Rhodium-catalyzed intermolecular C-H amination of simple hydrocarbons using the shelf-stable nonafluorobutanesulfonyl azide

Article abstract of DOI:10.1039/c3cc44594a

A new procedure has been developed for the direct intermolecular C-H amination of simple hydrocarbons using shelf-stable nonafluorobutanesulfonyl azide in the presence of a dirhodium(ii) tetracarboxylate catalyst under mild reaction conditions. Some mechanistic details are briefly discussed on the basis of control experiments.

Full text of DOI:10.1039/c3cc44594a

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Rhodium-catalyzed intermolecular C–H amination
of simple hydrocarbons using the shelf-stable
nonafluorobutanesulfonyl azide†
Cite this: Chem. Commun., 2013,
49, 9194
Received 19th June 2013,
Accepted 11th August 2013
´
´
´
Jose Ramon Suarez* and Jose Luis Chiara*
DOI: 10.1039/c3cc44594a
www.rsc.org/chemcomm
A new procedure has been developed for the direct intermolecular transformation mediated by TfN3.17f,18 In connection with our
C–H amination of simple hydrocarbons using shelf-stable nonafluoro- recent studies on new synthetic applications of NfN3,17b–d,f here
butanesulfonyl azide in the presence of a dirhodium(II) tetracarboxy- we describe how this reagent can perform the C–H amination of
late catalyst under mild reaction conditions. Some mechanistic details simple hydrocarbons under mild thermal conditions in the
are briefly discussed on the basis of control experiments.
presence of a metal catalyst.
We selected indane as a model substrate for an initial screening
The direct chemoselective transformation of unactivated sp3- of reaction conditions using 1.2 equivalents of NfN3 (Table 1). No
hybridized C–H bonds into C–N bonds has emerged as a powerful reaction occurred under simple thermal conditions in 1,2-dichloro-
tool in organic chemistry and the chemical industry that can ethane (DCE) at 90–110 1C (below the reported decomposition
streamline chemical synthesis by saving functional group transfor- temperature of NfN3 of ca. 120 1C)13e for 12 hours in the absence
mations (such as hydroxyl to amine) and protection–deprotection of a metal catalyst (entry 1). After testing several transition metal
steps.1 Typical aminating reagents used for this purpose are salts (5 mol%) (entries 2–5), we found that dirhodium(II) tetra-
high-energy species bearing electron-deficient N-substituents carboxylates promoted the reaction smoothly to afford the nona-
and capable of generating multiple bonds between late transition fluorobutanesulfonamide 1 in good isolated yields (entries 6, 12
metals and nitrogen, such as iminoiodinanes (often prepared and 13). The amination took place exclusively at the benzylic carbon.
in situ), N-haloamines, and azides. Intra- and intermolecular proto- Only a marginal improvement in product yield was obtained with
cols have been described based on Mn,2 Fe,2c,3 Ru,2b,4 Co,2c,5 Rh,3a,6 the more active Rh2(esp)2 catalyst (entry 13).6c A decrease in the
Ir,4b,7 Ni,2c Pd,8 Cu,1c,9 Ag,10 Au,11 and Zn12 catalysts, including reaction temperature had a dramatic deleterious effect, the reaction
asymmetric versions,2b,4b,6d, f,7 as well as under metal-free13,14 becoming sluggish below 70 1C (entries 7 and 8). Catalyst loadings
conditions. In most of these transformations the reactive as low as 1 mol% could be employed at the expense of a reduced,
species is believed to be a (metal-)nitrene intermediate, which
regioselectively inserts into the most electron-rich C–H bond
Table 1 Development of the intermolecular sulfamidation reaction
unless steric factors contravene.
The use of azides is particularly appealing in this context since
the reaction is highly atom-efficient and environmentally friendly,
producing only gaseous nitrogen as a by-product and not requiring
the addition of an oxidant. Polyfluoroalkanesulfonyl azides are the
Entry
Catalyst (mol%)
Temp (1C)
Yielda (%)
most electrophilic among organic azides, but have been very
scarcely used in amination reactions13e,15 probably due to the highly
hazardous nature of their simplest and most typically employed
representative, triflyl azide (TfN3).16 However, it has been recently
shown that the higher molecular weight analog nonafluoro-
butanesulfonyl azide (NfN3) is a more efficient, shelf-stable and
economic reagent in diazo-transfer reactions17 and other useful
1
2
3
4
5
6
7
8
None
Cu(OTf)2 (5)
CuBr (5)
Pd(OAc)2 (5)
AgOTf (5)
Rh2(OAc)4 (5)
Rh2(OAc)4 (5)
Rh2(OAc)4 (5)
Rh2(OAc)4 (3)
Rh2(OAc)4 (1)
Rh2(OAc)4 (5)
90–110
90
90
90
90
90
50
70
90
90
90
90
90
n.r.b
n.r.
n.r.
n.r.
n.r.
83
o5
20
9
82
63
75
80
10
11c
12
13
´
´
Instituto de Quımica Organica General, CSIC, Juan de la Cierva 3, 28006 Madrid,
Spain. E-mail: jl.chiara@csic.es; Fax: +34-915644853; Tel: +34-915622900
† Electronic supplementary information (ESI) available: Detailed experimental pro-
cedures and copies of 1H, 19F, and 13C NMR spectra. See DOI: 10.1039/c3cc44594a
Rh2(O2CC7H15 4
Rh2(esp)2 (5)
)
(5)
84
a
b
c
Isolated yield. No reaction. Two equivalents of NfN3 were used.
c
9194 Chem. Commun., 2013, 49, 9194--9196
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but still synthetically useful, amination yield (entry 10). Use of an
excess of NfN3 (2 equivalents) resulted in a slightly reduced product
yield without formation of polyaminated products or imine5a,9c
(entry 11). Optimum results were obtained at 90 1C employing a
3–5 mol% of catalyst and 1.2 equivalents of NfN3 (entries 6, 9,
12 and 13).
We next examined the substrate scope under the cost-efficient
optimized conditions using 5 mol% Rh2(OAc)4 at 90 1C in DCE.
Simple aromatic compounds bearing primary, secondary or tertiary
benzylic hydrogens where regioselectively monosulfamidated at the
benzylic position with moderate to good isolated yields (47–80%) Scheme 2 Intermolecular amination of simple cyclic alkanes.
(Scheme 1). Amination of the aromatic ring was never observed
under the employed experimental conditions.13a,15a,19 In the case of
at the methylene carbons to afford an inseparable 6.7 : 1 mixture of
21–31 sulfonamides 17 as single (unassigned) diastereoisomers, the
trans-isomer gave a 2.2 : 3.1 mixture of 21(2 diastereoisomers)–
31(single diastereoisomer) sulfonamides 18, respectively, in spite
of the 4 : 1 statistical preference for insertion at the methylene C–H
bonds in this molecule, indicating again the preferential amination
of the more accessible equatorially oriented methine C–H. We next
studied the regioselectivity of the reaction in isobutylbenzene and
1-ethyl-4-methylbenzene (Scheme 3). The observed reactivity ratio
for amination at benzylic vs. tertiary alkylic and at primary vs.
secondary benzylic C–H bonds were, respectively, 2 : 1 and 4.2 : 1
(statistically corrected), which follow the trend of their expected
relative C–H bond dissociation energies [BDE(Me3C–H) =
isochromane, the reaction occurred exclusively at the ethereal
benzylic carbon (compound 3). However, in contrast to related
Rh(II)-catalyzed amination reactions of aliphatic C–H bonds with
aryl azides,6i no reaction was observed for substrates bearing
carbonyl, ester, carbamoyl or sulfonamido groups, the starting
compound being recovered unchanged after heating at 90 1C for
16 h (Scheme 1, last row).
Encouraged by these results, we next examined the scope of
the transformation on simple hydrocarbon substrates bearing no
functional groups (Scheme 2). Moderate to good isolated yields
(45–70%) of monosulfamidated products were obtained under
the previous optimized conditions using the hydrocarbons as
limiting reagents (14–18) or as solvents (11–13). In the case of
adamantane, amination took place regioselectively at the tertiary
C–H bond, with no product arising from methylene amination
being detected in spite of the 3: 1 statistical preference for
insertion at the methylene C–H bonds in this molecule. In
contrast, trans-decalin was aminated exclusively at the methylene
carbons, yielding an inseparable 2 : 3 mixture (determined from
96.5 kcal molÀ1
BDE(PhCH(Me)–H) = 85.4 kcal molÀ1].20
;
BDE(PhCH2–H)
=
89.8 kcal molÀ1
;
A modest primary kinetic isotope effect (KIE, kH/kD = 2.47 at
90 1C; see ESI†) was measured for methylene C–H bond
amination in a competition reaction using a 1 : 1 mixture of
cyclohexane and cyclohexane-d12 and a limiting amount of NfN3.
This value is considerably lower than those previously reported for
reactions proceeding via a triplet nitrene C–H abstraction/radical
rebound amination mechanism (kH/kD > 5–6),1a,4a but it is in the
same range as those evaluated for analogous rhodium-catalyzed
C–H aminations (KIE = 1.2–2.6)1d proposed to proceed via con-
certed asynchronous singlet nitrene insertion. In line with this
observation is that the tertiary sulfonamides 17c and 18c were
diastereoisomerically different (see ESI†)14d suggesting that the
amination took place with retention of configuration, which can
rule out a radical stepwise mechanism. Based on these results, a
concerted asynchronous pathway can be reasonably proposed for
the present nitrene C–H insertion with only partial C–H bond
breaking in the transition state.
1
the H NMR of the crude) of two regio- or stereoisomers (15).
The larger steric encumbrance of the axially oriented methine
hydrogens probably explains this selectivity. Thus, in cis-decalin
an inseparable mixture of three regio- and/or stereo-isomeric
sulfonamides (16) was formed showing that amination at the
now more accessible methine carbon has taken place. The strong
1
signal overlap observed in the H NMR of the decalin reaction
products impeded their stereochemical assignment.9f A similar
change in 21–31 site selectivity was observed for cis- and trans-1,4-
dimethylcyclohexane. While the cis-isomer reacted preferentially
Scheme 3 Competitive benzylic vs. tertiary alkylic and primary vs. secondary
Scheme 1 Intermolecular amination of benzylic C–H bonds.
C–H bond amination.
c
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5013–5016; (e) K. W. Fiori and J. Du Bois, J. Am. Chem. Soc., 2007, 129,
562–568; ( f ) C. Liang, F. Collet, F. Robert-Peillard, P. Mu¨ller, R. H. Dodd
and P. Dauban, J. Am. Chem. Soc., 2007, 130, 343–350; (g) K. Huard and
H. Lebel, Chem.–Eur. J., 2008, 14, 6222–6230; (h) C. Lescot, B. Darses,
F. Collet, P. Retailleau and P. Dauban, J. Org. Chem., 2012, 77, 7232–7240;
(i) Q. Nguyen, K. Sun and T. G. Driver, J. Am. Chem. Soc., 2012, 134,
¨
7262–7265; ( j) A. Norder, S. A. Warren, E. Herdtweck, S. M. Huber and
T. Bach, J. Am. Chem. Soc., 2012, 134, 13524–13531.
7 M. Ichinose, H. Suematsu, Y. Yasutomi, Y. Nishioka, T. Uchida and
T. Katsuki, Angew. Chem., Int. Ed., 2011, 50, 9884–9887.
8 (a) G. He, Y. Zhao, S. Zhang, C. Lu and G. Chen, J. Am. Chem. Soc.,
2011, 134, 3–6; (b) E. T. Nadres and O. Daugulis, J. Am. Chem. Soc.,
2011, 134, 7–10.
Scheme 4 N-alkylation/reductive deprotection of sulfonamides.
The sulfonamide products could be further transformed taking
advantage of the known reactivity of polyfluoroalkanesulfon-
amides.21 Thus, N-alkylation could be readily performed by reac-
tion of the sulfonamide anion with an alkyl halide (Scheme 4). The
resultant N,N-disubstituted nonafluorobutanesulfonamide showed
restricted rotation around the S–N bond, which caused a consider-
´
´
9 (a) M. M. Dıaz-Requejo, T. R. Belderraın, M. C. Nicasio, S. Trofimenko
´
and P. J. Perez, J. Am. Chem. Soc., 2003, 125, 12078–12079;
´
´
(b) M. R. Fructos, S. Trofimenko, M. M. Dıaz-Requejo and P. J. Perez,
J. Am. Chem. Soc., 2006, 128, 11784–11791; (c) Y. M. Badiei, A. Dinescu,
X. Dai, R. M. Palomino, F. W. Heinemann, T. R. Cundari and
T. H. Warren, Angew. Chem., Int. Ed., 2008, 47, 9961–9964; (d) D. A.
Powell and H. Fan, J. Org. Chem., 2010, 75, 2726–2729; (e) R. T. Gephart,
D. L. Huang, M. J. B. Aguila, G. Schmidt, A. Shahu and T. H. Warren,
Angew. Chem., Int. Ed., 2012, 51, 6488–6492; ( f ) Q. Michaudel,
D. Thevenet and P. S. Baran, J. Am. Chem. Soc., 2012, 134, 2547–2550;
(g) Z. Ni, Q. Zhang, T. Xiong, Y. Zheng, Y. Li, H. Zhang, J. Zhang and
Q. Liu, Angew. Chem., Int. Ed., 2012, 51, 1244–1247.
1
able broadening of the H NMR signals at room temperature.22
Subsequent treatment with Red-Al in toluene under thermal con-
ditions afforded the corresponding N-alkylated amine in very good
yield. This efficient two-step process can allow simple access to a
variety of secondary amines, thus widely expanding the synthetic
potential of the present C–H bond amination approach.
´
´
10 (a) B. P. Gomez-Emeterio, J. Urbano, M. M. Dıaz-Requejo and
In summary, we have reported a new intermolecular C(sp3)–H
amination of simple hydrocarbons using the shelf-stable nona-
fluorobutanesulfonyl azide in the presence of a dirhodium(II)
tetracarboxylate catalyst. The amination products were obtained
in moderate to good yields and could be further transformed to
secondary amines via a simple two-step process. Possible
mechanistic pathways for the amination process were briefly
discussed on the basis of control experiments.
´
´
´
P. J. Perez, Organometallics, 2008, 27, 4126–4130; (b) A. Beltran,
´
´
C. Lescot, M. M. Dıaz-Requejo, P. J. Perez and P. Dauban, Tetra-
hedron, 2013, 69, 4488–4492.
11 (a) Z. Li, D. A. Capretto, R. O. Rahaman and C. He, J. Am. Chem. Soc.,
2007, 129, 12058–12059; (b) Y. Zhang, B. Feng and C. Zhu, Org.
Biomol. Chem., 2012, 10, 9137–9141.
12 B. Kalita, A. A. Lamar and K. M. Nicholas, Chem. Commun., 2008,
4291–4293.
13 For pioneering work, see: (a) D. S. Breslow, M. F. Sloan, N. R. Newburg
and W. B. Renfrow, J. Am. Chem. Soc., 1969, 91, 2273–2279;
(b) T. Shingaki, M. Inagaki, N. Torimoto and M. Takebayashi, Chem.
Lett., 1972, 1181–1184; (c) D. S. Breslow, E. I. Edwards, E. C. Linsay and
H. Omura, J. Am. Chem. Soc., 1976, 98, 4268–4275; (d) N. Torimoto,
T. Shingaki and T. Nagai, J. Org. Chem., 1978, 43, 631–633; (e) S.-Z. Zhu,
J. Chem. Soc., Perkin Trans. 1, 1994, 2077–2081.
14 (a) H. F. Bettinger, M. Filthaus, H. Bornemann and I. M. Oppel,
Angew. Chem., Int. Ed., 2008, 47, 4744–4747; (b) A. A. Lamar and
K. M. Nicholas, J. Org. Chem., 2010, 75, 7644–7650; (c) H. J. Kim, J. Kim,
S. H. Cho and S. Chang, J. Am. Chem. Soc., 2011, 133, 16382–16385;
(d) M. Ochiai, K. Miyamoto, T. Kaneaki, S. Hayashi and W. Nakanishi,
Science, 2011, 332, 448–451; (e) Q. Xue, J. Xie, H. Li, Y. Cheng and C. Zhu,
Chem. Commun., 2013, 49, 3700–3702.
15 (a) N. Kamigata, K. Yamamoto, O. Kawakita, K. Hikita,
H. Matsuyama, M. Yoshida and M. Kobayashi, Bull. Chem. Soc.
Jpn., 1984, 57, 3601–3602; (b) L. Benati, D. Nanni and P. Spagnolo,
J. Org. Chem., 1999, 64, 5132–5138.
16 B. A. Shainyan and L. L. Tolstikova, Chem. Rev., 2013, 113, 699–733.
17 (a) S. Yekta, V. Prisyazhnyuk and H.-U. Reissig, Synlett, 2007, 2069–2072;
We gratefully acknowledge support by the Spanish Ministerio
´
de Ciencia e Innovacion (project MAT2010-20646-C04-03), the
European Social Fund and Comunidad de Madrid (project
S2009/PPQ-1634 ‘‘AVANCAT’’), and CSIC for a JAEDOC contract
to J.R.S. Thanks are due also to Prof. Jesu´s Sanz (IQOG-CSIC) for
his valuable assistance with the KIE experiments.
Notes and references
1 (a) F. Collet, R. H. Dodd and P. Dauban, Chem. Commun., 2009,
5061–5074; (b) T. G. Driver, Org. Biomol. Chem., 2010, 8, 3831–3846;
(c) R. T. Gephart and T. H. Warren, Organometallics, 2012, 31,
7728–7752; (d) J. L. Roizen, M. E. Harvey and J. Du Bois, Acc. Chem.
Res., 2012, 45, 911–922.
2 (a) R. Breslow and S. H. Gellman, J. Chem. Soc., Chem. Commun.,
1982, 1400–1401; (b) J.-L. Liang, J.-S. Huang, X.-Q. Yu, N. Zhu and
C.-M. Che, Chem.–Eur. J., 2002, 8, 1563–1572; (c) S. Liang and
M. P. Jensen, Organometallics, 2012, 31, 8055–8058.
3 (a) R. Breslow and S. H. Gellman, J. Am. Chem. Soc., 1983, 105, 6728–6729;
(b) Z. Wang, Y. Zhang, H. Fu, Y. Jiang and Y. Zhao, Org. Lett., 2008, 10,
1863–1866; (c) Y. Liu and C.-M. Che, Chem.–Eur. J., 2010, 16, 10494–10501;
(d) L. Liang, H. Lv, Y. Yu, P. Wang and J.-L. Zhang, Dalton Trans., 2012, 41,
1457–1460; (e) S. M. Paradine and M. C. White, J. Am. Chem. Soc., 2012,
134, 2036–2039; ( f ) E. T. Hennessy and T. A. Betley, Science, 2013, 340,
591–595.
4 (a) S. K.-Y. Leung, W.-M. Tsui, J.-S. Huang, C.-M. Che, J.-L. Liang and
N. Zhu, J. Am. Chem. Soc., 2005, 127, 16629–16640; (b) Y. Nishioka,
T. Uchida and T. Katsuki, Angew. Chem., Int. Ed., 2013, 52, 1739–1742.
5 (a) J. D. Harden, J. V. Ruppel, G.-Y. Gao and X. P. Zhang, Chem. Commun.,
2007, 4644–4646; (b) H. Lu, H. Jiang, L. Wojtas and X. P. Zhang, Angew.
Chem., Int. Ed., 2010, 49, 10192–10196; (c) Y.-H. Ye, J. Zhang, G. Wang,
S.-Y. Chen and X.-Q. Yu, Tetrahedron, 2011, 67, 4649–4654.
´
´
(b) J. R. Suarez, B. Trastoy, M. E. Perez-Ojeda, R. Marin-Barrios and
J. L. Chiara, Adv. Synth. Catal., 2010, 352, 2515–2520; (c) B. Trastoy,
´
M. E. Perez-Ojeda, R. Sastre and J. L. Chiara, Chem.–Eur. J., 2010, 16,
´
3833–3841; (d) J. L. Chiara and J. R. Suarez, Adv. Synth. Catal., 2011, 353,
575–579; (e) J. Gu, W. Xiong, Z. Zhang and S. Zhu, Synthesis, 2011,
´
1717–1722; ( f ) J. R. Suarez, J. Kwiczak, K. Grenda, M. L. Jimeno and
J. L. Chiara, Adv. Synth. Catal., 2013, 355, 913–918.
18 (a) W. Xiong, Y. Xin, J. Han and S. Zhu, J. Fluorine Chem., 2010, 131,
867–872; (b) W. Xiong, Y. Xin, J. Zhao and S. Zhu, Synthesis, 2011,
1142–1148; (c) W. Xiong, H. Zhang, Y. Xin and S. Zhu, Tetrahedron,
2011, 67, 2232–2237; (d) W.-t. Xiong, J.-w. Zhao, J.-w. Gu and S. Zhu,
Tetrahedron, 2011, 67, 5235–5243.
19 S. Zhu and P. He, Tetrahedron, 2005, 61, 5679–5685.
20 (a) D. F. McMillen and D. M. Golden, Annu. Rev. Phys. Chem., 1982,
33, 493–532; (b) S. J. Blanksby and G. B. Ellison, Acc. Chem. Res.,
2003, 36, 255–263.
¨
21 (a) J. B. Hendrickson, R. Bergeron and D. D. Sternbach, Tetrahedron,
1975, 31, 2517–2521; (b) K. Miyamoto, M. M. Hoque and S. Ogasa,
J. Org. Chem., 2012, 77, 8317–8320.
6 (a) I. Nageli, C. Baud, G. Bernardinelli, Y. Jacquier, M. Moraon and
P. Mu¨llet, Helv. Chim. Acta, 1997, 80, 1087–1105; (b) C. G. Espino and J. Du
Bois, Angew. Chem., Int. Ed., 2001, 40, 598–600; (c) C. G. Espino,
¨
K. W. Fiori, M. Kim and J. Du Bois, J. Am. Chem. Soc., 2004, 126, 22 I. M. Lyapkalo, H.-U. Reissig, A. Schafer and A. Wagner, Helv. Chim.
15378–15379; (d) R. P. Reddy and H. M. L. Davies, Org. Lett., 2006, 8,
Acta, 2002, 85, 4206–4215.
c
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