Lewis basic selenium catalyzed chloroamidation of olefins using nitriles as the nucleophiles

Article abstract of DOI:10.1021/ol400249x

A Lewis base catalyzed chloroamidation of olefinic substrates was achieved using diphenyl selenide as the catalyst. The reaction conditions are mild and suitable for a wide range of substrates including those which are acid labile.

Full text of DOI:10.1021/ol400249x

ORGANIC
LETTERS
2013
Vol. 15, No. 6
1310–1313
Lewis Basic Selenium Catalyzed
Chloroamidation of Olefins Using Nitriles
as the Nucleophiles
Daniel Weiliang Tay,†,‡ Ivan Tan Tsoi,†,‡ Jun Cheng Er,† Gulice Yiu Chung Leung,*,‡
and Ying-Yeung Yeung*,†
Department of Chemistry, National University of Singapore, 3 Science Drive 3,
Singapore 117543, and A*STARÀInstitute of Chemical & Engineering Sciences,
11 Biopolis Way, Helios, #03-08, Singapore 138667
chmyyy@nus.edu.sg; leung_yiu_chung@ices.a-star.edu.sg
Received January 28, 2013
ABSTRACT
A Lewis base catalyzed chloroamidation of olefinic substrates was achieved using diphenyl selenide as the catalyst. The reaction conditions are
mild and suitable for a wide range of substrates including those which are acid labile.
Haloamidation of an olefin is a useful transformation
that produces a vicinal haloamide system, which provides
a reactive halogen handle for subsequent manipulation.1
In the literature, there are several methods for installing a
trans-1,2-haloamide/amine functionality directly from an
olefin.2 A common approach involves the use of a nitrogen
nucleophile to open a haliranium ion intermediate derived
from an olefin. To achieve the desired products with reason-
able reaction efficiency, Lewis acids are usually employed
to activate the stoichiometric halogen source in the olefin
halogenation process. For example, the use of strongly Lewis
acidic catalysts, such as SnCl4 and BF3•OEt2, in the bromo-
amidation of olefins using N-bromosuccinimide (NBS) as the
halogen source and acetonitrile as the nitrogen source has
been reported.3 Later, the Chandrakanth group reported
a similar procedure using InBr3 as the catalyst in the halo-
amidation of vinyl arene substrates.4 Herein, we disclose a
facile, mild, and efficient chloroamidation of olefins using
commercially available Lewis basic diphenyl selenide as
the catalyst with N-chlorosuccinimide (NCS) and aceto-
nitrile as the halogen and nitrogen source, respectively.
This method was found to be applicable to a wide range
† National University of Singapore.
‡ A*STARÀInstitute of Chemical & Engineering Science.
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r
10.1021/ol400249x
Published on Web 03/05/2013
2013 American Chemical Society

of substrates, which makes it suitable for acid-sensitive
compounds.
Triphenylphosphine oxide was found to be inactive in
catalyzing the haloamidation reaction. For the catalysts
3bÀh which contain a CdX or a PdX (X = S, Se) system,
very low reaction efficiency was observed. In fact, these
catalysts were unstable in the reaction system; elemental
sulfur (or selenium) evolved gradually during the reaction,
which could be attributed to the hydrolytic decomposi-
tion of the catalysts in the presence of water and a halogen
source.10 This result prompted further screening of the
diaryl sulfur and selenium catalysts,5c,9j which led to the
discovery that diphenyl selenide (3j) was exceptionally
active in catalyzing this type of reaction.
Recently, we have reported the use of Lewis basic sulfur
for the activation of halogenating reagents in various bro-
mocyclization processes.5À9 We rationalized that a similar
Lewis basic system can be used to catalyze the haloamida-
tion process, which can offer mild reaction conditions.
Thus, cyclohexene was used in our initial study, and
various Lewis basic chalcogen-containing catalysts 3 were
examined (Figure 1).
After identifying a suitable catalyst, other parameters
were optimized. The amount of water did not significantly
affect the reaction, and the yield was unchanged upon the
addition of up to 10 equiv of water (Table 1, entries 1À3).
In addition, no halohydrins were observed to form despite
the drastic increase in the amount of water. On the other
hand, the concentration did appreciably affect the reaction
yield, and the optimum concentration was found to be
0.4 M (Table 1, entries 4À6).
Table 1. Effect of Water and Concentration on the
Haloamidationa
entry
H2O (equiv)
concn (M)
yield (%)b
Figure 1. Haloamidation using different Lewis base catalysts.
Reactions were carried out with cyclohexene (1a) (0.25 mmol),
catalyst 3 (0.05 mmol), NBS (0.25 mmol), and water (0.30 mmol)
in MeCN (2.5 mL) at 25 °C. The yields indicated in the
parentheses were the isolated yields of 2a.
1
2
3
4
5
6
1.2
3.0
10
0.1
23
23
24
30
35
36
0.1
0.1
1.2
1.2
1.2
0.65
0.50
0.40
a Reactions were carried out with cyclohexene (1a) (0.25 mmol), NBS
(0.25 mmol), 3j (0.05 mmol), and water at 25 °C. b Yields were calculated
based on the 1H NMR analysis of the crude reaction mixture using
hexamethylbenezene as the internal standard.
(6) For studies using Lewis basic selenium as the catalyst in halolac-
tonization, see: (a) Mellegaard, S. R; Tunge, J. A. J. Org. Chem. 2004,
69, 8979–8981. (b) Balkrishna, S. J.; Prasad, C. D.; Panini, P.; Detty,
M. R.; Chopra, D.; Kumar, S. J. Org. Chem. 2012, 77, 9541–9542. For a
related work involving the use of Lewis basic selenophosphoramide in
the catalytic enantioselective thiofunctionalization process, see: (c) Den-
mark, S. E.; Kornfilt, D. J. P.; Vogler, T. J. Am. Chem. Soc. 2011, 133,
15308–15311.
(7) For related studies on the Lewis basic sulfur-activated halogenat-
ing agent, see: (a) Snyder, A. S.; Treitler, D. S.; Brucks, A. P. J. Am.
Chem. Soc. 2010, 132, 14303–14314. (b) Snyder, A. S.; Treitler, D. S.;
Brucks, A. P.; Sattler, W. J. Am. Chem. Soc. 2011, 133, 15898–15901.
(8) For related studies on the interaction between Lewis basic sulfur
(and selenium) and halogen, see: (a) Chu, Q.; Wang, Z.; Huang, Q.; Yan,
Various halogenating sources were also investigated. It
was found that brominating reagents including N-bromo-
phthalimide (NBP), N-bromoacetamide (NBA), 2,4,4,6-
tetrabromo-2,5-hexadienone (TABCO), and 1,3-dibromo-
5,5-dimethylhydantoin (DBH) gave similar yields to that
of NBS (Table 2, entries 1À5). Interestingly, a 52% yield of
the chlorinated product was obtained when NCS was used
(Table 2, entry 7), but N-iodosuccinimide (NIS) did not
result in any desired product (Table 2, entry 8). It was
found that the yields could be further enhanced by increas-
ing the amount of halogenating reagents (Table 2, entries
9À10). The reaction was also found to be readily scalable.
Upon identifying a suitable reaction system, we contin-
ued to explore the substrate scope; the results are tabulated
€ꢀ ꢁ
ꢀꢀ ꢁ
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Jiang, X.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2010, 132, 15474–
15476. (b) Tan, C. K.; Zhou, L.; Yeung, Y.-Y. Org. Lett. 2011, 13, 2738–
2741. (c) Zhou, L.; Chen, J.; Tan, C. K.; Yeung, Y.-Y. J. Am. Chem. Soc.
2011, 133, 9164–9167. (d) Chen, J.; Zhou, L.; Tan, C. K.; Yeung, Y.-Y.
J. Org. Chem. 2012, 77, 999–1009. (e) Chen, J.; Zhou, L.; Yeung, Y.-Y.
Org. Biomol. Chem. 2012, 10, 3808–3811. (f) Tan, C. K.; Le, C.; Yeung,
Y.-Y. Chem. Commun. 2012, 48, 5793–5795. (g) Jiang, X.; Tan, C. K.;
Zhou, L.; Yeung, Y.-Y. Angew. Chem., Int. Ed. 2012, 51, 7771–7775. (h)
Cheng, Y. A.; Chen, T.; Tan, C. K.; Heng, J. J.; Yeung, Y.-Y. J. Am.
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4892–4895.
Org. Lett., Vol. 15, No. 6, 2013
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Table 2. Effect of Halogen Source on Reaction Yielda
Table 3. Haloamidation of Olefins
entry
halogen source (equiv)
product
yield (%)b
1
NBS (1)
NBP (1)
NBA (1)
TABCO (1)
DBH (1)
DCH (1)
NCS (1)
NIS (1)
2a
2a
2a
2a
2a
4a
4a
5a
2a
4a
36
35
30
31
31
34
52
0
2
3
4
5
6
7
8
9
NBS (2)
NCS (2)
56
85
10c,d
a Reactions were carried out with cyclohexene (1a) (0.25 mmol), 3j
(0.05 mmol) in MeCN (0.65 mL) at 25 °C. b Yields were calculated based
on the 1H NMR analysis of the crude reaction mixture using hexam-
ethylbenezene as the internal standard. c Reactions conducted on 0.25, 1,
and 3 mmol scale, and the same yields were obtained. d Ca. 10% of desired
product was observed when strictly anhydrous conditions were applied.
in Table 3. The haloamidation was found to proceed
efficiently with both alkyl olefins and vinyl arenes giving
good yields. For the substituted cyclohexenes 1bÀ1e,
excellent diastereo- and regioselectivity were observed
(Table 3, entries 1À4). The high diastereoselectivity could
be explained by the stereoelectronic effect of the chairlike
transition state that is depicted in Scheme 1. Markovnikov-
type products were obtained for aryl olefins 1fÀ1h (Table 3,
entries 5À7).11 However, anti-Markovnikov product 4i was
achieved (86% yield) when using 1i as the substrate (Table 3,
entry 8). The selectivity can be rationalized by the stabiliza-
tion effect of the carbocation at the terminal carbon by the
SiÀC σ-bond.12
a Reactions were carried out with olefin 1 (0.25 mmol), NCS
(0.50 mmol), and 3j (0.05 mmol) in MeCN (0.65 mL) at 25 °C for 18 h.
b Isolated yield.
Scheme 1. Possible Transition State of the Chloroamidation
precursors (Table 4, entries 4 and 6) and the complex
mixture obtained (Table 4, entry 5) when the respective
Lewis acids were employed as catalysts.
To further illustrate the scope of the reaction, we pro-
ceeded to examine a variety of nitriles. As shown in Table 5,
both propio- and benzonitrile produced good yields of the
corresponding products 7 and 8, respectively.
Besides the wide substrate scope, it is also important to
note that the reaction can accommodate acid sensitive
functional groups. Thus, this Lewis base catalyzed halo-
amidation can be considered as a complementary method
to the corresponding Lewis acid protocols.3,4
During our mechanistic investigation, we initially sus-
pected that the active catalytic species might have been
diphenyl selenium oxide (9), which can be synthesized by
treating diphenyl selenide (3j) with NCS and MeOH/
H2O.13 We also observed that some diphenyl selenium
Some examples are shown in Table 4. Substrates 1jÀ1l
gave the desired products smoothly using catalyst 3j (Table 4,
entries 1À3); this was in comparison to the deprotected
(11) p-Methoxystyrene was also examined, but only ca. 5% product
was obtained.
(12) (a) Brook, M. A.; Hadi, M. A.; Neuy, A. J. Chem. Soc., Chem.
Commun. 1989, 957–958. (b) Zhang, W.; Stone, J. A.; Brook, M. A.;
McGibbon, G. A. J. Am. Chem. Soc. 1996, 118, 5764–5771.
(13) (a) Detty, M. R.; Friedman, A. E.; Oseroff, A. R. J. Org. Chem.
1994, 59, 8245–8250. (b) Detty, M. R. J. Org. Chem. 1980, 45, 274–279.
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Org. Lett., Vol. 15, No. 6, 2013

Table 4. Chloroamidation of Acid Labile Substratesa
Scheme 2. Examination of 9 as the Catalyst in the Chloroami-
dation of 1a
selenium oxide (9) instead of 3j as the catalyst, the reaction
was very sluggish (Scheme 2).
A plausible mechanism for the reaction is described in
Scheme 3.3,5,9j The first step is likely to involve the activa-
tion of the chlorine atom on NCS via the Lewis basic
diphenyl selenide to form intermediate A. The electrophilic
Cl might then be delivered to olefin 1 to form the halir-
anium intermediate B. At this point, acetonitrile could
attack intermediate B (i.e., BfC) which would subse-
quently be quenched by a molecule of water to form the
haloamide product 4.
Scheme 3. Proposed Mechanism of the Lewis Basic Selenium
Catalyzed Chloroamidation
a Reactions were carried out with olefin 1 (0.25 mmol), NCS (0.50
mmol), and 3j (0.05 mmol) in MeCN (0.65 mL) at 25 °C for 18 h.
b Isolated yield. c The reaction time was 3 days.
Table 5. Chloroamidation of 1a with Different Nitrile Partnersa
In summary, we have developed a highly efficient Lewis
base catalyzed chloroamidation which can be applied to a
wide range of substrates including those that are acid
labile. Further application of this methodology to other
areas is currently being investigated.
Acknowledgment. We thank the financial support from
Agency for Science, Technology and Research (A*STAR)
(Grant No. 143-000-536-305). D.T. would like to thank
A*STAR for sponsoring his PhD scholarship.
a Reactions were carried out with cyclohexene (1a) (0.25 mmol) and
3j (0.05 mmol) in RCN (0.65 mL) at 25 °C. b Isolated yield.
Supporting Information Available. Experimental pro-
cedures and additional information. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
oxide (9) was generated during the chloroamidation reac-
1
tion, which was elucidated by H NMR experiments of
the crude sample. Nonetheless, when we used diphenyl
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 6, 2013
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