Substitution reaction between functionalized Z-vinylic tellurides and lower order cyanocuprates: synthesis of Z or E alpha,beta unsaturated esters using the same Z-vinylic telluride

Abstracts

The substitution reaction between lower order cyanocuprates and functionalized Z-vinylic tellurides was investigated. alpha,beta-Unsaturated carbonyl compounds were obtained in excellent yields. Changes in the reaction conditions afforded alpha,beta-unsaturated esters in high diastereoselectivity.

tellurides; cyanocuprates; alpha,beta-unsaturated esters; alpha,beta-unsaturated ketones; diastereoselective synthesis

A reação de substituição entre cianocupratos de ordem inferior e teluretos vinílicos funcionalizados Z foi estudada. Cetonas cíclicas alfa,beta-insaturadas foram obtidas em excelentes rendimentos. Mudanças nas condições da reação forneceram ésters alfa,beta-insaturados com alta diastereosseletividade.

COMMUNICATION

Substitution reaction between functionalized Z-vinylic tellurides and lower order cyanocuprates. Synthesis of Z or E a,b unsaturated esters using the same Z-vinylic telluride

Priscila Castelani; João V. Comasseto^*

Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, 05508-900 São Paulo - SP, Brazil

ABSTRACT

The substitution reaction between lower order cyanocuprates and functionalized Z-vinylic tellurides was investigated. a,b-Unsaturated carbonyl compounds were obtained in excellent yields. Changes in the reaction conditions afforded a,b-unsaturated esters in high diastereoselectivity.

Keywords: tellurides, cyanocuprates, a,b-unsaturated esters, a,b-unsaturated ketones, diastereoselective synthesis

RESUMO

A reação de substituição entre cianocupratos de ordem inferior e teluretos vinílicos funcionalizados Z foi estudada. Cetonas cíclicas a,b-insaturadas foram obtidas em excelentes rendimentos. Mudanças nas condições da reação forneceram ésters a,b-insaturados com alta diastereosseletividade.

The diastereoselective synthesis of a, b-unsaturated ketones and esters constitutes a challenge to organic chemists due to their synthetic applications.¹ Several procedures have been described for the synthesis of these compounds² but a general and highly diastereoselective alternative route would still be desirable. In view of our longstanding interest in organic tellurium chemistry,³ we decided to explore some special features of the compounds of this element to prepare a,b-unsaturated carbonyl compounds. Z-Vinylic tellurides have been the most explored organotellurium compounds due to their ability to generate other reactive organometallic compounds, mainly through copper chemistry,^3,4 and to perform several coupling reactions.⁵ Cross-coupling reaction between Z-vinylic tellurides and cyanocuprates takes place when at least one gegenion in the higher order cyanocuprate is MgBr⁺.⁶ At the same time, the coupling is also observed when both cations (Li⁺ or MgBr⁺) are present in the lower order cyanocuprate, affording disubstituted olefins.⁷ An important feature of all these reactions is that the Z stereochemistry of the double bond is maintained. In this way, functionalized Z-vinylic tellurides could be interesting precursors of a,b-unsaturated systems with defined stereochemistry. In order to test this idea two functionalized vinylic tellurides (1 and 2) were prepared and reacted with lower order cyanocuprates. Telluride 1 was prepared through vinylic substitution reaction of the corresponding enol phosphate,⁹ by lithium butyltellurolate (Scheme 1)⁸ and telluride 2 was synthesized by hydrotelluration¹⁰ of ethyl propiolate (Scheme 2).¹¹

Tellurides 1 and 2 were reacted at room temperature with lithium cyanocuprates 3, generated in situ from the slow addition of one equivalent of an alkyllithium to a suspension of CuCN in THF at –78 ºC, affording the corresponding products 4 and 5, respectively. The products were purified and isolated by column chromatography in good to excellent yields (Scheme 3 – Table 1).¹²

The reaction was fast in all cases, reaching the completion at room temperature in 5 and 10 minutes for tellurides 1 and 2, respectively. When the reactions were performed with acyclic telluride 2, leading to 5b and 5c, the products formed presented total inversion of the Z configuration of the double bond, giving E a,b-unsaturated esters. On the other hand, product 5a was obtained as a 4:1 mixture of E : Z olefins.

Changing the telluride addition temperature from room temperature to –78 ºC, not surprisingly the reaction time increased. Due to the need for longer reaction times to have total consumption of telluride 2 as well as to the instability of cyanocuprates 3, the reactions were allowed to warm up to 0 ºC after the addition of the telluride.¹³ Under these conditions, the total consumption of telluride 2 ocurred in 20 minutes, and the products 5d-f showed the Z configuration (>99% selectivity). By GC-MS analysis, it was possible to detect traces of the E isomers in the crude mixtures of compounds 5e and 5f.

In conclusion, functionalized Z-vinylic tellurides react efficiently with lower order cyanocuprates in good yields. Depending on the reaction temperature, the product geometry present inversion or retention of the double bond configuration of the starting telluride. This stereochemistry control makes this method unique, allowing the synthesis of the Z or the E a, b-unsaturated carbonyl compounds only by changing the reaction temperature.

Acknowledgements

The authors thank FAPESP and CNPq for support.

References

1. Patai, S.; Rappoport, Z.; The Chemistry of Enones; John Wiley & Sons: New York, 1989; Kourouli, T.; Kefalas, P.; Ragoussis, N.; Ragoussis, V.; J. Org. Chem. 2002, 67, 4615.

2. Taber, D. F.; Herr, R. J.; Pack, S. K.; Geremia, J. M.; J. Org. Chem. 1996, 61, 2908; Yu, W.; Su, M.; Jin, Z.; Tetrahedron Lett. 1999, 40, 6725; Concellón, J. M.; Huerta, M.; Tetrahedron Lett. 2003, 44, 1931; Takeda, T.; Kabasawa, Y.; Fujiwara, T.; Tetrahedron 1995, 51, 2515.; Kelly, S. E.; Comprehensive Organic Synthesis; Pergamon Press: Oxford, 1991; Vol. 1.

3. Comasseto, J. V.; Barrientos-Astigarraga, R. E.; Aldrichimica Acta 2000, 33, 66.

4. Tucci, F. C.; Chieffi, A.; Comasseto, J. V.; J. Org. Chem. 1996, 61, 4975.

5. Zeni, G.; Comasseto, J. V.; Tetrahedron Lett. 1999, 40, 4619; Zeni, G.; Nogueira, C. W.; Panatieri, R. B.; Silva, D. O.; Menezes, P. H.: Braga, A. L.; Silveira, C. C.; Stefani, H. A.; Rocha, J. B. T.; Tetrahedron Lett. 2001, 42, 7921; Braga, A. L.; Vargas, F.; Zeni, G.; Silveira, C. C.; de Andrade, L. H.; Tetrahedron Lett. 2002, 43, 4399; for a review on Pd catalyzed couplings see: Zeni, G.; Braga, A. L.; Stefani, H. A.; Acc. Chem. Res. 2003, 36, 731; for Ni catalyzed couplings see: Raminelli, C.; Gargalaka Jr., J.; Silveira, C. C.; Comasseto, J. V. Tetrahedron Lett. 2004, 45, 4927; Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zeni, G. J. Org. Chem. 2003, 68, 662; for Cu promoted couplings see: Araujo, M. A.; Raminelli, C.; Comasseto, J. V. J. Braz. Chem. Soc. 2004, 15, 358; Araujo, M. A.; Comasseto, J. V. Synlett 1995, 1145.

6. Chieffi, A.; Comasseto, J. V.; Tetrahedron Lett. 1994, 35, 4063.

7. Chieffi, A.; Comasseto, J. V.; Synlett 1995, 671.

8. Barrientos-Astigarraga, R. E.; Castelani, P.; Sumida, C. Y.; Comasseto, J. V.; Tetrahedron Lett. 1999, 40, 7717; Barrientos-Astigarraga, R. E.; Castelani, P.; Sumida, C. Y.; Zukerman-Schpector, J.; Comasseto, J. V.; Tetrahedron 2002, 58, 1051.

9. Alberdice, M.; Weiler, L.; Sum, F. W.; Org. Synth. 1984, 64, 14.

10. For reviews see: Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani, H. A.; Synthesis 1997, 373; Vieira, M. L.; Zinn, F. K.; Comasseto, J. V.; J. Braz. Chem. Soc. 2001, 12, 586.

11. Rahmeier, L. H. S.; Comasseto, J. V.; Organometallics 1997, 16, 651.

12. General procedure for substitution reactions between functionalized tellurides and lower order cyanocuprates at room temperature: To a suspension of dry CuCN (0,089 g; 1 mmol) in THF (10 mL), under nitrogen at -78 ºC was slowly added alkyllithium (1 mmol). The reaction was stirred at this temperature for 20 min and a limpid and clear solution was obtained. The mixture was allowed to reach room temperature and the corresponding telluride (1 mmol) was added. The reaction was monitored by TLC, until the consumption of the telluride. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with a 1:1 solution of saturated aqueous NH₄Cl and NH₄OH (4 x 50 mL). The organic phase was dried with magnesium sulfate and the solvents were evaporated. The residue was purified by silica gel column chromatography eluting with hexane:ethyl acetate (9:1). (E)-ethyl 4-methylhex-2-enoate (5b). (0.123 g, 79%) [78023-52-6]. IR n_max/cm^-1: 2965, 2932, 2877, 1721, 1653, 1461, 1269, 1186, 1136, 1042 (neat). ¹H NMR (500 MHz, CDCl₃) d 6.86 (dd, J 15.7 Hz, 7.8 Hz, 1H), 5.78 (dd, J 15.7 Hz, 1.2 Hz, 1H), 4.18 (quart., J 7.1 Hz, 2H), 2.24-2.19 (m, 1H), 1.40-1.34 (m, 2H), 1.29 (t, J 7.1 Hz, 3H), 1.04 (d, J 6.7 Hz, 3H), 0.88 (t, J 7.0 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) d 167.0, 154.4, 119.8, 60.2, 38.2, 28.9, 19.2, 14.3, 11.6. LRMS m/z (rel. int.) 156 (M⁺, 20), 128 (14), 111 (41), 95 (34), 82 (40), 69 (40), 55 (100).

13. General procedure for substitution reactions between functionalized tellurides and lower order cyanocuprates at low temperatures: To a suspension of dry CuCN (0,089 g; 1 mmol) in THF (10 mL), under nitrogen at -78 ºC was slowly added alkyllithium (1 mmol). The reaction was stirred at this temperature for 20 min and a limpid and clear solution was obtained. Then the corresponding telluride (1 mmol) was added and the reaction was warmed up to 0 ºC. The reaction was maintained at this temperature and monitored by TLC, until the consumption of the telluride. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with a 1:1 solution of saturated aqueous NH₄Cl and NH₄OH (4 x 50 mL). The organic phase was dried with magnesium sulfate and the solvents were evaporated. The residue was purified by silica gel column chromatography eluting with hexane:ethyl acetate (9:1). (Z)-ethyl 4-methylhex-2-enoate (5e). (0.112 g, 72%) [169735-64-2]. IR n_max/cm^-1: 2966, 2933, 1723, 1645, 1416, 1188, 1131, 1035 (neat). ¹H NMR (300 MHz, CDCl₃) d 5.95 (dd, J 11.5 Hz, 10.2 Hz, 1H), 5.71 (dd, J 11.5 Hz, 0.8 Hz, 1H), 4.16 (quart., J 7.1 Hz, 2H), 3.45-3.35 (m, 1H), 1.44-1.31 (m, 2H), 1.28 (t, J 7.1 Hz, 3H), 1.00 (d, J 6.6 Hz, 3H), 0.87 (t, J 7.4 Hz, 3H). ¹³C NMR (75 MHz, CDCl₃) d 166.4, 155.9, 118.5, 59.7, 34.4, 29.8, 19.9, 14.2, 11.7. LRMS m/z (rel. int.) 156 (M⁺, 28), 128 (22), 111 (44), 95 (33), 82 (40), 69 (37), 55 (100).

Received: June 29, 2004

Published on the web: August 9, 2004

FAPESP helped in meeting the publication costs of this article.

Publication Dates

• Publication in this collection
  15 Sept 2004
• Date of issue
  Aug 2004

History

• Received
  29 June 2004