Pd(II)-catalyzed ortho-hydroxylation and intramolecular oxidative C - C coupling of N-Benzylbenzenesulfonamides

Full text of DOI:10.1002/bkcs.10126

Communication
DOI: 10.1002/bkcs.10126
BULLETIN OF THE
E. J. Jeong et al.
KOREAN CHEMICAL SOCIETY
Pd(II)-catalyzed ortho-Hydroxylation and Intramolecular Oxidative
C C Coupling of N-Benzylbenzenesulfonamides
*
Eun Joo Jeong, Yoon Hyung Jo, Min Jung Jang, and So Won Youn
Department of Chemistry and Research Institute for Natural Sciences, Center for New Directions in Organic
Synthesis, Hanyang University, Seoul 133-791, Korea. *E-mail: sowony73@hanyang.ac.kr
Received October 23, 2014, Accepted November 27, 2014
Keywords: Palladium, C H activation, Hydroxylation, C–C coupling, Sultams
In recent years, direct activation/functionalization of C H
bonds in aromatic compounds has emerged as an efficient,
atom-economical, and eco-friendly synthetic tool, with wide-
spread applications, providing a powerful alternative to the
classical coupling reaction using preformed organometallic
reagents.1 Despite the significant development in the past dec-
ades, transition-metal-catalyzed functionalization of C(sp2)
H bonds of NH-containing benzylamines has been reported
with limited success.2 Recently, we reported highly effective
Pd-catalyzed C C and/or C N bond formations via C H
activation of aniline derivatives.3 Considering the lack of
regioselective C(sp2) H hydroxylation of benzylamines,
our continued interest in Pd-catalyzed C H bond functiona-
lization prompted us to investigate the possibility of a Pd-
catalyzed ortho-hydroxylation of NH-containing benzyla-
mines. Here we disclose the discovery of the Pd-catalyzed
ortho-hydroxylation4 and/or intramolecular oxidative C C
coupling of N-benzylsulfonamides depending on the reaction
conditions (acid additive and solvent) (Scheme 1).
We focused our initial efforts on establishing optimal con-
ditions for the Pd-catalyzed ortho-hydroxylation of 1a, which
was selected as the test substrate for screening of reaction
parameters (a variety of Pd complexes, oxidants, solvents,
additives, temperatures, etc.) to promote C H activation.
Duringthestudies onthecatalytic system, wefoundthat asim-
ple change of the acid additive and solvent resulted in a signif-
icantly altered chemoselectivity, leading to either an
intermolecular C(sp2) H hydroxylation or intramolecular
oxidative C C coupling of benzylamines to give 2a and 3a,
respectively (Scheme 1). Pd(OAc)2 and K2S2O8 were found
as the catalyst and oxidant of choice, respectively, for both
transformations. The use of MeSO3H as an acid additive in
benzene solvent formed only 3a (of which structure was con-
firmed by X-ray analysis5), while the CF3CO2H/CH2Cl2
cosolvent system afforded 2a as a major product along with
a small amount of 3a. In sharp contrast to the known reactions
for the transition-metal-catalyzed ortho-hydroxylation reac-
tions and intramolecular coupling reactions for the related sul-
tam formation, noteworthy is that these newly established
protocols proceeded smoothly at room temperature. Benzo-
sultams (e.g., 3a) have emerged as privileged structures in
drug discovery because of their diverse biological properties.6
In general, synthesis of benzosultams can be achieved by the
Pd-catalyzed intramolecular arylation of either N-(2-bromo-
benzyl)benzenesulfonamides or N-benzyl-2-bromobenzene-
sulfonamides.7 Among the repertoire of synthetic methods,
this newly developed Pd-catalyzed intramolecular oxidative
coupling reaction of two C H bonds would be powerful
and greener variant of the classical coupling reaction which
circumvents the use of aryl halides.2i
With the optimized conditions in hand, we set out to explore
the substrate scope of these processes (Table 1). First, the sub-
stituenteffectofbothbenzylaminemoietyandbenzenesulfonyl
ring was examined for the selective formation of the seven-
membered benzosultam 3 under condition A (entries 1–6).
A delicately balanced electron density of both aryl rings was
required to achieve good efficiency for this reaction: R1 = H
and R2 = Mewerethepreferredgroups,whileothersubstituents
gave unsuccessful results. Oxidative cyclization of N-methyl-
N-Ts-benzylamine, an N-methyl derivative previously reported
to be inert in the related Pd-catalyzed intramolecular oxidative
coupling reaction,2i also proceeded uneventfully to give the
desired product in 53% yield (entry 6).
Next, the substituent effect was also explored in ortho-
hydroxylation under condition B. Again, the Ts group showed
generally better efficiency as an N-protecting group (entries
7–9, 10 and 11, 21 and 22). A variety of benzylamines under-
went ortho-hydroxylation smoothly, showing little steric
dependence. However, electron density of the benzylamine
moiety had a significant influence on the chemical reactivity:
Electron-rich substrates reacted considerably faster (entries
12–15), and a strongly electron-donating substituent (e.g.,
MeO) at the C4 position resulted in decomposition (entry
14), presumably as a consequence of the oxidation of the
NH
S
O
O
O
S
O O
S
O
5 mol% Pd(OAc)2
N
N
+
H
H
2 equiv K2S2O8
25 oC
H
H
OH
1a
2a
3a
Condition A: with MeSO3H (20 equiv) in benzene (0.1 M) for 17 h
only 3a (41%)
Condition B: in CF3CO2H/CH2Cl2 (1/1, 0.025 M) for 24 h
2a (65%) + 3a (12%)
Scheme 1. Pd-catalyzed C O or C C bond formation.
Bull. Korean Chem. Soc. 2015
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
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BULLETIN OF THE
Communication
KOREAN CHEMICAL SOCIETY
Table 1. Substrate scope.
Entry
R1
R2 R3 Condition t (h) 2 (%)a 3 (%)a
1
2
3
4
5
6
7
8
H
H
H
Me
H
Cl
H
H
H
H
H
A
A
A
A
A
Ac
B
B
B
B
B
B
B
B
B
B
B
B
B
B
Be
B
17
17
17
8
8
8
24
24
19
24
24
9
12
4
5
24
15
24
24
24
24
24
—
—
—
—
—
—
65
58
53
33
34
64
62
0b
54
52
47
61
0d
0d
46
39
41
34
22
32
0b
53
12
27
13
27
19
16
19
0b
12
16
22
16
0d
0d
20
26
Scheme 2. Proposed mechanism.
4-Cl
4-MeO Me
H
H
H
Me
Acknowledgment. This work was supported by the research
fund of Hanyang University (HY-2012-G).
Me Me
Me
H
Cl
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
References
9
H
1. Selected recent reviews: (a) E. M. Beccalli, G. Broggini, M. Marti-
nelli, S. Sottocornola, Chem. Rev. 2007, 107, 5318; (b) X. Chen, K.
M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem. Int. Ed. 2009, 48,
5094;(c) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147;
(d) D. Y.-K. Chen, S. W. Youn, Chem. Eur. J. 2012, 18, 9452.
2. Examples on C O bond formation of NH-free benzylamines: (a)
F.-R. Gou, X.-C. Wang, P.-F. Huo, H.-P. Bi, Z.-H. Guan, Y.-M.
Liang, Org. Lett. 2009, 11, 5726; (b) G. He, Y. Zhao, S. Zhang, C.
Lu, G. Chen, J. Am. Chem. Soc. 2012, 134, 3; (c) S.-Y. Zhang, G.
He, Y. Zhao, K. Wright, W. A. Nack, G. Chen, J. Am. Chem. Soc.
2012, 134, 7313; (d) J. Roane, O. Daugulis, Org. Lett. 2013, 15,
5842; Selected recent examples on C-C bond formation of NH-
free benzylamines: (e) K. Orito, A. Horibata, T. Nakamura, H.
Ushito, H. Nagasaki, M. Yuguchi, S. Yamashita, M. Tokuda,
J. Am. Chem. Soc. 2004, 126, 14342; (f ) A. Lazareva, O. Daugu-
lis, Org. Lett. 2006, 8, 5211; (g) Y.-T. Su, Y.-L. Wang, G.-W.
Wang, Chem. Commun. 2012, 48, 8132; (h) K. Morimoto, M.
Itoh, K. Hirano, T. Satoh, Y. Shibata, K. Tanaka, M. Miura,
Angew. Chem. Int. Ed. 2012, 51, 5359; (i) J. K. Laha, K. P. Jet-
hava, N. Dayal, J. Org. Chem. 2014, 79, 8010.
10
11
12
13
14
15
16
17
18
19
20
21
22
4-Cl
4-Cl
4-Me
2-Me
4-MeO Me
3-MeO Me
3-Ph
3-Br
2-Br
Me
Me
Me
Me
Me
Me
4-NO2
3-CO2Me Me
H
H
Me Me
Me
H
a Isolated yield.
b Decomposed and only TsNH2 was obtained.
c At 60 ꢀC.
d No reaction.
e In CF3CO2H/CH2Cl2 (1/1, 0.2 M).
3. (a)B. S. Kim, C. Jang, D. J. Lee, S. W. Youn,Chem. Asian J. 2010, 5,
2336; (b) M. J. Jang, S. W. Youn, Bull. Korean Chem. Soc. 2011, 32,
2865; (c) B. S. Kim, S. Y. Lee, S. W. Youn, Chem. Asian J. 2011, 6,
1952;(d)S. W. Youn, J. H. Bihn, B. S. Kim, Org. Lett. 2011,13, 3738;
(e) E. J. Jeong, S. W. Youn, Bull. Korean Chem. Soc. 2014, 35, 2611.
4. Reviews on transition-metal-catalyzed hydroxylation of arenes:(a) D.
A. Alonso, C. Nájera, I. M. Pastor, M. Yus, Chem. Eur. J. 2010, 16,
5274; (b) S. Enthaler, A. Company, Chem. Soc. Rev. 2011, 40, 4912.
5. CCDC 1030423 (3a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
6. Reviews on sultams: (a) L. Levy, Drugs Future 1992, 17, 451; (b)
K. C. Majumdar, S. Mondal, Chem. Rev. 2011, 111, 7749.
7. (a) K. C. Majumdar, S. Mondal, N. De, Synlett 2008, 18, 2851; (b)
D. K. Rayabarapu, A. Zhou, K. O. Jeon, T. Samarakoon, A. Rolfe,
H. Siddiqui, P. R. Hanson, Tetrahedron 2009, 65, 3180; (c) K. C.
Majumdar, S. Mondal, N. De, Synthesis 2009, 18, 3127; (d) S.
Rousseaux, S. I. Gorelesky, B. K. W. Chung, K. Fagnou, J.
Am. Chem. Soc. 2010, 132, 10692; (e) C. B. Bheeter, J. K. Bera,
H. Doucet, Adv. Synth. Catal. 2012, 354, 3533.
benzylic position followed by a hydrolysis to afford TsNH2. In
contrast, electron-deficient substrates containing NO2 or
CO2Me at the C3 or C4 position showed no reactivity (entries
19 and 20), indicating the electrophilic nature of the cyclopal-
ladation. m-Substituted substrates showed remarkable regios-
electivity, leading to only products originating from activation
of the less hindered C H bond (entries 15–17). N-Methyl-N-
benzylsulfonamides also underwent ortho-hydroxylation suc-
cessfully to give the desired products (entries 21 and 22). On
the other hand, this reaction failed with α-substituted benzyla-
mines, naphthylmethylamines, (Z)-N-Ts-dehydroamino acid
esters, and phenethylamines.
In summary, we have developed the Pd-catalyzed ortho-
hydroxylation and/or intramolecular oxidative C C coupling
of N-benzylsulfonamides, which operate through two differ-
ent postulated mechanistic routes, as depicted in Scheme 2,
depending on the reaction conditions.
Bull. Korean Chem. Soc. 2015
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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