Sodium hydride induced N-arylation of diisopropyl azodicarboxylate by aryl trifluoromethanesulfonates

Article abstract of DOI:10.1055/s-0034-1380143

A method for intermolecular N-arylation of the anionic species derived from diisopropyl azodicarboxylate and sodium hydride by aryl trifluoromethanesulfonates, in the presence of a ligand-free copper(I) oxide catalyst at 80 °C in N,N-dimethylformamide, is reported. A variety of functionalized aryl triflouromethanesulfonates were efficiently coupled by this method.

Full text of DOI:10.1055/s-0034-1380143

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 942–944
letter
942
I. Yavari et al.
Letter
Synlett
Sodium Hydride Induced N-Arylation of Diisopropyl Azodicarbox-
ylate by Aryl Trifluoromethanesulfonates
Issa Yavari*
Ar
N
Cu2O, NaH, LiI
DMF, 70 °C
CO2i-Pr
Majid Ghazanfarpour-Darjani
Mohammad J. Bayat
Alaleh Malekafzali
N
CO2i-Pr
ArOTf
+
N
i-PrO2C
N
i-PrO2C
H
13 examples; yields: 63–94%
Department of Chemistry, University of Tarbiat Modares,
P.O. Box 14115-175, Tehran, Iran
yavarisa@modares.ac.ir
Received: 21.11.2014
Accepted after revision: 14.01.2015
Published online: 18.02.2015
Ar
CO2i-Pr
NaH
N
N
N
CO2i-Pr
+ ArOTf
i-PrO2C
i-PrO2C
N
H
DOI: 10.1055/s-0034-1380143; Art ID: st-2014-d0959-l
1
2
3
Scheme 1
Abstract A method for intermolecular N-arylation of the anionic spe-
cies derived from diisopropyl azodicarboxylate and sodium hydride by
aryl trifluoromethanesulfonates, in the presence of a ligand-free cop-
per(I) oxide catalyst at 80 °C in N,N-dimethylformamide, is reported. A
variety of functionalized aryl triflouromethanesulfonates were efficient-
ly coupled by this method.
Initial investigations show that 10 mol% of CuI could ac-
complish the transformation, and the desired coupling
product was obtained in 45% yield, together with reduced
DIAD in 20% yield. Phenyl trifluoromethanesulfonate, NaH,
and DIAD were selected as prototypical reaction partners
for the Cu2O-catalyzed coupling reaction. The optimized re-
action conditions and catalyst system for this transforma-
tion involved phenyl trifluoromethanesulfonate (1 mmol),
DIAD (1.2 mmol), NaH (1.2 mmol), Cu2O (10 mol%), and
lithium iodide (1.0 mmol) in DMF (2 mL) at 80 °C (see Table
1).
Key words C–N cross-coupling, aryl trifluoromethanesulfonates, di-
isopropyl azodicarboxylate, copper(I) oxide
The past decade has witnessed significant progress in
the development of cross-coupling reactions.1 Transition
metals are effective catalysts in cross-coupling reactions,
particularly C–N bond-formation processes.2 Several N-nu-
cleophiles, such as amines, amides, hydrazines, and N-het-
erocycles, participate in C–N cross-coupling reactions,3–5
and the application of other compounds as amination re-
agents have been developed.6,7 Diisopropyl azodicarboxyl-
ate (DIAD) has been used as a suitable amination reagent
for the preparation of hydrazides that can be subsequently
deprotected to amines. However, this reaction has been
limited to electron-rich aromatic systems.8–10
Recently, we reported effective systems for the copper-
catalyzed coupling of aryl halides with the Mitsunobu re-
agent.11 In this Letter, we describe C–N coupling of aryl tri-
flates with the anionic adduct derived from DIAD and NaH,
which constitutes a useful method for intermolecular N-
arylation with aryl trifluoromethanesulfonates (ArOTfs) in
the presence of a ligand-free Cu2O catalyst and lithium io-
dide (Scheme 1).
Table 1 Optimization of Reaction Conditions for the Cu2O-Catalyzed
Formation of Aryl Hydrazidesa
Entry
Solvent
Additive
Yield (%)
1
2
3
4
5
6
7
8
9
DMSO
THF
none
none
none
none
LiI
41
15
24
45
83
69
74
76
56
MeCN
DMF
DMF
DMF
DMF
DMF
DMF
LiBr
LiOTf
LiI
KI
a Reactions conditions: phenyl trifluoromethanesulfonate (1.0 mmol),
DIAD (1.2 mmol), NaH (1.2 mmol), Cu2O (0.10 mmol), additive (1.0
mmol), in solvent (2 mL) at 80 °C for 8 h under argon.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 942–944

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I. Yavari et al.
Letter
Synlett
In addition, 1,10-phenanthroline can be used as a
unique ligand for the N-arylation with chlorobenzenes (Ta-
ble 2). However, this conversion required higher catalyst
loading (30 mol%) compared to those of aryl iodides, bro-
mides, and triflates.
A series of substituted aryl O-triflates, as shown in Table
2, was subjected to the reaction conditions described above.
Aryl O-triflates having electron-withdrawing, electron-re-
leasing, and bulky groups on the aromatic ring, afforded
moderate to good yields (Table 2).
In conclusion, we have described a novel system for the
copper-catalyzed N-arylation of diisopropyl azodicarboxyl-
ate in good to excellent yields. This system operates under
mild enough conditions and tolerates a wide array of func-
tional groups. Using this procedure iodobenzene was selec-
tively coupled with diisopropyl azodicarboxylate in the
presence of bromobenzene and benzene O-triflates.
References and Notes
(1) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719.
(2) Reviews: (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S.
L. Acc. Chem. Res. 1998, 31, 805. (b) Hartwig, J. F. Angew. Chem.
Int. Ed. 1998, 37, 2046. (c) Muci, A. R.; Buchwald, S. L. Top. Curr.
Chem. 2002, 219, 133.
(3) Shafir, A.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 8742.
(4) Larsson, P.; Bolm, C.; Norrby, P. Chem. Eur. J. 2010, 16, 13613.
(5) Swapna, K.; Murthy, S. N.; Nageswar, Y. V. Eur. J. Org. Chem.
2010, 6678.
(6) Monguchi, Y.; Maejima, T.; Mori, S.; Maegawa, T.; Sajiki, H.
Chem. Eur. J. 2010, 16, 7372.
(7) Terada, M.; Tsushima, D.; Nakano, M. Adv. Synth. Catal. 2009,
351, 2817.
(8) Katritzky, A. R.; Wu, J.; Verin, S. V. Synthesis 1995, 651.
(9) Velarde-Ortiz, R.; Guijarro, A.; Rieke, R. D. Tetrahedron Lett.
1998, 39, 9157.
(10) Uemura, T.; Chatani, N. J. Org. Chem. 2005, 70, 8631.
(11) Yavari, I.; Ghazanfarpour-Darjani, M.; Ahmadian, S.; Solgi, Y.
Synlett 2011, 1745.
(12) Typical Procedure for the Preparation of Aryl Hydrazides 3
To a stirred solution of DIAD (1.2 mmol) in DMF (2 mL) at 0 °C,
NaH (0.05 g, 1.2 mmol) was added in portions over 20 min.
Then, the aryl O-triflate (1.0 mmol), LiI (134 mg, 1mmol), and
Cu2O (15 mg, 0.1 mmol) were added to the reaction mixture,
which was stirred at 80 °C for 8 h under N2. The reaction was
cooled and quenched by adding CH2Cl2 (2 mL) and sat. aq NH4Cl
(3 mL). The mixture was stirred for an additional 30 min, and
two layers were separated. The aqueous layer was extracted
with CH2Cl2 (3 × 2 mL), the combined organic layers were dried
over MgSO4, filtered, and concentrated in vacuo. The residue
was purified by chromatography (silica gel; hexane–EtOAc, 3:1)
to give the product.
Table 2 Reaction Scope for Aryl Sources
Ar
Cu2O, NaH, LiI
DMF, 70 °C
CO2i-Pr
N
N
CO2i-Pr
ArOTf
+
N
i-PrO2C
N
i-PrO2C
H
1
2
3
Entry
Ar
Ph
Product
Yield (%) of 3
1
2
3a
3b
3c
3d
3e
3f
83
80
79
72
80
70
63
81
84
67
94
79
76
1-naphthyl
4-MeC6H4
2-MeC6H4
3-MeC6H4
4-MeOC6H4
2-F3CC6H4
3-F3CC6H4
4-NCC6H4
2-O2NC6H4
4-O2NC6H4
2-thienyl
3
4
5
6
7
3g
3h
3i
8
9
10
11
12
13
3j
3k
3l
2-ClC6H4
3m
The optimized reaction conditions given above were
compatible with the presence of functional groups such as
CN, NO2, CF3, OMe, and halogens on the aromatic rings of
the aryl halides and triflates. With iodobenzene as arylating
reagent, the reaction could be carried out at 25 °C in the
presence of Cu2O in DMF to achieve the desired product in
90% yield.
A plausible mechanism for the formation of products
312 is given in Scheme 2. The copper complex 4, formed
from 1 and Cu2O, undergoes a reduction reaction with NaH
to generate the salt 5. This salt is attacked by aryl trifluoro-
methanesulfonate 2 to afford aryl hydrazide 3.
Spectroscopic analyses of all derivatives except 3d and 3m have
been reported.11
Diisopropyl 1-o-Tolylhydrazine-1,2-dicarboxylate (3d)
Yellow solid; mp 101–103 °C; yield: 0.21 g (72%). IR (KBr): νmax
= 3242, 1541, 1518, 1330, 1140 cm–1
CDCl3): δ = 1.16 (6 H, d, J = 7.1 Hz, 2 Me), 1.25 (6 H, d, J = 7.0
.
1H NMR (500.1 MHz,
3
3
Hz, 2 Me), 2.33 (3 H, s, Me), 4.97–4.99 (2 H, m, 2 CHO), 7.06 (1
3
H, br s, NH), 7.19–7.22 (3 H, m, 3 CH), 7.44 (1 H, d, J = 7.8 Hz,
CH). 13C NMR (125.7 MHz, CDCl3): δ = 21.1 (2 Me), 21.4 (2 Me),
26.1 (Me), 68.9 (CHO), 70.1 (CHO), 113.1 (CH), 119.2 (CH), 126.3
(CH), 129.2 (CH), 130.9 (C), 140.5 (C), 155.7 (C=O), 156.1 (C=O).
MS: m/z (%) = 294 (4 [M+], 235 (57), 192 (42), 177 (40), 133
(100), 102 (76), 58 (34), 44 (28). Anal. Calcd (%) for C15H22N2O4
(294.35): C, 61.21; H, 7.53; N, 9.52. Found: C, 59.89; H, 7.59; N,
9.59.
ArOTf
NaH
H
CO2i-Pr
Cu2O
CO2i-Pr
2
N
N
1
3
N
N
i-PrO2C
i-PrO2C
Na
Cu2O
4
5
Diisopropyl 1-(2-Chlorophenyl)hydrazine-1,2-dicarboxylate
(3m)
Scheme 2
Colorless solid; mp 103–106 °C; yield 0.24 g (76%). IR (KBr):
ν
max = 3286, 1564, 1518, 1332, 1136 cm–1. 1H NMR (500.1 MHz,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 942–944

944
I. Yavari et al.
Letter
Synlett
CDCl3): δ = 1.13 (6 H, d, 3J = 6.9 Hz, 2 Me), 1.26 (6 H, d, 3J = 7.0
Hz, 2 Me), 4.98–5.01 (2 H, m, 2 CHO), 7.17 (1 H, br s, NH), 7.46–
7.53 (2 H, m, 2 CH), 7.62–7.67 (2 H, m, 2 CH). 13C NMR (125.7
MHz, CDCl3): δ = 21.9 (2 Me), 22.3 (2 Me), 70.1 (CHO), 71.0
(CHO), 123.8 (CH), 128.1 (CH), 131.6 (CH), 132.6 (CH), 133.0 (C),
139.4 (C), 154.3 (C=O), 156.0 (C=O). MS: m/z (%) = 314 (1) [M+],
225 (12), 212 (53), 197 (45), 152 (100), 102 (64), 111 (12), 58
(35), 44 (19). Anal. Calcd (%) for C14H19ClN2O4 (314.76): C, 53.42;
H, 6.08; N, 8.90. Found: C, 53.79; H, 6.04; N, 8.98.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 942–944

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