Catalytic asymmetric oxyselenenylation-elimination reactions using chiral selenium compounds

Article abstract of DOI:10.1016/S0957-4166(98)00031-7

Only catalytic amounts of chiral selenium reagents are necessary to achieve a sequence of methoxyselenenylation and oxidative β-hydride elimination of alkenes. Performing this reaction with peroxodisulfates and various metal salts led to enantiomeric excesses of up to 75%.

Full text of DOI:10.1016/S0957-4166(98)00031-7

Pergamon
Tetrahedron: Asymmetry 9 (1998) 547–550
Catalytic asymmetric oxyselenenylation–elimination reactions
using chiral selenium compounds
Thomas Wirth,∗ Sara Häuptli and Michele Leuenberger
Institut für Organische Chemie der Universität Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland
Received 7 January 1998; accepted 22 January 1998
Abstract
Only catalytic amounts of chiral selenium reagents are necessary to achieve a sequence of methoxyselenenylation
and oxidative β-hydride elimination of alkenes. Performing this reaction with peroxodisulfates and various metal
salts led to enantiomeric excesses of up to 75%. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
Very efficient and advanced methods have been established for some synthetic transformations to
highly enriched stereoisomers. But only a few useful methods are known for the stereoselective function-
alization of unactivated C_C double bonds. With alkenes as substrates, stoichiometric as well as catalytic
reactions to optically active products remain to be investigated. Recently we developed a variety of
chiral selenium compounds which can be used as efficient stoichiometric reagents for the stereoselective
functionalization of alkenes.1 Herein we report an asymmetric oxyselenenylation–elimination sequence
using only catalytic amounts of these chiral selenium compounds.
In the stoichiometric addition reactions mentioned above, the electrophilic selenium triflates are
generated from the corresponding diselenides. Because these reaction conditions are incompatible with
a subsequent elimination, we used peroxodisulfates for the generation of the selenium electrophiles.2 An
excess of these strong oxidizing reagents is then responsible for the subsequent oxidative elimination
reaction.
Electrochemical oxyselenenylation–elimination reactions have also been reported with diphenyl
diselenide.3 Furthermore it is possible to use diselenides with nitrogen-containing substituents in the
catalytic conversion of alkenes to allylic ethers.4 Very recently chiral diselenides have been investigated
in catalytic oxyselenenylation–elimination sequences leading to optically active allylic ethers.5
∗
Corresponding author. E-mail: wirth@ubaclu.unibas.ch
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00031-7

548
T. Wirth et al. / Tetrahedron: Asymmetry 9 (1998) 547–550
2. Results and discussion
The selenium electrophiles are formed from the corresponding diselenides 1 by reaction with per-
oxodisulfates. This process can be initiated by an electron-transfer or an SN2 process generating the
selenenylsulfates as electrophilic species.2a It is likely that in the presence of metal ions the electron-
transfer process occurs, as the metal-catalyzed decomposition to the sulfate radical anion and its
subsequent chemistry has been investigated intensively.6
After formation of the selenenyl sulfate 2 and methoxyselenenylation of the alkene 3, the selenide 4
is oxidized by the peroxodisulfate (or by the sulfate radical anion derived therefrom). The chiral allylic
ether 5 is obtained and the selenenyl sulfate 2 is cleaved off which then can undergo the next addition
reaction.
Chiral nitrogen-containing diselenides have been described as useful ligands in various transformations
such as the diethylzinc additions to aldehydes7 and asymmetric hydrosilylation reactions,8 as well as
transfer hydrogenations.9 We are using chiral diselenides of type 1 for the catalytic oxyselenenyl-
ation–elimination reaction with trans-β-methylstyrene 3 as alkene.10 First we employed the reaction
conditions reported by Tomoda et al.4a using the various diselenides 1 in the catalytic reaction. Table 1
shows that diselenide 1a yields the product 5 with the highest enantioselectivity (up to 56%).11 The
configuration of the main enantiomer of 5 is always R and was confirmed by independent synthesis.12
Potassium peroxodisulfate seems to be superior to sodium peroxodisulfate as well as ammonium
peroxodisulfate.13
Table 1
Addition–elimination using diselenides 114
Nitrogen-containing selenium compounds of type 1 and 2 can serve as ligands to metals.7–9 Further-
more it is known that metal ions can accelerate the decomposition of peroxodisulfates.6 a Therefore we
varied the metal salt added to the reaction and found a strong influence on the stereoselectivity. We
additionally found that there is no time-dependence of the enantiomeric excess of 5 during the catalytic
reaction. Because of the long reaction times, even in the presence of metal salts, the reactions summarized

T. Wirth et al. / Tetrahedron: Asymmetry 9 (1998) 547–550
549
Table 2
Addition–elimination sequence with catalytic amounts (10 mol %) of diselenide 1aa
a
1 mmol 3, 1 mmol K2S2O8, 3 ml MeOH, 200 mg molecular sieve 3 Å, r.t., 7 days.
Table 3
Addition–elimination sequence with diselenides 1 in MeOH:H2O (10:1)16
in Table 2 have been stopped after formation of some product and no yields are given in Table 2. Among
the various metal salts investigated we found that nickel nitrate (entry 10) has the strongest influence
upon the stereoselectivity, yielding product 5 in 71% ee.
Independent preparation of the methoxyselenenylated product 4 and treatment with potassium per-
oxodisulfate under the reaction conditions showed clearly that the oxidative elimination is very slow.
This is probably due to the very bad solubility of peroxodisulfates in organic solvents. After dissolving
the peroxodisulfate partially by addition of a small amount of water to the methanolic solution, the
elimination reaction was complete within one day.
As can be seen from Table 3, the enantiomeric excess of the product 5 in water-containing catalytic
reactions decreases. Using diselenide 1a the enantiomeric excess drops from 71% ee (Table 2, entry
10) to 58% ee (Table 3, entry 1). The reasons for this are not clear at present, but with the derivative
1f the stereoselectivity was improved to 63% ee (Table 3, entry 3). Catalytic reaction under anhydrous
conditions, however, yielded the product 5 in 75% ee (Table 3, entry 4). Although the turnover numbers
in the catalytic reaction described are still low, this is to our knowledge the highest enantiomeric
excess reported to date for a catalytic asymmetric oxyselenenylation–elimination reaction. The additional
methoxy group in the second ortho-position to selenium in 1f may stabilize the selenium cations. After
tosylation of the chiral alcohol 615 and subsequent treatment with dimethylamine, the diselenide synthesis
of 1f via the ortho-lithiation route was achieved.
Depending on the reaction conditions, side products can be formed which were identified to be
benzaldehyde and benzaldehyde dimethyl acetal. It is known that peroxodisulfates can cleave alkenes
to aldehydes probably via the 1,2-diols.17

550
T. Wirth et al. / Tetrahedron: Asymmetry 9 (1998) 547–550
Other alkenes can also be used in the catalytic addition–elimination sequence. While trans-β-
ethylstyrene18 gave comparable results, the stereoselectivity with indene is lower (24% ee) in the catalytic
reaction. We already established the stoichiometric selenenylation reaction to be a useful transformation
for natural product synthesis.19 Currently we are synthesizing modified diselenides and investigating
applications of the catalytic alkoxyselenenylation–elimination sequence in total synthesis.
Acknowledgements
This work was supported by the Deutschen Forschungsgemeinschaft, the Schweizer Nationalfonds
and the Treubel-Fonds. We thank Prof. B. Giese for his generous support.
References
1. Wirth, T. Angew. Chem. 1995, 107, 1872–1873; Angew. Chem. Int. Ed. Engl. 1995, 34, 1726–1728; Wirth, T.; Fragale, G.
Chem. Eur. J. 1997, 3, 1894–1902.
2. (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Bartoli, D. Tetrahedron Lett. 1989, 30, 1417–1420; (b) Tiecco, M.;
Testaferri, L.; Tingoli, M.; Bagnoli, L.; Santi, C. J. Chem. Soc., Chem. Commun. 1993, 637–639; (c) Tiecco, M.; Testaferri,
L.; Tingoli, M.; Bagnoli, L.; Marini, F.; Santi, C.; Temperini, A. Gazz. Chim. Ital. 1996, 126, 635–643.
3. Torii, S.; Uneyama, K.; Ono, M. Tetrahedron Lett. 1980, 21, 2653–2654; Torii, S.; Uneyama, K.; Ono, M.; Bannou, T. J.
Am. Chem. Soc. 1981, 103, 4606–4608.
4. (a) Iwaoka, M.; Tomoda, S. J. Chem. Soc., Chem. Commun. 1992, 1165–1167; (b) Kaur, R.; Singh, H. B.; Patel, R. P. J.
Chem. Soc., Dalton Trans. 1996, 2719–2726; (c) Fujita, K. Rev. Heteroatom. Chem. 1997, 16, 101–117.
5. Fujita, K.; Iwaoka, M.; Tomoda, S. Chem. Lett. 1994, 923–926; Wirth, T. Liebigs Ann./Recueil 1997, 2189–2196; Fukuzawa,
S.; Takahashi, K.; Kato, H.; Yamazaki, H. J. Org. Chem. 1997, 62, 7711–7716.
6. (a) House, D. A. Chem. Rev. 1962, 62, 185–203; (b) Norman, R. O. C.; Storey, P. M.; West, P. R. J. Chem. Soc. (B) 1972,
1087–1095.
7. Wirth, T. Tetrahedron Lett. 1995, 36, 7849–7852; Wirth, T.; Kulicke, K. J.; Fragale, G. Helv. Chim. Acta 1996, 79,
1957–1966.
8. Nishibayashi, Y.; Singh, J. D.; Segawa, K.; Fukuzawa, S.; Uemura, S. J. Chem. Soc., Chem. Commun. 1994, 1375–1376;
Nishibayashi, Y.; Segawa, K.; Singh, J. D.; Fukuzawa, S.; Ohe, K.; Uemura, S. Organometallics 1996, 15, 370–379.
9. Nishibayashi, Y.; Singh, J. D.; Arikawa, Y.; Uemura, S.; Hidai, M. J. Organomet. Chem. 1997, 531, 13–18.
10. Oxygen containing chiral diselenides as developed for the stoichiometric alkoxyselenenylations1 proved to be less efficient
in the catalytic reaction.
11. HPLC conditions: Chiracel OD, 2-propanol:hexane (0.01:99.99), 0.3 ml/min, 220 nm, (R)-5: tR=31.0 min, (S)-5: tR=40.9
min.
12. Commercially available (R)-1-phenyl-2-propen-1-ol was methylated: Kwart, H.; Sarner, S. F.; Slutsky, J. J. Am. Chem. Soc.
1973, 95, 5234–5242.
13. The use of Rb2S2O8 gave no further improvement. Mackenzie, J. E.; Marshall, H. J. Chem. Soc. 1908, 93, 1726–1739.
14. 1 mmol 3, 1 mmol Na2S2O8, 0.1 mmol Cu(NO3)2·3H2O, 3 mL MeOH, 200 mg molecular sieve 3 Å, r.t., 7 days.
15. Zhao, M.; King, A. O.; Larsen, R. D.; Verhoeven, T. R.; Reider, P. J. Tetrahedron Lett. 1997, 38, 2641–2644.
16. 1 mmol 3, 1 mmol K2S2O8, 0.1 mmol Ni(NO3)2·6H2O, 3 mL MeOH:H2O (10:1), r.t., 1 day.
17. Andreeva, L. K.; Birger, E. A.; Kheifits, L. A.; J. Org. Chem. USSR (Engl. Trans.) 1978, 14, 616; Greenspan, F. P.;
Woodburn, H. M. J. Am. Chem. Soc. 1954, 76, 6345–6349.
18. Seebach, D.; Schäfer, H.; Schmidt, B.; Schreiber, M. Angew. Chem. 1992, 104, 1680–1681; Angew. Chem. Int. Ed. Engl.
1992, 31, 1587–1588.
19. Wirth, T.; Kulicke, K. J.; Fragale, G. J. Org. Chem. 1996, 61, 2686–2689; Wirth, T. Liebigs Ann./Recueil 1997, 1155–1158;
Wirth, T.; Fragale, G. Synthesis 1998, in press.