Use of allylzinc halide as a source of halide: Differential addition of nucleophiles to Ts-aziridines and aldehydes under similar reaction conditions

Article abstract of DOI:10.1016/j.tetlet.2018.12.027

We have observed that the allylic zinc halide under identical reaction conditions acts in different modes for different electrophiles. For Ts-aziridines the halide part of the allylic halide has been introduced as a nucleophile and for the carbonyl compou

Full text of DOI:10.1016/j.tetlet.2018.12.027

Accepted Manuscript
Use of allylzinc halide as a source of halide: differential addition of nucleophiles
to Ts-aziridines and aldehydes under similar reaction conditions
Rana Chatterjee, Satyajit Samanta, Anindita Mukherjee, Sougata Santra,
Grigory V. Zyryanov, Adinath Majee
PII:
S0040-4039(18)31469-2
https://doi.org/10.1016/j.tetlet.2018.12.027
TETL 50490
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
7 November 2018
11 December 2018
13 December 2018
Please cite this article as: Chatterjee, R., Samanta, S., Mukherjee, A., Santra, S., Zyryanov, G.V., Majee, A., Use
of allylzinc halide as a source of halide: differential addition of nucleophiles to Ts-aziridines and aldehydes under
similar reaction conditions, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.12.027
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Rana Chatterjee, Satyajit Samanta, Anindita Mukherjee, Sougata Santra, Grigory V. Zyryanov, Adinath Majee*

1
Tetrahedron Letters
Use of allylzinc halide as a source of halide: differential addition of nucleophiles to
Ts-aziridines and aldehydes under similar reaction conditions
Rana Chatterjee,a Satyajit Samanta,a Anindita Mukherjee,b Sougata Santra,b Grigory V. Zyryanov,b,c and
Adinath Majeea, 
a
Department of Chemistry; Visva-Bharati (A Central University), Santiniketan 731235, India
Department of Organic and Biomolecular Chemistry, Chemical Engineering Institute, Ural Federal University, 19 Mira Street, 620002, Yekaterinburg, Russian
b
Federation
c I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy Street, 620219 Yekaterinburg, Russian
Federation
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We have observed that the allylic zinc halide under identical reaction conditions acts in different
modes for different electrophiles. For Ts-aziridines the halide part of the allylic halide has been
introduced as a nucleophile and for the carbonyl compounds the simple allylation reaction
occurs. To the best of our knowledge this is the first report where the allylic zinc halide is the
source of halide acting as nucleophile. The main advantages of the present procedure are easy to
handle, no need of inert atmosphere, mild reaction conditions, and applicability to a wide variety
of substrates for aziridines and carbonyl compounds.
Available online
Keywords:
Aziridine
Allylic halides
Halogenations
Carbonyls
2009 Elsevier Ltd. All rights reserved.
Allylation
The basic difference between the Barbier [1] and the Grignard
reaction [2] is that the former is a single step one-pot reaction
whereas the later, composes of a two-step procedure that requires
the formation of an alkyl metal in the first step followed by its
reaction with a carbonyl or targeted compound in the second step.
Both of these reactions are well studied since their innovation.
Particularly, allylation reaction has been studied extensively in
Barbier concept, due to the high reactivity of allylic halides
towards many low valent metals like Li [3], Mg [4], Mn [5], Zn
[6], Sn [7], Pb [8], Bi [9], Ce [10], In [11], and many others [12]
and the characteristic features of each metal has been well
documented. It is worthy to mention that both in Barbier and
Grignard concept we use the alkyl part as a nucleophilic source
for the addition reaction assuming the in situ formation of
organometallic reagent. To the best of our knowledge there is no
such report till date where the halide portion has been used as a
source of nucleophile for addition reactions from an
organometallic reagent by Barbier or Grignard concept.
the allylic halide has been added as a nucleophile while for the
carbonyl compounds the simple allylation reaction has occurred
(Scheme 1) under similar reaction conditions.
Scheme 1 Allylation and halogenations reactions of carbonyl
compounds and Ts-aziridines respectively.
Initially we were interested in the simple nucleophilic ring
opening of aziridine by allylation for which, N-tosylaziridines 1a
(1 mmol) and allylic bromide 2a (3 mmol) were taken as
substrates in presence of zinc dust (1 mmol) as reported by Doyle
et al. [14] at room temperature using Cu(OAc)2 as an additive.
We have observed in change of the starting material after 12 h.
Afterwards we carried out the same reaction at 60 °C and
observed a considerable conversion of aziridine to our expected
ring opening product. After careful work up and purification,
surprisingly we found that the corresponding ring opening
product of aziridine under these conditions using the additive
Cu(OAc)2 is not the allylation product rather it is the ring opening
product of aziridine by bromide as a nucleophile (Scheme 2).
Since two decades, our group is actively engaged in
developing new methodologies for different useful reactions in
organic synthesis and recently with aziridines giving special
emphasis on green chemistry [13]. Herein, we wish to report a
very much interesting and new finding of Ts-aziridine versus
simple carbonyl compounds under similar reaction conditions.
W—e—ha—ve observed that in cases of Ts-aziridine the halide part of
 Corresponding author. e-mail: adinath.majee@visva-bharati.ac.in

2
Tetrahedron Letters
7
1,4-Dioxone
EtOH
-
42
8
18
9
0
10c
11d
12e
13f
THF
Trace
83
THF
THF
80
THF
62
a Reaction conditions: A mixture of 1a (1 mmol) and 2a (3 mmol) was heated
at 60 °C for 6 h in presence of 10 mol% Cu(OAc)2 and 1 mmol of Zn dust.
b Isolated yields.
Scheme 2. Selectivity of nucleophile for aziridine ring-
opening.
c Reaction was carried out at room temperature.
d Reaction time 9 h.
In view of complete understanding and optimizing this
observation the reaction was carried out in various organic
solvents such as THF, DMSO, DMF, acetonitrile, 1,2-DCE,
toluene, 1,4-dioxane, ethanol, etc. at 60 °C temperature. The
results are summarized in Table 1. Either moderate or trace
amount of the desired product was observed in DMSO, DMF,
acetonitrile, 1,2-DCE, toluene, 1,4-dioxane and ethanol (Table 1,
entries 2-8) as the solvent. Whereas the targeted product was
obtained with maximum yield (84%) in THF solvent at 60 °C for
6 h (Table 1, entry 1), no significant amount of the desired
product was formed when the reaction was carried out at room
temperature (Table 1, entry 10). The best effective reaction
temperature was found to be 60 °C (Table 1, entry 1) and the
yield of the reaction did not improve by increasing the reaction
time from 6 h to 9 h (Table 1, entry 11). Increase of the
temperature was not beneficial (Table 1, entry 12) while
decreasing the reaction temperature decreased the yield of the
reaction (Table 1, entries 13). The use of Cu(OAc)2 (10 mol%)
gave the best result with excellent yield. The reaction has also
been carried out by using other copper salts (10 mol% each) such
as CuCl2, CuI, CuBr2, Cu(OTf)2, Cu2O, CuO nano etc. (Table 2)
but they were not so efficient as Cu(OAc)2. Increasing the
amount of Cu(OAc)2 from 10 to 20 mol% resulted no significant
change in the formation of product (Table 2, entry 8). On
decreasing the amount from 10 mol% to 5 mol% there was
notable decrease in product formation (Table 2, entry 9). The
reaction did not proceed at all without any catalyst (Table 2,
entry 10). In addition, Zn dust also made a vital contribution for
the reaction to proceed (Table 3, entry 1,). There is no reaction
without zinc dust (Table 3, entry 2) and use of indium powder
instead of Zn dust did not afford any product (Table 3, entry 3).
Use of other allylic bromides like crotyl bromide or cinnamyl
bromide gave no response as a source of bromine (Table 4, entry
2, entry 3). Accordingly, our final optimized reaction condition
was achieved using N-tosylaziridine (1 mmol) with allylic
bromide (3 mmol) in the presence of 10 mol% copper acetate, Zn
dust (1 mmol) and THF solvent at 60 °C temperature to give the
corresponding halogenated product under ambient air.
e Reaction was carried out at 80 °C.
f Reaction was carried out at 50 °C.
Table 2. Effects of various copper catalysts.a
Entry
Catalyst (mol%)
Cu(OAc)2 (10)
CuCl2 (10)
Yieldsb (%)
1
84
67
56
69
48
40
62
84
65
0
2
3
CuI (10)
4
CuBr2 (10)
Cu(OTf)2 (10)
Cu2O (10)
5
6
7
CuO nano (10)
Cu(OAc)2 (20)
Cu(OAc)2 (5)
-
8
9
10
a Reaction conditions: A mixture of 1a (1 mmol) and 2a (3 mmol) was heated
in THF (2 mL) at 60 °C for 6 h in presence of different copper catalysts and 1
mmol of Zn dust.
b Isolated yields.
Table 3. Effects of other metal on the halogenation reaction.a
Entry
Metal
Yieldsb (%)
1
2
3
Zn dust
-
84
0
Indium dust
Trace
Table 1 Screening of the solvent effects.a
a Reaction conditions: A mixture of 1a (1 mmol) and 2a (3 mmol) was heated
in THF (2 mL) at 60 °C for 6 h in presence of 10 mol% Cu(OAc)2 and 1
mmol of different additives.
b Isolated yields.
Table 4 Effects of different allylic bromides on the
halogenation reaction.a
Entry
Solvents (2 mL)
THF
Yieldsb (%)
1
2
3
4
5
6
84
DMSO
32
DMF
Trace
29
Yieldsb (%)
CH3CN
1,2-DCE
Toluene
Entry
R
51
1
2
H
84
35
CH3
NR

3
3
Ph
NR
conditions and reacted smoothly with allylic bromide to afford
the brominated amines (3f and 3g). Next, we turned our attention
using another allylic halide namely allylic chloride with various
substituted aziridine systems. N-tosylaziridine substituted with
various functionalities (such as –Cl, -Br) at the benzene ring
underwent smooth reaction (4a-4d). Aliphatic aziridine also
reacted smoothly with allylic chloride to give the desired
chlorinated amine (4e) with good yield. We have successfully
used allylic iodide to synthesize the corresponding compounds
(5a-5f) which increases the scope of this transformation. Both
aryl N-tosylaziridine (1a) and chloro- and bromo-substituted aryl
N-tosylaziridine reacted smoothly with good yields (5b-5d).
Aliphatic aziridine system also gave the desired product (5e).
However, N-tosylaziridine with electron-donating group like
methyl (1h) did not react with all three allylic halides under the
optimized reaction conditions. Again, N-tosylziridines from cis-
stilbene (1i) and another enantiomerically pure (s)-2-benzyl-1-
tosylaziridine (1j) are also inert under the present reaction
conditions.
a Reaction conditions: A mixture of 1a (1 mmol) and 2 (3 mmol) was heated
in THF (2 mL) at 60 °C for 6 h in presence of 10 mol% Cu(OAc)2 and 1
mmol of Zn dust.
b Isolated yields.
NR = No reaction.
After optimizing the reaction conditions, we explored the
scope of this reaction (Table 5). At first, our attention was
focused on the use of different aziridine systems with various
allylic halides to prove the general applicability of the reaction
conditions and the results are summarized in Table 5. It was
observed that allylic bromide, allylic chloride and allylic iodide
reacted efficiently with various aziridines to afford the desired
products with good yields under the present reaction conditions.
Simple phenyl N-tosylaziridine (1a) reacted well with allylic
bromide to give the desired product with good yield (3a).
Similarly, aryl N-tosylaziridine substituted with chloro- in the
benzene ring was found quite effective to afford the desired
products (3b and 3c) with excellent yield. Aziridines, substituted
by other halogens (such as –Br, -F) underwent smooth reactions
with allylic bromide which highlighted the general applicability
of this reaction (3d and 3e). In addition, the aliphatic aziridine
systems were also investigated under the present reaction
The present protocol has also been examined for epoxides and
it is worthy to mention that styrene epoxide (1k) reacted
smoothly with these three allylic halides (Table 6); yielding the
corresponding products 6a, 6b and 6c in 77%, 69% and 80%
yields, respectively.
Table 5 Scopes and limitations of the present protocol.a
Entry
Aziridines (1)
Allylic halides (2)
Products
Yieldsb (%)
84
1
2a
2a
2a
2a
86
79
82
80
2
3
4
5
6
7
2a
2a
73
70

4
Tetrahedron Letters
8
2a
NR
NR
9
2a
2a
10
NR
79
11
12
2b
2b
80
75
13
14
2b
77
2b
2b
71
15
16
NR
17
18
2b
2b
NR
NR
86
19

5
20
21
2c
2c
87
82
84
22
2c
23
24
2c
2c
76
NR
25
26
2c
2c
NR
NR
a Reaction conditions: A mixture of aziridine (1, 1 mmol) and allylic halide (2, 3 mmol) was heated in THF (2 mL) at 60 °C for 6 h in presence of 10 mol%
Cu(OAc)2 and 1 mmol of Zn dust.
b Isolated yields.
Table 6 Scope of the epoxide in the reaction with allylic halides.a
Entry
Epoxide
Allylic Halides
Products
Yieldsb (%)
77
1
2
3
1k
69
80
1k
a Reaction conditions: A mixture of epoxide (1k, 1 mmol) and allylic halide (2, 3 mmol) was heated in THF (2 mL) at 60 °C for 6 h in presence of 10 mol%
Cu(OAc)2 and 1 mmol of Zn dust.
b Isolated yields.

6
Tetrahedron Letters
All of the known synthesized compounds have been
allylation products (7a-7e) with excellent yields. Next we have
also examined few acetophenone derivatives which underwent
allylation reaction in very good yields (7f-7h).
characterized by spectral data and the new compounds by
spectral and analytical data. X-ray crystallographic analysis of
N-(2-chlorocyclohexyl)-4-methylbenzenesulfonamide (4e) was
performed to confirm the structure of the product as shown in
Figure 1 [15]. The reaction conditions were mild enough and
gave no decomposition of the products or polymerization of the
starting materials. We have not observed any by-products for all
the reaction combinations giving rise to high yields of desire
products and regioselectivity of the protocol. In all the cases the
halide part has been introduced as a nucleophile.
Before coming to any conclusion based on the above
observation, we thought to explore the same reaction conditions
using the carbonyl compounds where the halide addition in the
carbonyl functionality is not usual. To our delight we observed
the expected result and got the homoallyllic alcohol as the sole
product (Table 7). First, we have tested various aryl aldehydes
substituted with various functionalities. Both electron-donating
as well as electron-withdrawing substituents afforded the desired
Figure 1. X-ray crystal structure of N-(2-chlorocyclohexyl)-4-
methylbenzenesulfonamide (4e).
Table 7. Reaction of aldehydes and ketones with allylic bromide.a
Entry
1
Carbonyls
Allylic halide
Product
Time (h)
2
Yieldsb (%)
88
2
3
2a
2a
2
2
85
86
4
5
6
7
2a
2a
2a
2a
2
82
85
86
83
2
12
12

7
8
2a
12
84
a Reaction conditions: A mixture of aldehyde or ketone (1 mmol) and 2a (3 mmol) was heated in THF (2 mL) at 60 °C in presence of 10 mol% Cu(OAc)2 and 1
mmol of Zn dust.
b Isolated yield
It is worthy to mention that we have optimized the reaction
time (Table 1) using only allyl bromide and within 6 h the
reaction completed. We have found the same reaction time for
allyl chloride as well as iodide also. So, from this observation we
may conclude that under the reaction conditions zinc allylic
halide possesses ambident nucleophilic character where both the
allylic and halide are active nucleophile which is not observed
usually. The addition of the zinc allylic halide with these two-
different species may be explained from a literature survey [6].
The zinc allylic halide is formed under the experimental
conditions and the Cu(OAC)2 acts as the catalysis to activate the
carbonyl group as well as aziridine ring. In case of carbonyl
compound two competitive nucleophiles may add but as the
addition of halide is not thermodynamically favorable due to the
elimination of hydrogen halide from the gem halohydrin, the
resulting product is the homoallylic alcohol; whereas, in case of
aziridines, the halide ion is better nucleophile. Thus, the halide
ion readily attacks the available electrophilic carbon in the
aziridine as the zinc allylic species is relatively bound and
produce the corresponding nucleophilic ring-opening product of
aziridine [16] in presence of Lewis acid. Thus, the probable
mechanism of this observation is described in Scheme 3.
Scheme 3. Proposed reaction mechanism.
(b) J.L. Luche, J.C. Damiano, J. Am. Chem. Soc. 102 (1980)
7926–7927.
4. C. Blomberg, F. A. Hartog, Synthesis (1977) 18-30.
5. (a) T. Hiyama, M. Obayashi, A. Nakamura, Organometallics 1
(1982) 1249–1251;
(b) T. Hiyama, M. Sawahata, Y. Kusano. Chem. Lett. (1985) 611-
612.
6. (a) T. Hiyama, M. Sawahata, M. Obayashi, Chem. Lett. (1983)
1237–1238;
From the above observation we can conclude that the zinc
allylic halide under identical reaction conditions may produce
two effective nucleophiles which are very reactive and act in
differential mode for different electrophiles. Usually, under these
reaction conditions always the acting nucleophile is the allylic
part as reported in the literature even in case of aziridines. To the
best of our knowledge this is the first report where zinc allylic
halide is the source of halide. The reaction procedure is very easy
to handle there is no need of inert atmosphere, the condition is
mild, and applicable for a wide variety of substrates for aziridines
and carbonyl compounds. Thus, we hope that this observation
will be very useful for synthetic organic communities.
(b) G.P. Boldrini, D. Savoia, E. Tagliavini, C. Trombini, A.
Umani-Ronchi, J. Org. Chem. 48 (1983) 4108–4111;
(c) C, Perier, J.L. Luche, J. Org. Chem. 50 (1982) 910;
(d) C. Petrier, J. Einhorn, J.L. Luche, Tetrahedron Lett. 26 (1985)
1445–1448.
7. (a) T. Mukaiyama, T. Warada, S. Shoda, Chem. Lett. (1980) 1207;
(b) J. Nokami, J. Otera, T. Sudo, R. Okawara, Organometallics 2
(1983) 191–193.
Acknowledgments
8. H. Tanaka, S. Yamashita, T. Hamatani, Y. Ikemoto, S. Torii,
Chem. Lett. (1986) 1611.
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4212;
A. Majee acknowledges financial support from the DST-RSF
Major Research Project (Ref. No. INT/RUS/RSF/P-08). S. Santra
and G. V. Zyryanov acknowledge the Russian Science
Foundation – Russia (Ref. # 18-73-00301) for funding. We are
thankful to the DST-FIST and UGC-SAP programmes.
(b) M. Wada, H. Ohki, K.-y. Akiba, Tetrahedron Lett. 27 (1986)
4771-4774;
(c) M. Wada, H. Ohki, K.-y. Akiba, J. Chem. Soc., Chem.
Commun. (1987) 708.
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1959–1982;
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Soc. 99 (1977) 3179–3181;
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Trans. 1 (1971) 1655;

8
Tetrahedron
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3707-3708.
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V. Zyryanov, A. Majee, Synth. Commun. 48 (2018) 1857–1866;
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137–151.

9
Highlights


The allylic zinc halide acts in different modes
for different electrophiles.
Zinc alyllic halide is the source of halide in
aziriding ring-opening.


A probable reaction mechanism was proposed.
This approach bears broad substrate scopes for
aziridines and carbonyls.