Can we aminate Grignard reagents under Barbier conditions?

Article abstract of DOI:10.1016/S0040-4039(02)01328-X

The reaction of aryl bromides with acetone O-(2,4,6-trimethylphenylsulfonyl)oxime and magnesium in THF at reflux temperature for 3 h provides a one-pot procedure for amination of aryl Grignard reagents under Barbier conditions.

Full text of DOI:10.1016/S0040-4039(02)01328-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6237–6239
Can we aminate Grignard reagents under Barbier conditions?
Ender Erdik* and Tahir Das¸kapan
Ankara University, Science Faculty, Department of Chemistry Bes¸evler, Ankara 06100, Turkey
Received 9 April 2002; revised 29 May 2002; accepted 28 June 2002
Abstract—The reaction of aryl bromides with acetone O-(2,4,6-trimethylphenylsulfonyl)oxime and magnesium in THF at reflux
temperature for 3 h provides a one-pot procedure for amination of aryl Grignard reagents under Barbier conditions. © 2002
Elsevier Science Ltd. All rights reserved.
The formation of CꢀN bonds using electrophilic amina-
tion reagents is gaining importance due to the common-
place use of organometallic reagents and the
importance of amino functionalities in natural products
and drugs as well as building blocks in organic synthe-
sis. There are detailed reviews on the amination of
carbanions.1
and chiral enolates2b,13 or using enolates in the presence
of chiral catalysts14 or stereocontrolling units15 have
been reported. Azodicarboxylate esters have been used
extensively as aminating reagents for this purpose. Chi-
ral azodicarboxylate esters16 and azo dicarboxamides17
have also been synthesized for the electrophilic amina-
tion of achiral enolates.
Recent studies in this field have found several new
electrophilic amination reagents, such as lithium t-butyl
N-tosyloxycarbamate,2 ceric ammonium nitrate/sodium
azide,3 N-(tosylimino)phenyliodinane,4 diethyl N-ani-
syliminomalonate,5 new derivatives of O-substituted
hydroxylamines,6 N-protected aziridines,7 and oxime
O-sulfonates.8
Acetone O-(2,4,6-trimethylphenylsulfonyl)oxime 1 has
been developed in our laboratories for the electrophilic
amination of Grignard reagents and organozincs.
Reaction of mono or diorganozincs and triorganozin-
cates with 1 in THF in the presence of CuCN at room
temperature for 3 h resulted in the amination of the
organozincs in moderate to good yields. As organozincs
can be prepared by transmetallation of the correspond-
ing Grignard reagents and organolithiums, this amina-
tion protocol also provides an alternative method for
electrophilic amination of Grignard reagents and
organolithiums. In earlier papers,8a,b,18 we reported a
method for the amination of aryl Grignard reagents
with 1 in THF:toluene in the presence of CuI as a
Efficient methods are now available for electrophilic
amination
of
organolithiums,1,2a
Grignard
reagents,1,2a,5,8a,b,e,f organocuprates,1,2a,6,8a,c,d,f organo-
zincs,8c,d,9,10 and enolates.1,2b,3,4,7,11
In addition, successful asymmetric versions of elec-
trophilic amination using chiral Grignard reagents12
H3C
H2O
RNH2
+
(CH3)2 C NOSO2
CH3
[(CH3)2C NR]
RM
H3C
1
1
3
1
2
Zn,
ZnMgBr
M: MgBr, ZnCl(Br),
Scheme 1. Amination of organomagnesium and organozinc reagents with acetone O-(2,4,6-trimethylphenylsulfonyl)oxime.
* Corresponding author. Tel.: 90 312 2126720; fax: 90 312 223 23 95; e-mail: erdik@science.ankara.edu.tr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01328-X

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E. Erdik, T. Das¸kapan / Tetrahedron Letters 43 (2002) 6237–6239
Cu(I) catalysis or MgCl2 addition. However, we could
not succeed in the amination of n-hexyl, cyclohexyl and
benzyl magnesium bromides under Barbier conditions
and the yields of amines were found to be no higher
than 15%. We would also like to note that our earlier
attempts18 in the amination of pre-prepared n-hexyl
and benzyl Grignard reagents with 1 either in the
presence of CuI or MgCl2 catalysis or without catalysis
did not give yields higher than 22%. So, to our satisfac-
tion, the reaction of aryl bromides with magnesium and
acetone O-(2,4,6-trimethylphenylsulfonyl) oxime in
THF at reflux temperature provides a versatile route
for the synthesis of arylamines via a Barbier–Grignard
type amination.
catalyst or MgCl2 as a Lewis acid at reflux temperature
for 11–23 h.
In amination, 1 reacts with organomagnesium and
organozinc reagents by displacement of the mesitylsul-
fonyl group giving an imine, which upon hydrolysis
provides amines (Scheme 1).
In an effort to broaden the scope of electrophilic ami-
nation with 1, we investigated the feasibility of the
reaction under Barbier conditions,19,20 i.e. we tried to
carry out the reactions of organic halides with magne-
sium in the presence of 1. Although the use of previ-
ously prepared Grignard reagents does not pose any
practical problem in Cu(I) catalyzed electrophilic ami-
nation, the reaction of in situ prepared Grignard
reagents with 1 is, by all means, more pleasing. To this
end, we examined the reactivities of some aryl bro-
mides, n-hexyl, cyclohexyl and benzyl bromide in the
Barbier–Grignard type amination procedure.
Efforts to extend the magnesium mediated electrophilic
amination of organic halides are currently in progress.
Acknowledgements
The synthesis of arylamines was achieved with remark-
able ease by simultaneous addition of THF solutions of
the aryl bromide and 1 to magnesium and then heating
the mixture under reflux for about 3 h. The yields of
arylamines obtained in the reactions of aryl bromides
with magnesium and 121 are tabulated (Table 1) and the
yields of the reactions of aryl Grignard reagents with 1
under catalytic conditions8a,b,18 are also included for
comparison. As can be seen, Barbier conditions provide
arylamines in moderate yields, which are not lower
than those obtained with pre-prepared Grignard
reagents. In addition, amination of in situ prepared
Grignard reagents took place without a co-solvent and
in a much shorter time, and to our surprise without
We are grateful to the Turkish Scientific and Technical
Research Council (Grant No TBAG-1983 100T087) for
financial support.
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Table 1. Comparative amination of pre-prepared and in
situ prepared aryl Grignard reagents (Methods A and B,
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Method Aa
Mg
1. 1 Catalyst, Et O:toluene (1:4), 75°C, 11ꢀ23 h
2
ArBr “ ArMgBr ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢁ ArNH2
THF
2. conc. HCl, reflux, 2ꢀ4 h and rt, 24 h
Catalyst: CuI, MgCl2
Method Bb
1. THF, 75°C, 3 h
ArBr+Mg+1 ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢁ ArNH2
2. conc. HCl, rt, 24 h
Yield of ArNH2 (%)c
Method A Method B
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