Nucleophilic ring opening of mono-activated cyclopropanes with arylselenolates generated from diselenides in the presence of a Zn/AlCl 3 system

Article abstract of DOI:10.1055/s-0029-1217372

An efficient one-pot synthesis of γ-arylselenenyl ketones, acids, and nitriles is presented. The method uses Zn/AlCl₃-promoted cleavage of diselenides and subsequent ring-opening of mono-activated cyclopropanes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217372

LETTER
1803
Nucleophilic Ring Opening of Mono-Activated Cyclopropanes with Aryl-
selenolates Generated from Diselenides in the Presence of a Zn/AlCl3 System
R
ing Opening of Mono
o
-Activated
C
h
yclopropane
a
s
mmad Nazari, Barahman Movassagh*
Department of Chemistry, K. N. Toosi University of Technology, P. O. Box 16315-1618, Tehran, Iran
Fax +98(21)22853650; E-mail: bmovass1178@yahoo.com
Received 9 February 2009
ing to the malodorous nature of certain compounds such
Abstract: An efficient one-pot synthesis of g-arylselenenyl ke-
tones, acids, and nitriles is presented. The method uses Zn/AlCl3-
promoted cleavage of diselenides and subsequent ring-opening of
mono-activated cyclopropanes.
as benzeneselenol,4e,g,h the need for toxic solvents such as
HMPA,4e,h the use of alkali metals or very strong bases
such as sodium hydride,4e,g,h which are incompatible with
substrates having base-sensitive substituents, and the lack
of required reactivity of some of these salts.4a
Key words: mono-activated cyclopropanes, ring opening, disele-
nides, zinc selenolates, zinc
As part of our ongoing work on the application of zinc se-
lenolates in chemical reactions,11 we describe herein the
use of the Zn/AlCl3 system for the reductive cleavage of
diaryl diselenides followed by nucleophilic ring-opening
of a cyclopropyl ring, mono-activated with either ketone,
aldehyde, acid, or nitrile functionalities (Scheme 1). We
found that zinc selenolate (2a), generated from reductive
cleavage of diphenyl diselenide in the presence of Zn/
AlCl3, reacts smoothly with cyclopropyl methyl ketone
(3a) to give the corresponding g-phenylselenenyl ketone
(4a) in very good yield. After optimization of the reaction
conditions (solvent, temperature and molar ratios), and in
order to probe the generality of our methodology further,
we ran the reaction with different mono-activated cyclo-
propanes and various arylselenolates, generating the cor-
responding ring-opened products.12 The choice of zinc
selenolate as the ring-opening reagent is particularly
attractive for two reasons. Firstly, it is a highly potent
nucleophile which is able to react with mono-activated cy-
clopropanes bearing sensitive functionalities under mild
reaction conditions. Secondly, the arylselenenyl function-
alized chain products can be easily manipulated and/or the
arylselenenyl group can be removed under mild reaction
conditions.
Organoselenium compounds have found wide utility due
to their effects on numerous reactions, often affording
stereo- and regioselectivity and excellent yields under
relatively mild reaction conditions.1 Organoselenium
compounds are also promising pharmacological agents in
view of their antioxidant, antitumor, antimicrobial, and
antiviral properties.2
Among the methods for the introduction of a selenium
moiety into organic molecules, the use of selenide anions
(selenolates) is especially convenient and common. Al-
though, selenolates are weak bases, they are nevertheless
powerful, soft nucleophiles3 because of the high polariz-
ability of the selenium atom. In general, methods for the
preparation of selenide anions include reductive cleavage
of the Se–Se bond by various agents such as sodium boro-
hydride,4a sodium,4b samarium diiodide,4c lithium alumi-
num hydride,4d reaction of Grignard reagents with
selenium,4e and reaction of selenols with sodium hydride
or even with aqueous sodium hydroxide under certain
conditions.4f
The nucleophilic cleavage of electron-deficient cyclopro-
pane derivatives has been widely applied in organic syn-
thesis and is known as the homologous (or 1,5) version of
the classical Michael addition,5 which has found many ap-
plications in the total synthesis of natural products.5,6 Un-
like doubly-activated cyclopropanes, the corresponding
reaction of mono-activated analogues is limited to highly
strained bicyclic systems.7,8
The results of this study are illustrated in Table 1. Simply
stirring diselenides 1 with zinc dust in the presence of
anhydrous aluminum chloride in acetonitrile under an air
atmosphere at 70 °C generated the zinc selenolate 2. This
was followed by addition of mono-activated cyclopro-
panes 3, which gave the desired products 4, after work-up,
with yields ranging from 48–90% (Table 1). Different di-
aryl diselenides react with a variety of cyclopropane de-
rivatives, mono-activated by ketone, aldehyde, acid, ester,
and nitrile functionalities. The reaction of the diselenides
with cyclopropyl methyl ketone (entries 1, 6, and 9) took
place faster and gave higher yields than the others, while
cyclopropanecarbonitrile (entries 3 and 8) required longer
reaction times and gave lower yields. Because of the dom-
inant nucleophilic acyl-oxygen cleavage reaction of zinc
selenolates with esters,9 the reaction with cyclopropanes
To the best of our knowledge, there are only two reports
describing procedures for generating either sodium or
lithium phenylselenolate as the nucleophilic reagent for
ring opening of mono-activated cyclopropanes.9,10 How-
ever, these methods generally result in poor yields of
products. Furthermore, the clean and efficient generation
of selenolates continues to cause practical problems ow-
SYNLETT 2009, No. 11, pp 1803–1805
x
x
.x
x
.2
0
0
9
Advanced online publication: 12.06.2009
DOI: 10.1055/s-0029-1217372; Art ID: D04609ST
© Georg Thieme Verlag Stuttgart · New York

1804
M. Nazari, B. Movassagh
LETTER
X
Zn/AlCl3
3
(ArSe)2Zn
ArSe SeAr
ArSe
X
MeCN, 70 °C, 1 h
70 °C, 5–18 h
1
2
4
1a Ar = Ph
1b Ar = 4-ClC6H4
1c Ar = α-Naphthyl
3a X = COMe
3b X = COOH
3c X = CN
3d X = COOPh
3e X = CHO
Scheme 1
Table 1 Reaction of Mono-Activated Cyclopropanes with Diaryl Diselenides in the Presence of Zn/AlCl3
Entry
Diselenide 1
Cyclopropyl 3
Product 4
Time (h)
Yield (%)a
1
2
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
3a
3b
3c
3d
3e
3a
3b
3c
3a
3b
4a9
4b4e
4c9
4d9
4e
5
16
18
18
8
87
73
48
–
PhSe
PhSe
COMe
COOH
CN
3
PhSe
4
PhSe
COOPh
CHO
5
67
90
75
55
84
70
PhSe
6
4f
6
4-ClC6H4Se
4-ClC6H4Se
4-ClC6H4Se
α-NaphthylSe
α-NaphthylSe
COMe
7
4g
16
17
6
COOH
CN
8
4h
4i
9
COMe
COOH
10
4j
17
a Isolated yield.
(2) (a) Mugesh, G.; du Mont, W. W.; Sies, H. Chem. Rev. 2001,
101, 2125. (b) Malmstrom, J.; Jonsson, M.; Cotgreave, I. A.;
Hammarstrom, L.; Sjodin, M.; Engman, L. J. Am. Chem.
Soc. 2001, 123, 3434. (c) Back, T. G.; Moussa, Z. J. Am.
Chem. Soc. 2003, 125, 13455. (d) Lucas, M. A.; Nagugen,
O. T. K.; Schiesser, C. H.; Zheng, S. L. Tetrahedron 2000,
56, 3995.
(3) Monahan, R.; Brown, D.; Waykole, L.; Liotta, D. In
Organoselenium Chemistry; Liotta, D., Ed.; Wiley: New
York, 1987.
(4) (a) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95,
2697. (b) Aynsley, E. E.; Greenwood, N. N.; Leach, J. B.
Chem. Ind. (London) 1966, 379. (c) Zhang, Y.; Yu, Y.; Lin,
R. Synth. Commun. 1993, 23, 189. (d) Suzuki, H.;
Yoshinaga, M.; Takaoka, K.; Hiroi, Y. Synthesis 1985, 497.
(e) Liotta, D.; Sunay, U.; Santiesteban, H.; Markiewicz, W.
J. Org. Chem. 1981, 46, 2605. (f) Taboury, F. Bull. Soc.
Chem. Fr. 1903, 29, 761. (g) Liotta, D.; Markiewicz, W.;
Santiesteban, H. Tetrahedron Lett. 1977, 4365. (h) Liotta,
D.; Santiesteban, H. Tetrahedron Lett. 1977, 4369.
(5) (a) Danishefsky, S. Acc. Chem. Res. 1979, 12, 66.
(b) Danishefsky, S.; Mckee, R.; Singh, R. K. J. Am. Chem.
Soc. 1977, 99, 4783.
activated by an ester moiety (entry 4) was unsuccessful; in
this case we obtained phenol in nearly quantitative yield.
In conclusion, the present method introduces a simple Zn/
AlCl3-promoted one-pot procedure for ring opening of
different mono-activated cyclopropanes under neutral,
and relatively mild reaction conditions, without the need
for using an inert atmosphere. The method generates syn-
thetically useful g-arylselenenyl ketones, acids, nitriles
and aldehydes in moderate to excellent yields. This ap-
proach offers significant advantages over previously re-
ported procedures with regards to operation and yields,
and thus presents an efficient alternative to the existing
methods.9,10
Acknowledgment
The authors are grateful to the K. N. Toosi University of Technolo-
gy Research Council and Iranian National Science Foundation
(INSF) for financial support of this work.
(6) (a) Wrobel, T.; Takahashi, K.; Honkan, V.; Lannoye, G.;
Cook, T. M.; Bertz, S. H. J. Org. Chem. 1983, 48, 139.
(b) Zutterman, E.; De Wilde, H.; Mijngheer, R.; De Clercq,
P.; Vandewalle, H. Tetrahedron 1979, 35, 2389.
(7) (a) Taber, D. F. J. Am. Chem. Soc. 1977, 99, 3513.
(b) Caputo, R.; Ferreri, C.; Palumbo, G. Tetrahedron Lett.
References and Notes
(1) (a) Liotta, D. Organoselenium Chemistry; Wiley: New
York, 1987. (b) Back, T. G. Organoselenium Chemistry: A
Practical Approach; Oxford University Press: Oxford U. K.,
1999.
Synlett 2009, No. 11, 1803–1805 © Thieme Stuttgart · New York

LETTER
1984, 25, 577. (c) Kondo, K.; Umemoto, T.; Takahatake, Y.;
Tunemoto, D. Tetrahedron Lett. 1977, 23, 113.
(8) Meinwald, J.; Crandall, K. J. Am. Chem. Soc. 1966, 88,
1292.
(9) Smith, A. B.; Scarborough, R. M. Jr. Tetrahedron Lett. 1978,
1649.
(10) Scarborough, R. M. Jr.; Toder, B. H.; Smith, A. B. III. J. Am.
Chem. Soc. 1980, 102, 3904.
(11) (a) Nazari, M.; Movassagh, B. Tetrahedron Lett. 2009, 50,
1453. (b) Nazari, M.; Movassagh, B. Tetrahedron Lett.
2009, 50, 438. (c) Movassagh, B.; Tatar, A. Synlett 2007,
1954. (d) Movassagh, B.; Mirshojaei, F. Monatsh. Chem.
2003, 134, 831. (e) Movassagh, B.; Shamsipoor, M. Synlett
2005, 1316. (f) Movassagh, B.; Fazeli, A. Z. Naturforsch., B
2006, 61, 194. (g) Movassagh, B.; Shamsipoor, M.;
Joshaghani, M. J. Chem. Res., Synop. 2004, 148.
(h) Movassagh, B.; Shamsipoor, M. Synlett 2005, 127.
(i) Movassagh, B.; Fazeli, A. Monatsh. Chem. 2007, 138,
863.
Ring Opening of Mono-Activated Cyclopropanes
1805
52.95; H, 5.35. Compound 4f: IR (neat): 1714 cm–1. 1H
NMR (500 MHz, CDCl3): d = 1.96 (quin, J = 7.1 Hz, 2 H),
2.13 (s, 3 H), 2.59 (t, J = 7.0 Hz, 2 H), 2.91 (t, J = 7.2 Hz,
2 H), 7.24 (d, J = 8.5 Hz, 2 H), 7.43 (d, J = 8.5 Hz, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): d = 23.9, 27.5, 30.0,
42.9, 128.2, 129.2, 133.1, 134.0, 207.7 ppm. LRMS: m/z
(%) = 278 (7) [M + 4]+, 276 (15) [M + 2]+, 274 (7) [M]+, 191
(4), 156 (3), 125 (3), 85 (100), 43 (86). Anal. Calcd for
C11H13ClOSe: C, 47.93; H, 4.75. Found: C, 47.83; H, 4.39.
Compound 4g: mp 100–101 °C. IR (KBr disk): 1709, 2450–
3500 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.99 (quin,
J = 7.2 Hz, 2 H), 2.51 (t, J = 7.2 Hz, 2 H), 2.94 (t, J = 7.3 Hz,
2 H), 7.24 (d, J = 8.5 Hz, 2 H), 7.43 (d, J = 8.5 Hz, 2 H),
11.50 (br s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): d = 24.8,
27.1, 33.5, 127.7, 129.3, 133.3, 134.2, 179.3 ppm. LRMS:
m/z (%) = 280 (10) [M + 4]+, 278 (24) [M + 2]+, 276 (11)
[M]+, 192 (21), 156 (16), 112 (24), 87 (100), 43 (44). Anal.
Calcd for C10H11ClO2Se: C, 43.27; H, 3.99. Found: C, 43.16;
H, 3.83. Compound 4h: IR (neat): 2246 cm–1. 1H NMR (500
MHz, CDCl3): d = 2.00 (quin, J = 7.0 Hz, 2 H), 2.51 (t,
J = 7.0 Hz, 2 H), 2.99 (t, J = 7.1 Hz, 2 H), 7.27 (d, J = 8.5
Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (125
MHz, CDCl3): d = 17.1, 25.7, 26.4, 118.8, 127.0, 129.5,
133.9, 134.7 ppm. LRMS: m/z (%) = 261 (50) [M + 4]+, 259
(100) [M + 2]+, 257 (52) [M]+, 191 (14), 156 (14), 112 (11),
68 (14), 41 (27). Anal. Calcd for C10H10ClNSe: C, 46.44; H,
3.90; N, 5.42. Found: C, 46.73; H, 4.15; N, 5.58. Compound
4i: IR (neat): 1714 cm–1. 1H NMR (500 MHz, CDCl3):
d = 1.96 (quin, J = 7.1 Hz, 2 H), 2.13 (s, 3 H), 2.59 (t, J = 7.1
Hz, 2 H), 2.99 (t, J = 7.1 Hz, 2 H), 7.40 (t, J = 7.7 Hz, 1 H),
7.50–7.62 (m, 2 H), 7.78–7.89 (m, 3 H), 8.40 (d, J = 8.4 Hz,
1 H) ppm. 13C NMR (125 MHz, CDCl3): d = 24.0, 27.5,
29.7, 43.1, 125.8, 126.2, 126.6, 127.5, 128.3, 128.7, 129.2,
132.3, 134.1, 134.3, 207.9 ppm. LRMS: m/z (%) = 292 (17)
[M + 2]+, 290 (10) [M]+, 207 (6), 165 (6), 141 (6), 128 (15),
115 (17), 85 (100), 43 (99). Anal. Calcd for C15H16OSe: C,
61.86; H, 5.54. Found: C, 62.17; H, 5.76. Compound 4j: IR
(neat): 1708, 2400–3500 cm–1. 1H NMR (500 MHz, CDCl3):
d = 2.01 (quin, J = 7.2 Hz, 2 H), 2.53 (t, J = 7.3 Hz, 2 H),
3.02 (t, J = 7.2 Hz, 2 H), 7.41 (t, J = 7.7 Hz, 1 H), 7.51–7.63
(m, 2 H), 7.80–7.90 (m, 3 H), 8.45 (d, J = 8.4 Hz, 1 H),
11.41 (br s, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
d = 25.0, 27.1, 33.8, 125.8, 126.3, 126.7, 127.6, 128.5,
128.7, 129.1, 132.5, 134.1, 134.4, 179.3 ppm. LRMS: m/z
(%) = 294 (87) [M + 2]+, 292 (47) [M]+, 208 (38), 141 (14),
128 (100), 115 (65), 87 (67), 43 (24). Anal. Calcd for
C14H14O2Se: C, 57.35; H, 4.81. Found: C, 56.99; H, 5.03.
(12) General Procedure: A mixture of diaryl diselenide (0.5
mmol) and zinc powder (3.0 mmol) in anhydrous MeCN (15
mL), was stirred at 70 °C. After 15 min, anhydrous AlCl3
(3.0 mmol in 2 mL anhydrous MeCN) was added cautiously.
The mixture was stirred for 1 h at 70 °C, until the yellow
solution turned colorless. The mono-activated cyclopropane
(1.1 mmol) was then added to the solution and the mixture
was stirred at 70 °C for the period of time specified in
Table 1. The progress of reaction was monitored with TLC.
After the reaction was complete, the solution was filtered
and the solvent was evaporated. Aqueous HCl (10%) was
added to the crude product and the mixture was extracted
with EtOAc (2 × 30 mL). The combined organic layers were
dried over anhydrous Na2SO4, filtered, and the solvent was
removed under reduced pressure. Purification by preparative
TLC (silica gel; n-hexane–EtOAc, 3:1) gave the corres-
ponding arylselenenyl-functionalized ring-opened product.
All novel compounds were characterized by 1H and 13
NMR, IR, mass spectroscopy, and elemental analysis.
C
Compound 4e: IR (neat): 1723, 2725, 2825 cm–1. 1H NMR
(500 MHz, CDCl3): d = 2.06 (quin, J = 6.9 Hz, 2 H), 2.64 (t,
J = 6.9 Hz, 2 H), 2.98 (t, J = 7.0 Hz, 2 H), 7.23–7.61 (m,
5 H), 9.80 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
d = 22.9, 27.5, 29.3, 127.5, 129.4, 129.6, 132.7, 201.8 ppm.
LRMS: m/z (%) = 227 (25) [M + 2]+, 225 (12) [M]+, 185
(45), 183 (22), 171 (32), 169 (15), 157 (78), 155 (42), 123
(53), 105 (31), 91 (100), 77 (78), 71 (58), 55 (45), 41 (49).
Anal. Calcd for C10H12OSe: C, 52.87; H, 5.32. Found: C,
Synlett 2009, No. 11, 1803–1805 © Thieme Stuttgart · New York