Synthetic and theoretical investigations on the construction of oxanorbornenes by a Michael addition and intramolecular Diels-Alder furan reaction

Article abstract of DOI:10.1002/ejoc.200800681

The conjugate addition of nucleophiles such as allylmercaptan, allyl- and homoallylmalonate and diallylamine to β-furyl enones and acrylate, provides the Michael adducts in good yield. A facile intramolecular Diels-Alder reaction between the unsaturated tether and the furan diene ensues when these adducts are heated in a solvent such as toluene or xylene to afford the cycloadducts in good yield and excellent stereoselectivity in most cases. The structure and stereochemistry of these cycloadducts were confirmed by extensive NMR experiments and X-ray crystallography. Quantum chemical calculations on the transition state and product geometries suggest that the formation of the cycloadducts, in which the newly formed ring is exo-fused to the oxanorbornene framework, is favored over the endo-fused product due to less strain in the former and its transition state. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800681

FULL PAPER
DOI: 10.1002/ejoc.200800681
Synthetic and Theoretical Investigations on the Construction of
Oxanorbornenes by a Michael Addition and Intramolecular Diels–Alder Furan
Reaction
Mamta Dadwal,[a] Manoj K. Kesharwani,[b] Vaishalee Danayak,[b] Bishwajit Ganguly,*[b]
Shaikh M. Mobin,[c] Rajendran Muruganantham,[a] and Irishi N. N. Namboothiri*[a]
Keywords: Diels–Alder reaction / Michael addition / Oxanorbornene / B3LYP / Ab initio calculations
The conjugate addition of nucleophiles such as allylmercap-
tan, allyl- and homoallylmalonate and diallylamine to β-furyl
enones and acrylate, provides the Michael adducts in good
yield. A facile intramolecular Diels–Alder reaction between
the unsaturated tether and the furan diene ensues when
these adducts are heated in a solvent such as toluene or
xylene to afford the cycloadducts in good yield and excellent
NMR experiments and X-ray crystallography. Quantum
chemical calculations on the transition state and product geo-
metries suggest that the formation of the cycloadducts, in
which the newly formed ring is exo-fused to the oxanor-
bornene framework, is favored over the endo-fused product
due to less strain in the former and its transition state.
stereoselectivity in most cases. The structure and stereo- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
chemistry of these cycloadducts were confirmed by extensive
Germany, 2008)
Considerable effort has also been made by using compu-
tational methods toward accurate predictions of the stereo-
chemical outcome of many IMDA reactions.[5] Theoretical
approaches, including simple FMO models and quantum
chemical calculations of transition states and possible inter-
mediates of these reactions, have been considered to explain
the regio- and stereoselective aspects of the reaction.[5] In
some cases, secondary orbital interactions have been in-
voked to explain the stereoselectivity observed.[6] Recently,
the pseudo-intramolecular Diels–Alder reaction between a
2-substituted furan and an N-maleimide has been analyzed
with a DFT method.[7]
Recently, we reported a strategy involving the Michael
addition and intramolecular Diels–Alder reaction of the fu-
ran diene (IMDAF) for the synthesis of oxanorbornenes
fused to five- and six-membered rings with conjugated ni-
troalkenes as the key Michael acceptors.[8] The Michael ad-
ducts arising from the addition of various C- and hetero-
atom-centered nucleophiles to nitroalkenes underwent fac-
ile IMDAF reactions in a highly regio- and stereoselective
fashion to afford the products in moderate to high yield.
Herein, we show the development of this strategy as a full-
fledged Michael addition/IMDAF reaction by employing
other easily available Michael acceptors such as enones, en-
ediones and acrylates. The products, possessing four contig-
uous chiral centers, are immediate precursors to fused and
functionalized β,γ-enones and cyclohexenols.[8] We also re-
port our theoretical results on the various modes of cyclo-
addition of the Michael adducts, which show that ring
strain can determine the stereoselectivity observed for the
IMDA reactions.
Introduction
Intramolecular reactions are superior to their intermo-
lecular counterparts both in terms of substrate reactivity
and product selectivity. Whereas the proximal disposition
of functional groups that take part in cycloaddition/cycliza-
tion provides entropic advantages, the geometric constraints
associated with the substrate offer a high degree of regio-
and stereoselectivity. Intramolecular Diels–Alder (IMDA)
reactions have received great attention, as the two bonds
formed simultaneously result in two new rings making it an
excellent strategy for the synthesis of polycycles including
natural products.[1,2] Although various diene components
have been employed in IMDA reactions, the furan diene
has figured prominently in the literature because of its reac-
tivity and the cleavage options available for the product oxa-
norbornene.[3,4] However, the requirement of multi-step re-
actions to obtain suitable precursors is a major impediment
to this otherwise attractive synthetic strategy.
[a] Department of Chemistry, Indian Institute of Technology,
Bombay, Mumbai 400076, India
[b] Central Salt & Marine Chemicals Research Institute (CSIR),
Bhavnagar, Gujarat 364002, India
E-mail: ganguly@csmcri.org
[c] National Single Crystal X-ray Diffraction Facility, Indian Insti-
tute of Technology,
Bombay, Mumbai 400076, India
Fax: +91-22-2576-7152
E-mail: irishi@iitb.ac.in
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Synthetic and Theoretical Investigations on Oxanorbornenes
activating (COMe) groups to deliver Michael adduct 3c,
and later, the IMDAF products 4c and 5c, in good yield
Results and Discussion
Initially, we set out to construct a tetrahydrothiophene and excellent diastereoselectivity (Table 1, Entry 3).
ring fused to an oxanorbornene framework by the Michael Encouraged by the simplicity and efficiency of our
addition/IMDAF strategy. The requisite Michael acceptors, method in constructing the tricyclic skeleton possessing a
2-furyl enones 1a–c, were prepared according to reported fused and functionalized tetrahydrothiophene ring in a
aldol condensation methods.[9] These Michael acceptors stereoselective manner, we felt that the enones 1a,b and ac-
were then treated with allylmercaptan (2) in the presence of rylate 1d,[10] containing the key furyl moiety at the β-posi-
a suitable base to afford Michael adducts 3 (Table 1). For tion, would be suitable for constructing other carbo- and
instance, the triethylamine-mediated addition of allylmer- heterocycles fused to oxanorbornenes. We chose allylmalon-
captan (2) to enone 1a provided Michael adduct 3a in 64% ate 6a and its homoallyl analog 6b as the Michael donors
yield (Table 1, Entry 1). When 3a was heated in toluene at for the synthesis of precursors suitable for the IMDAF reac-
reflux for 4 d, an IMDAF reaction took place to afford ad- tion (Table 2). Allyl and homoallyl Grignard reagents were
ducts 4a and 5a in 67% total yield and an 86:14 ratio. We not suitable for this purpose, as the olefinic moiety in the
note that in both the isomers, the tetrahydrothiophene ring corresponding Michael adducts would not be sufficiently
was exo-fused to the oxanorbornene framework. These iso- activated to undergo the IMDAF reaction. The conjugate
mers are epimeric at the chiral center attached to the S addition of diethyl allylmalonate (6a) to enone 1a was car-
atom.
ried out under solvent-free conditions mediated by KOH
In a similar fashion, enone 1b was subjected to the conju- and benzyltriethylammonium chloride (TEBAC, Table 2,
gate addition of allylmercaptan (2) to afford 1,4-adduct 3b Entry 1). Michael adduct 7a, isolated in excellent yield
in comparable yield (63%, Table 1, Entry 2). Subsequently, (82%), underwent a smooth IMDAF reaction when heated
3b was transformed into the IMDAF adducts 4b and 5b in in toluene for 1 d to afford cycloadducts 8a and 9a contain-
59% yield and an 87:13 ratio. Despite the fact that the IM- ing a cyclopentane skeleton in 73% yield and 83:17 selecti-
DAF reaction time was shorter (3 d), similar reaction con- vity. We also observed a similar high yield and selectivity
ditions were suitable for Michael acceptor 1c possessing two when enone 1b was employed as the Michael acceptor
Table 1. Michael addition of allylmercaptan (2) to β-furyl enones 1a–c followed by the IMDAF reaction of the Michael adducts 3a–c.
Entry
1
R1, R2
Yield[a] of 3
IMDAF time
Yield[a] of 4 + 5
4/5
1
2
3
a
b
c
H, Me
H, Ph
COMe, Me
64%
63%
59%
4 d
4 d
3 d
67%
59%
51%
86:14
87:13
87:13[b]
[a] Isolated yield after purification by silica gel column chromatography. [b] The minor isomer 5c could not be isolated in pure form.
Table 2. Michael addition of allyl- and homoallylmalonates 6[a] to β-furyl enones 1a,b and acrylate 1d followed by an IMDAF reaction
of the Michael adducts 7.
Entry
1
R
6, n
MA time
Product, yield[b]
IMDAF solvent and time
Yield[b] of 8 + 9
8/9
1
2
3
4
5
6
a
b
d
a
b
d
Me
Ph
OEt
Me
Ph
6a, 1
6a, 1
6a, 1
6b, 2
6b, 2
6b, 2
10 h
8 h
72 h
16 h
15 h
106 h
7a, 82%
7b, 77%
7c, 38%
7d, 75%
7e, 69%
7f, 45%
toluene, 1 d
toluene, 1 d
toluene, 1.5 d
xylene, 7 d
xylene, 5 d
xylene, 7 d
73%
87%
83:17
82:18
84:16
100:0
93:7
–
77%
41%[c]
43%[d]
[e]
OEt
–
[a] 6: E = CO2Et. [b] Isolated yield after purification by silica gel column chromatography. [c] 40% of Michael adduct 7d was recovered.
[d] 35% of Michael adduct 7e was recovered. [e] 38% of 7f plus intractable material was recovered.
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B. Ganguly, I. N. N. Namboothiri et al.
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(Table 2, Entry 2). Although the yield of Michael adduct 7c 12,13 (Table 3, and see also the discussion of the NMR and
was low (38%) when acrylate 1d was treated with allylmal- computational results below).
onate 6a, 7c subsequently underwent an IMDAF reaction
to provide 8c and 9c in high yield (77%) and selectivity lates under a variety of conditions met with failure. There-
(84:16, Table 2, Entry 3). fore, we could not generate a tetrahydrofuran ring by our
All our attempts to add allyl alcohol to enones and acry-
We subsequently used substrates 1a,b and 1d to construct Michael/IMDAF strategy. In another attempt to synthesize
a cyclohexane skeleton fused to oxanorbornene (Table 2, a seven-membered ring fused to oxanorbornene, we carried
Entries 4–6). Thus, whereas the 1,4-addition of homoal- out the Michael addition of diallyl malonate (14) to 4-(2-
lylmalonate 6b to enones 1a,b proceeded well (75 and 69% furyl)but-3-en-2-one (1a), but the subsequent cycloaddition
yield, respectively, Table 2, Entries 4 and 5), the corre- of Michael adduct 15 to the desired IMDAF adduct 16 did
sponding reaction of 6b with acrylate 1d provided adduct not proceed, even under forcing conditions (refluxing
7f only in moderate yield (45%, Table 2, Entry 6). Never- xylene or mesitylene, Scheme 1).
theless, we subjected these Michael adducts to the IMDAF
reaction by refluxing them in xylene for 5–7 d (Table 2, En-
tries 4–6). As anticipated, these reactions remained incom-
plete even after such a prolonged reaction time, and con-
siderable amounts of Michael adducts were recovered.
However, the selectivities in these reactions were note-
worthy. Whereas we observed 100% selectivity when 7d was
subjected to the IMDAF reaction (Table 2, Entry 4), the re-
Scheme 1.
action of 7e also exhibited excellent selectivity (Table 2, En-
try 5).
Having constructed the tetrahydrothiophene, cyclopen-
tane and cyclohexane rings, we investigated the synthesis of
Structure and Stereochemistry
a pyrrolidine ring by our Michael/IMDAF strategy. Unfor-
If we consider the two modes of the IMDAF reaction,
tunately, our attempted Michael addition of diallylamine eight cycloadducts (18–25) are theoretically possible; four
(10) to enones 1a,b under a variety of conditions provided cycloadducts (18–21) would result from C2–C4Ј and C5–
either no product or a complex mixture. However, we suc- C5Ј bonding (path A), and the other four (22–25) would
ceeded in adding diallylamine (10) to (2-furyl)acrylate 1d derive from C2–C5Ј and C5–C4Ј bonding (path B,
under n-butyllithium-mediated conditions in 79% yield Scheme 2). Whereas path A provides fused or “ortho” prod-
(Table 3, Entry 1). Michael adduct 11d underwent a facile ucts, path B leads to bridged or “meta” products. However,
IMDAF reaction when refluxed in toluene for 2 d to afford path B appeared geometrically unfavorable as shown in Fig-
adducts 12d and 13d in a combined yield of 89% and a ure 1. In this path, severe strain is expected if the reacting
23:77 ratio. Analogously, furylidenemalonate 1e[11] provided centers in the Michael adduct that are relatively far apart
Michael adduct 11e, which was refluxed without purifica- have to come closer together. Therefore, we excluded path B
tion in toluene for 4 d to obtain pyrrolidines 12e and 13e and the associated cycloadducts 22–25 from further analy-
in lower yield (73%), but better selectivity (18:82, Table 3, sis.
Entry 2). We note that in contrast to the predominance of
We carried out extensive NMR studies to establish the
exo-cis isomers 4 and 8 over exo-trans isomers 5 and 9 in structure and stereochemistry of the cycloadducts. At the
the case of tetrahydrothiophenes 4,5 (Table 1) and cyclo- outset, we chose the isomers 4b/5b as representative exam-
pentanes 8,9 (Table 2), respectively, we obtained exo-trans ples, and we correctly assigned the protons with the assist-
isomers 13 as the major products in the case of pyrrolidines ance of a 1H-1H COSY experiment. Further analysis of the
Table 3. Michael addition of diallylamine (10)[a] to β-furylacrylate 1d and furylidenemalonate 1e followed by an IMDAF reaction of
Michael adducts 11.
Entry
1
R1, R2
Product, yield[b]
IMDAF time
Yield[b] of 12 + 13
12/13
1
2
d
e
H, CO2Et
CO2Et, CO2Et
11d, 79%
11e, –[c]
2 d
4 d
89%
73%
23:77
18:82
[a] 10: R = allyl. [b] Isolated yield after purification by silica gel column chromatography. [c] Crude Michael adduct 11e was used for the
next (IMDAF) step.
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Synthetic and Theoretical Investigations on Oxanorbornenes
Scheme 2.
Table 4. Comparison of 1H NMR, 1H-1H 2D-COSY and 1H-1H
2D-NOESY characteristics of isomers 4b and 5b.
Entry
1H-1H
4b
5b
J [Hz]
NOE[a]
J [Hz]
NOE[a]
Figure 1. Two modes of cycloaddition of the Michael adduct.
1
2
3
4
5
6
7
8
9
10
11
12
13
6-7α
6-7β
7α-7β
7α-7a
7β-7a
7a-1α
7a-1β
1α-1β
3-9
3-9Ј
3-4
4-9
4-9Ј
0.0
4.4
11.7
7.3
2.6
7.7
10.6
10.6
18.3
8.8
–
–
M
S
M
–
M
M
S
W
W
–
0.0
4.5
11.7
7.7
2.6
10.6
10.5
10.9
17.2
9.2
–
W
W
S
S
–
–
–
S
M
M
–
W
M
1H-1H couplings in 4b and 5b suggested that the newly
formed ring was exo-fused to the oxanorbornene moiety, as
in the previously reported cycloadducts obtained from the
Michael-initiated IMDAF reaction of nitro compounds.[8]
We observed in 4b and 5b that out of the two geminal pro-
tons H-7α and H-7β, only H-7β coupled with H-6 (J = 4.4
and 4.5 Hz, respectively, in 4b and 5b, Table 4, Entries 1 and
2). We observed no coupling between H-6 and H-7α due to
a dihedral angle of ca. 90° between the two protons.
Whereas the coupling for H-7α with H-7a was moderately
strong (J = 7.3 and 7.7 Hz, respectively, in 4b and 5b), that
between H-7β and H-7a was weak (J = 2.6 Hz in both 4b
–
–
–
–
–
–
[a] S = Strong; M = Medium; W = Weak.
and 5b, Table 4, Entries 4 and 5). Subsequently, we analyzed benzoyl group in 4b (Table 4, Entries 12 and 13). These re-
the 2D-NOESY data for the two isomers, which showed a sults agreed well with those obtained for corresponding ni-
medium (in 4b) and weak (in 5b) NOE between H-6 and tro compounds.[8] Finally, we unambiguously established
H-7β (Table 4, Entry 2), but no NOE (in 4b) or a weak the structure and stereochemistry by single-crystal X-ray
NOE (in 5b) between H-6 and H-7α (Table 4, Entry 1). We analysis of analog 8b (Figure 2). For instance, a dihedral
observed no NOE between H-7β and H-7a for either 4b or angle of 168.6° for C1–C7a–C3a–C4 in 8b confirmed that
5b (Table 4, Entry 5).
the five-membered ring was exo-fused to the oxanorbor-
After establishing that the newly formed ring was exo- nene, and a dihedral angle of 24.6° for O8–C3a–C3–C9
fused to the oxanorbornene framework, we addressed the confirmed the pseudo-equatorial orientation of the substit-
1
stereochemistry at position 3. The analysis of the H and uent at C-3 (numbering as in 4b,5b, Table 4).
1H-1H COSY NMR spectra did not divulge much infor-
Unlike in the case of tetrahydrothiophenes 4,5 and cyclo-
mation due to (i) the small difference in the coupling of H- pentanes 8,9, we could not independently analyze the
3 with the H-9 and H-9Ј protons (Table 4, Entries 9 and 10) stereochemistry at C-3 in pyrrolidines 12,13 (see Table 3) by
and (ii) the absence of any other couplings for H-3. How- 2D-NMR experiments or X-ray crystallography. Whereas
ever, weak and medium NOEs for H-4 with H-9 and H-9Ј, the 2D-NOESY spectra of 12d,e and 13d,e showed no char-
respectively, in 5b suggested that the benzoyl group was α- acteristic NOEs, all these samples were liquids, and
oriented in 5b (Table 4, Entries 12 and 13). This was further attempts to prepare solid derivatives suitable for single-crys-
supported by the absence of any NOE for H-4 with H-9 or tal X-ray analysis were unsuccessful. Finally, a careful
1
H-9Ј in 4b, which was indicative of the β-orientation of the analysis of the H NMR chemical shifts of H-3 in exo-cis
Eur. J. Org. Chem. 2008, 6106–6118
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B. Ganguly, I. N. N. Namboothiri et al.
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cult. Therefore, we unambiguously established the structure
and stereochemistry of one representative compound (8e)
by single-crystal X-ray analysis (Figure 4). Whereas a dihe-
dral angle of 174.5° for C5–C4a–C8a–C1 confirmed that
the six-membered ring is exo-fused to the oxanorbornene,
a dihedral angle of 61.4° for O9–C4a–C4–C10 confirmed
the equatorial orientation of the substituent at C-4 in 8e.
Figure 3. Stereochemistry of 8d,e and 9d,e.
Figure 2. Single-crystal X-ray structure of 8b.
isomers 4 and 8 and exo-trans isomers 5 and 9 suggested
that H-3 is considerably deshielded in exo-cis isomers as
compared to exo-trans isomers (Table 5, Entries 1–6). We
extended this key feature to the stereochemical analysis of
12d,e and 13d,e. Thus, since H-3 was deshielded in the
minor products 12d,e (Table 5, Entries 7 and 8), we assigned
the exo-cis stereochemistry to 12d,e. We further corrobo-
rated this assignment with results from high-level quantum
chemical calculations (vide infra), which predicted the pref-
erence for exo-trans isomer 13 over exo-cis isomer 12 in the
case of pyrrolidines 12,13.
Table 5. Comparison of the 1H NMR chemical shifts of H-3 in
tetrahydrothiphenes 4,5, cyclopentanes 8,9 and pyrrolidines 12,13.
Entry
X
E
δ of H-3 signal [ppm]
Figure 4. Single-crystal X-ray structure of 8e.
exo-cis-
exo-trans-
1
2
3
4
5
6
7
8
S
S
S
CH2COCH3
CH2COPh
CH(COCH3)2
4a: 4.22
4b: 4.45
4c: 4.50
8a: 3.90
8b: 4.00
8c: 3.90
5a: 3.97
5b: 4.20
5c: –
9a: 3.45
9b: 3.47–3.67
9c: 3.43
Computational Results
C(CO2Et)2 CH2COCH3
In order to probe the selectivities observed during the
intramolecular cycloadditions, we examined computation-
ally the formation of all the cycloadducts 18–21 by path A
(Figure 1 and Scheme 3) for X = S, N-allyl and C(CO2-
Me)2.[12,13] We performed the calculations with E =
C(CO2Et)2
C(CO2Et)2
N-allyl
CH2COPh
CH2CO2Et
CH2CO2Et
CH(CO2Et)2
12d: 3.64 13d: 3.27–3.30
12e: 3.64 13e: 3.22–3.29
N-allyl
The structural and stereochemical assignment of 8d, 8e CH2CHO in this study for simplicity. We calculated the rel-
and 9e were complicated by the overlapping peaks in their ative energies of the four possible reaction products (18–21)
1H NMR spectra. For instance, since the H-1a, H-1e, H-2a, and their transition states at the RHF/3-21G*[14] and
H-2e, H-8α, H-8β protons (Figure 3) appeared in the nar- B3LYP/6-31G*//RHF/3-21G*[15]
levels
of
theory
row range of δ = 1.30–1.90 ppm, we could not indepen- (Scheme 3). The calculated results, summarized in Table 6,
dently assign the stereochemistry of ring fusion between the clearly show that exo isomers 18,19 were preferred over
oxanorbornene framework and the six-membered ring. The endo isomers 20,21 in all cases. The relative energies of
absence of any appreciable scalar coupling or NOE interac- products 18–21 predict the formation of exo-cis isomers 18
tion for H-4 with protons other than H-10 and H-10Ј also for X = S and C(CO2Me)2 at both levels of theory (Table 6,
made the stereochemical assignment at C-4 extremely diffi- Entries 1–3, 8 and 9). In order to examine the effect of dif-
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Synthetic and Theoretical Investigations on Oxanorbornenes
Scheme 3.
Table 6. RHF/3-21G*- and B3LYP/6-31G*//RHF/3-21G*-calculated relative energies of the products 18–21 and their transition states in
kcalmol–1.
Entry
X
E
Theory
level
Product
Transition state
exo-cis-18 exo-trans-19 endo-cis-20 endo-trans-21 exo-cis exo-trans endo-cis endo-trans
1
2
3
4
5
6
7
8
9
S
CH2CHO RHF[a]
0.0
0.0
0.0
0.0
1.3
3.3
4.6
0.0
0.0
5.6
2.9
3.0
0.8
0.0
0.0
0.0
2.3
1.3
15.4
11.5
12.1
14.0
13.5
19.3
18.1
11.0
9.9
11.4
8.6
8.5
13.7
14.6
16.4
16.1
12.3
10.9
0.0
0.0
0.0
2.8
5.1
3.8
6.5
0.0
1.6
3.0
0.9
1.1
0.0
0.0
0.0
0.0
1.0
0.0
10.6
8.9
9.7
12.9
11.5
16.4
16.0
7.0
7.7
6.4
6.7
7.3
8.4
11.4
13.3
9.5
B/R[b]
B3[c]
N-allyl CH2CHO RHF
B/R
RHF
B/R
[d]
CHZ2
[d]
CZ2
CH2CHO RHF
B/R
8.9
9.7
[a] Relative energies at the RHF/3-21G* level. [b] Relative energies at the B3LYP/6-31G* level. [c] B3LYP/6-31+G*-optimized relative
energies. [d] Z = CO2Me.
fuse functions, when a heteroatom such as S is present in tion energies calculated for these IMDAF reactions were
the system, we performed calculations at the B3LYP/6- exergonic for the exo products; however, endo products were
31+G* level for X = S (Table 6, Entry 3). The calculated generally endergonic (Table 7). The transition state geome-
relative energy differences for transition state and ground tries for the exo and endo isomers indicated a concerted
state geometries were similar to results obtained at the reaction mechanism; however, the extent of bond formation
RHF/3-21G* and B3LYP/6-31G**//RHF/3-21G* levels. was slightly asymmetrical (Table S1).
Since the larger and smaller basis sets gave similar results,
this justified the general use of the smaller basis set.
Table 7. RHF/3-21G*- and B3LYP/6-31G*//RHF/3-21G*-calcu-
lated reaction energies of various IMDAF reactions in kcalmol–1.
Unlike in the case of X = S and C(CO2Me)2, where the
exo-cis isomer 18 was predicted and experimentally ob-
served as the major product (Table 6, Entries 1–3, 8 and 9),
our calculations favored the exo-trans isomer 19 for X =
N-allyl at the B3LYP/6-31G* level (Table 6, Entry 5). To
examine the discrepancy between the results for 19 from the
two methods, we performed additional calculations with E
= CH(CO2Me)2 (Table 6, Entries 6 and 7). The calculated
results show that the exo-trans configuration was preferred
over the exo-cis configuration at both levels of theory. Ex-
tending the study to transition state energy calculations, the
results show that the formation of exo-cis isomers 18 was
favored when X = S and C(CO2Me)2 (Table 6, Entries 1–3,
8 and 9), whereas the exo-trans isomer 19 was favored for
Entry
X
E
Theory
Reaction energy
level exo-cis exo-trans endo-cis endo-trans
1
2
3
4
5
6
7
8
S
CH2CHO RHF[a] –16.5
–10.9
–0.5
–11.4
–3.5
–16.5
–5.4
–13.3
–3.2
–1.2
+8.2
+1.8
+10.0
+2.8
+12.7
–4.6
–5.1
+5.2
+1.5
+11.1
–0.1
+8.8
–3.3
+6.5
B/R[b]
–3.4
–12.2
–2.2
–13.2
–0.8
N-allyl CH2CHO RHF
B/R
RHF
B/R
[c]
CHZ2
[c]
CZ2
CH2CHO RHF
B/R
–15.6
–4.4
+5.5
[a] Reaction energies at the RHF/3-21G* level. [b] Reaction ener-
gies at the B3LYP/6-31G* level. [c] Z = CO2Me.
The activation energies are higher for these IMDAF reac-
X = N-allyl (Table 6, Entry 4–7). However, the B3LYP/6- tions. For the preferred exo-cis isomer (X = S), the acti-
31G*//RHF/3-21G* result for X = C(CO2Me)2 showed the vation energy calculated at the B3LYP/6-31+G* level was
preferential formation of the exo-trans transition state. The 28.9 kcalmol–1. The incorporation of activation entropy at
formation of the major exo-cis isomers for X = S, C(CO2- 110 °C enhanced the activation free energy to
Me)2 and exo-trans for N-allyl agreed well with the experi- 34.4 kcalmol–1. These results suggest that the negative acti-
mentally observed products (Tables 1, 2, and 3). The reac- vation entropy (–14.3 eu) was much lower in this case,
Eur. J. Org. Chem. 2008, 6106–6118
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6111

B. Ganguly, I. N. N. Namboothiri et al.
FULL PAPER
which led to the formation of the 7-oxanorbornene ring. In staggered than τ2 (17.6°) in the case of X = S (Figure 6).
comparison, for the intermolecular DA reaction of butadi- However, the values were reversed for X = N-allyl, as τ1 =
ene and ethylene, the calculated activation entropy was 29.4ο and τ2 = 32.4ο, respectively (Figure 6).
–40.6 eu, and the activation free energy at the experimental
temperature of 165 °C was 42.6 kcalmol–1.[7] The large acti-
vation free energy for butadiene and ethylene is due to the
large activation entropy associated with this reaction.
The calculated results suggest that the formation of exo
isomers was both thermodynamically and kinetically pre-
ferred over that of the endo isomers. Therefore, even if there
was a retro-Diels–Alder reaction, one can envisage that the
products formed would be as predicted and observed. The
Figure 6. exo products for X = S and N-allyl.
formation of the exo isomer as the major product from the
IMDAF reaction appeared to result from the difference in
strain induced in the ring systems. To examine this, we took
Conclusions
the stable exo-cis-18 and endo-trans-21 isomers for X = S
as model systems (Table 6, Entry 1). The 7-oxanorbornene
rings formed in these isomers were isolated from the calcu-
lated geometries. Substituents were replaced by hydrogen
atoms without perturbing the geometry of the 7-oxanor-
bornane rings (Figure 5). The energies calculated for the 7-
oxanorbornene rings derived from the X = S product, and
transition state geometries suggest that the newly formed
norbornene ring in the exo isomer was much more stable
than that in the endo form at both the RHF/3-21G* and
B3LYP/6-31+G* levels of theory (Table 8). It appears that
ring strain contributed predominantly towards the forma-
tion of the exo isomers in these cases.
The synthesis of oxanorbornenes fused to five- and six-
membered carbocycles and heterocycles was carried out in
good yield and high stereoselectivity from readily available
β-furyl enones, an enedione and an acrylate. The protocol
involved the Michael addition of nucleophiles possessing an
unsaturated tether to the β-furyl α,β-unsaturated carbonyl
compounds followed by an intramolecular Diels–Alder re-
action between the furan diene and the olefinic moiety. We
rationalized the high stereoselectivity observed in these cy-
cloadditions through quantum chemical calculations. These
calculations revealed that the exo-fused cycloadduct was ki-
netically and thermodynamically favored over its endo-
fused isomer due to the difference in the strain for the for-
mation of 7-oxanorbornene rings in the transition states
and products. The dependence of the cis or trans stereo-
chemistry upon different substituents in the isomers arose
from a torsional effect.
Figure 5. 7-Oxanorbornene ring.
Experimental Section
General: Melting points were recorded with a Thermonik melting
point apparatus and are uncorrected. IR spectra were recorded
with an Impact 400/Nicolet or Perkin–Elmer Spectrum One FT
spectrometer. NMR spectra (1H, 13C, 1H-1H COSY and 1H-1H
NOESY) were recorded with TMS as the internal standard with
an AMX-400 (Varian Mercury Plus OXFORD, broad band, auto
switchable and inverse probe) or VXR-300S spectrometer. The
coupling constants (J values) are given in Hz. Mass spectra (low
and high resolution) were recorded at 60–70 eV with a Micromass
Q-TOF mass spectrometer under ESI mode. X-ray data were col-
lected with a Nonius MACH 3 diffractometer equipped with
graphite-monochromated Mo-Kα radiation. The structures were
solved by direct methods with SHELXS97 and refined by full-ma-
trix least-squares against F2 with SHELXL97 software. CCDC-
693540 (for 8b) and -693541 (for 8e) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif. Michael acceptors 1a–e
Table 8. RHF/3-21G*- and B3LYP/6-31+G*-calculated energy dif-
ferences [kcalmol–1] for 7-oxanorbornene rings derived from 18
and 21 (X = S) and transition state geometries.
Entry Configuration Theory level Product Transition state
1
2
3
4
exo-cis
RHF[a]
B/R[b]
RHF
B/R
0.0
0.0
6.6
5.9
0.0
0.0
4.3
3.9
endo-trans
[a] Relative energies at the RHF/3-21G* level. [b] Relative energies
at the B3LYP/6-31+G* level.
Further, we found the subtle difference in the stereo-
chemistry of the products with X = S, CO2Me versus those
with X = N-allyl interesting. Whereas the Michael adducts
with X = S and CO2Me provided exo-cis isomers, those
with X = N-allyl gave exo-trans isomers. The difference in
the stereochemistry presumably arose from the torsional ef- were prepared according to literature methods.[9–11]
fect in these systems.[16] Examining the torsion angles in the
Computational Methodology: All calculations were performed at
the RHF/3-21G* level of theory with the JAGUAR program.[12]
Complete vibrational analyses were performed to characterize the
ground state geometries of the exo-cis isomer (τ1 = O1–C2–
C3–C6) and of the exo-trans isomer (τ2 = O1–C2–C3–H7)
for X = S and N-allyl suggested that τ1 (29.5°) was more transition state and ground state geometries. In addition, single
6112 Eur. J. Org. Chem. 2008, 6106–6118
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthetic and Theoretical Investigations on Oxanorbornenes
point B3LYP/6-31G* calculations[13] with RHF/3-21G*-optimized
geometries were performed to estimate the energies of the transi-
tion states and ground states of these IMDAF reactions. To exam-
ine the basis set dependence on the energetics of the transition
states and ground states, the S-substituted derivative (X = S) was
optimized with the 6-31+G* basis set at the B3LYP level.
General Procedure for the Michael Addition of Diethyl Allylmalon-
ate (6a) and Diethyl Homoallylmalonate (6b) to Enones 1a,b and
Acrylate 1d: To a stirred mixture of 1a, 1b or 1d (1 mmol) and
diethyl allylmalonate (6a, 600 mg, 3 mmol) or diethyl homoallylma-
lonate (6b, 642 mg, 3 mmol) was added benzyltriethylammonium
chloride (TEBAC, 14 mg, 0.06 mmol) followed by powdered KOH
(3.3 mg, 0.06 mmol). The mixture was stirred until the reaction was
complete (as monitored by TLC, see also Table 2) and filtered. The
filtrate was concentrated in vacuo. The crude mixture was then
purified by silica gel chromatography with ethyl acetate/n-hexane
(1:10 to 1:5) as the eluent to afford pure 7a–f.
General Procedure for the Michael Addition of Allylmercaptan (2)
to 2-Furyl Enones 1a–c: To a stirred solution of allylmercaptan (2,
0.62 mL, 1.1 mmol) in THF (5 mL) at 0 °C under nitrogen was
added Et3N (0.01 mL, 0.1 mmol) followed by a solution of 1a, 1b
or 1c (1 mmol) in THF (5 mL). After the addition was complete,
the reaction mixture was stirred at reflux for 24 h. The reaction
mixture was then diluted with water (5 mL) and acidified with HCl
(10%, 10 mL). The aqueous layer was extracted with ethyl acetate
(3ϫ15 mL). The combined organic layers were then washed with
brine (20 mL), dried with anhydrous Na2SO4 and concentrated in
vacuo. The crude residue was then purified by silica gel chromatog-
raphy with ethyl acetate/n-hexane (1:50 to 1:25) as the eluent to
afford pure 3a, 3b or 3c.
Diethyl 2-Allyl-2-[1-(furan-2-yl)-3-oxobutyl]malonate (7a): Light
yellow oil. Yield 82% (275 mg). IR (neat): ν = 3055 (w), 2985 (m),
˜
1
1724 (s), 1266 (s) cm–1. H NMR (400 MHz, CDCl3): δ = 1.24 (t,
J = 7.3 Hz, 3 H), 1.29 (t, J = 7.3 Hz, 3 H), 2.06 (s, 3 H), 2.53
(ABqd, J = 14.7, 7.3 Hz, 2 H), 3.00 (dd, J = 17.4, 2.8 Hz, 1 H),
3.14 (dd, J = 17.4, 10.5 Hz, 1 H), 4.08 (dd, J = 10.5, 2.8 Hz, 1 H),
4.11–4.27 (m, 4 H), 5.05–5.09 (m, 2 H), 5.71–5.82 (m, 1 H), 6.12
(d, J = 2.9 Hz, 1 H), 6.25 (dd, J = 2.9, 1.8 Hz, 1 H), 7.27 (d, J =
1.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.7, 13.8,
29.7, 37.4, 38.2, 44.4, 60.4, 61.1 (2 C), 108.3, 110.0, 118.7, 132.5,
141.4, 152.4, 169.5, 169.8, 205.6 ppm. MS (ESI, Ar): m/z (%) = 359
(100) [M + Na]+. HRMS (ESI, Ar): calcd. for C18H24O6Na [M +
Na]+ 359.1471; found 359.1475.
4-(Allylthio)-4-(furan-2-yl)butan-2-one (3a): Light yellow oil. Yield
64% (135 mg). IR (neat): ν = 2917 (w), 1721 (s), 1361 (m), 1151
˜
(m) cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.15 (s, 3 H), 3.04
(ABqd, J = 17.1, 6.8 Hz, 2 H), 3.01–3.10 (m, 2 H), 4.38 (t, J =
7.3 Hz, 1 H), 5.10–5.17 (m, 2 H), 5.70–5.84 (m, 1 H), 6.17 (d, J =
3.4 Hz, 1 H), 6.30 (dd, J = 3.4, 2.0 Hz, 1 H), 7.35 (d, J = 2.0 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 30.5, 34.4, 36.1, 47.0,
107.1, 110.3, 117.6, 134.0, 142.1, 153.5, 205.1 ppm. MS (ESI, Ar):
Diethyl
2-Allyl-2-[1-(furan-2-yl)-3-oxo-3-phenylpropyl]malonate
(7b): Colorless oil. Yield 77% (307 mg). IR (neat): ν = 3058 (w),
˜
1
2984 (w), 1728 (s), 1688 (m), 1266 (s) cm–1. H NMR (300 MHz,
m/z (%) = 233 (100) [M + Na]+. HRMS (ESI, Ar): calcd. for CDCl3): δ = 1.23 (t, J = 7.0 Hz, 3 H), 1.33 (t, J = 7.0 Hz, 3 H),
C11H14O2NaS [M + Na]+ 233.0612; found 233.0619.
2.59 (ABqd, J = 14.4, 7.2 Hz, 2 H), 3.53 (dd, J = 17.6, 2.3 Hz, 1
H), 3.78 (dd, J = 17.6, 10.5 Hz, 1 H), 4.14–4.20 (m, 1 H), 4.22–
4.38 (m, 4 H), 5.11 (m, 2 H), 5.81 (m, 1 H), 6.14 (d, J = 3.0 Hz, 1
H), 6.22 (dd, J = 3.0, 1.4 Hz, 1 H), 7.25 (d, J = 1.4 Hz, 1 H). 7.40–
7.60 (m, 3 H), 7.92–7.94 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.2 (2 C), 38.0, 38.7, 40.1, 61.0, 61.5 (2 C), 108.7,
110.2, 119.0, 128.1, 128.6, 133.0 (ϫ2), 136.9, 141.7, 152.7, 170.1,
170.2, 197.5 ppm. MS (ESI, Ar): m/z (%) = 421 (72) [M +
Na]+, 199 (62). HRMS (ESI, Ar): calcd. for C23H26O6Na [M +
Na]+ 421.1627; found 421.1622.
3-(Allylthio)-3-(furan-2-yl)-1-phenylpropan-1-one (3b): Light yellow
oil. Yield 63% (172 mg). IR (neat): ν = 2912 (w), 1688 (s), 1448
˜
(w), 1353 (w), 1229 (w) cm–1. 1H NMR (300 MHz, CDCl3): δ =
3.09–3.13 (unresolved m, 2 H), 3.60 (ABqd, J = 17.2, 6.6 Hz, 2 H),
4.61 (dd, J = 7.7, 6.6 Hz, 1 H), 5.08–5.17 (m, 2 H), 5.70–5.84 (m,
1 H), 6.20 (d, J = 3.3 Hz, 1 H), 6.27 (dd, J = 3.3, 1.8 Hz, 1 H),
7.33 (d, J = 1.8 Hz, 1 H), 7.41–7.95 (m, 5 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 34.4, 36.3, 42.3, 107.0, 110.2, 117.5, 128.1,
128.6, 133.3, 134.0, 136.5, 142.0, 153.7, 196.3 ppm. MS (ESI, Ar):
m/z (%) = 295 (100) [M + Na]+, 105 (12). HRMS (ESI, Ar): calcd.
for C16H16O2NaS [M + Na]+ 295.0769; found 295.0756.
Triethyl 2-(Furan-2-yl)hex-5-ene-1,3,3-tricarboxylate (7c): Light yel-
low oil. Yield 38% (139 mg). IR (neat): ν = 3079 (m), 2984 (s),
˜
1
2939 (s), 2907 (m), 1729 (br., s), 1445 (s), 1266 (s) cm–1. H NMR
3-[(Allylthio)(furan-2-yl)methyl]pentane-2,4-dione (3c): Light yellow
(300 MHz, CDCl3): δ = 1.15 (t, J = 7.3 Hz, 3 H), 1.25 (t, J =
7.3 Hz, 3 H), 1.30 (t, J = 7.3 Hz, 3 H), 2.52 (dd, J = 14.3, 7.7 Hz,
the low-field half is further split into t, J = 1.3 Hz, 2 H), 2.93–2.99
(m, 2 H), 3.98–4.02 (m, 1 H), 4.03 (q, J = 7.3 Hz, 2 H), 4.17 (q, J
= 7.3 Hz, 2 H), 4.24 (q, J = 7.3 Hz, 2 H), 5.05–5.11 (m, 2 H), 5.70–
5.86 (m, 1 H), 6.14 (dd, J = 3.1, 0.7 Hz, 1 H), 6.26 (dd, J = 3.1,
1.8 Hz, 1 H), 7.29 (dd, J = 1.8, 0.7 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 13.9 (2 C), 14.0, 35.8, 38.4, 38.6, 60.2, 60.5,
61.2, 61.3, 108.4, 110.0, 118.8, 132.6, 141.7, 152.2, 169.4, 169.7,
171.5 ppm. MS (ESI, Ar): m/z (%) = 367 (2) [M + H]+, 321 (100),
303 (80), 275 (12), 229 (38), 167 (60). HRMS (ESI, Ar): calcd. for
C19H27O7 [M + H]+ 367.1757; found 367.1771.
oil. Yield 59% (149 mg). IR (neat): ν = 3055 (m), 2984 (m), 2922
˜
(m), 1734 (s), 1703 (s), 1423 (m), 1358 (m), 1266 (s), 740 (s) cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.03 (s, 3 H, keto form), 2.17 (s,
6 H, enol form), 2.31 (s, 3 H, keto form), 2.98–3.14 (m, 2 H, keto
form), 3.20–3.30 (m, 2 H, enol form), 4.47 (ABq, J = 12.0 Hz, 2
H, keto form), 4.93 (s, 1 H, enol form), 5.08–5.22 (m, 2 H, keto
and enol forms), 5.66–5.82 (m, 1 H, keto form), 5.83–5.96 (m, 1 H,
enol form), 6.18 (d, J = 3.7 Hz, 1 H, keto form), 6.27–6.29 (m, 1
H, enol form), 6.30 (dd, J = 3.7, 2.0 Hz, 1 H, keto form), 6.34 (dd,
J = 3.7, 2.0 Hz, 1 H, enol form), 7.35–7.36 (m, 1 H, keto and enol
forms), 17.28 (br. s, 1 H, enol form) ppm. 13C NMR (100 MHz,
CDCl3): δ = 29.3 (q, keto form), 34.2 (t, keto form), 39.9 (d, keto
form), 71.4 (d, keto form), 108.2 (d, keto form), 110.4 (d, keto
Diethyl 2-(But-3-enyl)-2-[1-(furan-2-yl)-3-oxobutyl]malonate (7d):
form), 118.1 (t, keto form), 133.3 (d, keto form), 142.4 (d, keto Light yellow oil. Yield 75% (263 mg). IR (neat): ν = 2982 (w), 1728
˜
form), 151.3 (s, keto form), 200.7 (s, keto form), 29.2 (q, enol form),
35.3 (t, enol form), 38.8 (d, enol form), 107.6 (d, enol form), 110.1
(s, enol form), 110.5 (d, enol form), 118.0 (t, enol form), 134.0 (d,
enol form), 142.1 (d, enol form), 153.7 (s, enol form), 200.9 (s, enol
form) ppm. MS (ESI, Ar): m/z (%) = 275 (55) [M + Na]+, 227
(s), 1365 (w), 1228 (w) cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.26
(t, J = 7.1 Hz, 3 H), 1.29 (t, J = 7.1 Hz, 3 H), 1.68–1.79 (m, 1 H),
1.88–2.02 (m, 2 H), 2.07 (s, 3 H), 2.09–2.16 (m, 1 H), 2.97 (dd, J
= 17.4, 2.7 Hz, 1 H), 3.14 (dd, J = 17.4, 10.5 Hz, 1 H), 4.10 (dd, J
= 10.5, 2.7 Hz, 1 H), 4.16–4.27 (m, 4 H), 4.93–5.02 (m, 2 H), 5.68–
(100), 153 (15). HRMS (ESI, Ar): calcd. for C13H16O3NaS [M + 5.78 (m, 1 H), 6.12 (d, J = 3.2 Hz, 1 H), 6.25 (dd, J = 3.2, 1.8 Hz,
Na]+ 275.0718; found 275.0709.
1 H), 7.26 (d, J = 1.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
Eur. J. Org. Chem. 2008, 6106–6118
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6113

B. Ganguly, I. N. N. Namboothiri et al.
FULL PAPER
δ = 14.2 (2 C), 29.0, 30.2, 33.3, 37.9, 44.8, 60.5, 61.4, 61.6, 108.5,
110.4, 115.1, 137.7, 141.7, 152.8, 170.2, 170.6, 206.2 ppm. MS (ESI,
Ar): m/z (%) = 373 (100) [M + Na]+, 137 (10). HRMS (ESI, Ar):
calcd. for C19H26O6Na [M + Na]+ 373.1627; found 373.1620.
97 (15). HRMS (ESI, Ar): calcd. for C15H22NO3 [M + H]+
264.1600; found 264.1593.
Diallyl 2-[1-(Furan-2-yl)-3-oxobutyl]malonate (15): To a stirred mix-
ture of 1a (136 mg, 1 mmol) and diallyl malonate (14, 276 mg,
1.5 mmol) in THF (10 mL) was added DBU (0.075 mL, 76 mg,
0.5 mmol). The reaction mixture was stirred for 6 h. The reaction
mixture was then diluted with water and acidified with HCl (10%,
10 mL). The aqueous layer was extracted with ethyl acetate
(3ϫ15 mL). The combined organic layers were then washed with
brine (15 mL), dried with anhydrous Na2SO4 and concentrated in
vacuo. The crude residue was then purified by silica gel chromatog-
raphy with ethyl acetate/n-hexane (1:20) as the eluent to afford pure
Diethyl 2-(But-3-enyl)-2-[1-(furan-2-yl)-3-oxo-3-phenylpropyl]mal-
onate (7e): Light yellow oil. Yield 69% (285 mg). IR (neat): ν =
˜
2981 (s), 1732 (s), 1693 (m), 1449 (m), 1015 (m) cm–1. 1H NMR
(300 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 3 H), 1.33 (t, J =
7.1 Hz, 3 H), 1.77–1.82 (m, 1 H), 1.95–2.05 (m, 2 H), 2.10–2.17 (m,
1 H), 3.50 (dd, J = 17.4, 2.5 Hz, 1 H), 3.76 (dd, J = 17.4, 11.0 Hz,
1 H), 4.10 (dd, J = 11.0, 2.5 Hz, 1 H), 4.18–4.35 (m, 4 H), 4.93
(dd, J = 10.1, 1.8 Hz, 1 H), 5.02 (dd, J = 17.0, 1.8 Hz, 1 H), 5.70–
5.80 (m, 1 H), 6.13 (d, J = 3.2 Hz, 1 H), 6.22 (dd, J = 3.2, 1.8 Hz,
1 H), 7.24 (d, J = 1.8 Hz, 1 H), 7.41–7.45 (m, 2 H), 7.51–7.55 (m,
1 H), 7.93–7.95 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
14.0 (2 C), 28.8, 33.3, 37.9, 39.9, 60.5, 61.2, 61.4, 108.3, 110.1,
114.9, 128.0, 128.4, 132.9, 136.8, 137.5, 141.5, 152.6, 170.2, 170.6,
197.5 ppm. MS (ESI, Ar): m/z (%) = 435 (9) [M + Na]+, 199 (100).
HRMS (ESI, Ar): calcd. for C24H28O6Na [M + Na]+ 435.1784;
found 435.1804.
15. Light yellow oil. Yield 72% (232 mg). IR (neat): ν = 3058 (m),
˜
2988 (m), 2950 (m), 1733 (s), 1267 (s), 1153 (s) cm–1. 1H NMR
(400 MHz, CDCl3): δ = 2.11 (s, 3 H), 2.98 (ABq, J = 17.2, high-
field half and low-field half were further split into d, J = 5.1 and
8.4 Hz, respectively, 2 H), 3.87 (d, J = 7.7 Hz, 1 H), 4.13 (ddd, J =
8.4, 7.7, 5.1 Hz, 1 H), 4.53 (dt, J = 5.9, 1.5 Hz, 2 H), 4.62 (dt, J =
5.9, 1.5 Hz, 2 H), 5.18–5.33 (m, 4 H), 5.73–5.93 (m, 2 H), 6.11 (dd,
J = 3.3, 0.7 Hz, 1 H), 6.25 (dd, J = 3.3, 1.8 Hz, 1 H), 7.28 (dd, J
= 1.8, 0.7 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 30.1,
34.0, 44.4, 54.9, 66.2 (2 C), 107.1, 110.3, 118.8 (2 C), 131.4 (2 C),
141.7, 153.4, 167.3, 167.5, 205.7 ppm. MS (ESI, Ar): m/z (%) = 343
(100) [M + Na]+, 263 (4), 205 (6). HRMS (ESI, Ar): calcd. for
C17H20O6Na [M + Na]+ 343.1158; found 343.1158.
Triethyl 2-(Furan-2-yl)hept-6-ene-1,3,3-tricarboxylate (7f): Light
yellow oil. Yield 45% (172 mg). IR (neat): ν = 2982 (w), 1732 (s),
˜
1021 (w) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.15 (t, J =
7.1 Hz, 3 H), 1.26 (t, J = 7.1 Hz, 3 H), 1.29 (t, J = 7.1 Hz, 3 H),
1.67–2.14 (m, 6 H), 2.92–2.94 (m, 1 H), 4.04 (q, J = 7.1 Hz, 2 H),
4.22 (two overlapped ABq, J = 7.1 Hz, 4 H), 4.93–5.02 (m, 2 H),
5.68–5.78 (m, 1 H), 6.13 (d, J = 3.2 Hz, 1 H), 6.27 (dd, J = 3.2,
1.8 Hz, 1 H), 7.29 (d, J = 1.8 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.2 (2 C), 14.3, 29.0, 33.5, 36.2, 39.3, 60.5, 60.6, 61.5,
61.6, 108.5, 110.3, 115.1, 137.7, 141.9, 152.6, 170.0, 170.6, 172.0
ppm. MS (ESI, Ar): m/z (%) = 403 (100) [M + Na]+. HRMS (ESI,
Ar): calcd. for C20H28O7Na [M + Na]+ 403.1733; found 403.1741.
General Procedure for the IMDAF Reaction of Michael Adducts 3,
7 and 11: A solution of the Michael adduct 3, 7 or 11 (1 mmol) in
dry toluene or xylene (10 mL) was refluxed for the specified time
(see Tables 1, 2, and 3). The reaction mixture was then cooled to
room temperature and concentrated in vacuo. The crude residue
was purified, and the two isomers, if any, were separated by silica
gel column chromatography with ethyl acetate/n-hexane (1:10 to
1:5) as the eluent.
General Procedure for the Michael Addition of Diallylamine (10)
to Acrylates 1d,e: To a stirred mixture of diallylamine (10, 97 mg,
1 mmol) in THF (5 mL) at –78 °C under nitrogen was added nBuLi
(0.63 mL, 1.6  solution in hexanes, 1 mmol) dropwise over 20 min.
After the addition was complete, the reaction mixture was brought
slowly to 0 °C and stirred for another 30 min at the same tempera-
ture. The reaction mixture was cooled to –78 °C, and a solution of
1d (166 mg, 1 mmol) or 1e (238 mg, 1 mmol) in THF (5 mL) was
added dropwise to the reaction mixture. After the addition was
complete, the reaction mixture was stirred at –78 °C for another
4 h. The reaction mixture was then quenched with saturated aque-
ous NH4Cl. The aqueous layer was extracted with ethyl acetate
(3ϫ15 mL). The combined organic layers were then washed with
brine (20 mL), dried with anhydrous Na2SO4 and concentrated in
vacuo. The crude residue was then purified by silica gel chromatog-
raphy with ethyl acetate/n-hexane (1:25) as the eluent to afford pure
11d or 11e.
Compounds 4a and 5a
4a: Colorless solid. Yield 58% (122 mg). M.p. 62 °C. Rf = 0.32
(EtOAc/n-hexane, 1:4). IR (KBr): ν = 3012 (m), 2937 (m), 2873
˜
(m), 1712 (s), 1384 (s), 1312 (m), 1164 (m) cm–1. 1H NMR
(300 MHz, CDCl3): δ = 1.51 (dd, J = 11.7, 7.3 Hz, 1 H), 1.79 (ddd,
J = 11.7, 4.8, 2.6 Hz, 1 H), 2.15 (s, 3 H), 2.31 (dddd, J = 10.4, 7.7,
7.3, 2.6 Hz, 1 H), 2.75 (dd collapsed to t, J = 10.4 Hz, 1 H), 2.85
(dd, J = 18.3, 8.8 Hz, 1 H), 3.01 (dd, J = 10.4, 7.7 Hz, 1 H), 3.08
(dd, J = 18.3, 5.2 Hz, 1 H), 4.22 (unresolved dd, J = 8.8, 5.2 Hz, 1
H), 5.03 (dd, J = 4.8, 1.5 Hz, 1 H), 6.30 (d, J = 5.8 Hz, 1 H), 6.40
(dd, J = 5.8, 1.5 Hz, 1 H) ppm. These data were confirmed by a
1H-1H COSY experiment (see also Table S2). 13C NMR (75 MHz,
CDCl3): δ = 30.1, 34.7, 36.6, 41.0, 46.4, 48.2, 79.7, 100.4, 136.0,
137.5, 206.9 ppm. MS (ESI, Ar): m/z (%) = 233 (82) [M + Na]+,
193 (98), 151 (100), 135 (22). HRMS (ESI, Ar): calcd. for
C11H14O2NaS [M + Na]+ 233.0612; found 233.0617.
Ethyl 3-(Diallylamino)-3-(furan-2-yl)propanoate (11d): Light yellow
5a: Light yellow oil. Yield 9% (19 mg). Rf = 0.23 (EtOAc/n-hexane,
oil. Yield 79% (209 mg). IR (neat): ν = 3078 (w), 2980 (s), 2938
1:4). IR (neat): ν = 2924 (s), 2855 (m), 1709 (s), 1368 (m), 1321
˜
˜
(m), 2816 (m), 1738 (s), 1288 (m), 1165 (s) cm–1. 1H NMR
(400 MHz, CDCl3): δ = 1.24 (t, J = 7.3 Hz, 3 H), 2.76–2.80 (m, 2
H), 2.81 (ABq, J = 14.7, high-field half and low-field half were
further split into d, J = 6.9 and 8.7 Hz, respectively, 1 H), 2.90 (dd,
J = 14.7, 8.7 Hz, 1 H), 3.24–3.29 (m, 2 H), 4.09–4.16 (m, 2 H), 4.45
(t, J = 7.8 Hz, 1 H), 5.10–5.19 (m, 4 H), 5.71–5.81 (m, 2 H), 6.13
(m), 1167 (m) cm–1. H NMR (300 MHz, CDCl3): δ = 1.51 (dd, J
1
= 11.3, 7.3 Hz, 1 H), 1.77 (ddd, J = 11.3, 4.4, 2.6 Hz, 1 H), 2.23
(s, 3 H), 2.29 (dddd, J = 11.0, 7.7, 7.3, 2.6 Hz, 1 H), 2.73 (dd
collapsed to t, J = 11.0 Hz, 1 H), 2.86 (dd, J = 17.2, 9.9 Hz, 1 H),
3.05 (dd, J = 11.0, 7.7 Hz, 1 H), 3.13 (dd, J = 17.2, 5.1 Hz, 1 H),
3.97 (dd, J = 9.9, 5.1 Hz, 1 H), 5.04 (dd, J = 4.4, 1.6 Hz, 1 H), 6.28
(d, J = 3.0 Hz, 1 H), 6.32 (dd, J = 3.0, 1.8 Hz, 1 H), 7.37 (d, J = (d, J = 5.8 Hz, 1 H), 6.46 (dd, J = 5.8, 1.6 Hz, 1 H) ppm. These
1.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.9, 36.4,
data were confirmed by 1H-1H COSY experiment (see also
53.2 (2 C), 60.0, 107.4, 109.5, 116.6, 136.6, 141.5, 153.0, 170.8 ppm.
Table S3). 13C NMR (75 MHz, CDCl3): δ = 30.3, 34.5, 36.7, 42.2,
MS (ESI, Ar): m/z (%) = 264 (100) [M + H]+, 167 (22), 125 (15), 47.3, 49.6, 79.5, 101.8, 133.5, 138.1, 205.6 ppm. MS (ESI, Ar): m/z
6114
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6106–6118

Synthetic and Theoretical Investigations on Oxanorbornenes
(%) = 233 (100) [M + Na]+, 193 (12), 151 (70). HRMS (ESI, Ar):
calcd. for C11H14O2NaS [M + Na]+ 233.0612; found 233.0608.
J = 4.4, 1.8 Hz, 1 H), 6.16 (d, J = 5.9 Hz, 1 H), 6.40 (dd, J = 5.9,
1.8 Hz, 1 H) ppm. These data were confirmed by 1H-1H COSY
experiment (see also Table S7). 13C NMR (100 MHz, CDCl3): δ =
13.8 (2 C), 30.1, 33.0, 38.5, 39.4, 40.2, 40.9, 61.1, 61.5, 65.1, 79.3,
98.1, 134.2, 137.2, 169.7, 171.8, 206.3 ppm. MS (ESI, Ar): m/z (%)
= 359 (100) [M + Na]+, 273 (8), 189 (10), 159 (18). HRMS (ESI,
Ar): calcd. for C18H24O6Na [M + Na]+ 359.1471; found 359.1469.
Compounds 4b and 5b
4b: Colorless solid. Yield 51% (139 mg). M.p. 73 °C. Rf = 0.27
(EtOAc/n-hexane, 1:4). IR (KBr): ν = 3056 (w), 2938 (w), 1683 (s),
˜
1
1591 (m), 1321 (m), 1268 (m) cm–1. H NMR (300 MHz, CDCl3):
δ = 1.53 (dd, J = 11.7, 7.3 Hz, 1 H), 1.82 (ddd, J = 11.7, 4.4, 2.6 Hz,
1 H), 2.38 (dddd, J = 10.6, 7.7, 7.3, 2.6 Hz, 1 H), 2.78 (dd collapsed
to t, J = 10.6 Hz, 1 H), 3.07 (dd, J = 10.6, 7.7 Hz, 1 H), 3.51 (ABq,
J = 18.3 Hz, high-field and low-field halves were further split into
d, J = 8.8 and 4.8 Hz, respectively, 2 H), 4.45 (dd, J = 8.8, 4.8 Hz,
1 H), 5.06 (dd, J = 4.4, 1.6 Hz, 1 H), 6.39 (ABq, J = 5.9 Hz, the
low-field half was further split into d, J = 1.6 Hz, 2 H), 7.41–7.44
(m, 2 H), 7.46–7.58 (m, 1 H), 7.97–7.99 (m, 2 H) ppm. These data
were confirmed by 1H-1H COSY and NOESY experiments (see
also Table S4). 13C NMR (75 MHz, CDCl3): δ = 34.5, 36.5, 41.2,
41.9, 48.0, 79.5, 100.3, 127.9, 128.3, 132.9, 135.8, 136.2, 137.4,
197.8 ppm. MS (ESI, Ar): m/z (%) = 295 (100) [M + Na]+, 255
(28), 105 (25). HRMS (ESI, Ar): calcd. for C16H16O2NaS [M +
Na]+ 295.0769; found 295.0775.
9a: Light yellow oil. Yield 12% (41 mg). Rf = 0.13 (EtOAc/n-hex-
ane, 1:4). IR (neat): ν = 3057 (m), 2986 (m), 1727 (m), 1266 (s)
˜
1
cm–1. H NMR (400 MHz, CDCl3): δ = 1.26 (two overlapped t, J
= 7.3 Hz, 6 H), 1.42 (dd, J = 11.4, 7.7 Hz, 1 H), 1.68 (ddd, J =
11.4, 4.4, 3.3 Hz, 1 H), 1.99 (dd, J = 13.2, 11.4 Hz, 1 H), 2.02–2.20
(m, 1 H), 2.21 (s, 3 H), 2.53 (dd, J = 13.2, 7.0 Hz, 1 H), 2.91 (d, J
= 7.3 Hz, 2 H), 3.45 (dd collapsed to t, J = 7.3 Hz, 1 H), 4.12–4.23
(m, 4 H), 4.98 (dd, J = 4.4, 1.5 Hz, 1 H), 6.24 (ABq, J = 5.9 Hz,
the high-field half was further split into d, J = 1.5 Hz, 2 H) ppm.
1
These data were confirmed by H-1H COSY experiment (see also
Table S8). 13C NMR (100 MHz, CDCl3): δ = 14.0 (2 C), 29.7, 32.3,
39.2, 41.9, 43.0, 43.2, 61.4 (2 C), 66.9, 79.8, 99.6, 134.3, 135.6,
170.9, 171.2, 206.4 ppm. MS (ESI, Ar): m/z (%) = 359 (100) [M +
Na]+, 273 (53), 189 (22), 159 (11), 61 (8). HRMS (ESI, Ar): calcd.
for C18H24O6Na [M + Na]+ 359.1471; found 359.1467.
5b: Colorless solid. Yield 8% (22 mg). M.p. 130 °C. Rf = 0.14
(EtOAc/n-hexane, 1:4). IR (KBr): ν = 3020 (w), 2920 (w), 1673 (s),
˜
Compounds 8b and 9b
1
1593 (m), 1446 (m), 1211 (m) cm–1. H NMR (300 MHz, CDCl3):
8b: Colorless solid. Yield 71% (283 mg). M.p. 105 °C. Rf = 0.33
δ = 1.53 (dd, J = 11.7, 7.7 Hz, 1 H), 1.80 (ddd, J = 11.7, 4.4, 2.6 Hz,
1 H), 2.35 (dddd collapsed to ddd, J = 10.8, 7.7, 2.6 Hz, 1 H), 2.75
(dd collapsed to t, J = 10.8 Hz, 1 H), 3.06 (dd, J = 10.8, 7.7 Hz, 1
H), 3.55 (ABq, J = 17.2 Hz, high-field and low-field halves were
further split into d, J = 9.2 and 5.3 Hz, respectively, 2 H), 4.20 (dd,
J = 9.2, 5.3 Hz, 1 H), 5.05 (dd, J = 4.4, 1.8 Hz, 1 H), 6.35 (d, J =
5.9 Hz, 1 H), 6.46 (dd, J = 5.9, 1.8 Hz, 1 H), 7.45–7.50 (m, 2 H),
7.56–7.61 (m, 1 H), 7.98–7.99 (m, 2 H) ppm. These data were con-
firmed by 1H-1H COSY and NOESY experiments (see also
Table S5). 13C NMR (75 MHz, CDCl3): δ = 34.5, 36.8, 42.5, 44.7,
47.4, 79.5, 101.9, 128.1, 128.7, 133.4, 133.7, 136.5, 137.9, 197.0
ppm. MS (ESI, Ar): m/z (%) = 295 (100) [M + Na]+, 255 (4), 135
(10), 105 (25), 77 (4). HRMS (ESI, Ar): calcd. for C16H16O2NaS
[M + Na]+ 295.0769; found 295.0770.
(EtOAc/n-hexane, 1:4). IR (KBr): ν = 3057 (w), 2985 (w), 1726 (br.,
˜
s), 1266 (s) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.19 (t, J =
7.1 Hz, 3 H), 1.26 (t, J = 7.1 Hz, 3 H), 1.46 (dd, J = 11.7, 7.8 Hz,
1 H), 1.72 (ddd collapsed to dt, J = 11.7, 4.4 Hz, 1 H), 1.86 (dddd
collapsed to ddd, J = 8.8, 7.8, 4.4 Hz, 1 H), 2.40 (ABqd, J = 13.2,
8.8 Hz, 2 H), 3.11 (dd, J = 17.8, 4.9 Hz, 1 H), 3.39 (dd, J = 17.8,
10.0 Hz, 1 H), 4.00 (dd, J = 10.0, 4.9 Hz, 1 H), 4.21 (m, 4 H), 4.92
(dd, J = 4.4, 1.5 Hz, 1 H), 6.15 (dd, J = 5.9, 1.5 Hz, 1 H), 6.46 (d,
J = 5.9 Hz, 1 H), 7.40–7.45 (m, 2 H), 7.50–7.55 (m, 1 H), 7.93–
1
7.96 (m, 2 H) ppm. These data were confirmed by H-1H COSY
and NOESY experiments (see also Table S9). 13C NMR (100 MHz,
CDCl3): δ = 14.0 (2 C), 33.4, 36.0, 39.0, 39.9, 41.1, 61.3, 61.7, 65.4,
79.5, 98.5, 128.1, 128.4, 132.8, 134.7, 137.0, 137.1, 170.2, 172.1,
197.9 ppm. MS (ESI, Ar): m/z (%) = 421 (100) [M + Na]+, 335
(50), 263 (20), 261 (54). HRMS (ESI, Ar): calcd. for C23H26O6Na
[M + Na]+ 421.1627; found 421.1638. Selected X-ray data:
C23H26O6, M = 398.44, orthorhombic, P212121, a = 8.3315(6) Å, b
= 13.9919(14) Å, c = 18.2911(15) Å, V = 2132.3(3) Å3, Z = 4,
Dcalcd. = 1.241 gcm–3, µ = 0.089 mm–1, size = 0.40ϫ0.35ϫ
0.30 mm, GOF = 0.922. Reflections collected: unique 9669/3730
[R(int) = 0.0325]. Final R indices [I Ͼ 2σ(I)]: R1 = 0.0488, wR2 =
0.1118; R indices (all data): R1 = 0.1069, wR2 = 0.1335 (see also
Table S17).
Compound 4c: Colorless solid. Yield 44% (111 mg). M.p. 109 °C.
R = 0.27 (EtOAc/n-hexane, 1:4). IR (neat): ν = 2938 (m), 1725 (s),
˜
f
1694 (m), 1250 (m) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.46
(dd, J = 11.7, 7.3 Hz, 1 H), 1.75 (ddd, J = 11.7, 4.4, 2.6 Hz, 1 H),
2.25 (s, 6 H), 2.27–2.38 (m, 1 H), 2.70 (dd collapsed to t, J =
10.6 Hz, 1 H), 2.96 (dd, J = 10.6, 7.3 Hz, 1 H), 4.29 (d, J = 11.2 Hz,
1 H), 4.50 (d, J = 11.2 Hz, 1 H), 5.02 (dd, J = 4.4, 1.6 Hz, 1 H),
6.27 (unresolved br. s, 2 H) ppm. These data were confirmed by
1H-1H COSY experiment (see also Table S6). 13C NMR (75 MHz,
CDCl3): δ = 29.5, 31.4, 34.1, 36.4, 45.3, 49.4, 71.5, 79.9, 99.3, 135.6,
137.0, 200.9, 202.1 ppm. MS (ESI, Ar): m/z (%) = 275 (4) [M +
Na]+, 193 (100). HRMS (ESI, Ar): calcd. for C13H16O3NaS [M +
Na]+ 275.0718; found 275.0725. The minor isomer 5c could not be
isolated in pure form.
9b: Light yellow oil. Yield 16% (64 mg). Rf = 0.16 (EtOAc/n-hex-
ane, 1:4). IR (neat): ν = 3055 (m), 2985 (w), 1725 (br., s), 1686 (m),
˜
1265 (s) cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.23 (t, J = 7.3 Hz,
6 H), 1.43 (dd, J = 11.2, 7.8 Hz, 1 H), 1.72 (ddd collapsed to dt, J
= 11.2, 4.4 Hz, 1 H), 2.02–2.06 (m, 2 H), 2.21–2.29 (m, 1 H), 2.57
(dd, J = 12.9, 6.6 Hz, 1 H), 3.47–3.67 (m, 2 H), 4.10–4.25 (m, 4
Compounds 8a and 9a
8a: Light yellow oil. Yield 61% (206 mg). Rf = 0.29 (EtOAc/n-hex- H), 4.99 (dd, J = 4.4, 1.5 Hz, 1 H), 6.21 (dd, J = 5.9, 1.5 Hz, 1 H),
ane, 1:4). IR (neat): ν = 3056 (m), 2986 (m), 1725 (br., s), 1266 (s)
6.23 (ABq, J = 5.9 Hz, 1 H), 7.44–7.49 (m, 2 H), 7.54–7.59 (m, 1
H), 8.00–8.02 (m, 2 H) ppm. These data were confirmed by 1H-1H
COSY and NOESY experiments (see also Table S10). 13C NMR
(75 MHz, CDCl3): δ = 14.1, 29.7, 32.4, 38.0, 39.4, 42.0, 43.1, 61.5
(2 C), 67.0, 79.9, 99.8, 128.2, 128.7, 133.2, 134.8, 135.4, 136.8,
171.0, 171.5, 197.6 ppm. MS (ESI, Ar): m/z (%) = 421 (100) [M +
Na]+, 335 (30), 261 (12). HRMS (ESI, Ar): calcd. for C23H26O6Na
[M + Na]+ 421.1627; found 421.1643.
˜
1
cm–1. H NMR (400 MHz, CDCl3): δ = 1.25 (two overlapped t, J
= 7.3 Hz, 6 H), 1.45 (dd, J = 11.4, 7.7 Hz, 1 H), 1.70 (ddd, J =
11.4, 4.4, 3.3 Hz, 1 H), 1.79 (dddd, J = 9.9, 8.1, 7.7, 3.3 Hz, 1 H),
2.12 (s, 3 H), 2.36 (ABq, J = 13.2 Hz, the low-field and high-field
halves were further split into d, J = 9.9 and 8.1 Hz, respectively, 2
H), 2.55 (dd, J = 17.2, 4.8 Hz, 1 H), 2.80 (dd, J = 17.2, 10.3 Hz, 1
H), 3.90 (dd, J = 10.3, 4.8 Hz, 1 H), 4.10–4.28 (m, 4 H), 4.93 (dd,
Eur. J. Org. Chem. 2008, 6106–6118
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6115

B. Ganguly, I. N. N. Namboothiri et al.
FULL PAPER
¯
413.1971. Selected X-ray data: C24H28O6: M = 412.46, triclinic, P1,
Compounds 8c and 9c
a
= 8.9557(3) Å, b = 9.8870(4) Å, c = 13.4143(5) Å, V =
8c: Colorless oil. Yield 65% (238 mg). Rf = 0.29 (EtOAc/n-hexane,
1070.23(7) Å3, Z = 2, Dcalcd. = 1.280 gcm–3, µ = 0.091 mm–1, size =
0.23ϫ0.18ϫ0.16 mm, GOF = 1.047. Reflections collected: unique
1:4). IR (neat): ν = 3056 (m), 2986 (m), 1729 (br., s), 1266 (s) cm–1.
˜
1H NMR (300 MHz, CDCl3): δ = 1.24 (three overlapped t, J =
7.3 Hz, 9 H), 1.44 (dd, J = 11.4, 7.7 Hz, 1 H), 1.70 (ddd, J = 11.4,
4.4, 3.3 Hz, 1 H), 1.76–1.85 (m, 1 H), 2.35–2.39 (m, 2 H), 2.53–
2.56 (m, 2 H), 3.90 (dd, J = 9.2, 6.6 Hz, 1 H), 4.06–4.28 (three
overlapped q, J = 7.3 Hz, 6 H), 4.97 (dd, J = 4.4, 1.5 Hz, 1 H),
6.19 (dd, J = 5.9, 1.5 Hz, 1 H), 6.41 (d, J = 5.9 Hz, 1 H) ppm.
9289/3766 [R(int)] = 0.0206. Final R indices [I Ͼ 2σ(I)]: R1
0.0379, wR2 = 0.0930; R indices (all data): R1 = 0.0565, wR2
0.0984 (see also Table S17).
=
=
9e: Light yellow oil. Yield 3% (13 mg). Rf = 0.23 (EtOAc/n-hexane,
1:4) IR (neat): ν = 2929 (s), 1732 (s), 1260 (m) cm–1. 1H NMR
˜
1
These data were confirmed by H-1H COSY experiment (see also
(400 MHz, CDCl3): δ = 1.16 (t, J = 7.0 Hz, 3 H), 1.17 (t, J =
7.0 Hz, 3 H), 1.22–1.55 (m, 2 H), 1.56–1.65 (m, 2 H), 1.87–1.94 (m,
1 H), 2.02–2.13 (m, 1 H), 2.43–2.49 (m, 1 H), 3.18 (dd, J = 18.5,
5.9 Hz, 1 H), 3.49 (dd, J = 18.5, 4.4 Hz, 1 H), 3.96–4.00 (m, 1 H),
4.01–4.22 (two overlapped q, J = 7.0 Hz, 4 H), 4.81 (dd, J = 4.4,
1.8 Hz, 1 H), 6.11 (d, J = 5.9 Hz, 1 H), 6.31 (dd, J = 5.9, 1.8 Hz,
1 H), 7.43–7.48 (m, 2 H), 7.53–7.55 (m, 1 H), 7.97–8.01 (m, 2 H)
Table S11). 13C NMR (100 MHz, CDCl3): δ = 13.8 (2 C), 13.9,
31.7, 32.9, 38.5, 40.2, 40.9, 60.1, 61.1, 61.5, 65.2, 79.4, 97.9, 134.5,
136.9, 169.4, 171.7, 171.8 ppm. MS (ESI, Ar): m/z (%) = 389 (100)
[M + Na]+, 303 (24), 229 (9). HRMS (ESI, Ar): calcd. for
C19H26O7Na [M + Na]+ 389.1576; found 389.1581.
9c: Light yellow oil. Yield 12% (45 mg). Rf = 0.13 (EtOAc/n-hex-
ppm. These data were confirmed by 1H-1H COSY experiment. 13
C
ane, 1:4). IR (neat): ν = 3055 (m), 2985 (w), 1729 (br., s), 1266 (s)
˜
1
cm–1. H NMR (400 MHz, CDCl3): δ = 1.26 (three overlapped t,
NMR (100 MHz, CDCl3): δ = 14.0, 14.1, 26.8, 27.9, 33.2, 35.2,
35.5, 39.3, 57.2, 61.7 (2 C), 78.1, 90.3, 128.2, 128.8, 133.2, 135.8,
137.1, 137.7, 170.4, 171.9, 197.2 ppm. MS (ESI, Ar): m/z (%) = 413
(2) [M + H]+, 395 (100). HRMS (ESI, Ar): calcd. for C24H29O6 [M
+ H]+ 413.1964; found 413.1957.
J = 7.0 Hz, 9 H), 1.42 (dd, J = 11.4, 7.7 Hz, 1 H), 1.67 (ddd col-
lapsed to dt, J = 11.4, 4.3 Hz, 1 H), 1.97 (dd, J = 12.8, 11.4 Hz, 1
H), 2.17–2.27 (dddd, J = 11.4, 7.7, 7.0, 4.3 Hz, 1 H), 2.53 (dd, J =
12.8, 7.0 Hz, 1 H), 2.80 (ABq, J = 16.5 Hz, the high-field and low-
field halves were further split to d, J = 9.9 and 5.5 Hz, respectively,
2 H), 3.43 (dd, J = 9.9, 5.5 Hz, 1 H), 4.18 (three overlapped q, J =
7.0 Hz, 6 H), 4.98 (dd, J = 4.3, 1.8 Hz, 1 H), 6.25 (dd, J = 5.9,
1.8 Hz, 1 H), 6.35 (d, J = 5.9 Hz, 1 H) ppm. These data were con-
firmed by 1H-1H COSY experiment (see also Table S12). 13C NMR
(75 MHz, CDCl3): δ = 14.0 (2 C), 14.2, 32.4, 34.0, 39.3, 42.6, 43.0,
60.7 (2 C), 61.5, 66.9, 79.8, 99.6, 134.3, 135.5, 170.8, 171.1, 171.7
ppm. MS (ESI, Ar): m/z (%) = 389 (100) [M + Na]+, 303 (94), 229
(73), 201 (25). HRMS (ESI, Ar): calcd. for C19H26O7Na [M +
Na]+ 389.1576; found 389.1577.
Compounds 12d and 13d
12d: Light yellow oil. Yield 20% (53 mg). Rf = 0.19 (EtOAc/n-hex-
ane, 1:5). IR (KBr): ν = 3076 (w), 2980 (w), 2938 (w), 2867 (w),
˜
1735 (s), 1180 (m) cm–1. H NMR (300 MHz, CDCl3): δ = 1.25 (t,
1
J = 7.3 Hz, 3 H), 1.48 (dd, J = 11.7, 7.8 Hz, 1 H), 1.72 (ddd col-
lapsed to dt, J = 11.7, 4.4 Hz, 1 H), 2.06 (dtd, J = 10.7, 7.8, 4.4 Hz,
1 H), 2.64–2.66 (m, 2 H), 2.83 (dd, J = 10.7, 7.8 Hz, 1 H), 2.90 (dd
collapsed to t, J = 10.7 Hz, 1 H), 3.15 (dd, J = 14.1, 7.3 Hz, 1 H),
3.43 (ddt, J = 13.7, 5.9, 1.5 Hz, 1 H), 3.64 (dd collapsed to t, J =
6.8 Hz, 1 H), 4.13 (q, J = 7.3 Hz, 2 H), 5.05 (dd, J = 4.4, 1.5 Hz,
1 H), 5.13 (d, J = 10.2 Hz, 1 H), 5.21 (dd, J = 17.1, 1.5 Hz, 1 H),
5.85–5.98 (m, 1 H), 6.26 (dd, J = 5.9, 1.5 Hz, 1 H), 6.40 (d, J =
5.9 Hz, 1 H) ppm. These data were confirmed by 1H-1H COSY
experiment (see also Table S13). 13C NMR (100 MHz, CDCl3): δ
= 14.0, 29.5, 32.4, 34.1, 41.1, 56.4, 57.2, 59.1, 60.1, 79.2, 97.9,
117.0, 135.3, 135.5, 172.0 ppm. MS (ESI, Ar): m/z (%) = 264 (100)
[M + H]+, 167 (10), 125 (9), 95 (6). HRMS (ESI, Ar): calcd. for
C15H22NO3 [M + H]+ 264.1600; found 264.1599.
Compound 8d: Light yellow oil. Yield 41% (145 mg). Rf = 0.39
(EtOAc/n-hexane, 1:4). IR (neat): ν = 2926 (w), 1732 (s), 1254 (s),
˜
1098 (w) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.26 (t, J =
7.3 Hz, 6 H), 1.36 (ddd, J = 11.7, 4.4, 2.0 Hz, 1 H), 1.45–1.57 (m,
3 H), 1.79–1.93 (m, 2 H), 2.12 (s, 3 H), 2.37–2.43 (m, 1 H), 3.06–
3.09 (m, 2 H), 3.50 (dd, J = 5.9, 3.9 Hz, 1 H), 4.07–4.28 (m, 4 H),
4.86 (dd, J = 4.4, 1.5 Hz, 1 H), 5.86 (d, J = 5.9 Hz, 1 H), 6.25 (dd,
1
J = 5.9, 1.5 Hz, 1 H) ppm. These data were confirmed by H-1H
COSY experiment. 13C NMR (100 MHz, CDCl3): δ = 14.1, 28.0,
29.8, 30.3, 32.8, 35.2, 36.2, 36.8, 43.9, 57.2, 61.0, 61.8, 78.7, 89.1,
136.4, 137.5, 170.1, 172.1, 208.1 ppm. MS (ESI, Ar): m/z (%) = 373
(100) [M + Na]+, 287 (10), 241 (38), 215 (50), 195 (30). HRMS
(ESI, Ar): calcd. for C19H26O6Na [M + Na]+ 373.1627; found
373.1632.
13d: Light yellow oil. Yield 69% (182 mg). Rf = 0.37 (EtOAc/n-
hexane, 1:5). IR (neat): ν = 3055 (m), 2984 (m), 1730 (s), 1266 (s)
˜
cm–1. H NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.3 Hz, 3 H),
1
1.32 (dd, J = 11.5, 7.5 Hz, 1 H), 1.68 (ddd, J = 11.5, 4.4, 2.8 Hz,
1 H), 1.98–2.08 (m, 1 H), 2.17 (dd, J = 10.3, 8.4 Hz, 1 H), 2.71
(ABq, J = 15.8 Hz, the high-field and low-field halves were further
split into d, J = 8.4 and 5.1 Hz, respectively, 1 H), 3.14 (dd, J =
13.6, 7.3 Hz, 1 H), 3.23–3.25 (m, 1 H), 3.27–3.30 (m, 1 H), 3.43
(ddt, J = 13.6, 5.9, 1.5 Hz, 1 H), 4.16 (q, J = 7.3 Hz, 2 H), 4.98
(dd, J = 4.4, 1.7 Hz, 1 H), 5.12 (dd, J = 10.3, 0.7 Hz, 1 H), 5.21
(dd, J = 17.2, 1.5 Hz, 1 H), 5.84–5.96 (m, 1 H), 6.30 (dd, J = 5.9,
1.7 Hz, 1 H), 6.41 (d, J = 5.9 Hz, 1 H) ppm. These data were con-
firmed by 1H-1H COSY experiment (see also Table S14). 13C NMR
(100 MHz, CDCl3): δ = 13.7, 29.1, 37.7, 41.0, 57.0, 57.9, 59.8, 60.6,
78.9, 98.7, 116.6, 133.6, 135.1, 135.3, 170.6 ppm. MS (ESI, Ar):
m/z (%) = 264 (100) [M + H]+, 167 (40), 125 (80), 97 (69), 95 (54),
81 (25). HRMS (ESI, Ar): calcd. for C15H22NO3 [M + H]+
264.1600; found 264.1605.
Compounds 8e and 9e
8e: Colorless solid. Yield 40% (166 mg). M.p. 99 °C. Rf = 0.37
(EtOAc/n-hexane, 1:4). IR (neat): ν = 2979 (w), 2928 (w), 1732 (s),
˜
1688 (m), 1449 (m), 1254 (m), 1096 (m) cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.09 (t, J = 7.0 Hz, 3 H), 1.31 (t, J = 7.0 Hz, 3 H),
1.39 (ddd, J = 11.0, 4.4, 2.6 Hz, 1 H), 1.47–1.63 (m, 2 H), 1.65–
1.70 (m, 1 H), 1.88–1.92 (m, 2 H), 2.41–2.48 (m, 1 H), 3.63–3.65
(m, 2 H), 3.79 (dd, J = 5.9, 3.7 Hz, 1 H), 3.96–4.14 (m, 2 H), 4.27
(q, J = 7.0 Hz, 2 H), 4.87 (dd, J = 4.4, 1.5 Hz, 1 H), 5.91 (d, J =
5.5 Hz, 1 H), 6.21 (dd, J = 5.5, 1.5 Hz, 1 H), 7.40–7.46 (m, 2 H),
7.51–7.56 (m, 1 H), 8.00–8.02 (m, 2 H) ppm. These data were con-
1
firmed by H-1H COSY experiment. 13C NMR (75 MHz, CDCl3):
δ = 13.9, 14.1, 27.9, 32.8, 35.2, 36.1, 36.8, 38.9, 57.2, 60.9, 61.6,
78.6, 89.2, 128.2, 128.4, 132.9, 136.4, 137.0, 137.3, 170.1, 171.9,
199.1 ppm. MS (ESI, Ar): m/z (%) = 413 (2) [M + H]+, 395 (100).
HRMS (ESI, Ar): calcd. for C24H29O6 [M + H]+ 413.1964; found
Compounds 12e and 13e
12e: Light yellow oil. Yield 13% (44 mg). Rf = 0.19 (EtOAc/n-hex-
ane, 1:5). IR (neat): ν = 3077 (w), 2926 (w), 1734 (s), 1180 (m)
˜
6116
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Eur. J. Org. Chem. 2008, 6106–6118

Synthetic and Theoretical Investigations on Oxanorbornenes
1
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= 6.9 Hz, 6 H), 1.47 (dd, J = 11.6, 7.9 Hz, 1 H), 1.70 (ddd, J =
11.6, 4.4, 3.0 Hz, 1 H), 2.07 (dddd, J = 9.5, 7.9, 7.3, 3.0 Hz, 1 H),
2.63–2.66 (m, 2 H), 2.83 (dd, J = 10.6, 7.3 Hz, 1 H), 2.90 (dd, J =
10.6, 9.5 Hz, 1 H), 3.15 (dd, J = 13.9, 7.3 Hz, 1 H), 3.43 (ddt, J =
13.9, 5.5, 1.5 Hz, 1 H), 3.64 (ABq, J = 6.6 Hz, 1 H), 4.12 (two
overlapped q, J = 6.9 Hz, 4 H), 5.05 (dd, J = 4.4, 1.5 Hz, 1 H),
5.16 (dq, J = 17.2, 1.5 Hz, 1 H), 5.85–5.98 (m, 1 H), 6.26 (dd, J =
5.9, 1.5 Hz, 1 H), 6.39 (d, J = 5.9 Hz, 1 H) ppm. These data were
confirmed by 1H-1H COSY experiment (see also Table S15). 13C
NMR (75 MHz, CDCl3): δ = 14.3, 32.7, 34.3, 41.3, 56.6, 57.5, 59.3,
60.5, 79.4, 98.2, 117.3, 135.5 (2 C), 135.7, 172.3 ppm. MS (ESI,
Ar): m/z (%) = 264 [M – CO2Et + H]+, (100), 167 (22), 125 (25),
95 (18). HRMS (ESI, Ar): calcd. for C15H22NO3 [M – CO2Et +
H]+ 264.1600; found 264.1591.
[2]
[3]
13e: Light yellow oil. Yield 60% (202 mg). Rf = 0.35 (EtOAc/n-
hexane, 1:5). IR (neat): ν = 3054 (m), 2986 (m), 1730 (m), 1266 (s)
˜
1
cm–1. H NMR (400 MHz, CDCl3): δ = 1.26 (t, J = 7.0 Hz, 6 H),
1.32 (dd, J = 11.4, 7.5 Hz, 1 H), 1.68 (ddd, J = 11.4, 4.4, 2.9 Hz,
1 H), 2.03 (dddd, J = 13.6, 10.6, 7.5, 2.9 Hz, 1 H), 2.16 (dd, J =
10.6, 8.4 Hz, 1 H), 2.60 (ABq, J = 8.4 Hz, 1 H), 2.74 (dd, J = 15.4,
5.1 Hz, 1 H), 3.13 (dd, J = 13.6, 7.3 Hz, 1 H), 3.22–3.29 (m, 2 H),
3.43 (ddt, J = 13.6, 5.9, 1.6 Hz, 1 H), 4.16 (q, J = 7.0 Hz, 4 H),
4.99 (dd, J = 4.4, 1.5 Hz, 1 H), 5.09–5.21 (m, 1 H), 5.82–5.96 (m,
1 H), 6.29 (dd, J = 5.9, 1.5 Hz, 1 H), 6.41 (d, J = 5.9 Hz, 1 H)
[4]
ppm. These data were confirmed by H-1H COSY experiment (see
1
also Table S16). 13C NMR (75 MHz, CDCl3): δ = 14.2, 29.6, 38.3,
41.6, 57.6, 58.5, 60.4, 61.1, 79.5, 99.2, 117.2, 134.1, 135.6, 135.8,
171.3 ppm. MS (ESI, Ar): m/z (%) = 264 (100) [M – CO2Et +
H]+, 167 (3), 125 (5). HRMS (ESI, Ar): calcd. for C15H22NO3 [M –
CO2Et + H]+) 264.1600; found 264.1602.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectroscopic data tables, copies of NMR spectra for
all new compounds, RHF/3-21G*- and B3LYP/6-31+G*-calcu-
lated coordinates of products and transition states.
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Acknowledgments
I. N. N. thanks the Department of Science and Technology, India
for financial assistance and the Sophisticated Analytical Instru-
mentation Facility, Indian Institute of Technology Bombay, for se-
lected NMR spectroscopic data. M. D. thanks the Council of Sci-
entific and Industrial Research, India, and M. K. K. thanks the
Department of Atomic Energy-Board of Research in Nuclear Sci-
ences for a research fellowship.
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Received: July 9, 2008
Published Online: November 18, 2008
6118
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Eur. J. Org. Chem. 2008, 6106–6118