Synthesis of substituted α,β-unsaturated δ-lactones from vinyl tellurides

Article abstract of DOI:10.1016/j.tet.2011.02.029

A new approach for the synthesis of α,β-unsaturated δ-lactones, a unit present in many natural products with interesting biological activities is described. The approach was based on the use of a vinyl telluride, and it is complementary to the methods usi

Full text of DOI:10.1016/j.tet.2011.02.029

Tetrahedron 67 (2011) 3003e3009
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of substituted
a,
b-unsaturated
d
-lactones from vinyl tellurides
a
a
b
a,
*
~
Juliana M. Oliveira , Juliano C. R. Freitas , Joao Valdir Comasseto , Paulo Henrique Menezes
a Depto. de Química Fundamental, Universidade Federal de Pernambuco, Avenida Professor Luiz Freire S/N, 50740-540 Recife, PE, Brazil
Instituto de Química, Universidade de Sao Paulo, Avenida Professor Lineu Prestes 748, 05508-000 Sao Paulo, SP, Brazil
b
~
~
a r t i c l e i n f o
a b s t r a c t
Article history:
A new approach for the synthesis of a,b-unsaturated d-lactones, a unit present in many natural products
Received 14 December 2010
Received in revised form 11 February 2011
Accepted 11 February 2011
Available online 18 February 2011
with interesting biological activities is described. The approach was based on the use of a vinyl telluride,
and it is complementary to the methods using ring-closing metathesis. The sequence was performed in
good overall yield with retention of the Z-double bond geometry.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Vinyl tellurides
a
,
b-Unsaturated
d-lactones
Massoialctone
1. Introduction
Substituted
chemistry.10 In addition, some organotellurium compounds are
potent in vitro antioxidants,11 showing very low toxicity, as well no
a,b-unsaturated
d-lactones unitsare present in a large
neurotoxic effects.11b,12
number of compounds isolated from plants and marine organisms.
Representative examples are goniothalamin,1 massoialactone,2 and
euscapholide3 (Fig. 1). These compounds possess a broad range of
biological activities. Noteworthily, structureeactivity relationships
Allylic alcohols containing a stereodefined double bond are im-
portant synthetic intermediates,13 and can be easily prepared when
hydroxy-alkynes are subjected to hydrotelluration conditions.14
Recently, we demonstrated the efficiency of TIPS as the protecting
group of propargyl and homo-propargyl alcohols in order to improve
the regioselectivity in the hydrotelluration reaction.15 In this paper
we describe the use of organotellurium compounds on the synthesis
have demonstrated that the a,b-unsaturated-d-lactone moiety plays
a key role in the bioactivity of many natural products. This is due to
the fact that this unit is an excellent potential Michael acceptor for
nucleophilic amino acid residues of the natural receptors interacting
with these compounds.4e6
of substituted
a,b-unsaturated d-lactones.
2. Results and discussion
In an initial approach propargyl alcohol was converted into its
TIPS, 1, derivative according to the literature procedure16 and then
subjected to hydrotelluration conditions to yield the corresponding
vinyl tellurides 2 and 3,15 which were easily separated by flash
column chromatography (Scheme 1).
Fig. 1. Natural products containing a,b-unsaturated d-lactones units.
Because of their biological activities, many approaches to these
lactones have been reported.7 The majority of them are based on
ring-closing metathesis strategies,8 which has become a powerful
tool in organic synthesis for the preparation of cyclic compounds
from diolefinic precursors.9
Scheme 1.
In the current decade, organotellurium compounds have
attained remarkable development as synthons in synthetic organic
The influence of the TIPS group was remarkable. When propargyl
alcohol was used as the alkyne source a 56:44 mixture of
regioisomers was observed. The regioisomeric ratio was determined
by 1H NMR and confirmed by 125Te NMR and gas chromatography.
* Corresponding author. Tel.: þ55 81 2126 7473; fax: þ55 81 2126 8442; e-mail
address: pmenezes@ufpe.br (P.H. Menezes).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.029

3004
J.M. Oliveira et al. / Tetrahedron 67 (2011) 3003e3009
In spite of the widespread use of bulky groups in organic
The vinyl telluride 2 was then transformed intothecorresponding
Z higher order vinyl cyanocuprate by the reaction with (2-Th)BuCu
(CN)Li2 with total retention of the double-bond configuration.20 The
reaction of the resulting higher order vinyl cyanocuprate in-
termediate with epoxides 4aee gave the corresponding homoallylic
alcohols 5aef. The crude product was treated with TBAF in THF21 to
givethecorresponding1,5-diols6aefingoodyields afterpurification
by chromatographic column (Table 1).
In all cases the homoallylic alcohols 6aef corresponding of the
attack to the less-substituted carbon atom were obtained. The
exception was the reaction with styrene oxide, 4e, which led to
a separable mixture of the regioisomeric diols 6e and 6f in a 1.2:1
ratio (Table 1, entry 5). When disubstituted epoxides 4f and 4g were
used, the corresponding products were not observed, even in the
presence of BF3$Et2O, probably due to the steric effects. The relative
volatile and non-polar byproduct containing tellurium formed in
the reaction was removed from the reaction mixture by flash
chemistry, there are few attempts at quantifying the intuitive
concept of bulkiness.17 The screening action of a bulky group on an
atom could be described by an angle.18 This concept of cone angle
was applied to silyl groups and the cone angle found for TIPS,
q
¼160ꢀ.19 In other words, the bulkiness of TIPS seems to be of the
correct magnitude as to exhibit a good compromise between useful
steric effects to give the desired regioisomer rather than electronic
factors.
Table 1
Synthesis of 1,5-diols from the reaction of 2/(2-Th)BuCu(CN)Li2 system with epox-
ides followed by deprotection
1) (2-Th)BuCu(CN)Li2
THF, 25oC, 1h
OH
TeBu
R
O
TIPSO
2)
R
TIPSO
5a-f
2
4a-g
-78 to 25oC, 2h
Table 2
Synthesis of
OH
R
a
,b
-unsaturated
d-lactones 7aef
TBAF
THF, 25oC, 1h
HO
O
BAIB, TEMPO
CH2Cl2, 25 ºC, 3h
O
6a-f
6a-f
R
Epoxide
1,5-Diol
Yielda (%)
7a-f
1,5-Diol
Lactone
Yielda (%)
OH
O
O
O
O
OH
O
1
2
3
4
5
70
O
OH
O
1
65
4a
4b
6a
OH
OH
6a
7a
O
71
70
73
65
OH
O
OH
O
O
6b
2
3
4
5
60
75
75
50
OH
OH
7b
6b
O
OH
OH
4c
O
6c
OH
OH
7c
6c
O
O
O
OH
O
O
OH
4d
O
6d
O
OH
OH
HO HO
O
7d
6d
+
O
OH
OH
O
4e
6e + 6f
OH
6e
O
7e
O
6
7
d
d
db
HO HO
4f
O
6
70
O
db
6f
4g
a
7f
Overall yield after two steps.
No reaction was observed.
b
a
Isolated yield.

J.M. Oliveira et al. / Tetrahedron 67 (2011) 3003e3009
3005
chromatography or by conversion into the methyl di-n-butyltel-
3. Conclusion
luronium iodide.22
Several conditions have been described to oxidize 1,5-diols into
In conclusion, the method demonstrates to be useful for the
synthesis of -unsaturated -lactones starting from vinyl tellu-
the corresponding
d-lactones. These conditions, however, led to the
a
,
b
d
formation of undesired ketoaldehyde or as a side product, resulting
in lower yields of the corresponding lactones.23 Thus, 6aef were
submitted to a more selective oxidative method based on the use of
bis-acetoxyiodobenzene (BAIB) and a catalytic amount of 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO).24 The products corre-
sponding to the oxidation of primary allylic diol 7aef were
obtained in moderate to good yield. The results are depicted in
Table 2.
The method was then applied to the synthesis of (R)-Massoia-
lactone, a natural product isolated from the bark of Cryptocarya
massoia2 and used as a constituent of native medicines. This com-
pound was later isolated as a defense substance of two species of
formicine ants of the genus Camponutus25 and as a flavor substance
from cane molasses26 and tuberose flowers.27 It is a powerful skin
irritant and produces systolic standstill in frog heart muscles.28
Sharpless asymmetric dihydroxylation29 of commercially avail-
rides. The approach is complementary to the methods using RCM
reactions and the sequence was performed in good overall yield
with retention of the double bond geometry. Finally, the method
offers future possibilities in the development of new organome-
tallic approaches to the compounds containing Z-double bonds.
4. Experimental section
4.1. Material
All reagents and solvents used were previously purified and
dried in agreement with the literature.34 THF was distilled from
sodium/benzophenone under N2 immediately before use. n-BuLi
was titrated using 1,10-phenanthroline as indicator prior to use.35
All operations were carried out in flame-dried glassware. Re-
actions were monitored by thin-layer chromatography on 0.25 mm
E. Merck silica gel 60 plates (F254) using UV light, vanillin and
p-anisaldehyde as visualizing agents. Column chromatographic
purification was performed using Silica Gel 60 (230e400 mesh)
unless indicated otherwise. All compounds purified by chroma-
tography were sufficiently pure for use in further experiments,
unless indicated otherwise.
able 1-heptene 8 under ‘standard conditions’ using AD-mix
a gave
the desired diol 9 in 92% isolated yield after chromatography and in
a 88% ee by di-Mosher ester formation.30 Treatment of diol 9 with
mesyl chloride (1 equiv) followed by the reaction with K2CO3 in
MeOH gave epoxide 10 in moderate yield (Scheme 2).31
4.2. Instrumentation
1H NMR data were recorded at 300 MHz using a Varian UNITY
PLUS spectrometer. 1H NMR chemical shifts are reported as delta (
d)
units in parts per million (ppm) relative to residual CDCl3
(7.26 ppm). Coupling constants (J) were reported in hertz (Hz). 13
NMR data were recorded at 75 MHz using a Varian UNITY PLUS
spectrometer. 13C NMR chemical shifts were reported as delta (
C
d
)
units in parts per million (ppm) relative to the central line of CDCl3
(77.0 ppm). 125Te NMR data were obtained at 94.6 MHz using
diphenyl ditelluride as an external reference (422.0 ppm). Typical
parameters were as follows: acquisition time equal to 0.64 s, pulse
of 45ꢀ, spectral window of 43.9 kHz; and line broadening equal to
5.0 Hz; a good compromise value because although a greater line
broadening would improve the signal-to-noise ratio of the tellu-
rium spectra, which would also imply in less signal resolution.
Low resolution mass spectra were obtained using a Shimadzu
QP-5050A Spectrometer (70 eV) using helium 4.5 as a carrier gas
Scheme 2.
The absolute configuration of the obtained epoxide 10 was
assigned by comparison of the measured optical rotation value with
that of the literature data.32
Thus, transmetalation of vinyl telluride 2 with (2-Th)BuCu(CN)
Li2 followed by the capture of the mixed cuprate with epoxide 10
and subsequent deprotection gave 11 in 75% overall yield. Further
oxidation gave (R)-Massoialactone 12 in 70% yield (Scheme 3).
(R)-Massoialactone was obtained in 52% overall yield after three
steps and the methodology shows efficiency when compared with
other previously described methodologies.7b,33
and a DB-5 column (30 mꢁ0.25
mm). High resolution mass spectra
~
were obtained by the Sao Paulo University, Chemistry Institute
mass spectrometry facility, run by the electro spray ionization
time-of-flight (ESI-TOF) mode on a Bruker Micro Tof Ic Bruker
Daltonics mass spectrometer.
Infra-red spectra were recorded using FT/IR spectrometer
Bruker IFS 66 and the samples were prepared as thin films on salt
plates or as KBr pellets. The melting points (mp) were obtained
using a Eletrothermal 9100 melting point apparatus and are not
corrected.
4.3. Typical procedure
4.3.1. Preparation of dibutylditelluride. A 2 L round-bottomed flask
equipped with a 250 mL pressure equalized dropping funnel was
charged with tellurium metal (20.1 g, 157 mmol) [dried prior to use
in an 85 ꢀC oven], dry THF (1 L) and cooled to 0 ꢀC. The addition
funnel was charged with n-butyllithium (180 mmol, 72 mL of
a 2.5 M solution in hexanes). The n-butyllithium was added drop-
wise. After the addition was completed, the ice bath was removed
and the reaction mixture was stirred at room temperature for 1 h. A
Scheme 3.

3006
J.M. Oliveira et al. / Tetrahedron 67 (2011) 3003e3009
saturated solution of NH4Cl (250 mL) was then slowly added. The
reaction was stirred at room temperature for about 3 h while open
to the atmosphere (O2). The organic layer was isolated and the
aqueous layer was extracted with EtOAc (2ꢁ150 mL). The combined
organic phases were dried over MgSO4 and filtered through a pad of
Celite. Concentration in vacuo provided 50.7 g (87%) of dibutyldi-
telluride as a red oil, which was used directly without further pu-
rification. IR (thin film) nmax 2955, 2921, 2868, 1457, 1175 cmꢂ1; 1H
THF previously cooled at ꢂ78 ꢀC. At the end of the addition, the
acetone/dry ice bath was exchanged for an ice bath. After 5 min the
flask was again placed in a dry ice/acetone bath and n-butyllithium
in hexanes (1.40 M, 7.10 mL, 10 mmol) was added dropwise. The
solution was maintained at this temperature for 15 min. The solu-
tion was then warmed up to 0 ꢀC and the vinylic telluride 2 (4.20 g,
10.5 mmol) dissolved in THF (10 mL) was added. After being stirred
for 1 h at room temperature, the mixture was cooled to ꢂ78 ꢀC and
the appropriate epoxide 4a-g (10 mmol) in THF (10 mL) was added.
The reaction mixture was warmed to 0 ꢀC. After 3 h at 0 ꢀC, it was
warmed to ambient temperature and stirred for an additional 1 h.
The reaction mixture was then cooled to ꢂ78 ꢀC and a solution of
saturated NH4Cl and aqueous NH4OH (9:1) was added. The mixture
was stirred for 15 min while the temperature of the system was
allowed to rise. After that, the mixture was extracted with EtOAc
(2ꢁ60 mL). The organic layer was washed with brine (2ꢁ100 mL).
The combined organic layers were dried over MgSO4 and concen-
trated in vacuo. The crude silyl ether 5aef was dissolved in THF
(5 mL) and TBAF (10 mL, 1 M solution in THF, 10 mmol) was added
dropwise. The reaction was monitored by TLC. The reaction was
then quenched by the addition of a saturated solution of NH4Cl
(10 mL). The aqueous layer was extracted with EtOAc and the
combined organic phases were washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified by chromatography on silica gel using hexanes/EtOAc
(50:50) to yield the corresponding 1,5-diols, 6aef.
NMR (300 MHz, CDCl3)
d
3.10 (t, J¼7.80 Hz, 4H, 2ꢁCH2), 1.80e1.60
(m, 4H, 2ꢁCH2), 1.46e1.30 (m, 4H, 2ꢁCH2), 0.92 (t, J¼7.50 Hz, 6H,
2ꢁCH3); 13C NMR (75 MHz, CDCl3)
13.3 (2ꢁCH2), 4.2 (2ꢁCH3).
d
35.6 (2ꢁCH2), 24.5 (2ꢁCH2),
4.3.2. Preparation of triisopropyl(prop-2-ynyloxy)silane (1). To
a round-bottomed flask under argon were added CH2Cl2 (30 mL),
imidazole (1.70 g, 25 mmol), and propargyl alcohol (0.56 g,
0.58 mL, 10 mmol) the mixture was cooled to 0 ꢀC and TIPSCl
(2.30 g, 2.55 mL, 12 mmol) was slowly added. The mixture was
stirred for 12 h, diluted with CH2Cl2 (20 mL) and quenched with
H2O (20 mL). The organic phase was washed with 3% HCl (10 mL),
saturated NaHCO3 (20 mL), and finally H2O. The organic phase was
then dried over MgSO4, filtered, and concentrated in vacuo. The
pure silyl ether was distilled from the residue under reduced
pressure (bp 110 ꢀC, 20 mmHg) to yield 2.0 g (95%) of the title
compound. 1H NMR (300 MHz, CDCl3)
2.38 (t, J¼2.7 Hz, 1H, CCH), 1.11e1.04 (m, 3H, 3ꢁCH, 18H, 6ꢁCH3);
13C NMR (75 MHz, CDCl3)
d
4.37 (d, J¼2.4 Hz, 2H, CH2),
d
81.4 (CHꢁCCH2), 72.5 (CH^CCH2), 51.7
(CH2), 17.8 (6ꢁCH3), 11.9 (3ꢁCH).
4.4.1. (Z)-6-Phenoxyhex-2-ene-1,5-diol (6a). Isolated as a colorless
oil; 1.45 g (70%); IR (KBr pellet) nmax 3330 (OH), 2926, 2875, 1598,
4.3.3. Preparation of (Z)-(3-(butyltellanyl)allyloxy)triiso-propylsilane
(2). Compound 1 (19.0 g, 90 mmol) and dibutylditelluride (16.8 g,
45 mmol) were dissolved in absolute ethanol (100 mL) at room
temperature. Finely powdered sodium borohydride was added in
portions to the above solution. Additional sodium borohydride was
added as necessary to maintain a yellow color (indicative of the
butyltellurolate anion). The solution was heated to reflux for 5 h
and cooled to room temperature. The reaction mixture was then
poured into a saturated solution of NaHCO3 (200 mL) and diluted
with EtOAc (200 mL). The organic layer was isolated and washed
with H2O (500 mL), and brine (500 mL) before drying over MgSO4.
The organic phase was filtered and concentrated in vacuo. Silica gel
chromatography using hexanes provided 30.6 g (85%) of the title
compound as a yellow oil. IR (thin film) nmax 2941, 2865, 1462, 1095,
1495,1292, 1244, 1078, 754 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d
7.34e7.25 (m, 2H, 2ꢁAreCH), 7.02e6.89 (m, 3H, 3ꢁAreCH),
5.96e5.83 (m, 1H, CH]CH), 5.73e5.61 (m, 1H, CH]CH), 4.26e4.18
(m, 1H, CHOH), 4.15e4.01 (m, 2H, CHOHCH2), 4.00e3.87 (m, 2H,
CH2CH]CH), 3.11 (br s, 2H, 2ꢁOH), 2.54e2.34 (m, 2H, CH]CHCH2);
13C NMR
d (75 MHz, CDCl3) d
158.3 (CqeAr), 131.6 (CH]CH), 129.5
(CH]CH), 128.2 (2ꢁCHeAr), 121.1 (CHeAr), 114.4 (2ꢁCHeAr), 71.2
(CHOHCH2), 68.9 (CHOH), 57.4 (CH2CH]CH), 31.0 (CH]CHCH2);
GCeMS (EI, rel int. %) m/z 208 ([Mþ], 3), 154, 136 (20), 119 (12), 108
(35), 94 (100), 77 (45), 65 (18), 55 (44), 51 (19), 43(38), 41 (26);
HRMS (ESI, MeOH/H2O) calcd for C12H16O3Na [MþNa]þ, 231.0997;
found 231.0991.
4.4.2. (Z)-Nona-2,8-diene-1,5-diol (6b). Isolated as a yellow oil,
1.11 g (71%); IR (KBr pellet) nmax 3329 (OH), 2933, 1640, 1436, 1076,
918 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
6.72 (dt, J¼9.9, 1.5 Hz, 1H,
TeCH]CH), 6.39 (dt, J¼9.9, 5.1 Hz, 1H, TeCH]CH), 4.22 (dd, J¼5.1,
1.5 Hz, 2H, CH]CHCH2), 2.7 (t, J¼7.8 Hz, 2H, CH2),1.90e1.60 (m, 2H,
CH2), 1.46e1.20 (m, 2H, CH2), 1.20e1.00 (m, 3H, 3ꢁCH, 18H, 6ꢁCH3),
1007, 911, 861 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 5.96e5.72 (m, 1H,
CH]CH, 1H, CH]CH2), 5.63e5.50 (m, 1H, CH]CH), 5.05e4.94 (m,
2H, CH]CH2), 4.15 (dd, J¼12.3, 7.2 Hz, 1H, CH2CH]CH), 4.02 (dd,
J¼12.3, 6.6 Hz, 1H, CH2CH]CH), 3.67e3.59 (m, 1H, CHOH), 3.25 (br s
2H, 2ꢁOH), 2.32e2.03 (m, 2H, CH]CHCH2, 2H, CH2CH]CH2),
1.59e1.52 (m, 2H, CH2CH2CH]CH2); 13C NMR (75 MHz, CDCl3)
0.92 (t, J¼7.50 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d 138.1
(TeCH]CH), 102.1 (TeCH]CH), 65.7 (CH]CHCH2), 33.8 (CH2), 24.9
(CH2), 17.5 (6ꢁCHCH3), 17.4 (CH2), 13.5 (CH3), 11.9 (3ꢁCHCH3); 125Te
NMR (94.6 MHz, CDCl3)
d
298.6; GCeMS (EI, rel int. %) m/z 400
d 138.2 (CH]CH2),131.1 (CH]CH),129.2 (CH]CH),114.8 (CH]CH2),
([Mþ], 6), 357 (83), 245 (41), 227 (12), 213 (29), 169 (100), 157 (24),
127 (60), 87 (10), 57 (7); HRMS (ESI, MeOH/H2O) calcd for
C16H34OSiTe [MþH]þ, 401.1519; found 400.9330.
69.9 (CHOH), 57.3 (CH2CH]CH), 35.9 (CHOHCH2), 34.9
(CHOHCH2CH2), 30.05 (CH]CHCH2); GCeMS (EI, rel int. %) m/z 138
(1), 83 (14), 79 (6), 71 (10), 67 (14), 54 (100), 41 (37); HRMS (ESI,
MeOH/H2O)calcd forC9H16O2Na [MþNa]þ,179.1048; found179.1051.
4.4. General procedure for the synthesis of 1,5-diols (6aef)
from the reaction of 2/(2-Th)BuCu(CN)Li2 system with
epoxides 4aef followed by deprotection
4.4.3. (Z)-Hept-2-ene-1,5-diol (6c). Isolated as a yellow oil, 0.91 g
(70%); IR (KBr pellet) nmax 3329 (OH), 3019, 2963, 2932, 2877, 1461,
1113, 1013 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 5.77e5.69 (m, 1H,
To a flask equipped with a stirring bar and a rubber septum
under argon atmosphere was added anhydrous THF (10 mL) and
distilled thiophene (1.05 g, 12.5 mmol). The solution was cooled to
ꢂ78 ꢀC and n-butyllithium in hexanes (1.40 M, 9.0 mL, 12.5 mmol)
was added dropwise. The resulting light-yellow solution was
warmed to ꢂ40 ꢀC and kept for 20 min. After that, this solution was
transferred via canula to a suspension of CuCN (0.89 g, 10 mmol) in
CH]CH), 5.58e5.49 (m, 1H, CH]CH), 4.10 (dd, J¼12.3, 7.2 Hz, 1H,
CH2CH]CH), 3.97 (dd, J¼12.3, 7.2 Hz, 1H, CH2CH]CH), 3.86 (br s,
2H, 2ꢁOH), 3.52e3.44 (m, 1H, CHOH), 2.18 (t, J¼7.5 Hz, 2H, CH]
CHCH2), 1.43 (qui, J¼7.5 Hz, 2H, CH2CH3), 0.89 (t, J¼7.5 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3)
d 130.8 (CH]CH), 129.1 (CH]CH), 71.8
(CHOH), 57.1 (CH2CH]CH), 34.3 (CH]CHCH2), 29.6 (CH2CH3), 9.9
(CH2CH3); GCeMS (EI, rel int. %) m/z 130 ([Mþ],1), 83 (8), 57 (33), 54

J.M. Oliveira et al. / Tetrahedron 67 (2011) 3003e3009
3007
(100), 41 (18); HRMS (ESI, MeOH/H2O) calcd for C7H14O2Na
756 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
7.30e7.15 (m, 2H,
[MþNa]þ, 153.0892, found 153.0899.
2ꢁAreCH), 6.94e6.82 (m, 3H, 3ꢁAreCH, 1H, CH]CHCH2), 6.04
(ddd, J¼9.6, 3.9, 2.2 Hz, 1H, CH]CHCH2), 4.77e4.68 (m, 1H, CH),
4.15e4.05 (m, 2H, CH2), 2.65e2.41 (m, 2H, CH]CHCH2); 13C NMR
4.4.4. (Z)-6-(Allyloxy)hex-2-ene-1,5-diol (6d). Isolated as a yellow
oil, 1.25 g (73%); IR (KBr) nmax 3355 (OH), 2865, 1647, 1423, 1087,
(75 MHz, CDCl3)
d
163.4 (C]O), 158.0 (CqeAr), 144.8 (CH]CH),
1006, 930, 668 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
5.92e5.74 (m,1H,
129.5 (2ꢁCHeAr), 121.3 (CH]CH), 121.1 (CHeAr), 114.4 (CHeAr),
75.5 (CH2CHO), 68.3 (CH2OeAr), 26.1 (CH2); GCeMS (EI, rel int. %)
m/z 204 ([Mþ], 43), 111 (28), 110 (36), 107 (24), 97 (100), 94 (33), 83
(15), 81 (16), 79 (17), 77 (67), 69 (56), 55 (25), 43 (70), 41 (59);
HRMS (ESI, MeOH/H2O) calcd for C12H12O3Na [MþNa]þ, 227.0684;
found 227.0672.
CH]CH, 1H, CH]CH2), 5.59e5.50 (m, 1H, CH]CH), 5.24 (ddd,
J¼17.0, 3.0, 1.5 Hz, 1H, CH]CH2), 5.16 (ddd, J¼10.8, 3.0, 1.5 Hz, 1H,
CH]CH2), 4.13 (dd, J¼12.3, 7.5 Hz, 1H, CH2CH]CH), 4.01 (dd,
J¼12.3, 7.5 Hz, 1H, CH2CH]CH), 3.97 (ddd, J¼7.2, 3.0, 1.5 Hz, 2H,
CH2CH]CH2), 3.82e3.75 (m, 1H, CHOH), 3.43e3.29 (m, 2H,
CHOHCH2, 2H, 2ꢁOH), 2.34e2.18 (m, 2H, CH2CH]CH); 13C NMR
(75 MHz, CDCl3)
d
134.2 (CH]CH2), 131.3 (CH]CH), 128.7 (CH]
4.5.2. 6-(But-3-enyl)-5,6-dihydro-2H-pyran-2-one (7b). Isolated as
a colorless oil, 0.23 g (60%); IR (thin film) nmax 1716 (C]O), 1388,
CH), 117.4 (CH]CH2), 73.7 (CHOHCH2), 72.1 (CH2CH]CH2), 69.2
(CHOH), 57.3 (CH2CH]CH), 31.0 (CH]CHCH2); GCeMS (EI, rel int.
%) m/z 136 (1),101 (5), 83 (31), 55 (56), 54 (48), 41 (100); HRMS (ESI,
MeOH/H2O) calcd for C9H16O3Na [MþNa]þ,195.0997; found
195.0998.
1065, 1039, 996, 955, 864, 817 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d
6.89 (ddd, J¼9.6, 5.1, 3.9 Hz, 1H, CH]CHCH2), 6.03 (dt, J¼9.6,
1.8 Hz, 1H, CH]CHCH2), 5.86e5.73 (m, 1H, CH]CH2), 5.10e4.98
(m, 2H, CH]CH2), 4.48e4.39 (m, 1H, CH), 2.36e2.21 (m, 4H,
2ꢁCH2); 13C NMR (75 MHz, CDCl3)
d 164.5 (C]O), 145.0 (CH]CH),
4.4.5. (Z)-5-Phenylpent-2-ene-1,5-diol (6e). Isolated as a yellow oil,
0.62 g (35%); IR (KBr pellet) nmax 3344 (OH), 3062, 2923, 1712, 1493,
137.1 (CH]CH2), 121.4 (CH]CH), 115.6 (CH]CH2), 77.1 (CH2CHO),
33.9 (CH2CHO), 29.3 (CH2), 28.8 (CH2); GCeMS (EI, rel int. %) m/z
152 ([Mþ], 1), 110 (17), 97 (85), 69 (53), 68 (100), 67 (52), 55 (34), 42
(20), 41 (79), 40 (34); HRMS (ESI, MeOH/H2O) calcd for C9H12O2Na
[MþNa]þ, 175.0735; found 175.0729.
1026, 760, 733, 700 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 7.32e7.26
(m, 5H, 5ꢁAreCH), 5.77 (m, 1H, CH]CH), 5.53 (m, 1H, CH]CH),
4.64 (dd, J¼8.1, 4.5 Hz, 1H, CHOH), 4.05 (dd, J¼12.3, 7.5 Hz, 1H,
CH2CH]CH), 3.90 (dd, J¼12.3, 6.6 Hz, 1H, CH2CH]CH), 3.03 (br s,
2H, 2ꢁOH), 2.62e2.51 (m, 1H, CH]CHCH2), 2.47e2.38 (m, 1H, CH]
4.4.3. 6-Ethyl-5,6-dihydro-2H-pyran-2-one (7c). Isolated as a color-
less oil, 0.24 g (75%); IR (thin film) nmax 1714 (C]O), 1251, 1036,
CHCH2); 13C NMR (75 MHz, CDCl3) 143.9 (CqeAr), 131.4 (CH]CH),
d
128.9 (CH]CH), 128.3 (2ꢁCHeAr), 127.5 (CHeAr), 125.6
(2ꢁCHeAr), 72.7 (CHOH), 57.3 (CH2CH]CH), 37.0 (CH]CH CH2);
GCeMS (EI, rel int. %) m/z 178 ([Mþ], 1), 107 (76), 106 (13), 105 (100),
79 (91), 78 (12), 77 (66), 54 (93), 51 (20); HRMS (ESI, MeOH/H2O)
calcd for C11H14O2Na [MþNa]þ 201.0892; found 201.0896.
865 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
6.87 (ddd, J¼9.6, 5.1, 3.3 Hz,
1H, CH]CHCH2), 6.02 (dt, J¼9.6,1.5 Hz,1H, CH]CHCH2), 4.39e4.30
(m, 1H, CH), 2.34e2.29 (m, 2H, CH]CHCH2), 1.85e1.64 (m, 2H,
CH2), 1.00 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d 164.6
(C]O), 145.1 (CH]CH), 121.3 (CH]CH), 79.1 (CH2CHO), 28.8 (CH2),
27.8 (CH2), 9.2 (CH3); GCeMS (EI, rel int. %) m/z 126 ([Mþ], 2), 97
(72), 69 (28), 68 (100), 41 (33), 40 (21); HRMS (ESI, MeOH/H2O)
calcd for C7H10O2Na [MþNa]þ, 149.0579; found 149.0230.
4.4.6. (Z)-4-Phenylpent-2-ene-1,5-diol (6f). Isolated as a yellow oil,
0.53 g (30%); IR (KBr pellet) nmax 3330 (OH), 2955, 2924, 2870, 1492,
1453, 1037, 699 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 7.36e7.30 (m,
2H, 2ꢁAreCH), 7.21e7.27 (m, 3H, 3ꢁAreCH), 5.97e5.88 (m, 1H,
CH]CH), 5.84e5.77 (m, 1H, CH]CH), 4.34 (ddd, J¼12.4, 7.4, 1.4 Hz,
1H, CH2CH]CH), 4.12 (ddd, J¼12.4, 6.3, 0.8 Hz, 1H, CH2CH]CH),
3.95e3.82 (m, 2H, CH2OH), 3.73e3.66 (m, 1H, CH), 2.16 (br s, 2H,
4.5.4. 6-(Allyloxymethyl)-5,6-dihydro-2H-pyran-2-one
(7d). Isolated as a colorless oil, 0.31 g (75%); IR (thin film) nmax
3524, 3079, 2914, 2867, 1722 (C]O), 1423, 1249, 130, 1051, 848,
663 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
6.89 (ddd, J¼9.6, 6.0, 2.7 Hz,
2ꢁOH); 13C NMR (75 MHz, CDCl3)
d
140.7 (CqeAr), 133.4 (CH]CH),
1H, CH]CHCH2), 5.97 (ddd, J¼9.6, 2.4, 0.9 Hz, 1H, CH]CHCH2),
5.92e5.79 (m, 1H, CH]CH2), 5.28e5.14 (m, 2H, CH]CH2),
4.60e4.51 (m, 1H, CH), 4.03 (dt, J¼5.7, 1.2 Hz, 2H, CH2CH]CH2),
3.62 (d, J¼4.5 Hz, 2H, CH2), 2.59e2.31 (m, 1H, CH]CHCH2),
130.9 (CH]CH), 128.8 (2ꢁCHeAr), 127.5 (2ꢁCHeAr), 126.9
(CHeAr), 66.3 (CH2), 58.0 (CH2CH]CH), 46.3 (CH); GCeMS (EI, rel
int. %) m/z 169 (1), 130 (100), 129 (75), 128 (29), 115 (32), 91 (70), 77
(18), 51 (16), 41 (21); HRMS (ESI, MeOH/H2O) calcd for C11H14O2Na
[MþNa]þ, 201.0892; found 201.0883.
2.32e2.43 (m, 1H, CH]CHCH2); 13C NMR (75 MHz, CDCl3)
d 163.7
(C]O), 145.0 (CH]CH), 134.0 (CH]CH2), 120.9 (CH]CH), 117.4
(CH]CH2), 76.5 (CHOCH2OCH2), 72.4 (CH2CHCH2), 70.6 (CH2CHO),
25.9 (CH]CHCH2); GCeMS (EI, rel int. %) m/z 169 ([Mþ1], 1), 154
(46), 126 (68), 97 (34), 81 (13), 69 (74), 55 (30), 43 (90), 41 (86), 40
(37); HRMS (ESI, MeOH/H2O) calcd for C9H12O3Na [MþNa]þ,
191.0684; found 191.0680.
4.5. General procedure for the synthesis of a,b-unsaturated d-
lactones (7aef) from the reaction of 1,5-diols (6aef) with
TEMPO/BAIB
To a stirred solution of the appropriate diol 6aef (2.5 mmol,
1 equiv) in CH2Cl2 (30 mL) was added bis-acetoxyiodobenzene
(BAIB) (2.5 g, 7.7 mmol, 3 equiv) and 2,2,6,6-tetramethyl-1-piper-
idinyloxy (TEMPO) (0.08 g, 20 mmol %) at room temperature. After
stirring for 3 h, the reaction was quenched with a saturated solution
of Na2S2O3 (10 mL) and was extracted with CH2Cl2 (2ꢁ25 mL). The
combined organic extracts were washed with saturated solutions of
NaHCO3 (10 mL), NH4Cl (10 mL) and brine (2ꢁ50 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The residue was puri-
fied by chromatography on silica gel using 100:0 to 90:10 hexanes/
EtOAc to yield the lactones 7aef.
4.4.5. 6-Phenyl-5,6-dihydro-2H-pyran-2-one (7e). Isolated as a col-
orless oil, 0.22 g (50%); IR (thin film) nmax 1722 (C]O), 1454, 1382,
1246, 1061, 1022, 816, 760, 699 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d
7.45e7.33 (m, 5H, 5ꢁAreCH), 6.98 (ddd, J¼10.0, 5.6, 3.2 Hz, 1H,
CH]CHCH2), 6.14 (ddd, J¼10.0, 2.4, 1.2 Hz, 1H, CH]CHCH2), 5.44
(dd, J¼10.8, 5.2 Hz, 1H, CH), 2.66e2.61 (m, 2H, CH2); 13C NMR
(75 MHz, CDCl3)
d
164.1 (C]O), 144.9 (CH]CH), 138.4 (CqeAr),
128.7 (2ꢁCHeAr), 128.6 (2ꢁAreCH), 126.0 (AreCH), 121.7 (CH]
CH), 79.2 (CH2CHO), 31.6 (CH2); GCeMS (EI, rel int. %) m/z 174 ([Mþ],
17), 128 (5), 105 (9), 77 (16), 68 (100), 51 (14); HRMS (ESI, MeOH/
H2O) calcd for C11H10O2Na [MþNa]þ, 197.0579; found 197.0575.
4.5.1. 6-(Phenoxymethyl)-5,6-dihydro-2H-pyran-2-one
(7a). Isolated as a white solid, 0.33 g (65%); mp 80e82 ꢀC; IR (KBr
pellet) nmax 1721 (C]O), 1599, 1495, 1386, 1238, 1087, 1044, 812,
4.5.6. 5-Phenyl-5,6-dihydro-2H-pyran-2-one (7f). Isolated as a col-
orless oil, 0.30 g (70%); IR (thin film) nmax 3061, 3029, 2892, 1730

3008
J.M. Oliveira et al. / Tetrahedron 67 (2011) 3003e3009
(C]O), 1492, 1398, 1225, 1085, 826, 798, 703, 513 cmꢂ1
(300 MHz, CDCl3)
;
1H NMR
GCeMS (EI, rel int. %) m/z 114 [Mþ] (0,5); 99 (2); 85 (15), 71 (100),
55 (63), 58 (57); 41 (89).
d
7.40e7.32 (m, 3H, 3ꢁAreCH), 7.26e7.21 (m, 2H,
2ꢁAreCH), 6.98 (ddd, J¼9.9, 3.0, 0.9 Hz, 1H, CH]CHCH2), 6.16 (dd,
J¼9.9, 2.1 Hz, 1H, CH]CHCH2), 4.55 (ddd, J¼11.4, 5.7, 1.2 Hz, 1H,
CH2), 4.31 (dd, J¼11.1, 9.6 Hz, 1H, CH2), 3.89e3.83 (m, 1H, CH); 13C
4.7. Synthesis of (R,Z)-dec-2-ene-1,5-diol (11) from the
reaction of 2/(2-Th)BuCu(CN)Li2 system with (10) followed by
deprotection
NMR (75 MHz, CDCl3)
d 163.3 (C]O), 148.9 (CH]CH), 137.0
(CqeAr), 128.9 (2ꢁAreCH), 127.8 (CHeAr), 127.7 (2ꢁAreCH), 121.2
(CH]CH), 72.1 (CH2), 40.1 (CH2CHO); GCeMS (EI, rel int. %) m/z 174
([Mþ], 14), 144 (100), 116 (66), 115 (81), 57 (45); HRMS (ESI, MeOH/
H2O) calcd for C11H10O2Na [MþNa]þ 197.0579; found 197.0577.
To a flask equipped with a stirring bar and a rubber septum
under argon atmosphere was added anhydrous THF (10 mL) and
distilled thiophene (1.05 g, 12.5 mmol). The solution was cooled to
ꢂ78 ꢀC and n-butyllithium in hexanes (1.40 M, 9.0 mL, 12.5 mmol)
was added dropwise. The resulting light-yellow solution was
warmed to ꢂ40 ꢀC and kept for 20 min. After that, this solution was
transferred via canula to a suspension of CuCN (0.89 g, 10 mmol) in
THF previously cooled to ꢂ78 ꢀC. At the end of the addition, the
acetone/dry ice bath was exchanged for an ice bath. After 5 min the
flask was again placed in a dry ice/acetone bath and n-butyllithium
in hexanes (1.40 M, 7.10 mL, 10 mmol) was added dropwise. The
solution was maintained at this temperature for 15 min. After that,
the solution was warmed up to 0 ꢀC and 2 (4.20 g, 10.5 mmol)
dissolved in THF (10 mL) was added. After being stirred for 1 h at
room temperature, the mixture was cooled to -78 ꢀC and the
epoxide 8 (1.14 g, 10 mmol) in THF (10 mL) was added. The reaction
mixture was warmed to 0 ꢀC. After 3 h at 0 ꢀC, it was warmed to
ambient temperature and stirred for an additional hour. The re-
action mixture was then cooled to ꢂ78 ꢀC and a solution of satu-
rated aqueous NH4Cl and aqueous NH4OH (9:1) was added. The
mixture was stirred for 15 min while the temperature of the system
was allowed to rise. After that, the mixture was extracted with
EtOAc (2ꢁ60 mL). The organic layer was washed with brine
(2ꢁ100 mL). The combined organic layers were dried over MgSO4
and concentrated in vacuo. The residue was then dissolved in THF
(5 mL) and TBAF (10 mL, 1 M solution in THF, 10 mmol) was added
dropwise. The reaction was monitored by TLC. The reaction was
then quenched by the addition of a saturated solution of NH4Cl
(10 mL). The aqueous layer was extracted with EtOAc and the
combined organic phases were washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was
4.5.7. (R)-Heptane-1,2-diol (9). To a 50 mL flask containing a sus-
pension of AD-mix a (5.6 g) in t-BuOH (20 mL) and water (20 mL) at
0 ꢀC was added 1-heptene (0.4 g, 4 mmol). The mixture was stirred
for 24 h at room temperature and then quenched by the addition of
a 0.05 M solution of Na2SO3 (20 mL). The aqueous layer was
extracted with EtOAc. The combined organic phases were washed
with 2 M KOH solution (40 mL), brine (2ꢁ40 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified by chromatography on silica gel using hexanes/EtOAc
(50:50) to yield 0.48 g (92%) of the title compound as a colorless oil.
26
[
a]
ꢂ14.1 (c 1.00, CH3OH); IR (thin film) nmax 3354, 2946, 2863,
D
1461, 1212, 927 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
4.09 (dd, J¼14.1,
7.2 Hz, 1H, CH2OH), 3.68 (br s, 1H, CH2OH), 3.65e3.56 (m, 2H,
CH2OH and CHOH), 3.40e3.34 (m, 1H, CHOH), 1.43e1.34 (m, 2H,
CH2), 1.30e1.21 (m, 6H, 3ꢁCH2), 0.85 (t, J¼7.2 Hz, 1H, CH3); 13C NMR
(75 MHz, CDCl3)
d 72.3 (CHOH), 66.6 (CH2OH), 32.9 (CH2), 31.8
(CH2), 25.2 (CH2), 22.5 (CH2), 13.9 (CH3); GCeMS (EI, rel int. %) m/z
132 [Mþ] (0.5); 115 (3); 101 (43), 83 (100), 61 (21). 55 (98), 41 (69);
HRMS (ESI, MeOH/H2O) calcd for C7H16O2Na [MþNa]þ, 155.1048;
found 155.1056.
4.6. Synthesis of Mosher esters from (9)
To a solution of diol 9 (0.02 g, 0.15 mmol) in CH2Cl2 (5 mL) at
0 ꢀC, was added DCC (0.06 g, 0.3 mmol) and DMAP (0.01 g,
0.02 mmol). After 5 min (R)-MTPA (0.08 g, 0.35 mmol) was added
and the mixture was stirred for 0.5 h at 0 ꢀC. The reaction was
allowed to warm to room temperature and stirred for an additional
4 h. After this period, the solvent was removed and the crude
product was dissolved in CDCl3 and submitted to a 19F NMR anal-
purified by chromatography on silica gel using 50:50 hexanes/
26
EtOAc to yield 1.28 g (75%) of the 1,5-diol, 11 as a yellow oil. [a]
D
ꢂ9.7 (c 1.00, CHCl3); IR (KBr pellet) nmax 3329 (OH), 2921, 2843,
1661, 1472, 1011, 867, 721 cmꢂ1 1H NMR (300 MHz, CDCl3)
5.90e5.82 (m, 1H, CH]CH), 5.67e5.58 (m, 1H, CH]CH), 4.17 (dd,
ysis. 19F NMR (282 MHz, CDCl3)
(S)-diol.
d
ꢂ71.8 for (R)-diol and ꢂ72.0 for
;
d
J¼12.0, 7.5 Hz, 1H, CH2CH]CH), 4.05 (dd, J¼12.3, 6.6 Hz, 1H,
CH2CH]CH), 3.66e3.58 (m, 1H, CHOH), 2.62 (br s, 2H, 2ꢁOH),
2.28e2.23 (m, 2H, CH]CHCH2), 1.49e1.40 (m, 2H, CHOHCH2),
1.35e1.27 (m, 6H, 3ꢁCH2), 0.89 (t, J¼6.9 Hz, 3H, CH3); 13C NMR
4.6.1. (R)-2-Pentyloxirane (10). In a flask containing a solution of 9
(0.74 g, 5.6 mmol) in CH2Cl2 (20 mL) under argon was added Et3N
(1.0 mL, 6.8 mmol). The solution was stirred for 5 min before
cooling to 0 ꢀC. Mesyl chloride (0.65 mL, 7 mmol) was added
dropwise and the resulting mixture was stirred at room tempera-
ture for 3 h. After diluting with Et2O (10 mL), the precipitate was
filtered and washed with Et2O (3ꢁ10 mL). The combined ethereal
solution was washed with saturated NaHCO3, dried over MgSO4 and
the solvents were removed in vacuo. The crude mesylate was
redissolved in MeOH (20 mL) and K2CO3 (1.6 g, 11 mmol) was
added. The suspension was stirred at room temperature for 3 h, and
then quenched with water (10 mL). The organic phase was
extracted with CH2Cl2 (3ꢁ10 mL), and the combined organic phases
were washed with water (10 mL) and brine (20 mL) before drying
over MgSO4. Removal of the solvent, followed by a careful bulb-to-
bulb distillation (80 ꢀC, 80 mmHg) gave 0.33 g (52%) of the title
(75 MHz, CDCl3)
d 131.8 (CH]CH), 129.1 (CH]CH), 70.0 (CHOH),
57.1 (CH2CH]CH), 36.6 (CH2), 34.5 (CH2), 31.8 (CH2), 25.0 (CH2),
22.1 (CH2), 13.6 (CH3); GCeMS (EI, rel int. %) m/z 154 (1), 99 (12), 55
(35), 54 (100), 43 (14), 41 (12); HRMS (ESI, MeOH/H2O) calcd for
C10H20O2Na [MþNa]þ, 195.1361; found 195.1364.
4.8. Synthesis of (R)-Massoialactone (12) from the reaction of
(11) with TEMPO/BAIB
To a stirred solution of the 11 (2.5 mmol, 0.43 g) in CH2Cl2
(30 mL) was added bis-acetoxyiodobenzene (BAIB) (2.5 g,
7.7 mmol, 3 equiv) and 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) (0.08 g, 20 mmol %) at room temperature. After stirring for
3 h, the reaction was quenched with a saturated solution of Na2S2O3
(10 mL) and was extracted with CH2Cl2 (2ꢁ25 mL). The combined
organic extracts were washed with saturated solutions of NaHCO3
(10 mL), NH4Cl (10 mL) and brine (2ꢁ50 mL), dried over MgSO4,
filtered, and concentrated. The residue was purified by chroma-
tography on silica gel using 100:0 to 90:10 hexanes/EtOAc to yield
compound as a colorless oil. [
a
]
26 ꢂ8.5 (c 1.00, CHCl3); IR (thin film)
D
nmax 2958, 2931, 2860, 1466, 1259, 917 cmꢂ1
;
1H NMR (300 MHz,
CDCl3)
d
2.84e2.81 (m, 1H, OCH2), 2.66 (t, J¼3.6 Hz, 1H, OCH), 2.38
(dd, J¼3.6, 2.1 Hz, 1H, OCH2), 1.49e1.21 (m, 8H, 4ꢁCH2), 0.84 (t,
J¼6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d 53.3 (CHO), 46.8
(CH2O), 32.3 (CH2), 31.5 (CH2), 25.5 (CH2), 22.4 (CH2), 13.8 (CH3);

J.M. Oliveira et al. / Tetrahedron 67 (2011) 3003e3009
3009
26
€
54, 4413e4450; (e) Furstner, A.; Grela, K. Angew. Chem., Int. Ed. 2000, 39,
1234e1236; (f) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 11998, 371e388.
10. (a) Freitas, J. C. R.; de Freitas, J. R.; Menezes, P. H. J. Braz. Chem. Soc. 2010, 21,
2169e2172; (b) Oliveira, R. A.; Oliveira, J. M.; Rahmeier, L. H. S.; Marino, J. P.;
Comasseto, J. V.; Menezes, P. H. Tetrahedron Lett. 2008, 49, 5759e5761; (c)
Oliveira, J. M.; Zeni, G.; Malvestti, I.; Menezes, P. H. Tetrahedron Lett. 2006, 47,
8183e8185.
(12)d(R)-Massoialactonedas a colorless oil, 0.28 g (70%). [a]
D
ꢂ115.6 (c 1.00, CHCl3); IR (thin film) nmax 2927, 2849, 1718, 1381,
1257, 1041, 812, 665 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d
6.80 (dd,
J¼9.6, 4.4 Hz, 1H, CH]CHCH2), 5.95 (d, J¼9.6 Hz, 1H, CH]CHCH2),
4.38e4.33 (m, 1H, CH), 2.27e2.23 (m, 2H, CH]CHCH2), 1.74e1.19
(m, 8H, 4ꢁCH2), 0.83 (t, J¼6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
11. (a) Engman, L.; Persson, J.; Vessman, K.; Ekstrom, M.; Berglund, M.; Andersson,
ꢀ
C. M. Free Radical Biol. Med. 1995, 19, 441e452; (b) Avila, D. S.; Colle, D.; Gubert,
P.; Palma, A. S.; Puntel, G.; Manarin, F.; Noremberg, S.; Nascimento, P. C.;
Aschner, M.; Rocha, J. B. T.; Soares, F. A. A. Toxicol. Sci. 2010, 115, 194e201.
d
164.2 (C]O), 144.7 (CH]CH), 120.9 (CH]CH), 77.6 (CH2CHO),
34.3 (CH]CHCH2), 31.5 (CH2), 28.9 (CH2), 24.4 (CH2), 22.0 (CH2),
13.5 (CH2); GCeMS (EI, rel int. %) m/z 169 ([Mþ1], 2), 154 (41), 137
(23), 126 (62), 109 (42), 97 (37), 95 (20), 55 (28), 43 (89), 42 (29), 41
(83), 40 (34); HRMS (ESI, MeOH/H2O) calcd for C10H16O2Na
[MþNa]þ, 191.1048; found 191.1045.
ꢀ
12. (a) Avila, D. S.; Gubert, P.; Dalla Corte, C. L.; Alves, D.; Nogueira, C. W.; Rocha, J.
ꢀ
B.; Soares, F. A. Life Sci. 2007, 80, 1865e1872; (b) Avila, D. S.; Gubert, P.; Palma,
A.; Colle, D.; Alves, D.; Nogueira, C. W.; Rocha, J. B.; Soares, F. A. Brain Res. Bull.
2008, 76, 114e123.
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The authors gratefully acknowledge CNPq (471252/2007-7),
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thankful to CNPq for their fellowships.
Supplementary data
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Supplementary data associated with this article can be found in
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