydrogen abstraction at the ¤-position (¢-
elimination in Scheme 1) and the vinyl gold intermediate (D in
Scheme 1) might be involved in the formation of 3.
Au
Bn
N
2 (or 5)
EtOH
H
Ph
A
Ph
-elimination
-elimination
O
O
OH
OH
Au
Au
Bn
H
H
Bn
N
N
H
Ph
Ph
B
C
Ph
Ph
NHBn
CH3
-H2O2
Bn
CHO CH3
CH3
CH3
N
5 atom% Au:PVP
Ph
+
Ph
-elimination
Au:PVP
Oxidative addition
ð3Þ
300 mol% base
EtOH, 50 °C
Ph
Ph
Ph
Ph
Au
Bn
N
NBn
Bn
N
6
-
4
5
O
Ph
Ph
Cs2CO3 (13 h)
CsOAc (27 h)
94%
H
Ph
22%
Ph
28%
Ph
7
D
Ph
3
Bn
N
N
NBn
CH3
5 atom% Au:PVP
O
+
Scheme 1. Possible oxidation route to 3.
ð4Þ
Ph
Ph
Ph
300 mol% base
EtOH, 50 °C, 27 h
Ph
Ph
Ph
and the yield is not satisfactory yet, these results strongly
suggest the high potential of the nanogold catalyst to develop a
new catalytic system for the oxidative cleavage of carbon-
carbon multiple bond under aerobic oxidation conditions.
Needless to say, the oxidative cleavage of carbon-carbon double
bond to carbonyl compounds is an important transformation in
organic synthesis. Ozonolysis is employed, or a transition-metal
oxidant such as OsO4, KMnO4, RuO4, and CrO3 and stoichio-
metric amount of oxygen donors such as NaIO4 have usually
been utilized.9 Therefore, the development of a catalytic method
using an ecologically/economically friendly oxidant such as
molecular oxygen is highly anticipated.10
7
3
8
-
Cs2CO3
CsOAc
21%
48%
20%
The possible reaction pathway to 3 is illustrated in
Scheme 1. The reaction would be initiated by the addition of
amine to the ³-activated alkene by the Au clusters (intermediate
A), which is the same step as the simple cycloaddition reaction
to form 2 (or 5).2 If further oxidation from A to D occurs, 3
would be formed, which was confirmed by the reaction from 7
(eq 4). Two routes might be considerable from A to D: one is the
formation of Au carbenoid-like species by ¡-hydrogen elimi-
nation, followed by the ¢-hydrogen elimination along with the
O2 reduction to H2O2, and the other route involves ¢-hydrogen
elimination, followed by the oxidative addition process. Al-
though we have not found any direct evidence, the former
mechanism might be preferable.8 However, the total reaction
mechanism is still mysterious. In particular, the mechanism of
the conversion from the intermediate D to 3 and the reason why
N-benzyl group directs the oxygenation reaction dependent on
the reaction conditions are under investigation.
Paper based on a presentation made at the International
Association of Colloid and Interface Scientists, Conference
(IACIS2012), Sendai, Japan, May 13-18, 2012.
References and Notes
1
H. Tsunoyama, H. Sakurai, N. Ichikuni, Y. Negishi, T.
Tsukuda, Langmuir 2004, 20, 11293.
2
a) T. Tsukuda, H. Tsunoyama, H. Sakurai, Chem.®Asian J.
2011, 6, 736. b) H. Sakurai, I. Kamiya, H. Kitahara, Pure
Appl. Chem. 2010, 82, 2005.
In conclusion, we observed two contradictory reactions
from N-benzyl secondary amines®addition reaction and oxy-
genative cleavage of alkene®under the Au:PVP-catalyzed
aerobic oxidation conditions, by only changing the base.
Although the details of the reaction mechanism are not clear
3
4
a) H. Kitahara, I. Kamiya, H. Sakurai, Chem. Lett. 2009, 38,
908. b) H. Kitahara, H. Sakurai, J. Organomet. Chem. 2011,
696, 442.
H. Kitahara, H. Sakurai, Chem. Lett. 2010, 39, 46.
Chem. Lett. 2012, 41, 1328-1330
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1330
5
6
I. Kamiya, H. Tsunoyama, T. Tsukuda, H. Sakurai, Chem.
Lett. 2007, 36, 646.
Calcd for C23H21NO: C, 84.37; H, 6.46; N, 4.28%. Found:
C, 84.30; H, 6.46; N, 4.28%. HRMS m/z Calcd for
C23H21NO: 327.1623. Found: 327.1617.
For example, when the enamine 9 was treated under
Au:PVP reaction conditions, 3 was not obtained.
Typical procedure using Cs2CO3: A test tube was placed
with 1 (0.1 mmol), Cs2CO3 (97.7 mg, 300 mol %), and dried
Au:PVP1-5 (5 atom %). EtOH (30 mL) was added and the
reaction mixture was stirred vigorously (1300 rpm) at 50 °C
for 10.5 h. The reaction mixture was extracted with ethyl
acetate (3 © 20 mL), and then the combined organic layers
were washed with water and brine, dried over Na2SO4, and
concentrated in vacuo. Purification of the product was
carried out by PTLC.
Typical procedure using CsOAc: A test tube was placed with
1 (0.1 mmol), CsOAc (57.9 mg, 300 mol %), and the dried
Au:PVP1-5 (5 atom %). EtOH (30 mL) was added and the
reaction mixture was stirred vigorously (1300 rpm) at 50 °C
for 35 h. The reaction mixture was extracted with ethyl
acetate (3 © 20 mL), and then the combined organic layers
were washed with water and brine, dried over Na2SO4, and
concentrated in vacuo. Purification of the product was
carried out by PTLC. 3: Colorless needle crystal; mp 151 °C;
IR (KBr): 3017, 1683, 1215 cm¹1; 1H NMR (CDCl3): ¤ 3.18
(s, 2H), 3.85 (s, 2H), 4.52 (s, 2H), 7.08-7.27 (m, 15H);
13C NMR: 173.16, 145.92, 135.91, 128.65, 128.58, 128.28,
127.65, 126.72, 126.55, 57.97, 48.68, 46.49, 44.86; Anal.
8
9
Bn
N
Ph
Ph
9
7
a) D. G. Lee, T. Chen, in Comprehensive Organic Synthesis,
ed. by B. M. Trost, I. Fleming, Pergamon, Oxford, 1991,
Vol. 7, p. 541. doi:10.1016/B978-0-08-052349-1.00202-X.
b) W. A. Herrmann, T. Weskamp, J. P. Zoller, R. W. Fischer,
J. Mol. Catal. A: Chem. 2000, 153, 49. c) K. Miyamoto, N.
Tada, M. Ochiai, J. Am. Chem. Soc. 2007, 129, 2772.
10 a) D. Xing, B. Guan, G. Cai, Z. Fang, L. Yang, Z. Shi, Org.
Lett. 2006, 8, 693. b) B. C. Ranu, S. Bhadra, L. Adak,
Tetrahedron Lett. 2008, 49, 2588. c) M. Tokunaga, Y.
Shirogane, H. Aoyama, Y. Obora, Y. Tsuji, J. Organomet.
Chem. 2005, 690, 5378. d) A. Das, R. Chaudhuri, R.-S. Liu,
Chem. Commun. 2009, 4046. e) X. Baucherel, J. Uziel, S.
Jugé, J. Org. Chem. 2001, 66, 4504.
Chem. Lett. 2012, 41, 1328-1330
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/