Concise total synthesis of (-)-cis-aerangis lactone and (-)-cis-cognac lactone

Article abstract of DOI:10.1055/s-0030-1260190

An efficient and concise stereoselective total synthesis of naturally occurring (-)-cis-aerangis lactone and (-)-cis-cognac lactone is described. The Sharpless asymmetric epoxidation of a primary allylic alcohol and TBSOTf-mediated intramolecular hydride

Full text of DOI:10.1055/s-0030-1260190

3168
PAPER
Concise Total Synthesis of (–)-cis-Aerangis Lactone and (–)-cis-Cognac
Lactone
(
–)-cis-A
e
h
rangis
L
acto
i
ne and
l
(–)-
c
i s
-
l
Cogna
u
c
L
actone S. Yadav,*a Ragam Nageshwar Rao,a Begari Prem Kumar,a Ragam Somaiah,a Kontham Ravindar,a
Basi V. Subba Reddy,a Ahamad Al Khazim Al Ghamdib
a
Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad – 500 007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Engineer Abdullah Bagshan for Bee Research, King Saudi University, Saudi Arabia
b
Received 30 April 2011; revised 8 July 2011
use of either a chiral auxiliary or enzymatic hydrolysis,
mainly Baker’s yeast reduction of 3-methyl-4-oxono-
nanoic acid or bioreduction of 3-methyl-4-oxononanoic
acid to introduce the chirality (Figure 1).9–11
Abstract: An efficient and concise stereoselective total synthesis of
naturally occurring (–)-cis-aerangis lactone and (–)-cis-cognac lac-
tone is described. The Sharpless asymmetric epoxidation of a pri-
mary allylic alcohol and TBSOTf-mediated intramolecular hydride
transfer of a chiral epoxy alcohol have been successfully utilized for
the construction of a key precursor with syn-aldol stereochemistry
using a non-aldol pathway.
O
O
O
O
Key words: lactones, Wittig olefination, Sharpless asymmetric ep-
oxidation, intramolecular hydride transfer, syn-aldol
(–)-cis-aerangis lactone (1)
(+)-trans-aerangis lactone (2)
O
O
O
(+)-trans-cognac lactone (4)
O
d-Lactones and g-butyrolactones are important structural
motifs in many biologically potent natural products.1
They are versatile building blocks for the synthesis of var-
ious biologically interesting natural products. These lac-
tone-derived molecules are present in Nature in particular
as pheromones and aroma compounds of many fruits,
flowers, and other natural products.2 (–)-cis-Aerangis lac-
tone [(4S,5S)-4-methyl-5-decanolide, 1] was discovered
by Kaiser in 1993 as the main odor component of the Af-
rican moth orchids Aerangis confusa and Aerangis kirkii
as a 1:1 mixture with its trans-diastereomer 2.3 Later, (–)-
cis-aerangis lactone was found to be the sole stereoisomer
in the scent of living white flowering orchids (Aerangis
confusa). The fragrance of this natural product was typical
for the lactonic odor of A. confusa and A. kirkii and was
identical to the olfactory qualities of natural aerangis lac-
tone. Its enantiomer (+)-cis-aerangis lactone was found to
be reminiscent of d-decalactone and its fragrance intensity
was much lower than (–)-cis-aerangis lactone (1).4
(–)-cis-cognac lactone (3)
Figure 1 Aerangis and cognac lactones 1–4
In continuation of our interest in the total synthesis of op-
tically active lactones and lactone-containing natural
products,12 herein we wish to report a facile synthesis of
(–)-cis-aerangis lactone (1) and (–)-cis-cognac lactone
(3).
O
O
(–)-cis-aerangis lactone (1)
OTBS O
H
5
O
O
(–)-cis-cognac lactone (3)
(–)-cis-Cognac lactone [(4S,5S)-cis-4-methyl-5-pentyl-
dihydrofuran-2(3H)-one, 3] is one of the Quercus lactones
which are known to present in various types of wood.
These Quercus lactones are responsible for the sensory
characteristics of wine and other alcoholic beverages such
as whisky, brandy, and cognac; they are extracted during
their ageing in oak barrels.5 (–)-cis-Cognac lactone was
found in both diastereomeric forms 3 and 4 in the litera-
ture.6 Consequently, many research groups were actively
involved in the synthesis of racemic and enantiomerically
pure cis- and trans-aerangis lactones7 and also cis- and
trans-cognac lactones.8 Most of these methods involve the
OH
O
n-hexanal
7
6
Scheme 1 Retrosynthetic analysis of (–)-cis-aerangis lactone and
(–)-cis-cognac lactone
In our approach, we utilized a common chiral aldehyde
precursor 5 for the construction of both the natural prod-
ucts (–)-cis-aerangis lactone (1) and (–)-cis-cognac lac-
tone (3). The stereoselective construction of aldehyde 5
was achieved by silyl triflate mediated regioselective
opening of epoxy alcohol 6, which in turn can be easily
accessed from commercially available and cost-effective
n-hexanal (7). This synthetic strategy was successfully
SYNTHESIS 2011, No. 19, pp 3168–3172
x
x.
x
x
.
2
0
1
1
Advanced online publication: 29.08.2011
DOI: 10.1055/s-0030-1260190; Art ID: Z42711SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
(–)-cis-Aerangis Lactone and (–)-cis-Cognac Lactone
3169
utilized by our group for the total synthesis of (–)-
TBSO
O
TBSO
maurenone13 and 5-epi-prelactone B (Scheme 1).14
a
b
H
OH
5
12
OH
O
a
b
TBSO
TBSO
n-hexanal
OEt
c
d
CN
OTs
7
8
9
13
14
OH
OTBS O
O
c
e
d
H
O
6
5
O
(–)-cis-cognac lactone (3)
OTBS
OTBS
f
CO2Et
CO2Et
Scheme 3 Reagents and conditions: (a) NaBH4, MeOH, 0 °C, 2 h,
92%; (b) TsCl, Et3N, DMAP, CH2Cl2, 0 °C, 4 h, 90%; (c) NaCN, NaI
(cat.), DMSO, 60 °C, 82%; (d) 1. 2 M NaOH, EtOH, 100 °C, 8 h; 2.
10% HCl, THF, 10 °C, 12 h, 70% over 2 steps.
11
10
g
alytic amount of sodium iodide.19 The crude nitrile 14 was
used as such without further work-up in the next step. The
subsequent base-induced hydrolysis of 14 followed by
lactonization gave the target molecule (–)-cis-cognac lac-
tone (3) in 70% yield. The spectroscopic (1H and 13C
NMR and IR) data and optical rotation of (–)-cis-cognac
lactone (3) were in good agreement with the literature
(Scheme 3).8
O
O
(–)-cis-aerangis lactone (1)
Scheme 2
Reagents and conditions: (a) Ph3P=C(CH3)CO2Et,
CH2Cl2, 0–25 °C, 2 h, 85%; (b) DIBAL-H, CH2Cl2, 0 °C, 2 h, 90%;
(c) t-BuOOH, (+)-DET, Ti(Oi-Pr)4, CH2Cl2, MS 4 Å, –25 °C, 90%;
(d) TBSOTf, i-Pr2NEt, CH2Cl2, MS 4 Å, –42 °C, 1 h, 85%; (e)
Ph3P=CHCO2Et, CH2Cl2, r.t., 12 h, 80%; (f) H2, Pd/C, EtOAc, 6 h,
95%; (g) AcOH, 1 M HCl, THF, 65 °C, 4 h, 65%.
In conclusion, we have demonstrated a highly efficient
and concise total synthesis of naturally occurring (–)-cis-
aerangis lactone and (–)-cis-cognac lactone via the stereo-
selective construction of a key aldehyde precursor with
syn-aldol stereochemistry using tert-butyldimethylsilyl
triflate and Hünig’s base mediated regioselective opening
of epoxy alcohol involving intramolecular hydride trans-
fer reaction. In contrast to previous reports, Sharpless
asymmetric epoxidation was used for the introduction of
chirality for the synthesis of both natural products. (–)-cis-
Aerangis lactone was obtained in 29% overall yield in
seven steps starting from n-hexanal and (–)-cis-cognac
lactone was obtained in 34% overall yield in eight steps.
The synthesis of remaining stereoisomers of aerangis lac-
tone and cognac lactone are in progress.
Accordingly, n-hexanal (7) was converted into the corre-
sponding a,b-unsaturated ester 8 using a stabilized Wittig
ylide [Ph3P=C(CH3)CO2Et] in 85% yield.15 Selective re-
duction of a,b-unsaturated ester 8 using diisobutylalumi-
num hydride gave the allyl alcohol 9 in 90% yield.
Sharpless asymmetric epoxidation of allyl alcohol 9 with
tert-butyl hydroperoxide and (+)-diethyl tartrate in
dichloromethane afforded the chiral epoxy alcohol 6 in
90% yield. Upon treatment of epoxy alcohol 6 with tert-
butyldimethylsilyl triflate at –42 °C gave the TBS-pro-
tected syn-aldol product 5 (common aldehyde precursor)
in 85% yield.16 The aldehyde 5 was further treated with
Ph3P=CHCO2Et in dichloromethane to obtain the a,b-un-
saturated ester 10 as a mixture of cis- and trans-isomers in
80% yield. The cis/trans mixture of ester 10 was then sub-
jected to catalytic hydrogenation over 10% palladium on
carbon to give the saturated ester 11 in 95% yield. Finally,
Column chromatography was performed using silica gel 60–120
mesh. All the solvents were dried and distilled prior to use. IR spec-
acid-catalyzed (AcOH, 1 M HCl, THF) desilylation of 11 tra were recorded on a Perkin-Elmer Infrared spectrophotometer ei-
ther neat or in CHCl3 as a thin film. 1H and 13C NMR were recorded
on a Varian Gemini 200MHZ and Bruker Avance 300 MHZ instru-
ments using TMS as an internal standard. Mass spectra were record-
ed on Micro mass VG 7070H mass spectrometer for EI, VG
Autospec mass spectrometer for FABMS and micromass Quatro
LC triple quadrupole mass spectrometer for ESI analysis. The opti-
followed by concomitant lactonization gave the (–)-cis-
aerangis lactone (1) in 65% yield.17 The spectroscopic (1H
and 13C NMR and IR) data and optical rotation of (–)-cis-
aerangis lactone (1) were in good agreement with the lit-
erature (Scheme 2).7
cal rotations were recorded on Jasco DIP-360 digital polarimeter.
The synthesis of (–)-cis-cognac lactone (3) commenced
from the common aldehyde precursor 5. Accordingly, al-
Ethyl (E)-2-Methyloct-2-enoate (8)
To a soln of ethyl 2-(triphenylphosphoranylidene)propanoate (72.0
g, 200 mmol) in CH2Cl2 (300 mL) was added n-hexanal (7; 10.0 g,
dehyde 5 was reduced to alcohol 12 using sodium borohy-
dride in methanol in 92% yield.18 This primary alcohol 12
was then treated with tosyl chloride in the presence of tri-
ethylamine and 4-(dimethylamino)pyridine in dichlo-
romethane to afford the tosylate 13 in 90% yield. Tosylate
13 was converted into corresponding nitrile 14 using sodi-
um cyanide in dimethyl sulfoxide in the presence of a cat-
100 mmol) at 0 °C and stirred at r.t. for 2 h. The solvent was re-
moved under reduced pressure and the residue was purified by col-
umn chromatography (silica gel, 8% EtOAc–hexane) to afford 8
(15.64 g, 85%) as a colorless liquid.
IR (neat): 2931, 2864, 1721, 1244, 1094 cm–1.
Synthesis 2011, No. 19, 3168–3172 © Thieme Stuttgart · New York

3170
J. S. Yadav et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 6.70 (td, J = 7.3, 5.8 Hz, 1 H), 4.17
(q, J = 7.3 Hz, 2 H), 2.16 (q, J = 6.5 Hz, 2 H), 1.81 (s, 3 H), 1.53–
1.23 (m, 9 H), 0.91 (t, J = 5.8 Hz, 3 H).
5 (14.63 g, 85%) as a colorless oil. This crude aldehyde was used as
such in the next step without further purification.
Ethyl (4S,5S,E)-5-(tert-Butyldimethylsiloxy)-4-methyldec-2-
enoate (10)
13C NMR (75 MHz, CDCl3): d = 168.1, 142.2, 127.5, 60.1, 31.6,
29.5, 29.4, 22.3, 14.1, 13.8, 12.1.
A soln of aldehyde 5 (2 g, 7.3 mmol) in anhyd CH2Cl2 (50 mL) was
added Ph3P=CHCO2Et (3.83 g, 11.0 mmol). The resulting mixture
was stirred for 12 h at r.t. and then extracted with Et2O (2 × 100
mL). The combined organic extracts were dried (anhyd Na2SO4)
and concentrated under reduced pressure to give 2.01 g (80%) of the
crude 10 (as a mixture of cis/trans isomers), which was used as such
in the next step.
MS (EI): m/z = 185 [M + H]+.
(E)-2-Methyloct-2-en-1-ol (9)
The ester 8 (15.64 g, 85 mmol) was dissolved in anhyd CH2Cl2 (200
mL) and then treated with 25% DIBAL-H in toluene (w/v) (96.52
mL, 170 mmol) in a dropwise fashion at 0 °C under an N2 atmo-
sphere. After stirring for 2 h at 0 °C, sat. aq potassium sodium tar-
trate (30 mL) was added and the mixture was extracted with Et2O
(3 × 150 mL). The combined organic layers were washed with
brine, dried (anhyd Na2SO4), and concentrated under reduced pres-
sure. The crude product was purified by column chromatography
(silica gel, 10% EtOAc–hexane) to afford the 9 (10.86 g, 90%) as a
colorless oil.
Ethyl (4S,5S)-5-(tert-Butyldimethylsiloxy)-4-methyldecanoate
(11)
A soln of ester 10 (2 g, 5.8 mmol) was dissolved in anhyd EtOAc
and then Pd/C (140 mg, 1.10 mmol) was added. The mixture was
stirred for 6 h at r.t. under H2 atmosphere. After completion, the cat-
alyst was filtered through a Celite pad and concentrated under re-
duced pressure. The resulting crude residue was purified by column
chromatography (silica gel) to give 11 (1.91 g, 95%).
IR (neat): 3337, 2925, 2857, 1460, 1379, 1012 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.34 (td, J = 5.8, 7.3 Hz, 1 H), 3.92
(s, 2 H), 1.98 (m, 2 H), 1.62 (s, 3 H), 1.54–1.15 (m, 6 H), 0.87 (t,
J = 5.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 128.8, 128.3, 68.1, 31.7, 28.5, 25.3,
22.5, 16.4, 13.9.
[a]D25 –5.2 (c 2.15, CHCl3).
IR (neat): 3450, 2950, 2857, 2246, 1740, 1637, 1464, 1383, 1254,
1088, 836, 774, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.08 (q, J = 7.3, 14.6 Hz, 2 H),
3.52–3.45 (m, 1 H), 2.26 (dd, J = 6.5, 14.6 Hz, 2 H), 1.44–1.18 (m,
18 H), 0.93–0.78 (m, 11 H), 0.01 (s, 6 H).
MS (EI): m/z = 165 [M + Na]+.
13C NMR (75 MHz, CDCl3): d = 174.1, 76.7, 60.2, 37.4, 33.7, 32.9,
[(2S,3S)-2-Methyl-3-pentyloxiran-2-yl]methanol (6)
A mixture of (+)-DET (2.36 g, 11.4 mmol) and Ti(Oi-Pr)4 (2.72 mL,
9.1 mmol) in CH2Cl2 (20 mL) containing 4Å molecular sieves was
stirred for 15 min at –25 °C under an N2 atmosphere. After 15 min,
4 M t-BuOOH in toluene (42 mL, 168 mmol) was added over a pe-
riod of 10 min and stirring was continued for 30 min. Then a soln of
allyl alcohol 9 (10.86 g, 76.4 mmol) in anhyd CH2Cl2 (100 mL) was
slowly added at –25 °C and the mixture was allowed to stir for 1.5
h at –25 °C and then 20% NaOH (9 mL) was added followed by
H2O (50 mL) at 0 °C. The resulting mixture was warmed up to r.t.
for 1 h and diluted with CH2Cl2. The mixture was filtered through
Celite and extracted with CH2Cl2 (2 × 250 mL). The combined or-
ganic layers were washed with H2O and brine soln and concentrated
under reduced pressure. Removal of the solvent followed by purifi-
cation by column chromatography (silica gel, 15% EtOAc–hexane)
afforded 6 (10.87 g, 90%) as a colorless oil.
32.6, 29.7, 26.1, 25.7, 22.8, 18.3, 14.7, –0.1.
HRMS (ESI): m/z [M + Na]+ calcd for C19H40O3NaSi: 367.2644;
found: 367.2653.
cis-(4S,5S)-4-Methyl-5-decanolide (1)
A soln of ester 11 (1 g, 2.9 mmol) in AcOH (10 mL), 1 M HCl (10
mL), and THF (10 mL) was stirred at 65 °C for 4 h. After comple-
tion, the mixture was quenched with sat. NaHCO3 soln (100 mL)
and extracted with EtOAc (3 × 150 mL). The combined organic lay-
ers were washed with brine, dried (anhyd Na2SO4), and concentrat-
ed under reduced pressure. The crude product was purified by flash
chromatography (silica gel, 50% EtOAc–hexane) to afford the pure
1 (0.34 g, 65%) as a colorless viscous oil.
[a]D25 –33 (c 1.25, CHCl3).
[a]D28 –13.5 (c 1.6, CHCl3).
IR (neat): 3427, 2956, 2927, 2862, 1461, 1382, 1040 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.71–3.39 (m, 2 H), 1.98 (m, 2 H),
2.96 (t, J = 5.1 Hz, 1 H), 1.61–1.20 (m, 9 H), 0.90 (t, J = 6.6 Hz, 3
IR (neat): 3452, 2930, 2863, 1734, 1460, 1378, 1246, 1122, 994,
909 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.33–4.21 (m, 1 H), 2.51 (t, J = 7.5
Hz, 2 H), 2.10–1.96 (m, 2 H), 1.74–1.24 (m, 9 H), 0.98 (d, J = 7.5
Hz, 3 H), 0.90 (t, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.1, 83.1, 35.8, 32.2, 32.1, 31.0,
28.4, 26.8, 26.1, 25.3, 14.6.
H).
13C NMR (75 MHz, CDCl3): d = 65.7, 61.2, 60.4, 31.5, 28.0, 26.0,
22.4, 14.0, 13.8.
HRMS (ESI): m/z [M + H]+ calcd for C9H19O2: 159.1385; found:
159.1390.
HRMS (ESI): m/z [M + Na]+ calcd for C11H20O2Na: 207.1360;
found: 207.1366.
(2S,3S)-3-(tert-Butyldimethylsiloxy)-2-methyloctan-1-ol (12)
A soln of aldehyde 5 (2 g, 7.3 mmol) in MeOH (30 mL) was treated
with NaBH4 (558 mg, 5 mmol) slowly at 0 °C. The mixture stirred
at 0 °C for 2 h. After completion, the solvent was removed under re-
duced pressure and then extracted with Et2O (3 × 50 mL). The com-
bined organic layers were washed with H2O, brine, dried (anhyd
Na2SO4) and concentrated under reduced pressure. The crude prod-
uct was purified by column chromatography (silica gel, 14%
EtOAc–hexane) to afford 12 (1.85 g, 92%) as a colorless oil.
(2R,3S)-3-(tert-Butyldimethylsiloxy)-2-methyloctanal (5)
To a cooled (–42 °C) suspension of 4 Å MS (3.0 g) in anhyd CH2Cl2
(80 mL) was added a soln of epoxy alcohol 6 (10 g, 63.2mmol) and
i-Pr2NEt (11.43 g, 88.6 mmol) in CH2Cl2. After 20 min, TBSOTf
(21.72 g, 82.2 mmol) was added dropwise over 15 min. The result-
ing soln was stirred for 1 h at –42 °C, then quenched by addition of
a buffer soln (25 mL) at pH 7.0 and was allowed to warm to r.t. The
resulting mixture was diluted with hexane and the phases were sep-
arated. The combined organic layers were washed sat. CuSO4 (2 ×)
followed by brine and then dried (anhyd Na2SO4), filtered through
Celite, and concentrated under reduced pressure to afford the crude
[a]D27 –4.0 (c 1.0, CHCl3).
IR (neat): 3452, 2920, 2852, 1464, 1360, 1174 cm–1.
Synthesis 2011, No. 19, 3168–3172 © Thieme Stuttgart · New York

PAPER
(–)-cis-Aerangis Lactone and (–)-cis-Cognac Lactone
3171
1H NMR (300 MHz, CDCl3): d = 3.80–3.72 (m, 1 H), 3.65 (dd,
J = 10.5, 2.0 Hz, 1 H), 3.49 (dd, J = 10.5, 5.0 Hz, 1 H), 1.98–1.87
(m, 1 H), 1.52–1.13 (m, 10 H), 0.92 (s, 12 H), 0.82 (d, J = 6.9 Hz, 2
H), 0.10 (d, J = 6.7 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 68.1, 66.5, 38.7, 34.4, 31.8, 25.7,
22.5, 18.1, 14.3, 10.5, 0.1,
chromatography (silica gel, 40% EtOAc–hexane) to afford pure 3
(420 mg, 70%).
[a]D25 –51 (c 1.0, CHCl3).
IR (neat): 2930, 2860, 1778, 1462, 1421, 1338, 1335, 1294, 1077,
933 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.46–4.31(m, 1 H), 2.60 (t, J = 7.3
Hz, 2 H), 2.25–2.0 (m, 1 H), 1.73–1.20 (m, 8 H), 1.0 (d, J = 7.3 Hz,
3 H), 0.90 (d, J = 6.6 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C15H34O2NaSi: 297.2225;
found: 297.2224.
13C NMR (75 MHz, CDCl3): d = 176.6, 83.3, 37.2, 32.6, 31.3, 29.5,
(2S,3S)-3-(tert-Butyldimethylsiloxy)-2-methyloctyl 4-Methyl-
benzenesulfonate (13)
To a soln of alcohol 12 (1.85 g, 6.7 mmol) in anhyd CH2Cl2 (20 mL)
at 0 °C, Et3N (1.87 mL, 13.5 mmol), TsCl (1.53 g, 8.1 mmol), and
DMAP (164 mg, 1.35 mmol) were added under an N2 atmosphere
and the stirring continued for a further 4 h. After completion, the
25.2, 22.1, 13.6, 13.4,.
HRMS (ESI): m/z [M + Na]+ calcd for C10H18O2Na: 193.1204;
found: 193.1212.
mixture was quenched with sat. aq NH4Cl soln and then diluted with Acknowledgment
EtOAc (2 × 50 mL), washed with H2O and brine, and dried
R.N.R., B.P.K., R.S., and K.R. thank the CSIR, New Delhi for the
(Na2SO4). Removal of the solvent followed by purification by col-
umn chromatography (silica gel, 10% EtOAc–hexane) afforded 13
(2.6 g, 90%) as a colorless oil.
award of fellowships. Author acknowledges the partial support by
King Saud University for Global Research Network for Organic
Synthesis (GRNOS).
[a]D27 +7.6 (c 1.1, CHCl3).
IR (neat): 3449, 2954, 2922, 2857, 1708, 1605, 1513, 1464, 1364,
1253, 1180, 1097, 1040, 967, 836, 773, 667, 554 cm–1.
References and Notes
1H NMR (300 MHz, CDCl3): d = 7.73 (d, J = 8.0 Hz, 2 H), 7.31 (d,
J = 8.0 Hz, 2 H), 4.03–3.57 (m, 3 H), 3.45 (s, 3 H), 1.99–1.79 (m, 1
H), 1.50–1.09 (m, 11 H), 0.89 (d, J = 3.67 Hz, 3 H), 0.81 (s, 9 H),
0.02 (d, J = 9.9 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 144.5, 133.0, 129.7, 127.8, 73.01,
71.8, 37.2, 33.7, 31.8, 25.7, 25.3, 17.9, 13.3, 10.4, –0.1, –3.6.
(1) Koch, S. S. C.; Chamberlin, A. R. In Enantiomerically Pure
g-Butyrolactones in Natural Products Synthesis; Atta-ur-
Rahman, Ed.; Elsevier Science: Amsterdam, 1995, 687.
(2) (a) Mori, K. In Techniques in Pheromone Research;
Hummel, H. H.; Miller, T., Eds.; Springer: New York, 1989.
(b) Silverstein, R. M. In Semiochemistry Flavours and
Pheromones; Acree, T.; Soderland, D. M., Eds.; Walter de
Gruyter: Berlin, 1985.
MS (ESI): m/z = 429 [M + H]+.
(3) Kaiser, R. The Scent of Orchids, Olfactory and Chemical
(3S,4S)-4-(tert-Butyldimethylsiloxy)-3-methylnonanenitrile
(14)
Investigations; Elsevier: Amsterdam, 1993.
(4) Bartschat, D.; Lehmann, D.; Dietrich, A.; Mosandl, A.;
Kaiser, R. Phytochem. Anal. 1995, 6, 130.
To a stirred soln of tosylate 13 (2 g, 4.6 mmol) in anhyd DMSO was
added a soln of NaI (700 mg, 4.6 mmol) and NaCN (915 mg, 18.6
mmol) in anhyd DMSO (15 mL). The mixture was stirred at 60 °C
for 12 h. After completion, the mixture was diluted with H2O and
extracted with Et2O (3 × 50 mL). The combined organic layers were
washed with brine, dried (anhyd Na2SO4), and concentrated under
reduced pressure. The crude product was purified by column chro-
matography (silica gel, 12% EtOAc–hexane) to give pure 14 (1.08
g, 82%) as a colorless oil.
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J. Chromatogr., A. 2006, 1102, 25. (b) Cerdan, T. G.;
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IR (neat): 3450, 2955, 2930, 2857, 2246, 1464, 1383, 1254, 1088,
836, 774 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.76–3.65 (m, 1 H), 2.45 (dd,
J = 16.1, 6.6 Hz, 1 H), 2.20 (dd, J = 16.1, 8.0 Hz, 1 H), 2.08–1.95
(m, 1 H), 1.50–1.20 (m, 11 H), 1.03 (d, J = 6.6 Hz, 3 H), 0.93 (s, 9
H), 0.11 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 119.0, 96.2, 73.7, 35.4, 33.3, 25.9,
25.4, 22.6, 20.8, 14.0, 13.6, –4.5, –4.1.
MS (ESI): m/z = 301 [M + H2O]+.
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(4S,5S)-cis-4-Methyl-5-pentyldihydrofuran-2(3H)-one (3)
A soln of nitrile 14 (1.0 g, 3.5 mmol) in abs EtOH (50 mL) in the
presence of 2 M NaOH in EtOH (10 mL) was heated at 100 °C for
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pH 2.0) with aq 10% HCl. The mixture was stirred at 10 °C for 12
h. Then the mixture was diluted with EtOAc (15 mL), washed with
NaHCO3, followed by H2O and brine, and the solvent was removed
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