Ag+ mediated deaminations of N-Boc aryl hydrazines for the efficient synthesis of N-Boc aryl amines

Article abstract of DOI:10.1016/S0040-4039(02)01800-2

N-Boc-aryl hydrazines were converted into N-Boc-aryl amines under the action of Ag⁺. Its mild reaction conditions tolerate the presence of a variety of functional groups.

Full text of DOI:10.1016/S0040-4039(02)01800-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7463–7464
+
Ag mediated deaminations of N-Boc aryl hydrazines for the
efficient synthesis of N-Boc aryl amines
Kang-Sang Lee, Young-Kwan Lim and Cheon-Gyu Cho*
Department of Chemistry, Hanyang University, Seoul, Republic of Korea 133-791
Received 30 July 2002; revised 26 August 2002; accepted 28 August 2002
+
Abstract—N-Boc-aryl hydrazines were converted into N-Boc-aryl amines under the action of Ag . Its mild reaction conditions
tolerate the presence of a variety of functional groups. © 2002 Elsevier Science Ltd. All rights reserved.
During the study involving Pd-catalyzed coupling reac-
tions of hydrazides with aryl halides, we have found
that the attempted coupling reaction of N-Boc phenyl
hydrazine (1a) with PhBr provided N-Boc-aniline (2a)
and recovered PhBr under the catalytic conditions com-
prised of Pd(PPh ) Cl /dppf and Ag CO in toluene
A set of experiments using different salts (Na CO ,
2 3
K CO , Cs CO ) confirmed that the reaction was
2
3
2
3
+
1
indeed mediated by Ag (data not shown). The reac-
tion did not go to completion even after 24 h, when the
reaction was run with less than 1.0 equiv. of Ag CO
2
3
+
(2.0 equiv. for Ag ). Thus, 1.1 equiv. of Ag CO was
3
2
2
2
3
2
3
(
Scheme 1).
used for the next deamination experiments.
The deamination reaction proceeded quite smoothly in
most organic solvents under anhydrous conditions.
Both reaction rates and chemical yields dropped rather
significantly when the reactions were carried out in wet
solvent. DME is slightly better than any other solvents
in terms of isolated product yields (Table 1). The
reaction rate appeared to be roughly proportional to
the solvent polarity.
Scheme 1.
Also found was that the deamination reaction pro-
ceeded without Pd catalyst, but not without Ag CO .
With DME as an optimal solvent, we investigated the
effect of counter ions by using different silver salts. We
2
3
There are few methods available in the literature for the
deamination of hydrazides, which includes Leblanc’s
condition using Zn metal with acetic acid. In most
Table 1. Deamination with Ag CO in various solvents
1
2
3
cases, the hydrazides were converted into hydrazines,
prior to the metal catalyzed hydrogenolytic NꢀN bond
2
cleavage to the corresponding amines. A thorough
literature search revealed no examples related to our
Ag mediated deamination reactions of aryl hydrazides.
Entry
Solvent
Time (h)
Yield (%)
+
1
2
3
4
5
6
7
8
9
Benzene
Toluene
THF
3
3
3.5
1
1
6.5
2.5
0.5
1
83
92
83
82
95
67
78
72
64
68
Prompted by the novelty and mild reaction conditions
of our deamination method, we studied its scope and
limitation in detail. Herein, we wish to present our new
deamination reaction of Boc-aryl hydrazides mediated
CH Cl
2
2
DME
EtOAc
MeCN
DMF
MeOH
DMSO
+
1 3
by Ag .
1
0
0.5
*
0
Corresponding author. E-mail: ccho@hanyang.ac.kr
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01800-2

7
464
K.-S. Lee et al. / Tetrahedron Letters 43 (2002) 7463–7464
Table 2. Deamination with other silver salts
The starting N-Boc aryl hydrazines were prepared from
the coupling reactions of the corresponding aryl halides
Entrya
Saltb
Time (h)
Yield (%)
with Boc hydrazine (Boc-NHNH ) according to the
2
4
literature method.
1
2
3
4
5
6
7
8
9
Ag CO
1
1.5
1.5
48
5
5
5
16
5
95
78
87
0
2
3
Ag O
2
N-Boc hydrazines with aryl substituents at N% position
did not undergo deamination reactions. No deaminated
products were obtained from the compounds bearing
usual NꢀN single bond, for example, phenyl hydrazine.
AgOAc
AgIO3
AgNO3
Ag SO
73
Trace
Trace
26
2
4
AgOTf
AgClO4
Ag PO
Neither N-aminophthalimide nor benzoic hydrazide
gave the desired deamination products (Scheme 2).
Trace
3
4
a
The reaction was conducted with N-Boc phenyl hydrazine in DME
at 80°C.
b
1
.1 equiv. of the salt was used in all reactions.
used 1.1 equiv. of silver salts, which is based on the
+
reagent, not on Ag . Thus, the actual equivalency of
+
Ag varies with the type of silver salts (Table 2).
Scheme 2. Attempted deaminations of other systems.
As seen, the reaction is highly dependent on the nature
of the counter ion; while Ag CO is better than any
In summary, we have found that N-Boc aryl hydrazines
undergo facile deamination reactions in the presence of
Ag CO or other silver salts to give rise to the corre-
sponding N-Boc aryl amines in good to excellent iso-
lated yields. Its mild reaction conditions tolerate the
presence of a variety of functional groups. Further
work is needed to elucidate its reaction mechanism.
2
3
other salts in terms of isolated yields, virtually no
reaction was observed with AgIO , Ag SO , AgOTf and
2
3
3
2
4
AgClO . Basicity (or nucleophilicity) of the counter ion
4
may be an important factor in the reaction. In fact, we
observed smooth deamination reactions with the silver
salts exhibited little activity (entries 4, 6, 7, 8 and 9),
when the reactions were carried out in the presence of
added NaOH. However, successful deamination with
Acknowledgements
AgNO carrying weak base (entry 5) does not fall into
3
our basicity hypothesis. Also notable is that 1.1 equiv.
of AgOAc gave a similar result to 1.1 equiv. of Ag CO
2
3
+
We would like to thank the financial support of
Hanyang University, Korea, made in the program year
of 1998.
(
2.2 equiv. for Ag ).
For experimental consistency, we continued to use
Ag CO for the deaminations of aryl hydrazides bear-
2
3
ing various functional groups to furnish the products
b–i (Table 3).
References
2
1
2
3
. (a) Deniau, E.; Enders, D. Tetrahedron Lett. 2000, 41,
As a general trend, aryl hydrazides with electron donat-
ing groups underwent faster deamination reactions than
those with electron withdrawing groups.
2
5
347; (b) Evans, D. A.; Johnson, D. S. Org. Lett. 1999, 1,
95; (c) McClure, C. K.; Mishra, P. K.; Grote, C. W. J.
Org. Chem. 1997, 62, 2437; (d) Leblanc, Y.; Fitzsimmons,
B. J. Tetrahedron Lett. 1989, 30, 2889.
. (a) Genari, C.; Colombo, L.; Bertolini, G. J. Am. Chem.
Soc. 1986, 108, 6394; (b) Evans, D. A.; Britton, T. C.;
Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108,
Table 3. Deaminations with other hydrazides
6396; (c) Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc.
1986, 108, 6397.
. Representative procedure: A mixture of N-Boc phenyl
Entry
R
Time (h)
Yield (%)
hydrazine (1a, 50 mg, 0.24 mmol), 1.1 equiv. of Ag CO3
2
(
73 mg, 0.26 mmol) in 2 mL of anhydrous DME was
1
2
3
4
5
6
7
8
9
H
Me
1
1
48
1.5
3
72
2.5
1
95
88
64
88
76
70
74
87
83
heated at 80°C for 1 h. Upon cooling to rt, the reaction
mixture was partitioned into CH Cl and H O. The sepa-
rated organic layer was dried over MgSO , concentrated in
vacuo and column chromatographed (hexanes/EtOAc: 15/
2
2
2
NO2
4
MeO
CN
CO Me
1
) to give 44 mg of N-Boc phenylamine 2a as a white solid
2
in 95% yield.
COMe
Ph
4
. (a) Wolter, M.; Klapars, A.; Buchwald, S. L. Org. Lett.
2001, 3, 3803; (b) Wang, Z.; Skerlj, R. T.; Bridger, G. J.
Tetrahedron Lett. 1999, 40, 3543.
t
Bu
1