beta-butyltellanyl carbonyl compounds: a useful source of masked metal homoenolates

Abstracts

Secondary higher order cyanocuprates and lithium homoenolates, were efficiently generated from beta-butyltellanylketals and reacted with benzaldehyde and 2-cyclohexen-1-one.

tellurides, tellurium; secondary lithium homoenolates; higher order cyanocuprates

Cianocupratos de ordem superior e homoenolatos de lítio secundários, foram eficientemente gerados a partir de beta-butil teluro cetais e submetidos a reação com benzaldeido e 2-cicloexen-1-ona.

COMMUNICATION

b-butyltellanyl carbonyl compounds: a useful source of masked metal homoenolates

Alcindo A. dos Santos^*; João V. Comasseto

Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, nº 748, 05508-900 São Paulo - SP, Brazil

ABSTRACT

Secondary higher order cyanocuprates and lithium homoenolates, were efficiently generated from b-butyltellanylketals and reacted with benzaldehyde and 2-cyclohexen-1-one.

Keywords: tellurides, tellurium / lithium exchange, secondary lithium homoenolates and higher order cyanocuprates

RESUMO

Cianocupratos de ordem superior e homoenolatos de lítio secundários, foram eficientemente gerados a partir de b-butil teluro cetais e submetidos a reação com benzaldeido e 2-cicloexen-1-ona.

Introduction

Homoenolate anions are important synthons in the Umpolung concept.¹ Unlike the enolate anions, the homoenolate anions cannot be stoichiometrically generated by deprotonation of a carbonyl compound, since the pk_a value of the b-hydrogen is only very slightly lowered.² In addition, the reactive homoenolates 1, especially lithium and sodium derivatives, spontaneously cyclize to the corresponding cyclopropanolate tautomer 2 (Scheme 1),² which does not react as a carbon-nucleophile with standard electrophiles.

Although the a-enolization of carbonyl compounds is readily carried out under mild conditions to yield high equilibrium concentrations of a-enolates, vigorous conditions are required to give low concentrations of short-lived intermediate homoenolates by b-deprotonation of nonenolizable ketones.² This fact makes the direct b-deprotonation of carbonyl compounds an impracticable method for preparative purposes. The use of a masked carbonyl unit is an alternative to circumvent this problem.³ However, this strategy is also limited to the presence of strongly electron-attracting substituents at the b-position to the masked carbonyl groups that promotes the stabilization of the carbanion formed. Classically, for this purpose nitro,⁴ phosphorus⁵ and sulphur⁶ based compounds are used. Moreover, this method requires previous preparation of the nitro, phosphorus or sulphur organic substrates and another further step, to remove reductively the activating group.

A simple strategy to circumvent this problem should be the preparation of b-butyltellanyl masked carbonyl compounds such as 3,⁷ and their transformation into the corresponding lithium homoenolates through a tellurium/lithium exchange reaction (Scheme 2).⁸

A general way to obtain compounds of type 3 should be the Michael addition of n-butyltellurol to a,b-unsaturated ketones, as recently described by us,⁹ followed by a ketalization reaction.

The n-butyltellurol, generated in situ by reaction of elemental tellurium with n-BuLi in THF, followed by addition of a proton source such as ethanol or water, reacts rapidly with Michael acceptors.⁹ Under these conditions the b-butyltellanylketones 5 and 6 were successfully prepared in 86% and 89% yield respectively (Scheme 3).

The b-butyltellanylketones 5 and 6 were converted into the corresponding b-butyltellanylketals 3 and 7 in high yields by reaction with ethylene glycol in benzene in a Dean-Stark apparatus (Scheme 4).^9,10

The light yellow tellurides 3 and 7 were transformed into the corresponding lithium masked homoenolates by reaction with t-butyllithium in THF at –70 ºC. The tellurium/lithium exchange showed to be very fast even to generate a secondary anion.

Trapping the lithium anions with benzaldehyde afforded the corresponding alcohols 8 and 10 (Scheme 5).¹¹ The lithium intermediates were also submitted to reaction with the copper soluble species CuCN.2LiCl¹² producing the corresponding higher order cyanocuprates.¹³ Michael addition of these intermediates to 2-cyclohexen-1-one produced the corresponding saturated ketones (Scheme 5).¹³

All tellurides described in this paper are stable to the ambient light and can be manipulated in the air. Most of them are almost odourless or present a smell not more unpleasant them most of the laboratory chemicals normally used in an organic synthesis laboratory.

It is worthy of note that the dibutyltelluride originated in the tellurium/lithium exchange step, is totally compatible with all the subsequent operations. It can be easily eliminated in an odourless operation by washing the organic phase with a diluted sodium hypochlorite solution.

In conclusion, b-butyltellanyl carbonyl compounds are a very practical source of homoenolate equivalents.

Acknowledgements

The authors thank FAPESP for support.

References

1. Seebach, D.; Angew. Chem. Int. Ed. Engl. 1979, 18, 239; Evans, D. A.; Andrews, G. C.; Acc. Chem. Res. 1974, 7, 14; Hoppe, D.; Angew. Chem. Int. Ed. Engl. 1984, 23, 932.

2. Werstiuk, N. H.; Tetrahedron 1983, 39, 205; Ryu, I.; Sonoda, N.; J. Syn. Org. Chem. Jpn. 1985, 43, 112; Nakamura, E.; J. Syn. Org. Chem. Jpn. 1989, 47, 931.

3. Büchi, G.; Wüest, H.; J. Org. Chem. 1969, 34, 1122; for a recent review see: Yus, M.; Torregrosa, R.; Pastor, I. M.; Molecules 2004, 9, 330.

4. Bakuzis, P.; Bakuzis, M. L. F.; Weingartner, T. F.; Tetrahedron Lett. 1978, 2371; Crumbie, R. L.; Nimetz, J. S.; Mosher, H. S.; J. Org. Chem. 1983, 47, 4040; Corey, E. J.; Vlattas, I.; Anderson, N. H.; Harding, K.; J. Am. Chem. Soc. 1968, 90, 3247.

5. Corey, E. J.; Shimoji, K.; J. Am. Chem. Soc. 1983, 105, 1662; Bell, A.; Davidson, A. H.; Earnshaw, C.; Norrish, H. K.; Torr, R. S.; Warren, S.; J. Chem. Soc. Chem. Comm. 1978, 988; Cristau, H. J.; Chabaud, B.; Niangoran, C.; J. Org. Chem. 1983, 48, 1527.

6. Kondo, K.; Tunemoto, T.; Tetrahedron Lett. 1975, 1007; Fayos, J.; Clardy, J.; Dolby, L. J.; Farham, T.; J. Org. Chem. 1977, 42, 1349.

7. The generation of 3 by a different approach and its transformation into a lithium homoenolate has been already described: Inoue, T.; Atarashi, Y.; Kambe, N.; Ogawa, A.; Sonoda, N.; Synlett 1995, 209.

8. Hiiro, T.; Kambe, N.; Ogawa, A.; Miyoshi, N.; Murai, S.; Sonoda, N.; Angew. Chem. Int. Ed. Engl. 1987, 26, 1187; for recent reviews see: Comasseto, J. V.; Barrientos-Astigarraga, R. E.; Aldrichimica Acta 2000, 33, 66; Petragnani, N.; Stefani, H. A.; Tetrahedron 2005, 61, 1613.

9. Zinn, F. K.; Righi, V. E.; Luque, S. C.; Formiga, H. B.; Comasseto, J. V.; Tetrahedron Lett. 2002, 43, 1625.

10. General procedure for the preparation of the b-butyltellanylketalls 3 and 7: To a two bottomed flask equipped with a Dean-Stark reflux apparatus were added the appropriate b-butyltellanylketone 5 or 6 (5 mmol), benzene (10 mL), ethylene glycol (8 mmol, 0.44 mL) and Amberlist^® (30 mg). The reaction mixture was refluxed under nitrogen atmosphere for 5 hours. The mixture was filtered and the residue washed with ethyl acetate. The solvents were removed under reduced pressure. The residue was purified by silica gel chromatography eluting with a mixture of hexane:ethyl acetate (15:1), to give 2-(2-(butyltellanyl)ethyl)-2-methyl-1,3-dioxolane (3). Yield: 1.43 g (96%); ¹H NMR: (300 MHz, CDCl₃, ppm) d 3.95 (m, 4 H); 2.60-2.66 (m, 4 H); 2.10-2.16 (m, 2 H); 1.72 (quint, J 7.3 Hz, 2 H); 1.38 (sext, J 7.3 Hz, 2 H); 1.32 (s, 3H); 0.92 (t, J 7.3 Hz, 3H); ¹³C NMR: (75 MHz, CDCl₃, ppm) d 110.2; 64.7; 42.1; 34.2; 25.0; 23.5; 13.3; 2.7; -5.6; LRMS m/z (rel. int.) 302 (M⁺, 3); 99 (4); 87 (100); 55 (15); 43 (58); IR (film) n_max /cm^-1: 2979; 2958; 2927; 2874; 1457; 1378; 1246; 1212; 1040; 944; ¹²⁵Te NMR (CDCl₃, 157.79 MHz / 298 K / Ph₂Te₂) d (ppm) 263.3; Anal. Calc. for C₁₀H₂₀O₂Te: C, 40.13; H, 6.68; Found: C, 40.35; H, 6.46. 7-butyltellanyl-1,4-dioxaspiro [4.5]hexane (7). Yield: 1.49 g (92%); ¹H NMR: (300 MHz, CDCl₃, ppm) d 3.94 (t, J 0.8 Hz, 4 H); 3.30 (m, 1 H); 2.66 (t, J 7.2 Hz, 2 H); 2.00-2.23 (m, 2 H); 1.50-1.90 (m, 8 H); 1.37 (sext, J 7.2 Hz, 2H); 0.91 (t, J 7.2 Hz, 3H); ¹³C NMR: (75 MHz, CDCl₃, ppm) d 108.7; 64.2; 44.8; 35.5; 34.5; 34.4; 25.2; 25.0; 16.1; 13.4; 2.3; LRMS m/z (rel. int.) 328 (M⁺, 10); 141 (87); 99 (100); 79 (12); 69 (18); 57 (13); 55 (44); 41 (70). IR(film) n_max/cm^-1: 2953; 2933; 1448; 1356; 1299; 1164; 1063; 1025; ¹²⁵Te NMR (CDCl₃, 157.79 MHz / 298 K / Ph₂Te₂) d (ppm) 423.31; Anal. Calc. for C₁₂H₂₂O₂Te: C, 44.30; H, 6.76; Found: C, 44.49; H, 6.72.

11. Typical procedure for the tellurium / lithium exchange reaction and capture of the resulting organolithium with benzaldehyde: to a solution of telluride 3 (1 mmol, 0.29 g) in THF (5 mL), at -70 ºC was added t-butyllithium (1.0 mmol, 0.89 mL, 1.12 mol L^-1 in pentane). After 5 min was added benzaldehyde (1 mmol, 0.1 mL). The reaction mixture was allowed to warm to 0 ºC. The mixture was stirred for 1 h and then diluted with ethyl acetate (5 mL). The organic phase was sequentially washed with a diluted solution of sodium hypochlorite (2 x 5 mL) and brine (2 x 5 mL), dried over magnesium sulphate, filtrated and evaporated. The residue was purified by column chromatography on silica gel using a 2:1 hexane:ethyl acetate mixture as eluent, to give 3-(2-methyl-1,3-dioxolan-2-yl)-1-phenylpropan-1-ol (8). Yield: 0.18 g (84%); CAS Nº: 167644-51-1.

12. Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J.; J. Org. Chem. 1988, 53, 2390.

13. Typical procedure to prepare the higher order cyanocuprate and its reaction with 2-cyclohexen-1-one: To a solution of the lithium anion of telluride 7 (1 mmol, 0.32 g, generated by the same procedure described in ref. 11) at -70 ºC, was added a solution of CuCN.2LiCl (0.5 mmol, 1 mol^-1 / THF, 0.5 Equiv.). The resulting orange solution was stirred for 20 min at the same temperature and then 2-cyclohexen-1-one (1 Equiv.) was added in one portion. The resulting solution was stirred for 1 h at -70 ºC and then allowed to warm to 0 ºC. A solution of saturated aqueous ammonium chloride and ammonium hydroxide was added (3 mL) and the mixture was stirred for 40 min. The organic phase was sequentially washed with a diluted solution of sodium hypochlorite (2 x 5 mL) and then with brine (2 x 10 mL), dried over magnesium sulphate, filtered and the solvents were removed. The residue was purified by silica gel chromatography using a 3:1 hexane:ethyl acetate mixture, to give a diastereomeric mixture of 3-(1,4-Dioxa-spiro[4.5]dec-7-yl)-cyclohexanone (11). Yield: 0.19 g (80%); ¹H NMR: (300 MHz, CDCl₃, ppm) d 3.92-3.94 (m, 4H); 2.22-2.50 (m, 3 H); 2.04-2.13 (m, 2 H); 1.04-1.7 (m, 12 H); 0.86-0.98 (m, 1 H); ¹³C NMR: (75 MHz, CDCl₃, ppm) d 212.1; 109.4; 64.3; 64.2; 45.4; 44.0; 43.9; 41.5; 40.3; 38.7; 38.5; 34.9; 34.8; 28.5; 28.4; 28.3; 25.5; 25.4; 23.2; 23.1; LRMS m/z (rel. int.) 238 (M⁺, 2); 195 (3); 141 (100); 113 (11); 112 (12); 99 (90); 86 (28); 55 (33); 42 (16); 41 (41); IR(film) n_max /cm^-1: 2938; 2866; 1711; 1448; 1355; 1159; 1085; 919; 516; Anal. Calc. for C₁₄H₂₂O₃: C, 70.49; H, 9.23; Found: C, 70.29; H, 9.11.

Received: March 17, 2005

Published on the web: April 29, 2005

Publication Dates

• Publication in this collection
  09 Aug 2005
• Date of issue
  June 2005

History

• Received
  17 Mar 2005
• Accepted
  29 Apr 2005