Sequential one-pot isomerization-Wittig olefination-hydrogenation

Article abstract of DOI:10.1055/s-0030-1260232

Primary allylic alcohols are isomerized to aldehydes in the presence of Pd(OH)₂ and homologated to α,β-unsaturated carbonyl derivatives in one-pot by addition of stabilized Wittig ylides in a sequential fashion. When the reaction was prolonged

Full text of DOI:10.1055/s-0030-1260232

PAPER
3661
Sequential One-Pot Isomerization–Wittig Olefination–Hydrogenation
S
equential
O
ne-Po
o
t
Isomerizati
w
on–Wittig
O
lefina
r
tion–H
y
a
drogenationvaram Sabitha,*a Sambit Nayak,a M. Bhikshapathi,a Maruthi Chittapragada,a J. S. Yadava,b
a
Division of Organic Chemistry I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
Fax +91(40)27160512; E-mail: gowravaramsr@yahoo.com; E-mail: sabitha@iict.res.in
Bee Research Chair, College of Food and Agriculture Science, King Saud University, Riyadh, Saudi Arabia
b
Received 6 July 2011; revised 26 August 2011
od of obtaining functionalized organic molecules. In con-
tinuation of our work on the development of a new
method for the isomerization of allylic alcohols,8 we here-
in report for the first time Pd(OH)2-catalyzed sequential
Abstract: Primary allylic alcohols are isomerized to aldehydes in
the presence of Pd(OH)2 and homologated to a,b-unsaturated carbo-
nyl derivatives in one-pot by addition of stabilized Wittig ylides in
a sequential fashion. When the reaction was prolonged by addition
of more catalyst, a hydrogenation step succeeds the Wittig olefina- one-pot isomerization–Wittig olefination as well as the
tion. In addition, sequential isomerization–Wittig olefination–oxa-
first, one-pot isomerization–Wittig olefination–hydroge-
Michael addition reaction provides tetrahydropyran with high dia-
stereoselectivity.
nation and one-pot isomerization–Wittig olefination–oxa-
Michael addition reactions of allylic alcohols.
Key words: isomerization, Wittig olefination, hydrogenation, oxa-
Michael reaction, aldehydes
When an allylic alcohol 1 was subjected to isomerization
conditions [7 mol% preactivated Pd(OH)2/C, benzene,
r.t.]8 in the presence of stabilized ylide 3, the a,b-unsatur-
ated ester 6a was isolated in 10% yield along with a good
Aldehydes are important and extremely versatile synthet-
amount of starting material. However, when stabilized
ic intermediates for various pharmaceuticals, agrochemi-
ylide 3 was added to the same pot after the isomerization
cals, and other fine chemicals.1 They can be converted
of the allylic alcohol 1 [catalyzed by preactivated
into alcohols, amines, carboxylic acids, and other deriva-
Pd(OH)2/C] to aldehyde 2, the exclusive formation of a,b-
tives. These conversions become difficult when the inter-
unsaturated ester 6a in very good yield was noted
mediate
aldehydes
are
unstable
leading
to
(Scheme 1). Thus, the isomerization of the allylic alcohol,
as well as the olefination of the aldehyde 2, have been per-
formed as a one-pot process.
decomposition,2,3 polymerization,4 or face difficulty in
isolation due to volatility and toxicity. Such problems can
be overcome by preparing the aldehydes and reacting
them in situ with other reagents. The conversion of multi-
step reactions into economically and environmentally fa-
vored one-pot processes,5–7 is a challenging task in syn-
thetic organic chemistry and has potential use in natural
product synthesis. Therefore, domino reaction under
isomerization conditions is a clean and economical meth-
Once the protocol was standardized, we carried out this
transformation with other allylic alcohols using different
ylides (Table 1). In the case of ylide 3, the Wittig olefina-
tion reaction occurred at room temperature, whereas other
ylides 4 and 5 required refluxing conditions after the
isomerization was complete. All reactions were clean and
efficient giving good yields of unsaturated carbonyl deriv-
Ph3P=CHCO2Et
COR3
Pd(OH)2/C
CHO
3
R1
R1
OH
R1
Ph3P=CHCOMe
R2
H2, C6H6
r.t.
4
1
2
Ph3P=C(Me)COMe
6a R2 = H, R3 = OEt
R1 = aliphatic
5
6b R2 = H, R3 = Me
C6H6, r.t./reflux
6c R2 = Me, R3 = OEt
H2, C6H6
r.t.
Pd(OH)2/C
COR3
R1
R2
7a R2 = H, R3 = OEt
7b R2 = H, R3 = Me
7c R2 = Me, R3 = OEt
Scheme 1 Sequential isomerization–Wittig olefination–hydrogenation
SYNTHESIS 2011, No. 22, pp 3661–3668
x
x.
x
x
.
2
0
1
1
Advanced online publication: 20.09.2011
DOI: 10.1055/s-0030-1260232; Art ID: Z67711SS
© Georg Thieme Verlag Stuttgart · New York

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G. Sabitha et al.
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atives 6. Allylic alcohols having PMB and TBS groups Thus, the same catalyst, that had catalyzed the initial
(Table 1) require the addition of 5 mol% of Et3N to avoid isomerization step, acted as a hydrogenation catalyst in
deprotection.
the final hydrogenation reaction of this three-step process.
All three stages, viz., the isomerization of the allylic alco-
hol, the olefination of the aldehyde, and the hydrogenation
of the Wittig product, have been performed as a one-pot
process. It is important to mention that in the case of the
isomerization of allylic alcohols in the presence of alkyl-
substituted stabilized ylides such as 5, the reaction stops
at the Wittig olefination stage and does not undergo final
hydrogenation reaction. However, enoate 6c obtained
from ylide 5, after isolation undergoes hydrogenation af-
fording 7c in good yields (Scheme 1). The results are
shown in Table 1.
After the isomerization of the allylic alcohol 1 as well as
the olefination of the aldehyde 2 to a,b-unsaturated ester
6 using ylide 3 or 4 have been performed as a one-pot pro-
cess, another 7 mol% of Pd(OH)2/C was added to the flask
under nitrogen atmosphere, the atmosphere again re-
placed with hydrogen gas and the stirring continued at
room temperature, which resulted in the formation of sat-
urated carbonyl derivative 7a or 7b, respectively
(Scheme 1). Hence, a sequential process involving three
separate steps had occurred in one step. The initial step is
an isomerization of allylic alcohol 1 to give the aldehyde
2 followed by Wittig olefination to furnish unsaturated es-
ter or enone 6, which was finally hydrogenated in the
same pot to give the saturated ester or ketone 7 (Table 1).
Table 1 Pd(OH)2-Catalyzed Sequential One-Pot Isomerization–Wittig Olefination and Sequential One-Pot Isomerization–Wittig Olefina-
tion–Hydrogenationa
Allylic alcohol
Ylide
Product
Time (h)
1.5
Temp
r.t.
Yield (%)b
89
Ph3P=CHCO2Et
3
O
O
O
O
OH
OH
COOEt
8
9a
Ph3P=CHCOMe
4
3.5
reflux
88
O
O
O
O
8
O
9b
Ph3P=CHCO2Et
3
1.5
3.5
r.t.
86
84
OH
OH
PMBO
COOEt
PMBO
11a
10
Ph3P=CHCOMe
4
reflux
PMBO
PMBO
O
10
11b
Ph3P=C(Me)CO2Et
5
4.5
1.5
reflux
r.t.
83
89
OH
PMBO
PMBO
COOEt
10
11c
OPMB
Ph3P=CHCO2Et
OPMB
3
OH
COOEt
12
12
13a
OPMB
Ph3P=CHCOMe
4
3.5
reflux
87
OPMB
OPMB
OH
OH
O
13b
OPMB
Ph3P=C(Me)CO2Et
5
4.5
1.5
reflux
r.t.
84
85
COOEt
12
13c
OTBS
Ph3P=CHCO2Et
OTBS
3
OH
COOEt
OTBS
OTBS
14
15a
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Sequential One-Pot Isomerization–Wittig Olefination–Hydrogenation
3663
Table 1 Pd(OH)2-Catalyzed Sequential One-Pot Isomerization–Wittig Olefination and Sequential One-Pot Isomerization–Wittig Olefina-
tion–Hydrogenationa (continued)
Allylic alcohol
Ylide
Product
Time (h)
3.5
Temp
reflux
Yield (%)b
83
Ph3P=CHCOMe
OTBS
OTBS
4
OH
O
OTBS
OTBS
15b
14
Ph3P=CHCOMe
4
3.5
1.5
reflux
r.t.
82
88
OH
3
BnO
BnO
3
OTBS
16
O
OTBS
17b
Ph3P=CHCO2Et
OMOM
OMOM
3
OH
Ph
CO2Et
CO2Et
Ph
18
19a
PhO
Ph3P=CHCO2Et
3
1.5
6.0
r.t.
86
86
PhO
OH
21a
20
Ph3P=CHCO2Et
r.t.d
3
O
O
O
O
O
OH
OH
COOEt
8
22a
Ph3P=CHCOMe
4
8.5
r.t.d
86
O
O
O
8
O
22b
Ph3P=CHCO2Et
3
6.0
8.0
r.t.d
r.t.d
84
83
OH
OH
PMBO
COOEt
PMBO
23a
10
Ph3P=CHCOMe
4
PMBO
PMBO
O
10
23b
Ph3P=CH(Me)CO2Et
5
6.0
8.5
r.t.d
r.t.d
84
85
OH
PMBO
PMBO
23cc
COOEt
10
Ph3P=CHCOMe
OPMB
OPMB
4
OH
12
O
O
24b
OPMB
Ph3P=CH(Me)CO2Et
5
8.5
8.5
6.0
r.t.d
r.t.d
r.t.d
81
80
80
OPMB
OH
OEt
12
24cc
OTBS
Ph3P=CHCOMe
4
OTBS
OH
O
OTBS
OTBS
25b
14
Ph3P=CHCO2Et
OMOM
OMOM
3
OH
Ph
CO2Et
Ph
18
26a
a Reactions were performed with Pd(OH)2 and stabilized Wittig ylides.
b Yields of products after purification.
c Final hydrogenation reaction was done after isolating the Wittig product.
d Final hydrogenation reaction was performed at r.t.
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G. Sabitha et al.
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O
OH
OH
PMBO
Pd(OH)2/C
3
PMBO
OH
H2, C6H6, r.t.
reflux
27
28
NOE
OH
TBAF
H
H
O
COOEt
PMBO
r.t., 6 h
77%
over 3 steps
PMBO
COOEt
2
6
29
30
Scheme 2 Sequential isomerization–Wittig reaction–oxa-Michael reaction
Substituted tetrahydropyrans having 2,6-syn configura-
OH
tion are found to be important structural motifs present in
HO
O
OMe
R
numerous natural products such as spirastrellolides A and
B,9 (–)-centrolobine,10 (–)-exiguolide,11 and bioactive
synthons12 (Figure 1). Thus, we envisaged the synthesis of
such tetrahydropyrans by exploiting the above developed
methodology. When the isomerization of the allyl alcohol
27 having free secondary hydroxyl group was performed,
the stabilized ylide 3 was added to the corresponding lac-
tol 28 in the same pot, which resulted in the formation of
hydroxyester 29. When the reaction was continued, after
the addition of excess TBAF, it subsequently underwent
intramolecular oxa-Michael reaction in highly
diastereoselective8,13 fashion to furnish 2,6-syn tetrahy-
dropyran 30 as the sole product in 77% yield (over three
steps) (Scheme 2).
O
O
O
O
O
O
HO
HO
OH
O
X
O
HO
X
spirastrellolide A: X = CH=CH, R = Cl
spirastrellolide B: X = CH2CH2, R = H
O
H
H
The relative syn relationship at C-2 and C-6 was con-
firmed through NOE experiments. Thus, all three stages,
the isomerization of the allylic alcohol, the olefination of
the lactol, and the oxa-Michael cyclization of the hydroxy
ester product have been performed as a one-pot process.
Extension of this work for the synthesis of various natural
products containing syn-tetrahydropyran moiety will be
published in due course.
HO
OMe
(–)-centrolobine
CO2Me
O
In conclusion, stabilized Wittig ylides are found to be
compatible with conditions of a Pd(OH)2-catalyzed
isomerization. This observation paved the way for the de-
velopment of efficient domino processes in which the
isomerization as an atom-economic carbon–carbon bond-
forming process was employed as the key step to generate
the aldehyde component of a succeeding Wittig olefina-
tion. This domino process is followed by a hydrogenation
O
O
O
MeO2C
(–)-exiguolide
Figure 1 Natural products with 2,6-syn-tetrahydropyran rings
reaction of the acceptor substituted alkene. With the alkyl-
substituted stabilized Wittig ylides, the domino process
can be stopped at the olefin stage and can be hydrogenated
after isolation to afford the saturated derivatives. Thus,
depending on the reaction conditions, sequential isomer-
ization–Wittig olefination and sequential isomerization–
Wittig olefination–hydrogenation processes or sequential
isomerization–Wittig olefination–oxa-Michael reaction
could be realized. The present work opens a new and effi-
cient one-pot synthetic route to chiral tetrahydropyran de-
rivatives directly from allylic alcohols.
Unless otherwise mentioned, all reactions were carried out using
standard syringe, septa, and cannula techniques. All glassware was
flame- or oven-dried and cooled under an inert atmosphere of N2
unless otherwise stated. Column chromatography was performed
using silica gel (60–120 mesh) and the column was usually eluted
with EtOAc–hexanes. The diastereomeric excesses of the products
were measured by chiral-phase HPLC using Chiralpak AS column.
Analytical TLC was performed on precoated silica gel-60 F254 (0.5
mm) glass plates. Visualization of the spots on TLC plates was
achieved either by exposure to iodine vapor or UV light or by dip-
ping the plates in H2SO4/b-naphthol or ethanolic anisaldehyde–
H2SO4–AcOH or phosphomolybdic acid–H2SO4 solution and heat-
ing the plates at 120 °C. 1H NMR spectra were recorded at 200, 300,
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Sequential One-Pot Isomerization–Wittig Olefination–Hydrogenation
3665
400, 500 MHz and 13C NMR spectra were recorded at 50, 75 MHz
in CDCl3 using TMS as the reference standard. Standard abbrevia-
tions were used to denote multiplicities of the signals. IR spectra
were recorded on PerkinElmer Infrared-683 spectrophotometer
with NaCl optics. Spectra were calibrated against the polystyrene
absorption at 1610 cm–1. Samples were scanned neat. The optical
rotations were measured on JASCO DIP-360 Digital Polarimeter.
Mass spectra were recorded on Micro Mass VG-7070H mass spec-
trometer for ESI and EI are given in mass units (m/z). High-resolu-
tion mass spectra (HRMS) [ESI+] were obtained using either a TOF
or a double focusing spectrometer.
HRMS (ESI): m/z calcd for C15H25O4 (M + H)+: 269.1752; found:
269.1766.
(E)-7-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]hept-3-en-2-one (9b)
Yield: 105 mg (88%); colorless liquid; Rf = 0.3 (EtOAc–hexane,
2:8).
[a]D28 –0.2 (c 1.4, CHCl3).
IR (neat): 2934, 2860, 1676, 1628, 1448, 1364, 1280, 1253, 1163,
1104, 1041, 980, 928 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.78 (td, J = 6.9, 15.8 Hz, 1 H),
6.07 (d, J = 15.8 Hz, 1 H), 4.08–3.97 (m, 2 H), 3.48 (t, J = 6.9 Hz,
1 H), 2.43–2.26 (m, 2 H), 2.21 (s, 3 H), 1.77–1.64 (m, 2 H), 1.63–
1.50 (m, 10 H).
Sequential One-Pot Isomerization–Wittig Olefination; General
Procedure
A 50 mL two-necked round-bottomed flask was charged with
Pd(OH)2/C (23 mg, 7 mol%) and benzene (3 mL). H2 gas then was
passed through the suspension via a balloon for 30 min (for the ac-
tivation of the catalyst). The H2 gas supply was stopped and strring
continued for 10 min after which a solution of allylic alcohol 1 (0.5
mmol) in benzene (3 mL) was added. The reaction mixture was
stirred for another 10 min. After complete conversion of allylic al-
cohol to the corresponding aldehyde, as indicated by TLC (eluent:
EtOAc–hexane, 2:8), the required stable Wittig ylide (0.65 mmol)
was added and the mixture stirred either at r.t. or at reflux conditions
(see Table 1). After completion of the reaction, the mixture was fil-
tered through a Celite pad and washed with EtOAc (10 mL). The fil-
trate was concentrated in vacuo and the residue was purified by
silica gel column chromatography (2–30% EtOAc–hexane as elu-
ent) to afford enoate/enone 6 (83–89%).
13C NMR (75.0 MHz, CDCl3): d = 198.5, 147.3, 131.4, 109.5, 74.7,
68.8, 36.6, 35.1, 32.2, 28.7, 26.8, 25.1, 24.0, 23.8.
HRMS (ESI): m/z calcd for C14H22O3 + Na (M + Na)+: 261.1466;
found: 261.1479.
Ethyl (E)-6-[(4-Methoxybenzyl)oxy]hex-2-enoate (11a)
Yield: 119 mg (86%); yellow oil; Rf = 0.6 (EtOAc–hexane, 2:8).
IR (neat): 2937, 2857, 1717, 1654, 1613, 1586, 1513, 1464, 1367,
1302, 1247, 1173 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.5 Hz, 2 H), 6.91 (td,
J = 7.0, 15.5 Hz, 1 H), 6.82 (d, J = 8.5 Hz, 2 H), 5.77 (td, J = 1.5,
15.5 Hz, 1 H), 4.39 (s, 2 H), 4.16 (q, J = 7.2 Hz, 2 H), 3.79 (s, 3 H),
3.42 (t, J = 6.0 Hz, 2 H), 2.29 (dq, J = 1.3, 7.2 Hz, 2 H), 1.79–1.69
(m, 2 H), 1.29 (t, J = 7.2 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 166.5, 159.0, 148.5, 130.3,
129.1, 121.5, 113.6, 72.5, 68.8, 60.0, 55.1, 29.7, 28.0, 14.1.
Sequential One-Pot Isomerization–Wittig Olefination–Hydro-
genation; General Procedure
A 50 mL two-necked round-bottomed flask was charged with
Pd(OH)2/C (23 mg, 7 mol%) and benzene (3 mL). H2 gas was then
passed through the suspension via a balloon for 30 min (for the ac-
tivation of the catalyst). The H2 gas supply was stopped and stirring
continued for 10 min after which a solution of the respective allylic
alcohol 1 (0.5 mmol) in benzene (3 mL) was added. The reaction
mixture was stirred for another 10 min. After complete conversion
of allylic alcohol to the corresponding aldehyde, as indicated by
TLC (eluent: EtOAc–hexane, 2:8), the required stable Wittig ylide
(0.65 mmol) was added and the mixture stirred either at r.t. or at re-
flux conditions (see Table 1). Then, the mixture was cooled to r.t.,
another portion of Pd(OH)2/C (7 mol%) was added under N2 atmo-
sphere and the mixture was stirred under H2 atmosphere. After com-
pletion of the reaction, the mixture was filtered through a Celite pad
a and washed with EtOAc (3 × 10 mL). The filtrate was concentrat-
ed in vacuo and the residue was purified by silica gel column chro-
matography (2–30% EtOAc–hexane as eluent) to afford product 7
(80–86%).
HRMS (ESI): m/z calcd for C16H22O4 + Na (M + Na)+: 301.1415;
found: 301.1429.
(E)-7-[(4-Methoxybenzyl)oxy]hept-3-en-2-one (11b)
Yield: 104 mg (84%); pale yellow oil; Rf = 0.3 (EtOAc–hexane,
2:8).
IR (neat): 2937, 2858, 1671, 1626, 1614, 1512, 1464, 1442, 1362,
1301, 1250, 1174, 1098, 1034, 979 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.5 Hz, 2 H), 6.82 (d,
J = 8.5 Hz, 2 H), 6.73 (dt, J = 7.0, 16.0 Hz, 1 H), 6.02 (d, J = 16.0
Hz, 1 H), 4.39 (s, 2 H), 3.79 (s, 3 H), 3.42 (t, J = 6.0 Hz, 2 H), 2.31
(q, J = 7.2 Hz, 2 H), 2.18 (s, 3 H), 1.79–1.69 (m, 2 H).
13C NMR (75.0 MHz, CDCl3): d = 198.5, 158.9, 147.7, 131.2,
130.1, 129.0, 113.5, 72.3, 68.6, 54.9, 29.0, 27.9, 26.5.
HRMS (ESI): m/z calcd for C15H20O3 + Na (M + Na)+: 271.1310;
found: 271.1301.
(E)-6-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]-1-methylenehex-2-enyl
Ethyl Ether (9a)
Yield: 120 mg (89%); colorless liquid; Rf = 0.6 (EtOAc–hexane,
2:8).
Ethyl (E)-6-[(4-Methoxybenzyl)oxy]-2-methylhex-2-enoate
(11c)
Yield: 121 mg (83%); pale yellow oil; Rf = 0.7 (EtOAc–hexane,
2:8).
[a]D28 –0.3 (c 1.5, CHCl3).
IR (neat): 2936, 2858, 1709, 1649, 1613, 1513, 1464, 1444, 1366,
1249, 1173, 1132, 1095, 1036 cm–1.
IR (neat): 2936, 2862, 1720, 1655, 1448, 1366, 1278, 1198, 1163,
1106, 985, 928 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.5 Hz, 2 H), 6.81 (d,
J = 8.5 Hz, 2 H), 6.70 (t, J = 7.5 Hz, 1 H), 4.39 (s, 2 H), 4.16 (q,
J = 7.2 Hz, 2 H), 3.79 (s, 3 H), 3.41 (t, J = 6.0 Hz, 2 H), 2.26 (q,
J = 7.2 Hz, 2 H), 1.82 (s, 3 H), 1.72 (m, 2 H), 1.30 (t, J = 7.2 Hz, 3
H).
13C NMR (75.0 MHz, CDCl3): d = 168.0, 159.0, 141.4, 130.4,
129.1, 128.1, 113.6, 72.5, 69.1, 60.3, 55.1, 28.5, 25.3, 14.2, 12.2.
1H NMR (300 MHz, CDCl3): d = 6.94 (td, J = 6.9, 15.6 Hz, 1 H),
5.80 (td, J = 1.5, 15.6 Hz, 1 H), 4.16 (q, J = 6.9 Hz, 2 H), 4.10–3.97
(m, 2 H), 3.51–3.45 (m, 1 H), 2.43–2.21 (m, 2 H), 1.80–1.64 (m, 2
H), 1.63–1.50 (m, 8 H), 1.44–1.36 (m, 2 H), 1.29 (t, J = 6.9 Hz, 3
H).
13C NMR (75.0 MHz, CDCl3): d = 166.5, 148.1, 121.7, 109.5, 74.7,
68.8, 60.2, 36.6, 35.2, 32.2, 28.5, 25.2, 24.0, 23.9, 14.3.
HRMS (ESI): m/z calcd for C17H24O4 + Na (M + Na)+: 315.1572;
found: 315.1584.
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G. Sabitha et al.
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Ethyl (E,6S)-6-[(4-Methoxybenzyl)oxy]hept-2-enoate (13a)
Yield: 130 mg (89%); colorless oil; Rf = 0.6 (EtOAc–hexane, 2:8).
[a]D29 +29.0 (c 1.1, CHCl3).
13C NMR (75.0 MHz, CDCl3): d = 166.6, 149.1, 121.4, 76.8, 71.4,
60.1, 33.1, 32.4, 26.0, 25.9, 23.4, 19.4, 18.2, 18.1, 14.3, –4.1, –4.2,
–4.5, –4.7.
HRMS (ESI): m/z calcd for C23H48O4Si2 + Na (M + Na)+: 467.2988;
found: 467.2991.
IR (neat): 2964, 2930, 1719, 1654, 1613, 1513, 1464, 1368, 1301,
1247, 1173, 1040 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.5 Hz, 2 H), 6.89 (td,
J = 6.9, 15.5 Hz, 1 H), 6.81 (d, J = 8.5 Hz, 2 H), 5.73 (td, J = 1.3,
15.5 Hz, 1 H), 4.48 (d, J = 11.3 Hz, 1 H), 4.31 (d, J = 11.3 Hz, 1 H),
4.15 (q, J = 6.9 Hz, 2 H), 3.79 (s, 3 H), 3.53–3.42 (m, 1 H), 2.37–
2.16 (m, 2 H), 1.75–1.50 (m, 2 H), 1.29 (t, J = 6.9 Hz, 3 H), 1.18 (d,
J = 6.0 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 166.6, 159.0, 148.9, 130.7,
129.2, 121.3, 113.7, 73.4, 70.0, 60.1, 55.2, 34.9, 28.2, 19.5, 14.2.
HRMS (ESI): m/z calcd for C17H24O4 + Na (M + Na)+: 315.1572;
found: 315.1584.
(E)-8,9-Bis[1-(tert-butyl)-1,1-dimethylsilyl]oxydec-3-en-2-one
(15b)
Yield: 172 mg (83%); yellow oil; Rf = 0.6 (EtOAc–hexane, 2:8).
[a]D29 +3.7 (c 1.0, CHCl3).
IR (neat): 2932, 2891, 2858, 1678, 1630, 1466, 1362, 1253, 1100,
1035, 834 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.73 (td, J = 6.8, 15.8 Hz, 1 H),
6.03 (td, J = 1.5, 15.8 Hz, 1 H), 3.67–3.59 (m, 1 H), 3.49–3.44 (m,
1 H), 2.25–2.16 (m, 5 H), 1.62–1.48 (m, 2 H), 1.46–1.36 (m, 2 H),
1.08 (d, J = 6.0 Hz, 3 H), 0.89 (s, 9 H), 0.88 (s, 9 H), 0.06 (s, 3 H),
0.05 (s, 3 H), 0.04 (s, 6 H).
13C NMR (75.0 MHz, CDCl3): d = 198.5, 148.2, 131.4, 76.8, 71.4,
33.1, 32.7, 26.8, 26.0, 25.9, 23.4, 19.5, 18.2, 18.1, –4.1, –4.2, –4.4,
–4.7.
(E,7S)-7-[(4-Methoxybenzyl)oxy]oct-3-en-2-one (13b)
Yield: 114 mg (87%); colorless oil; Rf = 0.4 (EtOAc–hexane, 2:8).
[a]D29 +25.3 (c 1.1, CHCl3).
IR (neat): 2930, 2857, 1673, 1613, 1513, 1460, 1361, 1301, 1248,
1173, 1030 cm–1.
HRMS (ESI): m/z calcd for C22H46O3Si2 + Na (M + Na)+: 437.2878;
found: 437.2866.
1H NMR (500 MHz, CDCl3): d = 7.19 (d, J = 7.7 Hz, 2 H), 6.81 (d,
J = 7.7 Hz, 2 H), 6.70 (td, J = 6.7, 15.5 Hz, 2 H), 5.97 (d, J = 15.5
Hz, 1 H), 4.49 (d, J = 10.6 Hz, 1 H), 4.29 (d, J = 10.6 Hz, 1 H), 3.79
(s, 3 H), 3.50–3.44 (m, 1 H), 2.36–2.21 (m, 2 H), 2.16 (s, 3 H), 1.72–
1.64 (m, 1 H), 1.61–1.54 (m, 1 H), 1.19 (d, J = 6.7 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 198.6, 159.1, 148.2, 131.2,
130.7, 129.2, 113.7, 73.3, 69.9, 55.2, 35.0, 28.5, 26.7, 19.4.
(5S,6S,E)-9-(Benzyloxy)-6-(tert-butyldimethylsilyloxy)-5-meth-
ylnon-3-en-2-one (17b)
Yield: 172 mg (82%); colorless oil; Rf = 0.6 (EtOAc–hexane, 2:8).
[a]D28 –9.0 (c 1.2, CHCl3).
IR (neat): 2937, 2857, 1677, 1628, 1459, 1362, 1253, 1097, 835,
773 cm–1.
HRMS (ESI): m/z calcd for C16H22O3 + Na (M + Na)+: 285.1466;
found: 285.1460.
1H NMR (500 MHz, CDCl3): d = 7.33–7.22 (m, 5 H), 6.72 (td,
J = 6.9, 15.8 Hz, 1 H), 6.03 (d, J = 15.8 Hz, 1 H), 4.47 (s, 2 H),
3.57–3.53 (m, 1 H), 3.45–3.40 (m, 2 H), 2.31–2.23 (m, 1 H), 2.20
(s, 3 H), 2.19–2.11 (m, 1 H), 1.70–1.60 (m, 2 H), 1.58–1.47 (m, 3
H), 1.46–1.38 (m, 2 H), 0.89 (s, 9 H), 0.85 (d, J = 6.9 Hz, 3 H), 0.03
(s, 3 H), 0.02 (s, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 198.7, 148.6, 138.5, 131.2,
128.3, 127.5, 127.4, 75.4, 72.8, 70.4, 37.6, 30.6, 30.4, 29.5, 26.7,
26.3, 25.8, 18.1, 14.5, –4.3, –4.4.
Ethyl (E,6S)-6-[(4-Methoxybenzyl)oxy]-2-methylhept-2-enoate
(13c)
Yield: 129 mg (84%); yellow oil; Rf = 0.7 (EtOAc–hexane, 2:8).
[a]D29 +19.3 (c 1.3, CHCl3).
IR (neat): 2969, 2932, 1708, 1648, 1613, 1513, 1460, 1368, 1247,
1202, 1172, 1134, 1089, 1036, 822 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.20 (d, J = 8.3 Hz, 2 H), 6.81 (d,
J = 8.3 Hz, 2 H), 6.68 (t, J = 7.5 Hz, 1 H), 4.49 (d, J = 11.3 Hz, 1
H), 4.31 (d, J = 11.3 Hz, 1 H), 4.16 (q, J = 6.8 Hz, 2 H), 3.79 (s, 3
H), 3.53–3.42 (m, 1 H), 2.24 (q, J = 8.3 Hz, 2 H), 1.81 (s, 3 H),
1.74–1.50 (m, 2 H), 1.29 (t, J = 6.8 Hz, 3 H), 1.19 (d, J = 6.0 Hz, 3
H).
13C NMR (75.0 MHz, CDCl3): d = 168.1, 159.0, 141.8, 130.9,
129.1, 127.8, 113.7, 73.7, 70.0, 60.3, 55.2, 35.3, 24.7, 19.5, 14.2,
12.2.
HRMS (ESI): m/z calcd for C25H42O3Si + Na (M + Na)+: 441.2800;
found: 441.2782.
(S,E)-Ethyl 6-(Methyloxymethoxy)-6-phenylhex-2-enoate (19a)
Yield: 122 mg (88%); yellow oil; Rf = 0.6 (EtOAc–hexane, 2:8).
[a]D28 –130.1 (c 1.3, CHCl3).
IR (neat): 2937, 1719, 1653, 1451, 1367, 1270, 1152, 1035, 703
cm–1.
1H NMR (500 MHz, CDCl3): d = 7.33–7.22 (m, 5 H), 6.92 (td,
J = 6.9, 15.8 Hz, 1 H), 5.78 (d, J = 15.8 Hz, 1 H), 4.55 (t, J = 5.9 Hz,
1 H), 4.47 (s, 2 H), 4.15 (q, J = 6.9 Hz, 2 H), 3.33 (s, 3 H), 2.36–2.28
(m, 1 H), 2.27–2.18 (m, 1 H), 2.02–1.93 (m, 1 H), 1.85–1.77 (m, 1
H), 1.28 (t, J = 6.9 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 166.5, 148.3, 141.3, 128.4,
127.7, 126.7, 121.6, 94.0, 77.1, 60.1, 55.6, 36.0, 28.4, 14.1.
HRMS (ESI): m/z calcd for C18H26O4 + Na (M + Na)+: 329.1728;
found: 329.1744.
Ethyl (E)-7,8-Bis[1-(tert-butyl)-1,1-dimethylsilyl]oxynon-2-
enoate (15a)
Yield: 189 mg (85%); yellow oil; Rf = 0.8 (EtOAc–hexane, 2:8).
[a]D29 +1.4 (c 1.2, CHCl3).
HRMS (ESI): m/z calcd for C16H22O4 + Na (M + Na)+: 301.1415;
found: 301.1409.
IR (neat): 2955, 2931, 2887, 2858, 1723, 1655, 1472, 1463, 1367,
1256, 1144, 1098, 1041, 982, 835 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.90 (td, J = 6.9, 15.5 Hz, 1 H),
5.76 (td, J = 1.5, 15.5 Hz, 1 H), 4.16 (q, J = 7.1 Hz, 2 H), 3.67–3.59
(m, 1 H), 3.49–3.44 (m, 1 H), 2.22–2.14 (m, 2 H), 1.64–1.37 (m, 4
H), 1.29 (t, J = 7.1 Hz, 3 H), 1.08 (d, J = 6.2 Hz, 3 H), 0.89 (s, 9 H),
0.88 (s, 9 H), 0.06 (s, 3 H), 0.04 (s, 9 H).
Ethyl (E)-6-Phenoxyhex-2-enoate (21a)
Yield: 94 mg (86%); yellow oil; Rf = 0.5 (EtOAc–hexane, 2:8).
IR (neat): 2939, 1718, 1654, 1595, 1494, 1243, 1169, 1042, 754
cm–1.
Synthesis 2011, No. 22, 3661–3668 © Thieme Stuttgart · New York

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Sequential One-Pot Isomerization–Wittig Olefination–Hydrogenation
3667
1H NMR (300 MHz, CDCl3): d = 7.26–7.19 (m, 2 H), 7.02–6.80 (m,
4 H), 5.82 (d, J = 15.8 Hz, 1 H), 4.17 (q, J = 7.5 Hz, 2 H), 3.96 (t,
J = 6.0 Hz, 2 H), 2.46–2.37 (m, 2 H), 2.02–1.90 (m, 2 H), 1.29 (t,
J = 7.5 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 166.5, 158.7, 148.0, 129.3,
121.9, 120.6, 114.4, 66.6, 60.1, 28.7, 27.7, 14.2.
13C NMR (75.0 MHz, CDCl3): d = 208.9, 159.0, 130.6, 129.1,
113.6, 72.4, 64.7, 55.1, 43.5, 29.7, 29.4, 25.7, 23.5.
HRMS (ESI): m/z calcd for C15H22O3 + Na (M + Na)+: 273.1466;
found: 273.1478.
Ethyl 6-[(4-Methoxybenzyl)oxy]-2-methylhexanoate (23c)
Yield: 124 mg (84%); yellow oil; Rf = 0.7 (EtOAc–hexane, 2:8).
HRMS (ESI): m/z calcd for C14H18O3 + Na (M + Na)+: 257.1153;
found: 257.1159.
IR (neat): 2937, 2859, 1731, 1613, 1513, 1461, 1371, 1248, 1174,
1096, 1035, 820 cm–1.
(2S)-2-(6-Ethoxyhept-6-enyl)-1,4-dioxaspiro[4.5]decane (22a)
Yield: 117 mg (86%); colorless liquid; Rf = 0.7 (EtOAc–hexane,
2:8).
[a]D29 +4.8 (c 0.9, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.6 Hz, 2 H), 6.81 (d,
J = 8.6 Hz, 2 H), 4.38 (s, 2 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.78 (s, 3
H), 3.38 (t, J = 6.4 Hz, 2 H), 2.43–2.32 (m, 1 H), 1.71–1.52 (m, 4
H), 1.48–1.30 (m, 4 H), 1.25 (t, J = 7.1 Hz, 3 H), 1.13 (d, J = 6.9 Hz,
3 H).
13C NMR (75.0 MHz, CDCl3): d = 176.7, 159.0, 130.6, 129.1,
113.7, 72.4, 69.7, 60.0, 55.2, 39.4, 33.5, 29.5, 23.8, 17.0, 14.2.
IR (neat): 2936, 2862, 1722, 1655, 1448, 1366, 1279, 1163, 1105,
1041, 985, 929 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.10 (q, J = 7.2 Hz, 2 H), 4.05–
3.94 (m, 2 H), 3.48–3.41 (m, 1 H), 2.28 (t, J = 7.2 Hz, 2 H), 1.71–
1.31 (m, 16 H), 1.26 (t, J = 7.2 Hz, 3 H).
HRMS (ESI): m/z calcd for C17H26O4 + Na (M + Na)+: 317.1728;
found: 317.1709.
13C NMR (75.0 MHz, CDCl3): d = 173.5, 109.1, 75.3, 69.0, 60.2,
(7S)-7-[(4-Methoxybenzyl)oxy]octan-2-one (24b)
Yield: 112 mg (85%); colorless oil; Rf = 0.5 (EtOAc–hexane, 2:8).
[a]D29 +17.6 (c 1.1, CHCl3).
36.5, 35.2, 34.1, 33.4, 25.3, 25.1, 24.8, 23.9, 23.8, 14.1.
HRMS (ESI): m/z calcd for C15H27O4 (M + H)+: 271.1909; found:
271.1916.
IR (neat): 2933, 2861, 1713, 1613, 1513, 1459, 1367, 1300, 1246,
1171, 1069, 1036, 821 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.3 Hz, 2 H), 6.81 (d,
J = 8.3 Hz, 2 H), 4.46 (d, J = 11.3 Hz, 1 H), 4.31 (d, J = 11.3 Hz, 1
H), 3.78 (s, 3 H), 3.49–3.39 (m, 1 H), 2.37 (t, J = 7.5 Hz, 2 H), 2.10
(s, 3 H), 1.57–1.24 (m, 6 H), 1.15 (d, J = 6.0 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 209.2, 158.9, 131.0, 129.1,
113.6, 74.1, 69.9, 55.2, 43.6, 36.3, 29.8, 25.0, 23.7, 19.5.
HRMS (ESI): m/z calcd for C16H24O3 + Na (M + Na)+: 287.1623;
7-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]heptan-2-one (22b)
Yield: 104 mg (86%); colorless liquid; Rf = 0.5 (EtOAc–hexane,
2:8).
[a]D29 +4.76 (c 1.1, CHCl3).
IR (neat): 2935, 2859, 1715, 1450, 1363, 1279, 1163, 1106, 1039,
932 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.07–3.94 (m, 2 H), 3.43 (t, J = 6.8
Hz, 1 H), 2.42 (t, J = 7.2 Hz, 2 H), 2.11 (s, 3 H), 1.64–1.24 (m, 16
H).
found: 287.1634.
13C NMR (75.0 MHz, CDCl3): d = 208.8, 109.2, 75.4, 69.0, 43.5,
Ethyl (6S)-6-[(4-Methoxybenzyl)oxy]-2-methylheptanoate (24c)
Yield: 125 mg (81%); colorless oil; Rf = 0.7 (EtOAc–hexane, 2:8).
[a]D29 +14.0 (c 1.0, CHCl3).
36.6, 35.2, 33.5, 29.8, 25.4, 25.2, 24.0, 23.9, 23.7.
HRMS (ESI): m/z calcd for C14H24O3 + Na (M + Na)+ : 263.1618;
found: 263.1589.
IR (neat): 2971, 2936, 2864, 1731, 1613, 1513, 1460, 1374, 1247,
1175, 1036, 819 cm–1.
Ethyl 6-[(4-Methoxybenzyl)oxy]hexanoate (23a)
Yield: 118 mg (84%); colorless oil; Rf = 0.6 (EtOAc–hexane, 2:8).
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.3 Hz, 2 H), 6.80 (d,
J = 8.3 Hz, 2 H), 4.46 (d, J = 11.3 Hz, 1 H), 4.33 (d, J = 11.3 Hz, 1
H), 4.10 (q, J = 6.8 Hz, 2 H), 3.78 (s, 3 H), 3.50–3.39 (m, 1 H),
2.41– 2.30 (m, 1 H), 1.65–1.31 (m, 6 H), 1.25 (t, J = 6.8 Hz, 3 H),
1.16–1.10 (m, 6 H).
13C NMR (75.0 MHz, CDCl3): d = 176.7, 159.0, 131.1, 129.1,
113.6, 74.2, 69.9, 60.0, 55.2, 39.4, 36.4, 33.7, 23.2, 19.5, 17.0, 14.2.
IR (neat): 2937, 2860, 1733, 1612, 1513, 1460, 1369, 1247, 1174,
1097, 1035, 820 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.19 (d, J = 8.6 Hz, 2 H), 6.81 (d,
J = 8.6 Hz, 2 H), 4.38 (s, 2 H), 4.09 (q, J = 6.7 Hz, 2 H), 3.78 (s, 3
H), 3.39 (t, J = 6.7 Hz, 2 H), 2.26 (t, J = 6.7 Hz, 2 H), 1.66–1.56 (m,
4 H), 1.43–1.36 (m, 2 H), 1.25 (t, J = 6.7 Hz, 3 H).
13C NMR (75.0 MHz, CDCl3): d = 173.5, 158.9, 130.5, 128.9,
113.5, 72.3, 69.6, 59.9, 54.9, 34.0, 29.2, 25.5, 24.5, 14.0.
HRMS (ESI): m/z calcd for C18H29O4 (M + H)+: 309.2065; found:
309.1911.
HRMS (ESI): m/z calcd for C16H24O4 + Na (M + Na)+: 303.1572;
found: 303.1563.
8,9-Bis[1-(tert-butyl)-1,1-dimethylsilyl]oxydecan-2-one (25b)
Yield: 166 mg (80%); colorless oil; Rf = 0.8 (EtOAc–hexane, 2:8).
7-[(4-Methoxybenzyl)oxy]heptan-2-one (23b)
Yield: 104 mg (83%); pale yellow oil; Rf = 0.4 (EtOAc–hexane,
2:8).
[a]D29 +1.1 (c 1.4, CHCl3).
IR (neat): 2932, 2891, 2857, 1719, 1466, 1362, 1253, 1105, 1038,
834 cm–1.
IR (neat): 2936, 2859, 1715, 1613, 1513, 1463, 1361, 1301, 1247,
1172, 1098, 1035, 821 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.3 Hz, 2 H), 6.81 (d,
J = 8.3 Hz, 2 H), 4.38 (s, 2 H), 3.78 (s, 3 H), 3.39 (t, J = 6.8 Hz, 2
H), 2.39 (t, J = 6.8 Hz, 2 H), 2.09 (s, 3 H), 1.63–1.50 (m, 5 H), 1.40–
1.30 (m, 3 H).
1H NMR (300 MHz, CDCl3): d = 3.67–3.58 (m, 1 H), 3.48–3.42 (m,
1 H), 2.39 (t, J = 7.5 Hz, 2 H), 2.10 (s, 3 H), 1.61–1.50 (m, 2 H),
1.40–1.23 (m, 6 H), 1.06 (d, J = 6.0 Hz, 3 H), 0.88 (s, 18 H), 0.05
(s, 3 H), 0.04 (s, 9 H).
13C NMR (75.0 MHz, CDCl3): d = 209.0, 77.1, 71.5, 43.7, 33.6,
29.8, 29.5, 26.0, 25.9, 24.8, 23.8, 19.1, 18.2, 18.1, –4.1, –4.3, –4.5,
–4.7.
Synthesis 2011, No. 22, 3661–3668 © Thieme Stuttgart · New York

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G. Sabitha et al.
PAPER
HRMS (ESI): m/z calcd for C22H48O3Si2 + Na (M + Na)+: 439.3040;
HRMS (ESI): m/z calcd for C18H26O5 + Na (M + Na)+: 345.1677;
found: 439.3040.
found: 345.1683.
Ethyl (S)-6-(Methoxymethoxy)-6-phenylhexanoate (26a)
Yield: 112 mg (80%); yellow oil; Rf = 0.5 (EtOAc–hexane, 2:8).
Acknowledgment
[a]D28 –114.0 (c 1.5, CHCl3).
S.N. and M.B. thank CSIR, New Delhi, India for the award of fel-
lowships. J.S.Y. acknowledges the partial support by King Saud
University for Global Research Network for Organic Synthesis
(GRNOS).
IR (neat): 2939, 1735, 1455, 1372, 1149, 1098, 1034, 918, 760, 702
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–7.18 (m, 5 H), 4.51 (dd,
J = 5.2, 7.5 Hz, 1 H), 4.45 (s, 2 H), 4.08 (q, J = 6.8 Hz, 2 H), 3.32
(s, 3 H), 2.25 (t, J = 7.5 Hz, 2 H), 1.90–1.76 (m, 1 H), 1.72–1.58 (m,
3 H), 1.53–1.40 (m, 1 H), 1.38–1.27 (m, 1 H), 1.23 (t, J = 6.8 Hz, 3
H).
13C NMR (75.0 MHz, CDCl3): d = 173.6, 149.9, 128.3, 127.5,
126.8, 94.0, 77.7, 60.1, 55.4, 37.5, 34.1, 25.4, 24.8, 14.2.
References
(1) (a) Organic Syntheses via Metal Carbonyls; Wender, I.;
Pino, P., Eds.; Wiley: New York, 1977. (b) New Syntheses
with Carbon Monoxide; Falbe, J., Ed.; Springer: Berlin,
1980, 1–225. (c) Kohlpaintner, C. W.; Frohning, C. D. In
Applied Homogeneous Catalysis with Organometallic
Compounds, Vol. 1; Cornils, B.; Herrmann, W. A., Eds.;
VCH: Weinheim, 1996, 1–39.
HRMS (ESI): m/z calcd for C16H24O4 + Na (M + Na)+: 303.1572;
found: 303.1570.
(2) Gold, H. In Houben–Weyl Methoden der Organischen
Chemie, Vol. 7/2b; Müller, E., Ed.; Thieme: Stuttgart, 1976,
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(3) Bayer, O. In Houben–Weyl Methoden der Organischen
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Sequential One-Pot Isomerization–Wittig Olefination–Oxa-
Michael Reaction; Ethyl 2-{(2R,6S)-6-[(4-Methoxyben-
zyl)oxy]methyltetrahydro-2H-2-pyranyl}acetate (30); Typical
Procedure
A 50 mL two-necked round-bottomed flask was charged with
Pd(OH)2/C (23 mg, 7 mol%) and benzene (3 mL). H2 gas was then
passed through the suspension via a balloon for 30 min (for the ac-
tivation of the catalyst). The H2 gas supply was stopped and stirring
continued for 10 min after which a solution of the allylic alcohol 27
(0.5 mmol) in benzene (3 mL) was added. The reaction mixture was
stirred for another 10 min. After complete conversion of allylic al-
cohol to the corresponding lactol, as indicated by TLC (eluent:
EtOAc–hexane, 3:7), the stable Wittig ylide 3 (0.65 mmol) was add-
ed and stirred at reflux conditions for 1 h. Then, the reaction mixture
was allowed to attain r.t. and treated with 1 M solution of TBAF in
THF (4.0 mmol) and the stirring was continued for 6 h. The mixture
was filtered through a Celite pad and washed with EtOAc (3 × 10
mL). The filtrate was concentrated in vacuo and the residue was pu-
rified by silica gel column chromatography (15% EtOAc–hexane as
eluent) to afford tetrahydropyran 30 as a colorless oil; yield: 124 mg
(77%, over three steps); Rf = 0.6 (EtOAc–hexane, 3:7); [a]D29 –5.1
(c 0.5, CHCl3).
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Andersen, R. J. J. Am. Chem. Soc. 2007, 129, 508.
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(12) (a) Haustedt, L. O.; Hartung, I. V.; Hoffmann, H. M. R.
Angew. Chem. Int. Ed. 2003, 42, 2711. (b) Marmsäter, F.
P.; West, F. G. Chem. Eur. J. 2002, 8, 4346. (c) Hale, K. J.;
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Prod. Rep. 2002, 19, 413.
IR (neat): 2932, 2858, 1736, 1613, 1513, 1455, 1374, 1247, 1190,
1096, 1036, 820 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.19 (d, J = 8.5 Hz, 2 H), 6.80 (d,
J = 8.5 Hz, 2 H), 4.44 (ABq, J = 11.7 Hz, 2 H), 4.10 (q, J = 7.2 Hz,
2 H), 3.78 (s, 3 H), 3.76–3.70 (m, 1 H), 3.59–3.50 (m, 1 H), 3.41
(dd, J = 5.6, 10.0 Hz, 1 H), 3.31 (dd, J = 4.9, 10.0 Hz, 1 H), 2.54
(dd, J = 7.1, 15.1 Hz, 1 H), 2.33 (dd, J = 6.0, 15.1 Hz, 1 H), 1.90–
1.81 (m, 1 H), 1.68–1.50 (m, 3 H), 1.29–1.18 (m, 5 H).
13C NMR (75.0 MHz, CDCl3): d = 171.3, 159.0, 130.4, 129.2,
113.6, 77.2, 74.3, 73.0, 72.8, 60.3, 55.2, 41.6, 31.0, 27.7, 22.9, 14.1.
(13) Sabitha, G.; Reddy, D. V.; Rao, A. S.; Yadav, J. S.
Tetrahedron Lett. 2010, 51, 4195.
Synthesis 2011, No. 22, 3661–3668 © Thieme Stuttgart · New York