The soft nucleophilicity of organotellurolates driving the S N2-type lactone ring-opening reaction

Article abstract of DOI:10.1016/j.tetlet.2009.09.023

Lithium and magnesium organotellurolates were reacted with lactones producing the corresponding tell-urocarboxylic acids. Treatment of the reaction mixture with lithium aluminum hydride allowed the isolation of the corresponding hydroxytellurides in a one-pot operation.

Full text of DOI:10.1016/j.tetlet.2009.09.023

Tetrahedron Letters 50 (2009) 6498–6501
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Tetrahedron Letters
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The soft nucleophilicity of organotellurolates driving the SN2-type lactone
ring-opening reaction
*
Márcio S. Silva, Alcindo A. Dos Santos, João V. Comasseto
Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cx.P. 26077, 05508-900 São Paulo, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Lithium and magnesium organotellurolates were reacted with lactones producing the corresponding tell-
urocarboxylic acids. Treatment of the reaction mixture with lithium aluminum hydride allowed the iso-
lation of the corresponding hydroxytellurides in a one-pot operation.
Received 3 August 2009
Revised 1 September 2009
Accepted 3 September 2009
Available online 9 September 2009
Ó 2009 Published by Elsevier Ltd.
Keywords:
SN2 lactone ring opening
Metal organochalcogenolates
Soft nucleophiles
One of the most expressive characteristics of chalcogenolate
anions is their soft nucleophilicity and low basicity.1 The lithium,
sodium, and magnesium chalcogenolates are able to undergo
SN2-type reactions in the presence of acidic functionalities, for
example, alcohols,2 allowing the incorporation of the chalcogen
moiety into organic substrates. This property of the metal chalco-
genolates associated with their peculiar reactivity has been ex-
plored in the preparation of multi-functionalized chalcogen
compounds, which can be submitted to further transformations
based on the rich chalcogen chemistry.3,4
For many years we have been devoting our attention to the
chemistry of organotellurides,5 and more recently we became
especially interested in applying these compounds as starting
materials for natural product synthesis, exploring their inherent
chemical properties.6
opening reactions by lithium organotellurolates,8 aiming to obtain
multifunctional building blocks with potential application in or-
ganic synthesis.
The most practical method to prepare metal tellurolates, which
has been extensively employed by us in recent years, is the direct
reaction of an organolithium or Grignard reagent with elemental
tellurium in THF at room temperature, so avoiding the manipula-
tion of bad-smelling alkaneditellurides.8
Reaction of metal organotellurolates with lactones in THF under
reflux gave the corresponding tellurocarboxylic acids.9 Treatment
of the reaction mixture with lithium aluminum hydride led to
the corresponding hydroxytellurides in a one-pot operation10
(Scheme 1).
Initially, screening was carried out looking for the best nucleo-
philic tellurium species for the lactone ring opening of the c-buty-
Organotellurium entities present a dual reactivity, that is, in
metal organotellurolates the tellurium atom behaves as a soft
nucleophile and in diorganotellurides it is attacked by nucleo-
philes, especially organolithiums, generating a new anionic center
at the carbon atom where the tellurium atom was originally at-
tached. This concept has been applied by us in the preparation of
functionalized organolithium reagents by Te/Li exchange, and
other organometallics by further transmetallation of the originally
obtained organolithiums.5,6 These organometallics have been used
in the synthesis of bioactive compounds.6,7
rolactone 1a (Table 1).
As can be seen in Table 1, n-butyltellurol, the supposed nucleo-
philic tellurium species resulting of the reaction of lithium n-butyl-
tellurolate with a proton source, failed to react with lactone 1a
even at long reaction times under reflux (Table 1, entries 1–3). So-
dium n-butyltellurolate generated in situ by reacting the bad-
smelling n-dibutylditelluride with sodium borohydride in THF
gave the desired product in 42% isolated yield (Table 1, entry 4).
Two equivalents of sodium n-butyltellurolate increased the yield,
but not satisfactorily (Table 1, entry 5). On the other hand, when
lithium n-butyltellurolate, prepared from elemental tellurium
and n-butyllithium in THF, was reacted with 1a, compound 4a
was isolated in 80% yield after 9 h under reflux (Table 1, entry 6).
Use of 1.5 and 2.0 equiv of the nucleophile did not improve signif-
icantly the product yield (Table 1, entries 7 and 8). The magnesium
In this work, taking advantage of the high soft character of the
metal organotellurolates, we performed SN2-type lactone ring-
* Corresponding author. Tel.: + 55 16 3351 8213; fax: + 55 16 3351 8350.
E-mail address: jvcomass@iq.usp.br (J.V. Comasseto).
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.09.023

M. S. Silva et al. / Tetrahedron Letters 50 (2009) 6498–6501
6499
Te 0
R
R
H3O+
R1
M
R1Te
R1Te
CO2H
OH
(
(
)
n
O
R
4
5
1
(2)
R TeM
R1Te
CO2M
O
( )
n
THF / Reflux
(
)
n
3
1) LiAlH4
2) H3O+
R
)
n
1
n = 1, 2, 3
M = Li, MgBr
Scheme 1. Lactone ring opening by metal organotellurolates and reduction of the obtained carboxylate to the corresponding alcohol.
Table 1
n-butyltellurolate presented reactivity similar to that of the lith-
ium analog (Table 1, entry 9).
Use of HMPA or 18-crow-6 ether did not improve the yields.
With these results in hands the best reaction conditions were ap-
plied to other lactones and metal organotellurolates. Table 2 sum-
marizes the results obtained.
Influence of the metal butyltellurolate in the ring-opening reaction of the
c
-butyrolactone 1a
O
O
nBuTeM
nBuTe
O
OH
Conditions
1a
4a
t (h)
Lithium and magnesium organotellurolates reacted with five,
six, and seven-member ring lactones in moderate to good yields
(Table 2, entries 1–8). Some 4-substituted five-member ring lac-
tones (Table 2, entries 7–10) were also reacted with metal
organotellurolates. Albeit lactone 1d underwent reaction with
both lithium and magnesium tellurolates in good yields (Table
2, entries 7 and 8), the more sterically hindered homologous 1e
and 1f failed to react in the same conditions (Table 2, entries 9
and 10).
As mentioned before, we are interested in developing functional-
ized tellurides aiming their use in the synthesis of biologically active
compounds. In this context, we developed extensive studies on the
preparation of C,O-dianions from hydroxytellurides.6,7 As an exten-
Entry
nBuTeM (equiv)
Conditionsc
Yield of 4a (%)
1
2
3
4
5
6
7
8
9
nBuTeLi (1.0)a
nBuTeLi (1.0)a
(nBuTe)2 (0.5)a
(nBuTe)2 (0.5)
(nBuTe)2 (1.0)
nBuTeLi (1.0)a
nBuTeLi (1.5)a
nBuTeLi (2.0)a
nBuTeMgBr (1.5)b
THF/H2O
THF/EtOH
EtOH/NaBH4
THF/NaBH4
THF/NaBH4
THF
THF
THF
THF
24
24
24
12
12
9
9
8
10
—
—
—
42
55
80
86
88
82
a
b
c
Generated by reacting elemental tellurium with n-butyllithium.
Generated by reacting elemental tellurium with n-butylmagnesium bromide.
Reactions performed at room temperature gave 4a in low yields.
Table 2
Tellurocarboxylic acids prepared by lactone ring opening
Entry
1
RTeM (reaction time, h)
Lactone
O
Product
Yielda (%)
86
OH
O
n-BuTe
nBuTeLi (2a) (9)
O
4a
4b
1a
OH
C6H5Te
n-BuTe
2
3
4
C6H5TeMgBr (2b) (10)
78
88
77
O
O
O
O
2a (8)
OH
4c
1b
O
o-Me-C6H4TeMgBr (2c) (10)
o-MeC6H4Te
n-BuTe
OH
4d
O
O
OH
5
6
2a (12)
60
O
4e
1c
OH
p-MeOC6H4Te
p-MeO-C6H4TeMgBr (2d) (12)
68
O
4f
(continued on next page)

6500
M. S. Silva et al. / Tetrahedron Letters 50 (2009) 6498–6501
Table 2 (continued)
Entry
RTeM (reaction time, h)
Lactone
Product
Yielda (%)
80
O
O
OH
n-BuTe
7
8
2a (10)
O
1d
4g
OH
o-MeC6H4Te
2c (11)
2a (24)
2a (24)
68
—
O
4h
3
O
O
9
1e
41
C6H5
O
O
C6H5
OH
n-BuTe
10
—
O
1f
4j
a
Isolated yields.
Table 4
Hydroxytellurides prepared
sion of these studies it would be interesting to transform the organyl
tellurocarboxylic acids 2 into hydroxytellurides 5 (Table 3).
To this end, initially several reducing agents were tested to
transform 3 into 5c, as shown in Table 3.
Stoichiometric or excess amounts of sodium borohydride under
reflux gave the hydroxyl telluride 5c in only modest yields (Table 3,
entries 1 and 2). Under similar conditions the use of DIBAL-H led to
the desired product in better yields (Table 3, entries 3 and 4). How-
ever lithium aluminum hydride gave the best results (Table 3, en-
tries 5–7) allowing the preparation of 5c in a one-pot process in
75% yield when 0.8 equiv of LiAlH4 was used. When higher
amounts of LiAlH4 were used lower yields were obtained (Table
3, entries 5 and 6).
The conditions employed for entry 7 (Table 3) were applied in
the preparation of hydroxytellurides 5a–5e as presented in Table 4.
Only moderated yields were achieved in the reaction of lactones
1c and 1d with lithium n-butyltellurolate (Table 4, entries 4 and 5).
By using phenyltelluro magnesium bromide as the nucleophile in
the reaction with lactone 1a compound 5a was obtained in 65%
isolated yield, after treating the reaction medium with LiAlH4 (Ta-
Entry RTeM (reaction time, h) Lactone Product
Yielda (%)
65
C6H5Te
OH
1
2
3
4
5
2b (15)
2a (15)
2a (15)
2a (20)
2a (17)
1a
1a
1b
1c
1d
4
5a
n-BuTe
OH
OH
72
75
50
58
4
5b
n-BuTe
5
5c
n-BuTe
OH
6
5d
ble 4, entry 1). The carboxylate, produced by opening c-valerolac-
OH
n-BuTe
3
5e
Table 3
One-pot reduction of carboxylates to the corresponding alcohols
a
Isolated yields.
nBuTe
OH
5c
Te 0
nBuLi
tone1b with 2a, was reduced in situ to the corresponding alcohol 5c
in 75% isolated yield (Table 4, entry 3).
reducing agents
O
As mentioned before, the Te/Li exchange reaction is one of the
most synthetically useful reactions of the organotellurium com-
pounds. In view of this fact, we submitted the prepared hydroxy-
tellurides to the reaction conditions for this transformation. The
hydroxytellurides 5b and 5c were treated with n-butyllithium
in THF and then octanal (6) was added to the reaction mixture.
In the case of compound 5b, the diol 7a was obtained in 75%
yield. Under the same reaction conditions 5c failed to react, being
recovered unchanged on the work-up. When 5c was transformed
into the corresponding THP ether, the Te/Li exchange was suc-
cessful, leading to compound 7b in 69% yield on reaction with 6
(Scheme 2).
O
[nBuTeLi]
O
nBuTe
OLi
THF, reflux
3
1b
Entry
Reducing agent (equiv)
Reaction time (h)
Yield (%)
1
2
3
4
5
6
7
NaBH4 (1.0)
NaBH4 (1.5)
DIBAL-H (1.0)
DIBAL-H (1.5)
LiAlH4 (1.0)
LiAlH4 (1.5)
LiAlH4 (0.8)
12
12
5
5
8
30
36
52
60
65
50
75
5
8

M. S. Silva et al. / Tetrahedron Letters 50 (2009) 6498–6501
6501
Comasseto, J. V.; Dos Santos, A. A. J. Braz. Chem. Soc. 2008, 19, 811–812; (e)
Comasseto, J. V.; Gariani, R. A. Tetrahedron 2009, 65, 8447–8459; (f) Ferrarini, R.
S.; Comasseto, J. V.; Dos Santos, A. A. Tetrahedron: Asymmetry, 2009.
doi:10.1016/j.tetasy.2009.08.003.
OH
(
1) nBuLi
Yield (%)
n-BuTe
OR
RO
(
)
)
6
n= 4; R= H
n= 5; R= H
75 (7a)
0
n= 5; R= THP 69 (7b)
O
n
2)
n
5
7
7. As far as we know, there is just one report in the literature describing the
lactone ring opening by phenyltellurotrimethylsilane. Contrary to our
approach, the reported ring opening employs a Lewis acid as catalyst Sasaki,
K.; Aso, Y.; Otsubo, T.; Ogura, F. Tetrahedron Lett. 1985, 26, 453–456.
(
)
6
H
6
8. Comasseto, J. V.; Gariani, R. A.; Princival, J. L.; Dos Santos, A. A.; Zinn, F. K. J.
Organomet. Chem. 2008, 693, 2929–2936 and references therein.
Scheme 2. Te/Li exchange reaction and capture of the corresponding organolithium
with 6.
9. Typical procedure for the lactone ring opening by lithium n-butyltellurolate. 4-(n-
butyltellanyl)butanoic acid (4a). To a dry two-necked 50 mL round-bottomed
flask equipped with magnetic stirring, reflux condenser, and a rubber septum
under nitrogen, was added elemental tellurium (0.51 g, 4.0 mmol) previously
dried overnight in an oven at 100 °C. Then dry tetrahydrofuran (15 mL) was
added. To the stirred suspension was added n-butyllithium (2.9 mL, 1.4 M in
hexane). The mixture was then heated to 80 °C and the lactone 1a (0.22 g,
2.6 mmol) was added all at once. The reaction was monitored by gas
chromatography. After 9 h at 80 °C the reaction medium was allowed to
reach the room temperature and then it was diluted with AcOEt (20 mL) and
washed with saturated solution of NH4Cl (15 mL). The phases were separated
and the aqueous phase was extracted with AcOEt (2 Â 20 mL). The organic
phase was dried over MgSO4 and the solvents were evaporated under reduced
pressure. The residue was purified by flash column chromatography eluting
first with hexane to remove dibutylditelluride and then with hexane/AcOEt
(8:2) to remove the product. Yield: 0.61 g (86%). 1H NMR: (300 MHz, CDCl3,
ppm) d 10.79 (br s, 1H); 2.66 (t, J = 7.5 Hz, 2H); 2.65 (t, J = 7.5 Hz, 2H); 2.48 (t,
J = 7.2 Hz, 2H); 2.06 (quint., J = 7.5 Hz, 2H); 1.73 (quint., J = 7.2 Hz, 2H); 1.38
(sext., J = 7.5 Hz, 2H); 0.92 (t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3, ppm) d
179.43; 36.10; 34.28; 27.12; 25.07; 13.41; 2.83; 1.10. LRMS m/z (rel. int.) 274
(M+, 15); 87 (100); 57 (54); 41 (70). IR mmax (neat) 3053, 2957, 1646, 1370.
10. Typical procedure for the reduction of the organotelluro carboxylic acids. 4-
(Phenyltellanyl)but-1-ol (5a) (one-pot procedure). To a dry two-necked 50 mL
round-bottomed flask equipped with magnetic stirring, reflux condenser, and a
rubber septum under nitrogen, was added elemental tellurium (0.51 g,
4.0 mmol) previously dried overnight in an oven at 100 °C. Then dry
tetrahydrofuran (15 mL) was added. To the stirred suspension was added
phenylmagnesium bromide (2.9 mL, 1.4 M in hexane). The mixture was then
heated to 80 °C and the lactone 1a (0.22 g, 2.6 mmol) was dissolved in THF
(5 mL) and added all at once. The reaction was monitored by gas
chromatography. After heating at 80 °C for 10 h, LiAlH4 (0.079 g, 2.1 mmol)
was added in small portions. After 5 h at 80 °C the reaction mixture was
allowed to reach the room temperature and then it was diluted with AcOEt
(30 mL), treated with NaOH (1 mL, 1 M), and filtered under vacuum. The
organic phase was washed with saturated solution of NH4Cl (15 mL). The
phases were separated and the organic phase was washed with AcOEt
(2 Â 20 mL). The organic phase was dried with MgSO4, filtered, and the
solvent was evaporated. The residue was purified by column flash
chromatography eluting first with hexane to remove diphenylditelluride and
then with hexane/AcOEt (8:2) to remove the product. Yield: 0.47 g (65%). 1H
NMR: (300 MHz, CDCl3, ppm) d 7.71 (dd, J = 6.9 Hz and 1.2 Hz, 2H); 7.16–7.29
(m, 3H); 3.61 (t, J = 6.3 Hz, 2H); 2.91 (t, J = 7.5 Hz, 2H); 2.31 (br s, 1H); 1.87
(quint., J = 7.2 Hz, 2H); 1.63 (quint., J = 6.6 Hz, 2H). 13C NMR (75 MHz, CDCl3,
ppm) d 138.31; 129.13; 127.53; 111.63; 62.03; 34.77; 28.08; 8.23. LRMS m/z
(rel. int.) 280 (M+, 18); 73 (96); 55 (100); 43 (48). IR mmax (neat) 3372, 2930,
1059, 732, 691.
Finally, it must be pointed out that all the organotellurides pre-
pared in this work, except dibuylditelluride and dibutyltelluride,
are not bad smelling and are stable to air and light.
In conclusion, a practical method to prepare organotellurocarb-
oxylic acids in a single operation has been developed by using in
situ-generated metal organotellurolates in a SN2-type reaction
with lactones. In addition, the intermediate organyl telluride car-
boxylates can be directly reduced to the corresponding hydroxyl
tellurides, which are synthetic equivalents of the corresponding
organolithiums by Te/Li exchange reaction.
Acknowledgments
The authors thank FAPESP, CNPq, and CAPES for financial
support.
References and notes
1. (a) Liotta, D.; Markiewicz, W.; Santiesteban, H. Tetrahedron Lett. 1977, 18,
4365–4367; (b) Liotta, D.; Santiesteban, H. Tetrahedron Lett. 1977, 18, 4369–
4372; (c) Scarborough, R.; Smith, A. B. Tetrahedron Lett. 1977, 18, 4361–4364;
(d) Gunther, W. H. J. Org. Chem. 1966, 31, 1202–1205; (e) Liotta, D.; Sunay, U.;
Santiesteban, H.; Markiewicz, W. J. Org. Chem. 1981, 46, 2605–2610.
2. Princival, J. L.; Dos Santos, A. A.; Comasseto, J. V. unpublished results.
3. Gariani, R. A.; Keppler, A. F.; Lopes, D. G.; Comasseto, J. V. Tetrahedron Lett.
2009, 50, 2181–2184 and references therein.
4. (a) Comasseto, J. V.; Barrientos-Astigarraga, R. E. Aldrichim. Acta 2000, 33, 66–
78; (b) Petragnani, N.; Stefani, H. Tetrahedron 2005, 61, 1613–1679; (c) Zeni, G.;
Lüdtke, D. S.; Panatieri, R. B.; Braga, A. L. Chem. Rev. 2006, 106, 1032–1076; (d)
Comasseto, J. V.; Clososki, G. C.; Cunha, R. L. O. R.. In Tellurium in: Comprehensive
Organometallic Chemistry III; Mingos, D. M. P., Crabtree, R. H., Eds.; Elsevier:
Amsterdam, 2007; Vol. 9, pp 587–648.
5. (a) Dos Santos, A. A.; Wendler, E. P. Synlett 2009, 7, 1034–1040. and references
therein; (b) Comasseto, J. V.; Dos Santos, A. A. Phosphorus, Sulfur Silicon Relat.
Elem. 2008, 183, 939–947.
6. (a) Dos Santos, A. A.; Ferrarini, R. S.; Princival, J. L.; Comasseto, J. V. Tetrahedron
Lett. 2006, 47, 8933–8935; (b) Dos Santos, A. A.; Princival, J. L.; Comasseto, J. V.;
De Barros, S. M. G.; Neto, J. E. B. Tetrahedron 2007, 63, 5167–5172; (c) Bassora,
B. K.; Da Costa, C. E.; Gariani, R. A.; Comasseto, J. V.; Dos Santos, A. A.
Tetrahedron Lett. 2007, 48, 1485–1487; (d) Ferrarini, R. S.; Princival, J. L.;