Construction of tricyclic pyran derivatives through intramolecular [2+2+2] cycloaddition of allenynes with tethered aldehydes

Article abstract of DOI:10.1016/j.tet.2013.04.068

Rh(I)-catalyzed intramolecular [2+2+2] cycloaddition of allenynes with tethered aldehydes was investigated. The cyclizations proceeded smoothly under mild conditions to give various tricyclic compounds containing a pyran ring in good to high yields in a stereoselective manner.

Full text of DOI:10.1016/j.tet.2013.04.068

Tetrahedron 69 (2013) 7713e7718
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Tetrahedron
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Construction of tricyclic pyran derivatives through intramolecular
[2þ2þ2] cycloaddition of allenynes with tethered aldehydes
*
*
Yoshihiro Oonishi , Yoshitaka Kitano, Yoshihiro Sato
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Rh(I)-catalyzed intramolecular [2þ2þ2] cycloaddition of allenynes with tethered aldehydes was in-
vestigated. The cyclizations proceeded smoothly under mild conditions to give various tricyclic com-
pounds containing a pyran ring in good to high yields in a stereoselective manner.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 27 February 2013
Received in revised form 13 April 2013
Accepted 15 April 2013
Available online 27 April 2013
Keywords:
Rhodium
[2þ2þ2] cycloaddition
Allene
Alkyne
Aldehyde
1. Introduction
Transition-metal-catalyzed [2þ2þ2] cycloaddition between
three components of multiple bonds is a promising strategy for
construction of complex polycyclic skeletons from simple starting
materials.1 In this context, our group has also reported a variety of
[2þ2þ2] cycloadditions using various transition metals such as Ni,
Pd, and Ru, and some applications of those cycloadditions to the
synthesis of natural products have already been reported.2 Herein
we report a novel Rh-catalyzed [2þ2þ2] cycloaddition between
alkyne, allene, and aldehyde, giving a tricyclic compound contain-
ing a pyran ring. The [2þ2þ2] cycloaddition was found during our
ongoing investigation of a Rh(I)-catalyzed cyclopropanation/cycli-
zation cascade between an allene having a tert-butyl substituent
and tethered alkynes.3 That is, the reaction of 1 in the presence of
a catalytic amount of [Rh(IiPr)(cod)]ClO4 provided cyclic com-
pounds containing a cyclopropane ring in good to high yields, no-
tably in which an sp3 CeH bond activation occurs at the stage of
conversion of rhodacycle intermediate A to B along with the for-
mation of a cyclopropane ring (Scheme 1). In this cyclization, the
reaction of allenyne 1a (n¼4), having an aldehyde five carbons
away from the terminus of alkyne in the chain, proceeded without
any interference by the existence of the aldehyde moiety, giving the
•
cat.
( )n
X
( )n
X
[Rh(IiPr)(cod)]ClO4
H
Cyclopropanative
Cyclization
R
1
2
R
up to 92% yield
H
C-H activation
( )n
X
( )n
X
Rh
Rh H
R
R
A
B
Scheme 1. Cyclization through C(sp3)eH bond activation.
expected cyclopropanation/cyclization product 2a in 91% yield
(Scheme 2). On the other hand, the reaction of 1b, which has an
aldehyde four carbons away from the terminus of alkyne in the
chain (n¼3), gave the tricyclic compound 3b instead of 2b as
a major product.
The stereochemistry of 3b with respect to the ring junction was
determined to be syn by an NOE experiment, as shown in Scheme 2.
This result means that a [2þ2þ2] cycloaddition between alkyne,
allene, and aldehyde moieties in 1b proceeded in a stereoselective
manner through insertion of C]O bonds of the aldehyde moiety
* Corresponding authors. Tel.: þ81 11 706 3722; fax: þ81 11 706 4982; e-mail
addresses: oonishi@pharm.hokudai.ac.jp (Y. Oonishi), biyo@pharm.hokudai.ac.jp (Y.
Sato).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.068

7714
Y. Oonishi et al. / Tetrahedron 69 (2013) 7713e7718
the desired product 3b in modest to good yields (runs 4e6). The
yield of 3b was improved to 66% in the reaction of 1b using
[Rh(IMe)(cod)]ClO4, but the reaction was very slow (run 6). In-
terestingly, it was found that the cyclization of 1b with 10 mol %
[Rh(cod)]ClO4 in the absence of both phosphines and NHC ligands
proceeded smoothly, giving the desired cyclic compound 3b in 69%
yield (run 7).
Next, the effects of both the counteranion parts of cationic Rh
complexes and solvents were investigated (Table 2). Change in the
counteranion of Rh cation complex from ClOꢀ4 to SbF6ꢀ did not in-
fluence the yield of 3b but slowed down the reaction rate (run 1).
The reaction of 1b using ½RhðcodÞꢁPFꢀ6 was also slow, but the desired
product 3b was obtained in 77% yield (run 2). It was found that the
use of ½RhðcodÞꢁBFꢀ4 greatly improved the yield of 3b up to 83% (run
3). Change in the solvent from ClCH2CH2Cl to THF or toluene
seemed to retard the reaction, and the product 3b was obtained
only in 10 or 20% yield along with the recovery of the starting
material 1b in 28 or 39% yield, respectively (runs 4 and 5).
Scheme 2. Cyclization of allenynes with tethered aldehyde.
into the rhodacycle intermediate A.4,5 Although numerous exam-
ples of inter- or intramolecular [2þ2þ2] cycloaddition of alkynes or
alkenes as a multiple bond component have been reported,
[2þ2þ2] cycloaddition of substrates including an allene as a cou-
pling partner is limited to several examples.6e11 Furthermore, there
have been only a few reports on intramolecular [2þ2þ2] cycload-
ditions involving C]O bonds such as aldehydes and ketones.12e14
Thus, we investigated in detail the Rh-catalyzed [2þ2þ2] cyclo-
addition of allenynes 1 having an aldehyde moiety in the chain.
Table 2
Effects of counteranions and solvents
2. Results and discussion
We initially examined various Rh(I) complexes in this reaction in
order to improve the yield of [2þ2þ2] cyclized product 3b (Table 1).
The reaction of 1b using 10 mol % of cationic Rh complexes having
phosphine ligands such as dppe and dppb instead of [Rh(IiPr)(cod)]
ClO4 (cf. Scheme 2) provided no desired tricyclic compound 3b and
the starting material was recovered in 37 and 13% yields, re-
spectively (runs 1 and 2). Also, the use of Wilkinson’s catalyst
(Rh(PPh3)3Cl) was not effective in this reaction, and the desired
product was not obtained (run 3). Compared to the above
Rhephosphine catalysts, the RheNHC catalyst seemed to be ef-
fective in the reaction of 1b.
Run
[Rh(cod)]Xa
Solvent
Time (h)
Yield (%)
3b
2b
SM rec.
1
2
3
4
5
[Rh(cod)]SbF6
[Rh(cod)]PF6
[Rh(cod)]BF4
[Rh(cod)]BF4
[Rh(cod)]BF4
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
THF
23
23
2
24
24
69
77
83
10
20
12
9
2
23
15
d
d
d
28
39
toluene
Thus, the use of cationic RheNHC complexes including [Rh(I-
Mes)(cod)]ClO4, [Rh(IPr)(cod)]ClO4, and [Rh(IMe)(cod)]ClO4 gave
a
[Rh(cod)]X complexes were prepared in situ from [Rh(cod)Cl]2 and AgX.
Table 1
Having established the optimal conditions for the [2þ2þ2] cy-
cloaddition of allenyne with tethered aldehyde, we turned our at-
tention to investigating the cycloaddition of various substrates
(Table 3). The cyclization of 1c and 1d proceeded smoothly, giving
the corresponding tricyclic products 3c and 3d in 59 and 80% yields,
respectively (runs 1 and 2). The reaction of 1e, having an oxygen
atom in the chain, did not afford the corresponding product 3e
under the standard optimal conditions. However, the addition of
1.0 equiv of 2,2,2-trifluoroethanol (TFE) to the reaction mixture
promoted the cycloaddition, giving the product 3e in 25% yield
(run 3).15 In the case of 1f, containing a nitrogen atom in the chain,
the corresponding heterocycle 3f was obtained in a moderate yield
without addition of TFE (run 4). The reactions of allenynes 1g and
1h, having an aromatic ring and a methyl group on the terminus of
allene, respectively, afforded the corresponding [2þ2þ2] products
3g and 3h in good yields (runs 5 and 6). In those cases, however, the
product 3g was obtained as a single isomer, while the product 3h
was obtained as a mixture of isomers with respect to the ring
junction (syn/anti¼2.3:1). Each isomer of 3h was separated into syn-
4h and anti-4h after conversion of a mixture of 3h to 4h, and those
stereochemistries were unambiguously determined by NOESY
spectra (Scheme 3). Notably, the [2þ2þ2] cycloaddition is applica-
ble to construction of a 5-6-5 fused tricyclic ring system, and the
corresponding product 3i was obtained from 1i in 81% yield (run 7).
[2þ2þ2] Cycloaddition of 1b using various Rh(I) complexes
Run
Rh complex
Time (h)
Yield (%)
3b
2b
SM rec.
1a
2a
3
[Rh(dppe)]ClO4
[Rh(dppb)]ClO4
Rh(PPh3)3Cl
[Rh(IMes)(cod)]ClO4
[Rh(IPr)(cod)]ClO4
[Rh(IMe)(cod)]ClO4
[Rh(cod)]ClO4
20
23
20
2
1
24
2
d
d
d
44
34
66
69
d
d
d
44
12
16
16
37
13
45
d
d
d
d
4b
5b
6b
7c
a
[Rh(phosphine)]ClO4 was prepared in situ by treatment of [Rh(cod)2]ClO4 and
ligand with H2.
b
c
[Rh(NHC)(cod)]ClO4 was prepared in situ from Rh(NHC)(cod)Cl and AgClO4.
[Rh(cod)]ClO4 was prepared in situ from [Rh(cod)Cl]2 and AgClO4.

Y. Oonishi et al. / Tetrahedron 69 (2013) 7713e7718
7715
Table 3
[2þ2þ2] Cycloaddition of various substratesa
Run
Substrate
Conditions
Productb
1
1c
0
ꢂC, 1 h 3c: 59%
Scheme 3. Determination of the stereochemistry of 3h.
2
1d
rt, 1 h
3d: 80%
3c 1e (X¼O)
rt, 24 h
rt, 20 h
3e: 25%
3f: 47%
Scheme 4. Reaction of 1j.
4
1f (X¼NTs)
On the basis of the above-described results, the possible re-
action mechanism for the [2þ2þ2] cycloaddition is proposed in
Scheme 5. Initially, a rhodacycle A would be formed by oxidative
cycloaddition of the alkyne part and one C]C bond of the allene
moiety of 1 to a cationic Rh(I) complex.17 Insertion of an aldehyde
moiety of 1 into A through B would occur to produce the rhodacycle
C, from which reductive elimination gives the tricyclic [2þ2þ2]
cycloadduct 3 along with regeneration of the Rh(I) complex.
5
6
1g (R¼Ph)
1h (R¼Me)
rt, 3 h
rt, 1 h
3g: 67%
3h: 70% (syn/anti¼2.3:1)
7
1i
rt, 1 h
3i: 81%
a
All reactions were carried out using 5 mol % [Rh(cod)Cl]2 and 10 mol % AgBF4 in
ClCH2CH2Cl.
b
The stereochemistries of all products except for 3h were determined by NOE
experiments in a manner similar to that shown in Scheme 2.
c
TFE of 1.0 equiv was added.
With the aim of construction of tricyclic ring system containing
a seven-membered ring via [2þ2þ2] cycloaddition, the reaction of
allenyne 1j, having four carbon units between allene and alkyne,
under optimal conditions was carried out (Scheme 4). As a result,
the expected cycloadduct 3j was not obtained at all, but a ketone 5j
was obtained in 52% yield. The product 5j would be formed through
rearrangement of the 5-alkynal moiety in the substrate.16
Scheme 5. Catalytic cycle of [2þ2þ2] cycloaddition.

7716
Y. Oonishi et al. / Tetrahedron 69 (2013) 7713e7718
Since the substrates 1ae1i have an aldehyde moiety in the
stereoselective manner. Despite extensive studies on various tran-
sition-metal-catalyzed [2þ2þ2] cycloadditions, a reaction that can
utilize an allene or a carbonyl group as a component of multiple
bonds is very rare, and the present study is valuable in that it not
only provides a methodology for construction of polycyclic skele-
tons containing a pyran ring but also a mechanistic information
about [2þ2þ2] cycloadditions.
chain, other reactions such as hydroacylation via oxidative addition
of CeH bond of the aldehyde moiety might be thought to occur as
a competitive reaction.18 However, the reactions of 1ae1i under the
optimal conditions gave only the corresponding [2þ2þ2] cyclo-
adducts. These results indicate that oxidative addition of aldehyde
moiety might occur but should be non-productive process in this
reaction. In the case of 1j, formation of the corresponding rhoda-
cycle intermediate, having a 7-5 bicyclic ring system, would be
unfavorable, which resulted in producing 5j via rearrangement of
the 5-alkynal moiety.16
4. Experimental section
4.1. General
As shown in Table 3, the [2þ2þ2] cycloaddition proceeded in
a highly stereoselective manner, and syn-3 was exclusively pro-
duced in most cases except for the reaction of 1h. The stereo-
selectivity between a syn-isomer and an anti-isomer should
appear at the stage of insertion of the C]O bond of aldehyde into
the rhodacycle (i.e., from B to C in Scheme 5), and the plausible
stereochemical reaction course is depicted in Scheme 6. There are
two possible coordination modes of the C]O bond to the Rh metal
(i.e., syn-B and anti-B), and the intermediates, syn-B and anti-B,
would be in equilibration via intermediate A. The syn-product 3
and anti-product 3 should be produced via insertion of the C]O
bond into the C(sp2)eRh bond in syn-B and anti-B,, respectively,
followed by reductive elimination. According to molecular model-
based analysis, the reaction course via syn-B that leads to syn-3
seemed to proceed smoothly without any interference. On the
other hand, another reaction course producing anti-3 would cause
All manipulations were performed under an argon atmo-
sphere unless otherwise mentioned. THF and toluene were pu-
rified using The Ultimate Solvent System (Glass Counter Inc.).
ClCH2CH2Cl was distilled under an argon atmosphere from CaH2.
Infrared spectral measurements were carried out with a JASCO
FT/IR-460 Plus spectrometer and only significant absorptions
were listed. 1H and 13C NMR spectra were recorded on Jeol
ECX400 (400 MHz), Jeol ECS400 (400 MHz), and Jeol ECA500
(500 MHz) NMR spectrometers. Chemical shifts are reported in
parts per million (ppm) using CHCl3 (7.26 ppm) and C6H6
(7.16 ppm) for 1H NMR and CDCl3 (77.00 ppm) and C6D6
(128.06 ppm) for 13C NMR as an internal standard. Mass spectra
were measured with JEOL JMS-T100LP, JMS-T100GCv, and JMS-
FAB mate mass spectrometer for LRMS (EI) and HRMS (EI), and
Thermo Scientific Exactive mass spectrometer for LRMS (ESI) and
HRMS (ESI).
a steric repulsion between the substituent R and
a-CH2 of the
carbonyl group (i.e., anti-B0), which would prevent the formation
of anti-3. In the case of 1h (R¼Me), the methyl substituent is
obviously smaller than other substituents (R¼tBu and Ph), which
reduced the steric repulsion in anti-B0, resulting in a low syn/anti-
selectivity of the product 3h.
4.2. General procedure for [2D2D2] cycloaddition using
[Rh(cod)]BF4
A solution of [Rh(cod)Cl]2 (5 mol % of the complex to a sub-
strate (i.e., 10 mol % as a rhodium catalyst to a substrate)) and
AgBF4 (10 mol % to a substrate) in degassed ClCH2CH2Cl (0.013 M to
the complex) was stirred at room temperature for 10 min. A so-
lution of substrate in the degassed solvent (0.16 M solution of the
substrate) was added to the mixture, and the reaction mixture was
stirred at the indicated temperature until the substrate dis-
appeared on TLC. After removal of the solvent, the residue was
purified by column chromatography on silica gel to give the cor-
responding product.
3. Conclusion
We have succeeded in developing a novel Rh(I)-catalyzed
intramolecular [2þ2þ2] cycloaddition between alkyne, allene,
and aldehyde moieties through insertion of C]O bonds of the al-
dehyde moiety into the rhodacycle intermediate derived from
allenyne. The reaction conditions are very mild, and tricyclic carbo-
and heterocyclic compounds containing a pyran ring system are
formed from acyclic substrates in one-pot in
a
highly
Scheme 6. Stereochemical reaction course.

Y. Oonishi et al. / Tetrahedron 69 (2013) 7713e7718
7717
4.3. Spectral data of the cyclized products
(m,1H),1.85e1.77 (m,1H),1.70e1.59 (m,1H), 1.31e1.21 (m, 2H), 0.89
(s, 9H); 13C NMR (125 MHz, CDCl3)
143.6, 138.0, 133.3, 129.8 (2C),
d
4.3.1. Dimethyl (E)-4-(2,2-dimethylcyclopropyl)-5-(5-oxopentylidene)
cyclohex-3-ene-1,1-dicarboxylate (2b). IR (neat) 1737, 1437, 1254,
129.6 (2C), 127.6, 119.1, 115.9, 83.2, 74.3, 44.6, 44.1, 36.8, 32.5, 27.6
(3C), 24.9, 21.5, 19.8; EI-LRMS m/z 387 [(M)þ], 330, 174, 57; EI-HRMS
calcd for C22H29NO3S 387.1868, found 387.1868.
1058 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
9.80 (t, J¼1.6 Hz, 1H), 5.60
(dd, J¼7.2, 7.2 Hz, 1H), 5.43 (dd, J¼4.5, 4.5 Hz, 1H), 3.72 (s, 3H), 3.61
(s, 3H), 3.06 (d, J¼19.2 Hz, 1H), 2.80 (dd, J¼17.2, 4.5 Hz, 1H),
2.65e2.56 (m, 2H), 2.51e2.46 (m, 2H), 2.29e2.15 (m, 2H), 1.76 (tt,
J¼7.2, 7.2 Hz, 2H), 1.16 (dd, J¼7.7, 7.7 Hz,1H), 1.41 (s, 3H), 0.68 (s, 3H),
4.3.7. Dimethyl (3aR
[c]isochromene-8,8(1H)-dicarboxylate (3g). IR (neat) 1732, 1436,
1255 cmꢀ1; 1H NMR (500 MHz, CDCl3)
7.29e7.26 (m, 5H), 5.44 (dd,
*
,5R)-5-phenyl-2,3,3a,5,7,9-hexahydrocyclopenta
d
0.50e0.45 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
202.5, 171.9, 171.5,
J¼4.2, 4.2 Hz, 1H), 5.36 (s, 1H), 3.86 (dd, J¼9.7, 9.7 Hz, 1H), 3.74 (s,
3H), 3.72 (s, 3H), 3.02 (d, J¼14.9 Hz,1H), 2.91 (dd, J¼17.8, 4.2 Hz,1H),
2.75e2.70 (m, 2H), 2.55e2.29 (m, 2H), 1.97e1.84 (m, 1H), 1.82e1.77
136.5, 133.3, 126.0, 122.1, 54.0, 52.8 (2C), 43.5, 32.4, 30.7, 29.5, 28.8,
27.7, 22.0, 19.5, 17.2, 16.7; EI-LRMS m/z 348 [(M)þ], 289, 230, 157, 59;
EI-HRMS calcd for C20H28O5 348.1937, found 348.1937.
(m, 1H), 1.55e1.42 (m, 2H); 13C NMR (125 MHz, CDCl3)
d 171.7, 171.4,
140.3, 139.7, 130.9, 128.2 (2C), 128.0 (2C), 127.6, 120.6, 118.6, 77.9,
72.7, 53.8, 52.8, 52.7, 31.9, 31.5, 30.9, 25.9, 20.4; EI-LRMS m/z 368
[(M)þ], 309, 291, 225, 165, 77, 59; EI-HRMS calcd for C22H24O5
368.1624, found 368.1619.
4.3.2. Dimethyl (3aR
*
,5R )-5-(tert-butyl)-2,3,3a,5,7,9-hexahydrocyclo
*
penta[c]isochromene-8,8(1H)-dicarboxylate (3b). Mp 142e143 ꢂC
(recrystallized from hexane/AcOEt); IR (film, CHCl3) 1737, 1434,
1256 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
5.35 (td, J¼4.0, 4.0 Hz, 1H),
4.51 (dt, J¼7.5, 7.5 Hz, 1H), 3.85 (s, 1H), 3.72 (s, 3H), 3.68 (s, 3H), 2.93
(d, J¼14.8 Hz, 1H), 2.88 (dd, J¼17.5, 4.0 Hz,1H), 2.69 (d, J¼14.8 Hz, 1H),
2.64 (dd, J¼17.5, 4.0 Hz, 1H), 2.41e2.34 (m, 2H), 2.10e2.05 (m, 1H),
1.85e1.76 (m, 1H), 1.68e1.57 (m, 1H), 1.37e1.18 (m, 1H), 0.92 (s, 9H);
4.3.8. (3aR
1H-spiro[cyclopenta[c]isochromene-8,50-[1,3]dioxane] (syn-4h). IR
(neat) 1734,1442 cmꢀ1; 1H NMR (500 MHz, CDCl3)
*
,5R
)-5-Methyl-20,20-dimethyl-2,3,3a,5,7,9-hexahydro-
*
d
5.34 (dd, J¼4.3,
4.3 Hz, 1H), 4.29 (dd, J¼8.3, 8.3 Hz, 1H), 4.22e4.18 (m, 1H), 3.54 (s,
4H), 2.45e2.25 (m, 3H), 2.17e2.05 (m, 3H), 1.88e1.82 (m, 2H),
1.67e1.57 (m, 2H), 1.43 (s, 3H), 1.41 (s, 3H), 1.39 (d, J¼6.5 Hz, 3H);
13C NMR (125 MHz, CDCl3)
d 171.8, 171.3, 138.3, 130.6, 120.7, 118.6,
84.0, 74.7, 53.7, 52.8, 52.7, 36.8, 33.1, 31.7, 31.0, 27.7 (3C), 25.4, 20.0; EI-
LRMS m/z 348 [(M)þ], 291, 262, 230, 59, 57; EI-HRMS calcd for
C20H28O5 348.1937, found 348.1936.
13C NMR (125 MHz, CDCl3)
d 140.2, 135.6, 121.7, 114.7, 98.2, 79.3,
72.7, 68.8, 67.8, 32.2, 32.0, 31.4, 31.2, 25.9, 23.9, 23.6, 20.6, 18.5; EI-
LRMS m/z 290 [(M)þ], 275, 262; EI-HRMS calcd for C18H26O3
290.1882, found 290.1879.
4.3.3. (3aR
*
,5R
)-5-(tert-Butyl)-20,20-dimethyl-2,3,3a,5,7,9-hexahydro-
*
1H-spiro[cyclopenta[c]isochromene-8,50-[1,3]dioxane] (3c). Mp 137
e140 ꢂC (recrystallized from hexane/AcOEt); IR (film, CHCl3) 1460,
4.3.9. (3aR
1H-spiro[cyclopenta[c]isochromene-8,50-[1,3]dioxane] (anti-4h). IR
(neat) 1730,1443 cmꢀ1; 1H NMR (500 MHz, CDCl3)
*
,5S
)-5-Methyl-20,20-dimethyl-2,3,3a,5,7,9-hexahydro-
*
1376, 1128, 1081 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
5.27 (dd, J¼9.0,
9.0 Hz, 1H), 4.49 (dd, J¼8.3, 8.3 Hz, 1H), 3.85 (s, 1H), 3.57 (s, 4H), 2.40
(dd, J¼17.5, 9.0 Hz, 1H), 2.30 (dd, J¼17.5, 9.0 Hz, 1H), 2.25 (s, 2H),
2.08e2.02 (m, 2H), 1.84e1.78 (m, 1H), 1.64e1.57 (m, 1H), 1.42 (s, 3H),
1.41 (s, 3H),1.37e1.23 (m, 2H), 0.95 (s, 9H); 13C NMR (125 MHz, CDCl3)
d
5.25 (dd, J¼4.5,
4.5 Hz, 1H), 4.48 (q, J¼6.7 Hz, 1H), 4.38 (dd, J¼8.3, 8.3 Hz, 1H), 3.59
(s, 4H), 2.45e2.27 (m, 4H), 2.19e2.16 (m, 1H), 2.09e2.00 (m, 2H),
1.85e1.79 (m, 1H), 1.68e1.61 (m, 2H), 1.43 (s, 3H), 1.42 (s, 3H), 1.30
d
138.4, 130.7, 121.4, 118.6, 98.1, 84.1, 74.6, 68.7, 68.2, 37.0, 33.1, 32.1,
(d, J¼6.7 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 139.0, 134.6, 120.1,
31.4, 31.3, 28.0 (3C), 25.5, 24.2, 23.3, 20.0; EI-LRMS m/z 332 [(M)þ],
115.3, 98.2, 72.9, 72.1, 69.1, 67.5, 32.4, 32.3, 32.2, 31.0, 30.9, 25.8,
24.0, 23.5, 20.4; EI-LRMS m/z 290 [(M)þ], 275, 262; EI-HRMS calcd
for C18H26O3 290.1882, found 290.1885.
275, 218, 57; EI-HRMS calcd for C21H32O3 332.2351, found 332.2354.
4.3.4. (3aR
7,8,9-octahydrocyclopenta[c]isochromene (3d). IR (neat) 1455, 1377,
1101, 1027 cmꢀ1 1H NMR (400 MHz, CDCl3)
7.30e7.17 (m, 10H),
*
,5R
*
)-8,8-Bis((benzyloxy)methyl)-5-(tert-butyl)-1,2,3,3a,5,
4.3.10. Dimethyl (3aR
*
,5R )-5-(tert-butyl)-2,3,3a,8-tetrahydro-1H-
*
;
d
dicyclopenta[b,d]pyran-7,7(5H)-dicarboxylate (3i). Mp 128 ꢂC (recry
stallized from hexane/AcOEt); IR (film, CHCl3) 1737, 1435, 1249,
5.23e5.21 (m, 1H), 4.48e4.41 (m, 5H), 3.80 (s, 1H), 3.36 (s, 4H), 2.33
(dd, J¼17.2, 8.0 Hz, 1H), 2.26e2.11 (m, 4H), 2.06e1.99 (m, 2H),
1.77e1.70 (m, 1H), 1.62e1.49 (m, 1H), 1.34e1.19 (m, 1H), 0.90 (s, 9H);
1166 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
5.64 (s, 1H), 4.40 (dd, J¼8.2,
8.2 Hz, 1H), 4.16 (s, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 3.05 (s, 2H),
2.33e2.28 (m, 2H), 2.13e2.06 (m, 1H), 1.84e1.77 (m, 1H), 1.66e1.58
(m, 1H), 1.35e1.23 (m, 1H), 0.94 (s, 9H); 13C NMR (100 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d 138.8, 137.1, 130.1 (2C), 128.2 (2C), 128.1
(2C), 127.2 (4C), 127.1 (2C), 122.2, 119.5, 84.2, 74.5, 73.5, 73.4, 73.2
(2C), 38.6, 36.9, 33.1, 30.1, 29.8, 27.9 (3C), 25.2, 19.9; ESI-LRMS m/z
495 [(MþNa)þ]; ESI-HRMS calcd for C32H40NaO3 495.2875, found
495.2876.
d
171.6,171.1,141.7,134.1,131.4,123.0, 80.7, 74.2, 64.6, 52.8 (2C), 36.8,
34.0, 32.9, 27.2 (3C), 25.9, 20.0; EI-LRMS m/z 334 [(M)þ], 277, 190,
144, 59, 57; EI-HRMS calcd for C19H26O5 334.1780, found 334.1778.
4.3.5. (5R
penta[b]pyrano[3,4-d]pyran (3e). IR (neat) 1475, 1363, 1100,
1078 cmꢀ1; 1H NMR (400 MHz, CDCl3)
*
,6aR
*
)-5-(tert-Butyl)-3,5,6a,7,8,9-hexahydro-1H-cyclo-
4.3.11. Dimethyl 2-(2-(cyclopent-1-en-1-yl)-2-oxoethyl)-2-(6,6-
dimethylhepta-3,4-dien-1-yl)malonate (5j). IR (neat) 1960, 1737,
d
5.45 (dd, J¼3.4, 3.4 Hz, 1H),
1671, 1434, 1234, 1197 cmꢀ1; 1H NMR (500 MHz, C6D6)
d 6.12 (s, 1H),
4.53 (dd, J¼8.6, 8.6 Hz, 1H), 4.34e4.22 (m, 4H), 3.91 (s, 1H),
2.34e2.13 (m, 2H), 2.11e2.07 (m, 1H), 1.85e1.79 (m, 1H), 1.68e1.61
(m, 1H), 1.43e1.32 (m, 1H), 1.00 (s, 9H); 13C NMR (100 MHz, CDCl3)
5.18e5.14 (m, 2H), 3.53 (s, 2H), 3.39 (s, 6H), 2.56e2.52 (m, 2H), 2.43
(t, J¼7.2 Hz, 2H), 2.10 (td, J¼10.3, 5.3 Hz, 2H), 2.02e1.98 (m, 2H), 1.47
(tt, J¼7.2, 7.2 Hz, 2H), 1.02 (s, 9H); 13C NMR (125 MHz, C6D6)
d 201.6,
d
134.7, 128.7, 119.5, 83.0, 74.5, 65.4, 64.9, 36.9, 32.7, 27.8 (3C), 24.5,
194.3, 171.3 (2C), 145.5, 143.4, 104.2, 92.3, 55.4, 52.2 (2C), 42.2, 33.9,
33.1, 31.8, 30.8 (3C), 30.3, 25.2, 22.6; EI-LRMS m/z 362 [(M)þ], 305,
253, 95, 67, 57; EI-HRMS calcd for C21H30O5 362.2093, found
362.2093.
21.0, 20.0; EI-LRMS m/z 234 [(M)þ], 192, 177, 121, 57, 42; EI-HRMS
calcd for C15H22O2 234.1620, found 234.1620.
4.3.6. (5R
lopenta[5,6]pyrano[4,3-c]pyridine (3f). IR (neat) 1482, 1354,
1100 cmꢀ1; 1H NMR (400 MHz, CDCl3)
*
,6aR
*
)-5-(tert-Butyl)-2-tosyl-1,2,3,5,6a,7,8,9-octahydrocyc
Acknowledgements
d
7.66 (d, J¼8.4 Hz, 2H), 7.28
(d, J¼8.4 Hz, 2H), 5.28 (dd, J¼3.9, 3.9 Hz, 1H), 4.45 (dd, J¼8.6, 8.6 Hz,
1H), 3.89e3.68 (m, 5H), 2.40 (s, 3H), 2.37e2.25 (m, 1H), 1.08e2.02
This work was financially supported by Grants-in-Aid for Young
Scientist (B) (No. 20790002) and for Scientific Research (B)

7718
Y. Oonishi et al. / Tetrahedron 69 (2013) 7713e7718
Chem. Commun. 2004, 532; (e) Bennacer, B.; Fujiwara, M.; Lee, S.-Y.; Ojima, I. J.
Am. Chem. Soc. 2005, 127, 17756.
8. For Rh-catalyzed intermolecular [2þ2þ2] cycloaddition of allene-allene-allene,
see: (a) Lu, P.; Ma, S. Org. Lett. 2007, 9, 5319; (b) Chen, G.; Jiang, X.; Fu, C.; Ma, S.
Chem. Lett. 2010, 39, 78.
9. For Rh-catalyzed intermolecular [2þ2þ2] cycloaddition of allene-allene-ene,
see Brusoe, A. T.; Alexanian, E. J. Angew. Chem., Int. Ed. 2011, 50, 6596; For Rh-
catalyzed asymmetric intermolecular [2þ2þ2] cycloaddition of allene-allene-
alkene, see: Brusoe, A. T.; Edwankar, R. V.; Alexanian, E. J. Org. Lett. 2012, 14,
6096.
10. For Ni-catalyzed intermolecular [2þ2þ2] cycloaddition of allene-isocyanide-
isocyanide, see: Miura, T.; Morimoto, M.; Murakami, M. J. Am. Chem. Soc. 2010,
132, 15836.
(No. 23390001) from the Japan Society for the Promotion of Science
(JSPS) and also by a Grant-in-Aid for Scientific Research on In-
novative Areas ‘Molecular Activation Directed toward Straightfor-
ward Synthesis (No. 23105501)’ from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. Y.O. acknowledges
the Akiyama Foundation for financial support.
Supplementary data
Experimental details for the synthesis of substrates and copies
of 1H NMR and 13C NMR spectra of all substrates and products.
Supplementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2013.04.068.
11. For recent reviews on transition metal-catalyzed cycloaddition of allene and
ꢀ
~
unsaturated bonds, see: (a) Lopez, F.; Mascarenas, J. Chem.dEur. J. 2011, 17, 418;
(b) Aubert, C.; Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A. Chem. Rev.
2011, 111, 1954; (c) Inagaki, F.; Kitagaki, S.; Mukai, C. Synlett 2011, 594.
12. For an example of Rh(I)-catalyzed intramolecular [2þ2þ2] cycloaddition in-
volving C]O bonds, see: Suda, T.; Noguchi, K.; Tanaka, K. Angew. Chem., Int. Ed.
2011, 50, 4475 and also see: Ref. 7e.
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