γ-Butyltelluro-2-butanol: A route to reactive 1,4-dianion intermediates

Article abstract of DOI:10.1016/j.tetlet.2005.05.002

γ-Butyltelluro-2-butanol was reacted with 2 equiv of n-butyllithium. Both tellurium/lithium exchange and the proton abstraction reactions took place in a single step and the lithium dianion intermediate efficiently reacted with aldehydes and ketones, producing the corresponding diols.

Full text of DOI:10.1016/j.tetlet.2005.05.002

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4423–4425
c-Butyltelluro-2-butanol: a route to reactive
1,4-dianion intermediates
Jefferson L. Princival,a Simone M. G. de Barros,a Joa˜o V. Comassetob and
Alcindo A. Dos Santosb,*
aDQF, Universidade Federal de Pernambuco, CEP 50740-540, Recife, Pe, Brazil
bIQ, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes, 748, CEP 05508-900, Sa˜o Paulo, SP, Brazil
Received 25 April 2005; revised 2 May 2005; accepted 3 May 2005
Abstract—c-Butyltelluro-2-butanol was reacted with 2 equiv of n-butyllithium. Both tellurium/lithium exchange and the proton
abstraction reactions took place in a single step and the lithium dianion intermediate efficiently reacted with aldehydes and ketones,
producing the corresponding diols.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Elemental tellurium reacts with Grignard1 or organo-
lithium2 reagents, producing the corresponding organo-
metallic tellurolate, which react with electrophiles,
leading to symmetrical and unsymmetrical tellurides.3–5
Organic tellurides can be transformed into the corre-
sponding lithium derivatives through a tellurium/lithium
exchange reaction.6 It was found that this is one of the
fastest metalloid/lithium exchange reactions.7
homoenolate 3a, that was reacted with benzaldehyde.
The lithium intermediate 3a was also transformed into
the functionalized higher order cyanocuprate 3b by reac-
tion with CuCNÆ2LiCl and reacted with enones (Scheme
1).10
Herein we describe the chemoselective reduction of iso-
lated telluride 1 to the corresponding c-butyltelluro
alcohol 211 and its transformation into the 1,4-dianion
intermediate 4. Alternatively, 2 was produced in a one-
pot procedure by sequential Michael addition of butyl-
tellurol to methyl vinyl ketone followed by in situ
carbonyl reduction of the resulting b-butyltelluro
ketone.12 By the last procedure, the alcohol 2 was gener-
ated in 70% isolated yield.
Organolithium compounds are probably the most popu-
lar organometallic species, due to their excellent nucleo-
philic character. Their importance and versatility8 are
not only due to their capacity to act as nucleophile or
base, but also to their ability to be converted into other
reactive organometallics by transmetallation. Basically,
every metal more electronegative than lithium can be
used for this purpose.
O
TeBu
M
ref. 10
O
O
a
86%
Aiming to develop more efficient synthetic processes
based in organotellurium chemistry, we are exploring
the preparation of functionalized organolithium inter-
mediates by tellurium/lithium exchange. Recently, we
have generated b-butyltelluro carbonyl compounds by
the Michael addition of n-butyltellurol to a,b-unsatu-
rated ketones (e.g., 1).9 Compound 1 was transformed
into the corresponding ketal and submitted to a tellu-
rium/lithium exchange producing the masked lithium
1
3
b
Te0
85%
Li
OLi
this work
OH TeBu
a, b
70%
2
4
a: 1)n-BuLi
2) H2O
M = Li, (3a)
1/2Cu(CN)Li2, (3b)
3) methyl vinyl ketone
b: 1) NaBH4
Keywords: Tellurium/lithium exchange; 1,4-Dianion and diols.
*
Scheme 1. Conversion of tellurides into organometallic reactive
species.
Corresponding author. Tel./fax: +55 (011) 3091 2176; e-mail:
alcindo@iq.usp.br
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.002

4424
J. L. Princival et al. / Tetrahedron Letters 46 (2005) 4423–4425
OH
OH
Ph
Ph
OH TeBu
O
a: 2 Eq n-BuLi / THF
6a, 92%
6d, 74%
OH
OH
OH
OH
OH
OH
2
a
°
- 70 C
b: RCOR1 (5a-f)
OH
OH
Ph
6e, 73%
6b, 89%
OH
Li
OLi
b
OH
OH
R
R1
4
6a-f
OH
6c, 77%
6f, 63%
Scheme 2. Reaction of lithium dianion with aldehydes and ketones.
Cohen reported the generation of dilithio intermediates
like 4 by sequential treatment of phenylthiocarbinols
with butyllithium and lithium di-tert-butylbiphenylide
(Li-DTBB).13 Butyllithium promotes the deprotonation
of the hydroxy unit and the pre-generated Li-DTBB per-
forms the reductive lithiation of the phenylsulfide rest.
the tellurium/lithium exchange step is totally compatible
with all subsequent operations and can be easily re-
moved in an odorless operation by washing of the or-
ganic phase with a diluted sodium hypochlorite solution.
In conclusion, we showed that a functionalized organoli-
thium can be easily prepared from an organotelluride
obtained from commercially available elemental tellu-
rium, n-butyllithium and methyl vinyl ketone.
In this work the reactive 1,4-dianion 4 was generated in
a single operation by reacting c-butyltelluro alcohol 2
with 2 equiv of commercially available n-butyllithium.
Both aldehydes and ketones reacted with 4 affording
the corresponding diols in good yields (Scheme 2).14
Acknowledgements
The authors thank FAPESP, CAPES and FACEPE for
´
support and Petroflex Indu´stria e Comercio S.A. (Re-
cife-Br) for a generous gift of n-butyllithium.
Preliminary studies using equimolar amounts of both
dianion 4 and the eletrophiles, afforded the desired diols
6a–f only in moderated yields (38–63%). Substantial in-
creases of yields were obtained by using 2 equiv of 4 rel-
ative to 5. The 1,2-addition reaction worked very well
even using ketones as the eletrophile. Diols 6a and b,
are analogs of 4-ipomeanol, a naturally occurring pneu-
motoxin under development for treatment of lung
cancer.15
References and notes
1. Haller, W. S.; Irgolic, K. J. J. Organomet. Chem. 1972, 38,
97.
2. Engman, L.; Cava, M. P. Synth. Comm. 1982, 12, 163.
3. Clive, D. L. J.; Chittattu, G. J.; Farina, V.; Kiel, W. A.;
Menchen, S. M.; Russell, C. G.; Singh, A.; Wong, C. K.;
Curtis, N. J. J. Am. Chem. Soc. 1980, 102, 4438.
4. Dabdoub, M. L.; Dabdoub, V. B.; Comasseto, J. V.;
Petragnani, N. J. Organomet. Chem. 1987, 308, 211.
5. Comasseto, J. V.; Lang, E. S.; Ferreira, J. T. B.; Simonelli,
F.; Correia, V. R. J. Organomet. Chem. 1987, 334, 329.
6. (a) Comasseto, J. V.; Barrientos-Astigarraga, R. Aldri-
chim. Acta 2000, 33, 66; (b) Petragnani, N.; Stefani, H. A.
Tetrahedron 2005, 61, 1613.
The diols 6a–d were cyclized by reacting with catalytic
amount of p-TSA in dichloromethane yielding the corre-
sponding tetrahydrofurans (Scheme 3).16
The reaction of dianion 4 with a range of other electro-
philes is under investigation in order to obtain function-
alized compounds such as spiroketals and chiral diols.
The tellurides described here are stable odourless yellow
oils and can be easily generated in a one-pot procedure
from elemental tellurium. Dibutyltelluride produced in
7. Reich, H. J.; Green, D. P.; Phillips, N. H.; Borst, J. P.;
Reich, I. L. Phosphorus Sulfur Silicon Relat. Elem. 1992,
67, 83.
´
8. (a) Chinchilla, R.; Najera, C.; Yus, M. Tetrahedron 2005,
61, 3139; (b) Foubelo, F.; Yus, M. Tetrahedron: Asym-
´
metry 1996, 7, 2911; (c) Najera, C.; Yus, M. Curr. Org.
Chem. 2003, 7, 867.
O
O
Ph
Ph
O
9. Zinn, F. K.; Righi, V. E.; Luque, S. C.; Formiga, H. B.;
Comasseto, J. V. Tetrahedron Lett. 2002, 43, 1625.
10. Dos Santos, A. A.; Comasseto, J. V. J. Braz. Chem. Soc.
2005, 16, 11.
R1
R
OH
a
O
7a, 74%
7c, 77%
OH
R1
O
O
Ph
Ph
11. Reduction of 4-(butyltelluro)butan-2-one (1) to 4-(butyl-
telluro)butan-2-ol (2): to a round bottomed flask were
added the telluride 1 (5 mmol, 1.28 g) and ethanol
(20 mL). To the resulting solution was added dropwise
an ethanolic solution of NaBH4 (5.5 mmol, 0.21 g in 6 mL
ethanol). The mixture was stirred at room temperature
and the progress of the reaction was monitored by TLC.
6a-d
7a-d
R
a: cat. p-TSA,
7b, 89%
7d, 85%
CH2Cl2
Scheme 3. Cyclization reaction of diols 6a–d to the corresponding
tretrahydrofurans.

J. L. Princival et al. / Tetrahedron Letters 46 (2005) 4423–4425
4425
The reaction mixture was quenched with water (50 mL)
and diluted with a mixture of ethyl acetate–hexane 1:1
(50 mL). The phases were separated and the aqueous
phase was extracted with a mixture of ethyl acetate–
hexane (1:1, 2 · 50 mL). The organic phases were com-
bined, dried with magnesium sulfate, filtered and the
solvents were removed under reduced pressure. The
residue was purified by silica gel column chromatography
eluting with a mixture of hexane–ethyl acetate (15:1), to
give 4-(butyltelluro)butan-2-ol (2); yield: 1.09 g, (85%); 1H
NMR: (200 MHz, CDCl3, ppm) d 0.85 (t, J = 7.2 Hz, 3H);
1.13 (d, J = 6.3 Hz, 3H); 1.31 (sext, J = 7.2 Hz, 2H); 1.65
(quint, J = 7.2 Hz, 2H); 1.76–1.85 (m, 2H); 2.53–2.69 (m,
4H); 3.75 (sext, J = 6 Hz, 1H); 13C NMR: (50 MHz,
CDCl3, ppm) d À2.3; 2.7; 13.4; 23.2; 25.0; 34.2; 41.1; 69.1;
LRMS m/z (rel. int.) 260 (M++2, 13); 258 (M+, 13); 256
(7); 255 (3); 254 (2); 215 (3); 186 (8); 72 (5); 57 (73); 55
(100); 45 (44); 125Te NMR (CDCl3, 157.79 MHz/298 K/
Ph2Te2) d (ppm) 251.43.
in hexanes) was added dropwise. The solution was stirred
at the same temperature for 20 min and benzaldehyde
(0.053 g, 0.5 mmol) was added. The reaction solution was
warmed to 0 ꢁC and a saturated solution of NH4Cl (1 mL)
was added. The mixture was transferred to a separatory
funnel and the aqueous phase was extracted with ethyl
acetate (3 · 5 mL). The organic phases were combined,
washed with a diluted sodium hypochlorite solution, dried
with magnesium sulfate, filtered and the solvents were
removed under reduced pressure. The residue was purified
by silica gel chromatography eluting with cyclohexane
then with a gradient of ethyl acetate–cyclohexane (2:1), to
give 6b, 1-phenylpentane-1,4-diol (CAS. 38299-94-4), as a
diastereomeric mixture; yield: 0.08 g, (89%); 1H NMR:
(200 MHz, CDCl3, ppm) d 1.12 (d, J = 6.3 Hz, 3H); 1.13
(d, J = 6.3 Hz, 3H); 1.39–1.58 (m, 2H); 1.75–1.85 (m, 2H);
3.70–3.83 (m, 1H); 4.61 (t, J = 5.1 Hz 1H); 4.66 (t,
J = 6.0 Hz, 1H); 7.21–7.32 (m, 5H); 13C NMR: (50 MHz,
CDCl3, ppm) d 23.2; 23.5; 34.7; 34.9; 35.9; 36.1; 67.6; 68.1;
73.9; 74.5; 125.7; 125.8; 127.2; 127.3; 128.3; 144.6; 144.8;
LRMS m/z (rel. int.) 180 (M+, 20); 162 (35); 161 (44); 147
(22); 129 (16); 121 (21); 120 (77); 118 (31); 117 (53); 115
(15); 106 (100); 105 (63); 104 (30); 80 (20); 79 (80); 78 (47);
77 (70); 65 (11); 57 (17); 56 (59); 51 (47).
12. One-pot preparation of 4-(butyltelluro)butan-2-ol (2): to a
flame dried two necked flask under nitrogen atmosphere
were sequentially added elemental tellurium (5 mmol,
0.64 g) and THF (10 mL). Under vigorous stirring was
added dropwise a solution of n-butyllithium (5 mmol,
3.5 mL from 1.4 mol LÀ1 hexane solution). To the result-
ing light yellow solution was added deoxygenated water
(10 mmol, 0.18 mL). The mixture was stirred for 5 min
and then methyl vinyl ketone (5 mmol, 0.35 g, 0.4 mL) was
added in one portion. The resulting red mixture was
stirred for 30 min and then an aqueous solution of NaBH4
(6 mmol, 0.22 g; 6 mL of a 1 mol LÀ1) was added by
means of a dropping funnel. The progress of reaction was
monitored by TLC then diluted with water (20 mL) and a
mixture of ethyl acetate–hexane 1:1 (50 mL). The phases
were separated and the aqueous phase was washed with a
mixture of ethyl acetate–hexane (1:1, 2 · 50 mL). The
organic phases were combined, dried with magnesium
sulfate, filtered and 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 4-(butyltelluro)butan-2-ol (2); yield:
0.89 g, (70%).
15. (a) Desai, D.; Nunes, M.; Chang, L.; Lin, J.-M.; Jiao, D.;
Amin, S. Cancer Lett. 1995, 97, 155; (b) Desai, D.; Chang,
L.; Amin, S. Cancer Lett. 1996, 108, 263.
16. Typical procedure for the cyclization of diols to the
corresponding tetrahydrofurans: to a round bottomed
flask containing the diol 6b (1 mmol, 0.18 g) in dichloro-
methane (3 mL) was added p-TSA (10 mg). The solution
was refluxed for 12 h then diluted with a mixture of
hexane–ethyl acetate (5 mL, 1:1) and washed with brine
(2 · 3 mL). The organic phase was dried with magnesium
sulfate, filtered and the solvents were removed under
reduced pressure. The residue was purified by silica gel
chromatography eluting with cyclohexane–ethyl acetate
(30:1), to give 7b, tetrahydro-2-methyl-5-phenylfuran
(CAS. 4457-59-4), as a diastereomeric mixture; yield:
1
0.14 g, (89%); H NMR: (300 MHz, CDCl3, ppm) d 1.33
(d, J = 6.0 Hz, 3H); 1.38 (d, J = 6.0 Hz, 3H); 1.55–1.95 (m,
2H); 2.04–2.44 (m, 2H); 4.13–4.42 (m, 1H); 4.89 (t,
J = 7.2 Hz 1H); 5.05 (dd, J = 8.4, 6.6 Hz, 1H); 7.23–7.39
(m, 5H); 13C NMR: (75 MHz, CDCl3, ppm) d 21.3; 21.5;
33.0; 34.2; 34.6; 35.6; 75.8; 75.9; 80.2; 80.9; 125.5; 125.8;
126.9; 127.0; 128.0; 128.2; 143.4; 143.9; LRMS m/z (rel.
int.) 180 (M+, 20); 162 (35); 161 (44); 147 (22); 129 (16);
121 (21); 120 (77); 118 (31); 117 (53); 115 (15); 106 (100);
105 (63); 104 (30); 80 (20); 79 (80); 78 (47); 77 (70); 65 (11);
57 (17); 56 (59); 51 (47).
13. (a) Ahn, Y.; Cohen, T. J. Org. Chem. 1994, 59, 3142; (b)
Liu, H.; Cohen, T. J. Org. Chem. 1995, 60, 2022; (c)
Cohen, T.; Tong, S. Tetrahedron 1997, 53, 9487.
14. Typical procedure for the preparation of the 1,4-dianion 4
and its reaction with aldehydes and ketones: To a round
bottomed flask containing the hydroxytelluride 2 (0.25 g,
1 mmol) in THF (5 mL) at À70 ꢁC under stirring, n-
butyllithium (1.57 mL, 2.2 mmol from 1.4 mol/L solution