Aryl C-N bond formation by electrophilic amination of diarylcadmium reagents with O-substituted ketoximes

Article abstract of DOI:10.1080/00397911.2016.1177729

Diorganocadmium reagents cannot react with ketoxime at room temperature. CuCN catalysis allows diarylcadmium reagents to react with ketoxime and to give corresponding arylamines in good to high yields at room temperature. According to the electronic effects of the substituent attached to the aromatic ring, functionalized diarylcadmium reagents show meta-para selectivity in their amination reactions. Also compared to diarylzinc reagents, diarylcadmium reagents react with O-substituted ketoxime under milder reaction conditions and they form corresponding arylamines in higher yields. CuCN cannot help dialkyl-, dicycloalky-, and dibenzylcadmium reagents to react with ketoxime. Our Aryl C-N bond formation method does not include cadmium excretion into the environment.

Full text of DOI:10.1080/00397911.2016.1177729

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Aryl C-N bond formation by electrophilic
amination of diarylcadmium reagents with O-
substituted ketoximes
Tahir Daşkapan & Adem Korkmaz
To cite this article: Tahir Daşkapan & Adem Korkmaz (2016) Aryl C-N bond formation by
electrophilic amination of diarylcadmium reagents with O-substituted ketoximes, Synthetic
Communications, 46:9, 813-817, DOI: 10.1080/00397911.2016.1177729
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1177729
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Date: 02 June 2016, At: 04:30

SYNTHETIC COMMUNICATIONS®
2016, VOL. 46, NO. 9, 813–817
http://dx.doi.org/10.1080/00397911.2016.1177729
Aryl C-N bond formation by electrophilic amination of
diarylcadmium reagents with O-substituted ketoximes
Tahir Daşkapan and Adem Korkmaz
Department of Chemistry, Science Faculty, Ankara University, Ankara, Turkey
ABSTRACT
ARTICLE HISTORY
Received 2 March 2016
Diorganocadmium reagents cannot react with ketoxime at room
temperature. CuCN catalysis allows diarylcadmium reagents to react
with ketoxime and to give corresponding arylamines in good to high
yields at room temperature. According to the electronic effects of the
substituent attached to the aromatic ring, functionalized diarylcad-
mium reagents show meta-para selectivity in their amination reactions.
Also compared to diarylzinc reagents, diarylcadmium reagents react
with O-substituted ketoxime under milder reaction conditions and
they form corresponding arylamines in higher yields. CuCN cannot
help dialkyl-, dicycloalky-, and dibenzylcadmium reagents to react with
ketoxime. Our Aryl C-N bond formation method does not include
cadmium excretion into the environment.
KEYWORDS
Amination; amines;
benzamides; copper
catalysis; organocadmium;
oximes
GRAPHICAL ABSTRACT
Introduction
Electrophilic amination of organometallic reagents is an important and useful synthetic
method for the synthesis of organic compounds bearing amino functionality and is
continuing to gain the attentions of chemists.[1,2] To date, various procedures for C-N bond
formation by electrophilic amination of organomagnesium,[3–6] organozinc,[7–12] and
organocopper reagents[12–17] have been reported. Organocadmium reagents have been
mostly used for the synthesis of ketones from acid halides or acid anhydrides. They have
been also used for regioselective alkylation of quinones.[18,19] Recently diarylcadmium
reagents prepared by depronative cadmation using LiCd(TMP)3 (prepared from LiTMP
and CdCl2 · TMEDA (N,N,N',N'-tetramethylethylenediamine)) have been reacted with
some electrophiles successfully.[20–22] To our knowledge, there has not been any publi-
cation about electrophilic amination of organocadmium reagents with oximes to date.
Previously, our research group described high-yielding processes for electrophilic
amination of organozinc reagents.[23–25] Organozinc reagents are prepared using ZnCl2
or ZnBr2 and both of these zinc compounds are hygroscopic. Therefore, extra care and pre-
cautions are needed while working with these compounds. Organocadmiums can tolerate
CONTACT Tahir Daşkapan
daskapan@science.ankara.edu.tr
Ankara University, Science Faculty, Department of
Chemistry, 06100 Beşevler, Ankara, Turkey.
Supplemental data for this article can be accessed on the publisher’s website.
© 2016 Taylor & Francis

814
T. DAŞKAPAN AND A. KORKMAZ
several functional groups and therefore allow synthesis of functionalized organic
compounds, like organozinc reagents. For this reason, we had concluded that examining
C-N bond formation using organocadmium reagents would be useful in terms of synthetic
organic chemistry.
Results and discussion
In this article, reaction of diaryilcadmium reagents with ketoxime under catalyst-free
conditions, a CuCN-catalyzed aryl C-N bond-formation method, and the determination
of applicability of this method using functionalized diarylcadmiums are given.
We used acetone O-(2,4,6-trimethylphenylsulfonyl)oxime 1, which is a sp2-N containing
reagent and reacts with organometallic reagents by displacement of the mesitylsulfonyloxy
group to give an imine, as aminating agent (Scheme 1). Diarylcadmium reagents were
prepared by transmetallation of the corresponding arylmagnesium bromides with CdI2 in
tetrahydrofuran (THF) and controlled by Gilman’s color test.[26] Amination reaction was
performed by cannulation of THF solution of 1 into organocadmium reagent. Since CdI2
is not a hygroscopic compound, it was too easy to work with it compared to zinc halides.
Arylamines as the final products were removed from the reaction mixture as their
benzamide derivatives and these known compounds were identified from their melting
points[27,28] and 1H NMR analysis.[28–32] Cadmium was removed from reaction
mixture as a white-colored salt (Cd(OH)2) during basification of the reaction mixture after
hydrolysis with concentrated HCl. Thereby cadmium was not discarded as waste.
Reaction of diphenylcadmium with 1 under catalyst-free reaction conditions at room
temperature to furnish aniline resulted in failure (Table 1, entry 1). For this reason, we
decided to try CuCN catalysis: 10 mol% CuCN helped diphenylcadmium to react with
ketoxime, but the yield of aniline was low (entry 2). Decreasing the amount of CuCN from
10 mol% to 5 mol% led to a dramatic yield increase (entry 3). When reaction time was
kept less than 90 min the yield started to decrease (entries 3–5). The highest yield was
obtained when reaction was run for 90 min at room temperature in the presence of
5 mol% CuCN (entry 6). Less than 1 mmol of diphenylcadmium was not sufficient to
obtain aniline in high yield (entry 8). Use of CdCl2 for the preparation of diphenyl-
cadmium led to slight decrease in yield; in addition CdCl2 is too hygroscopic and it
was difficult to work with it (entry 9). Use of phenyllithium, prepared in ether, instead
of PhMgBr in THF for the preparation of diphenylcadmium led to decrease in the yield
of aniline (entry 10).
After setting the optimal reaction conditions, we turned our attention to examine the
scope of the electrophilic amination method that we developed for diarylcadmiums.
Electron-withdrawing or electron-releasing substituted anilines were synthesized in good
Scheme 1. Aryl C-N bond formation by electrophilic amination of diarylcadmiums with acetone
O-(2,4,6-trimethylphenylsulfonyl)oxime.

SYNTHETIC COMMUNICATIONS®
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Table 1. CuCN-catalyzed electrophilic aminaton of Ph2Cd.
Entry
CuCN (%)
Time (min)
PhNH2 (%)
1
2
—
10
5
60
60
60
45
30
90
90
90
90
—
41
3
72
4
5
61
5
5
5
2.5
5
5
5
56
6
78
7
48
8
42b
68c
50d
9
10
aPh2Cd/ketoxime ¼ 1:1.
bPh2Cd/ketoxime ¼ 0.8:1.
cPh2Cd was prepared using CdCl2 instead of CdI2.
dPh2Cd was prepared using PhLi /Et2O.
eYield of aniline was isolated as its benzamide derivative.
to high yields under optimized reaction conditions (Table 2). In the reaction of þM > À I
type group substituted diarylcadmiums with 1, meta-functionalized aniline was obtained in
higher yield than para-functionalized aniline (entries 3 and 4). In contrast, in the case of
À I >> þM type substituent, diarylcadmium bearing the substituent at the para-position
gave better yield than meta-substituted diarylcadmium (entries 5 and 6).
Naphtylamine was afforded in moderate yield. Alkyl-, cycloalkyl-, and benzylcadmium
reagents gave unsuccessful reactions with ketoksime.
The data obtained from this study showed that aryl C-N bond formation reaction using
diarylcadmium reagents is higher yielding than the same reaction of diarylzinc reagents.
[11,12]
For example, both aniline and 4-anisylamine were obtained in 51% yields using cor-
responding diarylzinc reagents in the presence of 20% mol of CuCN at room temperature,
in 3 h. As seen in Table 2, these amines obtained in higher yields (78% and 71% respect-
ively) using corresponding diarylcadmium reagents in the presence of 4 times less amount
of CuCN without any need to use cosolvent or additive, at room temperature in 1.5 h. In
Table 2. Functionalized arylamine preparation using Ar2Cd.
Entry
Ar
ArNH2 (%)
1
2
3
4
5
6
7
8
9
10
C6H5
78
79
71
77
75
68
71
63
64
56
4-CH3SC6H4
4-CH3OC6H4
3-CH3OC6H4
4-ClC6H4
3-ClC6H4
3,5-(Cl)2C6H3
4-FC6H4
2,5-(CH3)2C6H3
1-Naphtyl
aAr2Cd/ketoxime ¼ 1:1.
bYields of amines were isolated as their benzamide derivatives.

816
T. DAŞKAPAN AND A. KORKMAZ
addition, since organocadmium reagents were prepared using nonhygroscopic CdI2, it was
easier to work with them compared to organozinc reagents.
Conclusions
In summary, this work contains the first data about the electrophilic amination of
diorganocadmium reagents with ketoximes. We have shown that arylamines can be
synthesized at room temperature using diarylcadmium reagents in the presence of 5 mol%
CuCN, without any cadmium excretion into the environment.
Experimental
All reactions involving organocadmium reagents were performed in flame-dried glassware
with standard syringe / cannula techniques[33] under an atmosphere of dry, oxygen-free
argon. Melting points were determined on a Gallencamp capillary melting point. 1H
NMR spectra were recorded in CDCl3 or dimethylsulfoxide (DMSO-d6) at room tempera-
ture on a Varian-Mercury 400-MHz (FT) NMR spectrometer. All chemical shifts were
given in parts per million (ppm) downfield from tetramethylsilane (TMS).
THF was freshly distilled from solution of sodium / benzophenone under dry argon.
Copper(I) cyanide was purified prior to use[34] and kept under a dry argon atmosphere.
Magnesium turnings for Grignard reactions (Fischer) and cadmium iodide (Merck)
were used without any purification. Aryl bromides (Sigma-Aldrich) were in high purities
and used without any further purification.
Organomagnesium bromides were prepared in THF by conventional standard methods
and their concentrations were determined by the method of Watson and Eastham.[35]
Acetone O-(2,4,6-trimethylphenylsulfonyl)oxime 1 was prepared and purified according
to the method described in the literature.[36]
General procedure: CuCN-catalyzed electrophilic amination of diphenylcadmium
with acetone O-(2,4,6-trimethylphenylsulfonyl)oxime
A solution of CdI2 (0.3664 g, 1 mmol) in anhydrous THF (3 ml) was cooled to À 3 °C under
an argon atmosphere and 2 mmol of phenylmagnesium bromide in THF was added
dropwise by syringe. The reaction mixture was stirred for an additional 10 min, the cooling
bath was removed, and the resulting suspension was stirred at room temperature for
10 min. To this mixture, CuCN (0.05 mmol 5%) and a solution of 1 (1 mmol) in dry
THF (2 ml) were added. The reaction mixture was stirred at room temperature for 1.5 h
and then worked up by addition of concentrated HCl and stirred overnight at room
temperature. The aqueous phase was washed with diethyl ether (2 � 50 ml) and made basic
with concentrated NaOH, and the free amine was extracted with diethyl ether (3 � 50 ml).
The organic layer was dried over Na2SO4, the solvent was evaporated, and the crude
product was converted to its N-benzoyl derivative by reaction with benzoyl chloride
in the presence of NaOH. The product was recrystallized from ethanol–water (4:1).
Mp: 160–162 °C (lit.[27] 160 °C); 1H NMR (400 MHz, CDCl3, ppm): δH 7.96 (s, 1 H),
7.85–7.88 (m, 2 H), 7.64–7.67 (m, 2 H), 7.52–7.56 (m, 1 H), 7.44–7.48 (m, 2 H),
7.34–7.39 (m, 2 H), 7.13–7.17 (m, 1 H).

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817
Funding
Financial support from Ankara University Research Foundation (Grant No. 15L0430009) and
Turkish Higher Education Council (ÖYP Program) are greatly acknowledged by the authors.
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