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desired product 3a was obtained in 75% yield after 24 h (Table 1,
entry 1). To our satisfaction, increasing the temperature to 50 °C,
the reaction proceeds smoothly and the desired product 3a was ob-
tained in 94% yield in only 1.5 h (Table 1, entry 2). In another
experiment, it was observed that by using 0.7 mmol of 2a, the
product 3a was obtained in only 54% yield (Table 1, entry 3). In
search for better solvents, the reaction was performed also in
PEG/H2O, ethanol, glycerol, and THF, but the results on the forma-
tion of 3a were not satisfactory (Table 1, entries 4–10). By using
ethanol, 3a was obtained in 45% yield after refluxing for 1.5 h
and a similar result was observed even after 6 h of reaction (Table 1,
entries 6 and 7). At shorter reaction time only 38% of 3a was ob-
tained, while at longer reaction time, was observed decomposition
of 3a and regeneration of diphenyl diselenide 2a, which was recov-
ered (Table 1, entries 5 and 8).
In an optimized reaction, NaBH4 was added to a yellow mixture
of diphenyl diselenide 2a and PEG-400. The heterogeneous reac-
tion mixture was stirred for 10 min at 50 °C under N2 atmosphere,
when the color turns whitish, indicating the cleavage of the Se–Se
bond. Then, methyl acrylate 1a was added and the mixture was
stirred for additional 1.5 h, affording methyl 3-(phenylselanyl)pro-
panoate 3a in 94% yield.
3. Hanessian, S.; Roy, P. J.; Petrini, M.; Hodges, P. J.; Fabio, R. D.; Carganico, G. J.
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4965.
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2011, 52, 588.
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2949.
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Helv. Chim. Acta 2009, 92, 1080.
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1987, 28, 3271.
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Organomet. Chem. 2008, 693, 2929.
14. Miyashita, M.; Yoshikoshi, A. Synthesis 1980, 664.
To extend the scope of our methodology, the possibility of per-
forming the reaction with other electron-deficient alkenes and
diselenides was investigated and, in most cases, the reaction pro-
ceeded smoothly to give the respective 3-organoselenium esters, ni-
trile, and ketones 3b–g in good yields (Table 2). It was observed that
the presence of electron-withdrawing and electron-donating groups
in the aryl diselenide did not affect the reactivity of the selenium
species (Table 2, entries 2 and 3). Thus, when bis-(4-chlorophenyl)
diselenide 2b was used, methyl 3-(4-chlorophenylselanyl)propano-
ate 3b was obtained after 1.0 h in 80% yield (entry 2), while bis-(2-
methoxyphenyl) diselenide 2c gave 3c in 78% yield after the same
time (Table 2, entry 3). The use of dibutyl diselenide 2d instead of
aryl ones, 2a–c, was also tested and the respective methyl 3-
(butylseleno)propanoate 3d was obtained in 93% yield after 1 h. This
finding shows that the reaction is insensitive to the nucleophilic
character of the selenium species.
15. Movassagh, B.; Ameneh, T. Synlett 2007, 1954.
16. Ranu, B. C.; Das, A. Adv. Synth. Catal. 2005, 347, 712.
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18. Lenardão, E. J.; Silva, M. S.; Sachini, M.; Lara, R. G.; Jacob, R. G.; Perin, G.
ARKIVOC 2009, xi, 221.
19. Perin, G.; Borges, E. L.; Alves, D. Tetrahedron Lett. 2012, 53, 2066.
20. General procedure for the direct synthesis of b-phenylselanylcarbonyl compounds:
To a mixture of diorganyl diselenide 2 (1.0 mmol) in PEG-400 (3 mL) under N2
atmosphere, NaBH4 (0.046 g, 1.2 mmol) was added at room temperature and
the temperature was slowly raised to 50 °C and stirred for 10 min. Then, the
appropriate alkene 1 (1.0 mmol) was added and the reaction progress was
followed by TLC. After the time indicated in Table 2, the solution was cooled to
room temperature, diluted with ethyl acetate (10 mL), and washed with water
(3 Â 10 mL). The organic phase was separated, dried over MgSO4, and the
solvent was evaporated under reduced pressure. The product was isolated by
column chromatography using hexane or hexane/ethyl acetate as eluent. All
the compounds were characterized and the spectral data are listed below:
Methyl 3-(phenylselanyl)propanoate 3a:21 Yield: 0.229 g (94%). 1H NMR (CDCl3,
500 MHz): d 7.50–7.53 (m, 2H), 7.24–7.29 (m, 3H), 3.66 (s, 3H), 3.09 (t,
J = 7.4 Hz, 2H), 2.72 (t, J = 7.4 Hz, 2H). MS: m/z (rel. int.) 244 (37.2), 157 (26.1),
87 (100.0), 77 (36.8). Methyl 3-(4-chlorophenylselanyl)propanoate 3b: Yield:
0.222 g (80%). 1H NMR (CDCl3, 300 MHz): d 7.34–7.38 (m, 2H), 7.13–7.19 (m,
3H), 3.59 (s, 3H), 3.00 (t, J = 7.2 Hz, 2H), 2.63 (t, J = 7.2 Hz, 2H). 13C NMR
(75 MHz, CDCl3); d (ppm): 172.4, 134.7, 133.6, 129.3, 127.4, 51.8, 35.0, 22.2.
MS: m/z (rel. int.) 278 (27.9), 156 (13.1), 87 (100.0). Methyl 3-(2-
methoxyphenylselanyl)propanoate 3c: Yield: 0.214 g (78%). 1H NMR (CDCl3,
300 MHz): d 7.28–7.31 (m, 1H), 7.12–7.19 (m, 1H), 6.75–6.85 (m, 2H), 3.79 (s,
3H), 3.59 (s, 3H), 3.02 (t, J = 7.2 Hz, 2H), 2.66 (t, J = 7.5 Hz, 2H). 13C NMR
(75 MHz, CDCl3); d (ppm): 172.7, 158.1, 131.9, 128.2, 121.4, 118.5, 110.6, 55.8,
51.8, 35.0, 19.0. MS: m/z (rel. int.) 274 (68.8), 157 (16.0), 108 (73.3), 87 (100.0),
77 (35.1). HRMS (ESI): m/z Calcd for C11H14O3Se [M+Na]+: 297.0006. Found:
297.0011. Methyl 3-(butylselanyl)propanoate 3d: Yield: 0.208 g (93%). 1H NMR
(CDCl3, 300 MHz): d 3.63 (s, 3H), 2.61–2.74 (m, 4H), 2.52 (t, J = 7.5 Hz, 2H),
1.52–1.63 (m, 2H), 1.27–1.40 (m, 2H), 0.85 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
CDCl3); d (ppm): 173.0, 51.9, 35.8, 32.8, 24.3, 23.2, 17.6, 13.8. MS: m/z (rel. int.)
224 (62.1), 168 (58.7), 136 (100.0), 57 (47.2). HRMS (ESI): m/z Calcd for
C8H16O2Se [M+Na]+: 247.0213. Found: 247.0204. 3-(Phenylselanyl)
propanenitrile 3e:21 Yield: 0.158 g (75%). 1H NMR (CDCl3, 500 MHz): d 7.54–
7.57 (m, 2H), 7.28–7.34 (m, 3H), 3.04 (t, J = 7.4 Hz, 2H), 2.66 (t, J = 7.4 Hz, 2H).
MS: m/z (rel. int.) 211 (60.0), 157 (33.2), 91 (100.0), 77 (59.6). 3-
(Phenylselanyl)cyclohexanone 3f:1f Yield: 0.180 g (71%). MS: m/z (rel. int.) 254
(23.8), 157 (9.5), 97 (94.7), 69 (100.0), 41 (87.1). 4-(Phenylselanyl)propan-2-one
Using a,b-unsaturated esters, nitrile, and ketones the respective
Michael adducts were obtained in good yields, but using acrylic
acid 1e, a large decrease in product yield was observed (Table 2,
entry 8). A noteworthy result was obtained when cyclohexanone
1c was used; the respective adduct b-phenylselenocyclohexanone
was obtained in 71% after stirring for 2 h using our method (Table 2,
entry 6). This is a remarkable result because when EtOH was used,
only a poor yield of product was obtained (8%).14
In summary, by using the new system (RSe)2/NaBH4/PEG to
generate the nucleophilic species of selenium, several Se-function-
alized Michael adducts were easily and selectively obtained. By
this new protocol, a range of b-selenyl ketones, esters, nitrile,
and acid were directly obtained, without the need to use any
additive.
Acknowledgments
The authors are grateful to FAPERGS and CNPq (PRONEX 10/
0005-1, PRONEM 11/2026-4, and PqG 11/0719-3), CAPES and FIN-
EP for the financial support.
References and notes
1. For recent examples, see: (a) Azizi, N.; Khajeh-Amiri, A.; Ghafuri, H.;
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Org. Chem. 2003, 68, 2109; (d) Chu, C.-M.; Gao, S.; Sastry, M. N. V.; Yao, C.-F.