Stereoselective total synthesis of tarchonanthuslactone and formal synthesis of (-)-colletol

Article abstract of DOI:10.1055/s-2007-990850

A simple and efficient stereoselective total synthesis of tarchonanthuslactone and formal synthesis of (-)-colletol is described using as the key steps Jacobsen's kinetic resolution and a Sharpless asymmetric epoxidation. The synthesis of tarchonanthus-la

Full text of DOI:10.1055/s-2007-990850

PAPER
3639
Stereoselective Total Synthesis of Tarchonanthuslactone and Formal
Synthesis of (–)-Colletol
Synthesis
.
of
T
archona
n
S
thuslactone an
.
d (–)-Collet
Y
ol adav,* P. Murali Krishna Reddy, Manoj K. Gupta, Ch. Janardhana Chary
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 14 August 2007; revised 27 August 2007
classes of compounds have shown significant activity
against various pathogenic microorganisms.6 The promis-
ing biological activity and the unique structure of these
families make them attractive synthetic targets. There
Abstract: A simple and efficient stereoselective total synthesis of
tarchonanthuslactone and formal synthesis of (–)-colletol is de-
scribed using as the key steps Jacobsen’s kinetic resolution and a
Sharpless asymmetric epoxidation. The synthesis of tarchonanthus-
lactone and the seco acid proceeded in 14% and 13% overall yield, have been several synthetic efforts toward the synthesis of
tarchonanthuslactone (1)7 and (–)-colletol (3),8 however,
respectively, starting from chiral (R)-propylene oxide.
their syntheses using inexpensive and readily available
raw materials with short and facile routes continue to be
challenging endeavors.
Keywords: hydrolytic kinetic resolution, PMB acetal formation,
Sharpless asymmetric epoxidation, lactonization, one-pot oxida-
tion/alkenation, esterification
O
O
Natural products possessing the lactone framework have
attracted considerable attention in organic synthesis due
to their unique structures and potent biological activity.1
Tarchonanthuslactone (1), an a,b-unsaturated d-lactone
was isolated in 1979 by Bohlmann from the leaves of the
tree Tarchonanthus trilobus (Figure 1).2 Later, Nakata et
al. established its absolute configuration by asymmetric
synthesis.3 The basic structure of tarchonanthuslactone (a
dihydrocaffeic acid ester) consists of a syn-1,3-diol unit
with one hydroxy group involved in an unsaturated lac-
tone and the other esterified with 3,4-dihydroxyhydrocin-
namic acid. A few years ago, Hsu et al. showed that 1
lowered the plasma glucose level in diabetic rats.4 This
important biological activity gave an indication that tar-
chonanthuslactone (1) or its analogues have potential to
be used in human beings. Similarly, (–)-colletol (3), a 14-
membered bis-macrolactone, was first isolated in 1973
from the fermentation broth of Colletotrichum capsici to-
gether with other related metabolites.5 Moreover, these
O
O
HO
HO
O
O
HO
1
O
O
O
3
OH
O
2
Figure 1 Tarchonanthuslactone (1), 2, and (–)-colletol (3)
In continuation of our programme on the synthesis of bio-
active lactones,9 herein we report a facile stereoselective
synthesis of tarchonanthuslactone (1) and formal synthe-
sis of (–)-colletol (3). Our retrosynthetic strategy for 1 is
outlined in Scheme 1. The first disconnection involved
cleavage to give lactone 2 and acid 4. It was envisioned
C6H4(4-OMe)
O
O
TBSO
O
OH
O
1
+
OH
TBSO
5
4
O
2
O
OMe
O
OTHP
+
7
6
Scheme 1 Retrosynthetic analysis of 1 and 2
SYNTHESIS 2007, No. 23, pp 3639–3646
x
x.
x
x
.
2
0
0
7
Advanced online publication: 29.10.2007
DOI: 10.1055/s-2007-990850; Art ID: Z18707SS
© Georg Thieme Verlag Stuttgart · New York

3640
J. S. Yadav et al.
PAPER
OH
O
OPMB
a
OTHP
b
OTHP
OTHP
+
77%
92%
7
8
6
9
OPMB
OPMB
OPMB
O
c
e
f
d
OH
OH
80%
83%
87%
92%
OH
12
10
11
C6H4(4-OMe)
O
C6H4(4-OMe)
O
C6H4(4-OMe)
O
PMBO
OH
O
i
O
h
O
g
86%
CHO
92%
78%
OH
OH
5
13
15
14
O
OMe
O
O
O
TBSO
TBSO
OH
O
l
j
k
O
O
1
82%
90%
83%
16
2
Scheme 2 Reagents and conditions: (a) n-BuLi, BF3·OEt2, THF, –78 °C, 3 h, 77%; (b) NaH, PMBBr, THF, 0 °C to r.t., 6 h, 92%; (c) MeOH,
CSA (cat.), r.t., 4 h, 87%; (d) LiAlH4, THF, r.t., 4 h, 92%; (e) (–)-DIPT, Ti(Oi-Pr)4, t-BuOOH, –20 °C, 6 h, 80%; (f) Red-Al, THF, –20 °C to
r.t., 1 h, 83%; (g) DDQ, CH2Cl2, 0 °C, 2 h, 78%; (h) DMP, CH2Cl2, r.t., 3 h; 92%; (i) MeO2CCH2P(O)(OCH2CF3)2, NaH, THF, –78 °C, 30 min,
86%; (j) PTSA, benzene, r.t., 5 h, 90%; (k) DCC, DMAP, 4, CH2Cl2, r.t., 15 h, 83%; (l) TBAF, THF, r.t., 1 h, 82%.
that the key fragment 2 could be obtained by lactonization yield. Regioselectively hydride transfer of 12 with Red-
of 5, which is obtained by iterative hydrolytic kinetic res- Al13 provided 1,3-diol 13 in 83% yield, treatment of which
olution from propylene oxide 610 followed by Sharpless with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1
asymmetric epoxidation that fixed both the stereogenic equiv) in anhydrous dichloromethane under controlled
centers.
conditions resulted in the formation of 4-methoxyben-
zylidenedioxy acetal14 14 in 78% yield.
Accordingly, metalation of 3-(tetrahydro-2H-pyran-2-
yloxy)propyne (7) with n-butyllithium at –78 °C in Primary alcohol 14 was oxidized with Dess–Martin per-
tetrahydrofuran11 followed by addition of boron trifluo- iodinane to afford aldehyde 15, which was subjected to a
ride–diethyl ether complex and (R)-propylene oxide (6)12 modified Wadsworth–Emmons olefination reaction in the
gave the homopropargyl alcohol 8 in 77% yield presence of sodium hydride in tetrahydrofuran, to provide
(Scheme 2). The secondary alcohol was then protected as the key fragment 5 in 79% yield (2 steps). Treatment of 5
the 4-methoxybenzyl ether using sodium hydride and 4- with 4-toluenesulfonic acid in benzene permitted simulta-
methoxybenzyl bromide in tetrahydrofuran and followed neous deprotection of the acetal and lactonization15 to
by deprotection of the tetrahydropyranyl ether to give pri- give the desired lactone 2 in 90% yield. Classical esterifi-
mary alcohol 10 in 80% yield (2 steps). The resulting pri- cation of lactone 2 with acid 4 in the presence of N,N¢-di-
mary alcohol 10 was converted into homoallylic alcohol cyclohexylcarbodiimide and 4-(dimethylamino)pyridine
11 by lithium aluminum hydride reduction in tetrahydro- followed by removal of the phenol protecting groups af-
furan in 92% yield; 11 was subjected to Sharpless asym- forded tarchonanthuslactone (1) in 68% yield (2 steps),
metric epoxidation to afford epoxy alcohol 12 in 80% whose spectral data were identical with that reported.7
O
O
lactonization
OPMB
OH OTBS
3
COOH
CO2Et
+
OTBS
18
19
COOH
OH
17
OPMB
PMBO
OH
OH
OH
11
13
Scheme 3 Retrosynthetic analysis of 3
Synthesis 2007, No. 23, 3639–3646 © Thieme Stuttgart · New York

PAPER
Synthesis of Tarchonanthuslactone and (–)-Colletol
3641
OPMB
OPMB
OPMB
b
a
CHO
COOH
OH
83%
90%
11
20
18
PMBO
PMBO
OTBS
PMBO
OH
OH
c
d
CO2Et
CO2Et
87%
87%
OH
22
13
21
OH
OTBS
e
CO2Et
84%
19
Scheme 4 Reagents and conditions: (a) DMP, CH2Cl2, r.t., 3 h; 90%; (b) NaH2PO4, 2-methylbut-2-ene, NaClO2, t-BuOH–H2O (3:1), 0 °C, 4
h, 83%; (c) (i) PhI(OAc)2, TEMPO (cat.), CH2Cl2, r.t., 2 h. (ii) Ph3P=CHCO2Et (2 equiv), r.t., 2 h, 87%; (d) TBDMSCl, imidazole, CH2Cl2, 0
°C to r.t., 2 h, 87%; (e) DDQ, CH2Cl2–H2O (17:1), r.t., 1 h, 84%.
The disconnection approach to 17, which could be ob- Having made both the fragments 18 and 19 successfully,
tained from lactonization of key fragments 18 and 19 is they were then subjected to esterification (Scheme 5) un-
shown in Scheme 3. The acid 18 could be prepared from der Shiina’s conditions17 using 2-methyl-6-nitrobenzoic
the homoallylic alcohol 11, and 19 could be obtained from anhydride (MNBA) and 4-(dimethylamino)pyridine in
13.
dichloromethane at room temperature to furnish 23 in
84% yield. The PMB ether of 23 was cleaved by 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone in dichloro-
methane–water (17:1) to afford 24 in 81% yield. Selective
removal of the ethyl ester group in 23 with lithium hy-
droxide monohydrate in tetrahydrofuran–water (4:1) gave
seco acid 17 in 80% yield.
Accordingly, homoallylic alcohol 11 was oxidized using
Dess–Martin periodinane and subsequently oxidized to
the acid 18 by conventional methods (Scheme 4). The pri-
mary hydroxy group of 13 was subjected to one-pot oxi-
dation/alkenation following Vatele’s protocol;16 thus, the
primary hydroxy group was oxidized with (diacetoxy-
iodo)benzene and catalytic TEMPO to afford the alde- We have described a simple and efficient route for the to-
hyde , which was subsequently subjected to a two-carbon tal synthesis of tarchonanthuslactone (1) and formal syn-
homologation using (ethoxycarbonylmethylene)triphe- thesis of (–)-colletol (3) starting from a chiral epoxide
nylphosphorane in dichloromethane to furnish (E)-a,b- obtained from Jacobsen’s salen reagent and later using
unsaturated ester 21 in 87% yield. The secondary alcohol Sharpless asymmetric epoxidation to fix both the chiral
was then protected as the silyl ether using tert-butyldi- centers. This route is amenable, economic, and uses easily
methylsilyl chloride and imidazole in dichloromethane handled reagents to synthesize tarchonanthuslactone (1)
followed by deprotection of the PMB ether using 2,3- and (–)-colletol (3).
dichloro-5,6-dicyano-1,4-benzoquinone in dichloro-
methane–water (17:1) to afford the fragment 19.
O
O
O
O
OH
OTBS
b
c
a
CO2Et
81%
80%
84%
TBSO
TBSO
19
CO2Et
OPMB
23
CO2Et
OH
O
24
O
O
O
d
TBSO
HO
COOH
OH
17
O
O
3
Scheme 5 Reagents and conditions: (a) 18, MNBA, DMAP, CH2Cl2, r.t. 2 h, 84%; (b) DDQ, CH2Cl2–H2O (17:1), r.t., 1 h, 81%; (c) LiOH·H2O
(1 equiv), THF–H2O (4:1), r.t., 6 h, 80%; (d) ref. 8b.
Synthesis 2007, No. 23, 3639–3646 © Thieme Stuttgart · New York

3642
J. S. Yadav et al.
PAPER
All solvents and reagents were purified by standard techniques.
Column chromatography was performed using silica gel 60–120
mesh. All solvents were dried and distilled prior to use. IR spectra
were recorded on a Perkin–Elmer Infrared spectrophotometer as
KBr wafers, neat or in CHCl3 as a thin film. 1H and 13C NMR were
recorded on a Varian Gemini 200, Bruker Avance 300 or Varian
Unity 400 instrument (1H operating frequencies of 300 MHz and
400 MHz, respectively) using TMS as an internal standard. MS
spectra were obtained on an Agilent Technologies LC/MSD Trap
SL. HRMS were measured on a Varian MAT-711 and MAT-95.
The optical rotations were recorded on a JASCO DIP-360 digital
polarimeter at 25 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C19H26NaO4: 341.1728;
found: 341.1724.
(5R)-5-(4-Methoxybenzyloxy)hex-2-yn-1-ol (10)
MeOH (20 mL) and CSA (cat.) were added to 9 (4.0 g, 12.57 mmol)
at r.t. After 4 h the solvent was removed in vacuo, and crude residue
was diluted with CH2Cl2 (20 mL) and sat. aq NaHCO3 (15 mL). The
organic layer was separated, washed with brine (2 × 15 mL) and
H2O (20 mL) and then dried (Na2SO4). The filtrate was concentrat-
ed under reduced pressure and the residue was purified by column
chromatography (EtOAc–hexane, 2:8).
Colorless liquid; yield: 2.56 g (87%); [a]D25 +7.5 (c 1.0, CHCl3).
IR (KBr): 3412, 2931, 2868, 1612, 1513, 1247, 1030, 821, 575
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.22 (d, J = 9.0 Hz, 2 H), 6.81 (d,
J = 9.0 Hz, 2 H), 4.44 (s, 2 H), 4.12 (s, 2 H), 3.76 (s, 3 H), 3.59 (q,
J = 6.0 Hz, 1 H), 2.74 (br s, 1 H), 2.48–2.28 (m, 2 H), 1.25 (d,
J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 19.4, 26.0, 50.9, 55.1, 70.1, 72.7,
80.1, 82.4, 113.6, 129.1, 130.3, 159.0.
MS (ESI): m/z = 257.1 [M + Na]+, 217.2, 173.1, 121.1.
HRMS (ESI): m/z [M + Na]+ calcd for C14H18NaO3: 257.1153;
(2R)-6-(Tetrahydro-2H-pyran-2-yloxy)hex-4-yn-2-ol (8)
A 1.6 M n-BuLi in hexane (26.7 mL, 42.8 mmol) was added slowly
to a suspension of 7 (5.0 g, 35.71 mmol) in anhyd THF (60 mL) at
–78 °C and the mixture was stirred for 1 h. BF3·OEt2 (6.77 g, 42.84
mmol) followed by 2-methyloxirane (6, 4.14 g, 71.37 mmol) were
added and the mixture was stirred at –78 °C for 1 h. On completion
of the reaction (TLC, ca. 1 h), the mixture was quenched with sat.
NH4Cl (20 mL) followed by sat. NaHCO3 (20 mL). After a few min,
the layers were separated and the aqueous layer was extracted with
EtOAc (3 × 60 mL). The combined organic layers were dried
(Na2SO4) and concentrated to afford a residue that was purified by
column chromatography (EtOAc–hexane, 2:8).
found: 257.1150.
Colorless liquid; yield: 5.4 g (77%); [a]D25 +10.5 (c 2.8, CHCl3).
(5R,E)-5-(4-Methoxybenzyloxy)hex-2-en-1-ol (11)
IR (KBr): 3421, 2940, 2871, 1638, 1448, 1349, 1201, 1117, 1022,
941, 563 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.78 (t, J = 3.0 Hz, 1 H), 4.21 (dt,
J = 2.2, 4.5, 6.7 Hz, 2 H), 3.89 (q, J = 6.0 Hz, 1 H), 3.85–3.67 (m, 1
H), 3.54–3.47 (m, 1 H), 2.63 (br s, 1 H), 2.37–2.33 (m, 2 H), 1.88–
1.50 (m, 6 H), 1.25 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 18.9, 22.1, 25.1, 29.2, 30.1, 54.4,
61.8, 66.1, 78.1, 82.8, 96.6.
ESI/MS: m/z = 221.1 [M + Na]+, 199.1 [M+], 173.1, 102.2, 85.2.
LiAlH4 (0.467 g, 12.30 mmol) was added portionwise to 10 (2.4 g,
10.25 mmol) dissolved in anhyd THF (30 mL) at 0 °C. The mixture
was warmed to r.t. and stirred for 4 h. On completion of the reaction
(TLC) it was quenched by slow addition of sat. aq Na2SO4 (10 mL)
at 0 °C. After a few min, the layers were separated and the aqueous
layer was extracted with Et2O (3 × 15 mL). The combined organic
layers were dried (Na2SO4), and concentrated to afford a residue
that was purified by column chromatography (EtOAc–hexane, 2:8).
Colorless liquid; yield: 2.2 g (92%); [a]D25 –3.6 (c 1.0, CHCl3).
HRMS (ESI): m/z [M + Na]+ calcd for C11H18NaO3: 221.1153;
found: 221.1152.
IR (KBr): 3450, 2929, 2865, 1612, 1513, 1247, 1032, 821, 517
cm–1.
1H NMR (200 MHz, CDCl3): d = 7.21 (d, J = 9.1 Hz, 2 H), 6.82 (d,
J = 9.1 Hz, 2 H), 5.63–5.59 (m, 2 H), 4.40 (d, J = 6.6 Hz, 2 H), 3.98
(br d, J = 2.2 Hz, 2 H), 3.76 (s, 3 H), 3.49 (q, J = 6.6 Hz, 1 H), 2.32
(br s, 1 H), 2.26–2.14 (m, 2 H), 1.16 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 19.2, 38.8, 55.0, 63.1, 69.7, 73.9,
113.5, 128.3, 128.9, 130.7, 131.4, 158.8.
MS (ESI): m/z = 259.1 [M + Na]+, 219.1, 159.1, 121.1.
HRMS (ESI): m/z [M + Na]+ calcd for C14H20NaO3: 259.1310;
2-[(5R)-5-(4-Methoxybenzyloxy)hex-2-ynyloxy]tetrahydro-2H-
pyran (9)
To a well-stirred suspension of freshly activated NaH (60% disper-
sion in mineral oil; 1.09 g, 45.45 mmol) in anhyd THF (40 mL), was
added dropwise at 0 °C a soln of 8 (4.5 g, 22.75 mmol) in anhyd
THF (15 mL). After 30 min, 4-methoxybenzyl bromide (5.0 g,
24.96 mmol) was added and the mixture was warmed to r.t. and
stirred for 5.5 h. The reaction was quenched with crushed ice and
product was extracted with Et2O (3 × 45 mL). The combined organ-
ic layers were washed with H2O (45 mL) and brine (2 × 15 mL) and
dried (Na2SO4). The mixture was filtered and the volatiles removed
under reduced pressure to give a crude product that was purified by
column chromatography (EtOAc–hexane, 5:9.5).
found: 259.1302.
{(2R,3R)-3-[(2R)-2-(4-Methoxybenzyloxy)propyl]oxiran-2-
yl}methanol (12)
Anhyd CH2Cl2 (20 mL) was cooled to –20 °C under N2, Ti(Oi-Pr)4
(0.31 g, 1.10 mmol) and (–)-DIPT (0.30 g, 1.27 mmol) were sequen-
tially added and stirred for 5–10 min. A soln of alcohol 11 (2.0 g,
8.47 mmol) in CH2Cl2 (5 mL) followed by t-BuOOH (1.52 g, 16.94
mmol) were added to the mixture, which was stirred at –20 °C for 6
h. The mixture was allowed to warm to 0 °C, quenched with 10%
aq NaOH soln saturated with NaCl (10 mL), and stirred vigorously
for 1 h. The mixture was filtered through Celite and extracted with
EtOAc (2 × 25 mL). The combined organic layers were washed
with brine (10 mL), dried (Na2SO4), evaporated under reduced pres-
sure, and purified by column chromatography (EtOAc–hexane,
2.5:7.5).
Pale yellow liquid; yield: 6.6 g (92%); [a]D25 –2.8 (c 1.0, CHCl3).
IR (KBr): 2941, 2869, 1724, 1629, 1444, 1129, 1076, 1030, 972,
813 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.23 (d, J = 9.0 Hz, 2 H), 6.81 (d,
J = 9.0 Hz, 2 H), 4.77 (t, J = 3.0 Hz, 1 H), 4.45 (s, 2 H), 4.18 (td,
J = 2.2, 4.5, 6.7 Hz, 1 H), 3.83–3.78 (m, 1 H), 3.78 (s, 3 H), 3.67–
3.45 (m, 2 H), 2.55–2.46 (m, 1 H), 2.32 (ddt, J = 2.2, 4.5, 7.5 Hz, 1
H), 1.88–1.48 (m, 7 H), 1.25 (d, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 19.0, 19.5, 25.3, 26.3, 30.2, 54.4,
55.1, 61.8, 70.2, 72.9, 83.2, 96.5, 113.6, 129.0, 130.5, 159.0.
Colorless liquid; yield: 1.7 g (80%); [a]D25 –7.3 (c 1.0, CHCl3).
MS (ESI): m/z = 341.1 [M + Na]+, 245.1.
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PAPER
Synthesis of Tarchonanthuslactone and (–)-Colletol
3643
IR (KBr): 3423, 2969, 2927, 2863, 1612, 1513, 1247, 1033, 821,
516 cm–1.
(2.5 mL) at r.t. After 3 h, the pale pink mixture was transferred to an
Erlenmeyer flask containing sat. aq NaHCO3 (25 mL). The separat-
ed organic layer was washed with brine (2 × 10 mL) and H2O (10
mL), dried (Na2SO4), and filtered and the solvent was removed in
vacuo. Crude 15 was utilized in the next step without further purifi-
cation. Yellow oil; yield 0.64 g (92%).
1H NMR (300 MHz, CDCl3): d = 7.21 (d, J = 9.0 Hz, 2 H), 6.82 (d,
J = 9.1 Hz, 2 H), 4.51 (d, J = 11.3 Hz, 1 H), 4.35 (d, J = 11.3 Hz, 1
H), 3.80–3.76 (m, 1 H), 3.78 (s, 3 H), 3.64 (q, J = 6.0 Hz, 1 H),
3.58–3.51 (m, 1 H), 3.01 (dt, J = 2.2, 6.0, 8.0 Hz, 1 H), 2.84–2.81
(m, 1 H), 1.87–1.62 (m, 2 H), 1.25 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 19.4, 38.2, 53.1, 55.1, 58.1, 61.6,
69.7, 71.8, 113.6, 129.1, 130.5, 158.9.
Methyl (Z,5S,7R)-5,7-(4-Methoxybenzylidenedioxy)oct-2-
enoate (5)
To soln of bis(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phos-
phonate (0.70 g, 2.2 mmol) in anhyd THF (10 mL) was added NaH
(60% dispersion in mineral oil, 96 mg, 4.0 mmol) at 0 °C; vigorous
gas evolution was observed. After 45 min, to the resulting clear soln
was added aldehyde 15 (0.5 g, 2.0 mmol) in anhyd THF (5 mL)
dropwise at –78 °C. After 30 min, the mixture was diluted with H2O
(20 mL) and extracted with EtOAc (3 × 20 mL). The combined or-
ganic layers were washed with H2O (2 × 20 mL) and brine (2 × 20
mL) and dried (Na2SO4). Solvent was removed and the residue was
purified by column chromatography (EtOAc–hexane, 3:7).
MS (ESI): m/z = 275.1 [M + Na]+, 231.1, 121.0.
HRMS (ESI): m/z [M + Na]+ calcd for C14H20NaO4: 275.1259;
found: 275.1257.
(3S,5R)-5-(4-Methoxybenzyloxy)hexane-1,3-diol (13)
Red-Al (65% in toluene; 10.0 mL) was added dropwise to 12 (1.5 g,
5.95 mmol) dissolved in anhyd THF (20 mL) at –20 °C. Vigorous
gas evolution was observed. After 1 h, the reaction was quenched
with sat. aq potassium sodium tartrate soln and stirred for 3 h. Two
clear layers were obtained which were separated and the aqueous
layer was extracted with Et2O (2 × 25 mL). The combined organic
layers were dried (Na2SO4) and filtered and the solvent was re-
moved by rotary evaporation to afford a residue that was purified by
column chromatography (EtOAc–hexane, 2:8).
Colorless liquid; yield: 1.25 g (83%); [a]D25 –44.6 (c 1.0, CHCl3).
IR (KBr): 3396, 2927, 1612, 1513, 1247, 1033, 819, 567, 418 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.18 (d, J = 8.8 Hz, 2 H), 6.81 (d,
J = 8.8 Hz, 2 H), 4.57 (d, J = 11.0 Hz, 1 H), 4.31 (d, J = 11.0 Hz, 1
H), 4.41–3.65 (m, 4 H), 3.78 (s, 3 H), 1.83–1.45 (m, 4 H), 1.22 (d,
J = 5.8 Hz, 3 H).
Colorless liquid, yield: 0.53 g (86%); [a]D25 –18.6 (c 0.5, CHCl3).
IR (KBr): 2925, 2854, 1721, 1615, 1518, 1249, 1175, 1034, 827,
674, 591 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35 (d, J = 8.3 Hz, 2 H), 6.83 (d,
J = 8.3 Hz, 2 H), 6.46 (dt, J = 7.4, 11.6, 14.1 Hz, 1 H), 5.83 (dt,
J = 1.6, 3.3, 11.6 Hz, 1 H), 5.41 (s, 1 H), 3.97–3.81 (m, 2 H), 3.80
(s, 3 H), 3.69 (s, 3 H), 3.14–2.99 (m, 1 H), 2.91–2.75 (m, 1 H), 1.65–
1.40 (m, 2 H), 1.27 (d, J = 5.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 29.6, 35.5, 38.1, 51.0, 55.2, 72.8,
75.8, 100.7, 113.5, 120.7, 127.4, 131.3, 145.8, 159.8, 166.7.
MS (ESI): m/z = 329.1 [M + Na]+, 211.0, 186.1, 171.0, 12.0, 93.0.
HRMS (ESI): m/z [M + Na]+ calcd for C17H22NaO5: 329.1364;
13C NMR (50 MHz, CDCl3): d = 19.8, 38.6, 43.7, 55.2, 61.0, 69.6,
71.8, 75.6, 113.8, 129.3, 129.9, 159.3.
MS (ESI): m/z = 277.0 [M + Na]+, 121.1.
found: 329.1375.
(S)-6-[(R)-2-Hydroxypropyl]-5,6-dihydro-2H-pyran-2-one (2)
A soln of 5 (0.2 g, 0.65 mmol) in benzene (2 mL) was added PTSA
(cat.) was stirred at r.t. for 5 h. The solvent was removed and residue
was diluted with EtOAc (10 mL), and quenched with sat. NaHCO3
(2 mL); the layers were separated and aqueous layer was extracted
with EtOAc (3 × 6 mL). The combined organic layers were washed
with brine (2 × 6 mL) and H2O (6 mL), dried (Na2SO4), and concen-
trated to give a residue that was purified by column chromatography
(EtOAc–hexane, 3:7).
Colorless liquid; yield: 91 mg (90%); [a]D25 –110 (c 0.8, CHCl3).
IR (KBr): 3420, 2925, 2853, 1715, 1386, 1251, 1117, 1046 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.89 (ddd, J = 3.0, 6.0, 9.8 Hz, 1
H), 6.08 (dt, J = 3.0, 9.8 Hz, 1 H), 4.62–4.59 (m, 1 H), 4.12–4.09
(m, 1 H), 2.47–2.36 (m, 2 H), 2.00–1.75 (m, 2 H), 1.26 (d, J = 6.0
Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C14H22NaO4: 277.1415;
found: 277.1414.
(3S,5R)-3,5-(4-Methoxybenzylidenedioxy)hexan-1-ol (14)
Compound 13 (1.1 g, 4.33 mmol) was added slowly to a suspension
of DDQ (1.0 g, 4.33 mmol) and anhyd CH2Cl2 (15 mL) at 0 °C and
the mixture was stirred for 2 h. On completion of the reaction
(TLC), it was quenched by slow addition of sat. aq NaHCO3 (10
mL) at 0 °C. After a few min, the layers were separated and aqueous
layer was extracted with CH2Cl2 (3 × 15 mL). The combined organ-
ic layers were dried (Na2SO4) and concentrated to afford a residue,
which was purified by column chromatography (EtOAc–hexane,
1:9).
Colorless liquid, yield: 0.85 g (78%); [a]D25 –27.2 (c 0.72, CHCl3).
IR (KBr): 3421, 2924, 2854, 1614, 1516, 1248, 1030, 827, 772
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34 (d, J = 8.8 Hz, 2 H), 6.83 (d,
J = 8.8 Hz, 2 H), 5.45 (s, 1 H), 4.07–3.86 (m, 2 H), 3.81–3.76 (m, 2
H), 3.78 (s, 3 H), 1.86–1.71 (m, 2 H), 1.59–1.41 (m, 2 H), 1.30 (d,
J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 21.5, 37.9, 38.4, 55.1, 60.0, 72.8,
75.7, 100.6, 113.5, 127.3, 131.1, 159.8.
MS (ESI): m/z = 275.1 [M + Na]+, 24.2, 172.0.
HRMS (ESI): m/z [M + Na]+ calcd for C14H20NaO4: 275.1259;
13C NMR (75 MHz, CDCl3): d = 23.6, 29.7, 43.5, 65.2, 75.6, 121.3,
145.4, 164.1.
MS (ESI): m/z = 179.0 [M + Na]+, 157.0 [M]+, 130.1.
HRMS (ESI): m/z [M + Na]+ calcd for C8H12NaO3: 179.0684;
found: 179.0692.
(R)-1-Methyl-2-[(S)-6-oxo-3,6-dihydro-2H-pyran-2-yl]ethyl 3-
[3,4-Bis(tert-butyldimethylsiloxy)phenyl]propanoate (16)
To the soln of acid 4 (0.23 g, 0.54 mmol) and DCC (0.11 g, 0.54
mmol) in CH2Cl2 (8 mL), was added to a soln of 2 (70 mg, 0.45
mmol) in CH2Cl2 (2 mL). After 10 min, DMAP (65 mg, 0.54 mmol)
was added and the mixture was stirred for 15 h at r.t. The solid res-
idue was filtered and solvent was evaporated. The crude product
was purified by column chromatography (EtOAc–hexane, 1:9).
found: 275.1265.
(3R,5R)-3,5-(4-Methoxybenzylidenedioxy)hexanal (15)
A soln 14 (0.7 g, 2.77 mmol) in anhyd CH2Cl2 (10 mL) was added
by cannula to a soln of DMP (1.7 g, 4.16 mmol) in anhyd CH2Cl2
Synthesis 2007, No. 23, 3639–3646 © Thieme Stuttgart · New York

3644
J. S. Yadav et al.
PAPER
Colorless liquid; yield: 0.2 g (83%); [a]D25 –42.8 (c 0.8, CHCl3).
Colorless liquid; yield: 177 mg (83%); [a]D25 –4.3 (c 1.1, CHCl3).
IR (KBr): 2960, 2860, 1740, 1690, 1600, 1575, 1500, 1450 cm–1.
IR (KBr): 2970, 2932, 1696, 1513, 1248, 1175, 1034, 821, 749, 518
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.82–6.62 (m, 4 H), 5.99 (d,
J = 9.8 Hz, 1 H), 5.13–5.04 (m, 1 H), 4.44–4.40 (m, 1 H), 2.83 (t,
J = 7.0 Hz, 2 H), 2.53 (t, J = 7.0 Hz, 2 H), 2.40–2.37 (m, 2 H), 2.23–
1.72 (m, 2 H), 1.25 (d, J = 7.0 Hz, 3 H), 0.96 (s, 9 H), 0.95 (s, 9 H),
0.19 (s, 6 H), 0.17 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = –4.2, 18.3, 20.2, 25.8, 29.0, 30.1,
36.1, 40.7, 67.0, 74.8, 120.76, 120.97, 121.02, 121.17, 133.3, 144.7,
145.1, 146.5, 163.8, 172.3.
1H NMR (300 MHz, CDCl3): d = 7.20 (d, J = 8.6 Hz, 2 H), 7.04 (dt,
J = 7.5, 14.9, 15.6 Hz, 1 H), 6.81 (d, J = 8.6 Hz, 2 H), 5.83 (dt,
J = 1.3, 2.8, 15.6 Hz, 1 H), 4.44 (q, J = 11.5 Hz, 2 H), 3.78 (s, 3 H),
3.62 (q, J = 6.0 Hz, 1 H), 2.52–2.31 (m, 2 H), 1.20 (d, J = 6.2 Hz, 3
H).
13C NMR (75 MHz, CDCl3): d = 19.7, 39.4, 55.2, 70.2, 73.0, 113.8,
122.7, 129.2, 130.4, 148.4, 159.1, 171.6.
MS (ESI): m/z = 571.1 [M + Na]+.
MS (ESI): m/z = 273.12 [M + Na]+, 121.1.
Anal. Calcd for C29H48O6Si2 (548.86); C, 63.46; H, 8.81. Found: C,
62.51; H, 8.57.
HRMS (ESI): m/z [M + Na]+ calcd for C14H18NaO4: 273.1102;
found: 273.1101.
(R)-1-Methyl-2-[(S)-6-oxo-3,6-dihydro-2H-pyran-2-yl]ethyl 3-
(3,4-Dihydroxyphenyl)propanoate (1)
Ethyl (5S,7R,E)-5-Hydroxy-7-(4-methoxybenzyloxy)oct-2-
enoate (21)
Compound 16 (100 mg, 0.18 mmol) was added to a suspension of
TBAF (142 mg, 0.54 mmol) in anhyd THF (8 mL) at r.t. The mix-
ture was stirred for 1 h at r.t., diluted with EtOAc (10 mL) and aq
NaHCO3 (10 mL). The layers were separated and the aqueous layer
was extracted with EtOAc (2 × 6 mL). The combined organic lay-
ers were washed with brine (2 × 6 mL) and H2O (6 mL), dried
(Na2SO4), and concentrated to give a residue that was purified by
column chromatography (EtOAc–hexane, 3:7).
To a suspension of PhI(OAc)2 (126 mg, 0.40 mmol) and 13 (100
mg, 0.40 mmol) in anhyd CH2Cl2 (10 mL) at 0 °C was added
TEMPO (cat.), and the mixture was stirred at r.t. for 2 h. On com-
pletion of the reaction (TLC), (ethoxycarbonylmethylene)triphe-
nylphosphorane (274 mg, 0.79 mmol) was added and the mixture
was stirred at r.t. for 2 h. On completion of the reaction (TLC), the
mixture was diluted with CH2Cl2 (10 mL) and H2O (10 mL), and
stirred for 5 min. The layers were separated and the aqueous layer
was extracted with CH2Cl2 (3 × 10 mL). The combined organic lay-
ers were washed with brine (2 × 6 mL) and H2O (6 mL), dried
(Na2SO4), and concentrated; this gave a residue that was purified by
column chromatography (EtOAc–hexane, 2:8).
25
White solid; yield: 48 mg (82%); mp 89–90 °C; [a]D –80 (c 0.4,
CHCl3).
IR (KBr): 3341, 2925, 2853, 1715, 1606, 1522, 1415 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.84 (ddd, J = 3.0, 6.0, 9.8 Hz, 1
H), 6.77 (d, J = 10.5 Hz, 1 H), 6.74 (d, J = 2.2 Hz, 1 H), 6.58 (dd,
J = 2.2, 8.3 Hz, 1 H), 5.99 (ddd, J = 3.0, 9.8, 12.0 Hz, 1 H), 5.12–
5.02 (m, 1 H), 4.17 (dddd, J = 3.7, 6.0, 10.5, 12.8 Hz, 1 H), 2.85 (t,
J = 6.7 Hz, 2 H), 2.62 (t, J = 6.7 Hz, 2 H), 2.42–2.00 (m, 3 H), 1.77
(ddd, J = 3.7, 6.7, 11.3, 14.3 Hz, 1 H), 1.25 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 20.2, 28.8, 30.1, 36.0, 40.5, 67.2,
75.2, 115.2, 120.1, 120.5, 132.4, 142.4, 144.0, 146.0, 165.3, 173.0.
MS (ESI): m/z = 343.1 [M + Na]+.
Colorless liquid; yield: 110 mg (87%); [a]D25 –34.8 (c 0.3, CHCl3).
IR (KBr): 3474, 2971, 2934, 1716, 1514, 1249, 1036 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.20 (d, J = 8.4 Hz, 2 H), 6.93 (dt,
J = 7.5, 12.4, 15.6 Hz, 1 H), 6.82 (d, J = 8.4 Hz, 2 H), 5.83 (dt,
J = 1.3, 2.8, 15.6 Hz, 1 H), 4.59 (d, J = 11.1 Hz, 1 H), 4.32 (d,
J = 11.1 Hz, 1 H), 4.14 (q, J = 7.1 Hz, 2 H), 3.90–3.81 (m, 2 H),
3.78 (s, 3 H), 2.38–2.29 (m, 2 H), 1.68–1.49 (m, 2 H), 1.28 (t,
J = 7.1 Hz, 3 H), 1.23 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 14.2, 19.6, 40.2, 43.2, 55.2, 60.2,
69.9, 70.6, 75.7, 114.0, 123.5, 129.4, 129.8, 145.3, 159.3, 166.4.
MS (ESI): m/z = 345.1 [M + Na]+, 74.2.
Anal. Calcd for C17H20O6 (320.336); C, 63.74; H, 6.29; Found: C,
63.37; H, 6.08.
(5R,E)-5-(4-Methoxybenzyloxy)hex-2-enal (20)
HRMS (ESI): m/z [M + Na]+ calcd for C18H26NaO5: 345.1677;
found: 345.1680.
A soln of 11 (0.2 g, 0.85 mmol) in anhyd CH2Cl2 (10 mL) was added
by cannula to a soln of DMP (0.4 g, 0.94 mmol) in anhyd CH2Cl2
(2.5 mL) at r.t. After 3 h, the pale pink mixture was transferred into
an Erlenmeyer flask containing sat. aq NaHCO3 (25 mL) The sepa-
rated organic layer was washed with brine (2 × 10 mL) and H2O (10
mL), dried (Na2SO4), and filtered and the solvent was removed in
vacuo. Crude 20 was utilized in the next step without further purifi-
cation. Yellow liquid; yield: 0.18 g (90%).
Ethyl (5S,7R,E)-5-(tert-Butyldimethylsiloxy)-7-(4-methoxyben-
zyloxy)oct-2-enoate (22)
TBDMSCl (84 mg, 0.56 mmol) in CH2Cl2 (2 mL) was added drop-
wise to a stirred soln of 21 (90 mg, 0.28 mmol) in anhyd CH2Cl2 (10
mL) and imidazole (50 mg, 0.73 mmol) at 0 °C. The mixture was
stirred at r.t. for 2 h and then diluted with H2O (10 mL) and stirred
for a few min, the layers were separated and aqueous layer was ex-
tracted with CH2Cl2 (3 × 10 mL). The combined organic layers
were washed with brine (2 × 10 mL) and H2O (10 mL), and dried
(Na2SO4). The solvent was concentrated under reduced pressure
and the residue was purified by column chromatography (EtOAc–
hexane, 1:9).
(5R,E)-5-(4-Methoxybenzyloxy)hex-2-enoic Acid (18)
NaH2PO4 (152 mg, 1.27 mmol) and 2-methylbut-2-ene (89 mg, 1.27
mmol) were added to a soln of 20 (200 mg, 0.85 mmol) in a mixture
of t-BuOH (6 mL) and H2O (2 mL) at 0 °C. The mixture was stirred
for 5 min and then NaClO2 (114 mg, 1.27 mmol) was added at this
temperature. After completion of the reaction (ca. 4 h), the solvent
was removed in vacuo. The residue was diluted with EtOAc (10
mL) and H2O (10 mL). After 5 min, the layers were separated and
the aqueous layer was extracted with EtOAc (3 × 10 mL). The com-
bined organic layers were washed with brine (2 × 10 mL) and H2O
(10 mL) and dried (Na2SO4) and concentrated under reduced pres-
sure. The residue was purified by column chromatography (EtOAc–
hexane, 3:7).
Colorless liquid; yield: 106 mg (87%); [a]D25 –6.7 (c 0.6, CHCl3).
IR (KBr): 2931, 2856, 1719, 1512, 1250, 1170, 1043, 833, 773
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.22 (d, J = 8.8 Hz, 2 H), 6.96 (dt,
J = 6.6, 9.3, 15.4 Hz, 1 H), 6.84 (d, J = 8.8 Hz, 2 H), 5.75 (d,
J = 15.4 Hz, 1 H), 4.51 (d, J = 11.7 Hz, 1 H), 4.32 (d, J = 11.7 Hz,
1 H), 4.18 (q, J = 6.6 Hz, 2 H), 3.89 (quint, J = 8.0, 13.9 Hz, 1 H),
3.80 (s, 3 H), 3.54 (q, J = 5.8 Hz, 1 H), 2.39–2.22 (m, 1 H), 1.92–
Synthesis 2007, No. 23, 3639–3646 © Thieme Stuttgart · New York

PAPER
Synthesis of Tarchonanthuslactone and (–)-Colletol
3645
1.39 (m, 3 H), 1.28 (t, J = 6.6 Hz, 3 H), 1.18 (d, J = 6.6 Hz, 3 H),
0.86 (s, 9 H), 0.09 (s, 3 H), 0.03 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = –4.6, 14.2, 17.9, 19.6, 25.6, 25.7,
39.9, 44.5, 60.0, 68.5, 69.9, 70.9, 113.7, 123.3, 123.4, 128.9, 129.1,
130.8, 145.4, 145.8, 159.1, 166.3.
MS (ESI): m/z = 459.3 [M + Na]+, 345.1, 301.1.
HRMS (ESI): m/z [M + Na]+ calcd for C24H40NaO5Si: 459.2542;
r.t. and the mixture was stirred for 1 h. On completion of the reac-
tion (TLC) it was quenched by slow addition of sat. aq NaHCO3 (5
mL) at 0 °C. After a few min, the layers were separated and the
aqueous layer was extracted with CH2Cl2 (3 × 5 mL). The combined
organic layers were washed with aq NaHCO3 (3 × 5 mL), dried
(Na2SO4), and concentrated to afford a residue that was purified by
column chromatography (EtOAc–hexane, 2:8).
Colorless liquid; yield: 16 mg (81%); [a]D25 –7.4 (c 0.7, CHCl3).
IR (KBr): 3482, 2980, 2934, 2412, 1692, 1655 cm–1.
found: 459.2555.
Ethyl (5S,7R,E)-5-(tert-Butyldimethylsiloxy)-7-hydroxyoct-2-
enoate (19)
1H NMR (300 MHz, CDCl3): d = 6.94 (d, J = 10.2 Hz, 2 H), 5.86
(dt, J = 2.9, 7.3, 15.4 Hz, 2 H), 5.18–4.94 (m, 1 H), 4.18 (q, J = 6.6
Hz, 2 H), 3.85 (q, J = 6.6 Hz, 1 H), 2.44–2.24 (m, 4 H), 1.95–1.60
(m, 4 H), 1.33–1.22 (m, 9 H), 0.89 (s, 9 H), 0.06 (s, 3 H), 0.05 (s, 3
H).
13C NMR (75 MHz, CDCl3): d = –4.6, 14.1, 20.2, 23.5, 26.1, 39.4,
42.1, 43.4, 60.3, 67.0, 68.2, 68.6, 123.4, 123.8, 144.9, 145.2, 165.4,
166.2.
MS (ESI): m/z = 451.2 [M + Na]+, 395.2, 353.2, 337.2, 332.2, 315.2,
297.2.
HRMS (ESI): m/z [M + Na]+ calcd for C22H40NaO6Si: 451.2491;
found: 451.2495.
Compound 22 (80 mg, 0.18 mmol) was added slowly to a suspen-
sion of DDQ (41.6 mg, 0.18 mmol) and CH2Cl2–H2O (17:1, 10 mL)
at r.t. and the mixture was stirred for 1 h. On completion of the re-
action (TLC), it was quenched by slow addition of sat. aq NaHCO3
(10 mL) at 0 °C. After a few min, the layers were separated and the
aqueous layer was extracted with CH2Cl2 (3 × 15 mL). The com-
bined organic layers were dried (Na2SO4) and concentrated to af-
ford a residue that was purified by column chromatography
(EtOAc–hexane, 2:8).
Colorless liquid; yield: 48 mg (84%); [a]D25 +8.3 (c 0.8, CHCl3).
IR (KBr): 3445, 2956, 2928, 2855, 1720, 1257, 1048, 853, 775, 664
cm–1.
(1R,E)-5-[(5S,7R,E)-5-(tert-Butyldimethylsiloxy)-7-hydroxyoct-
2-enoyloxy]-1-methylpent-2-enoic Acid (17)
1H NMR (300 MHz, CDCl3): d = 6.66 (dd, J = 1.4, 5.9, 14.0 Hz, 1
H), 5.78 (d, J = 14.0 Hz, 1 H), 4.15 (q, J = 7.4 Hz, 2 H), 4.01 (quint,
J = 5.9, 12.5 Hz, 1 H), 3.89 (quint, J = 6.6, 16.9 Hz, 1 H), 2.54 (br
s, 1 H), 2.40 (tt, J = 1.4, 3.7, 7.4, 8.8 Hz, 2 H), 1.56 (d, J = 6.6 Hz,
2 H), 1.29 (t, J = 6.6 Hz, 3 H), 1.15 (d, J = 6.6 Hz, 3 H), 0.90 (s, 9
H), 0.11 (s, 3 H), 0.09 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = –4.7, –4.2, 14.2, 23.6, 25.6, 25.7,
40.6, 45.1, 60.2, 66.5, 71.2, 123.9, 144.4, 166.2.
MS (ESI): m/z = 339.1 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C16H32NaO4Si: 339.1967;
Ester 24 (13 mg, 0.03 mmol) was dissolved in THF–H2O (4:1, 5
mL), followed by slow addition of LiOH·H2O (1.4 mg, 0.036
mmol). The mixture was stirred at r.t. for 6 h.; the reaction progress
was monitored by TLC. On completion of the reaction, EtOAc (8
mL) was added and the mixture was extracted with H2O (4 mL).
The aqueous layer was neutralized (pH ~6.0) with NaHSO4 and the
aqueous layer was extracted with EtOAc (3 × 8 mL). The combined
organic layers were washed with brine (2 × 4 mL) and H2O (4 mL),
dried (Na2SO4), and concentrated under vacuum. The crude acid
was washed with hexane (3 × 4 mL) to remove the nonpolar impu-
rities.
found: 339.1969.
Colorless liquid; yield: 10 mg (80%); [a]D25 –10.8 (c 0.4, CHCl3).
(1R,E)-5-Ethoxy-1-methyl-5-oxopent-3-enyl (5S,7R,E)-5-(tert-
Butyldimethylsiloxy)-7-(4-methoxybenzyloxy)oct-2-enoate (23)
To a soln of 19 (30 mg, 0.094 mmol), MNBA (39 mg, 0.11 mmol),
and DMAP (28 mg, 0.22 mmol) in CH2Cl2 (8 mL) at r.t. was slowly
added a soln of 18 (24 mg, 0.096 mmol) in CH2Cl2 (2 mL) with a
mechanically driven syringe over 1 h period. After addition of the
soln, the mixture was additionally stirred for 1 h. On completion of
the reaction (TLC), sat. aq NaHCO3 (5 mL) was added and aqueous
layer was extracted with CH2Cl2 (3 × 6 mL). The combined organic
layers were washed with brine (2 × 6 mL) and H2O (6 mL), dried
(Na2SO4), and concentrated; this gave a residue that was purified by
column chromatography (EtOAc–hexane, 3:7).
IR (KBr): 3484, 2978, 3934, 1716, 1655, 1450, 1430, 1381, 1370,
1300, 1268, 1219, 1170 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.10 (dt, J = 7.3, 14.6 Hz, 1 H),
6.94 (dt, J = 7.3, 14.6 Hz, 1 H), 5.86–5.84 (m, 2 H), 5.18–4.94 (m,
1 H), 4.01–3.96 (m, 1 H), 3.85–3.82 (m, 1 H), 2.42–2.25 (m, 4 H),
1.85–1.62 (m, 2 H), 1.22 (d, J = 4.8 Hz, 3 H), 1.18 (d, J = 4.8 Hz, 3
H), 0.87 (s, 9 H), 0.06 (s, 3 H), 0.04 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = –4.6, –4.4, 17.8, 20.4, 22.9, 25.6,
39.5, 41.4, 43.2, 66.6, 67.8, 68.0, 123.0, 123.7. 145.0, 147.9, 165.4,
170.6.
MS (ESI): m/z = 423.5 [M + Na]+.
Colorless liquid; yield: 43.7 mg (84%); [a]D25 +3.6 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.27 (d, J = 9.0 Hz, 2 H), 7.0–6.90
(m, 2 H), 6.88 (d, J = 9.0 Hz, 2 H), 5.86 (dt, J = 3.7, 6.7, 15.8 Hz, 2
H), 5.12–4.93 (m, 1 H), 4.48 (q, J = 11.3 Hz, 2 H), 4.19 (q, J = 6.7
Hz, 2 H), 3.81 (s, 3 H), 3.64 (q, J = 6.0 Hz, 1 H), 2.65–2.35 (m, 4
H), 1.95–1.61 (m, 3 H), 1.32–1.20 (m, 9 H), 0.88 (s, 9 H), 0.06 (s, 3
H), 0.04 (s, 3 H).
Acknowledgment
P.M.K. and C.J.C. thank UGC New Delhi and M.K.G. thanks CSIR,
New Delhi for research fellowships.
MS (ESI): m/z = 571.1 [M + Na]+, 393.1, 287.1, 189.19, 60.3.
References
HRMS (ESI): m/z [M + Na]+ calcd for C30H48NaO7Si: 571.3067;
found: 571.3071.
(1) (a) Casiraghi, G.; Zanardi, F.; Rassu, G.; Pinna, L. Org.
Prep. Proced. Int. 1996, 28, 641. (b) Hartmann, T.; Witte,
L. Alkaloids: Chemical and Biological Perspectives;
Pelletier, S. W., Ed.; Pergamon: New York, 1995, Chap. 4,
155. (c) Yadav, J. S.; Gupta, M. K.; Pratahp, I. Synthesis
2007, 1343; and references cited therein. (d) Smith, A. B.
III; Freeze, B. S.; LaMarche, M. J.; Hirose, T.; Brouard, I.;
(1R,E)-5-Ethoxy-1-methyl-5-oxopent-3-enyl (5S,7R,E)-5-(tert-
Butyldimethylsiloxy)-7-hydroxyoct-2-enoate (24)
Compound 23 (25 mg, 0.045 mmol) was added slowly to a suspen-
sion of DDQ (13 mg, 0.06 mmol) and CH2Cl2–H2O (17:1, 6 mL) at
Synthesis 2007, No. 23, 3639–3646 © Thieme Stuttgart · New York

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PAPER
6606. (c) Shimizu, I.; Omura, T. Chem. Lett. 1993, 1759.
Rucker, P. V.; Xian, M.; Sundermann, K. F.; Shaw, S. J.;
Burlingame, M. A.; Horwitz, S. B.; Myles, D. C. Org. Lett.
2005, 7, 311; and references cited therein.
(d) Sharma, G. V. M.; Raja Rao, A. V. S.; Murthy, V. S.
Tetrahedron Lett. 1995, 36, 4117. (e) Solladie, G.; Gressot,
L.; Colobert, F. Eur. J. Org. Chem. 2000, 357. (f) Hunter,
T. J.; O’Doherty, G. A. Org. Lett. 2002, 4, 4447.
(9) (a) Yadav, J. S.; Reddy, P. M. K.; Reddy, P. V. Tetrahedron
Lett. 2007, 48, 1037. (b) Yadav, J. S.; Prathap, I.; Tadi, B. P.
Tetrahedron Lett. 2006, 47, 3773. (c) Yadav, J. S.; Rao, K.
V.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2006, 47,
4393. (d) Yadav, J. S.; Srinivas, R.; Sathaih, K. Tetrahedron
Lett. 2006, 47, 1603. (e) Yadav, J. S.; Reddy, M. S.; Prasad,
A. R. Tetrahedron Lett. 2005, 46, 2133. (f) Yadav, J. S.;
Reddy, K. B.; Sabitha, G. Tetrahedron Lett. 2004, 45, 6475.
(10) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.;
Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N.
J. Am. Chem. Soc. 2002, 124, 1307.
(11) Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983, 24, 391.
(12) (R)-Propylene oxide(6) was obtained by a literature
procedure [Co(OAc)(R,R-Salen) (0.003 equiv), distd H2O
(0.55 equiv.), 0 °C, 12 h, yield: 47% of 6, 48% of (S)-
propane-1,3-diol]10 and is easily isolated from the more
polar diol (S)-propane-1,3-diol by distillation. Compound 6:
[a]25D +11.6 (neat) {Lit.10 (S)-propylene oxide [a]25D –11.7
(neat)}.
(2) Bohlmann, F.; Suwita, A. Phytochemistry 1979, 18, 677.
(3) Akata, T.; Hata, N.; Iida, K.; Oishi, T. Tetrahedron Lett.
1987, 28, 5661.
(4) Hsu, F. L.; Chen, Y. C.; Cheng, J. T. Planta Med. 2000, 66,
228.
(5) (a) MacMillan, J.; Pryce, R. J. Tetrahedron Lett. 1968, 9,
5497. (b) MacMillan, J.; Simpson, T. J. J. Chem. Soc.,
Perkin Trans. 1 1973, 1487.
(6) Ronald, R. C.; Curusiddaih, S. Tetrahedron Lett. 1980, 21,
681.
(7) (a) Yadav, J. S.; Kumar, N. N.; Reddy, M. S.; Prasad, A. R.
Tetrahedron 2007, 63, 2689. (b) Scott, M. S.; Luckhurst, C.
A.; Dixon, D. J. Org. Lett. 2005, 7, 5813. (c) Sabitha, G.;
Sudhakar, K.; Reddy, N. M.; Rajkumar, N.; Yadav, J. S.
Tetrahedron Lett. 2005, 46, 6567. (d) Baktharaman, S.;
Selvakumar, S.; Singh, V. K. Tetrahedron Lett. 2005, 46,
7527. (e) Gupta, P.; Naidu, V.; Kumar, P. Tetrahedron Lett.
2005, 46, 6571. (f) Enders, D.; Steinbusch, D. Eur. J. Org.
Chem. 2003, 4450. (g) Garaas, S. D.; Hunter, T. J.;
O’Doherty, G. A. J. Org. Chem. 2002, 67, 2682. (h)Reddy,
M. V. R.; Yucel, A. J.; Ramachandran, P. V. J. Org. Chem.
2001, 66, 2512. (i) Solladie, G.; Gressot-Kempf, L.
Tetrahedron: Asymmetry 1996, 7, 2371. (j) Mori, Y.;
Kageyama, H.; Suzuki, M. Chem. Pharm. Bull. 1990, 38,
2574. (k) Mori, Y.; Suzuki, M. J. Chem. Soc., Perkin Trans.
1 1990, 1809. (l) Nakata, T.; Hata, N.; Iida, K.; Oishi, T.
Tetrahedron Lett. 1987, 28, 5661.
(13) Honda, H.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett.
1984, 25, 3857.
(14) Yadav, J. S.; Chander, M. C.; Joshi, B. V. Tetrahedron Lett.
1988, 29, 2732.
(15) Radha Krishna, P.; Srinivas, R. Tetrahedron Lett. 2007, 48,
2013.
(8) (a) BouzBouz, S.; Cossy, J. Tetrahedron Lett. 2006, 47,
901. (b) Keck, G. E.; Murry, J. A. J. Org. Chem. 1991, 56,
(16) Vatele, J. M. Tetrahedron Lett. 2006, 47, 715.
(17) Shiina, I.; Kubota, M.; Ibuka, R. Tetrahedron Lett. 2002, 43,
7535.
Synthesis 2007, No. 23, 3639–3646 © Thieme Stuttgart · New York