Tellurium/lithium exchange reactions in the synthesis of spiroketals and 1,6-dioxygenated systems

Article abstract of DOI:10.1016/j.tet.2007.03.178

1,4-C,O-dianions have been generated through concomitant acid/base and tellurium/lithium exchange reactions. The di-lithium salts were transmetallated with cerium chloride to the corresponding di-cerium salts and subsequently reacted with lactones and carboxylic acid anhydrides to yield the respective spiroketals. The di-lithium entities were also converted into the corresponding cyanocuprates that add in a 1,4-manner to 2-cyclohexen-1-one to form 1,6-dioxygenated compounds.

Full text of DOI:10.1016/j.tet.2007.03.178

Tetrahedron 63 (2007) 5167–5172
Tellurium/lithium exchange reactions in the synthesis of
spiroketals and 1,6-dioxygenated systems
b
b
Alcindo A. Dos Santos,a, Jefferson L. Princival, Joao V. Comasseto,
*
~
Simone M. G. de Barros and Jose E. Brainer Neto
c
c
ꢀ
aDepartamento de Quꢀımica, Universidade Federal de Sa~o Carlos, 13565-905 Sa~o Carlos, SP, Brazil
bInstituto de Quꢀımica, Universidade de Sa~o Paulo, C. P. 26077, 05599-070 Sa~o Paulo, SP, Brazil
cDepartamento de Quꢀımica Fundamental, Universidade Federal de Pernambuco, 50740-540 Recife, PE, Brazil
Received 6 March 2007; revised 29 March 2007; accepted 30 March 2007
Available online 6 April 2007
Abstract—1,4-C,O-dianions have been generated through concomitant acid/base and tellurium/lithium exchange reactions. The di-lithium
salts were transmetallated with cerium chloride to the corresponding di-cerium salts and subsequently reacted with lactones and carboxylic
acid anhydrides to yield the respective spiroketals. The di-lithium entities were also converted into the corresponding cyanocuprates that add
in a 1,4-manner to 2-cyclohexen-1-one to form 1,6-dioxygenated compounds.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Recent interest in the biological activities of spiroketal
compounds has lead to the development of a number of stra-
tegies for the synthesis of this ring system.1,2 The principal
route to 1 involves the acid-catalysed cyclisation of dihy-
droxy ketones 2 or their equivalents (Scheme 1).1
The spiroketal ring system (1, Scheme 1) is a subunit that is
found in naturally occurring compounds derived from a wide
variety of different sources including bacteria, fungi, plants
and insects.1 Although the subunit may be encountered both
in structurally very simple and in highly complex molecules,
the majority of natural products bearing the spiroketal
moiety comprises 1,7-dioxaspiro[5.5]undecane, 1,6-dioxa-
spiro[4.5]decane or 1,6-dioxaspiro[4.4]nonane ring sys-
tems.1,2 Moreover, such systems are also present in most
of the pheromones that possess a spiroketal ring,1 and hence
much of the research in this area has focused on these spe-
cific structural classes.
A useful approach to the synthesis of 2 involves organo-
metallic species, particularly organolithium compounds, of
the type 3 (Scheme 1). Various methods are available for
the preparation of appropriate organolithium analogues, the
most common of which involves halogen/lithium or tin/lith-
ium exchange.3 Organolithium species can be subsequently
transformed into other organometallics by transmetallation
with salts of metals that are more electronegative than
lithium. Formation of organolithium compounds via
tellurium/lithium exchange appears to offer a number of ad-
vantages over alternative methods in that it is both fast and
clean.4 However, this methodology is not often employed,
probably as a consequence of negative comments in the
literature concerning the unpleasant odour and the relative
instability of organotellurium compounds. As we have
pointed out recently, these comments do not always apply.5
O
O
O
m
n
m
n
OH
OH
2
1
M
M
O
O
M = Li, ...
m
n
We have previously demonstrated that the functionalised
alkyltellurides 4 and 5 are efficient precursors of homoeno-
lates 66,7 and dianionic species 78 (Scheme 2). In the present
study, we have employed the lithium salts 7 and 7a (derived
from hydroxy tellurides 5 and 5a, respectively) as precursors
of 1,6-[4.4]-spiroketals and 1,6-hydroxy-ketones in a reac-
tion sequence involving transformation of the initially ob-
tained lithium compounds into cerium and copper species.
3
Scheme 1.
Keywords: Organocerium; Tellurium/lithium exchange; Spiroketals.
* Corresponding author. Tel./fax: +55 16 3351 8299; e-mail: alcindo@dq.
ufscar.br
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.178

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A. A. Dos Santos et al. / Tetrahedron 63 (2007) 5167–5172
excess (ee) but in very low isolated yield (<5%). The obser-
1) n-BuLiref. 6,7
O
R
O
6a, M = Li
6b, M = 1/2CuCNLi LiCl
O
O
vation of a white powder in the reaction medium, coupled
with the poor yield obtained, suggested that 5 was probably
transformed into a telluroxide. This problem was solved by
performing the enzymatic resolution of 5 in THF in which
the acetate (R)-10 was produced in 36% yield and with
high enantioselectivity (>200). The unreacted alcohol could
be recovered in 30% yield and with a high ee (99%) (Scheme
4; Table 1).
.
.
2) CuCN 2LiCl
TeBu
TeBu
M
4
6
1) 2 Eq n-BuLiref. 8
OH
OLi
R
Li
7, R = Me
5, R = Me
5a, R = H
7a, R = H
Scheme 2.
OAc
CALB
solvent
Bu
Bu
Bu
Te OH
Te OH
Te OAc
2. Results and discussion
+
(S)-5
(R)-10
(R,S)-5
n-Butyltellurol, generated in situ from elemental tellurium
and n-butyllithium in the presence of a proton source such
as water or ethanol, reacts with methyl vinyl ketone to pro-
duce the corresponding b-butyltelluro ketone 8.9 This tellu-
ride can be transformed into the telluro-ketal 1 by reaction
with ethylene glycol in the presence of AmberlystÒ, and
into the hydroxy telluride 5 when treated with an ethanolic
or aqueous solution of sodium borohydride (Scheme 3).
Alternatively, 5 could be synthesised in 74% isolated yield
in a one-pot process by hydrotelluration of methyl vinyl
ketone and subsequent in situ reduction of 8 by the addition
of sodium borohydride to the reaction mixture. Hydroxy tel-
luride 5a could be prepared in 78% yield by hydrotelluration
of methyl acrylate (9), followed by reduction of the ester
group with lithium aluminium hydride. These protocols
complement our earlier studies on the reduction of butyltel-
luro carbonyl compounds to the corresponding alcohols.5
Scheme 4.
The absolute configurations of the chiral acetate 10 and of
the unreacted alcohol 5 obtained from the enzymatic process
were assigned indirectly by conversion of 10 into the natural
product g-valerolactone (11) (Scheme 5) followed by com-
parison of the optical rotation of the synthetic product with
literature data.11 Treatment of the 1,4-C,O-dianion, gener-
ated by the reaction of (R)-5 with 2 equiv of n-butyllithium
in THF, with carbon dioxide followed by an acid workup
yielded 11 in 52% isolated yield.
O
1) BuLi
2) CO2
Bu
Bu
K2CO3
MeOH
92%
Te OAc
Te OH
O
3) H3O+
52%
(R)-10
(R)-5
(R)-11: [α]2D3 = +30
(S)-11: lit. [α]2D3 = -26.7
d
O
O
O
Scheme 5.
TeBu
TeBu
a,b
a,c
4
TeBu
OH
The lithium salts 7 and 7a (Scheme 2) were transformed into
the cerium analogues by transmetallation with cerium tri-
chloride. These intermediates could be reacted with lactones
and anhydrides which, following acid workup, afforded the
corresponding spiroketals 1a–1g. Initially, these reactions
were performed according to the classical procedures for
the preparation of organocerium compounds, namely, gener-
ation of the organolithium compound followed by addition
of a suspension of cerium trichloride in THF.12 This process
is typically carried out at ca. ꢀ40 ꢁC, and often requires
a long reaction time (>1 h). In the present study, however,
mixtures of cerium trichloride and 5 or 5a in THF were
prepared at ꢀ70 ꢁC and then reacted with n-butyllithium
(Scheme 6). TLC analysis revealed that the hydroxy tellu-
ride was totally consumed within 5 min following the addi-
tion of n-butyllithium. The di-cerium salt was then added to
the appropriate lactone or anhydride in diethyl ether at
8
e
f
Te0
5
O
OH
5a
MeO
TeBu
TeBu
9
Scheme 3. (a) (1) n-BuLi; (2) H2O; (b) methyl vinyl ketone; (c) methyl
acrylate; (d) ethylene glycol, AmberlystÒ; (e) NaBH4 (aqueous solution);
(f) LiAlH4 (3 equiv).
The enzymatic kinetic resolution of hydroxy telluride 5 was
carried out using a typical procedure10 involving the sequen-
tial addition of Candida antarctica lipase-B (CALB) and
vinyl acetate to a racemic mixture of 5 dissolved in an
appropriate solvent (i.e., hexane or THF). In hexane, the chi-
ral acetate (R)-10 was obtained with a 96% enantiomeric
Table 1. Enzymatic resolution of hydroxy telluride (R,S)-5a
Entry Solvent Reaction time (h) Conversion (%) Enantiomeric excess (S)-5 (%) Enantiomeric excess (R)-10 (%) Yield (%) Enantioselectivity
1
2
3
4
Hexane
Hexane
THF
1
4
8
12
45
49
48
50
80
90
93
99
96
95
99
98
—
<5
120
THF
36
>200
a
Substrate (0.5 mmol); CALB 30 mg in hexane (10 mL) or 50 mg in THF (10 mL); temperature 30 ꢁC.

A. A. Dos Santos et al. / Tetrahedron 63 (2007) 5167–5172
5169
ꢀ70 ꢁC (Scheme 6; Table 2). This procedure is operationally
The volatile spiroketals 1e, 1f and 1g were isolated in pure
form but only in low yields (<30%), even after most careful
distillation of the solvent. This result is in agreement with
previous reports concerning this class of volatile com-
pounds.13
far simpler than that of previously published methods.
1) n-BuLi
(2 equivalents)
R1
Bu
O
Te OH
+ CeCl3
2) lactone or
anhydride
R
O
5, R = Me
5a, R = H
As a part of our studies concerning the preparation of func-
tionalised organometallics, the dianions 7 and 7a were also
converted into the corresponding cyanocuprates by reacting
with the complex CuCN$2LiCl (1/2 equivalent). The pre-
formed cyanocuprate14 was added to a solution of 2-cyclo-
hexen-1-one and the corresponding hydroxy ketones 13
and 13a were obtained, respectively, in isolated yields of
62 and 67% (Scheme 8).
R
1a-g
Scheme 6.
Reasonable yields of spiroketals were obtained using the de-
scribed protocols (Table 2). The mono-spiroketals 1c and 1d
were the only products formed even when 2 equiv of the di-
cerium salt were employed. In the case of spiroketals 1a, 1c,
1e and 1f, mixtures of E and Z stereomers were produced and
the quoted yields refer to the sum of the isomers.
Finally, it is noteworthy that, as has been the case for many
other tellurides prepared in our laboratory, those described
in the present study are light yellow oils and are either odour-
less or present a smell that is not more unpleasant than other
chemicals usually employed in organic synthesis. Moreover,
the compounds are stable under ambient conditions and can
be manipulated using normal procedures with no appreciable
decomposition. However, prolongedcontactof telluridesolu-
tions, especially those involving hexane, with air should be
avoided in order to prevent transformation of substrate into
telluroxide. This problem can be minimised through the use
of deoxygenated solvents. Tellurides are totally compatible
with many common functional group transformations, in-
cluding carbonyl reduction or protection, enzymatic and
chemical acylation and de-acylation. The applicability of
hydroxy tellurides as versatile sources of functionalised
organometallics has been amply demonstrated in the present
study.
In the synthesis of the chiral spiroketal 1e, (S)-g-valerolac-
tone (11; produced by the route shown in Scheme 5) was
reacted with the chiral di-cerium salt (R)-12 (derived from
(R)-5) with the inverse configuration. Compound 1e was
formed as a 1:1 mixture of E,Z- and Z,E-stereomers (Fig.
1B), whilst less than 3% of the other stereomers was detected
following chiral GC analysis (Scheme 7, Fig. 1A and B).
Table 2. Reaction of di-cerium salts with lactones and anhydrides
Entry
Substrate
Telluridea
Product
Yield (%)
O
O
1
5
65b
O
1a
O
O
3. Experimental section
3.1. General
O
O
2
3
5a
5
65b
1b
O
Tellurium metal (<200 mesh), lithium aluminium hydride,
sodium borohydride and cerium trichloride heptahydrate
were purchased from Sigma Aldrich. Immobilised lipase-B
from C. antarctica (CALB; Novozym 435Ò; 10,000 PLU/g)
was kindly donated by Novozymes Inc. All reagents and
solvents were previously purified and dried.15 THF was
distilled under nitrogen from sodium/benzophenone just
before use. n-Butyllithium was titrated using 1,10-phenan-
throline as indicator prior to use. Nitrogen gas was deoxy-
genated and dried. Cerium trichloride heptahydrate was
dried according to a reported procedure.16 All operations
were carried out in flame-dried glassware.
O
52b
1c
O
O
O
O
4
5a
5
56b
74c
1d
O
O
O
O
O
O
O
1e
5
6
O
O
66c
68d
Column chromatographic separations were performed over
Vetec silica gel 60 (0.063–0.200 mm; 70–230 mesh) or
Acros Organics silica gel (0.035–0.075 mm; pore diameter
ca. 6 nm). NMR spectra were recorded on Bruker model
AC-200 and Varian model FT-300 spectrometers with sam-
ples dissolved in deuterochloroform. The internal references
were TMS (1H NMR), the central peak of the deuterochloro-
form signal (13C NMR) and a capillary of diphenyl ditellur-
5
1f
O
O
7
5a
1g
O
a
n-Butyllithium was added to the mixture of hydroxy telluride and cerium
trichloride.
Isolated yield.
Yield determined by GC analyses (spiroketal 1g was employed as internal
b
c
ide 1 mol Lꢀ1 125Te NMR). IR spectra were recorded on
(
a Bomem MB-100 spectrophotometer, whilst optical rota-
tions were determined on a Jasco DIP 370 digital
standard).
Yield determined by GC analyses (spiroketal 1f was employed as internal
standard).
d

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A. A. Dos Santos et al. / Tetrahedron 63 (2007) 5167–5172
Figure 1.
1) BuLi
2) CeCl3
40 mmol) in dry THF (80 mL). Deoxygenated water
Bu
Bu
K2CO3
MeOH
Te OAc
Te OH
Cl
2Ce OCeCl2
(1.8 mL, 100 mmol) was added to the light yellow solution
of lithium butyl tellurolate so formed, and the resulting
red-brown mixture was stirred at room temperature for
10 min and subsequently cooled to 0 ꢁC. Methyl vinyl ke-
tone (3.32 mL, 40 mmol) was added in a single portion,
and the resulting mixture was stirred whilst being warmed
to room temperature. The progress of the reaction was mon-
itored by TLC. After stirring for 1 h at room temperature,
sodium borohydride (1.52 g, 40 mmol) was added to the
mixture, which was then gently warmed to 50 ꢁC. After a
reaction time of 10 min, all of the telluro ketone had been
converted into hydroxy telluride (as determined by TLC
analysis), and the resulting brown solution was cooled to
room temperature. Deoxygenated water (20 mL) was added
slowly over a period of 20 min, the reaction mixture was
shaken vigorously, a further 40 mL of deoxygenated water
was introduced and the phases were separated. The organic
phase was washed with saturated ammonium chloride solu-
tion (100 mL), and the aqueous phases were combined and
extracted with ethyl acetate (2ꢂ200 mL). The organic
phases were combined, dried over magnesium sulfate, fil-
tered and the solvent removed under reduced pressure. The
crude product was purified by CC over silica gel eluted
with cyclohexane/ethyl acetate (4:1) to yield 7.7 g (74%)
of oil 5 (CAS No. 861399-10-2).
(R)-10
(R)-5
(R)-12
O
1) BuLi
2) CO2
Bu
Te OH
O
3) H3O+
52%
(S)-5
96% e.e.
(S)-11
96% e.e.
O
O
+
O
O
(2R,5S,7S)-1e 1 : 1 (2R,5R,7S)-1e
(E,Z) (Z,E)
Scheme 7.
O
1) BuLi
2) CuCN 2LiCl
Bu
.
Te OH
O
R
R
3)
5, R = Me
5a, R = H
OH
13, R = Me, 62%
13a, R = H, 67%
Scheme 8.
3.1.2. One-pot procedure for the preparation of 3-(butyl-
tellanyl)propan-1-ol (5a). n-Butyllithium (1.69 mol Lꢀ1 in
hexane: 17.7 mL, 30 mmol) was added slowly at room tem-
perature to a suspension of elemental tellurium (3.83 g,
30 mmol) in dry THF (60 mL). Deoxygenated water
(1.35 mL, 75 mmol) was added to the light yellow solution
of lithium butyl tellurolate so formed, and the resulting
red-brown mixture was stirred at room temperature for
10 min and subsequently cooled to 0 ꢁC. Methyl acrylate
(2.7 mL, 30 mmol) was added in a single portion, and the re-
sulting mixture was stirred whilst being warmed to room
temperature. The progress of the reaction was monitored
by TLC. After stirring for 1 h at room temperature, the
polarimeter. Chiral GC analyses were performed on a Shi-
madzu GC-17A instrument coupled to a flame ionisation de-
tector and equipped with a Varian ChromopackÔ Chirasil-
Dex CB (b-cyclodextrin packing) capillary column (25 mꢂ
0.25 mm i.d.; 0.25 mm) with hydrogen as the carrier gas.
Mass spectra were recorded by coupling the GC to a Shi-
madzu model QP 5050A mass spectrometer.
3.1.1. One-pot procedure for the preparation of 4-(butyl-
tellanyl)butan-2-ol (5).8 n-Butyllithium (1.69 mol Lꢀ1 in
hexane: 23.7 mL, 40 mmol) was added slowly at room tem-
perature to a suspension of elemental tellurium (5.10 g,

A. A. Dos Santos et al. / Tetrahedron 63 (2007) 5167–5172
5171
reaction mixture was cooled to 0 ꢁC and lithium aluminium
hydride (3.4 g, 90 mmol) was added slowly in three portions
(0.5, 1.0 and 1.9 g, respectively). The mixture was warmed
to room temperature and then gently heated at 50 ꢁC. After
a reaction time of 20 min, all of the telluro ester had been
converted into hydroxy telluride (as determined by TLC
analysis), and the resulting mixture was cooled to 0 ꢁC. De-
oxygenated water (ca. 30 mL) was added slowly over a pe-
riod of 30 min, the resulting slurry was filtered and the
residue washed with diethyl ether (2ꢂ30 mL). The organic
phases were combined, washed with saturated ammonium
chloride solution (2ꢂ30 mL), dried over magnesium sulfate,
filtered and the solvent removed under reduced pressure. The
crude product was purified by CC over silica gel eluted with
cyclohexane/ethyl acetate (3:1) to afford 5.7 g (78%) of oil
5a—1H NMR (300 MHz, CDCl3), d (ppm): 0.89 (t,
added to a solution of hydroxy telluride (R)-5 (96% ee,
1.28 g, 5 mmol) dissolved in dry THF (25 mL) that had
been cooled to ꢀ70 ꢁC. The resulting light yellow solution
was stirred at ꢀ70 ꢁC for 5 min and dry carbon dioxide
gas was introduced, by means of a needle immersed into
the solution, producing a white gel after ca. 15 min. The
mixture was warmed to room temperature, hydrochloric
acid (50% v/v, 6 mL) was added, the whole stirred for
30 min at room temperature and the phases separated. The
aqueous phase was washed with ethyl acetate (2ꢂ5 mL),
and the combined organic phases dried over magnesium sul-
fate, filtered and the solvent removed by distillation. The re-
sulting residue was purified by CC over silica gel eluted with
hexane/ethyl acetate (1:1) to yield 0.26 g (52%) of the
colourless oil (R)-11 (CAS No. 58917-25-2).
3
3J¼7.2 Hz, 3H), 1.36 (sext, J¼7.2 Hz, 2H), 1.70 (quint,
3.1.6. General procedure for the preparation of spiro-
ketals. n-Butyllithium (1.4 mol Lꢀ1 in hexane: 2.87 mL,
4 mmol) was added slowly to a mixture of anhydrous cerium
chloride (0.98 g, 4 mmol) and hydroxy telluride 5 (0.51 g,
2 mmol) or 5a (0.48 g, 2 mmol) in dry THF (40 mL) that
had been cooled to ꢀ70 ꢁC. The whole was stirred at
ꢀ70 ꢁC for 2 h, warmed to ꢀ40 ꢁC, stirred for 1 h at this
temperature, re-cooled to ꢀ70 ꢁC and finally transferred
via a cannula to another flask containing a solution of the
appropriate carbonyl compound (lactone or anhydride,
2 mmol) in diethyl ether (5 mL). The resulting mixture
was stirred for 1.5 h at ꢀ70 ꢁC, warmed to room tempera-
ture, and hydrochloric acid (10% v/v, 20 mL) added with
constant stirring for 20 min. The phases were separated
and the aqueous phase was extracted with diethyl ether
(2ꢂ5 mL). The combined organic phases were washed,
dried and the solvent removed under reduced pressure (com-
pounds 1a–1d) or by distillation (volatile spiroketals 1e–1g).
In each case the resulting residue was purified by CC over
silica gel to produce the respective products.
3
3J¼7.5 Hz, 2H), 1.91–2.00 (m, 3H), 2.63 (t, J¼7.5 Hz),
2.66 (t, 3J¼7.5 Hz), 3.66 (t, 3J¼6.3 Hz); 13C NMR
(75 MHz, CDCl3), d (ppm): 2.1, 2.8, 13.3, 25.0, 34.2, 34.6,
63.9; 125Te NMR (157.79 MHz, 298 K, CDCl3), d (ppm):
244.45; MS, m/z (%): 246 (26%) [M2+], 244 (24%) [M+],
242 (15%), 240 (3%), 188 (6%), 186 (7%), 172 (23%),
170 (23%), 168 (13%), 144 (4%), 142 (2%), 130 (6%),
126 (4%), 57 (100%), 41 (86%): Anal. Calcd for
C7H16OTe: C, 34.49; H, 6.61. Found: C, 34.79; H, 6.56.
3.1.3. Enzymatic kinetic resolution of 4-(butyltellanyl)-
butan-1-ol (5). Hydroxy telluride 5 (0.13 g, 0.5 mmol) was
dissolved in 10 mL of deoxygenated hexane or THF, and vi-
nyl acetate (5 equiv) and CALB (0.03 g for hexane or 0.05 g
for THF) were added. The reaction mixture was stirred and
the course of the reaction was monitored by chiral GC. After
ca. 50% conversion had been achieved, the enzyme was
removed by filtration and the resulting solution was concen-
trated under reduced pressure. The organic residue was sub-
jected to CC over silica gel eluted with hexane/ethyl acetate
(4:1) to yield 0.019 g (30%) of an oil corresponding to the al-
cohol (S)-5 ([a]2D2 +7 (c 1.0, CH2Cl2); ee¼99%), and 0.027 g
(36%) of an oil corresponding to the acetate (R)-10—1H
NMR (300 MHz, CDCl3), d (ppm): 0.92 (t, J¼7.5 Hz, 3H),
1.23 (d, J¼6.3 Hz, 3H), 1.38 (sext, J¼7.5 Hz, 2H), 1.72
(quint, J¼7.5 Hz, 2H), 2.04 (s, 3H), 1.87–2.11 (m, 2H), 2.49–
2.67 (m, 4H); 13C NMR (75 MHz, CDCl3), d (ppm): 3.6, 2.8,
13.4, 19.5, 21.3, 25.0, 34.2, 38.8, 72.2, 170.6; 125Te NMR
(157.79 MHz, 300 K, CDCl3), d (ppm): 270.15; [a]2D2 +18
(c 1.0, CH2Cl2); ee¼98%. Anal. Calcd for C10H20O2Te: C,
40.05; H, 6.72. Found: C, 40.02; H, 6.53.
The oil 1a was obtained in a yield of 0.74 g (65%) follow-
ing elution with hexane/diethyl ether (7:1)—1H NMR
(300 MHz, CDCl3), d (ppm): 1.32 (d, 3J¼6.3 Hz, 1H), 1.41
(d, 3J¼6.0 Hz, 1H), 1.71–1.87 (m, 1H), 2.30–2.47 (m, 3H),
4.37 (sext, 3J¼6.0 Hz, 1H), 4.45 (sext, 3J¼6.3 Hz, 1H), 4.95
1
1
(d, J¼12.6 Hz, 1H), 4.98 (d, J¼12.6 Hz, 1H), 5.17 (d,
1J¼12.6 Hz, 1H), 5.22 (d, J¼12.6 Hz, 1H), 7.23–7.27 (m,
1
1H), 7.33–7.37 (m, 3H); 13C NMR (75 MHz, CDCl3), d
(ppm): 21.2, 22.4, 32.6, 32.8, 37.1, 38.5, 70.6, 70.7, 75.4,
77.2, 116.9, 117.0, 121.0, 121.9, 127.6, 127.7, 128.7, 139.4,
139.5, 139.9, 140.0; MS, m/z (%): 190 (22%) [M+], 175
(29%), 146 (35%), 135 (100%), 117 (16%), 105 (25%), 89
(21%), 77 (26%), 63 (10%), 51 (12%), 41 (11%). Anal. Calcd
for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.66; H, 7.53.
3.1.4. Hydrolysis of (R)-4-(butyltellanyl)butan-2-yl ace-
tate (10). Potassium carbonate (0.03 g, 0.2 mmol) was
added to telluride (R)-10 (0.30 g, 1 mmol) dissolved in
methanol (5 mL) and water (1 mL), and the mixture stirred
for 1 h at room temperature, diluted with water (5 mL) and
extracted with ethyl acetate (2ꢂ5 mL). The organic phase
was washed with brine (2 mL), dried over magnesium sul-
fate and the solvent removed under reduced pressure. The re-
sulting residue was purified by CC over silica gel eluted with
hexane/ethyl acetate (4:1) to yield 0.24 g (92%) of the light
yellow oil (R)-5.
The oil 1b (CAS No. 139697-84-0) was obtained in a yield
of 0.72 g (65%) following elution with hexane/diethyl ether
(7:1).
The oil 1c (CAS No. 180198-87-2) was obtained in a yield of
0.21 g (52%) following elution with hexane/ethyl acetate
(1:2).
The oil 1d (CAS No. 177780-65-3) was obtained in a yield
of 0.21 g (56%) following elution with hexane/ethyl acetate
(1:2).
3.1.5. Synthesis of (R)-(D)-g-valerolactone (11). n-Butyl-
lithium (1.4 mol Lꢀ1 in hexane: 7.15 mL, 10 mmol) was

5172
A. A. Dos Santos et al. / Tetrahedron 63 (2007) 5167–5172
Compound 1e (CAS No. 106356-13-2) was obtained in
a yield of 74% (determined by GC analysis with 1g as inter-
nal standard) following elution with pentane/diethyl ether
(5:1).
Acknowledgements
The authors wish to thank the Brazilian granting authorities
FAPESP, CAPES and CNPq for financial support. Generous
gifts of lipase and n-butyllithium from Novozymes Inc. and
Petroflex Inc., respectively, are gratefully acknowledged.
Compound 1f (CAS No. 5451-15-0) was obtained in a yield
of 66% (determined by GC analysis with 1g as internal stan-
dard) following elution with pentane/diethyl ether (5:1).
References and notes
Compound 1g (CAS No. 76041-89-9) was obtained in a yield
of 68% (determined by GC analysis with 1f as internal stan-
dard) following elution with pentane/diethyl ether (5:1).
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3.1.7. General procedure for the preparation of cyano-
cuprates from hydroxy tellurides 5 and 5a, and their
reaction with 2-cyclohexen-1-one. A solution of the appro-
priate dianion 7 or 7a (4 mmol; prepared similarly as de-
scribed in Section 3.1.5) was added to a solution of the
complex CuCN$2LiCl (1 mol Lꢀ1 in THF, 2 mL, 2 mmol)
that had been further diluted with THF (10 mL) and cooled
to ꢀ70 ꢁC. The resulting clear, light yellow solution was
stirred at ꢀ70 ꢁC for 1 h and then transferred via a cannula
to another flask containing 2-cyclohexen-1-one (0.2 g,
2 mmol) in THF (4 mL). The resulting mixture was stirred
at ꢀ70 ꢁC for 30 min, warmed to room temperature and
then diluted with ammonium hydroxide/ammonium chlo-
ride solution (10% m/v, 5 mL) and diethyl ether (5 mL).
The mixture was maintained under vigorous stirring for
30 min and the phases separated. The organic phase was
washed with brine (2ꢂ3 mL) and the aqueous phase was ex-
tracted with ethyl acetate (5 mL). The combined organic
phases were dried over magnesium sulfate, filtered and the
solvent removed under reduced pressure. In each case the re-
sulting residue was purified by CC over silica gel eluted with
ethyl acetate/hexane (3:1).
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61, 3139–3176; (b) Najera, C.; Sansano, J. M.; Yus, M.
Tetrahedron 2003, 59, 9255–9303.
4. (a) Comasseto, J. V.; Barrientos-Astigarraga, R. E. Aldrichimica
Acta 2000, 33, 66–78; (b) Petragnani, N. Tellurium in Organic
Synthesis; Best Synthetic Methods; Academic: London, 1994;
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Braga, A. L. Chem. Rev. 2006, 106, 1032–1076.
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The oil 13 was obtained in a yield of 0.21 g (62%)—1H
NMR (300 MHz, CDCl3), d (ppm): 1.19 (d, 3J¼6.1 Hz,
3
3H), 1.33–2.48 (m, 13H), 3.77 (sext, J¼6.1 Hz, 1H); 13C
NMR (75 MHz, CDCl3), d (ppm): 23.4, 25.0, 25.1, 31.0,
31.2, 32.5, 36.1, 36.2, 38.9, 39.0, 41.3, 47.9, 48.0, 67.8,
67.9, 212.0; MS, m/z (%): 170 (2%) [M+], 152 (6%), 110
(69%), 97 (100%), 82 (48%), 67 (62%), 55 (82%), 45
(84%), 41 (88%). Anal. Calcd for C10H18O2: C, 70.55; H,
10.66. Found: C, 70.35; H, 10.53.
ꢀ
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1995, 60, 4988–4990.
14. Thestoichiometryofthisreagentwasnotdirectlydeterminedbut
was assumed to be of the type R2CuLi$LiCN (R¼C,O-dianion).
15. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals; Pergamon: Oxford, 1980.
The oil 13a (CAS No. 69441-81-2) was obtained in a yield of
0.21 g (67%).
16. Dimitrov, V.; Kostova, K.; Genov, M. Tetrahedron Lett. 1996,
37, 6787–6790.