Intramolecular addition of toluenesulfonamide to unactivated alkenes catalyzed by gold nanoclusters under aerobic conditions

Article abstract of DOI:10.1246/cl.2009.908

Gold nanoclusters stabilized by a hydrophilic polymer, poly-(N-vinyl-2- pyrrolidone) (Au:PVP), catalyzed the intramolecular addition of toluenesulfonamide to unactivated alkenes in EtOH under aerobic conditions. Copyright

Full text of DOI:10.1246/cl.2009.908

908
Chemistry Letters Vol.38, No.9 (2009)
Intramolecular Addition of Toluenesulfonamide to Unactivated Alkenes
Catalyzed by Gold Nanoclusters under Aerobic Conditions
Hiroaki Kitahara,1 Ikuyo Kamiya,2 and Hidehiro Sakuraiꢀ1;2;3
1School of Physical Science, The Graduate University for Advanced Studies, Myodaiji, Okazaki 444-8787
2Research Center for Molecular Scale Nanoscience, Institute for Molecular Science, Myodaiji, Okazaki 444-8787
3PRESTO, Japan Science and Technology Agency, Tokyo 102-0075
(Received July 1, 2009; CL-090619; E-mail: hsakurai@ims.ac.jp)
Table 1. Au:PVP-catalyzed hydroamination of toluenesulfonamides7,8
Gold nanoclusters stabilized by a hydrophilic polymer, poly-
(N-vinyl-2-pyrrolidone) (Au:PVP), catalyzed the intramolecular ad-
dition of toluenesulfonamide to unactivated alkenes in EtOH under
aerobic conditions.
Ts
CH3
R3
NHTs
R3
N
5 atom% Au:PVP
R1
R2
R1
300 mol% Cs2CO3
EtOH, 50 °C, air, time
R2
1
2
Entry
Yield/%a
Alkene
Time/h
Hydroamination of the carbon–carbon multiple bond offers an
efficient atom-economical route to nitrogen-containing molecules
and is one of the most extensively studied transformations.1 In partic-
ular, intramolecular reaction provides a useful method for the con-
struction of heterocycles. Various types of activating reagents have
been reported for the hydroamination of unactivated alkenes, includ-
ing transition metals,2 and acids.3 However, many of the reported cat-
alysts have a limited scope of substrates, sensitivity towards moisture
and oxygen, and sluggish rates for reactions involving unactivated
substrates. In the reaction with toluenesulfonamides,2 He and co-
workers reported that cationic AuI complexes act as catalysts for in-
tramolecular addition to unactivated alkenes. When 1a was treated
with 5 mol % of cationic Au catalyst generated by the addition of
PPh3AuCl and AgOTf in toluene at 85 ꢁC for 17 h, the corresponding
cyclized product 2a was obtained in 96% yield (eq 1).2a It is proposed
that the cationic Au catalyst behaves as a ꢀ-Lewis acid to activate the
alkene, assisting the nucleophilic attack of toluenesulfonamide.
Ts
CH3
R3
NHTs
R3
N
R1
R2
R1
1a−1f
2a−2f
R2
1a R1, R2 = Ph, R3 = H
1
1
2a >99
2a 0b
2a 0c
2
3
4
1a
1a
1b R1 = Ph, R2 = CH3, R3 = H
2b 93 (1.9:1)d
2c 89 (1.2:1)d
2d 81
4
4
1c R1 = Ph, R2, R3 = H
1d R1, R2 = CH3, R3 = H
5
6
16
1e R1, R2 , R3 = H
7
16
2e 41
NHTs
NTs
8
9
1f
2f 87
1
1
Ts
NHTs
N
5 mol% Ph3PAuCl/AgOTf
CH3
Ts
N
NHTs
Ph
Ph
Ph
Ph
Ph
ð1Þ
CH3
2g >99
toluene, 85 °C
Ph
17 h, 96%
1g
Ph
Ph
1a
2a
On the other hand, we have previously demonstrated that gold
nanoclusters (average size: 1.3 nm) stabilized by a hydrophilic poly-
mer, poly(N-vinyl-2-pyrrolidone) (Au:PVP),4 behave as a formal
Lewis acid catalyst, promoting the intramolecular hydroalkoxyla-
tion of unactivated alkenes at 50 ꢁC (eq 2).5 The characteristic fea-
tures of the reaction are the basic aqueous and aerobic conditions, in
contrast to the standard Lewis acidic conditions used for the cationic
Au catalyst. It is proposed that the O2 adsorbed on the gold cluster
surface might play a key role as the catalytic center.6 Therefore,
oxygen is essential to promote the reaction and basic conditions
are necessary to assist adsorption of the alcohols by increasing the
nucleophilicity. According to an analogous reactivity, it is expected
that intramolecular addition of toluenesulfonamides to unactivated
alkenes could proceed using the Au:PVP catalyst under milder, ba-
sic, and aerobic conditions.
aIsolated yield. bUnder Ar. c9.5 nm Au:PVP. d 1H NMR ratio.
tion did not occur under carefully degassed conditions (Entry 2), or
with the use of the larger size of Au:PVP (average size: 9.5 nm) cat-
alyst (Entry 3).4–6 These results indicate that molecular oxygen plays
an essential role in the hydroamination reaction, as for the hydroal-
koxylation reaction.5 The geminal effect at the ꢁ-position was then
investigated. The cyclization proceeded smoothly in the reaction
with methyl-, phenyl- (1b), phenyl- (1c), and dimethyl- (1d) substi-
tutes, to afford the corresponding pyrrolidine derivatives 2b, 2c, and
2d in excellent yields, respectively (Entries 4–6). Cyclization even
took place using 1e without the geminal effect, resulting in a mod-
erate yield (Entry 7). These results are in contrast to those for the re-
action with alcohols, which displayed an unusual substituent effect
on the ꢁ-position.5 The bicyclic product 2f was also obtained in
good yield (Entry 8). The diphenyl substitute at the ꢂ-position 1g
also underwent quantitative cyclization after 1 h (Entry 9).
There are some differences in the reactivity between alcohols
and toluenesulfonamides, not only due to the ꢁ-substituent effect.
For example, in the reaction of ꢃ-methyl-substituted alkene 1h or
3i, 1h quantitatively afforded 2h, while the reactivity was signifi-
cantly decreased by introducing a methyl group in the case of alco-
hol addition5 (eqs 3 and 4). As for the benzylic substrates, aerobic
oxidation of alcohol occurred predominantly from 3j, providing
OH
Ph
Ph
10 atom% Au:PVP
O
CH3
ð2Þ
Ph
200 mol% DBU, H2O/DMF
50 °C, 16 h, air, 87%
Ph
Representative results of the hydroamination of toluenesulfon-
amides are summarized in Table 1. Pyrrolidine derivative 2a was ob-
tained in quantitative yield when toluenesulfonamide (1a) was treat-
ed with 5 atom % of Au:PVP and 300 mol % of Cs2CO3 at 50 ꢁC for
1 h in EtOH as solvent under aerobic conditions (Entry 1).9 Cycliza-
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.9 (2009)
909
the ketone 5j.5 In contrast, no benzylic oxidation occurred, but cyc-
lization from 1j to 2j (eq 5) did proceed.
7
8
Although many inorganic/organic bases can be used in the reaction, CsCO3 gave
the best result among them.
General procedure for the hydroamination reaction of tosyl amide is as follows:
into a test tube (ꢄ ¼ 30 mm) was placed 1 (0.1 mmol), Cs2CO3 (97.7 mg,
0.30 mmol), and dried Au:PVP (38:1 mg ¼ 5 atom %). EtOH (30 mL) was added
and the reaction mixture was stirred vigorously (1300 rpm) at 50 ꢁC for the time
specified. The reaction mixture was extracted with ethyl acetate (3 ꢂ 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.
Ts
CH3
CH3
NHTs
CH3
N
5 atom% Au:PVP
ð3Þ
ð4Þ
ð5Þ
Ph
Ph
300 mol% Cs2CO3
EtOH, 50 °C, air, 3 h, >99%
Ph
Ph
2h
1h
OH
10 atom% Au:PVP
Ph
Ph
CH3
CH3
O
Ph
9
1b: Pale yellow solid; mp 67–68 ꢁC; IR (KBr): 3441, 3278, 2977, 2920, 1425,
Ph
200 mol% DBU, H2O/DMF
50 °C, 16 h, air, 38%
CH3
1328, 1161, 1093 cmꢃ1
;
1H NMR (CDCl3): ꢃ 1.31 (s, 3H), 2.29 (dd, J ¼ 13:7,
4i
3i
7.4 Hz, 1H), 2.43 (s, 3H), 2.45–2.49 (m, 1H), 3.04 (dd, J ¼ 12:2, 7.9 Hz, 1H),
3.12 (dd, J ¼ 12:2, 5.1 Hz, 1H), 3.97–3.99 (br, 1H), 4.99 (dd, J ¼ 17:7,
2.3 Hz, 1H), 5.00 (dd, J ¼ 10:4, 2.3 Hz, 1H), 5.48 (dddd, J ¼ 17:7, 10.4, 7.4,
6.7 Hz, 1H), 7.18 (d, J ¼ 8:3 Hz, 2H), 7.21–7.32 (m, 5H), 7.63 (d, J ¼ 8:3,
2H); 13C NMR: ꢃ 143.55, 143.33, 136.62, 133.52, 129.65, 128.69, 127.02,
126.65, 126.28, 118.23, 53.19, 44.40, 41.28, 22.48, 21.51; Anal. Calcd for
XH
X
X
+
5j 77% (X=O)
1j (X=NTs)
3j (X=O)
2j 95% (X=NTs)
C
19H23NO2S: C, 69.27; H, 7.04; N, 4.25; S, 9.73%. Found: C, 69.38; H, 7.16;
N, 4.28; S, 9.75%; HRMS m=z: Calcd for C19H23NO2S: 329.1449; found:
329.1443. 1g: Pale yellow solid; mp 137–138 ꢁC; IR (KBr): 3285, 3249, 3061,
;
2931, 1326, 1157 cmꢃ1 1H NMR (CDCl3): ꢃ 1.86–1.92 (m, 2H), 2.32 (s, 3H),
1j : 5 atom% Au:PVP, 300 mol% Cs2CO3, H2O/EtOH, 50 °C, air, 4 h.
3j :10 atom% Au:PVP, 200 mol% DBU, H2O/DMF, 50 °C, air, 24 h.
To elucidate the source of hydrogen at the methyl group of the
product, 1a was treated with 300 mol % Cs2CO3 at 50 ꢁC in EtOD or
EtOH-d6. Hydroamination proceeded quantitatively in EtOD after
6 h; however, 2a-D was not obtained. 2a-D was obtained in 96%
yield (69.5%D) after 20 h when EtOH-d6 was employed, which re-
veals that the hydrogen is introduced from the ethyl group of
EtOH.10 From these results, the reaction mechanism is likely to be
similar to that of hydroalkoxylation. Firstly, the toluenesulfonamide
anion is generated under the basic conditions and then adsorbed to
the gold surface activated by molecular oxygen. From the adsorbed
intermediate, nucleophilic attack of amide to the alkene proceeds.
Ethoxide is also adsorbed on the gold surface, and then the hydrogen
of the ethyl group is abstracted to yield the corresponding cyclized
compound.
As described above, Au:PVP is a good catalyst for the intramo-
lecular addition of toluenesulfonamides to unactivated alkenes. The
Au:PVP catalyst system is expected to be applied to various types
of formal Lewis acidic reactions in addition to oxidation reactions,
due to its activity under basic, mild, and atmospheric reaction con-
ditions.
2.60–2.64 (m, 2H), 4.95 (dd, J ¼ 17:9, 1.5 Hz, 1H), 4.96 (dd, J ¼ 9:9, 1.5 Hz,
1H), 5.77 (dddd, J ¼ 17:9, 9.9, 6.6, 6.6 Hz, 1H), 6.94 (d, J ¼ 8:2 Hz, 2H),
7.10–7.13 (m, 10H), 7.22 (d, J ¼ 8:2 Hz, 2H); 13C NMR: ꢃ 143.57, 142.23,
138.59, 138.01, 128.92, 127.84, 127.47, 126.97, 126.87, 114.94, 66.96, 38.18,
28.56, 21.36; Anal. Calcd for C24H25NO2S: C, 73.62; H, 6.44; N, 3.58; S,
8.19%. Found: C, 73.40; H, 6.72; N, 3.62; S, 8.01%. HRFAB m=z: Calcd for
C24H26NO2S ½M þ Hꢄþ: 392.1684; found: 392.1674. 1j: Colorless solid; mp
147–149 ꢁC; IR (KBr): 3422, 3247, 2932, 1334, 1162 cmꢃ1 1H NMR (CDCl3):
;
ꢃ 1.51–1.61 (m, 1H), 1.79–1.83 (m, 2H), 1.95 (ddd, J ¼ 14:7, 7.7, 7.4 Hz, 1H),
2.36 (ddd, J ¼ 14:7, 5.7, 5.4 Hz, 1H), 2.40 (s, 3H), 2.69 (ddd, J ¼ 17:3, 9.4,
7.1 Hz, 1H), 2.82 (ddd, J ¼ 17:3, 5.4, 5.4 Hz, 1H), 4.48 (dd, J ¼ 9:2, 3.9 Hz,
1H), 4.70 (d, J ¼ 9:2 Hz, 1H), 4.99 (dd, J ¼ 9:7, 1.3 Hz, 1H), 5.00 (dd,
J ¼ 18:1, 1.3 Hz, 1H), 5.77 (dddd, J ¼ 18:1, 9.7, 7.4, 5.7 Hz, 1H), 6.69 (d,
J ¼ 7:5 Hz, 1H), 6.92 (dd, J ¼ 7:5, 7.5 Hz, 1H), 7.03 (d, J ¼ 7:5 Hz, 1H),
7.11 (dd, J ¼ 7:5, 7.5 Hz, 1H), 7.30 (d, J ¼ 8:2 Hz, 2H), 7.76 (d, J ¼ 8:2 Hz,
2H); 13C NMR: ꢃ 143.25, 138.72, 136.38, 136.01, 129.60, 129.08, 128.65,
127.57, 127.13, 125.95, 116.29, 55.62, 38.14, 34.91, 27.29, 23.08, 21.50; HRMS
m=z: Calcd for C20H23NO2S: 341.1449; found: 341.1443. 2b: Yellow oil; IR
(neat): 2966, 2872, 1345, 1159, 1092 cmꢃ1 1H NMR (CDCl3, diastereomer
;
ratio = 1.9:1, major diastereomer): ꢃ 0.84 (s, 3H), 1.40 (d, J ¼ 6:2 Hz, 3H),
1.92 (dd, J ¼ 12:4, 9.4 Hz, 1H), 2.21 (dd, J ¼ 12:4, 6.4 Hz, 1H), 2.43 (s, 3H),
3.64 (pseud s, 2H), 3.87 (ddq, J ¼ 9:4, 6.4, 6.2 Hz, 1H), 7.05–7.22 (m, 5H),
7.33 (d, J ¼ 8:1 Hz, 2H), 7.79 (d, J ¼ 8:1 Hz, 2H); (minor diastereomer): ꢃ
1.45 (s, 3H), 1.54 (d, J ¼ 6:3 Hz, 3H), 1.80 (dd, J ¼ 12:0, 6.0 Hz, 1H), 2.35–
2.40 (m, 1H), 2.37 (s, 3H), 3.41 (d, J ¼ 9:5 Hz, 1H), 3.59 (ddq, J ¼ 8:7, 6.3,
6.0 Hz, 1H), 3.68 (d, J ¼ 9:5 Hz, 1H), 6.05–7.22 (m, 5H), 7.29 (d, J ¼ 8:1 Hz,
2H), 7.60 (d, J ¼ 8:1 Hz, 2H); 13C NMR (diastereomer mixture): ꢃ 146.66,
146.56, 143.19, 143.05, 135.80, 133.72, 129.52, 129.38, 128.43, 128.39,
127.44, 127.27, 126.34, 126.05, 125.45, 125.31, 60.90, 59.64, 55.52, 47.10,
46.26, 44.55, 29.70, 27.54, 23.38, 22.32, 21.45, 21.38; HRMS m=z: Calcd for
C19H23NO2S: 329.1449; found: 329.1458. 2g: Colorless solid; mp 131–
This work was supported by PRESTO-JST (Search for Nano-
manufacturing Technology and Its Development), and NEDO. We
also thank Ms. Noriko Kai for preparation of the Au:PVP catalyst.
References and Notes
1
a) T. E. Muller, M. Beller, Chem. Rev. 1998, 98, 675. b) T. E. Muller, K. C.
¨ ¨
Hultzsch, M. Yus, F. Foubelo, M. Tada, Chem. Rev. 2008, 108, 3795.
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133 ꢁC; IR (KBr): 2979, 1339, 1162, 1095 cmꢃ1 1H NMR (CDCl3): ꢃ 1.51 (d,
;
2
J ¼ 6:4 Hz, 3H), 1.64–1.69 (m, 1H), 2.10–2.23 (m, 1H), 2.36 (s, 3H), 2.72 (m,
2H), 4.45–4.53 (m, 1H), 6.82 (d, J ¼ 8:1 Hz, 2H), 6.97 (d, J ¼ 8:1 Hz, 2H),
7.20–7.40 (m, 6H), 7.36 (d, J ¼ 7:2 Hz, 2H), 7.55 (d, J ¼ 7:2 Hz, 2H);
13C NMR: ꢃ 141.77, 130.16, 128.61, 128.49, 127.56, 127.15, 126.98, 126.68,
76.40, 58.78, 44.76, 32.05, 22.47, 21.33; Anal. Calcd for C24H25NO2S: C,
73.62; H, 6.44; N, 3.58; S, 8.19%. Found: C, 73.54; H, 6.68; N, 3.57; S,
8.30%. HRMS m=z: Calcd for C24H25NO2S: 391.1606; found: 391.1608. 2j: Pale
3
4
a) D. C. Rosenfeld, S. Shekhar, A. Takemiya, M. Utsunomiya, J. F. Hartwig,
Org. Lett. 2006, 8, 4179. b) B. Schlummer, J. F. Hartwig, Org. Lett. 2002, 4,
1471.
yellow solid; mp 162–164 ꢁC; IR (KBr): 2934, 1338, 1159 cmꢃ1 1H NMR
;
PVP K-30 having average molecular weight of 40 kDa was used. For the details
of the preparation of Au:PVP, see: H. Tsunoyama, H. Sakurai, N. Ichikuni, Y.
Negishi, T. Tsukuda, Langmuir 2004, 20, 11293.
(CDCl3): ꢃ 1.24 (d, J ¼ 5:6 Hz, 3H), 1.31–1.40 (m, 1H), 1.49–1.57 (m, 1H),
1.73 (m, 1H), 1.86–1.96 (m, 2H), 2.45 (s, 3H), 2.55–2.62 (m, 1H), 2.69–2.77
(m, 1H), 3.68–3.76 (m, 1H), 4.74 (d, J ¼ 6:8 Hz, 1H), 7.03 (d, J ¼ 7:6 Hz,
1H), 7.17 (dd, J ¼ 7:6, 7.6 Hz, 1H), 7.27 (dd, J ¼ 7:6, 7.6 Hz, 1H), 7.34 (d,
J ¼ 8:3 Hz, 2H), 7.80 (d, J ¼ 8:3 Hz, 2H), 7.92 (d, J ¼ 7:6 Hz, 1H); 13C NMR:
ꢃ 143.34, 136.38, 135.72, 135.37, 129.73, 129.45, 127.71, 127.59, 126.75,
126.59, 61.48, 57.43, 37.32, 36.37, 25.07, 23.94, 23.26, 21.54; HRMS m=z:
Calcd for C20H23NO2S: 341.1449; found: 341.1457.
5
6
I. Kamiya, H. Tsunoyama, T. Tsukuda, H. Sakurai, Chem. Lett. 2007, 36, 646.
a) H. Tsunoyama, H. Sakurai, Y. Negishi, T. Tsukuda, J. Am. Chem. Soc. 2005,
127, 9374. b) H. Tsunoyama, H. Sakurai, T. Tsukuda, Chem. Phys. Lett. 2006,
429, 528. c) H. Tsunoyama, T. Tsukuda, H. Sakurai, Chem. Lett. 2007, 36,
212. d) H. Sakurai, H. Tsunoyama, T. Tsukuda, Trans. Mater. Res. Soc. Jpn.
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Tsukuda, Synlett 2009, 245.
10 In the case of hydroalkoxylation, it was found that the hydrogen source was the
formyl hydrogen11 of the co-solvent DMF.5
11 Unpublished result.
Published on the web (Advance View) August 22, 2009; doi:10.1246/cl.2009.908