Catalytic dicyanative [4 + 2] cycloaddition triggered by cyanopalladation using ene-enynes and cyclic enynes with methyl acrylate

Article abstract of DOI:10.1021/jo100995k

Palladium-catalyzed dicyanative [4 + 2] cycloaddition using various ene-enynes was investigated. The key species in this process is a cyanoallene intermediate that is obtained by the cyanopalladation of conjugated enynes followed by 5-exo-cyclization. To

Full text of DOI:10.1021/jo100995k

pubs.acs.org/joc
Catalytic Dicyanative [4 þ 2] Cycloaddition Triggered
by Cyanopalladation Using Ene-Enynes and Cyclic Enynes
with Methyl Acrylate
Shigeru Arai,* Yuka Koike, Hirohiko Hada, and Atsushi Nishida
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku,
Chiba 263-8522, Japan
arai@p.chiba-u.ac.jp
Received May 21, 2010
Palladium-catalyzed dicyanative [4 þ 2] cycloaddition using various ene-enynes was investigated.
The key species in this process is a cyanoallene intermediate that is obtained by the cyanopalladation
of conjugated enynes followed by 5-exo-cyclization. To achieve an efficient [4 þ 2] cycloaddition
reaction, both the smooth generation of this species and critical control of regioselectivity in the
6-endo-cyclization step are quite important. A study of the substrate scope revealed that the reaction
is strongly affected by the steric bulk of the substituents on the enyne and alkene units and prefers to
give trans-fused cycloadducts. The stereochemistry of olefins was reasonably transferred to the
corresponding products. Further study proved that this transformation includes not a thermal [4 þ 2]
cycloaddition process via 1,2-dicyanoalkenes generated in situ but rather a palladium-mediated
stepwise cyclization sequence to control a maximum of five contiguous stereogenic centers in a single
operation. An intermolecular version using methyl acrylate with conjugated cyclic enynes and
TMSCN also gave the corresponding [4 þ 2] cycloadducts in a regioselective manner.
Introduction
has been recently applied to the introduction of various
elements2-8 together with a CN group. In general, a cyano
function on a transition metal acts as a pseudo halide (due to
its lower nucleophilicity) and is unlikely to be transferred to
C-C triple bonds as a nucleophile. Therefore, the reported
Since the first report of cyanation using simple alkynes
with HCN under transition-metal catalysis,1 the introduc-
tion of a cyano function into simple and nonactivated
carbon-carbon multiple bonds has been one of the most
significant issues in synthetic organic chemistry, and the
above cyanation protocol by nickel and palladium catalysis
(5) For thiocyanation, see: Kamiya, I.; Kawakami, J.; Yano, S.; Nomoto,
A.; Ogawa, A. Organometallics 2006, 25, 3562.
(6) For a review of transition-metal-catalyzed carbocyanation of carbon-
ꢀ
(1) For hydrocyanation, see: (a) Funabiki, T.; Yamazaki, Y.; Tarama, K.
J. Chem. Soc., Chem. Commun. 1978, 63. (b) Fallon, G. D.; Fitzmaurice,
N. J.; Jackson, W. R.; Perlmutter, P. J. Chem. Soc., Chem. Commun. 1985, 4.
(c) Fitzmaurice, N. J.; Jackson, W. R.; Perlmutter, P. J. Organomet. Chem.
1985, 285, 375.
(2) For silylcyanation, see: (a) Chatani, N.; Hanafusa, T. J. Chem. Soc.,
Chem. Commun. 1985, 838. (b) Chatani, N.; Takeyasu, T.; Horiuchi, N.;
Hanafusa, T. J. Org. Chem. 1988, 53, 3539. (c) Chatani, N.; Hanafusa, T.
Tetrahedron Lett. 1986, 27, 4201. (d) Suginome, M.; Kinugasa, H.; Ito, Y.
Tetrahedron Lett. 1994, 35, 8635.
(3) For germylcyanation, see: (a) Chatani, N.; Horiuchi, N.; Hanafusa,
T. J. Org. Chem. 1990, 55, 3393. (b) Chatani, N.; Morimoto, T.; Toyoshige,
M.; Murai, S. J. Organomet. Chem. 1994, 473, 335.
(4) For stannylcyanation, see: Obora, Y.; Baleta, A. S.; Tokunaga, M.;
Tsuji, Y. J. Organomet. Chem. 2002, 660, 173.
carbon multiple bonds, see: (a) Najera, C.; Sansano, J. M. Angew. Chem., Int.
Ed. 2009, 45, 2452. (b) Nakao, Y.; Oda, S.; Hiyama, T. J. Am. Chem. Soc.
2004, 126, 13904. (c) Nakao, Y.; Kanyiva, K.; Oda, S.; Hiyama, T. J. Am.
Chem. Soc. 2006, 128, 8146. (d) Nakao, Y.; Ebata, S.; Yada, A.; Hiyama, T.;
Ikawa, M.; Ogoshi, S. J. Am. Chem. Soc. 2008, 130, 12874. (e) Cheng, Y.;
Duan, Z.; Yu, L.; Li, Z.; Zhu, Y.; Wu, Y. Org. Lett. 2008, 10, 901.
(7) For acylcyanation, see: (a) Nozaki, K.; Sato, N.; Takaya, H. J. Org.
Chem. 1994, 59, 2679. (b) Kobayashi, Y.; Kamisaki, H.; Yanada, R.;
Takemoto, Y. Org. Lett. 2006, 8, 2711. (c) Nishihara, Y; Inoue, Y.; Izawa,
S.; Miyasaka, M.; Tanemura, K.; Nakajima, K.; Takagi, K. Tetrahedron
2006, 62, 9872.
(8) For cyanoboration, see: (a) Suginome, M.; Yamamoto, A.; Murakami,
M. J. Am. Chem. Soc. 2003, 125, 6358. (b) Suginome, M.; Yamamoto, A.;
Murakami, M. Angew. Chem., Int. Ed. 2005, 44, 2380. (c) Suginome, M.;
Yamamoto, A.; Murakami, M. J. Organomet. Chem. 2005, 690, 5300.
DOI: 10.1021/jo100995k
r
Published on Web 10/26/2010
J. Org. Chem. 2010, 75, 7573–7579 7573
2010 American Chemical Society

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SCHEME 1. syn- and anti-Cyanopalladation of Alkynes
SCHEME 2. Proposed Catalytic Cycloaddition Using Ene-Enynes
methods for the introduction of a cyano functionality by Ni
and Pd catalysis usually involve reductive elimination from
an alkenyl-MII-CN species (M=metal) that is generated
through X-C bond formation, and alkenyl-CN is obtained
together with M(0) (eq 1). On the other hand, we previously
reported that the nucleophilic addition of cyanide by the use
of TMSCN was effectively promoted under Pd(II) catalysis in
the presence of oxygen,9 and these results are, to the best of our
knowledge, the first example of the cyanometalation of simple
and nonactivated alkynes.10a According to our protocol, a
catalytic cyanation of internal alkynes was also applicable10
and the substrate-controlled 5-exo- and 6-endo-cyclizations
of various enynes triggered by syn-cyanopalladation have
been established.10a,c In this paper, we present a new applica-
tion based on the above findings to establish a new protocol
for dicyanative [4 þ 2] cycloaddition triggered by cyano-
palladation.10d
Results and Discussion
We recently developed a catalytic 1,2-dicyanation of
various alkynes through the use of TMSCN with Pd(II)
under aerobic conditions and proposed that both syn- and
anti-cyanopalladation to C-C triple bonds are key reactions
(Scheme 1).10a,b In addition, we revealed that the former
transformation plays an important role in the 5-exo- and
6-endo-cyclization sequences that give the functionalized
heterocycles.10a,c
For a further application of this approach, we next
investigated a new cycloaddition protocol using ene-enynes.
If a cyanoallene species10c could be generated as a key
intermediate in a catalytic cycle and react with an organo-
palladium species to promote ring formation, this strategy
(9) For reviews on palladium catalysis with oxidants, see: (a) Stahl, S. S.
Angew. Chem., Int. Ed. 2004, 43, 3400. (b) Beccalli, E. M.; Broggini, G.;
Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318. Pd-catalyzed
enantioselective oxidative [2 þ 1] cycloadditions have been reported; see: (c)
Welbes, L. L.; Lyons, T. W.; Cychosz, K. A.; Sanford, M. S. J. Am. Chem.
Soc. 2007, 129, 5836. (d) Tsujihara, T.; Takenaka, K.; Onitsuka, K.;
Hatanaka, M.; Sasai, H. J. Am. Chem. Soc. 2009, 131, 3452.
(10) For dicyanation, see: (a) Arai, S.; Sato, T.; Koike, Y.; Hayashi, M.;
Nishida, A. Angew. Chem. 2009, 121, 4598. Angew. Chem., Int. Ed. 2009, 48,
4528. (b) Arai, S.; Sato, T.; Nishida, A. Adv. Synth. Catal. 2009, 351, 1897. (c)
Arai, S.; Koike, Y.; Nishida, A. Adv. Synth. Catal. 2010, 352, 893. (d) Arai, S.;
Koike, Y.; Hada, H.; Nishida, A. J. Am. Chem. Soc. 2010, 132, 4522.
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SCHEME 3. Reaction of 1a
would enable easy access to functionalized cycloalkenes
(Scheme 2). To realize the above transformation, we initially
designed ene-enyne 1 having a conjugated enyne: nucleophilic
cyanation (cyanopalladation) would occur at the terminal
sp-carbon of the conjugated enynes and subsequent exo-
cyclization via an allylpalladium intermediate would give the
corresponding alkylpalladium species that would react with
the C-C double bonds of the cyanoallene to afford cyclized
products. The features of this reaction include (1) four C-C
bond-forming reactions in a single operation, (2) regiocon-
trol of C-C double bonds of cyanoallene in a second
cyclization, (3) stereocontrol at the ring juncture, and (4) facile
synthesis of highly functionalized cycloalkenes.
To realize our expectation, we initially examined the
reaction using 1a to evaluate their reactivity (Scheme 3).
Interestingly, the stereochemistry of the conjugated enyne
was found to be critical in this reaction. For example, the
reaction of (E)-1a proceeded smoothly to give the cis- and
trans-fused cyclohexene derivatives (2a) in respective yields
of 28% and 32%. On the other hand, (Z)-1a was recovered
quantitatively even after 7 h under similar conditions with-
out any trace of the 1,2-dicyanated products, which means
that the terminal C-C triple bond in the latter substrate was
not effectively activated by Pd(II). These results suggest that
the terminal C-C triple bond in (E)-1a is more suitable for
activation by Pd(II) and the diene moiety of the Z-isomer
could act as a bidentate ligand to Pd(II) and significantly
prevent the activation of a terminal C-C triple bond.
Based on these observations, we further studied the scope
and limitations of this reaction (Table 1). As shown in entries
1 and 2, the stereoselectivity at the ring juncture is strongly
influenced by R1, and a bulkier substituent gave a higher
trans selectivity. The stereochemistry of both cis- and trans-
2b was determined by X-ray crystallographic analysis.11 To
investigate the influence of the olefin geometry, both 1d and
1e were examined under similar conditions. As a result, the
former gave a separable mixture of cis- and trans-2d in 15%
yield (entry 3), and the latter was smoothly transformed to 2e
with a shorter reaction time and in better yield (entry 4). A
careful investigation of the NMR results revealed that the
stereochemistry of the methyl group in 1d,e was successfully
transferred to the corresponding products. We next exam-
ined the effect of R2 using 1f-h. A substrate with a phenyl
group as R2, such as 1f, gave the corresponding trans adducts
(2fa) in 59% yield together with 2fb in 5% yield (entry 5). In
the case of 1g, the reaction was completely prohibited;
however a substrate with a cyclopropyl group (1h) gave the
trans adduct in 27% yield (entries 6 and 7). When the
reaction using 1i was performed under similar conditions,
the formation of five contiguous stereogenic centers was
completely controlled in a single operation to give 2i as a
sole cycloadduct in 60% yield (entry 8). The reactivity of a
substrate with alkylidene cyclopropane (1j, k) also depended
on the steric bulk of R1 and 1j gave a separable mixture of cis-
and trans-fused cycloadducts in 60% yield (entry 9). How-
ever, 1k was completely inert for this cycloaddition reaction
(entry 10). In the case of malonate derivatives, R1 had a
significant effect, and bulkier substituents gave trans selec-
tivity. For example, 1j gave an inseparable 1:1 mixture of cis
and trans adducts in 60% yield (entry 11), and both 1k and 1l
were exclusively transformed to the corresponding trans
adducts in respective yields of 78% and 56% (entries 12
and 13). As described in entries 14 and 15, the steric bulk of
R2 dramatically decreased the reactivity of 1o and 1p even
when R1 was H, and the latter gave an inseparable mixture
of cycloadducts cis- and trans-2p in 41% yield. The sub-
stituents at both the R1 and R2 positions in 1q and 1r
completely prevented the reaction (entries 16 and 17).
Bisacetoxymethyl instead of an ethoxycarbonyl group gave
trans-2s in 59% yield exclusively when R2 was phenyl group
(entry 18).
Next, we sought to prepare a tricyclic skeleton using this
protocol (Scheme 4). Both substrates (3a,b) were successfully
converted to the corresponding nitrogen heterocycles in a
stereoselective manner. The stereochemistry of all of the
products was fully assigned by NMR analysis.
To confirm the reaction pathways and catalytic cycle, 5a
was examined for the formation of the third ring by the
insertion of terminal carbon-carbon double bonds if orga-
nopalladium species could be generated as key intermediates
and were sufficiently reactive (Scheme 5). We realized that
both the [4 þ 2] cycloadducts (6aa) and the expected tricyclic
product were obtained. The latter product (6ab) was fully
characterized, and its stereochemistry was assigned based on
the results of an NOE experiment between CH2CN and
CHCN. This result constitutes direct evidence for the gen-
eration of an alkenylpalladium species that reacts with a
cyanoallene intermediate before reductive elimination.
Other substrates 5b-d revealed the reactivity of cyanoal-
lene intermediates. When alkenyl chains were introduced at
the ortho position in a phenyl group, the [4 þ 2] cycloaddition
reaction was favored and terminal C-C double bonds were
(11) Supplemental crystallographic data is available free of charge from
the Cambridge Crystallographic Data Centre (nos. 746745 and 748867 for
cis- and trans-2b, respectively).
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TABLE 1. Substrate Scope of [4 þ 2] Cycloadditiona
aAll reactions were carried out in the prepsence of Pd(CN)2 (10 mol %) with TMSCN (2.5 equiv) in EtCN at 90 °C under O2 atmosphere (1 atm).
intact during the reactions (Scheme 6). For example, 5b was
successfully transformed to 6b in 48% yield as a single
stereoisomer. Compounds 5c and 5d showed similar reactiv-
ity to give 6c and 6d without any trapping by the terminal
C-C double bonds, with respective yields of 34% and 52%.
Finally, we concluded that alkyl- or benzylpalladium species
would quickly react with cyanoallene intermediates via a
6-endo mode rather than 5- or 6-exo-cyclization with term-
inal C-C double bonds in 5b-d.
According to the experimental details described above, we
propose a plausible catalytic cycle for this [4 þ 2] cycloaddi-
tion (Scheme 7). A terminal C-C triple bond of the con-
jugated enyne is initially activated by Pd(II) and nucleophilic
cyanation with TMSCN at a terminal sp carbon (cyano-
palladation) gives allylpalladium species A that promotes
5-exo-cyclization by the insertion of olefin. This first cycliza-
tion step obviously determines the stereochemistry of the
ring juncture, and the results in Table 1 suggest that the steric
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SCHEME 4. Application to the Synthesis of a Tricyclic Core
SCHEME 5. Sequential Ring Formation Using 5a
SCHEME 6. Cycloaddition Using 5b-d
Finally, the dicyanated bicyclic products 2 are obtained by
reductive elimination from D together with Pd(0), which
could be smoothly converted to Pd(CN)2 by oxygen with
TMSCN via PdO2. When a butenyl side chain is introduced
to a conjugated enyne such as 5d, D1 could be trapped by
insertion for the third cyclization before reductive elimina-
tion, and would give 6ab with Pd(0). The above results can
explain why this cycloaddition proceeds via a palladium-
mediated sequence that includes organopalladium inter-
mediates A-D.12
Next, we applied this protocol to an intermolecular ver-
sion. When a conjugated enyne 7a was examined, methyl
acrylate (MA) gave [4 þ 2] cycloadducts 8a as an exclusive
product with a 1:1 mixture of diastereomers in 60% yield
(entry 1). Substrates with a seven- and eight-membered ring
were also applicable to give 8b,c in respective yields of 44 and
56% (entries 2 and 3). Compound 7d was also converted to
the corresponding cycloadducts in moderate yield. These
results are summarized in Table 2.
When the syn-1,2-dicyano adduct from 7a with methyl
acrylate was employed under similar thermal conditions,
traces of the cycloadducts were obtained as a mixture of
regioisomers. Even in the presence of TMSCN and/or Pd(II)
bulk of R1 and R2 is quite important for both the reactivity
and selectivity in this cyclization. On the basis of the results
of 1b vs 1g, 1j vs 1k, and 1m vs 1r, the steric repulsion between
R1 and R2 would prevent exo-cyclization. On the other hand,
higher trans selectivity was observed when bulky substituents
were introduced. These results explain why intermediate B1
from A is preferred to B2, so that cycle I could proceed
predominantly when the reaction proceeds trans-selectively.
These schemes reasonably explain the results in entries 3
and 4. The reactivity is dependent on the stereochemistry of
the olefin because an E-methyl group rather than Z- would
cause more critical steric repulsion against R1 to prevent the
first cyclization. The stereogenic center on R3 is completely
controlled because the A13 strain in the transition state in
the first cyclization step would cause R3 to be at a pseudo-
equatorial position. When 5-exo-cyclization successfully
occurred, the corresponding alkyl palladium(II) species C1
and C2 could be generated. In the case of 1d, 1g and 1q, the
reactions proceeded smoothly against the steric bulk of
the phenyl group. This could be explained by the notion that
the corresponding benzylpalladium species (R2 = Ph) could be
stabilized due to η1-η3 equilibrium and subsequent insertion
of the double bond of cyanoallene would complete 6-endo-
cyclization to give alkenyl palladium species D1 and D2.
(12) As the one of the reviewers indicates, another reaction pathway is
also possible. If the alkenylpalladium species by initial cyanopalladation
could be directly converted to cyclohexenylpalladium species via [4 þ 2]
cycloaddition, the following reductive elimination would give the same
products, as shown below. Further investigation to evaluate this possibility
is currently underway.
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SCHEME 7. Plausible Catalytic Cycle
TABLE 2. Intermolecular Dicyanative [4 þ 2] Cycloaddition
a regioselective fashion. These observations could provide a
new perspective on palladium chemistry, and further appli-
cation of this dicyanation of alkynes is currently underway.
Experimental Section
Typical Procedure for Pd-Catalyzed Enyne Cyclization of 1d
(Table 1, Entry 3). To a solution of enyne 1d (0.3 mmol) in EtCN
(3.0 mL) were added palladium cyanide (4.8 mg, 0.03 mmol, 10
mol %) and TMSCN (0.1 mL, 0.75 mmol) at room temperature.
The mixture was stirred for 3 h at 90 °C under an oxygen
atmosphere. After the reaction was monitored by TLC, subse-
quent direct column chromatography (hexane-AcOEt) gave
the cyclized products cis-2d and trans-2a, respectively.
entry
substrate 7
time (h) yield of 8 (%) diastereo ratio
1
2
3
4
7a: X = CH2, n = 1
7b: X = CH2, n = 2
7c: X = CH2, n = 3
7d: X = CHt-Bu, n = 1
24
24
43
24
8a: 60
8b: 44
8c: 56
8d: 35
1:1
2:1
1:1
1:1
For cis-2d: colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.15
(d, J = 6.4 Hz, 3H), 1.47-1.56 (m, 1H), 2.00-2.05 (m, 1H),
2.84-2.90 (m, 2H), 3.04 (ddd, J = 2.0, 2.4, 9.2 Hz, 1H), 3.29
(dd, J = 3.6, 11.2 Hz, 1H), 3.53 (dd, J = 6.8, 11.2 Hz, 1H), 3.68
(dd, J = 12.4, 14.0 Hz, 1H), 6.62 (dd, J = 2.8, 4.0 Hz, 1H), 7.38
(d, J= 8.4 Hz, 2H), 7.71 (d, J= 8.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 18.3, 21.6, 32.0, 35.3, 38.2, 40.9, 50.6, 50.7, 109.5, 115.5,
116.8, 127.5, 130.0, 132.5, 144.6, 145.0; IR (ATR) ν 2924, 2221,
1341, 1156, 1091, 814, 753 cm-1; LRMS (EI) m/z 341 (Mþ), 275,
238, 186 (Mþ - Ts), 155 (Ts), 140, 105, 91, 58; HRMS (EI) calcd
for C18H19N3O2S, 341.1198 (Mþ), found 341.1186.
and/or oxygen, the results were not improved at all. These
results suggest that this cycloaddition reaction includes not a
concerted mechanism but a palladium-mediated stepwise
cyclization pathway through the reaction (see the Support-
ing Information).
Conclusion
We have demonstrated a palladium-catalyzed dicyanative
[4 þ 2] cycloaddition of various dienynes and propose a
catalytic cycle that offers a reasonable explanation for the
observed stereoselectivity. This cycloaddition includes (1)
the sequential formation of four C-C bonds, (2) easy access
to functionalized cyclohexenes, and (3) facile construction of
a polycyclic ring system. For example, ene-enynes 1 and 3
were successfully converted to the corresponding dicyano
cycloadducts 2 and 4, respectively. The former reaction was
strongly influenced by the substituents on carbon-carbon
multiple bonds and their steric repulsion was quite important
for achieving higher trans selectivity. Furthermore, cycload-
dition using 1 can control a maximum of five contiguous
stereogenic centers. In the case of 3, a tricyclic core was easily
constructed in a single operation. The reaction using
enynes 7 with MA gave the corresponding cycloadducts in
1
For trans-2d: colorless solid; H NMR (400 MHz, CDCl3)
δ 1.22 (d, J = 6.8 Hz, 3H), 1.58-1.69 (m, 1H), 1.99-2.08 (m,
1H), 2.34-2.42 (m, 1H), 2.46 (s, 3H), 2.95 (dd, J = 9.2, 11.6 Hz,
1H), 3.05 (dd, J = 9.6, 11.2 Hz, 1H), 3.53 (m, 1H), 3.60 (dd, J =
7.2, 9.6 Hz, 1H), 3.79 (dd, J = 7.6, 9.2 Hz, 1H), 6.83-6.85
(m, 1H), 7.36 (d, J=8.4 Hz, 2H), 7.71 (d, J=8.4 Hz, 2H); 13
C
NMR (100 MHz, CDCl3) δ 16.8, 21.6, 33.5, 36.9, 43.2, 43.7,
49.5, 49.7, 110.5, 115.2, 115.8, 127.2, 130.1, 134.2, 144.1, 145.3;
IR (ATR) ν 2969, 2923, 2225, 1322, 1157, 1099, 809, 766 cm-1
;
LRMS (EI) m/z 341 (Mþ), 277, 198, 186 (Mþ - Ts), 155 (Ts), 91,
83, 58; HRMS (EI) calcd for C18H19N3O2S 341.1198 (Mþ),
found 341.1201; mp 196-197 °C.
Typical Procedure for Pd-Catalyzed Intermolecular [4 þ 2]
Cycloaddition Using Conjugated Enynes 7a with Methyl Acrylate
(Table 2, Entry 1). To a solution of a starting enyne (162 mg,
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1.0 mmol) in propionitrile (1.0 mL) were added TMSCN (298 mg,
3.0 mmol), methyl acrylate (400 mg, 5.0 mmol), and Pd(CN)2
(16 mg, 0.1 mmol) at room temperature. The resulting mixture
was heated under oxygen atmosphere (1 atm) at 100 °C for 24 h.
The following direct flash column chromatography (hexane/
AcOEt = 2:1) gave inseparable diastereomixture of the desired
[4 þ 2] cycloadducts as yellow oil (106.2 mg, 35%).
ν 2953, 2870, 2214, 1735, 1202 cm-1; LRMS (EI) m/z 300 (Mþ),
285 (Mþ - Me), 273 (Mþ - HCN), 244, 230, 217, 185, 158; HRMS
(EI) calcd for C18H24N2O2 300.1838 (Mþ), found 300.1835.
Acknowledgment. S.A. thanks KAKENHI (No. 21590003)
for financial support. We thank Prof. Shinji Harada (Chiba
University) for his kind support with the X-ray crystallographic
analysis.
Major two isomers are assigned: 1H NMR (400 MHz, CDCl3)
δ 0.85 (s, 9H X 0.5), 0.89 (s, 9H X 0.5), 1.10-1.68 (m, 4H),
1.72-1.85 (m, 1H), 1.95-2.05 (m, 1H), 2.32-2.87 (m, 4H), 3.76
(s, 3H X 0.5), 3.82 (s, 3H X 0.5); 13C NMR (100 MHz, CDCl3) δ
21.5, 21.6, 23.8, 26.8, 26.9, 27.4, 27.8, 29.0, 29.2, 30.1, 31.2, 31.6,
32.6, 33.1, 34.6, 35.8, 40.4, 41.3, 41.7, 43.1, 52.1, 52.7, 99.7, 100.9,
115.3, 115.7, 116.8, 117.9, 164.2, 166.4, 170.1, 171.5; IR (ATR)
Supporting Information Available: Full characterization of
new compounds of cycloadducts and cyclization precursors
via 1H and 13C NMR. This material is available free of charge
via the Internet at http://pubs.acs.org.
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