Thermal and Lewis acid promoted intramolecular Diels-Alder reaction of furanose tethered 1,3,9-decatriene systems: A synthetic and computational investigation

Article abstract of DOI:10.1039/c6ra10456h

The intramolecular Diels-Alder (IMDA) reaction of furanose tethered 1,3,9-decatrienes (4a-4r) was investigated under thermal conditions and in the presence of a Lewis acid. The stereoselectivity was determined by establishing the structures of adducts through single crystal X-ray diffraction and ¹H NMR spectroscopy. It was found that contrary to expectations, the thermal IMDA reaction of (3E) and (3Z)-1,3,9-decatrienes proceeded with nearly equal rate and furnished IMDA adducts (6-25) with moderate stereoselectivity. In some cases, rearranged products (9, 12, 17 and 24) arising out of a 1,5-sigmatropic shift, cis-trans isomerization followed by IMDA reaction were formed. In contrast, a Lewis acid promoted IMDA reaction afforded only one adduct albeit in lower yields. Not surprisingly, cis-boat transition states were favored over trans-boat transition states. Experimental results were corroborated with transition state modeling of these reactions by applying density functional theory based electronic structure calculations.

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Thermal and Lewis acid Promoted Intramolecular Diels-Alder Reaction of Furanose
Tethered 1,3,9-Decatriene Systems: A Synthetic and Computational Investigation
Hanuman P. Kalmode,† Dilip K. Maity,*,‡,§ and Prakash M. Bhate*,†
†Department of Dyestuff Technology, Institute of Chemical Technology, Mumbai 400019, India
‡Theoretical Chemistry Section, Bhabha Atomic Research Centre, Mumbai 400085, India
§Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India
Abstract: The intramolecular Diels–Alder (IMDA) reaction of furanose tethered 1,3,9-decatrienes (4a-
4r) was investigated under thermal conditions and in the presence of a Lewis acid. The stereoselectivity
was determined by establishing the structures of adducts through single crystal X-ray diffraction and 1H
NMR spectroscopy. It was found that contrary to expectations, the thermal IMDA reaction of (3E) and
(3Z)-1,3,9-decatrienes proceeded with nearly equal rate and furnished IMDA adducts (6-25) with
moderate stereoselectivity. In some cases, rearranged products (9, 12, 17 and 24) arising out of 1,5-
sigmatropic shift, cis-trans isomerization followed by IMDA reaction were formed. In contrast, Lewis
acid promoted IMDA reaction afforded only one adduct albeit in lower yields. Not surprisingly, cis-boat
transition states were favored over trans-boat transition states. Experimental results were corroborated
with transition state modeling of these reactions by applying density functional theory based electronic
structure calculation.
Introduction
The intramolecular Diels-Alder (IMDA) reaction is a powerful technique that offers an efficient, atom
economic and versatile solution to the problem of constructing multicyclic molecules1 and biologically
active natural products.2 However, the full potential of this important reaction will be realized only when
the stereochemical outcome of such IMDA reactions can be predicted. This goal remains elusive despite

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significant progress made towards understanding various factors that control stereochemistry of adducts
formed. While several acyclic 1,3,9-decatrienes have been prepared and subjected3 to thermal and Lewis
acid catalyzed IMDA reaction in order to study the stereoselectivity of adduct formation, IMDA
reactions of 1,3,9-decatrienes tethered on a cyclic chiral scaffold offering an entry into functionalized
chiral cyclic systems have received4 comparatively less attention.
In a study involving 1,3,9-decatrienes tethered on a six membered chiral dioxane scaffold, Nay and
co-workers4 obtained two adducts, one endo and the other exo. Only one adduct and that too exo was
observed by Miyashita et al.5 when they subjected a 1,3,9-decatrienes tethered on a chiral cyclohexane
derivative to the IMDA reaction. Paddon-Row and co-workers have described the cis/trans selectivity
in thermal and Lewis acid promoted IMDA reactions of ethylene-tethered and benzo-tethered 1,3,9-
decatriene systems and its validity by DFT methods6a-d in the analysis of IMDA reaction transition state
structures. They also describe the exo-selective IMDA reaction of benzo-tethered 1,3,9-decatrienes
promoted by sterically hindered aluminium tris(2,6-diphenyl phenoxide) (ATPH) catalyst. It is well
known7 that in thermal inter- and intramolecular Diels-Alder reactions acyclic (3Z)-1,3-dienes are
substantially less reactive than their (3E)-counterparts. As a result, their use in Diels-Alder reaction is
limited.8
We describe here the preparation and isolation of various (3E)- and (3Z)- 1,3,9-decatrienes (4a-4r)
tethered onto a D-xylo-furanose template (Scheme 1 and 2) and their thermal and Lewis acid promoted
IMDA reactions. To the best of our knowledge, this is the first report that describes the IMDA reaction
of (3E)- as well as the corresponding (3Z)- 1,3,9-decatrienes. Equally noteworthy is our finding that
both geometric isomers react at nearly the same rate and with almost identical stereoselectivity. We
propose an empirical method for assigning stereochemistry of isochromenone system based on the
difference in the chemical shift of the olefinic protons. We describe the formation of a byproduct arising
out of a rearrangement followed by the IMDA reaction. We also present results obtained by applying

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density functional theory based computational techniques to transition state modeling of these reactions
and show that these are in accordance with experimental results.
Results and discussion
Synthesis of IMDA substrates:
Scheme 1 Synthesis of furanose derived acyclic 1,3,9-decatrienes. Reagents and conditions: i) I2,
acetone, aq. Na2S2O3 solution, 24 h, 50%; ii) 60% Aq. acetic acid, 21 h, 96%; iii) NaIO4, MeOH:H2O
[1:1], 0 °C, 1 h, 100%; iv) Allyl triphenylphosphonium bromide, KHMDS (0.5 M solution in toluene),
THF, 0 °C to rt; v) Acryloyl chloride or methacryloyl chloride or trans-crotonyl chloride, Et3N, CH2Cl2,
0 °C to rt, 3 h; vi) Monoethyl ester of fumaric acid or monoethyl ester of maleic acid, DCC, DMAP,
CH2Cl2, 0 °C to rt, 3-24 h.
IMDA precursor 1,3,9-decatrienes (4a-4r), differing in the nature of dienophile were prepared in five
straightforward steps (Scheme 1 and 2). Thus, 1,2-O-isopropylidene-α-D-xylo-pentodialdo-1,4-furanose
(2), readily obtained in three steps from D-glucose9 (1) was subjected to the Wittig10 reaction to furnish
the (3E)- (3a) and (3Z)-diene (3b) which were easily separated by flash column chromatography.

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Esterification11 with acryloyl chloride or methacryloyl chloride or trans-crotonyl chloride afforded
1,3,9-decatrienes 4a-4f (Scheme 1). Steglich esterification12 with monoethyl ester of fumaric acid or
monoethyl ester of maleic acid or cyclohexene-1-carboxylic acid or cyclopentene-1-carboxylic acid or
4,5-dihydrofuran-3-carboxylic acid or 3,4-dihydro-2H-pyran-5-carboxylic acid afforded 1,3,9-
decatrienes 4g-4r (Scheme 1 and 2).
Scheme 2 Synthesis of furanose derived 1,3,9-decatrienes having acyclic diene and cyclic dienophile.
Reagents and conditions: i) Cyclohexene-1-carboxylic acid or cyclopentene-1-carboxylic acid or 4,5-
dihydrofuran-3-carboxylic acid or 3,4-dihydro-2H-pyran-5-carboxylic acid, DCC, DMAP, CH2Cl2, 0
°C to rt, 3-28 h.
Thermal IMDA reactions
In principle, the IMDA reaction of 1,3,9-decatrienes (4a-4r) is expected to give four adducts (Scheme
3). When a solution (1M in toluene) of the acrylate derived (3E)-1,3,9-decatrienes (4a) was boiled under
reflux at ambient pressure, a complex mixture of several products along with a significant amount of
starting material was obtained even after 48 hours. Three adducts (6, 7, 8) and a rearranged product (9)
were formed in a combined yield of 84% along with less polar byproducts when the reaction was

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o
conducted at 200-220 C for 7 h in a sealed tube with xylene as the solvent in the presence of sub-
stoichiometric amounts of 2,6-di-tert-butyl-4-hydroxytoluene (BHT). These conditions were used for
conducting the IMDA reaction with the rest of the 1,3,9-decatrienes. The methacrylate derived (3E)-
1,3,9-decatriene (4c) afforded two adducts (10, 11) and a rearranged product (12) in a total yield of 31%.
The crotonate derived (3E)-1,3,9-decatriene (4e) furnished adducts (13, 14) in low yield (9%). In the
case of the fumarate (4g) and the maleate derived 1,3,9-decatriene (4i) possessing an activated
dienophile, two (15, 16) and three adducts (18, 19, 20) in 43% and 60% yield respectively were obtained.
Fumarate derived 1,3,9-decatriene (4g) also provide a rearranged product 17 in 8% yield.
Scheme 3 Thermal IMDA reactions of acyclic ester derived 1,3,9-decatrienes

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Table 1 Thermal IMDA reactions (see Scheme 3 and 4)
Transition states
Adducts
total
yield
[%]
Sr.
IMDA
T
t
Cycloadducts R1/R1a
R2
R3
cis- cis- trans-
boat1 boat2 boat1
[%] [%] [%]
No. substrate
[oC] [h]
1
2
3
4
5
6
7
8
6, 7 and 8
6, 7 and 8
10 and 11
10 and 11
13 and 14
13 and 14
15 and 16
15 and 16
18, 19 and 20
18, 19 and 20
22
H
H
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
207
207
7
7
38
35
8
6
6
16
17
23
20
3
2
-
-
19
20
32
30
33
29
27
26
-
22
21
-
-
-
84a
79a
35a
31a
9b
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
215 18
215 18
218 30
218 30
210 17
210 17
H
CH3
CH3
CO2Et
CO2Et
H
5
-
7b
24
22
25
23
-
-
-
-
-
19
20
16
14
-
-
-
-
-
51a
49a
60
57
32
9
CO2Et 212 16
CO2Et 212 16
10
11
12
13
14
15
16
17
18
H
H
-(CH2)3-CH2-
-(CH2)3-CH2-
-(CH2)2-CH2-
-(CH2)2-CH2-
-(CH2)2-O-
H
H
H
H
H
H
H
H
219 29
219 29
220 24
220 24
217 32
217 32
216 35
216 35
30
22
23
23
25
25
-
-
52a
47a
27
-(CH2)2-O-
-(CH2)3-O-
-(CH2)3-O-
-
-
-
-
-
-
26
c
-
c
-
-
aTotal yield including rearranged product. bIMDA adduct along with trace amount of rearranged product
was observed. Dihydropyran derived (3E)- and (3Z)-1,3,9-decatriene after IMDA reaction gives an
c
unseparable mixture of products.
The acrylate, methacrylate, crotonate, fumarate, and maleate derived (3Z)-1,3,9-decatrienes (4b, 4d,
4f, 4h, 4j) afforded an almost identical product profile as that obtained from (3E)-1,3,9-decatrienes (4a,
4c, 4e, 4g, 4i). The order of the reactivity of the five furanose tethered substrates towards the IMDA
reaction as judged from the time taken for the (3E)-1,3,9-decatriene to disappear was: acrylate 4a >
maleate 4i > fumarate 4g > methacrylate 4c > crotonate 4e. A very similar order of reactivity was
observed in case of (3Z)-1,3,9-decatrienes. The reaction rate of crotonate derived 1,3,9-decatrienes (4e
and 4f) was significantly slower. Considerable decomposition was also observed.
The thermal IMDA reactions of cyclohexene derived (3E)-1,3,9-decatrienes (4k) stereoselectively
afforded adduct (22) in 32% yield (Scheme 4). Similarly, cyclopentene derived (3E)-1,3,9-decatrienes

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(4m) underwent the thermal IMDA reaction to afford adduct 23 in 33% yield along with a rearranged
product 24 (Scheme 4). Adduct 25 was obtained in (27%) yield by the thermal IMDA reactions of
dihydrofuran derived (3E)-1,3,9-decatrienes (4o).
Scheme 4 Thermal IMDA reactions of cyclic ester derived 1,3,9-decatrienes
A comparable product profile was obtained when geometrical isomers of (3Z)-1,3,9-decatrienes
underwent thermal IMDA reactions. The order of reactivity of these 1,3,9-decatrienes was as follows:
cyclopentene 4m > cyclohexene 4k > dihydrofuran 4o. The dihydropyran derived (3E)- and (3Z)-1,3,9-
decatrienes (4q and 4r) afforded an unseparable mixture of products.
Selectivity in thermal IMDA reactions:
Fig. 1 depicts cis/trans boat transition state conformers of the (3E)/(3Z)-1,3,9-decatriene precursors
(4a-4j) leading to four possible cycloadducts. Formation of adduct (21) was not observed (Scheme 3) in
1,3,9-decatrienes (4a-4j)

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Fig. 1 Thermal 3Z-3E isomerization of furanose tethered 1,3,9-decatrienes
because the trans boat2 transition state is sterically unfavorable. This is in accordance with previous
literature reports4. As can be seen in Scheme 3 adducts (6, 10, 13, 15 and 18) are formed from cis boat1
transition states (Fig. 2, 5a1, 5a6, 5a9, 5a11 and 5a13) and adducts (7, 11, 14, and 19) are formed from
cis boat2 transition states (Fig. 2, 5a3, 5a7, 5a10 and 5a14) respectively. The trans fused adducts (8, 16,
and 20) arise from trans boat1 transition states (5a2, 5a12 and 5a15). Adducts 22, 23 and 25 are
selectively formed from cis boat2 transition states (Fig. 2, 5a19, 5a23 and 5a27) respectively.
tether C=O
cis selective
5a1
tether C=O
trans selective
5a2

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tether C=O
cis selective
tether C=O
cis selective
5a3
5a6
tether C=O
cis selective
5a7
5a9
tether C=O
cis selective
5a10
5a11
tether C=O
cis selective
5a13
tether C=O
trans selective
5a12

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tether C=O
trans selective
5a15
5a14
tether C=O
cis selective
5a19
tether C=O
cis selective
5a23
tether C=O
cis selective
5a27
Fig. 2 Transition states for thermal IMDA reactions
Adducts are formed in the ratio cis1:cis2:trans1 = 2:1:1.3 when there are no substituents in the diene
and dienophile portions (Table-1, entries 1 and 2). The trans transition state is not favoured when the
dienophile bears an C9-methyl substituent (Table-1, entries 3 and 4). The cis selectivity is also reversed
and adducts are formed in the ratio cis1:cis2 = 1:3. A substituent such as methyl group at the C10-position

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(Table-1, entries 5 and 6) in the dienophile results in very low yields (~8%). An electron withdrawing
substituent (such as –CO2Et) present on the dienophile (Table-1, entries 7-10) had no substantial effect
on the yield. The cis-boat2 transition state was not observed in the case of fumarate derived 1,3,9-
decatrienes (4g-4h). The maleate derived 1,3,9-decatrienes (4i) and (4j) also formed adducts in the ratio
cis1:cis2:trans1 = 1:0.76:0.64. Cyclohexene, cyclopentene and dihydrofuran derived 1,3,9-decatrienes
(4k-4p) selectively afforded only one IMDA adduct arising from the cis boat2 transition states but in
low yields (Table-1, entries 11-16).
Influence of geometrical isomerism on the IMDA reaction
As shown in Scheme 3 and 4, the IMDA reaction of (3Z)-1,3,9-decatrienes (4b, 4d, 4f, 4h, 4j, 4l, 4n
and 4p) afforded a mixture of adducts that was almost identical to that obtained with (3E)-1,3,9-
decatrienes. There is severe steric hindrance between the diene in the cisoid conformation and the
furanose tether in these (3Z)-1,3,9-decatrienes (Fig. 1). Thus, thermal as well as Lewis acid promoted
IMDA reaction can occur only with the (3E)-1,3,9-decatrienes. This indicates that the (3Z)-1,3,9-
decatrienes undergo geometrical isomerization and the resulting (3E)-1,3,9-decatrienes undergo the
IMDA reaction. Such (3Z)-(3E) isomerization, followed by IMDA reaction has been previously
observed by Overman and co-workers.7b-7c
Lewis acid promoted IMDA reactions
In the presence of a Lewis acid (Et2AlCl, 1.0 M solution in n-hexane) 1,3,9-decatrienes (4a-4p)
afforded only one of the four possible cycloadducts in CH2Cl2 at 0-25 oC in lower yields (23-35%) along
with degradation products (Table 2). Adducts (6, 10, 15, and 18) via the cis-boat1 transition state (Table
2) were obtained with high stereoselectivity by Lewis acid promoted IMDA reaction of 1,3,9-decatrienes
(4a-4d and 4g-4j). In case of 1,3,9-decatrienes (4e) and (4f) the cis-boat2 transition state was exclusively
preferred. The Lewis acid promoted IMDA reactions of 1,3,9-decatrienes (4k-4p) afforded adducts 22,

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23, and 25 selectively via the cis-boat2 transition state but in lower yield (Table 2). The rearranged
product was not formed under these conditions. The IMDA reaction did not proceed in presence of other
Lewis acids (5 mol % TiCl4, DCM, 0-25 oC, 48 h and ZnCl2.OEt2, pyridine, DCM, 25 oC, 28 h).
Table 2 Lewis acid promoted IMDA reactionsa (see Scheme 3 and 4 for IMDA substrate and adduct structure)
Transition states
Sr.
No.
IMDA
substrate
T
t
cis-
boat1
[%]
cis-
boat2
[%]
Cycloadducts
R1/R1a
R2
R3
[oC]
[h]
1
2
H
H
H
H
H
H
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
0-R.T.
38
38
72
90
95
90
80
82
78
84
49
50
45
46
62
59
32
29
30
28
-
-
-
4a
4b
4c
4d
4e
4f
6
6
3
CH3
CH3
H
H
H
-
10
10
14
14
15
15
18
18
22
22
23
23
25
25
4
H
H
-
5
CH3
CH3
CO2Et
CO2Et
H
H
31
26
-
6
H
H
-
7
H
H
30
28
35
26
-
4g
4h
4i
8
H
H
-
9
H
CO2Et
CO2Et
H
-
10
11
12
13
14
15
16
H
H
-
4j
-(CH2)3-CH2-
-(CH2)3-CH2-
-(CH2)2-CH2-
-(CH2)2-CH2-
-(CH2)2-O-
29
31
27
24
23
21
4k
4l
H
-
H
-
4m
4n
4o
4p
H
-
H
-
-(CH2)2-O-
H
-
aReagents and conditions: Et2AlCl (1.0 M solution in n-hexane), DCM, 0-25 oC, 38-95 h.
Structural determination of IMDA adducts
While the proton count of high field 1H NMR spectra of compounds (6-25) obtained from the IMDA
1
reaction indicated these products to be IMDA adducts, H NMR spectroscopy was not sufficient for
structural assignment. Fortunately we were able to grow crystals of adducts (6, 7, 8 and 11) and hence
structural assignments could be unambiguously made by single crystal X-ray diffraction (see Fig. 3 for
the ORTEP drawing of these adducts).

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6
7
8
11
Fig. 3 ORTEP drawings of compounds 6, 7, 8 and 11 at 50% probability of thermal ellipsoids.
Structural assignments of oily IMDA adducts were based on:
a) Co-relation between the difference in the chemical shift (∆δ) of the olefinic protons and the stereochemistry
of –R1a and –Hb (see Table 3). ∆δ is large when -R1a and -Hb are β, β; medium when α, α and small when
α, β. It is observed that such ∆δs of previously reported IMDA adducts follow this trend (see Supporting
Information pp. S158-S159). Mondal et al. have used the difference in chemical shifts of acetonide methyl
protons for stereochemical assignment of IMDA adducts.13
b) The fact that adducts arising out of the trans boat2 transition state are not4b, 6a-6c formed. We have
also not observed such adducts in our work.
c) 1D, 2D NOESY and HMBC studies.

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Table 3 Stereochemistry of oily IMDA adducts (see Scheme 3 and 4)
-R1a
From XRD
-Hb
Sr. No. Adduct
Nature
∆δ (ppm)
Transition state
1
2
3
4
β
β
α
α
β
β
α
β
0.387
0.435
0.272
0.060
cis-boat2
cis-boat2
cis-boat1
7
11
6
Crystalline
trans-boat1
8
From ∆δ values
5
6
7
8
9
10
11
12
13
14
15
α
β
α
α
α
β
α
α
β
β
β
α
β
α
α
β
β
α
β
β
β
β
0.311
0.122
0.113
0.116
0.100
0.374
0.126
0.098
0.412
0.416
0.367
cis-boat1
cis-boat2
cis-boat1
cis-boat1
trans-boat1
cis-boat2
cis-boat1
trans-boat1
cis-boat2
cis-boat2
cis-boat2
10
14
13
15
16
19
18
20
22
23
25
Oily
In case of the adduct pair (10) and (11), the oily adduct is assigned structure (10) based on its ∆δ value
(0.311 ppm) which is only slightly lower than that exhibited (0.435 ppm) by the crystalline adduct (11).
Maleate derived 1,3,9-decatrienes (4i-4j) afforded three oily adducts of which the one exhibiting the
lowest ∆δ value (0.098 ppm) is assigned structure (20). The adduct exhibiting a high ∆δ value (0.374
ppm) is assigned structure (19) and that exhibiting a lower ∆δ value of 0.126 ppm is assigned structure
(18). 1D-NOESY spectrum of adduct (20) does not show an NOE enhancement between –R1a and –Hb
and hence the formed ring junction geometry is trans. NOE enhancement between –R1a and –Hb of
adduct (19) indicate that both these groups are on the same face of the molecule. Furthermore, an NOE
enhancement between –R1a and the anomeric proton displayed by adduct (19) indicates that –R1a is β.
Thus –R1a and –Hb are β, β in adduct (19) and hence α, α in adduct (18) thereby supporting structural
assignment based on ∆δ values. These structural assignments are in accordance with those reported by
Paddon-Row and others6a-6c in case of their acyclic maleate derived 1,3,9-decatrienes.

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In case of the fumarate derived 1,3,9-decatrienes (4g-4h) two adducts are obtained of which the one
exhibiting a significantly lower ∆δ value of 0.100 ppm is assigned structure (16), arising out of the trans-
boat1 transition state. The trans ring junction geometry in adduct (16) is confirmed by 1D and 2D
NOESY spectra. The other adduct is assigned structure (15) arising out of the cis-boat1 transition state
since its ∆δ value (0.116 ppm) is comparable to that exhibited (0.126 ppm) by adduct (18). The cis ring
junction geometry in adduct (15) is also confirmed by an NOE enhancement between –R1a and –Hb in
its 1D-NOESY spectrum.
Crotyl derived 1,3,9-decatrienes (4e-4f) gave two adducts of which the one exhibiting a ∆δ value
(0.113 ppm) similar to that of adduct (15) is assigned structure (13) obtained from cis-boat1 transition
state. The other adduct with a slightly higher ∆δ value (0.122 ppm) is assigned structure (14) arising out
of the cis-boat2 transition state. Adduct 22 was obtained from the cis-boat2 transition state for
cyclohexene derived 1,3,9-decatrienes (4k-4l), since it exhibits a high ∆δ value (0.412 ppm).
Cyclopentene and dihydrofuran derived 1,3,9-decatrienes (4m-4p) afforded one adduct each and that
too exhibiting a high ∆δ value (0.416 and 0.367 ppm) respectively. Thus, these adducts are assigned
structures 23 and 25 arising out of the cis-boat2 transition state. The 1D-NOESY spectra of adducts 22,
23 and 25 (see Scheme 4 for adduct structures) do not show an NOE enhancement between -Hb and -
Hc indicating that these two protons are not on the same face of molecule. Additionally, an NOE
enhancement between -Hb and the anomeric proton displayed by adduct 23 and 25 indicates that -Hb is
β. The HMBC spectra of adducts 22, 23 and 25 do not show co-relation between -Hb and the carbon
having -Hc proton. Thus –Hb and -Hc are β, α in adduct 22, 23 and 25 thereby supporting structural
assignments based on ∆δ values.
Structural determination of rearranged products
Structural determination of rearranged products was done by using spectroscopic techniques. The
rearranged products exhibited a higher carbonyl stretching frequency (1772-1793 cm-1) in the IR

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spectrum than that exhibited (1724-1758 cm-1) by the corresponding IMDA adducts indicating a ring
contraction in the cyclic lactone portion of the molecule. The proton count exhibited by rearranged
products and IMDA adducts is identical. However, in case of the rearranged product (9), signals from
one of the low field carbohydrate protons and two protons in the aliphatic region were replaced by a
signal that was characteristic of a methyl group adjacent to a carbon atom bearing one hydrogen atom.
Scheme 5 Structural determination of rearranged products
A DEPT study of the rearranged product (17 and 24), obtained from the fumarate derived 1,3,9-
decatriene (4g) and the cyclopentene derived 1,3,9-decatriene (4m) respectively, indicated the presence
of an additional quaternary center. On the basis of these spectroscopic analyses we assigned structure
24a to the rearranged product (Scheme 5). The configurations at positions a and b in 24a were
24
Fig. 4 ORTEP drawing of compound 24 at 50% probability of thermal ellipsoid

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confirmed to be S and S from the single crystal X-ray analysis (see Fig. 4 for an ORTEP drawing of this
compound) of the rearranged product (24). Scheme 5 also depicts the formation of the rearranged
product (24). Thus, the cyclopentene derived 1,3,9-decatriene (4m) undergoes a [1,5] sigmatropic
hydride shift to give the sterically crowded furanose tethered cis-piperylene derived 1,3,9-decatriene
(4m1). Cis-trans isomerization of the 1,3,9-decatriene (4m1) gives the trans-piperylene derived 1,3,9-
decatriene (4m2) which readily undergoes IMDA reaction to form the rearranged product (24). Such
rearrangements have been previously observed.14 On this basis, the rearranged products from the
acrylate (4a, 4b), maleate (4c, 4d) and fumarate derived 1,3,9-decatriene (4g, 4h) are assigned structures
9, 12 and 17 (Scheme 5) respectively.
Functionally embellished furo[3,2-b]furanone scaffolds has been widely encountered as a
characteristic sub-structure among a diverse range of natural products.15a-e The obtained rearranged
products can be converted into derivatives of 2,6-dioxabicyclo[3.3.0]octane-3,7-dione (bis-lactone)
which is a useful intermediate in some important biologically active compounds.16a-c These rearranged
products are structurally similar to the arteannuin B core and so, could be possible intermediates for its
synthesis in fewer number of steps than what is reported.13
Theoretical Results
Thirty two different transition states (TS) are envisaged for nine different reactants considered at
present leading to thirty two products of which fifteen products are observed. To provide mechanistic
insights about these reactions leading to isolated products, theoretical calculations were carried out on
minimum energy structure of reactants, transition states and products by applying density functional
theory.17 Optimized geometrical parameters of TS structures are supplied in supplementary information.
Transition state structures with selected bond distance parameters are displayed in Fig. 2. All the
transition states calculated have boat like structures. For the TS structure (5a1), C1-C10 and C4-C9
distances are calculated as 2.11 and 2.46 Å respectively. Bonds C1-C2, C3-C4 and C9-C10 in TS

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elongates to 1.39 Å from 1.33 Å in the reactant structure. As expected, in TS C2-C3 bond shrinks to
1.41 Å from 1.54 Å of reactant geometry. Calculated bond distances suggest shift of  bond in this
intramolecular Diels-Alder (IMDA) reaction of diene leading to the formation of product (6) from
acrylate, (4a). It is worth to mention that TS structure is confirmed by Hessian calculation producing
only one imaginary frequency (456 cm-1) and the corresponding normal mode connects to the reactant
(4a) and product (6). Bond distance parameters and the imaginary frequency of TS structures (5a2),
(5a3) and (5a4) are also in the same range. It is to be noted that in case of TS (5a4) leading (transition
states of theoretically expected adducts are shown in Fig. 5 see supporting information) to product (t1)
which is not observed experimentally, C1-C10 distance is the minimum (2.03 Å) and C4-C9 distance is
the maximum (2.60 Å) out of these four possible TS structures. Table 4 lists calculated Gibbs free energy
for reaction energy at 298K by applying M06-2X functional leading to thirty two different possible
products from nine reactants. The Table also provides barrier energy in terms of electronic energy
calculated considering B3LYP as well as M06-2X functional. Barrier energy is also calculated in terms
of Gibb’s free energy at 298 K and 500 K by applying M06-2X functional. Full geometry optimizations
and Hessian calculations have been carried out at B3LYP level. Single point energy calculations have
been performed at M06-2X level with the B3LYP structures. Calculated B3LYP free energy parameters
have been improved considering the electronic energy difference between M06-2X and B3LYP level as
the correction factor and modified values are shown in Table 4 as free energy at M06-2X level. For
acrylate (4a), the calculated barrier height (Gibbs free energy) is the minimum (21.8 kcal/mol) at 500 K
for TS (5a1) implying product (6) to be the major product corroborating experimental finding. When
barrier height is calculated from total electronic energy, M06-2X functional does predict TS (5a1) to be
the lowest lying TS for acrylate. Since the calculated barrier height for product t1 is less than that for
product 7, full geometry optimization and frequency calculation has also been carried out for these four
TS (5a1, 5a2, 5a3, 5a4) applying M06-2X functional. However, predicted barrier energy values are in
the same order.

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Similarly for methacrylate (4c), the barrier height for TS (5a7) is the lowest among four possible routes
when it is calculated from electronic energy as well as Gibbs’s free energy. This explains the product
(11) to be observed as the major product supporting experimental observation. Geometrical parameters
of all the four TS structures are very close as shown in Fig. 2. In case of reactant crotylacrylate (4e),
M06-2X predicts barrier energy to be the minimum for TS (5a9) showing product (13) as the major
product. Calculated Gibb’s free energy at 500K does also support similar observation. Similarly for
reactant fumarate the observed major product (16) may be explained based on the calculated barrier
energy for the concerned TS (5a11) based on energy calculated following M06-2X functional. Again
for maleate the barrier energy parameter based on M06-2X can explain the observed major product.
For cyclohexene derived 1,3,9-decatriene (4k), three TS structures are predicted. TS for fourth possible
conformer could not be obtained and this may be attributed to the fact that possible steric hindrance may
not allow the formation of the product. Calculated smaller barrier height for TS, 5a19 explains the
observed major product (22). Similarly in case of cyclopentene (4m) as well as dihydrofuran (4o)
derived 1,3,9-decatriene, the formation of major product 23 and 25 can be explained based on computed
low barrier energy for TS, 5a23 and 5a27. In case of dihydropyran derived 1,3,9-decatriene (4q),
theoretically it is predicted the product formed through TS, 5a31 as the major product. However,
synthetically a mixture of products is obtained and individual product from this mixture is inseparable.
All these reactions are predicted to be exothermic showing formation of products to be
thermodynamically feasible.
Table 4 Calculated Electronic and Gibbs free energy (kcal mol-1) for reaction barrier and reaction
energy of different reaction paths
Barrier Energy
Gibb’s Free Energy
Electronic Energy
Reactanta Transition Stateb
(M06-2X)
500K
Productc,d Reaction Energye
B3LYP M06-2X 298 K
18.9
18.8
14.4
15.3
21.0
18.8
21.8
23.1
6
8
-23.2
-20.9
4a
4a
5a1
5a2

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26.1
20.9
24.9
23.7
19.1
20.2
23.3
23.2
30.2
25.7
18.1
22.9
25.5
18.3
22.1
29.5
20.8
23.4
24.1
26.3
20.1
18.3
20.4
15.6
21.1
22.0
18.8
26.5
28.6
22.1
21.3
25.1
21.1
23.7
21.9
16.0
19.3
22.9
22.6
27.5
24.7
15.1
18.0
18.8
15.8
19.4
26.8
19.3
21.8
27.9
30.1
24.3
20.6
23.7
18.7
22.5
23.7
21.0
27.7
30.1
24.4
28.6
25.0
30.9
25.2
24.7
26.5
23.8
24.5
29.7
27.3
18.1
20.4
19.9
18.8
26.6
33.4
26.7
27.7
31.9
34.0
28.5
24.3
19.3
22.7
26.4
27.4
24.3
31.0
33.7
28.3
7
t1
t2
10
11
t3
13
t4
14
t5
15
t6
-25.2
-24.7
-18.7
-20.5
-20.0
-17.6
-17.1
-18.8
-18.9
-15.5
-16.0
-18.1
-22.7
-18.2
-23.8
-27.1
-24.7
-26.5
-20.4
-19.8
-21.2
-26.7
-26.8
-28.9
-24.2
-24.7
-26.6
-18.5
-19.0
-20.9
4a
4a
4c
4c
4c
4c
4e
4e
4e
4e
4g
4g
4g
4g
4i
5a3
5a4h
17.6
20.4
18.3
15.0
15.3
17.2
17.9
23.6
20.9
11.7
15.9
16.3
12.6
16.5
23.9
16.7
19.7
21.1
23.3
17.5
14.6
17.8
12.7
17.1
18.4
15.9
23.2
25.1
19.2
5a5h
5a6
5a7
5a8h
5a9
5a9-ah
5a10
5a10-ah
5a11
5a11-ah
5a12
5a12-ah
5a13
5a14
5a15
5a16h
5a17h
5a18h
5a19
5a21h
5a22h
5a23
5a25h
5a26h
5a27
5a29h
5a30h
5a31h
t7
16
18
19
20
t8
4i
4i
4i
4kf
4k
4k
4mf
4m
4m
4of
4o
4o
4qf
4q
4q
t9
t10
22
t11
t12
23
t13
t14
25
g
g
g
aRefer to Scheme 1 and 2 for reactant structures. Refer to Fig. 2 for experimentally formed TS
b
c
d
structures. Refer to Scheme 3 and 4 for product structures. Products (t1 to t14) are not observed.
eGibb’s free energy at 298K applying B3LYP functional. For these reactants, TS for the 4th possible
f
conformer (5a20, 5a24, 5a28, 5a32) could not be obtained by present DFT calculations. gA mixture of
unseparable products are obtained. hTransition states of theoretically expected adducts are shown in Fig.
5 (see supporting information page no. S200-S202).
Conclusion
We have conducted the first systematic survey of the IMDA reaction of furanose tethered 1,3,9-
decatriene and have shown that under thermal conditions adducts are formed from cis-boat and trans-
boat1 transition states. The trans-boat2 transition state was not observed. Our model may be used to
predict the stereochemical outcome of such IMDA reactions. Our work has also uncovered an alternative
pathway for the synthesis of Arteannuin B core. Only one adduct was obtained but in low yields (21-

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35%) when the reaction was carried out in presence of a Lewis acid promoter. The furanose tether was
found to be resistant to harsh reaction conditions such as high temperature and long reaction time.
The following empirical rules can be deduced:
1) Cis-trans geometry in the diene portion has no effect on yield and stereochemistry of the IMDA
reaction.
2) Highest yields (~75%) are obtained when there are no substituents in the diene and dienophile portion
of 1,3,9-decatrienes.
3) Yields are further reduced (~30%) when there is a substituent at the C9 position of the dienophile.
4) Thermal IMDA reactions of 1,3,9-decatrienes having cyclic dienophiles selectively afford IMDA
adducts obtained from the cis-boat2 transition state.
5) Lewis acid promoted IMDA reactions are stereoselective but low yielding.
Our studies indicate that acyclic 1,3,9-decatrienes such as acrylate (4a), crotylacrylate (4e), fumarate
(4g) and maleate (4i) predominantly adopt the cis-boat1 transition state whereas the acyclic methacrylate
derived 1,3,9-decatriene (4c) and cyclic 1,3,9-decatrienes (cyclohexene 4k, cyclopentene 4m,
dihydrofuran 4o and dihydropyran 4q) adopt the cis-boat2 transition state. Similar conclusions are drawn
by the analysis of IMDA reaction transition state structures by using DFT methods thereby giving
important insights into furanose tethered adducts. We thus reassert the validity of DFT method in
modeling reaction path of IMDA reaction and note that DFT functional M06-2X is able to predict
reaction barrier in correct orders for most of these reactions.
Experimental section
General Information
Unless noted, all commercial reagents and solvents were used without further purification. All
reactions were carried out under N2 atmosphere in anhydrous solvents such as DCM, THF, MeOH,
toluene, xylene and acetone. Anhydrous THF was distilled from sodium benzophenone and
dichloromethane was distilled from calcium hydride. Aluminum TLC sheets (silica gel 60 F254) of 0.25

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mm thickness were used to monitor the reactions. The spots were visualized with short wavelength UV
light or by charring after being sprayed with a solution prepared from one of the following solutions:
phosphomolybdic acid (5.0 g) in 95% EtOH (100 mL), 10% ethanolic H2SO4 and 2,4-dinitrophenyl
hydrazine (2,4-DNP). Melting points were determined by capillary apparatus and are uncorrected.
Yields refer to spectroscopically (1H, 13C NMR) homogeneous material obtained after column
chromatography performed on silica gel (100-200 and 230-400 mesh size). Air-sensitive reagents were
transferred by syringe or a double-ended needle. Optical rotations were measured by using a polarimeter
at the indicated temperature with a sodium lamp (D line, 589 nm). Infrared spectra were recorded by
1
using an FT/IR spectrometer with ATR PRO450-S and the absorption is expressed in cm-1. H NMR
13
and C NMR spectra were obtained by using 500, 600 and 125.0, 150.0 MHz NMR spectrometers,
respectively. Chemical shifts (δ) are reported in parts per million (ppm) downfield from
tetramethylsilane and are referenced to the solvent peak: CDCl3 (δ 7.26 for 1H NMR and δ 77.16 for 13C
NMR). The peak patterns of 1H NMR are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; dd, doublet of doublet; dt, doublet of triplet; br, broad. The coupling constants, J, are
reported in hertz (Hz). Assignment of carbon signals was assisted by DEPT experiments. To assign the
structures under consideration, the relative stereochemistry was assigned using one and two dimensional
NOE and HMBC experiments. High-resolution mass spectra were obtained by using positive
electrospray ionization (ESI) by Time of Flight (TOF) method.
Computational Methods
The minimum-energy structures of reactants, transition states and products were obtained by applying
density functional theory (DFT) based electronic structure calculations. A popular hybrid density
functional, namely, Becke three parameter hybrid exchange functional and the Lee-Yang-Parr
correlation functional (B3LYP) as well as a modern density functional, namely, M06-2X was used for
these calculations. The quasi-Newton-Raphson-based algorithm was used to carry out geometry
optimization by adopting Gaussian type split valence atomic basis function, 6-31G(d,p) for all the atoms.

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All transition state structures were characterized by one and only one imaginary frequency representing
the correct reaction coordinate. The Gibbs free energies were obtained by including the thermal and
entropic contributions to the energies obtained from the optimized structures. Calculated Gibbs free
energy values employed for discussions in the text are the obtained through this approach. These energy
values were further refined through zero point energy corrections for the calculation of reaction barrier
and reaction energy. All electronic structure calculations are carried out employing GAMESS suite of
ab initio package.
Experimental procedure and product characterization data
1,2:5,6-O-Diisopropylidene-α-D-glucofuranose (1a):
D-Glucose (6.9 g, 38.3 mmol) was converted into 1,2:5,6-O-diisopropylidene-α-D-glucofuranose (1a)
(yellowish crystals, 5.0 g, 50.2%) by reaction with excess of acetone in presence of I2 as described by
Bennet and co-workers,18a mp 107-109 oC (110-111 oC, lit.18b), Rf = 0.6 (50% EtOAc/n-hexanes). [α]D25
= -13.3 (c 1, CHCl3) (lit.18c [α]2D5 = -12.5 (CHCl3)).
1,2-O-Isopropylidene-α-D-glucofuranose (1b):
1,2:5,6-O-Diisopropylidene-α-D-glucofuranose (1a) (6.5 g, 25 mmol) was converted into 1,2-O-
isopropylidene-α-D-glucofuranose (1b) (white crystals, 5.3 g, 96.4%) by stirring with 60% aqueous
o
o
AcOH at 25-30 C for 21 h as described by Madsen and co-workers,18d mp 153-154 C (H2O) (lit.18e
159–160 ºC), Rf = 0.4 (80% EtOAc/n-hexanes). [α]D25 = -3.67 (c 0.53, H2O) (lit.18f [α]2D5 = -12.2 (H2O)).
1,2-O-Isopropylidene-α-D-xylo-pentodialdo-1,4-furanose (2):
1,2-O-Isopropylidene-α-D-glucofuranose (1b) (5.2 g, 23.61 mmol) was oxidized to 1,2-O-
isopropylidene-α-D-xylo-pentodialdo-1,4-furanose (2) (4.44 g, 100%) by reaction with aqueous sodium
o
o
metaperiodate in MeOH at 0 C for 1 h as described by Madsen and co-workers,18d mp 162-164 C

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o
(lit.18g mp 162–164 ºC (monomer, H2O)), (lit.18h mp 181-182 C (dimer, EtOAc/n-hexane)). Rf = 0.5
(60% EtOAc/n-hexanes).
(3aR,5R,6S,6aR)-5-((E)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol
(3a) and (3aR,5R,6S,6aR)-5-((Z)-buta-1,3-dien-1-yl)-2,2-dimethyl tetrahydrofuro[2,3-d]-
[1,3]dioxol-6-ol (3b):
To a solution of allyl triphenylphosphonium bromide (4.074 g, 10.63 mmol) in THF (6 mL) at 0 oC was
added a solution of potassium hexamethyldisilazide (23.1 mL, 0.5 M solution in toluene, 11.55 mmol).
o
The yellow suspension was stirred at 0 C for 1 h and a solution of 1,2-O-isopropylidene-α-D-xylo-
pentodialdo-1,4-furanose (2) (1 g, 5.32 mmol) in THF (3 mL) was added. The resultant brown
suspension was allowed to warm to 25-30 oC, stirred for 3 h and quenched with saturated NH4Cl solution
(50 mL). Diethyl ether (50 mL) was added and a white solid was removed by filtration through a pad of
celite. The separated aqueous layer was extracted with diethyl ether (3 × 40 mL). The combined organic
extracts were dried over anhydrous Na2SO4 and evaporated under reduced pressure to give a crude
product, which was purified by flash column chromatography over silica gel by using n-hexane/ethyl
acetate (83:17) to afford alcohol (3a) (0.35 g, 31%) as an off white solid and alcohol (3b) (0.1 g, 9%)
as a yellowish oily liquid.
Isomer (3a): Rf = 0.74 (50% EtOAc/n-hexanes), m.p. 122-124 oC; [α]2D5 = -73.64 (c 0.865, CHCl3); IR
1
(ATR) ṽ (cm-1): 3399, 2974, 1604, 1370, 1211, 1162, 963, 939, 907; H NMR (500 MHz, CDCl3): δ
6.49 (dd, J = 15.5, 11.0 Hz, 1H), 6.38 (dt, J = 17.0, 10.5, 6.5 Hz, 1H), 5.95 (d, J = 4.0 Hz, 1H), 5.72 (dd,
J = 15.5, 5.5 Hz, 1H), 5.28 (d, J = 17.0 Hz, 1H), 5.17 (d, J = 10.0 Hz, 1H), 4.77 (d, J = 5.0 Hz, 1H), 4.58
(d, J = 3.5 Hz, 1H), 4.09 (d, J = 2.5 Hz, 1H), 1.71 (br s, 1H) 1.51 (s, 3H), 1.33 (s, 3H); 13C NMR (125
MHz, CDCl3): δ 135.8, 135.1, 125.7, 118.8, 111.6, 104.5, 84.9, 80.4, 76.0, 26.6, 26.1; HRMS (ESI):
calcd. for C11H17O4 [M+H]+ 213.1127, found 213.1125.
Isomer (3b): Rf = 0.72 (50% EtOAc/n-hexanes); [α]D25= -26.42 (c 1.03, CHCl3); IR (ATR) ṽ (cm-1):
3426, 2922, 1639, 1594, 1375, 1213, 1162, 911, 711; 1H NMR (500 MHz, CDCl3): δ 6.65 (dt, J = 17.0,

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10.5, 6.5 Hz, 1H), 6.28 (t, J = 11.0 Hz, 1H), 5.97 (d, J = 3.5 Hz, 1H), 5.52 (dd, J = 11.0, 7.0 Hz, 1H),
5.32 (d, J = 17.0 Hz, 1H), 5.26 (d, J = 10.0 Hz, 1H), 5.07 (d, J = 7.0 Hz, 1H), 4.58 (d, J = 3.5 Hz, 1H),
13
4.15 (d, J = 2.0 Hz, 1H), 1.80 (br s, 1H), 1.53 (s, 3H), 1.33 (s, 3H); C NMR (125 MHz, CDCl3): δ
133.8, 131.7, 124.0, 120.7, 111.6, 104.5, 84.9, 77.5, 76.8, 26.7, 26.1; HRMS (ESI): calcd for
C11H16O4Na (M+Na+) 235.0946, found 235.0952.
General procedure for the esterification of alcohols (3a) and (3b) by using acid chloride
To a stirred solution of the alcohol (3a or 3b) (1 mmol) and triethylamine (2.5 mmol) in DCM (2.5 mL)
was added acryloyl chloride or methacryloyl chloride or trans-crotonyl chloride (2.2 mmol) dropwise
o
at 0 C. The resulting mixture was stirred at room temperature for 3 h, quenched with water (10 mL)
and extracted with DCM (3 × 20 mL). The combined organic layers were washed with water (2 × 30
mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford a crude product
that was purified by column chromatography over silica gel by using n-hexane/ethyl acetate (92.5:7.5)
as an eluent to afford the desired acrylate (4a-4f) respectively.
(3aR,5R,6S,6aR)-5-((E)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
acrylate (4a): Yield = 0.460 g, 61%; yellowish oily liquid; Rf = 0.82 (80% EtOAc/n-hexanes); [α]D25 =
-21.19 (c 0.645, CHCl3); IR (ATR) ṽ (cm-1): 2921, 1728, 1655, 1626, 1377, 1260, 1160, 963, 891, 857,
730; 1H NMR (500 MHz, CDCl3): δ 6.65 (dt, J = 17.0, 10.5, 6.5 Hz, 1H), 6.43 (distorted dd, J = 17.5,
7.5 Hz, 1H), 6.21 (t, J = 11.0 Hz, 1H), 6.11 (dd, J = 17.0, 10.5 Hz, 1H), 5.97 (d, J = 4.0 Hz, 1H), 5.88
(d, J = 17.5 Hz, 1H), 5.42 (t, J = 19.0, 8.5 Hz, 1H), 5.30 (distorted d, J = 16.0 Hz, 1H), 5.28 (d, J = 2.5
Hz, 1H), 5.26 (d, J = 10.0 Hz, 1H), 5.21 (d, J = 8.0, 2.5 Hz, 1H), 4.59 (d, J = 4.0 Hz, 1H), 1.57 (s, 3H),
13
1.33 (s, 3H); C NMR (150 MHz, CDCl3): δ 164.9, 135.9, 135.4, 132.1, 127.6, 125.2, 118.9, 112.1,
104.6, 83.6, 79.6, 77.7, 26.7, 26.3; HRMS (ESI): calcd for C14H19O5 [M+H]+ 267.1232, found 267.1244.
(3aR,5R,6S,6aR)-5-((Z)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
acrylate (4b): Yield = 0.060 g, 30%; yellowish oily liquid; Rf = 0.80 (80% EtOAc/n-hexanes); [α]D25 =

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-40.60 (c 0.36, CHCl3); IR (ATR) ṽ (cm-1): 2925, 1729, 1634, 1375, 1259, 1161,920, 807, 721; 1H NMR
(500 MHz, CDCl3): δ 6.65 (dt, J = 17.0, 10.5, 6.0 Hz, 1H), 6.44 (distorted d, J = 17.5 Hz, 1H), 6.21 (t,
J = 11.0 Hz, 1H), 6.11 (distorted dd, J = 17.0, 10.5 Hz, 1H), 5.97 (d, J = 4.0 Hz, 1H), 5.88 (d, J = 10.5
Hz, 1H), 5.43 (t, J = 10.5, 8.5 Hz, 1H), 5.30 (distorted d, J = 15.5 Hz, 1H), 5.28 (d, J = 2.5 Hz, 1H), 5.26
(d, J = 10.0 Hz, 1H), 5.21 (dd, J = 8.0, 2.5 Hz, 1H), 4.59 (d, J = 4.0 Hz, 1H), 1.57 (s, 3H), 1.33 (s, 3H);
13C NMR (150 MHz, CDCl3): δ 164.8, 134.3, 132.2, 131.6, 127.6, 122.9, 120.8, 112.1, 104.6, 83.7, 77.9,
75.2, 26.8, 26.2; HRMS (ESI): calcd for C14H19O5 [M+H]+ 267.1232, found 267.1234.
(3aR,5R,6S,6aR)-5-((E)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
methacrylate (4c): Yield = 0.480 g, 46%; yellowish oily liquid; Rf = 0.84 (20% EtOAc/n-hexanes);
[α]D25 = -33.256 (c 0.6, CHCl3); IR (ATR) ṽ (cm-1): 2988, 2931, 1725, 1637, 1606, 1375, 1215, 1154,
952, 901, 865, 737; 1H NMR (500 MHz, CDCl3): δ 6.39 (dd, J = 15.0, 10.5 Hz, 1H), 6.30 (dt, J = 16.5,
10.5, 6.5 Hz, 1H), 6.10 (s, 1H), 5.96 (d, J = 3.5 Hz, 1H), 5.63 (dd, J = 15.0, 6.5 Hz, 1H), 5.59 (s, 1H),
5.24 (d, J = 16.5 Hz, 1H), 5.23 (d, J = 3.0 Hz, 1H), 5.12 (d, J = 9.5 Hz, 1H), 4.84 (dd, J = 6.5, 2.5 Hz,
1H), 4.59 (d, J = 4.0 Hz, 1H), 1.92 (s, 3H), 1.55 (s, 3H), 1.33 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
166.0, 135.8, 135.6, 135.0, 126.4, 125.2, 118.6, 111.9, 104.5, 83.5, 79.5, 77.7, 26.6, 26.1, 18.1; HRMS
(ESI-MS): m/z [M+Na]+ calcd for C15H20O5Na: 303.1208; found: 303.1215.
(3aR,5R,6S,6aR)-5-((Z)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
methacrylate (4d): Yield = 0.025 g, 31%; yellowish oily liquid; Rf = 0.83 (15% EtOAc/n-hexanes);
[α]D25 = -73.773 (c 0.705, CHCl3); IR (ATR) ṽ (cm-1): 2988, 2925, 1725, 1637, 1375, 1215, 1153, 951,
917, 864, 757; 1H NMR (500 MHz, CDCl3): δ 6.65 (dt, J = 17.0, 10.5, 6.5 Hz, 1H), 6.20 (t, J = 11.5,
11.0 Hz, 1H), 6.13 (s, 1H), 5.96 (d, J = 3.5 Hz, 1H), 5.61 (s, 1H), 5.44 (t, J = 10.5, 8.5 Hz, 1H), 5.30 (d,
J = 16.5 Hz, 1H), 5.25 (distorted d, J = 8.5 Hz, 1H), 5.24 (distorted d, J = 3.0 Hz, 1H), 5.22 (distorted
dd, J = 8.5, 2.0 Hz, 1H), 4.59 (d, J = 3.5 Hz, 1H), 1.93 (s, 3H), 1.57 (s, 3H), 1.33 (s, 3H); 13C NMR (125
MHz, CDCl3): δ 165.9, 135.5, 134.0, 131.4, 126.5, 123.0, 120.6, 111.9, 104.5, 83.5, 77.9, 75.2, 26.7,
26.1, 18.1; HRMS (ESI-MS): m/z [M+Na]+ calcd for C15H20O5Na: 303.1208; found: 303.1215.

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(E)-(3aR,5R,6S,6aR)-5-((E)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dio-
xol-6-yl but-2-enoate (4e): Yield = 0.050 g, 26%; yellowish oily liquid; Rf = 0.82 (20% EtOAc/n-
hexanes). [α]D25 = -19.577 (c 0.44, CHCl3); IR (ATR) ṽ (cm-1): 2987, 2924, 1744, 1644, 1605, 1375,
1215, 1159, 958, 916, 858, 726; 1H NMR (500 MHz, CDCl3): δ 6.38 (dd, J = 15.0, 10.5 Hz, 1H), 6.30
(dt, J = 17.0, 10.0, 6.5 Hz, 1H), 5.95 (d, J = 4.0 Hz, 1H), 5.60 (dd, J = 15.0, 6.5 Hz, 1H), 5.24 (distorted
d, J = 18.0 Hz, 1H), 5.22 (distorted d, J = 3.5 Hz, 1H), 5.16 (distorted d, J = 19.0 Hz, 1H), 5.14 (distorted
d, J = 19.5 Hz, 1H), 5.13 (distorted d, J = 9.5 Hz, 1H), 4.81 (dd, J = 6.0, 2.5 Hz, 1H), 4.55 (d, J = 4.0
13
Hz, 1H), 3.08 (d, J = 7.0 Hz, 3H), 1.53 (s, 3H), 1.32 (s, 3H); C NMR (125 MHz, CDCl3): δ 170.1,
135.8, 134.9, 129.5, 125.2, 119.0, 118.6, 111.9, 104.4, 83.4, 79.3, 77.5, 38.8, 26.6, 26.1; HRMS (ESI-
MS): m/z [M+Na]+ calcd for C15H20O5Na: 303.1208; found: 303.1217.
(E)-(3aR,5R,6S,6aR)-5-((Z)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]diox-ol-6-
yl but-2-enoate (4f): Yield = 0.045 g, 29.6%; yellowish oily liquid; Rf = 0.81 (20% EtOAc/n-hexanes);
[α]D25 = -56.850 (c 0.615, CHCl3); IR (ATR) ṽ (cm-1): 2988, 2923, 1745, 1643, 1375, 1250, 1159, 960,
917, 808, 736; 1H NMR (500 MHz, CDCl3): δ 6.64 (dt, J = 16.5, 10.5, 6.0 Hz, 1H), 6.20 (t, J = 11.0 Hz,
1H), 5.95 (d, J = 3.0 Hz, 1H), 5.40 (t, J = 10.0, 9.0 Hz, 1H), 5.30 (d, J = 16.5 Hz, 1H), 5.25 (d, J = 10.0
Hz, 1H), 5.23 (d, J = 2.0 Hz, 1H), 5.21 (distorted d, J = 17.5 Hz, 1H), 5.17 (distorted d, J = 15.5 Hz,
1H), 5.16 (distorted dd, J = 6.5, 3.5 Hz, 1H), 4.54 (d, J = 3.5 Hz, 1H), 3.10 (d, J = 7.0 Hz, 3H), 1.55 (s,
3H), 1.32 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 170.1, 134.1, 131.5, 129.5, 122.8, 120.6, 119.0, 111.9,
104.4, 83.5, 77.7, 75.2, 38.7, 26.6, 26.1; HRMS (ESI-MS): m/z [M+Na]+ calcd for C15H20O5Na:
303.1208; found: 303.1205.
General procedure for the Steglich esterification of alcohols 3a and 3b
A stirred solution of the alcohol (3a or 3b) (1 mmol), 4-dimethylaminopyridine (DMAP) (0.2 mmol)
and monoethyl ester of fumaric acid or monoethyl ester of maleic acid or cyclohexene-1-carboxylic acid
or cyclopentene-1-carboxylic acid or 4,5-dihydrofuran-3-carboxylic acid or 3,4-dihydro-2H-pyran-5-

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o
carboxylic acid (1.3 mmol) in dry DCM (10 mL) was cooled in an ice-water bath at 0 C under N2
atmosphere. Dicyclohexyl carbodiimide (DCC) (1.5 mmol) was added in one portion. After stirring for
30 min. at 0 oC the reaction mixture was allowed to warm up to R. T. followed by stirring for another 3-
28 h. The reaction mass was filtered through a pad of celite and extracted with DCM (3 × 30 mL). The
combined organic layers were washed with water (2 × 30 mL), dried over anhydrous Na2SO4 and
concentrated under reduced pressure to afford a crude product that was purified by column
chromatography over silica gel by using n-hexane/ethyl acetate (94:6) as an eluent to afford the desired
1,3,9-decatrienes (4g-4r) respectively.
(3aR,5R,6S,6aR)-5-((E)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
ethyl fumarate (4g): Yield = 0.070 g, 44%; yellowish oily liquid; Rf = 0.84 (15% EtOAc/n-hexanes);
[α]D25 = -30.00 (c 0.4, CHCl3); IR (ATR) ṽ (cm-1): 2919, 1765, 1728, 1638, 1383, 1236, 1088, 892, 788;
1H NMR (500 MHz, CDCl3): δ 6.83 (distorted dd, J = 15.5 Hz, 2H), 6.39 ( dd, J = 15.5, 10.5 Hz, 1H),
6.30 (dt, J = 16.5, 10.5, 6.5 Hz, 1H), 5.97 (d, J = 3.5 Hz, 1H), 5.60 (dd, J = 15.5, 7.0 Hz, 1H), 5.27 (d,
J = 3.0 Hz, 1H), 5.22 (distorted dd, J = 16.0, 1.5 Hz, 1H), 5.13 (d, J = 10.0 Hz, 1H), 4.84 (dd, J = 6.5,
2.5 Hz, 1H), 4.59 (d, J = 4.0 Hz, 1H), 4.26 (q, J = 7.5 Hz, 2H), 1.54 (s, 3H), 1.33 (s, 3H), 1.32 (t, J =
13
7.5 Hz, 3H); C NMR (125 MHz, CDCl3): δ 164.7, 163.8, 135.9, 135.5, 135.0, 132.4, 124.9, 119.1,
112.3, 104.6, 83.6, 79.5, 78.5, 61.6, 26.8, 26.3, 14.2; HRMS (ESI-MS): m/z calcd. for C17H23O7 [M+H]+
339.1444, found 339.1454.
(3aR,5R,6S,6aR)-5-((Z)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
ethyl fumarate (4h): Yield = 0.060 g, 37%; yellowish oily liquid; Rf = 0.82 (15% EtOAc/n-hexanes).
[α]D25 = -106.4 (c 1, CHCl3); IR (ATR) ṽ (cm-1): 2922, 1736, 1701, 1643, 1381, 1235, 1159, 1089, 892,
763; 1H NMR (600 MHz, CDCl3): δ 6.85 (distorted dd, J = 16.2, 15.6 Hz, 2H), 6.63 (dt, J = 16.8, 10.8,
6.6 Hz, 1H), 6.20 (t, J = 11.4, 10.8 Hz, 1H), 5.97 (d, J = 3.6 Hz, 1H), 5.40 (t, J = 10.2, 8.4 Hz, 1H), 5.31
(d, J = 16.8 Hz, 1H), 5.31 (d, J = 3.0 Hz, 1H), 5.27 (d, J = 10.2 Hz, 1H), 5.21 (d, J = 7.8 Hz, 1H), 4.59
13
(d, J = 3.6 Hz, 1H), 4.26 (q, J = 7.2 Hz, 2H), 1.54 (s, 3H), 1.33 (s, 3H), 1.32 (t, J = 7.2 Hz, 3H); C

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NMR (125 MHz, CDCl3): δ 165.3, 164.0, 136.1, 135.4, 135.1, 128.9, 123.5, 117.8, 112.7, 104.7, 84.5,
80.8, 79.1, 61.1, 26.9, 26.4, 15.4; HRMS (ESI-MS): m/z calcd. for C17H22O7Na [M+Na]+ 361.1263,
found 361.1274.
(3aR,5R,6S,6aR)-5-((E)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
ethyl maleate (4i): Yield = 0.110 g, 68%; yellowish oily liquid; Rf = 0.83 (15% EtOAc/n-hexanes);
[α]D25 = -43.5 (c 1.025, CHCl3); IR (ATR) ṽ (cm-1): 2934, 1731, 1700, 1639, 1603, 1383, 1212, 1158,
1
1017, 912, 856, 729; H NMR (500 MHz, CDCl3): δ 6.39 (distorted dd, J = 15.0, 10.5 Hz, 1H), 6.32
(distorted dt, J = 17.0, 10.0, 6.5 Hz, 1H), 6.27 (distorted d, J = 12.0 Hz, 1H), 6.19 (distorted d, J = 12.0
Hz, 1H), 5.92 (d, J = 3.5 Hz, 1H), 5.64 (dd, J = 15.0, 7.0 Hz, 1H), 5.26 (distorted s, 1H), 5.23 (d, J =
2.5 Hz, 1H), 5.13 (distorted t, J = 8.5, 2.0 Hz, 1H), 4.81 (dd, J = 7.0, 2.5 Hz, 1H), 4.70 (d, J = 4.0 Hz,
1H), 4.24 (qd, J = 7.5, 2.0 Hz, 2H), 1.54 (s, 3H), 1.33 (s, 3H), 1.30 (t, J = 7.5 Hz, 3H); 13C NMR (125
MHz, CDCl3): δ 164.9, 164.0, 135.9, 135.4, 130.7, 128.8, 125.2, 118.8, 112.0, 104.5, 83.0, 79.2, 78.4,
61.3, 26.6, 26.2, 13.9; HRMS (ESI-MS): m/z calcd. for C17H22O7Na [M+Na]+ 361.1263, found
361.1270.
(3aR,5R,6S,6aR)-5-((Z)-Buta-1,3-dien-1-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl
ethyl maleate (4j): Yield = 0.410 g, 59%; yellowish oily liquid; Rf = 0.81 (15% EtOAc/n-hexanes);
[α]D25 = -36.5 (c 1.075, CHCl3); IR (ATR) ṽ (cm-1): 2923, 1735, 1701, 1642, 1428, 1381, 1235, 1159,
1088, 892, 762; 1H NMR (500 MHz, CDCl3): δ 6.63 (dt, J = 17.0, 10.5, 6.5 Hz, 1H), 6.29 (distorted d,
J = 12.0 Hz, 1H), 6.21 (distorted t, J = 9.5, 8.0 Hz, 1H), 6.20 (distorted d, J = 12.0 Hz, 1H), 5.93 (d, J =
4.0 Hz, 1H), 5.45 (t, J = 10.5, 9.0 Hz, 1H), 5.28 (dd, J = 16.5, 10.5 Hz, 2H), 5.24 (distorted d, J = 3.0
Hz, 1H), 5.20 (d, J = 8.0 Hz, 1H), 4.71 (d, J = 4.0 Hz, 1H), 4.25 (qd, J = 7.5, 1.5 Hz, 2H), 1.56 (s, 3H),
1.34 (s, 3H), 1.32 (t, J = 6.5 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 165.1, 164.1, 134.4, 131.5, 131.0,
128.7, 122.9, 120.8, 112.1, 104.6, 83.1, 78.7, 74.7, 61.1, 26.8, 26.3, 14.3; HRMS (ESI-MS): m/z calcd.
for C17H23O7 [M+H]+ 339.1444, found 339.1446.