Rhodium(III)-catalyzed C(sp2)-H activation and electrophilic amidation with N-fluorobenzenesulfonimide

Article abstract of DOI:10.1002/adsc.201201133

An electrophilic amidation via a cationic rhodium(III)-catalyzed C(sp ²)-H activation has been developed with the commercially available N-fluorobenzenesulfonimide as the amino source under external oxidant-free conditions. This amidation requires only a catalytic amount of base and exhibits excellent functional group tolerance and regioselectivity, providing a new avenue in direct C(sp²)-H amidation. Copyright

Full text of DOI:10.1002/adsc.201201133

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DOI: 10.1002/adsc.201201133
2
À
Rhodium
G
N
Amidation with N-Fluorobenzenesulfonimide
Ren-Jin Tang,a Cui-Ping Luo,a Luo Yang,a,* and Chao-Jun Lib,*
a
Key Laboratory for Environmentally Friendly Chemistry and Application of the Ministry of Education, Department of
Chemistry, Xiangtan University, Hunan 411105, Peopleꢀs Republic of China
Fax : (+86)-731-5829-2251; phone: (+86)-731-5829-8351; e-mail: yangluo@xtu.edu.cn
Department of Chemistry, McGill University, Montreal, QC, Canada H3A 2K6
b
Fax : (+1)-514-398-8457; phone: (+1)-514-398-3797; e-mail: cj.li@mcgill.ca
Received: December 31, 2012; Published online: February 22, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201201133.
Abstract: An electrophilic amidation via a cationic
2
À
rhodium
(III)-catalyzed
C
(sp ) H activation has
been developed with the commercially available N-
fluorobenzenesulfonimide as the amino source
under external oxidant-free conditions. This amida-
tion requires only a catalytic amount of base and
exhibits excellent functional group tolerance and re-
gioselectivity, providing a new avenue in direct C-
2
À
A
2
À
Keywords: amidation; C
ACHTUNGTNER(NUNG sp ) H activation; cationic
rhodium(III); N-fluorobenzenesulfonimide
ACHTUNGTRENNUNG
The prevalence of the arylamine motif in natural
products, pharmaceuticals, agrochemicals and materi-
2
À
Scheme 1. Various routes for CACTHUNTGRNEUNG(sp ) N bond formations
2
À
als has positioned C
G
the agenda of synthetic chemists.[1] The classical syn-
thesis of aromatic amines/amides relies on the cross-
N-Fluorobenzenesulfonimide (NFSI) is
a well-
À
coupling of aryl (pseudo)halides with amines/amides known fluorination reagent and oxidant in C H trans-
as exemplified by the Ullmann–Goldberg[2] and Buch- formation reactions.[7] Recently, it was found to be an
wald–Hartwig couplings[3] [Scheme 1 (a)]. With the efficient amino source in both sp and sp C H ami-
2
3
À
rapid advances of transition metal-catalyzed C H ac- dations catalyzed by Pd[8a–c] or Cu[8d]. As part of our
À
2
À
tivation, the direct C
N
pears to be highly appealing, especially if high regio- nucleophilic reactions, we recently reported the
2
À
selectivity can be achieved, which either employs Rh
(III)-catalyzed C
(sp ) H activation and nucleo-
parent amines/amides in the presence of external oxi- philic addition to aldehydes[9] or a,b-unsaturated car-
dants[4] [Scheme 1 (b)] or utilizes activated amino pre- bonyl compounds[10] under mild conditions. Other
cursors[5] such as chloramines or their analogs groups[11] also reported similar C
(sp ) H addition to
2
À
[Scheme 1 (c)]. While these routes complemented aldimines. Based on these results and the mechanistic
2
2
each other to make CACTHNUTRGENNGU ACHTUNGTRNE(NUGN sp ) H ac-
(sp ) N bond formation avail- study[11f] by Shi et al., we postulated that C
À
À
able for most substrates, the majority of them were tivation and nucleophilic substitution should take
realized under cross-coupling or nitrene insertion[4,6] place when the C=O and C=N unsaturated bonds
2
À
mechanisms. Herein, we report a new C
G
formation reaction based on the electrophilic substitu- bonds. These considerations led us to envision a
2
À
tion pathway using N-fluorobenzenesulfonimide Rh
(NFSI) as the amino source [Scheme 1 (d)].
(III)-catalyzed C
(sp ) H activation and electro-
philic amidation with NFSI.[12]
Adv. Synth. Catal. 2013, 355, 869 – 873
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2
[a]
À
Table 1. Optimization of the rhodium-catalyzed CACTHUNRTGNEUNG(sp ) H amidation.
Entry
Catalyst (mol%)
[Cp*RhCl2] (1.25)
Rh* (2.5)
Rh* (5.0)
Rh* (2.5)
Rh* (2.5)
Rh* (2.5)
Additive (10 mol%)
Temp. [oC]
Solvent
Yield [%][b]
1
2
3
4
G
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
–
CH3CO2H
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
100
100
100
80
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
65
81
83
56
48
68
0
5
60
6[c]
7
100
100
100
100
100
100
100
100
100
100
Pd
ACHTUNGTRENNUNG
8
9
Cu
G
0
Rh* (2.5)
Rh* (2.5)
Rh* (2.5)
Rh* (2.5)
Rh* (2.5)
Rh* (2.5)
Rh* (2.5)
55
49
44
62
55
39
<5
10
11
12
13
14
15
toluene
CH3CN
DMF
[a]
Conditions: 1a (0.2 mmol), NFSI (0.4 mmol), additive, solvent (0.2 mL), reacted for 24 h under argon unless otherwise
noted; Rh*=(CH3CN)3Cp*Rh(SbF6)2.
The yield of isolated product is reported.
NFSI (0.24 mmol) was added.
AHCTUNGTRENNUNG
[b]
[c]
To begin our study, we first examined the reaction crease of the yields (entries 9–11), which implys that
of 2-phenylpyridine (1a) and NFSI using rhodium cat- a catalytic amount of base can accelerate the deproto-
2
À
alyst based on our early work. Unexpectedly, product nation step in the rhodium-catalyzed C
G
2a was isolated instead of the desired N-arylbenzene- tion. The influence of the solvent on this reaction was
sulfonimide (2a’) in moderate yield (Table 1, entry 1), studied next and the most satisfactory yield was ob-
likely because product 2a was less sterically hindered tained in low polarity DCE. Other common solvents
and stabilized by the intramolecular hydrogen bond- such as THF, toluene and acetonitrile were also appli-
ing with the nitrogen of the directing pyridine motif. cable; however displayed lower yields. More polar
The cationic Rh
ACHTUNGTRENNUNG(III) catalyst, (CH3CN)3Cp*RhACTHUNGTRENNUNG
(Rh*, Cp*=pentamethylcyclopentadienyl) turned out
to be more reactive and the yield of 2a was increased the substrate scope of this novel rhodium-catalyzed
2
À
to 81% in 1,2-dichloroethane (DCE) at 1008C
C
(sp ) H activation and electrophilic amidation with
(entry 2). The by-product of NFSI was characterized NFSI was explored. As shown by the results in
by GC-MS, H NMR and 13C NMR as benzenesulfon- Table 2, all the 2-phenylpyridine analogs tested (1a–
1
yl fluoride (PhSO2F) in 84% isolated yield.[13] While 1m) reacted with NFSI smoothly to produce the cor-
doubling the catalyst loading exerted little improve- responding sulfamides efficiently, regardless of wheth-
ment on the yield (entry 3), decreasing the reaction er the phenyl group was substituted by electron-with-
temperature gave much inferior yield (entries 4 and drawing or electron-donating groups. We were
5). An excess of NFSI was required to promote the pleased to observe that functional groups such as
complete consumption of 2-phenylpyridine; thus the alkoxy (2b), acetoxy (2c), halides (2i–2k) and
yield diminished considerably when 1.2 equiv. of methoxy
ACHTUNGTRENUNcNG arbonyl (2l) were all tolerated. The influ-
NFSI were added (entry 6). Surprisingly, other transi- ence of substituents at different positions of the
tion metal catalysts such as PdACTHNUTRGNEN(UG OAc)2 and CuACHTUGNTREN(NUGN OAc)2 phenyl ring was also examined. To our delight, this
2
À
À
were completely ineffective in this CACTHNUGRTNEUNG(sp ) H amida- C H amidation demonstrated a high regioselectivity.
2
À
tion reaction (entries 7 and 8). A catalytic amount of While the less hindered CACTHNUTRGNE(NUG sp ) H of the meta-methyl
Cs2CO3 was essential for the high yield, and replacing substrate 1f reacted with NFSI in good yield, the
it with K2CO3 or acetic acid led to a dramatic de- more sterically hindered ortho-methyl substrate 1g
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Adv. Synth. Catal. 2013, 355, 869 – 873

2
À
RhodiumACHTUNGTRENNUNG(III)-Catalyzed CACHTUNGTERN(NUGN sp ) H Activation and Electrophilic Amidation
2
[a]
À
Table 2. The CACHTUNGTRENNUNG(sp ) H amidation of 2-phenylpyridine analogs with NFSI.
1a: R=H
1d: R=p-t-Bu
1g: R=o-CH3
1j: R=p-Cl
1m: R=p-CF3
1p: 2-methyl-6-phenylpyridine
1b: R=p-CH3O
1e: R=p-CH3
1h: R=p-Ph
1k: R=p-Br
1n: 2-(b-naphthyl)-pyridine
1q: 2-phenylpyrimidine
1c: R=p-AcO
1f R=m-CH3
1i: R=p-F
1l: R=p-CO2Me
1o: 2-( a-naphthyl)-pyridine
1r: 1-phenylpyrazole
[a]
Conditions: (CH3CN)3Cp*RhACHTGNUTERN(NUNG SbF6)2 (0.005 mmol, 2.5 mol%), 1a–1r (0.2 mmol), NFSI (0.4 mmol), Cs2CO3 (0.02 mmol),
DCE (0.2 mL), reacted for 24 h under argon unless otherwise noted. The yield of isolated product is reported.
Adv. Synth. Catal. 2013, 355, 869 – 873
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Ren-Jin Tang et al.
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gave a much lower yield. Likewise, 2-b-naphthylpyri- source. This reaction does not require any external
dine (1n) and 2-a-naphthylpyridine (1o) were also ap- oxidant and only a catalytic amount of base was
plicable in this reaction with the former providing needed. The amidation could tolerate a wide range of
only the monoamidation product 2n. Pyridinyl direct- functional groups such as alkoxy, acetoxy, halides and
ing group with a methyl substituent at C-6 (1p) also methoxycarbonyl and was highly regioselective, occur-
showed good reactivity, giving 2p in 73% yield. Other ring exclusively at the less hindered ortho-position
nitrogen-containing heterocyclic substituents such as relative to the 2-pyridyl (even in the presence of
pyrimidinyl and pyrazolyl can also act as the directing other potential chelate groups). The detailed reaction
group,[13] albeit the corresponding C H amidation mechanism and applications of this novel amidation
À
products 2q and 2r were obtained in lower yields.
are under investigation.
A plausible mechanism to rationalize this novel
2
À
rhodium-catalyzed C
G
philic amidation with NFSI is illustrated in Scheme 2. Experimental Section
General Experimental Procedure
An oven-dried reaction vessel was charged with
(CH3CN)3Cp*Rh(SbF6)2 (Rh*, 4.2 mg, 2.5 mol%,
AHCTUNGTRENNUNG
0.005 mmol), DCE (0.2 mL), 2-phenylpyridine (1a, 31 mg,
0.2 mmol), Cs2CO3 (0.02 mmol), and NFSI (126 mg,
0.4 mmol) under argon. The vessel was sealed and heated at
1008C (oil bath temperature) for 24 h. The resulting mixture
was cooled to room temperature, filtered through a short
silica gel pad and transferred to silica gel column directly
and eluted with hexanes and ethyl acetate (3:1) to give
products 2a (yield: 50 mg, 81%) and benzenesulfonyl fluo-
ride (yield: 27 mg, 84%).
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21202138), Xiangtan University “Aca-
demic Leader Program” (11QDZ20), New Teachersꢀ Fund
for
Doctor
Stations,
Ministry
of
Education
(20124301120007), University Student Innovation Program of
Hunan Province and Project of Hunan Provincial Natural
Science Foundation (12JJ7002).
Scheme 2. Tentative mechanism for the rhodium-catalyzed
2
À
C
N
First, the coordination of rhodium catalyst (Rh*) to 2-
phenylpyridine and subsequent electrophilic substitu-
tion generates the arylrhodium complex 3 and one
equivalent of proton,[11f] which is captured by the
Cs2CO3. Then, the fluorine atom on the NFSI coordi-
nates to the arylrhodium complex 4 to produce arylr-
hodium complex 5, which is followed by the substitu-
References
[1] a) Amino Group Chemistry, From Synthesis to the Life
Sciences, (Ed.: A. Ricci), Wiley-VCH, Weinheim, 2007;
b) R. Hili, A. K. Yudin, Nat. Chem. Biol. 2006, 2, 284.
[2] a) F. Ullmann, Ber. Dtsch. Chem. Ges. 1903, 36, 2382;
b) I. Goldberg, Ber. Dtsch. Chem. Ges. 1906, 39, 1691;
c) G. Evano, N. Blanchard, M. Toumi, Chem. Rev. 2008,
108, 3054; d) F. Monnier, M. Taillefer, Angew. Chem.
2009, 121, 7088; Angew. Chem. Int. Ed. 2009, 48, 6954.
[3] a) F. Paul, J. Patt, J. F. Hartwig, J. Am. Chem. Soc.
1994, 116, 5969; b) A. S. Guram, S. L. Buchwald, J. Am.
Chem. Soc. 1994, 116, 7901; c) J. F. Hartwig, Acc.
Chem. Res. 2008, 41, 1534; d) D. S. Surry, S. L. Buch-
wald, Angew. Chem. 2008, 120, 6438; Angew. Chem.
Int. Ed. 2008, 47, 6338; e) J. P. Wolfe, S. Wagaw, J.-F.
Marcoux, S. L. Buchwald, Acc. Chem. Res. 1998, 31,
805.
À
tion of the F in the polarized N F bond by the nucle-
2
À
ophilic C
G
mide complex 6.[12] Due to the steric hinderance and
instability of this N-arylbenzenesulfonimide, the fluo-
ride will further substitute the sulfonyl group to re-
lease the benzenesulfonyl fluoride (7)[14] and the N-ar-
ylbenzenesulfonamide anion, to provide the product
2a and regenerate of the rhodium catalyst (Rh*) after
protonation.
In summary, we have developed an efficient C-
2
2
À
U
À
[4] For selected reviews on C
G
with NFSI as the commercially available amino
Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147–1169;
872
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 869 – 873

2
À
RhodiumACHTUNGTRENNUNG(III)-Catalyzed CACHTUNGTERN(NUGN sp ) H Activation and Electrophilic Amidation
b) M. M. Diaz-Requejo, P. J. Pꢂrez, Chem. Rev. 2008,
108, 3379; c) E. M. Beccalli, G. Broggini, M. Martinelli,
S. Sottocornola, Chem. Rev. 2007, 107, 5318; d) F.
Collet, R. H. Dodd, P. Dauban, Chem. Commun. 2009,
5061; e) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem.
Soc. Rev. 2011, 40, 5068.
Org. Chem. 2010, 75, 6294; f) T. Xu, S. Qiu, G. Liu, J.
Organomet. Chem. 2011, 696, 46; g) A. Lozano, G.
Blessley, T. M. del Campo, A. L. Thompson, G. T. Giuf-
fredi, M. Bettati, M. Walker, R. Borman, V. Gouver-
neur, Angew. Chem. 2011, 123, 8255; Angew. Chem.
Int. Ed. 2011, 50, 8105; h) K. L. Hull, W. Q. Anani,
M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 7134.
[8] For recent amidations with NFSI, see: a) K. Sun, Y. Li,
T. Xiong, J. Zhang, Q. Zhang, J. Am. Chem. Soc. 2011,
133, 1694; b) A. Iglesias, R. Alvarez, A. R. de Lera, K.
Muniz, Angew. Chem. 2012, 124, 2268; Angew. Chem.
Int. Ed. 2012, 51, 2225; c) T. Xiong, Y. Li, Y. Lv, Q.
Zhang, Chem. Commun. 2010, 46, 6831; d) Z. Ni, Q.
Zhang, T. Xiong, Y. Zheng, Y. Li, H. Zhang, J. Zhang,
Q. Liu, Angew. Chem. 2012, 124, 1270; Angew. Chem.
Int. Ed. 2012, 51, 1244; e) H. J. Kim, J. Kim, S. H. Cho,
S. Chang, J. Am. Chem. Soc. 2011, 133, 16382; f) K.
Muniz, J. Kirsch, P. Chavez, Adv. Synth. Catal. 2011,
353, 689.
[5] For recent amidations with electrophilic nitrogen sour-
ces, see: a) T. Kawano, K. Hirano, T. Satoh, M. Miura,
J. Am. Chem. Soc. 2010, 132, 6900; b) K.-H. Ng,
A. S. C. Chan, W. Y. -Yu, J. Am. Chem. Soc. 2010, 132,
12862; c) N. Matsuda, K. Hirano, T. Satoh, M. Miura,
Org. Lett. 2011, 13, 2860; d) K.-H. Ng, Z. Zhou, W. Y.
-Yu, Org. Lett. 2012, 14, 272; e) C. Grohmann, H.
Wang, F. Glorius, Org. Lett. 2012, 14, 656; f) J. Y. Kim,
S. H. Park, J. Ryu, S. H. Cho, S. H. Kim, S. Chang, J.
Am. Chem. Soc. 2012, 134, 9100; g) J. Ryu, K. Shin,
S. H. Park, J. Y. Kim, S. Chang, Angew. Chem. 2012,
124, 10042; Angew. Chem. Int. Ed. 2012, 51, 9904;
h) E. J. Yoo, S. Ma, T.-S. Mei, K. S. L. Chan, J.-Q. Yu, J.
Am. Chem. Soc. 2011, 133, 7652; i) Y. Tan, J. F. Hart-
wig, J. Am. Chem. Soc. 2010, 132, 3676; j) X.-Y. Liu, P.
Gao, Y.-W. Shen, Y.-M. Liang, Org. Lett. 2011, 13,
4196.
[9] a) L. Yang, C. A. Correia, C.-J. Li, Adv. Synth. Catal.
2011, 353, 1269; b) F.-F. Wang, C.-P. Luo, Y. Wang, G.
Deng, L. Yang, Org. Biomol. Chem. 2012, 10, 8605.
[10] L. Yang, Q. Shuai, C.-J. Li, Org. Biomol. Chem. 2011,
9, 7176–7179.
À
[6] For excellent reviews on C H activation through ni-
trenes, see: a) D. N. Zalatan, J. D. Bois, Top. Curr.
Chem. 2010, 292, 347–378; b) G. Dequirez, V. Pons, P.
Dauban, Angew. Chem. Int. Ed. 2012, 124, 7498;
Angew. Chem. Int. Ed. 2012, 51, 7384; c) P. Muller, C.
Fruit, Chem. Rev. 2003, 103, 2905; d) J. L. Roizen,
M. E. Harvey, J. Du Bois, Acc. Chem. Res. 2012, 45,
911; e) H. Lu, X. P. Zhang, Chem. Soc. Rev. 2011, 40,
1899; f) F. Collet, C. Lescot, P. Dauban Chem. Soc.
Rev. 2011, 40, 1926; g) C. M. Che, V. K.-Y. Lo, C. Y.
Zhou, J.-S. Huang, Chem. Soc. Rev. 2011, 40, 1950.
[11] a) Y. Li, W.-H. Wang, W.-P. Huang, X.-S. Zhang, K.
Chen, Z.-J. Shi, Angew. Chem. 2011, 123, 2163; Angew.
Chem. Int. Ed. 2011, 50, 2115; b) A. S. Tsai, M. E. Tau-
chert, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc.
2011, 133, 1248; c) K. D. Hesp, R. G. Bergman, J. A.
Ellman, J. Am. Chem. Soc. 2011, 133, 11430; d) B.-J. Li,
Z.-J. Shi, Chem. Sci. 2011, 2, 488; e) Y. Li, X.-S. Zhang,
H. Li, W.-H. Wang, K. Chen, B.-J. Li, Z.-J. Shi, Chem.
Sci. 2012, 1634; f) J. Takaya, N. Iwasawa, J. Am. Chem.
Soc. 2011, 133, 1251; g) Y. Li, X.-S. Zhang, K. Chen,
K.-H. He, F. Pan, B.-J. Li, Z.-J. Shi, Org. Lett. 2012, 14,
636.
[7] For recent examples using NFSI as fluorination reagent
or oxidant, see: a) P. A. Sibbald, C. F. Rosewall, R. D.
Swartz, F. E. Michael, J. Am. Chem. Soc. 2009, 131,
15945; b) M. Rurda-Becerril, C. C. Sazepin, J. C. T.
Leung, T. Okbinoglu, P. Kennepohl, J.-F. Paquin, G. M.
Sammis, J. Am. Chem. Soc. 2012, 134, 4026; c) Y. H.
Lim, Q. Ong, H. A. Duong, T. M. Nguyen, C. W. Jo-
hannes, Org. Lett. 2012, 14, 5676; d) S. Qiu, T. Xu, J.
Zhou, Y. Guo, G. Liu, J. Am. Chem. Soc. 2010, 132,
2856; e) D. V. Liskin, P. A. Sibbald, C. F. Rosewall, J.
[12] E. Erdik, Tetrahedron 2004, 60, 8747.
[13] The nitrogen-containing heterocycles are effective di-
recting group but difficult to remove, so another syn-
thetically more useful substrate such as N-(pivaloyl-
AHCTUNGTREGUNoNN xy)benzamide would be chosen in the further re-
search.
[14] The spectral data of benzenesulfonyl fluoride are also
listed in the Supporting Information.
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