Synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans via (3,5)-oxonium-ene reaction

Article abstract of DOI:10.1039/c2ob06832j

An efficient method for the synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans has been developed from the reaction of aldehydes and ethyl 2-(1-hydroxyalkyl/hydroxy(phenyl)methyl)-5-methylhex-4-enoate using (3,5)-oxonium-ene reaction promoted by boron

Full text of DOI:10.1039/c2ob06832j

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PAPER
Synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans via (3,5)-oxonium-ene
reaction†
Pipas Saha, Anup Bhunia and Anil K. Saikia*
Received 24th October 2011, Accepted 25th January 2012
DOI: 10.1039/c2ob06832j
An efficient method for the synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans has been developed
from the reaction of aldehydes and ethyl 2-(1-hydroxyalkyl/hydroxy(phenyl)methyl)-5-methylhex-4-
enoate using (3,5)-oxonium-ene reaction promoted by boron trifluoride etherate in good yields under mild
conditions.
Introduction
could be considered as starting materials for the synthesis of
tetrasubstituted tetrahydropyrans.
The tetrahydropyrans are important structural features in syn-
thetic organic chemistry as they are core units of many biologi-
cally active molecules and natural products. The polyether
1
antibiotics, marine toxins and pheromones are such biologically
active natural products. The 2,3,5,6-tetrasubstituted tetrahydro-
2
Results and discussion
pyran units are found in antibiotics such as FR-901464 and
The reaction of alcohols ethyl 2-(1-hydroxyethyl)-5-methylhex-
3
X-206. Tetrahydropyrans are prepared by hetero-Diels–Alder
4
-enoate 1a (1 : 1 diastereomeric mixture) and ethyl 2-(1-hydro-
4
5
reactions, manipulations of carbohydrates, intramolecular
xypropyl)-5-methylhex-4-enoate 1b (1 : 1 diastereomeric
mixture) with different aldehydes in dry toluene in the presence
of boron trifluoride etherate afforded a mixture of diastereomeric
products 3 and 4 with an epimeric center on C-3 bearing an ester
group (Table 1). In all the cases the diastereomeric ratio was
6
7
8
Michael reactions, Prins cyclization and other methods.
Several 2,4-, 2,3,6-, 2,4,5-, 2,4,6-, 2,3,4,6- and 2,4,5,6-substi-
tuted tetrahydropyrans have been synthesized using these
approaches. To our knowledge the synthetic procedures for the
synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans are
1
: 1. The diastereomers 3 and 4 could be separated by column
9
limited. Oxonium-ene reactions are considered as powerful
chromatography. The stereochemistry of 3 and 4 was determined
1
0
12
tools for the construction of various cyclic ethers. Recently, we
have demonstrated the utility of the oxonium-ene reaction for the
synthesis of 2,2,5,6- and 2,4,6-substituted tetrahydropyrans and
by NOE experiment and X-ray crystallographic analysis. In the
1
H NMR spectrum the axial proton at position C-4 (H ) of 3a
4a
shows a ddd with coupling constants 12.8, 12.4 and 12.4 Hz at δ
.99 ppm, which indicates that the proton is coupled with two
11
bicyclic ethers. Herein, we now report an efficient method-
ology for the synthesis of 2,3,5,6-tetrasubstituted tetrahydropyr-
ans from aldehydes and ethyl 2-(1-hydroxyalkyl/hydroxy
1
neighbouring axial protons H3a and H . On the other hand same
5a
proton (H ) of 4a shows a ddd with coupling constants 13.6,
4a
(
phenyl)methyl)-5-methylhex-4-enoate using (3,5)-oxonium-ene
1
2.8 and 5.2 Hz at δ 1.90 ppm, which is indicative of coupling
reaction promoted by boron trifluoride etherate under mild con-
ditions. Our aim is to introduce an ester group onto the tetrahy-
dropyran ring, from which diverse functionalization could be
achieved in the tetrahydropyran molecule and therefore, ethyl 2-
with one axial H5a and one equatorial proton H . This clearly
3e
indicates that 3a and 4a are epimeric at C-3. A comparison of
1
other H NMR signals of 3a and 4a is shown in Table 2.
The mechanism for the formation of two diastereomers 3 and
(1-hydroxyalkyl/hydroxy(phenyl)methyl)-5-methylhex-4-enoate
4
(
from alcohols 1a and 1b can be explained as follows
Scheme 1). Here, Lewis acid activates the aldehyde 2 for the
nucleophilic attack by alcohols 1a and 1b to give acetals 5 and
, which after decomposition generate oxocarbenium ions 7 and
6
Department of Chemistry, Indian Institute of Technology Guwahati,
Guwahati 781039, Assam, India. E-mail: asaikia@iitg.ernet.in; Fax:
8. The species 7 and 8, after (3,5)-oxonium-ene reaction, form
carbocations 9 and 10, which after deprotonation give 3 and 4 in
equal amounts.
The reaction was also performed with anti- and syn-alcohols
1c and 1d. The reaction of aldehyde 2 with anti-ethyl
+91 361 2690762; Tel: +91 361 258 2316
†
Electronic supplementary information (ESI) available: General exper-
1
13
imental methods, copies of H and C NMR spectra of all compounds.
CCDC 819363–819366. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c2ob06832j
2470 | Org. Biomol. Chem., 2012, 10, 2470–2481
This journal is © The Royal Society of Chemistry 2012

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1
Table 1 Synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans
Table 2 Comparison of H NMR data of 3a and 4a
Alcohol
a,b
1
a, R = Me, 1b,
Time
(min)
3 + 4 Yield
(%)
Entry R = Et
Aldehyde R′=
Coupling
constants (Hz)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
C
6
H
5
60
60
60
60
60
60
60
30
30
30
90
90
90
50
50
50
78
72
66
62
64
62
68
86
82
84
74
70
68
88
80
84
Assignment δ (ppm)
Multiplicity
p-Me-C
p-Br-C
p-Cl-C
p-F-C
p-NO
p-MeO
C
C
(CH
6 4
H
6
H
4
13-CH
9-CH
12-CH
3
1.27 (3a)
1.32 (4a)
1.28 (3a)
1.33 (4a)
1.43 (3a)
1.42 (4a)
1.99 (3a)
1.90 (4a)
2.09 (3a)
2.14 (4a)
2.33 (3a)
2.60–2.67 (4a)
2.46 (3a)
d
d
t
t
s
s
ddd
ddd
ddd
ddd
ddd
m
ddd
ddd
m
m
7.2
6.4
7.2
7.2
—
6
H
4
6
H
-C
4
3
2
6
H
4
2
C-C
6
H
4
3
H
H
7
—
3
H
H
4a
4e
12.8, 12.4, 12.4
13.6, 12.8, 5.2
12.8, 4.0, 4.0
13.6, 4.0, 4.0
12.4, 10.4, 4.0
—
12.4, 10.0, 4.0
12.8, 12.4, 3.6
—
6
13
3
)
2
CHCH
2
C
6
H
5
Et
Et
Et
Et
p-Me-C
p-MeO
C
C
6
H
4
2
C-C
6
H
4
H
H
H
3a
3e
5a
3
H
H
7
6
13
Et
(CH
3
)
2
CHCH
2
3.01 (4a)
H
2a
3.76–3.85 (3a)
3.82–3.89 (4a)
4.17 (3a)
a
1
The ratio of formation of 3 and 4 is (1 : 1) and is determined by H
—
7.2
—
b
NMR of crude products. Total isolated yield of 3 and 4. The
compounds were characterized by IR, H, C, F NMR and mass
spectroscopy.
8-CH
2
-
q
m
1
13
19
4.14–4.28 (4a)
(overlapping)
d
m
H
6a
4.29 (3a)
10.0
—
4
.14–4.28 (4a)
(
overlapping)
1
1H
1H
Ar–H
brs
brs
brs
brs
m
—
—
—
—
—
—
4
1
2
-(hydroxy(phenyl)methyl)-5-methylhex-4-enoate
1c
gave
single diastereomer 11 in good yields (Table 3).
m
Similarly, the reaction of syn-ethyl 2-(hydroxy(phenyl)
methyl)-5-methylhex-4-enoate 1d gave single diastereomer 12 in
good yields (Table 4). The stereochemistry of the compounds
was determined by NOE experiment and X-ray crystallographic
12
analysis.
It was observed from Tables 1,3–4 that aliphatic aldehydes
gave better yields compared to the aromatic aldehydes. The aro-
matic aldehydes having electron-withdrawing groups gave lower
yield than the aromatic aldehydes having electron-donating
groups. This might be due to the better stability imparted to the
oxocarbenium ions 7 and 8 (Scheme 1) by the aliphatic alde-
hydes and aromatic aldehydes having electron donating groups
on the aromatic ring, which in turn are attacked by the double
bond efficiently. On the other hand, aromatic aldehydes having
electron withdrawing groups on the ring destabilize the oxocar-
benium ions 7 and 8.
The mechanisms for the formation of 2,3,5,6-substituted tetra-
hydropyrans 11 and 12 is similar to the one shown in Scheme 1.
The reaction of salicylaldehyde with anti/syn-ethyl 2-(hydroxy
(
phenyl)methyl)-5-methylhex-4-enoate, 1c/1d gave tricyclic
Scheme 1 Mechanism for the formation of tetrahydropyrans.
chromene compounds 13 and 14 with 58% and 55% yields,
respectively (Scheme 2). Here in both the cases 30% unreacted
starting materials were recovered. The structure and stereo-
chemistry of the compounds were determined from NOE exper-
cyclization of 16 is attacked by nucleophilic phenolic group to
form the tricyclic chromene compounds 13 and 14. The mechan-
ism is in accordance with the mechanism reported in the
1
2
iment and X-ray crystallographic analysis.†
The mechanism for the formation of chromenes is shown in
10c,11c
Scheme 3. Here the carbocation 17 formed after oxonium-ene
literature.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2470–2481 | 2471

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Table 3 Synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans from
anti-alcohol 1c
a
Entry
Aldehyde R′=
Time (min)
Product
Yield (%)
1
2
3
4
5
6
7
8
C
6
H
5
(a)
p-Me-C
p-MeO-C
p-F-C
p-NO
p-MeO
(g)
CHCH
60
60
60
60
60
60
30
30
11a
11b
11c
11d
11e
11f
80
70
74
60
60
65
92
87
6
H
6
4
(b)
Scheme 2 Reaction with salicylaldehyde.
H
4
(c)
6
H
4
-C
(d)
H
6 4
2
(e)
2
C-C
6
H
4
(f)
C
(CH
2
H
5
)
11g
11h
3
2
2
(h)
a
Yields refer to isolated yield. The compounds were characterized by
1
13
19
IR, H, C, F NMR and mass spectroscopy.
Table 4 Synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans from
syn-alcohol 1d
Scheme 3 Mechanism for the formation of chromenes.
1
.1 equiv.). To this solution ethyl 2-(1-hydroxyalkyl/hydroxy
a
Entry
Aldehyde R′=
Time (min)
Product
Yield (%)
(phenyl)methyl)-5-methylhex-4-enoate (1 mmol, 1 equiv.) in
dry toluene (2 mL) was added drop by drop over 5 min. The
reaction mixture was stirred at that temperature for a specified
time. The progress of the reaction was monitored by TLC with
ethyl acetate and hexane as eluents. After completion of the reac-
1
2
3
4
5
6
p-Me-C
p-Br-C
p-Cl-C
p-MeO
(e)
cyclo-C
6
H
4
4
(a)
(b)
(c)
C-C
60
60
60
60
30
30
12a
12b
12c
12d
12e
12f
72
58
55
62
90
80
6
H
6
H
2
4
6
H
4
(d)
C
3
H
7
tion, it was quenched with saturated solution of NaHCO . The
3
6
H11 (f)
product was extracted with ethyl acetate (30 mL) and then
washed with water (15 mL) and brine (15 mL). The organic
layer was dried (Na SO ) and evaporated to leave the crude
a
Yields refer to isolated yield. The compounds are characterized by IR,
1
13
H, C NMR and mass spectroscopy.
2
4
product, which was purified by short column chromatography
over silica gel to give the title compounds.
Conclusions
In conclusion we have developed an efficient methodology for
the synthesis of 2,3,5,6-tetrasubstituted tetrahydropyrans from
aldehydes and δ-unsaturated alcohols using (3,5)-oxonium-ene
reaction mediated by boron trifluoride etherate in good yields
under mild conditions. Synthesis of highly substituted tetrahy-
dropyrans is of great importance in organic synthesis as they are
the key structural features in many biologically active natural
products and pharmaceuticals. Therefore, the present method
would be beneficial to synthetic chemistry community.
Synthesis of (2R*,3S*,5S*,6R*)/(2R*,3R*,5S*,6R*)-ethyl
tetrahydro-2-methyl-6-phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-
carboxylate (3a & 4a)
To a solution of benzaldehyde (106 mg, 1.00 mmol) in dry
toluene (2 mL) at 0 °C was added boron trifluoride etherate
(156 mg, 1.10 mmol). To this solution ethyl 2-(1-hydroxyethyl)-
5
-methylhex-4-enoate (200 mg, 1 mmol) in dry toluene (2 mL)
was added drop by drop over 5 min. The reaction mixture was
stirred at that temperature for another 55 min. The progress of
the reaction was monitored by TLC with ethyl acetate and
hexane (1 : 24) as eluents. After completion of the reaction, it
Experimental section
was quenched with saturated solution of NaHCO . The product
3
was extracted with ethyl acetate (30 mL) and then washed with
water (15 mL) and brine (15 mL). The organic layer was dried
General procedure for the synthesis of 2,3,5,6-tetrasubstituted
tetrahydropyrans and chromenes
(
Na SO ) and evaporated to leave the crude products, which
2 4
To a solution of aldehyde (1 mmol, 1 equiv.) in dry toluene
were separated by column chromatography over silica gel to give
(2 mL) at 0 °C was added boron trifluoride etherate (1.1 mmol,
3a (115 mg, 40%) and 4a (110 mg, 38%) as colourless oils.
2472 | Org. Biomol. Chem., 2012, 10, 2470–2481
This journal is © The Royal Society of Chemistry 2012

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(2R*,3S*,5S*,6R*)-Ethyl tetrahydro-2-methyl-6-phenyl-5-(prop-
(2R*,3S*,5S*,6R*)-Ethyl 6-(4-chlorophenyl)-tetrahydro-2-
1
-en-2-yl)-2H-pyran-3-carboxylate (3a)
methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (3d)
1
1
Colourless oil (115 mg, 40%); H NMR (400 MHz, CDCl ): δ
Colourless oil (106 mg, 33%); H NMR (400 MHz, CDCl ): δ
3
3
1
.27 (d, J = 6.4 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3
1.25 (d, J = 6.0 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.45 (s, 3
H), 1.97 (ddd, J = 12.8, 12.8 and 12.4 Hz, 1 H), 2.09 (ddd, J =
12.8, 4.0 and 3.6 Hz, 1 H), 2.25 (ddd, J = 12.8, 12.8 and 3.6 Hz,
1 H), 2.44 (ddd, J = 12.4, 10.0 and 4.0 Hz, 1 H), 3.76–3.84 (m,
1 H), 4.17 (q, J = 7.2 Hz, 2 H), 4.27 (d, J = 10.0 Hz, 1 H), 4.62
(brs, 1 H), 4.68 (brs, 1 H), 7.23 (d, J = 8.4 Hz, 2 H), 7.26 (d, J =
H), 1.99 (ddd, J = 12.8, 12.4 and 12.4 Hz, 1 H), 2.09 (ddd, J =
1
1
1
2.8, 4.0 and 4.0 Hz, 1 H), 2.33 (ddd, J = 12.4, 10.4 and 4.0 Hz,
H), 2.46 (ddd, J = 12.4, 10.0 and 4.0 Hz, 1 H), 3.76–3.85 (m,
H), 4.17 (q, J = 7.2 Hz, 2 H), 4.29 (d, J = 10.0 Hz, 1 H), 4.62
1
3
(brs, 1 H), 4.66 (brs, 1 H), 7.22–7.32(m, 5 H); C NMR
13
(100 MHz, CDCl ): δ 14.4, 20.3, 21.5, 34.0, 49.5, 49.8, 60.6,
8.8 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.4, 20.3, 21.6,
3
3
7
5.1, 84.1, 113.0, 127.5, 128.0, 128.3, 140.7, 145.1, 173.9; IR
33.9, 49.7 (2C), 60.7, 75.2, 83.2, 113.4, 128.5, 128.8, 133.6,
139.3, 144.7, 173.8; IR (KBr, neat): 2978, 2932, 2866, 1729,
(KBr, neat): 2978, 2933, 1730, 1644, 1452, 1375, 1175, 1102,
−1
−1
1
064, 755, 699 cm . HRMS (APCI) cald for C H O (M +
1645, 1449, 1376, 1175, 1099, 1067, 894, 824 cm . HRMS
1
8 24 3
+
+
H) requires 289.1803; found 289.1803. APCI-MS: m/z (relative
intensity): 289.2 ((M + H) , 42%), 287.2 (11), 243.1 (9), 197.1
(APCI) cald for C H ClO (M + H) requires 323.1414; found
18
23
3
+
35
323.1407 ( Cl). APCI-MS: m/z (relative intensity): 325.1 ((M +
H) , 3%, Cl), 323.2 ((M + H) , 10, Cl), 267.2 (10), 200.1
9), 199.1 (66), 181.1 (100), 157.1 (18), 124.1 (83).
+
37
+
35
(9), 157.1 (26), 124.1 (100), 123.1 (44), 82.0 (25).
(
(
2R*,3S*,5S*,6R*)-Ethyl 6-(4-fluorophenyl)-tetrahydro-2-
(
2R*,3S*,5S*,6R*)-Ethyl tetrahydro-2-methyl-5-(prop-1-en-2-
methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (3e)
yl)-6-p-tolyl-2H-pyran-3-carboxylate (3b)
1
1
Colourless oil (89 mg, 29%); H NMR (400 MHz, CDCl
1
H), 1.97 (ddd, J = 14.0, 12.8 and 12.0 Hz, 1 H), 2.09 (ddd, J =
3
): δ
Colourless oil (115 mg, 38%); H NMR (400 MHz, CDCl ): δ
1
H), 1.97 (ddd, J = 12.8, 12.6 and 12.4 Hz, 1 H), 2.10 (ddd, J =
1
3
.25 (d, J = 6.0 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.44 (s, 3
.24 (d, J = 6.4 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.45 (s, 3
1
1
1
(
(
3
1
1
(
1
(
3
4.0, 4.0 and 4.0 Hz, 1 H), 2.27 (ddd, J = 12.8, 10.4 and 4.0 Hz,
H), 2.44 (ddd, J = 12.0, 10.0 and 4.0 Hz, 1 H), 3.76–3.84 (m,
H), 4.17 (q, J = 7.2 Hz, 2 H), 4.28 (d, J = 10.0 Hz, 1 H), 4.62
2.8, 4.0 and 3.6 Hz, 1 H), 2.30 (s, 3 H), 2.34 (ddd, J = 12.6,
2.4 and 3.6 Hz, 1 H), 2.44 (ddd, J = 12.4, 10.4 and 4.0 Hz, 1
1
H), 3.75–3.84 (m, 1 H), 4.16 (q, J = 7.2 Hz, 2 H), 4.26 (d, J =
0.4 Hz, 1 H), 4.63 (brs, 1 H), 4.65 (brs, 1 H), 7.09 (d, J = 7.6
brs, 1 H), 4.67 (brs, 1 H), 6.98 (t, J = 8.4 Hz, 2 H), 7.24–7.28
1
13
m, 2 H); C NMR (100 MHz, CDCl ): δ 14.4, 20.3, 21.5,
1
3
3
Hz, 2 H), 7.17 (d, J = 8.0 Hz, 2 H); C NMR (100 MHz,
CDCl ): δ 14.4, 20.3, 21.3, 21.5, 34.1, 49.3, 49.8, 60.6, 75.1,
8
neat): 2977, 2929, 2857, 1731, 1375, 1101, 1065, 812 cm
HRMS (APCI) cald for C H O (M + H) requires 303.1960;
found 303.1952. APCI-MS: m/z (relative intensity): 303.2
(
3.9, 49.7, 49.8, 60.7, 75.2, 83.2, 113.2, 115.0 (d, J = 21.3 Hz),
3
29.1 (d, J = 8.4 Hz), 136.7, 144.9, 162.5 (d, J = 244.1 Hz),
3.8, 112.9, 127.5, 129.0, 137.6, 137.7, 145.3, 174.0; IR (KBr,
19
73.8;
F NMR (376 MHz, CDCl /C F ): δ −218.70–
−1
3
6 6
.
−218.62) (m, 1F); IR (KBr, neat): 2979, 2934, 2867, 1729,
644, 1450, 1376, 1176, 1102, 1065, 832, 788 cm . HRMS
APCI) cald for C H FO (M + H) requires 307.1709; found
+
1
9
26
3
−1
+
+
18 23 3
(M + H) , 50%), 285.2 (27), 211.1 (34), 173.1 (19), 157.1 (27),
+
07.1715. APCI-MS: m/z (relative intensity): 307.2 ((M + H) ,
2%), 289.2 (12), 215.1 (12), 184.1 (14), 157.1 (53), 124.1
1
24.1 (100), 82.0 (44).
4
(100).
(
2R*,3S*,5S*,6R*)-Ethyl 6-(4-bromophenyl)-tetrahydro-2-
(2R*,3S*,5S*,6R*)-Ethyl tetrahydro-2-methyl-6-(4-nitrophenyl)-
5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (3f)
methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (3c)
1
1
Colourless oil (132 mg, 36%); H NMR (400 MHz, CDCl ): δ
Colourless oil (117 mg, 35%); H NMR (400 MHz, CDCl ): δ
3
3
1
.24 (d, J = 6.0 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.45 (s, 3
1.27 (d, J = 6.0 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.47 (s, 3
H), 1.99 (ddd, J = 13.2, 12.5 and 12.4 Hz, 1 H), 2.12 (ddd, J =
13.2, 3.6 and 3.6 Hz, 1 H), 2.24 (ddd, J = 12.8, 12.5 and 3.6 Hz,
1 H), 2.47 (ddd, J = 12.4, 10.0 and 3.6 Hz, 1 H), 3.78–3.87 (m,
1 H), 4.18 (q, J = 7.2 Hz, 2 H), 4.41 (d, J = 10.0 Hz, 1 H), 4.61
H), 1.98 (ddd, J = 12.8, 12.4 and 12.4 Hz, 1 H), 2.09 (ddd, J =
1
1
1
2.8, 4.0 and 3.6 Hz, 1 H), 2.25 (ddd, J = 12.8, 11.6 and 3.6 Hz,
H), 2.44 (ddd, J = 12.4, 10.0 and 4.0 Hz, 1 H), 3.75–3.83 (m,
H), 4.17 (q, J = 7.2 Hz, 2 H), 4.26 (d, J = 10.0 Hz, 1 H), 4.62
(
brs, 1 H), 4.68 (brs, 1 H), 7.17 (d, J = 8.4 Hz, 2 H), 7.42 (d, J =
(brs, 1 H), 4.70 (brs, 1 H), 7.46 (d, J = 8.8 Hz, 2 H), 8.16 (d, J =
13
13
8
3
1
1
.4 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.4, 20.3, 21.6,
8.8 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.4, 20.2, 21.6,
3
3
3.9, 49.7 (2C), 60.7, 75.2, 83.3, 113.4, 121.8, 129.2, 131.4,
39.9, 144.8, 173.9; IR (KBr, neat): 2977, 2931, 2866, 1729,
33.7, 49.5, 50.2, 60.9, 75.3, 82.8, 114.0, 123.5, 128.3, 144.1,
147.7, 148.2, 173.6; IR (KBr, neat): 2975, 2935, 2871, 1726,
−1
−1
644, 1375, 1175, 1102, 1069, 894, 810 cm . HRMS (APCI)
1643, 1519, 1372, 1344, 1170, 1101, 1060, 849 cm . HRMS
+
+
cald for C H BrO (M + H) requires 367.0909; found
3
(APCI) cald for C H NO (M + H) requires 334.1654; found
1
8
23
3
18 23
5
7
9
+
67.0905 ( Br). APCI-MS: m/z (relative intensity): 369.1 ((M +
334.1652. APCI-MS: m/z (relative intensity): 334.2 ((M + H) ,
1%), 263.2 (3), 245.2 (12), 201.2 (13), 177.1 (25), 125.1 (10),
124.1 (100), 99.0 (27).
+
81
+
79
H) , 4%, Br), 367.1 ((M + H) , 6, Br), 303.2 (5), 211.2 (3),
01.1 (26), 157.1 (19), 124.1 (100).
2
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2470–2481 | 2473

View Online
(
2R*,3S*,5S*,6R*)-Ethyl 6-(4-(methoxycarbonyl)phenyl)-
tetrahydro-2-methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate
3g)
(2R*,3S*,5S*,6S*)-Ethyl tetrahydro-6-isobutyl-2-methyl-5-
(prop-1-en-2-yl)-2H-pyran-3-carboxylate (3j)
(
1
Colourless oil (110 mg, 41%); H NMR (400 MHz, CDCl ): δ
3
1
Colourless oil (125 mg, 36%); H NMR (400 MHz, CDCl ): δ
1
H), 1.99 (ddd, J = 12.8, 12.8 and 12.4 Hz, 1 H), 2.10 (ddd, J =
1
1
1
0.85 (d, J = 6.8 Hz, 3 H), 0.89 (d, J = 6.8 Hz, 3 H), 1.19 (d, J =
6.0 Hz, 3 H), 1.24–1.30 (m, 2 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.66
(s, 3 H), 1.76–1.99 (m, 4 H), 2.28 (ddd, J = 10.0, 10.0 and 4.0
Hz, 1 H), 3.37 (dt, J = 10.0 and 7.6 Hz, 1 H), 3.54–3.62 (m, 1
H), 4.12 (q, J = 7.2 Hz, 2 H), 4.75 (brs, 1 H), 4.77 (brs, 1 H);
3
.27 (d, J = 6.0 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3
2.8, 4.0 and 3.6 Hz, 1 H), 2.28 (ddd, J = 12.8, 12.0 and 4.0 Hz,
H), 2.47 (ddd, J = 12.4, 10.0 and 3.6 Hz, 1 H), 3.78–3.86 (m,
H), 3.90 (s, 3 H), 4.17 (q, J = 7.2 Hz, 2 H), 4.35 (d, J = 10.0
13
C NMR (100 MHz, CDCl ): δ 14.4, 20.1, 20.2, 21.6, 24.0,
3
Hz, 1 H), 4.60 (brs, 1 H), 4.66 (brs, 1 H), 7.36 (d, J = 8.4 Hz, 2
24.2, 33.9, 42.4, 49.3, 49.8, 60.5, 74.6, 77.9, 112.8, 146.1,
174.1; IR (KBr, neat): 2955, 2928, 2870, 1732, 1644, 1451,
1
3
H), 7.97 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz, CDCl ): δ
3
−1
1
1
2
8
4.3, 20.1, 21.5, 33.7, 49.5, 49.8, 52.1, 60.6, 75.0, 83.4, 113.3,
27.4, 129.5, 130.2, 144.4, 145.8, 167.0, 173.6; IR (KBr, neat):
979, 2936, 2867, 1725, 1645, 1437, 1376, 1279, 1102, 1066,
1374, 1176, 1115, 1068, 1035, 892 cm . HRMS (APCI) cald
+
for C H O (M + H) requires 269.2116; found 269.2122.
1
6 28 3
+
APCI-MS: m/z (relative intensity): 269.2 ((M + H) , 100%),
−1
96, 772, 706 cm . HRMS (APCI) cald for C H O (M +
213.2 (11), 180.1 (11), 157.1 (17), 124.1 (30).
2
0 26 5
+
H) requires 347.1858; found 347.1865. APCI-MS: m/z (relative
intensity): 347.2 ((M + H) , 8%), 315.2 (3), 202.2 (10), 201.1
+
(75), 181.1 (11), 157.1 (5), 124.1 (100), 123.1 (54), 82.0 (47).
(
2R*,3S*,5S*,6R*)-Ethyl 2-ethyl-tetrahydro-6-phenyl-5-(prop-1-
en-2-yl)-2H-pyran-3-carboxylate (3k)
1
Colourless oil (118 mg, 39%); H NMR (400 MHz, CDCl ): δ
3
(
2R*,3S*,5S*,6S*)-Ethyl tetrahydro-2-methyl-5-(prop-1-en-2-
0
1
.96 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3 H),
.46–1.57 (m, 1 H), 1.58–1.68 (m, 1 H), 2.01 (ddd, J = 12.8,
yl)-6-propyl-2H-pyran-3-carboxylate (3h)
1
Colourless oil (115 mg, 45%); H NMR (400 MHz, CDCl ): δ
0
7
12.4 and 12.0 Hz, 1 H), 2.08 (ddd, J = 12.8, 4.4 and 4.0 Hz, 1
H), 2.28 (ddd, J = 12.4, 10.0 and 4.0 Hz, 1 H), 2.56 (ddd, J =
12.0, 10.0 and 4.4 Hz, 1 H), 3.64 (ddd, J = 10.0, 7.2, 3.2 Hz, 1
H), 4.16 (q, J = 7.2 Hz, 2 H), 4.28 (d, J = 10.0 Hz, 1 H), 4.62
(brs, 1 H), 4.66 (brs, 1 H), 7.24–7.30 (m, 5 H); C NMR
(100 MHz, CDCl ): δ 9.7, 14.4, 21.6, 27.2, 34.2, 47.5, 49.8,
60.6, 79.7, 83.9, 113.0, 127.5, 127.8, 128.2, 141.1, 145.3, 174.2;
IR (KBr, neat): 2963, 2929, 2855, 1724, 1644, 1447, 1379,
1177, 1102, 1061, 1027, 747, 697 cm . HRMS (APCI) cald for
3
.88 (t, J = 7.2 Hz, 3 H), 1.19 (d, J = 6.4 Hz, 3 H), 1.26 (t, J =
.2 Hz, 3 H), 1.27–1.35 (m, 2 H), 1.42–1.56 (m, 2 H), 1.67 (s, 3
H), 1.80 (ddd, J = 12.8, 12.4 and 12.0 Hz, 1 H), 1.91 (ddd, J =
13
1
1
9
2.8, 4.0 and 3.6 Hz, 1 H), 1.99 (ddd, J = 12.4, 10.0 and 3.6 Hz,
H), 2.27 (ddd, J = 12.0, 10.0 and 4.0 Hz, 1 H), 3.31 (dt, J =
.2 and 7.2 Hz, 1 H), 3.54–3.63 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2
3
1
3
H), 4.76 (brs, 1 H), 4.77 (brs, 1 H); C NMR (100 MHz,
CDCl ): δ 14.1, 14.3, 18.8, 20.2(2C), 33.8, 35.5, 48.8, 49.8,
−1
3
+
6
2
7
2
2
0.5, 74.5, 79.5, 112.7, 146.1, 174.1; IR (KBr, neat): 2960,
C H O (M + H) requires 303.1960; found 303.1962.
19 26 3
+
937, 2872, 1732, 1644, 1452, 1376, 1150, 1113, 1037, 893,
APCI-MS: m/z (relative intensity): 303.2 ((M + H) , 15%),
257.2 (9), 211.2 (14), 171.1 (16), 125.1 (9), 124.1 (100), 97.1
(5), 79.0 (11).
−
1
+
50 cm . HRMS (APCI) cald for C H O (M + H) requires
1
5 26 3
55.1960; found 255.1964. APCI-MS: m/z (relative intensity):
+
55.2 ((M + H) , 17%), 254.7 (100), 179.7 (7), 156.8 (4), 123.8
(41).
(
2R*,3S*,5S*,6R*)-Ethyl 2-ethyl-tetrahydro-5-(prop-1-en-2-yl)-
6
-p-tolyl-2H-pyran-3-carboxylate (3l)
(
2R*,3S*,5S*,6S*)-Ethyl 6-hexyl-tetrahydro-2-methyl-5-(prop-1-
1
Colourless oil (108 mg, 34%); H NMR (400 MHz, CDCl ): δ
0
3
en-2-yl)-2H-pyran-3-carboxylate (3i)
.94 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.45 (s, 3 H),
1
Colourless oil (127 mg, 43%); H NMR (400 MHz, CDCl ): δ
0
(
3
1
1
8
H), 4.75 (brs, 1 H), 4.77 (brs, 1 H); C NMR (100 MHz,
CDCl ): δ 14.3, 14.4, 20.2(2C), 22.9, 25.7, 29.5, 32.1, 33.5,
3
1.47–1.55 (m, 1 H), 1.56–1.65 (m, 1 H), 2.00 (ddd, J = 12.8,
12.0 and 12.0 Hz, 1 H), 2.07 (ddd, J = 12.8, 4.0 and 4.0 Hz, 1
H), 2.31 (s, 3 H), 2.32 (ddd, J = 12.0, 10.4 and 4.0 Hz, 1 H),
2.54 (ddd, J = 12.0, 10.0 and 4.0 Hz, 1 H), 3.62 (ddd, J = 10.4,
7.2 and 3.2 Hz, 1 H), 4.15 (q, J = 7.2 Hz, 2 H), 4.25 (d, J = 10.0
Hz, 1 H), 4.63 (brs, 1 H), 4.66 (brs, 1 H), 7.09 (d, J = 7.6 Hz, 2
3
.87 (t, J = 6.8 Hz, 3 H), 1.20 (d, J = 6.0 Hz, 3 H), 1.24–1.34
m, 8 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.47–1.52 (m, 2 H), 1.67 (s,
H), 1.80 (ddd, J = 12.8, 12.4 and 12.0 Hz, 1 H), 1.91 (ddd, J =
2.8, 4.0 and 3.6 Hz, 1 H), 1.97 (ddd, J = 12.4, 10.4 and 3.6 Hz,
H), 2.28 (ddd, J = 12.0, 10.4 and 4.0 Hz, 1 H), 3.29 (dt, J =
.8 and 8.4 Hz, 1 H), 3.55–3.64 (m, 1 H), 4.13 (q, J = 7.2 Hz, 2
13
H), 7.18 (d, J = 8.0 Hz, 2 H); C NMR (100 MHz, CDCl ): δ
3
1
3
9.7, 14.4, 21.4, 21.5, 27.1, 34.3, 47.5, 49.5, 60.6, 79.7, 83.6,
112.8, 127.4, 128.9, 137.4, 138.1, 145.5, 174.2; IR (KBr, neat):
2965, 2935, 2862, 1730, 1645, 1451, 1375, 1173, 1108, 1067,
967, 891, 815, 768 cm . HRMS (APCI) cald for C H O
0 28 3
(M + H) requires 317.2116; found 317.2128. APCI-MS: m/z
(relative intensity): 317.2 ((M + H) , 29%), 299.2 (18), 271.2
(16), 253.2 (11), 225.2 (18), 171.1 (16), 151.1 (5), 124.1 (100),
123.1 (22), 82.0 (40).
3
3.9, 48.8, 49.8, 60.6, 74.6, 79.9, 112.8, 146.1, 174.2; IR (KBr,
−1
neat): 2929, 2858, 1732, 1643, 1455, 1376, 1174, 1115, 1035,
2
−
1
+
+
8
2
2
92 cm . HRMS (APCI) cald for C H O (M + H) requires
1
8 32 3
+
97.2429; found 297.2424. APCI-MS: m/z (relative intensity):
+
97.2 ((M + H) , 45%), 211.2 (11), 180.1 (4), 150.1 (10), 124.1
(
100), 123.1 (59), 82.0 (43).
2474 | Org. Biomol. Chem., 2012, 10, 2470–2481
This journal is © The Royal Society of Chemistry 2012

View Online
(
2R*,3S*,5S*,6R*)-Ethyl 6-(4-(methoxycarbonyl)phenyl)-2-
ethyl-tetrahydro-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate
3m)
(2R*,3S*,5S*,6S*)-Ethyl 2-ethyl-tetrahydro-6-isobutyl-5-(prop-
1-en-2-yl)-2H-pyran-3-carboxylate (3p)
(
1
Colourless oil (124 mg, 44%); H NMR (400 MHz, CDCl ): δ
3
1
Colourless oil (133 mg, 37%); H NMR (400 MHz, CDCl ): δ
0.86 (d, J = 6.8 Hz, 3 H), 0.90 (d, J = 6.8 Hz, 3 H), 0.97 (t, J =
7.6 Hz, 3 H), 1.17–1.58 (m, 4 H), 1.25 (t, J = 7.2 Hz, 3 H), 1.66
(s, 3 H), 1.78–2.00 (m, 4 H), 2.33 (ddd, J = 12.0, 10.0 and 4.0
Hz, 1 H), 3.32–3.38 (m, 2 H), 4.12 (q, J = 7.2 Hz, 2 H), 4.75
3
0
1
1
.96 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3 H),
.48–1.58 (m, 1 H), 1.60–1.69 (m, 1 H), 2.02 (ddd, J = 13.2,
2.8 and 12.0 Hz, 1 H), 2.09 (ddd, J = 13.2, 4.0 and 4.0 Hz, 1
13
H), 2.24 (ddd, J = 12.8, 10.4 and 4.0 Hz, 1 H), 2.57 (ddd, J =
(brs, 1 H), 4.76 (brs, 1 H); C NMR (100 MHz, CDCl ): δ
3
1
1
2.0, 10.0 and 4.0 Hz, 1 H), 3.65 (ddd, J = 10.4, 7.2 and 2.8 Hz,
H), 3.90 (s, 3 H), 4.16 (q, J = 7.2 Hz, 2 H), 4.33 (d, J = 10.0
10.4, 14.4, 20.1, 21.4, 24.1, 24.3, 27.4, 34.1, 42.5, 48.4, 49.4,
60.5, 77.8, 79.8, 112.8, 146.1, 174.3; IR (KBr, neat): 2956,
2928, 2870, 1732, 1644, 1462, 1374, 1175, 1153, 1117, 1070,
Hz, 1 H), 4.60 (brs, 1 H), 4.67 (brs, 1 H), 7.36 (d, J = 8.4 Hz, 2
H), 7.97(d, J = 8.8 Hz, 2 H); C NMR (100 MHz, CDCl ): δ
1
3
−1
1016, 892, 856 cm . HRMS (APCI) cald for C H O (M +
3
17 30 3
+
9
1
.6, 14.4, 21.7, 27.1, 34.0, 47.4, 50.0, 52.2, 60.7, 76.7, 83.3,
13.4, 127.4, 129.5(2C), 144.7, 146.2, 167.2, 174.0; IR (KBr,
neat): 2935, 2857, 1726, 1645, 1437, 1375, 1278, 1176, 1108,
H) requires 283.2273; found 283.2275. APCI-MS: m/z (relative
intensity): 282.6 (M , 33%), 177.7 (4), 124.8 (8), 123.8 (100),
+
122.8 (36), 81.9 (10).
−1
1
069, 895, 760 cm . HRMS (APCI) cald for C H O (M +
21 28 5
+
H) requires 361.2015; found 361.2023. APCI-MS: m/z (relative
intensity): 361.2 ((M + H) , 1%), 178.1 (4), 125.1 (11), 124.1
+
(
2R*,3R*,5S*,6R*)-Ethyl tetrahydro-2-methyl-6-phenyl-5-(prop-
1
-en-2-yl)-2H-pyran-3-carboxylate (4a)
(100), 123.1 (20), 85.0 (4), 82.0 (34).
1
Colourless oil (110 mg, 38%); H NMR (400 MHz, CDCl ): δ
3
(
6
2R*,3S*,5S*,6S*)-Ethyl 2-ethyl-tetrahydro-5-(prop-1-en-2-yl)-
-propyl-2H-pyran-3-carboxylate (3n)
1.32 (d, J = 6.4 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 1.42 (s, 3
H), 1.90 (ddd, J = 13.6, 12.8 and 5.2 Hz, 1 H), 2.14 (ddd, J =
1
1
3
7
3.6, 4.0 and 4.0 Hz, 1 H), 2.60–2.67 (m, 1 H), 3.01 (ddd, J =
2.8, 12.4 and 4.0 Hz, 1 H), 3.82–3.89 (m, 1 H), 4.14–4.28 (m,
H), 4.63 (brs, 1 H), 4.67 (brs, 1 H), 7.22–7.25 (m, 1 H),
1
Colourless oil (113 mg, 42%); H NMR (400 MHz, CDCl ): δ
3
0
7
1
.89 (t, J = 6.8 Hz, 3 H), 0.98 (t, J = 7.2 Hz, 3 H), 1.25 (t, J =
.2 Hz, 3 H), 1.28–1.58 (m, 6 H), 1.67 (s, 3 H), 1.82 (ddd, J =
2.8, 12.4 and 12.0 Hz, 1 H), 1.92 (ddd, J = 12.8, 4.0 and 3.6
Hz, 1 H), 1.98 (ddd, J = 12.4, 10.0 and 3.6 Hz, 1 H), 2.34 (ddd,
J = 12.0, 10.0 and 4.0 Hz, 1 H), 3.28 (dt, J = 10.0 and 7.2 Hz, 1
H), 3.36 (dt, J = 10.0 and 6.8 Hz, 1 H), 4.12 (q, J = 7.2 Hz, 2
H), 4.75 (brs, 1 H), 4.77 (brs, 1 H); C NMR (100 MHz,
CDCl ): δ 10.2, 14.1, 14.4, 19.0, 20.2, 27.5, 34.0, 35.6, 48.3,
9.1, 60.5, 79.4, 79.6, 112.7, 146.1, 174.3; IR (KBr, neat): 2960,
937, 2873, 1732, 1644, 1454, 1375, 1175, 1116, 1038, 1011,
93, 859 cm . HRMS (APCI) cald for C H O (M + H)
13
.26–7.31 (m, 2 H), 7.32–7.36 (m, 2 H); C NMR (100 MHz,
CDCl ): δ 14.6, 20.0, 21.8, 32.7, 44.4, 45.2, 60.3, 74.3, 85.0,
3
112.6, 127.7, 127.8, 128.2, 141.3, 145.8, 173.0; IR (KBr, neat):
2
7
2
2
1
979, 2934, 1732, 1644, 1449, 1383, 1174, 1160, 1073, 758,
00 cm . HRMS (APCI) cald for C H O (M + H) requires
89.1803; found 289.1799. APCI-MS: m/z (relative intensity):
89.2 ((M + H) , 77%), 225.1 (36), 197.1 (64), 159.1 (26),
−1
+
18 24 3
1
3
+
3
4
2
8
57.1 (42), 124.1 (100), 123.1 (31), 99.0 (9), 82.0 (58).
−1
+
1
6 28 3
requires 269.2116; found 269.2108. APCI-MS: m/z (relative
intensity): 269.2 ((M + H) , 61%), 223.2 (16), 195.2 (9), 178.1
(2R*,3R*,5S*,6R*)-Ethyl tetrahydro-2-methyl-5-(prop-1-en-2-
yl)-6-p-tolyl-2H-pyran-3-carboxylate (4b)
+
(5), 125.1 (8), 124.1 (100), 123.1 (18), 101.1 (1), 82.0 (35).
1
Colourless oil (103 mg, 34%); H NMR (400 MHz, CDCl ): δ
3
1
.32 (d, J = 6.8 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 1.44 (s, 3
H), 1.90 (ddd, J = 13.6, 13.2 and 4.8 Hz, 1 H), 2.14 (ddd, J =
3.6, 4.0 and 4.0 Hz, 1 H), 2.30 (s, 3 H), 2.59–2.66 (m, 1 H),
3.02 (ddd, J = 13.2, 10.4 and 4.0 Hz, 1 H), 3.80–3.89 (m, 1 H),
(
2R*,3S*,5S*,6S*)-Ethyl 2-ethyl-6-hexyl-tetrahydro-5-(prop-1-
en-2-yl)-2H-pyran-3-carboxylate (3o)
1
1
Colourless oil (127 mg, 41%); H NMR (400 MHz, CDCl ): δ
3
4
7
.15–4.28 (m, 3 H), 4.64 (brs, 1 H), 4.67 (brs, 1 H), 7.09 (d, J =
0
7
1
1
.87 (t, J = 6.4 Hz, 3 H), 0.98 (t, J = 7.2 Hz, 3 H), 1.25 (t, J =
.2 Hz, 3 H), 1.25–1.35 (m, 9 H), 1.37–1.46 (m, 1 H),
.47–1.57 (m, 2 H), 1.66 (s, 3 H), 1.82 (ddd, J = 12.4, 12.4 and
2.4 Hz, 1 H), 1.92 (ddd, J = 12.4, 4.0 and 3.6 Hz, 1 H), 1.98
13
.6 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H); C NMR (100 MHz,
CDCl ): δ 14.6, 20.1, 21.4, 21.7, 32.8, 44.5, 45.0, 60.3, 74.3,
3
8
4.8, 112.5, 127.6, 129.0, 137.4, 138.4, 146.1, 173.1; IR (KBr,
neat): 2978, 2927, 2855, 1733, 1644, 1380, 1174, 1157, 1075,
(
ddd, J = 12.4, 10.0 and 3.6 Hz, 1 H), 2.33 (ddd, J = 12.4, 10.0
and 4.0 Hz, 1 H), 3.27 (dt, J = 10.0 and 8.8 Hz, 1 H), 3.35 (dt, J
10.0 and 6.8 Hz, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 4.75 (brs, 1
−
1
+
8
10 cm . HRMS (APCI) cald for C H O (M + H) requires
19 26 3
3
03.1960; found 303.1958. APCI-MS: m/z (relative intensity):
=
+
13
303.2 ((M + H) , 52%), 285.2 (51), 239.1 (20), 211.1 (31),
84.1 (36), 173.1 (28), 150.1 (15), 124.1 (100).
H), 4.77 (brs, 1 H); C NMR (100 MHz, CDCl ): δ 10.2, 14.3,
3
1
1
6
2
4.4, 20.2, 22.8, 25.7, 27.4, 29.3, 32.1, 33.5, 34.0, 48.3, 49.1,
0.5, 79.6, 79.7, 112.7, 146.1, 174.3; IR (KBr, neat): 2930,
−
1
857, 1732, 1640, 1454, 1375, 1173, 1117, 1038, 892 cm
.
(
2R*,3R*,5S*,6R*)-Ethyl 6-(4-bromophenyl)-tetrahydro-2-
+
HRMS (APCI) cald for C H O (M + H) requires 311.2586;
found 311.2587. APCI-MS: m/z (relative intensity): 310.6 (M ,
1
1
1
9 34 3
methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (4c)
+
1
00), 255.6 (4), 254.6 (23), 212.7 (4), 179.7 (11), 176.7 (15),
70.7 (8), 123.8 (81).
Colourless oil (110 mg, 30%); H NMR (400 MHz, CDCl ): δ
1.31 (d, J = 5.6 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 1.44 (s, 3
3
This journal is © The Royal Society of Chemistry 2012
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H), 1.90 (ddd, J = 13.6, 12.8 and 5.2 Hz, 1 H), 2.13 (ddd, J =
(s, 3 H), 1.89 (ddd, J = 14.0, 12.8 and 5.2 Hz, 1 H), 2.16 (ddd, J
= 14.0, 4.0 and 2.0 Hz, 1 H), 2.63–2.70 (m, 1 H), 2.95 (ddd, J =
12.8, 12.4 and 4.0 Hz, 1 H), 3.84–3.92 (m, 1 H), 4.17–4.28 (m,
2 H), 4.37 (d, J = 10.4 Hz, 1 H), 4.62 (brs, 1 H), 4.72 (brs, 1 H),
1
1
3
7
2
1
2
8
3.6, 4.0 and 3.6 Hz, 1 H), 2.60–2.67 (m, 1 H), 2.95 (ddd, J =
2.8, 12.8 and 4.0 Hz, 1 H), 3.81–3.88 (m, 1 H), 4.12–4.28 (m,
H), 4.62 (brs, 1 H), 4.68 (brs, 1 H), 7.22 (d, J = 8.4 Hz, 2 H),
1
3
13
.41 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.6,
7.51 (d, J = 8.8 Hz, 2 H), 8.16 (d, J = 8.8 Hz, 2 H); C NMR
3
0.0, 21.8, 32.6, 44.2, 45.2, 60.3, 74.3, 84.1, 113.0, 121.7,
29.4, 131.4, 140.5, 145.4, 172.9; IR (KBr, neat): 2979, 2934,
855, 1732, 1644, 1446, 1383, 1174, 1157, 1074, 921,
(100 MHz, CDCl ): δ 14.6, 19.9, 21.7, 32.4, 44.0, 45.6, 60.5,
3
74.3, 83.6, 113.6, 123.5, 128.5, 144.7, 147.6, 148.8, 172.8; IR
(KBr, neat): 2979, 2935, 2858, 1728, 1643, 1520, 1447, 1345,
−
1
+
−1
13 cm . HRMS (APCI) cald for C H BrO (M + H)
1174, 1077, 851, 752 cm . HRMS (APCI) cald for C H NO
5
1
8
23
3
18 23
7
9
+
requires 367.0909; found 367.0911 ( Br). APCI-MS: m/z (rela-
tive intensity): 369.1 ((M + H) , 19%, Br), 367.1 ((M + H) ,
(M + H) requires 334.1654; found 334.1666. APCI-MS: m/z
(relative intensity): 334.2 ((M + H) , 1%), 250.0 (2), 180.1 (2),
+
81
+
+
7
9
2
0, Br), 351.1 (9), 349.1 (9), 275.1 (6), 202.2 (13), 201.2
136.1 (4), 125.1 (10), 124.1 (100), 123.1 (20), 82.0 (36).
(100), 184.1 (9), 124.1 (75).
(
2R*,3R*,5S*,6R*)-Ethyl 6-(4-(methoxycarbonyl)phenyl)-
(2R*,3R*,5S*,6R*)-Ethyl 6-(4-chlorophenyl)-tetrahydro-2-
tetrahydro-2-methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate
methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (4d)
(4g)
1
1
Colourless oil (94 mg, 29%); H NMR (400 MHz, CDCl ): δ
Colourless solid; M.P.: 100–102 °C (111 mg, 32%); H NMR
3
1
.32 (d, J = 6.0 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3
(400 MHz, CDCl ): δ 1.33 (t, J = 7.2 Hz, 3 H), 1.34 (d, J = 6.8
3
H), 1.89 (ddd, J = 13.2, 12.8 and 4.8 Hz, 1 H), 2.14 (ddd, J =
Hz, 3 H), 1.41 (s, 3 H), 1.92 (ddd, J = 14.0, 12.8 and 5.2 Hz, 1
H), 2.15 (ddd, J = 14.0, 4.0 and 2.0 Hz, 1 H), 2.63–2.70 (m, 1
H), 2.97 (ddd, J = 12.8, 10.0 and 4.0 Hz, 1 H), 3.81–3.88 (m, 1
H), 3.89 (s, 3 H), 4.16–4.28 (m, 2 H), 4.30 (d, J = 10.0 Hz, 1
H), 4.62 (brs, 1 H), 4.68 (brs, 1 H), 7.42 (d, J = 8.4 Hz, 2 H),
1
1
3
7
2
1
2
8
3.2, 4.0 and 3.6 Hz, 1 H), 2.60–2.68 (m, 1 H), 2.95 (ddd, J =
2.8, 12.8 and 3.6 Hz, 1 H), 3.80–3.89 (m, 1 H), 4.16–4.29 (m,
H), 4.62 (brs, 1 H), 4.69 (brs, 1 H), 7.26 (d, J = 8.8 Hz, 2 H),
1
3
.41 (d, J = 8.8 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.6,
3
13
0.0, 21.8, 32.6, 44.2, 45.3, 60.3, 74.3, 84.1, 113.0, 128.4,
29.0, 133.4, 140.0, 145.5, 172.9; IR (KBr, neat): 2978, 2933,
857, 1731, 1644, 1447, 1382, 1174, 1157, 1076, 894,
7.97 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.6,
3
19.9, 21.8, 32.5, 44.2, 45.4, 52.2, 60.4, 74.3, 84.4, 113.1, 127.6,
129.6 (2C), 145.2, 146.5, 167.2, 172.9; IR (KBr, neat): 2955,
2928, 2873, 1726, 1643, 1449, 1277, 1173, 1158, 1076, 772,
−
1
+
15 cm . HRMS (APCI) cald for C H ClO (M + H)
1
8
23
3
3
5
−1
+
requires 323.1414; found 323.1405 ( Cl). APCI-MS: m/z (rela-
705 cm . HRMS (APCI) cald for C H O (M + H) requires
20 26 5
+
37
+
tive intensity): 325.0 ((M + H) , 3%, Cl), 323.0 ((M + H) , 7,
347.1858; found 347.1868. APCI-MS: m/z (relative intensity):
3
5
+
Cl), 259.0 (4), 231 (9), 184.0 (7), 157 (13), 124.0 (100), 123.0
17), 85.0 (5), 82.0 (29).
347.2 ((M + H) , 5%), 315.2 (2), 297.2 (3), 184.1 (3), 157.1 (5),
(
150.1 (10), 124.1 (100), 123.1 (70), 85.0 (6).
(
2R*,3R*,5S*,6R*)-Ethyl 6-(4-fluorophenyl)-tetrahydro-2-
(2R*,3R*,5S*,6S*)-Ethyl tetrahydro-2-methyl-5-(prop-1-en-2-
yl)-6-propyl-2H-pyran-3-carboxylate (4h)
methyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (4e)
1
1
Colourless oil (107 mg, 35%); H NMR (400 MHz, CDCl ): δ
Colourless oil (104 mg, 41%); H NMR (400 MHz, CDCl ): δ
3
3
1
.32 (d, J = 6.4 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3
0.97 (t, J = 7.6 Hz, 3 H), 1.27 (t, J = 7.2 Hz, 3 H), 1.28 (d, J =
6.0 Hz, 3 H), 1.30–1.42 (m, 2 H), 1.43–1.58 (m, 2 H), 1.67 (s, 3
H), 1.72 (ddd, J = 13.6, 12.8 and 5.2 Hz, 1 H), 1.98 (ddd, J =
13.6, 4.0 and 2.4 Hz, 1 H), 2.49–2.55 (m, 1 H), 2.63 (ddd, J =
H), 1.89 (ddd, J = 13.6, 12.8 and 4.6 Hz, 1 H), 2.14 (ddd, J =
1
1
3
7
2
3.6, 4.0 and 3.6 Hz, 1 H), 2.60–2.67 (m, 1 H), 2.97 (ddd, J =
2.8, 10.4 and 4.0 Hz, 1 H), 3.82–3.89 (m, 1 H), 4.18–4.28 (m,
H), 4.63 (brs, 1 H), 4.69 (brs, 1 H), 6.98 (t, J = 8.8 Hz, 2 H),
12.8, 10.0 and 4.0 Hz, 1 H), 3.26 (dt, J = 10.0 and 6.0 Hz, 1 H),
13
13
.30–7.34 (m, 2 H); C NMR (100 MHz, CDCl ): δ 14.6, 20.0,
3.62–3.70 (m, 1 H), 4.11–4.21 (m, 2 H), 4.77 (brs, 2 H);
C
3
1.8, 32.6, 44.3, 45.4, 60.3, 74.3, 84.1, 112.8, 115.1 (d, J = 20.6
NMR (100 MHz, CDCl ): δ 14.1, 14.4, 18.8, 19.8, 20.2, 32.6,
3
Hz), 129.3 (d, J = 9.7 Hz), 137.3, 145.7, 162.5 (d, J = 244.1
35.6, 44.2, 44.3, 60.1, 73.9, 80.7, 112.4, 146.7, 173.0; IR (KBr,
neat): 2960, 2936, 2872, 1735, 1648, 1382, 1173, 1115, 1084,
992, 892 cm . HRMS (APCI) cald for C H O (M + H)
15 26 3
19
Hz), 173.0; F NMR (376 MHz, CDCl –C F ): δ −219.09–
3
6 6
−1
+
(
1
−219.01) (m, 1F); IR (KBr, neat): 2979, 2934, 2858, 1732,
−1
644, 1448, 1382, 1176, 1157, 1075, 832 cm . HRMS (APCI)
requires 255.1960; found 255.1965. APCI-MS: m/z (relative
+
+
cald for C H FO (M + H) requires 307.1709; found
intensity): 255.2 ((M + H) , 16%), 254.6 (97), 198.7 (4), 179.7
18
23
3
+
3
2
1
07.1702. APCI-MS: m/z (relative intensity): 307.0 ((M + H) ,
8%), 289.0 (35), 243.0 (18), 215.0 (40), 177.0 (26), 157.0 (30),
24.0 (100), 123.0 (16), 82.0 (26).
(13), 176.7 (19), 156.7 (100).
(
(
2R*, 3R*, 5S*, 6S*)-Ethyl 6-hexyl-tetrahydro-2-methyl-5-
prop-1-en-2-yl)-2H-pyran-3-carboxylate (4i)
(
5
2R*,3R*,5S*,6R*)-Ethyl tetrahydro-2-methyl-6-(4-nitrophenyl)-
-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (4f)
1
Colourless oil (116 mg, 39%); H NMR (400 MHz, CDCl ): δ
0
3
.87 (t, J = 7.2 Hz, 3 H), 1.20–1.40 (m, 8 H), 1.27 (t, J = 7.2
Hz, 3 H), 1.28 (d, J = 6.0 Hz, 3 H), 1.45–1.53 (m, 2 H), 1.67
(s, 3 H), 1.72 (ddd, J = 12.8, 12.8 and 5.2 Hz, 1 H), 1.97 (ddd,
1
Colourless oil (90 mg, 27%); H NMR (400 MHz, CDCl ): δ
1
3
.33 (d, J = 5.6 Hz, 3 H), 1.34 (t, J = 7.2 Hz, 3 H), 1.46
2476 | Org. Biomol. Chem., 2012, 10, 2470–2481
This journal is © The Royal Society of Chemistry 2012

View Online
J = 12.8, 4.0 and 2.0 Hz, 1 H), 2.50–2.56 (m, 1 H), 2.63 (ddd, J
3.54 (dt, J = 7.2 and 4.4 Hz, 1 H), 4.14–4.26 (m, 3 H), 4.64
=
12.8, 10.0 and 4.0 Hz, 1 H), 3.25 (dt, J = 10.0 and 8.4 Hz, 1
(brs, 1 H), 4.67 (brs, 1 H), 7.09 (d, J = 7.6 Hz, 2 H), 7.22 (d, J =
13
13
H), 3.62–3.69 (m, 1 H), 4.11–4.21 (m, 2 H), 4.77 (brs, 2 H);
C
8.0 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 10.8, 14.6, 21.4,
3
NMR (100 MHz, CDCl ): δ 14.3. 14.5, 19.9, 20.4, 22.9, 25.8,
21.7, 27.1, 32.9, 42.6, 45.3, 60.2, 80.4, 84.8, 112.5, 127.6,
128.9, 137.3, 138.5, 146.2, 173.1; IR (KBr, neat): 2961, 2935,
2956, 1733, 1644, 1449, 1376, 1174, 1160, 1074, 890,
3
2
1
9.5, 32.1, 32.6, 33.6, 44.3, 44.4, 60.2, 74.0, 81.1, 112.5, 146.8,
73.1; IR (KBr, neat): 2927, 2856, 1735, 1640, 1445, 1380,
−1
−1
+
1173, 1113, 1083, 892 cm . HRMS (APCI) cald for C H O
813 cm . HRMS (APCI) cald for C H O (M + H) requires
20 28 3
18
32
3
+
(
(
M + H) requires 297.2429; found 297.2424. APCI-MS: m/z
317.2116; found 317.2122. APCI-MS: m/z (relative intensity):
+
+
relative intensity): 297.2 ((M + H) , 81%), 279.2 (4), 158.1 (7),
317.2 ((M + H) , 22%), 299.2 (25), 269.2 (8), 253.2 (14), 225.2
1
57.1 (81), 124.1 (100), 123.1 (58), 101.1 (7).
(21), 198.2 (18), 171.2 (25), 125.1 (11), 124.1 (100).
(
(
2R*,3R*,5S*,6S*)-Ethyl tetrahydro-6-isobutyl-2-methyl-5-
prop-1-en-2-yl)-2H-pyran-3-carboxylate (4j)
(2R*,3R*,5S*,6R*)-Ethyl 6-(4-(methoxycarbonyl)phenyl)-2-
ethyl-tetrahydro-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate
(
4m)
1
Colourless oil (115 mg, 43%); H NMR (400 MHz, CDCl ): δ
3
1
0
.84 (d, J = 6.4 Hz, 3 H), 0.88 (d, J = 6.4 Hz, 3 H), 1.19 (ddd, J
Colourless oil (112 mg, 31%); H NMR (400 MHz, CDCl ): δ
3
=
=
10.4, 8.0 and 6.0 Hz, 1 H), 1.27 (t, J = 6.8 Hz, 3 H), 1.28 (d, J
6.4 Hz, 3 H), 1.39 (ddd, J = 10.4, 6.4 and 4.0 Hz, 1 H), 1.67
0.97 (t, J = 7.6 Hz, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 1.42 (s, 3 H),
1.57–1.74 (m, 2 H), 1.89 (ddd, J = 12.8, 12.8 and 5.2 Hz, 1 H),
2.16 (ddd, J = 12.8, 4.0 and 2.0 Hz, 1 H), 2.71–2.77 (m, 1 H),
2.98 (ddd, J = 12.8, 10.4 and 4.0 Hz, 1 H), 3.56 (dt, J = 9.6 and
3.2 Hz, 1 H), 3.89 (s, 3 H), 4.17–4.30 (m, 2 H), 4.28 (d, J =
10.4 Hz, 1 H), 4.62 (brs, 1 H), 4.68 (brs, 1 H), 7.42 (d, J = 8.0
(s, 3 H), 1.73 (ddd, J = 13.6, 13.2 and 5.2 Hz, 1 H), 1.83–1.91
(m, 1 H), 1.98 (ddd, J = 13.6, 4.0 and 2.0 Hz, 1 H), 2.49–2.55
(m, 1 H), 2.60 (ddd, J = 13.2, 10.8 and 4.0 Hz, 1 H), 3.32 (dt, J
=
10.8 and 8.4 Hz, 1 H), 3.62–3.69 (m, 1 H), 4.11–4.21 (m, 2
13
13
H), 4.77 (brs, 2 H); C NMR (100 MHz, CDCl ): δ 14.5, 19.9,
Hz, 2 H), 7.97 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz,
3
2
0.2, 21.6, 24.0, 24.1, 32.7, 42.5, 44.3, 44.8, 60.2, 74.0, 79.0,
CDCl ): δ 10.7, 14.6, 21.8, 27.1, 32.7, 42.4, 45.7, 52.2, 60.3,
3
1
1
12.5, 146.8, 173.1; IR (KBr, neat): 2954, 2928, 2868, 1736,
80.3, 84.5, 113.0, 127.7, 129.3, 129.5, 145.4, 146.7, 167.3,
172.9; IR (KBr, neat): 2935, 2851, 1726, 1644, 1436, 1376,
−1
644, 1448, 1383, 1173, 1116, 1082, 1026, 892 cm . HRMS
+
−1
(APCI) cald for C H O (M + H) requires 269.2116; found
1278, 1176, 1112, 1078, 859, 767 cm . HRMS (APCI) cald for
16 28 3
+
+
2
4
69.2112. APCI-MS: m/z (relative intensity): 269.1 ((M + H) ,
2%), 251.1 (6), 177.1 (7), 158.0 (10), 157.0 (100), 124.0 (12),
C H O (M + H) requires 361.2015; found 361.2012.
2
1 28 5
+
APCI-MS: m/z (relative intensity): 361.2 ((M + H) , 5%), 303.2
111.0 (24).
(23), 271.3 (14), 211.2 (15), 178.1 (30), 155.1 (23), 124.1 (100),
9
1.1 (23), 84.1 (42).
(2R*,3R*,5S*,6R*)-Ethyl 2-ethyl-tetrahydro-6-phenyl-5-(prop-1-
en-2-yl)-2H-pyran-3-carboxylate (4k)
(2R*,3R*,5S*,6S*)-Ethyl 2-ethyl-tetrahydro-5-(prop-1-en-2-yl)-
6
-propyl-2H-pyran-3-carboxylate (4n)
1
Colourless oil (106 mg, 35%); H NMR (400 MHz, CDCl ): δ
3
1
0
1
2
3
2
.97 (t, J = 7.6 Hz, 3 H), 1.32 (t, J = 7.2 Hz, 3 H), 1.43 (s, 3 H),
.57–1.74 (m, 2 H), 1.88 (ddd, J = 13.6, 13.2 and 5.6 Hz, 1 H),
.16 (ddd, J = 13.6, 4.0 and 2.0 Hz, 1 H), 2.70–2.76 (m, 1 H),
.03 (ddd, J = 13.2, 10.4 and 4.0 Hz, 1 H), 3.55 (dt, J = 6.8 and
.8 Hz, 1 H), 4.16–4.26 (m, 3 H), 4.63 (brs, 1 H), 4.67 (brs, 1
H), 7.20–7.31 (m, 3 H), 7.33–7.35 (m, 2 H); C NMR
100 MHz, CDCl ): δ 10.8, 14.6, 21.8, 27.1, 32.8, 42.5, 45.5,
0.3, 80.4, 85.1, 112.6, 127.7, 128.0, 128.2, 141.5, 146.0, 173.0;
Colourless oil (123 mg, 46%); H NMR (400 MHz, CDCl ): δ
3
0.88 (t, J = 7.2 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H), 1.26 (t, J =
7.2 Hz, 3 H), 1.29–1.51 (m, 4 H), 1.52–1.64 (m, 2 H), 1.67 (s, 3
H), 1.71 (ddd, J = 14.0, 12.4 and 5.2 Hz, 1 H), 1.98 (ddd, J =
14.0, 4.0 and 2.0 Hz, 1 H), 2.56–2.62 (m, 1 H), 2.64 (ddd, J =
12.4, 10.0 and 4.0 Hz, 1 H), 3.23 (dt, J = 10.0 and 6.8 Hz, 1 H),
3.35 (ddd, J = 8.4, 5.6 and 3.2 Hz, 1 H), 4.08–4.20 (m, 2 H),
1
3
(
3
13
6
4.77 (brs, 2 H); C NMR (100 MHz, CDCl ): δ 11.0, 14.1,
3
IR (KBr, neat): 2965, 2935, 2856, 1733, 1644, 1453, 1376,
14.5, 19.0, 20.4, 27.2, 32.7, 35.7, 43.0, 44.9, 60.1, 80.1, 80.9,
112.4, 146.9, 173.1; IR (KBr, neat): 2960, 2936, 2874, 1736,
−1
1
173, 1071, 892, 756, 699 cm . HRMS (APCI) cald for
+
−1
C H O (M + H) requires 303.1960; found 303.1969.
APCI-MS: m/z (relative intensity): 303.2 ((M + H) , 11%),
1644, 1456, 1379, 1174, 1115, 1084, 1033, 892 cm . HRMS
1
9 26 3
+
+
(APCI) cald for C H O (M + H) requires 269.2116; found
1
6 28 3
+
2
1
85.2 (8), 257.2 (6), 239.2 (7), 211.2 (16), 171.1 (5), 159.1 (7),
25.1 (9), 124.1 (100), 82.0 (27).
269.2125. APCI-MS: m/z (relative intensity): 269.2 ((M + H) ,
37%), 251.2 (6), 172.1 (10), 171.1 (100), 125.1 (5), 124.1 (44),
9
7.1 (13).
(2R*,3R*,5S*,6R*)-Ethyl 2-ethyl-tetrahydro-5-(prop-1-en-2-yl)-
6
-p-tolyl-2H-pyran-3-carboxylate (4l)
(2R*,3R*,5S*,6S*)-Ethyl 2-ethyl-6-hexyl-tetrahydro-5-(prop-1-
en-2-yl)-2H-pyran-3-carboxylate (4o)
1
Colourless oil (114 mg, 36%); H NMR (400 MHz, CDCl ): δ
3
1
0
1
2
2
.96 (t, J = 7.6 Hz, 3 H), 1.32 (t, J = 7.2 Hz, 3 H), 1.45 (s, 3 H),
.57–1.72 (m, 2 H), 1.86 (ddd, J = 13.6, 13.2 and 5.2 Hz, 1 H),
.15 (ddd, J = 13.6, 4.0 and 2.0 Hz, 1 H), 2.30 (s, 3 H),
.68–2.74 (m, 1 H), 3.03 (ddd, J = 13.2, 10.8 and 4.0 Hz, 1 H),
Colourless oil (121 mg, 39%); H NMR (400 MHz, CDCl ): δ
3
0.87 (t, J = 6.8 Hz, 3 H), 0.99 (t, J = 7.6 Hz, 3 H), 1.24–1.40
(m, 10 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.47–1.54 (m, 1 H),
1.55–1.64 (m, 1 H), 1.67 (s, 3 H), 1.71 (ddd, J = 13.2, 12.8 and
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2470–2481 | 2477

View Online
1
3
5
2
3
3
.2 Hz, 1 H), 1.98 (ddd, J = 13.2, 4.0 and 1.6 Hz, 1 H),
.55–2.61 (m, 1 H), 2.64 (ddd, J = 12.8, 10.4 and 4.0 Hz, 1 H),
.22 (dt, J = 10.4 and 8.4 Hz, 1 H), 3.34 (ddd, J = 8.4, 5.6 and
7.22–7.30 (m, 5 H), 7.38 (d, J = 7.6 Hz, 2 H); C NMR
(100 MHz, CDCl ): δ 14.0, 21.3, 21.6, 34.2, 49.5, 50.5, 60.4,
3
81.8, 84.3, 113.1, 127.2, 127.4, 128.1, 128.3, 128.9, 137.5,
137.6, 140.3, 145.1, 173.2; IR (KBr, neat): 2978, 2930, 2865,
1
3
.2 Hz, 1 H), 4.09–4.20 (m, 2 H), 4.77 (brs, 2 H); C NMR
−1
(100 MHz, CDCl ): δ 10.9, 14.2, 14.4, 20.3, 22.8, 25.8, 27.1,
1728, 1644, 1452, 1373, 1173, 1062, 892, 768 cm . HRMS
3
+
2
1
9.4, 32.1, 32.7, 33.6, 42.9, 44.8, 60.0, 80.1, 81.1, 112.3, 146.8,
73.0; IR (KBr, neat): 2930, 2857, 1736, 1644, 1457, 1378,
(APCI) cald for C H O (M + H) requires 365.2116; found
365.2112. APCI-MS: m/z (relative intensity): 365.2 ((M + H) ,
24 28 3
+
−1
1173, 1157, 1085, 1032, 892 cm . HRMS (APCI) cald for
10%), 243.1 (5), 202.1 (16), 125.1 (9), 124.1 (100).
+
C H O (M + H) requires 311.2586; found 311.2588.
1
9 34 3
+
APCI-MS: m/z (relative intensity): 311.3 ((M + H) , 29%),
93.3 (4), 219.2 (4), 172.1 (6), 171.1 (65), 125.1 (8), 124.1
100).
(
2S*,3S*,5S*,6R*)-Ethyl tetrahydro-6-(4-methoxyphenyl)-2-
phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (11c)
2
(
1
Colourless solid, M.P. 114–116 °C (281 mg, 74%); H NMR
(
2
2
400 MHz, CDCl ): δ 1.00 (t, J = 7.2 Hz, 3 H), 1.49 (s, 3 H),
.16–2.21 (m, 2 H), 2.47 (ddd, J = 10.0, 9.6 and 2.8 Hz, 1 H),
.84 (ddd, J = 10.0, 9.6 and 3.2 Hz, 1 H), 3.75 (s, 3 H), 3.93 (q,
3
(
(
2R*,3R*,5S*,6S*)-Ethyl 2-ethyl-tetrahydro-6-isobutyl-5-
prop-1-en-2-yl)-2H-pyran-3-carboxylate (4p)
1
Colourless oil (113 mg, 40%); H NMR (400 MHz, CDCl ): δ
0
7
J = 7.2 Hz, 2 H), 4.44 (d, J = 10.0 Hz, 1 H), 4.68–4.73 (m, 3
H), 6.82 (d, J = 7.8 Hz, 2 H), 7.20–7.31 (m, 5 H), 7.38 (d, J =
7.6 Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.1, 21.7, 34.3,
3
.85 (d, J = 6.8 Hz, 3 H), 0.88 (d, J = 6.8 Hz, 3 H), 0.99 (t, J =
.2 Hz, 3 H), 1.19 (ddd, J = 10.8, 8.8 and 8.4 Hz, 1 H), 1.26 (t,
13
3
J = 7.2 Hz, 3 H), 1.42 (ddd, J = 10.4, 6.4 and 4.0 Hz, 1 H),
49.7, 50.6, 55.3, 60.5, 81.9, 84.1, 113.1, 113.6, 127.3, 128.2,
128.4, 128.7, 133.0, 140.3, 145.2, 159.3, 173.2; IR (KBr, neat):
2936, 2868, 1727, 1643, 1454, 1372, 1174, 1059, 1039, 910,
1
4
2
4
2
2
1
1
.50–1.64 (m, 2 H), 1.66 (s, 3 H), 1.73 (ddd, J = 12.8, 12.8 and
.0 Hz, 1 H), 1.85–1.94 (m, 1 H), 1.98 (ddd, J = 12.8, 4.0 and
.0 Hz, 1 H), 2.55–2.61 (m, 1 H), 2.62 (ddd, J = 12.8, 10.0 and
.0 Hz, 1 H), 3.27–3.37 (m, 2 H), 4.08–4.20 (m, 2 H), 4.77 (brs,
−
1
+
768 cm . HRMS (APCI) cald for C H O (M + H) requires
24 28 4
381.2066; found 381.2062. APCI-MS: m/z (relative intensity):
13
+
H); C NMR (100 MHz, CDCl ): δ 11.1, 14.5, 20.2, 21.4,
381.0 ((M + H) , 24%), 363.0 (5), 189.0 (6), 151.0 (14), 137.0
3
4.0, 24.1, 27.1, 32.7, 42.5, 43.0, 45.2, 60.1, 79.1, 80.2, 112.5,
46.7, 173.1; IR (KBr, neat): 2956, 2934, 2870, 1735, 1643,
(91), 124.1 (100).
−1
465, 1382, 1173, 1116, 1084, 1015, 891, 853 cm . HRMS
+
(2S*,3S*,5S*,6R*)-Ethyl 6-(4-fluorophenyl)-tetrahydro-2-
phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (11d)
(APCI) cald for C H O (M + H) requires 283.2273; found
17 30 3
+
2
83.2280. APCI-MS: m/z (relative intensity): 283.2 ((M + H) ,
1
1
1%), 282.6 (63), 170.7 (17), 124.8 (8), 123.8 (100), 122.8 (56),
00.9 (7), 81.9 (14).
1
Colourless oil (221 mg, 60%); H NMR (400 MHz, CDCl ): δ
1
3
.00 (t, J = 7.2 Hz, 3 H), 1.49 (s, 3 H), 2.17–2.21 (m, 2 H), 2.42
(ddd, J = 10.4, 10.0 and 2.4 Hz, 1 H), 2.85 (ddd, J = 10.0, 9.6
and 2.8 Hz, 1 H), 3.93 (q, J = 7.2 Hz, 2 H), 4.47 (d, J = 10.4
Hz, 1 H), 4.68–4.72 (m, 3 H), 6.98 (t, J = 8.4 Hz, 2 H),
(
2
2S*,3S*,5S*,6R*)-Ethyl tetrahydro-2,6-diphenyl-5-(prop-1-en-
-yl)-2H-pyran-3-carboxylate (11a)
13
7
.23–7.34 (m, 5 H), 7.38 (d, J = 7.6 Hz, 2 H); C NMR
1
Colourless oil (280 mg, 80%); H NMR (400 MHz, CDCl ): δ
(100 MHz, CDCl ): δ 14.1, 21.7, 34.1, 50.0, 50.5, 60.5, 82.0,
3
3
1
.01 (t, J = 6.8 Hz, 3 H), 1.48 (s, 3 H), 2.17–2.23 (m, 2 H), 2.48
83.8, 113.4, 115.0 (d, J = 21.4 Hz), 127.2, 128.4 (d, J = 10.7
Hz), 129.0, 129.1, 136.6, 140.1, 144.8, 162.5 (d, J = 243.2 Hz),
(ddd, J = 10.4, 10.0 and 3.2 Hz, 1 H), 2.87 (ddd, J = 10.0, 9.6
19
and 2.4 Hz, 1 H), 3.94 (q, J = 6.8 Hz, 2 H), 4.49 (d, J = 10.0
Hz, 1 H), 4.69–4.73 (m, 3 H), 7.23–7.32 (m, 4 H), 7.33–7.40
173.1;
F NMR (376 MHz, CDCl /C F ): δ −219.01–
3
6 6
(−218.94) (m, 1F); IR (KBr, neat): 2929, 2857, 1728, 1640,
1453, 1374, 1174, 1157, 1086, 1064, 836, 769 cm . HRMS
(APCI) cald for C H FO (M + H) requires 369.1866; found
13
−1
(m, 6 H); C NMR (100 MHz, CDCl ): δ 14.1, 21.7, 34.2,
3
+
4
9.7, 50.5, 60.4, 81.8, 84.6, 113.2, 127.2, 127.4, 127.9, 128.2
23
25
3
+
(2C), 128.4, 140.2, 140.6, 144.9, 173.1; IR (KBr, neat): 2978,
369.1873. APCI-MS: m/z (relative intensity): 369.2 ((M + H) ,
2
6
3
3
934, 2865, 1728, 1644, 1452, 1373, 1174, 1089, 1064, 755,
8%), 277.2 (4), 178.1 (4), 177.1 (14), 125.1 (8), 124.1 (100).
−
1
+
99 cm . HRMS (APCI) cald for C H O (M + H) requires
2
3 26 3
51.1960; found 351.1962. APCI-MS: m/z (relative intensity):
+
(2S*,3S*,5S*,6R*)-Ethyl tetrahydro-6-(4-nitrophenyl)-2-phenyl-
51.2 ((M + H) , 6%), 335.1 (8), 243.1 (12), 212.1 (19), 177.1
5
-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (11e)
(11), 136.1 (23), 119.1 (100).
1
Colourless oil (237 mg, 60%); H NMR (400 MHz, CDCl ): δ
3
1
.01 (t, J = 6.8 Hz, 3 H), 1.52 (s, 3 H), 2.18–2.30 (m, 2 H), 2.40
(
2S*,3S*,5S*,6R*)-Ethyl tetrahydro-2-phenyl-5-(prop-1-en-2-
(ddd, J = 10.0, 10.0 and 2.4 Hz, 1 H), 2.89 (ddd, J = 10.4, 10.0
yl)-6-p-tolyl-2H-pyran-3-carboxylate (11b)
and 2.4 Hz, 1 H), 3.95 (q, J = 6.8 Hz, 2 H), 4.61 (d, J = 10.0
Hz, 1 H), 4.68 (brs, 1 H), 4.74 (d, J = 10.0 Hz, 1 H), 4.76 (brs, 1
H), 7.26–7.41 (m, 5 H), 7.52 (d, J = 8.8 Hz, 2 H), 8.16 (J = 8.8
1
Colourless oil (255 mg, 70%); H NMR (400 MHz, CDCl ): δ
1
(
3
.00 (t, J = 7.2 Hz, 3 H), 1.50 (s, 3 H), 2.16–2.21 (m, 2 H), 2.29
s, 3 H), 2.48 (ddd, J = 9.6, 9.6 and 2.4 Hz, 1 H), 2.84 (ddd, J =
13
Hz, 2 H); C NMR (100 MHz, CDCl ): δ 14.1, 21.6, 33.9,
3
9
9
.6, 9.6 and 2.8 Hz, 1 H), 3.93 (q, J = 7.2 Hz, 2 H), 4.45 (d, J =
.6 Hz, 1 H), 4.69–4.72 (m, 3 H), 7.08 (d, J = 7.6 Hz, 2 H),
50.1, 50.2, 60.7, 81.9, 83.3, 114.2, 123.5, 127.2, 128.2, 128.6
(2C), 139.6, 143.9, 147.6, 147.9, 172.9; IR (KBr, neat): 2978,
2478 | Org. Biomol. Chem., 2012, 10, 2470–2481
This journal is © The Royal Society of Chemistry 2012

View Online
2869, 1730, 1644, 1371, 1173, 1093, 1066, 849, 699 cm−
1
.
2
6
927, 2855, 1729, 1606, 1522, 1347, 1176, 1070, 751,
−1
+
+
99 cm . HRMS (APCI) cald for C H NO (M + H)
HRMS (APCI) cald for C H O (M + H) requires 331.2273;
21 30 3
2
3
25
5
requires 396.1811; found 396.1815. APCI-MS: m/z (relative
intensity): 396.2 ((M + H) , 1%), 390.4 (1), 177.1 (4), 125.1
found 331.2262. APCI-MS: m/z (relative intensity): 331.2 ((M +
H) , 25%), 329.2 (11), 285.2 (7), 245.2 (16), 178.1 (6), 177.1
+
+
(10), 124.1 (100), 120.1 (4).
(37), 125.1 (9), 124.1 (100).
(
2S*,3S*,5S*,6R*)-Ethyl 6-(4-(methoxycarbonyl)phenyl)-
tetrahydro-2-phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate
11f)
(2S*,3R*,5S*,6R*)-Ethyl tetrahydro-2-phenyl-5-(prop-1-en-2-
yl)-6-p-tolyl-2H-pyran-3-carboxylate (12a)
(
1
Colourless oil (262 mg, 72%); H NMR (400 MHz, CDCl ): δ
3
1
Colourless solid, M.P.: 118–120 °C (266 mg, 65%); H NMR
400 MHz, CDCl ): δ 1.01 (t, J = 7.2 Hz, 3 H), 1.48 (s, 3 H),
0.89 (t, J = 7.2 Hz, 3 H), 1.47 (s, 3 H), 2.12 (ddd, J = 14.0, 12.8
and 5.2 Hz, 1 H), 2.23 (ddd, J = 14.0, 4.4 and 4.0 Hz, 1 H), 2.32
(s, 3 H), 3.01–3.03 (m, 1 H), 3.15 (ddd, J = 12.8, 10.4 and 4.0
Hz, 1 H), 3.83 (q, J = 7.2 Hz, 2 H), 4.38 (d, J = 10.4 Hz, 1 H),
4.70 (brs, 1 H), 4.72 (brs, 1 H), 4.86 (d, J = 3.2 Hz, 1 H), 7.12
(
2
2
3
.17–2.23 (m, 2 H), 2.44 (ddd, J = 10.0, 9.6 and 2.8 Hz, 1 H),
.89 (ddd, J = 10.0, 9.6 and 3.2 Hz, 1 H), 3.89 (s, 3 H), 3.94 (q,
J = 7.2 Hz, 2 H), 4.54 (d, J = 10.0 Hz, 1 H), 4.67 (brs, 1 H),
4
7
.72 (brs, 1 H), 4.73 (d, J = 9.6 Hz, 1 H), 7.27–7.33 (m, 3 H),
.39–7.43 (m, 4 H), 7.97 (d, J = 8.4 Hz, 2 H); C NMR
(d, J = 8.0 Hz, 2 H), 7.18–7.21 (m, 1 H), 7.24–7.29 (m, 2 H),
1
3
13
7.32–7.37 (m, 4 H); C NMR (100 MHz, CDCl ): δ 14.0, 21.4,
3
(
100 MHz, CDCl ): δ 14.0, 21.6, 33.9, 49.9, 50.3, 52.0, 60.4,
21.9, 32.8, 45.1, 45.7, 60.0, 79.4, 84.9, 112.7, 125.7, 127.3,
127.6, 128.0, 128.9, 137.4, 138.4, 140.7, 145.9, 172.4; IR (KBr,
neat): 2926, 2854, 1731, 1644, 1451, 1373, 1174, 1067, 1028,
3
8
1
2
7
4
4
8
1.7, 83.9, 113.5, 127.1, 127.3, 128.2, 128.3, 129.4, 129.6,
39.9, 144.2, 145.6, 166.9, 172.8; IR (KBr, neat): 2978, 2950,
862, 1725, 1643, 1374, 1278, 1176, 1111, 1065, 897,
−1
+
814, 748 cm . HRMS (APCI) cald for C H O (M + H)
24 28 3
−
1
+
63 cm . HRMS (APCI) cald for C H O (M + H) requires
requires 365.2116; found 365.2108. APCI-MS: m/z (relative
2
5 28 5
+
09.2015; found 409.2025. APCI-MS: m/z (relative intensity):
intensity): 365.2 ((M + H) , 7%), 301.1 (1), 274.1 (4), 125.1 (9),
+
08.3 (M , 1%), 177.7 (4), 124.8 (8), 123.8 (100), 122.8 (37),
124.1 (97), 123.0 (100).
1.9 (10).
(
2S*,3R*,5S*,6R*)-Ethyl 6-(4-bromophenyl)-tetrahydro-2-
(2S*,3S*,5S*,6S*)-Ethyl 6-ethyl-tetrahydro-2-phenyl-5-(prop-1-
phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (12b)
en-2-yl)-2H-pyran-3-carboxylate (11g)
1
Colourless oil (249 mg, 58%); H NMR (400 MHz, CDCl ): δ
3
1
Colourless oil (278 mg, 92%); H NMR (400 MHz, CDCl ): δ
0.88 (t, J = 7.2 Hz, 3 H), 1.48 (s, 3 H), 2.11 (ddd, J = 13.6, 12.8
and 4.8 Hz, 1 H), 2.23 (ddd, J = 13.6, 4.0 and 2.0 Hz, 1 H),
2.98–3.02 (m, 1 H), 3.10 (ddd, J = 12.8, 10.0 and 4.0 Hz, 1 H),
3.84 (q, J = 7.2 Hz, 2 H), 4.38 (d, J = 10.0 Hz, 1 H), 4.69 (brs,
1 H), 4.75 (brs, 1 H), 4.86 (d, J = 3.2 Hz, 1 H), 7.09 (d, J = 8.0
3
0
.93 (t, J = 7.2 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H), 1.38–1.47
(m, 1 H), 1.61–1.71 (m, 1 H), 1.72 (s, 3 H), 1.99–2.05 (m, 2 H),
2
1
.20 (ddd, J = 10.4, 10.0 and 5.6 Hz, 1 H), 2.67 (ddd, J = 10.0,
0.0 and 5.6 Hz, 1 H), 3.47 (ddd, J = 10.4, 10.0 and 7.6 Hz, 1
13
H), 3.91 (q, J = 7.2 Hz, 2 H), 4.51 (d, J = 10.0 Hz, 1 H), 4.82
Hz, 2 H), 7.20–7.36 (m, 5 H), 7.45 (d, J = 8.4 Hz, 2 H);
NMR (100 MHz, CDCl ): δ 14.0, 21.9, 32.6, 45.2, 45.5, 60.0,
C
1
3
(
brs, 2 H), 7.24–7.36 (m, 5 H); C NMR (100 MHz, CDCl ): δ
3
3
9
1
2
6
3
3
.8, 14.1, 20.2, 26.2, 34.0, 47.8, 50.4, 60.4, 81.2, 81.4, 112.9,
27.2, 128.1, 128.4, 140.8, 146.0, 173.5; IR (KBr, neat): 2961,
931, 2875, 1730, 1644, 1374, 1344, 1174, 1067, 894, 754,
79.3, 84.2, 113.2, 126.1, 127.4, 128.1, 129.4, 130.7, 131.3,
140.3, 140.5, 145.2, 172.3; IR (KBr, neat): 2978, 2934, 2859,
−1
1730, 1644, 1484, 1374, 1174, 1070, 1031, 817, 748 cm
.
−
1
+
+
99 cm . HRMS (APCI) cald for C H O (M + H) requires
HRMS (APCI) cald for C H BrO (M + H) requires
23 25 3
1
9
26
3
79
03.1960; found 303.1954. APCI-MS: m/z (relative intensity):
429.1065; found 429.1060 ( Br). APCI-MS: m/z (relative inten-
+
+
81
+
79
03.2 ((M + H) , 21%), 301.2 (8), 285.2 (7), 245.2 (11), 211.2
sity): 431.1 ((M + H) , 1%, Br), 429.1 ((M + H) , 1, Br),
264.2 (7), 263.2 (39), 245.1 (56), 178.1 (13), 177.1 (100), 131.0
(5), 177.1 (29), 125.1 (9), 124.1 (100).
(18), 124.1 (90), 82.0 (11).
(
(
2S*,3S*,5S*,6S*)-Ethyl tetrahydro-6-isobutyl-2-phenyl-5-
prop-1-en-2-yl)-2H-pyran-3-carboxylate (11h)
(2S*,3R*,5S*,6R*)-Ethyl 6-(4-chlorophenyl)-tetrahydro-2-
phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate (12c)
1
Colourless oil (288 mg, 87%); H NMR (400 MHz, CDCl ): δ
0
7
(
3
1
.84 (d, J = 6.4 Hz, 3 H), 0.85 (d, J = 7.2 Hz, 3 H), 1.00 (t, J =
.2 Hz, 3 H), 1.26 (ddd, J = 14.0, 10.0 and 2.0 Hz, 1 H), 1.40
ddd, J = 14.0, 10.0 and 4.0 Hz, 1 H), 1.71 (s, 3 H), 1.77–1.87
m, 1 H), 1.99–2.05 (m, 2 H), 2.11 (ddd, J = 9.6, 9.6 and 5.2
Colourless oil (212 mg, 55%); H NMR (400 MHz, CDCl ): δ
3
0.88 (t, J = 7.2 Hz, 3 H), 1.48 (s, 3 H), 2.12 (ddd, J = 14.0, 12.8
and 4.8 Hz, 1 H), 2.23 (ddd, J = 14.0, 4.0 and 2.0 Hz, 1 H),
2.99–3.03 (m, 1 H), 3.10 (ddd, J = 12.8, 10.4 and 4.0 Hz, 1 H),
3.84 (q, J = 7.2 Hz, 2 H), 4.40 (d, J = 10.4 Hz, 1 H), 4.69 (brs,
1 H), 4.75 (brs, 1 H), 4.86 (d, J = 3.2 Hz, 1 H), 7.20–7.31 (m, 5
(
Hz, 1 H), 2.68 (ddd, J = 10.0, 10.0 and 5.6 Hz, 1 H), 3.57 (dt, J
10.0 and 7.6 Hz, 1 H), 3.92 (q, J = 7.2 Hz, 2 H), 4.51 (d, J =
0.0 Hz, 1 H), 4.81 (brs, 2 H), 7.25–7.29 (m, 2 H), 7.29–7.35
=
1
(
(
1
13
H), 7.35(d, J = 8.8 Hz, 2 H), 7.39 (J = 8.4 Hz, 2 H); C NMR
13
m, 3 H); C NMR (100 MHz, CDCl ): δ 14.1, 20.1, 21.6, 24.0
(100 MHz, CDCl ): δ 13.9, 21.9, 32.5, 45.2, 45.5, 60.0, 79.3,
3
3
2C), 34.2, 42.5, 49.1, 50.1, 60.3, 78.5, 81.2, 113.0, 127.1,
28.0, 128.3, 140.8, 145.9, 173.5; IR (KBr, neat): 2954, 2928,
84.2, 113.1, 125.6, 127.4, 128.1, 128.3, 129.0, 130.3, 140.0,
140.3, 145.2, 172.2; IR (KBr, neat): 2978, 2933, 2857, 1730,
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 2470–2481 | 2479

View Online
−
1
13
1
(
3
644, 1452, 1374, 1174, 1088, 1069, 895, 748 cm . HRMS
H); C NMR (100 MHz, CDCl ): δ 14.0, 20.2, 25.7, 26.8, 26.9,
3
+
APCI) cald for C H ClO (M + H) requires 385.1570; found
85.1565 ( Cl). APCI-MS: m/z (relative intensity): 387.1 ((M +
H) , 1%, Cl), 385.1 ((M + H) , 3, Cl), 289.2 (6), 263.2 (12),
45.1 (17), 197.1 (10), 177.1 (33), 157.1 (4), 125.1 (10), 124.1
100), 123.1 (16), 99.0 (8), 82.0 (29).
27.0, 31.3, 32.8, 39.7, 40.1, 45.6, 59.8, 78.9, 84.8, 112.8, 125.6,
127.0, 128.0, 141.5, 146.6, 172.3; IR (KBr, neat): 2933, 2854,
1737, 1643, 1373, 1168, 1157, 1099, 1058, 890, 751 cm .
HRMS (APCI) cald for C H O (M + H) requires 357.2429;
23 32 3
found 357.2435. APCI-MS: m/z (relative intensity): 357.3
(M + H) , 7%), 219.1 (3), 178.1 (4), 125.1 (11), 124.1 (100),
23
25
3
35
+
37
+
35
−1
+
2
(
+
(
1
23.1 (14), 82.0 (25).
(
2S*,3R*,5S*,6R*)-Ethyl 6-(4-(methoxycarbonyl)phenyl)-
tetrahydro-2-phenyl-5-(prop-1-en-2-yl)-2H-pyran-3-carboxylate
12d)
(
(
2S*,3S*,4aR*,10bR*)-Ethyl 2,3,4,4a,5,10b-hexahydro-5,5-
1
Colourless oil (253 mg, 62%); H NMR (400 MHz, CDCl ): δ
dimethyl-2-phenylpyrano[3,2-c]chromene-3-carboxylate (13)
3
0
.90 (t, J = 7.2 Hz, 3 H), 1.46 (s, 3 H), 2.13 (ddd, J = 14.0, 12.8
1
Colourless solid; M.P.: 166–169 °C (213 mg, 58%); H NMR
and 4.8 Hz, 1 H), 2.25 (ddd, J = 14.0, 4.0 and 2.4 Hz, 1 H),
3
3
H), 4.69 (brs, 1 H), 4.74 (brs, 1 H), 4.88 (d, J = 3.2 Hz, 1 H),
7
7
(
400 MHz, CDCl ): δ 1.00 (t, J = 7.2 Hz, 3 H), 1.27 (s, 3 H),
.45 (s, 3 H), 1.82 (ddd, J = 12.4, 12.0 and 12.0 Hz, 1 H), 1.91
ddd, J = 12.4, 4.0 and 3.2 Hz, 1 H), 2.21 (ddd, J = 12.0, 10.0
and 3.2 Hz, 1 H), 2.77 (ddd, J = 12.0, 10.0 and 4.0 Hz, 1 H),
3.94 (q, J = 7.2 Hz, 2 H), 4.53 (d, J = 10.0 Hz, 1 H), 4.77 (d, J
10.0 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1 H), 6.84–6.88 (m, 1 H),
.14–7.19 (m, 1 H), 7.28–7.43 (m, 6 H); C NMR (100 MHz,
CDCl ): δ 14.1, 20.7, 27.9, 29.6, 43.9, 50.4, 60.7, 73.8, 78.3,
1.5, 116.9, 120.1, 122.0, 126.6, 127.4, 128.4 (2C), 129.2,
3
.02–3.06 (m, 1 H), 3.12 (ddd, J = 12.8, 10.4 and 4.0 Hz, 1 H),
.86 (q, J = 7.2 Hz, 2 H), 3.91 (s, 3 H), 4.48 (d, J = 10.4 Hz, 1
1
(
.20–7.24 (m, 1 H), 7.26–7.32 (m, 2 H), 7.34–7.38 (m, 2 H),
1
3
.53 (d, J = 8.4 Hz, 2 H), 8.01 (d, J = 8.4 Hz, 2 H); C NMR
=
7
(100 MHz, CDCl ): δ 13.9, 21.9, 32.5, 45.3, 45.5, 52.1, 59.9,
3
13
7
1
2
7
4
4
9.3, 84.5, 113.3, 125.6, 127.4, 127.6, 128.1, 128.4, 129.5,
40.2, 145.0, 146.5, 167.2, 172.2; IR (KBr, neat): 2983, 2951,
857, 1725, 1644, 1372, 1276, 1177, 1100, 1070, 898,
3
8
−
1
+
140.1, 152.8, 173.2; IR (KBr, neat): 2978, 2934, 2855, 1731,
58 cm . HRMS (APCI) cald for C H O (M + H) requires
2
5 28 5
−
1
1
612, 1458, 1371, 1167, 1122, 1065, 759, 704; cm . HRMS
09.2015; found 409.2021. APCI-MS: m/z (relative intensity):
+
+
(APCI) cald for C H O (M + H) requires 367.1909; found
23 26 4
67.1905. APCI-MS: m/z (relative intensity): 367.2 ((M + H) ,
%), 366.1 (2), 351.1 (3), 261.1 (2), 177.1 (3), 125.1 (6), 124.1
09.0 ((M + H) , 67%), 391.0 (20), 359.0 (9), 317.0 (11), 245.0
+
3
1
(9), 215.0 (9), 173.0 (5), 150.0 (13), 137.0 (26), 124.0 (100).
(80), 123.0 (100).
(2S*,3R*,5S*,6S*)-Ethyl tetrahydro-2-phenyl-5-(prop-1-en-2-
yl)-6-propyl-2H-pyran-3-carboxylate (12e)
1
(2S*,3R*,4aR*,10bR*)-Ethyl 2,3,4,4a,5,10b-hexahydro-5,5-
dimethyl-2-phenylpyrano[3,2-c]chromene-3-carboxylate (14)
Colourless oil (285 mg, 90%); H NMR (400 MHz, CDCl ): δ
0
3
.83 (t, J = 7.2 Hz, 3 H), 0.91 (t, J = 6.8 Hz, 3 H), 1.39–1.46
(
m, 1 H), 1.49–1.68 (m, 3 H), 1.72 (s, 3 H), 1.94 (ddd, J = 13.6,
1
Colourless solid; M.P.: 150–152 °C (202 mg, 55%); H NMR
1
2
3
3.2 and 5.6 Hz, 1 H), 2.10 (ddd, J = 13.6, 3.6 and 2.0 Hz, 1 H),
.79 (ddd, J = 13.2, 10.4 and 3.6 Hz, 1 H), 2.94–2.98 (m, 1 H),
.47 (ddd, J = 10.4, 7.2 and 7.2 Hz, 1 H), 3.77 (q, J = 7.2 Hz, 2
(
400 MHz, CDCl ): δ 0.77 (t, J = 7.2 Hz, 3 H), 1.23 (s, 3 H),
3
1
(
.44 (s, 3 H), 1.74 (ddd, J = 13.2, 12.8 and 5.2 Hz, 1 H), 2.27
ddd, J = 13.2, 3.8 and 2.0 Hz, 1 H), 2.57 (ddd, J = 12.8, 10.8
and 3.8 Hz, 1 H), 3.06–3.11 (m, 1 H), 3.67–3.79 (m, 2 H), 4.45
d, J = 10.8 Hz, 1 H), 4.96 (d, J = 3.2 Hz, 1 H), 6.80 (d, J = 8.0
Hz, 1 H), 6.88–6.92 (m, 1 H), 7.15–7.19 (m, 1 H), 7.23–7.42
H), 4.69 (d, J = 3.2 Hz, 1 H), 4.83 (brs, 1 H), 4.84 (brs, 1 H),
7
CDCl ): δ 13.8, 14.3, 18.7, 20.3, 32.6, 35.6, 43.9, 45.3, 59.7,
7
1
3
.20–7.26 (m, 2 H), 7.28–7.36 (m, 3 H); C NMR (100 MHz,
(
3
8.9, 80.8, 112.6, 125.5, 127.0, 128.0, 141.2, 146,5, 172.3; IR
13
(
m, 5 H), 7.52 (d, J = 7.6 Hz, 1 H); C NMR (100 MHz,
CDCl ): δ 13.8, 20.4, 27.8, 28.1, 39.6, 45.2, 60.0, 74.5, 78.4,
(KBr, neat): 2958, 2934, 2871, 1732, 1643, 1378, 1175, 1098,
3
−1
1
047, 894, 746 cm . HRMS (APCI) cald for C H O (M +
20 28 3
7
1
1
9.2, 116.8, 120.0, 122.3, 125.7, 126.5, 127.3, 128.1, 129.0,
40.6, 153.0, 171.8; IR (KBr, neat): 2979, 2942, 2862, 1731,
+
H) requires 317.2116; found 317.2110. APCI-MS: m/z (relative
intensity): 317.0 ((M + H) , 47%), 299.0 (11), 245.0 (21), 219.0
+
−1
607, 1459, 1371, 1172, 1100, 1076, 760, 748 cm . HRMS
(36), 199.0 (15), 173.0 (12), 124.0 (100), 123.0 (28), 101.0 (12),
+
(
APCI) cald for C H O (M + H) requires 367.1909; found
23 26 4
8
2.0 (45).
+
3
1
1
67.1914. APCI-MS: m/z (relative intensity): 367.2 ((M + H) ,
%), 366.2 (1), 311.2 (10), 261.2 (3), 178.1 (3), 177.1 (17),
25.1 (10), 124.1 (100).
(
(
2S*,3R*,5S*,6S*)-Ethyl 6-cyclohexyl-tetrahydro-2-phenyl-5-
prop-1-en-2-yl)-2H-pyran-3-carboxylate (12f)
1
Colourless oil (285 mg, 80%); H NMR (400 MHz, CDCl ): δ
3
Acknowledgements
0
1
5
2
3
.84 (t, J = 7.2 Hz, 3 H), 1.15–1.28 (m, 4 H), 1.43–1.66 (5 H),
.72 (s, 3 H), 1.75–1.87 (m, 2 H), 1.94 (ddd, J = 13.6, 12.4 and
.2 Hz, 1 H), 2.08 (ddd, J = 13.6, 4.4 and 2.0 Hz, 1 H),
.90–2.93 (m, 1 H), 3.04 (ddd, J = 12.4, 10.0 and 4.0 Hz, 1 H),
.32 (d, J = 10.0 Hz, 1 H), 3.77 (q, J = 7.2 Hz, 2 H), 4.64 (d, J
Authors are grateful to Council of Scientific and Industrial
Research (CSIR), New Delhi for financial support (Grant No. 01
(2332)/09/EMR-II). Authors gratefully acknowledge the X-ray
facility provided by the Department of Science and Technology
(DST), under FIST programme.
=
3.2 Hz, 1 H), 4.83 (brs, 1 H), 4.84 (brs, 1 H), 7.20–7.40 (m, 5
2480 | Org. Biomol. Chem., 2012, 10, 2470–2481
This journal is © The Royal Society of Chemistry 2012

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T. Iwamoto and J. Tanaka, Org. Lett., 2009, 11, 3262–3265;
References
(h) R. W. Bates and K. Palani, Tetrahedron Lett., 2008, 49, 2832–2834;
1
(a) P. A. Clarke and S. Santos, Eur. J. Org. Chem., 2006, 2045–2053 and
references cited therein (b) Y. J. Class and P. DeShong, Chem. Rev., 1995,
(i) M. Iqbal, N. Mistry and P. A. Clarke, Tetrahedron, 2011, 67, 4960–
4966.
9
5, 1843–1857; (c) D. J. Kopecky and S. D. Rychnovsky, J. Am. Chem.
7 (a) S. R. Crosby, J. R. Harding, C. D. King, G. D. Parker and
C. L. Willis, Org. Lett., 2002, 4, 577–580; (b) C. S. Barry, N. Bushby,
J. R. Harding, R. A. Hughes, G. D. Parker, R. Roe and C. L. Willis,
Chem. Commun., 2005, 3727–3729; (c) J. S. Yadav, B. V. S. Reddy,
T. Maity and G. G. K. S. N. Kumar, Tetrahedron Lett., 2007, 48, 8874–
8877; (d) J. S. Yadav, B. V. S. Reddy, T. Maity and
G. G. K. S. N. Kumar, Tetrahedron Lett., 2007, 48, 7155–7159;
(e) K.-P. Chan, A.-H. Seow and T.-P. Loh, Tetrahedron Lett., 2007, 48,
37–41; (f) J. S. Yadav, B. V. S. Reddy, G. G. K. S. N. Kumar and
T. Swamy, Tetrahedron Lett., 2007, 48, 2205–2208; (g) F. Liu and
T.-P. Loh, Org. Lett., 2007, 9, 2063–2066; (h) P. J. Jervis, B. M. Kariuki
and L. R. Cox, Org. Lett., 2006, 8, 4649–4652; (i) U. C. Reddy,
B. R. Raju, E. K. P. Kumar and A. K. Saikia, J. Org. Chem., 2008, 73,
1625–1630; ( j) U. C. Reddy, S. Bondalapati and A. K. Saikia,
Eur. J. Org. Chem., 2009, 1625–1630; (k) U. C. Reddy, S. Bondalapati
and A. K. Saikia, J. Org. Chem., 2009, 74, 2605–2608;
(l) S. Bondalapati, U. C. Reddy, D. S. Kundu and A. K. Saikia, J. Fluor-
ine Chem., 2010, 131, 320–324; (m) J. S. Yadav, B. V. S. Reddy,
Y. J. Reddy, B. P. Reddy and P. A. Reddy, Tetrahedron Lett., 2010, 51,
1236–1239; (n) A. K. Ghosh and D. R. Nicponski, Org. Lett., 2011, 13,
4328–4331; (o) P. V. Ramachandran and P. D. Gagare, Tetrahedron Lett.,
2011, 52, 4378–4381; (p) D. Clarisse, B. Pelotier, O. Piva and F. Fache,
Chem. Commun., 2012, 48, 157–159; (q) J. Robertson, C. North and
Soc., 2001, 123, 8420–8421; (d) Y. Wang, J. Janjic and S. A. Kozmin, J.
Am. Chem. Soc., 2002, 124, 13670–13671; (e) D. L. Aubele, S. Wan and
P. E. Floreancig, Angew. Chem., Int. Ed., 2005, 44, 3485–3488;
(
f) K. B. Bahnck and S. D. Rychnovsky, Chem. Commun., 2006, 2388–
2
2
2
390; (g) X. Tian, J. J. Jaber and S. D. Rychnovsky, J. Org. Chem.,
006, 71, 3176–3183; (h) P. Singh and A. Bhardwaj, J. Med. Chem.,
010, 53, 3707–3717.
2
3
(a) Polyether Antibiotics, ed. J. W. Westley, M. Dekker, New York, 1983,
vol. I and II; (b) D. J. Faulkner, Nat. Prod. Rep., 1998, 15, 113–158;
(c) M. C. Elliott, Contemp. Org. Synth., 1997, 4, 238–259; (d) M. Sasaki
and H. Fuwa, Nat. Prod. Rep., 2008, 25, 401–426.
(a) C. F. Thompson, T. F. Jamison and E. N. Jacobsen, J. Am. Chem.
Soc., 2001, 123, 9974–9983; (b) D. A. Evans, S. L. Bender and
J. Morris, J. Am. Chem. Soc., 1988, 110, 2506–2526; (c) B. J. Albert,
A. Sivaramakrishna, T. Naka and K. Koide, J. Am. Chem. Soc., 2005,
1
28, 2792–2793.
4
(a) D. L. Boger and S. M. Weinreb, Hetero Diels–Alder Methodology in
Organic Synthesis, Academic Press, San Diego, 1987; (b) K. Gademann,
D. E. Chavez and E. N. Jacobsen, Angew. Chem., Int. Ed., 2002, 41,
3
5
Chem.–Eur. J., 2007, 13, 9478–9485; (e) I. Paterson, A. Steven and
C. A. Luckhurst, Org. Biomol. Chem., 2004, 2, 3026–3038; (f) P. Liu
and E. N. Jacobsen, J. Am. Chem. Soc., 2001, 123, 10772–10773;
059–3061; (c) V. Gouverneur and M. Reiter, Chem.–Eur. J., 2005, 11,
806–5815; (d) G. Desimoni, G. Faita, M. Toscanini and M. Boiocchi,
J.
E.
R.
Sadig,
Tetrahedron,
2011,
67,
5011–5023;
(r) P. V. Ramachandran and P. D. Gagare, Tetrahedron Lett., 2011, 52,
4378–4381; (s) J. S. Yadav, M. R. Pattanayak, P. P. Das and
D. K. Mohapatra, Org. Lett., 2011, 13, 1710–1713; (t) M. Jacolot,
M. Jean, N. Levoin and P. van de Weghe, Org. Lett., 2012, 14, 58–61.
8 (a) V. Böhrsch and S. Blechert, Chem. Commun., 2006, 1968–1970;
(b) T. D. Avery, D. Caiazza, J. A. Culbert, D. K. Taylor and
E. R. T. Tiekink, J. Org. Chem., 2005, 70, 8344–8351; (c) A. B. Leuc,
T. P. Lebold and M. A. Kerr, J. Org. Chem., 2009, 74, 8414–8416.
9 J. Kjellgren and K. J. Szabó, Tetrahedron Lett., 2002, 43, 1123–1126.
10 (a) T. A. Blumenkopf, G. C. Look and L. E. Overman, J. Am. Chem.
Soc., 1990, 112, 4399–4403; (b) H. R. Sonawane, D. K. Maji, G. H. Jana
and G. Pandey, Chem. Commun., 1998, 1773–1774; (c) T.-P. Loh,
Q.-Y. Hu, K.-T. Tan and H.-S. Cheng, Org. Lett., 2001, 3, 2669–2672;
(d) T.-P. Loh, J.-Y. Yang, L.-C. Feng and Y. Zhou, Tetrahedron Lett.,
2002, 43, 7193–7196.
11 (a) P. Saha, U. C. Reddy, S. Bondalapati and A. K. Saikia, Org. Lett.,
2010, 12, 1824–1826; (b) S. Bonbdalapati, U. C. Reddy, P. Saha and
A. K. Saikia, Org. Biomol. Chem., 2011, 9, 3428–3438; (c) P. Saha,
P. Gogoi and A. K. Saikia, Org. Biomol. Chem., 2011, 9, 4626–4634.
12 The crystallographic data for compounds 4g, 11f, 13 and 14 have been
deposited with the Cambridge Crystallographic Data Centre as Sup-
plementary publication numbers CCDC 819363, 819365, 819364 and
819366†.
(
2
g) E. A. Voight, H. Seradj, P. A. Roethle and S. D. Burke, Org. Lett.,
004, 6, 4045–4048; (h) A. T. Parsons and J. S. Johnson, J. Am. Chem.
Soc., 2009, 131, 14202–14203.
5
(a) S. Hanessian, in Total Synthesis of Natural products: The Chiron
Approach, ed. J. E. Baldwin, Pergamon, Oxford, 1983; (b) J. C. Esteveza,
A. J. Fairbanks and G. W. J. Fleet, Tetrahedron, 1998, 54, 13591–13620;
(c) H. M. I. Osborn, N. Gemmel and L. M. Harwood, J. Chem. Soc.,
Perkin Trans. 1, 2002, 2419–2438; (d) T. K. M. Shing, W.-C. Fung and
C.-H. Wong, J. Chem. Soc., Chem. Commun., 1994, 449–450; (e) M.
A. Leeuwenburgh, R. E. J. N. Litjens, J. D. C. Codee, H. S. Overkleeft,
G. A. Van der Marel and J. H. Van Boom, Org. Lett., 2000, 2, 1275–
1
2
277; (f) P. Srihari, B. Kumaraswamy and J. S. Yadav, Tetrahedron,
009, 65, 6304–6309.
6
(a) P. A. Clarke, S. Santos and W. H. C. Martin, Green Chem., 2007, 9,
38–440; (b) P. A. Clarke, W. H. C. Martin, J. M. Hargreaves, C. Wilson
and A. J. Blake, Org. Biomol. Chem., 2005, 3, 3551–3563;
c) P. A. Clarke, W. H. C. Martin, J. M. Hargreaves, C. Wilson and
4
(
A. J. Blake, Chem. Commun., 2005, 1061–1063; (d) M. L. Bolla,
B. Patterson and S. D. Rychnovsky, J. Am. Chem. Soc., 2005, 127,
1
1
6044–16045; (e) C. R. Reddy and B. Srikanth, Synlett, 2010, 1536–
538; (f) M. Venkataiah, G. Somaiah, G. Reddipalli and N. W. Fadnavis,
Tetrahedron: Asymmetry, 2009, 20, 2230–2233; (g) J. Uenishi,
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