Palladium(0)-catalyzed tandem cyclization of alleneues: Direct construction of tricyclic heterocycles through aromatic C-H activation

Article abstract of DOI:10.1002/chem.200500050

Palladium(0)-catalyzed tandem cyclization of allenenes is described. Treatment of allenenes with an aryl halide, potassium carbonate, and catalytic [Pd(PPh₃)₄] in dioxane afforded tri- or tetracyclic heterocycles in moderate to good

Full text of DOI:10.1002/chem.200500050

Palladium(0)-Catalyzed Tandem Cyclization of Allenenes: Direct
À
Construction of Tricyclic Heterocycles through Aromatic C H Activation
Hiroaki Ohno,* Kumiko Miyamura, Tsuyoshi Mizutani, Yoichi Kadoh, Yusuke Takeoka,
Hisao Hamaguchi, and Tetsuaki Tanaka*[a]
Abstract:
Palladium(0)-catalyzed
allenic moiety, intramolecular carbo-
olefin terminus has proven to be essen-
tial for the success of the tandem cycli-
zation. The reaction with heterocyclic
aryl halides such as iodopyrazine or 4-
bromo-1-methylindole afforded tri- or
tetracyclic heteroaromatic products in
good yields.
À
tandem cyclization of allenenes is de-
scribed. Treatment of allenenes with an
aryl halide, potassium carbonate, and
catalytic [Pd(PPh3)4] in dioxane afford-
ed tri- or tetracyclic heterocycles in
moderate to good yields through inser-
tion of arylpalladium(ii) halide into the
palladation, and aromatic C H bond
activation. The substituent on the
À
Keywords: allenes · C H activa-
tion · heterocycles · palladium · tan-
dem cyclization
Introduction
trast, to the best of our knowledge, tandem carbon–carbon
À
bond formation including C H activation of aromatic rings
À
Palladium-catalyzed C H activation of an aromatic group
by use of allenic compounds is unknown.
has received considerable attention in recent years due to
the wide variety of reactions that afford condensed ring sys-
tems by using a nonfunctionalized aryl group.[1,2,3,4] In partic-
ular, tandem carbon–carbon bond formations through this
process are useful in that complex molecules can be directly
obtained in a single operation. Although palladium-cata-
lyzed monocyclization onto an aryl ring forming two,[5]
three,[6] or four carbon–carbon bonds[7] in a one-pot manner
is well documented, the tandem reaction involving a bis-cyc-
lization process is extremely rare. Grigg and co-workers re-
ported that an aryl halide bearing a carbon–carbon multiple
bond and an additional aryl group undergoes bis or tris cyc-
lization when treated with a palladium(0) catalyst.[8] More
recently, palladium(0)-catalyzed tandem cyclization of
alkyne-substituted phenyl iodide with a terminal alkyne to
form condensed aromatic rings was also reported.[9] In con-
Currently, transition-metal-catalyzed cyclizations of al-
lenes are becoming an attractive approach for the construc-
tion of heterocycles.[10] Cyclizations of allenes of type 1 with
a nucleophilic functionality in the presence of a palladium
catalyst to give 3 or 4 are well documented (Scheme 1).[11,12]
Recently, cyclizations of bisallenes on treatment with silyl-
stannane and palladium(0) were independently reported by
two research groups.[13] Palladium(ii)-catalyzed oxidative
cyclization of allene-substituted alkenes and palladium(0)-
catalyzed cyclization of allenes bearing an allyl ester moiety
were reported by Bꢀckvall et al.[14,15] Furthermore, we re-
cently reported a novel palladium(0)-catalyzed cyclization
of allenenes giving 2,3-cis-pyrrolidines or 3-azabicyclo-
[3.1.0]hexanes.[16] However, palladium(0)-catalyzed tandem
[a] Dr. H. Ohno, K. Miyamura, T. Mizutani, Y. Kadoh, Y. Takeoka,
Dr. H. Hamaguchi, Prof. Dr. T. Tanaka
Graduate School of Pharmaceutical Sciences
Osaka University, 1–6 Yamadaoka, Suita
Osaka 565-0871 (Japan)
Fax : (+81)6-6879-8214
E-mail: hohno@phs.osaka-u.ac.jp
t-tanaka@phs.osaka-u.ac.jp
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Scheme 1. Palladium(0)-catalyzed cyclization of allenes (Nu=nucleo-
phile, X=halide).
3728
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/chem.200500050
Chem. Eur. J. 2005, 11, 3728 – 3741

FULL PAPER
cyclizations of an allene that contains an additional multiple
bond have scarcely been investigated.[17] We expected that
allenene 5 could undergo a tandem cyclization of the type
shown in Scheme 1, through insertion of arylpalladium(ii)
halide into an allenic moiety (step 1), carbopalladation onto
Tandem cyclization of allenenes with iodobenzene deriva-
tives: We recently reported that treatment of amino allene
derivatives of type 14 bearing an allyl group on the nitrogen
atom with an aryl halide and potassium carbonate in the
presence of [Pd(PPh3)4] affords 2,3-cis-pyrrolidines of type
17 through carbocyclization on the double bond of 15 and
subsequent b-hydride elimination of the resulting alkylpalla-
dium intermediate 16 (Scheme 3).[16b] It is apparent that in-
hibition of the b-hydride elimination from 16 is essential for
À
a carbon–carbon double bond (step 2), and aromatic C H
activation of the resulting palladium(ii) intermediate 7 (step
3). Herein we present a full account of our investigation
into the palladium(0)-catalyzed tandem cyclization of alle-
nenes.[18]
À
the success of the tandem cyclization and the aromatic C H
activation.
Results and Discussion
Synthesis of requisite allenenes for the palladium-catalyzed
tandem cyclization: With a view to synthesizing nitrogen
heterocycles, we prepared allenenes of type 10 by reaction
of (E)-cinnamyl bromide with known amino allenes of type
9 (Scheme 2), which, in turn, were easily obtained from (S)-
Scheme 3. Palladium(0)-catalyzed pyrrolidine formation through b-hy-
dride elimination.
In an initial experiment, we investigated the reaction of
known allenene 18[16] bearing a methyl group on the double
bond instead of the eliminative hydrogen atom (Scheme 4).
Scheme 4. Palladium(0)-catalyzed tandem cyclization of 2’-methylated al-
lenene 18.
Unfortunately, the reaction of 18 is extremely slow to afford
the desired cyclized product 19 in only a 5% yield with re-
covery of the starting material. However, this result clearly
shows that inhibition of the b-hydride elimination does pro-
mote the desired tandem cyclization onto an aryl group
Scheme 2. Synthesis of requisite allenenes (Mts=2,4,6-trimethylphenyl-
sulfonyl). [a] Determined by H NMR spectroscopy.
À
through C H activation, although in a low yield.
1
We next investigated the cyclization of allenenes of type
10 with a phenyl substituent at the 3’-position, as the intro-
duction of a substituent at the olefin terminus might impede
the required arrangement of the palladium center relative to
the hydrogen atom for b-hydride elimination to occur.[22,23]
To our delight, allenene 10a reacted with iodobenzene, po-
tassium carbonate, and a catalytic amount of palladium(0)
in dioxane to give a separable diastereomeric mixture of the
benzoisoindole derivatives 20a and 21a in moderate yields
(41 and 10%, respectively; Table 1, entry 1). This is the first
example of a successful palladium(0)-catalyzed tandem cyc-
lization of allenenes. Introduction of an electron-donating
amino acids through the diethylzinc-mediated reductive syn-
thesis of amino allenes catalyzed by palladium(0).[19] The
corresponding isomer (Z)-10a and dimethylated allenene 11
were similarly prepared by treatment of 9a with (Z)-cin-
namyl bromide[20] or 4-bromo-2-methylbut-2-ene, respective-
ly. Reaction of amino allenes of type 9 with racemic 3-bro-
mocyclohexene followed by separation of the resulting dia-
stereomixtures afforded (cyclohexenyl)amino allene deriva-
tives of type 12 and 13 in moderate to good yields.[21]
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3729

H. Ohno, T. Tanaka et al.
Table 1. Palladium(0)-catalyzed tandem cyclization of allenenes with iodobenzene derivatives.[a]
Entry
Substrate
ArI
t [h]
Product (yield)
1
2
3
4
10a
10a
10a
10a
PhI
7.5
7
3.5
5
20a: R=H (41%)
21a: R=H (10%)
21b: R=Me (18%)
21c: R=OMe (20%)
21da: R=10-OMe (trace)
21db: R=12-OMe (trace)
21e: R=13-OMe (2%)
4-MePhI
4-MeOPhI
3-MeOPhI
20b: R=11-Me (37%)
20c: R=11-OMe (43%)
20da: R=10-OMe (19%)
20db: R=12-OMe (17%)
20e: R=13-OMe (36%)
5
10a
2-MeOPhI
10
6[b]
7
10b
10b
PhI
4-MeOPhI
29
13
22a: R=H (21%)
22b: R=OMe (32%)
23a: R=H (14%)
23b: R=OMe (36%)
8
10c
PhI
PhI
23
24 (30%)
25 (24%)
9[b,c]
10d
6
26 (34%)
27 (7%)
10
11
10e
4-MeOPhI
3
28 (34%)
29 (31%)
10 f
PhI
30
30 (16%)
31 (35%)
12[b]
13
11
11
PhI
4-MeOPhI
28
30
32a: R=H (42%)
32b: R=OMe (45%)
[a] Unless otherwise stated, reactions were carried out with [Pd(PPh3)4] (10 mol%), ArI (2 equiv), and K2CO3 (2 equiv) in dioxane under reflux. [b] In-
creased amounts of ArI (4 equiv) and K2CO3 (4 equiv) were used. [c] Considerable amount of unidentified products were obtained.
substituent such as a methyl and methoxy group at the 4-po-
sition of iodobenzene increased the reaction rate and slight-
ly improved the yields of the tricyclic products (entries 2
and 3).[24] However, the reaction with 2-iodoanisole (entry 5)
gave lower yields of the desired benzoisoindoles 20e (36%)
and 21e (2%), presumably due to the steric hindrance of
3730
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3728 – 3741

Cyclization of Allenenes
FULL PAPER
the 2-anisyl group. It should be noted that, as we expected,
the reaction with 3-iodoanisole (entry 4) yielded two regio-
isomeric products, 10- and 12-methoxy derivatives 20da
(19%) and 20db (17%), respectively.
pounds, we investigated the reaction of N-cyclohexenyl de-
rivatives of type 12 (Scheme 6). Treatment of 12a under the
Similarly, other N-cinnamylamino allenes 10b and 10c
(entries 6–8) in which the a substituent is smaller, also react-
ed to afford the expected tricyclic products 22–25, although
prolonged reaction times were required. When allenene 10d
with a bulky tert-butyl group on the a position to the allenic
moiety was used, the corresponding benzoisoindoles 26 and
27 were obtained in a relatively lower combined yield
(41%). Similar to allenene 10a (entries 1–5), allenene 10e
bearing a branched alkyl group (sec-butyl) is more reactive
and gives the desired tricyclic products 28 and 29 in good
yields (65% combined yields, entry 10). A Boc group
(Boc=tert-butoxycarbonyl) can also be used as the nitro-
gen-protecting group (entry 11). Interestingly, 3,7-cis isomer
31 predominated over its trans isomer 30 (30/31=16:35), al-
though the exact reason is unclear. Substituents other than a
phenyl group at the olefin terminus can also promote the
tandem cyclization. Thus, reaction of the N-(3,3-dimethylal-
lyl)amino derivative 11 yielded the expected cyclized prod-
ucts of type 32 with geminal dimethyl substitution at C8 in a
stereoselective manner (entries 12 and 13).
The cyclized products were fully characterized by
1H NMR, 13C NMR, NOE, and COSY spectroscopic analy-
ses, and the structure of 21a was also confirmed by HMQC
and HMBC analyses. The configuration of the cyclized prod-
ucts were determined by NOE analyses (see the Supporting
Information). Although the combined isolated yields are
moderate (35–68%) due to the formation of some undesired
byproducts, such as compounds 58 and 59[25] (see the Experi-
mental Section), the yields of the desired tricycic com-
pounds are synthetically acceptable as three carbon–carbon
bonds are successively formed in a single operation.
Scheme 6. Palladium(0)-catalyzed tandem cyclization of 12. [a] A mixture
of 12b and 13b (1:1) was used. Yield of 34 (51%) is based on 12b (see
Scheme 1 for abbreviations).
standard cyclization conditions led to the formation of the
desired tetracyclic compound 34a in a 49% yield as a single
isomer. The structure of 34a was confirmed by NMR analy-
sis, including NOE and COSY experiments. It is worth
noting that three stereogenic centers are newly created with
complete stereoselectivity. In contrast, the reaction of 13a
(Scheme 2), the corresponding C1’ epimer to 12a, gave a
complex mixture of unidentified products when exposed to
identical cyclization conditions, presumably due to steric
reasons. Allenenes 12b and 12c were cyclized into tetracy-
clohexadecatriene derivatives 34b and 34c, respectively, also
in a stereoselective manner. These results clearly demon-
strate the utility of our tandem cyclization as a novel
method for the synthesis of complex heterocycles.
Stereoselectivity and mechanism of the tandem cyclization:
In all cases listed in Table 1, the stereochemistry of the first
cyclization (which dictates the relative configuration at C3
and C4 in the product) was the opposite of that observed in
the pyrrolidine formation. As we have already described,[16b]
the observed 2,3-cis selectivity in the pyrrolidination is at-
tributed to an unfavorable steric interaction between
pseudo-axial protons and the phenyl group in 35
(Scheme 7). Thus, the ring formation would proceed prefer-
entially from the more abundant conformers 37 and/or 38 to
yield cis-pyrrolidine 39 as the sole isolable isomer.
Next, the reaction of (Z)-cinnamyl derivative, (Z)-10a,
was investigated (Scheme 5). Exposure of 10a to the identi-
Scheme 5. Palladium(0)-catalyzed tandem cyclization of (Z)-10a (see
Scheme 1 for abbreviations).
cal reaction conditions for 7.5 h yielded 33 (26%) and 20a
(16%). It should be mentioned that isomer 33 was not de-
tected in the reaction of (E)-10a (Table 1, entry 1). The cyc-
lization of (Z)-10a for a prolonged reaction time (15 h) gave
33 and 20a in essentially the same product ratio (33/20a=
1.4:1), which strongly suggests that the reaction is kinetically
controlled.
In order to examine the scope of the tandem cyclization
as a useful synthetic method of various polycyclic com-
Scheme 7. Stereoselectivity of the monocyclization (PG=protecting
group=SO2Ar).
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3731

H. Ohno, T. Tanaka et al.
Although the exact reason for the opposite stereoselectiv-
ity at the C3 position in the tandem cyclization is not clear,
it is apparent that the substituent at the olefin terminus
plays an important role in the stereoselectivity of the first
cyclization, not only in the inhibition of the b-hydride elimi-
nation. If the first cyclization proceeded with the same ster-
eoselectivity as the pyrrolidine formation, tricyclic com-
pounds 44 or 45 would be obtained through intermediate 40
or 41 (Scheme 8). In sharp contrast to intermediate 37 in the
À
Scheme 9. Possible reaction pathways for the C H functionalization.
stereomutation furnishing the required syn elimination,[26]
presumably by the h3–h1–h3 mechanism of the allylpalladi-
um(ii) species.[27] In addition, the anti elimination might be
one rationalization for the rearomatization of 54 (path B);[28]
3) Alternatively, electrophilic attack by the palladium(ii) in-
termediate 52 onto the aromatic carbon would give cationic
intermediate 55, deprotonation of which and subsequent re-
ductive elimination would afford 50 or 51 (path C).[2]
Scheme 8. Stereoselectivity of the tandem cyclization.
If path C is the major reaction pathway, an electron-do-
nating methoxy substituent on the 3-position of the aryl
halide would strongly promote the second cyclization by sta-
bilizing the cationic intermediate 55. However, the tandem
cyclization with 3- and 4-iodoanisole gave similar results
(Table 1, entries 4 and 5), which indicates that the cation-
stabilizing effect of the methoxy group is relatively unimpor-
tant and that path C will not be the major reaction pathway.
At the present stage of our understanding, it is difficult to
determine which is the most favorable reaction course in
this case, as well as in related reactions.[3]
pyrrolidination (Scheme 7), the upper side of intermediate
40 is highly sterically hindered because of the existence of a
phenyl group on the double bond. Furthermore, if the first
cyclization proceeded through intermediate 41, the second
cyclization step might be hampered by the relatively long
distance between the reaction sites, as shown in 43. The 2,3-
cis configuration of the minor products generated by the b-
hydride elimination[25] also supports the theory of the poor
reactivity of the alkylpalladium intermediate of type 43
toward the second cyclization. Accordingly, predominant
formation of the two diastereomers 50 and 51 through 46
and 47 is understandable.
Tandem cyclization of allenenes with heteroaryl halides: Fi-
nally, we investigated the direct synthesis of tri- or tetracy-
clic heterocycles by using the tandem cyclization with hetero-
aromatic halides. The results are summarized in Table 2.
The reaction of allenene 10a with 2-bromothiophene yield-
ed tricyclic products 56a and 57a in 59% combined isolated
yields (entry 1). The cyclization using 3-bromofuran afford-
ed tricyclic furan 56b as a single isolable diastereomer
(entry 2). The relatively low yield (31%) is due to instability
of 56b. We next investigated the reaction with bicyclic hetero-
aryl halides such as 4-bromo-1-methylindole and 3-bromo-
benzothiophene and found that these halides are good part-
ners for the tandem cyclization of allenene 10a (entries 3
À
Three possible mechanistic pathways for the final C H
activation are shown in Scheme 9: 1) Intramolecular oxida-
À
tive addition of an aromatic C H bond to palladium(ii) to
form palladium(iv) intermediate 53,[1] which gives the ben-
zoisoindoles 50 and 51 on loss of HI and subsequent reduc-
tive elimination (path A); 2) Carbopalladation onto the aryl
group in 52 would give the palladium(ii) intermediate 54, in
which the b hydrogen has an anti configuration to the palla-
dium atom. In most cases, the subsequent b-hydride elimina-
tion proceeds with the syn stereochemistry.[23] Accordingly,
the rearomatization to 50/51 might proceed through a facile
3732
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3728 – 3741

Cyclization of Allenenes
FULL PAPER
Table 2. Palladium(0)-catalyzed tandem cyclization of allenene 10a with heteroaryl halides.[a]
with 10a, affording the desired
products in lower yields (30–
42%) with some undesired by-
products after a prolonged re-
action time (30 h). This prob-
lem has been overcome by
using 2-iodopyridine (entry 5)
and iodopyrazine (entry 6) to
give 56e and 56 f, respectively,
in moderate yields (49 and
62%, respectively).
Entry
Substrate
ArX
t [h]
Product (yield)
1
10a
8
56a (47%)
57a (12%)
Conclusion
2
3
4
10a
10a
10a
5
56b (31%)
57b (trace)
In conclusion, we have devel-
oped a novel tandem-cycliza-
tion reaction of allenenes for
the synthesis of tri- and tetracy-
clic heterocycles. We found that
inhibition of the b-hydride
elimination of the monocyclized
alkylpalladium(ii) intermediate
by introducing a substituent on
the double bond efficiently pro-
motes the second cyclization
onto an aromatic ring. This
study demonstrates that alle-
nenes can undergo a tandem
12
56c (43%)
57c (6%)
À
cyclization involving C H acti-
vation of benzene or heteroaro-
matic rings such as thiophene,
furan, and indole, in the pres-
ence of a palladium(0) catalyst.
The tandem cyclization forming
three carbon–carbon bonds is
synthetically useful in that com-
plex heterocyclic skeletons can
be constructed from readily
prepared allenenes.
6
56d (45%)
57d (trace)
5[b]
10a
10
56e (49%)
Experimental Section
6
10a
8
56 f (62%)
General methods: All reactions were
carried out under a positive pressure
of argon, and glassware and syringes
were dried in an electric oven at
1008C prior to use. THF was distilled
from sodium benzophenone ketyl
under N2. Other solvents and reagents
[a] Unless otherwise stated, reactions were carried out with [Pd(PPh3)4] (10 mol%), ArI (2 equiv), and K2CO3
(2 equiv) in dioxane under reflux. [b] Increased amount of [Pd(PPh3)4] (20 mol%) was used.
and 4). In most cases using heteroaryl halides, the reaction
were used without further purification. Melting points are uncorrected.
1H NMR spectra (270, 300, or 500 MHz) were recorded using CDCl3 as
solvent. Chemical shifts are reported in parts per million downfield from
internal Me4Si (s=singlet, d=doublet, dd=double doublet, ddd=dou-
blet of double doublet, t=triplet, m=multiplet). For flash chromatogra-
phy, silica gel 60 (230—400 mesh, Merck) was employed. Known com-
pounds 9a,[19b] 9b,[16b] 9c,[19b] 9d,[16b] 9e,[16b] 9 f,[16b] 18,[16b] and (Z)-cinnamyl
bromide[20] were synthesized according to the literature.
proceeded smoothly to give the desired products even with
aryl bromides, presumably due to the electron-rich nature of
these heteroaryl rings. This trend is in good agreement with
the results for electron-rich iodobenzene derivatives (see
Table 1). In contrast, our results suffered from lower reactiv-
ities of 2-bromopyridine and chloropyrazine in the reaction
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3733

H. Ohno, T. Tanaka et al.
General procedure for the synthesis of allenenes
(2C), 134.1, 136.4, 140.1 (2C), 142.1, 209.1 ppm; IR (KBr): n˜ =1956 (C=
C=C), 1323, 1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 366 (33) [M++H],
117 (100); HRMS (FAB): calcd for C26H34NO2S [M++H]: 424.2310;
found: 424.2319.
N-[(1S)-1-Isopropylbuta-2,3-dienyl]-2,4,6-trimethyl-N-[(E)-3-phenyl-2-
propenyl]phenylsulfonamide (10a):
A
solution of 9a (250 mg,
0.852 mmol) in DMF (2 mL) at 08C was added to a stirred suspension of
60% NaH (117 mg, 2.90 mmol) in DMF (3 mL), and the mixture was stir-
red for 10 min. (E)-Cinnamyl bromide (572 mg, 2.90 mmol) was added to
the mixture at 08C, and the mixture was stirred for 2 h at this tempera-
ture, followed by quenching with saturated NH4Cl (1 mL). All of this was
extracted with Et2O and the extract was washed with water and brine,
and dried over MgSO4. Concentration of the filtrate under reduced pres-
sure followed by flash column chromatography over silica gel with n-
hexane/EtOAc (40:1) gave allenene 10a as colorless crystals (372 mg,
99%). M.p. 73–748C; [a]2D2 =+14.7 (c=0.075, CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.92 (d, J=6.3 Hz, 3H; CMe), 0.93 (d, J=6.3 Hz,
3H; CMe), 1.89–2.01 (m, 1H; Me2CH), 2.22 (s, 3H; PhCH3), 2.63 (s, 6H;
2ꢂPhCH3), 3.88–3.95 (m, 1H; 1-H), 3.98 (dd, J=6.9, 1.5 Hz, 2H; 1’-
CH2), 4.71 (dd, J=6.9, 1.5 Hz, 2H; 4-CH2), 5.24 (dt, J=7.8, 6.9 Hz, 1H;
2-H), 6.03 (dt, J=15.9, 6.9 Hz, 1H; 2’-H), 6.34 (d, J=15.9 Hz, 1H; 3’-H),
6.88 (s, 2H; Ph), 7.17–7.30 ppm (m, 5H; Ph); 13C NMR (75.5 MHz,
CDCl3): d=20.1, 20.7, 20.8, 23.3 (2C), 30.5, 45.8, 63.2, 76.1, 88.9, 126.3
(2C), 126.9, 127.5, 128.4 (2C), 131.6, 131.9 (2C), 133.9, 136.5, 140.1 (2C),
142.2, 209.2 ppm; IR (KBr): n˜ =1955 (C=C=C), 1322 (SO2N), 1155 cmÀ1
(SO2N); MS (FAB): m/z (%): 410 (24) [M++H], 366 (100); HRMS
(FAB): calcd for C25H32NO2S [M++H]: 410.2154; found: 410.2150.
N-{(1S)-1-[(1S)-1-Methylpropyl]buta-2,3-dienyl}-2,4,6-trimethyl-N-[(E)-3-
phenyl-2-propenyl]phenylsulfonamide (10e): By using a procedure iden-
tical to that described for the synthesis of 10a, amino allene 9e (100 mg,
0.325 mmol) was converted into allenene 10e (137 mg, 99%). Colorless
oil; [a]2D2 =+2.49 (c=1.00, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.79
(t, J=7.3 Hz, 3H; CMe), 0.88 (d, J=6.1 Hz, 3H; CMe), 0.90–0.91 (m,
1H; 2’’-CHH), 1.66–1.71 (m, 1H; 1’’-H), 1.75–1.80 (m, 1H; 2’’-CHH),
2.22 (s, 3H; PhCH3), 2.62 (s, 6H; 2ꢂPhCH3), 3.91–4.04 (m, 3H; 1-H and
1’-CH2), 4.64–4.71 (m, 2H; 4-CH2), 5.19 (ddd, J=7.4, 6.7, 6.7 Hz, 1H; 2-
H), 6.04 (ddd, J=15.9, 7.3, 7.3 Hz, 1H; 2’-H), 6.34 (d, J=15.9 Hz, 1H; 3’-
H), 6.89 (s, 2H; Ph), 7.19–7.29 ppm (m, 5H; Ph); 13C NMR (67.8 MHz,
CDCl3): d=11.4, 16.7, 20.9, 23.4 (2C), 25.7, 37.1, 46.1, 62.1, 76.0, 88.6,
126.2 (2C), 126.8, 127.5, 128.3 (2C), 131.6, 131.9 (2C), 133.8, 136.4, 140.0
(2C), 142.2, 209.0 ppm; IR (KBr): n˜ =1952 (C=C=C), 1315 (SO2N),
1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 424 (100) [M++H]; HRMS
(FAB): calcd for C26H34NO2S [M++H]: 424.2310; found: 424.2304.
N-[(1S)-1-Isopropylbuta-2,3-dienyl]-N-[(E)-3-phenyl-2-propenyl]-tert-bu-
tylcarbamate (10 f): By using a procedure identical to that described for
the synthesis of 10a, amino allene 9 f (100 mg, 0.473 mmol) was convert-
ed into allenene 10 f (124 mg, 80%). Colorless oil; [a]2D6 =À19.9 (c=1.31,
CHCl3); 1H NMR (300 MHz, CDCl3, 328 K): d=0.89–0.96 (m, 6H; 2ꢂ
CMe), 1.44–1.49 (m, 9H; CMe3), 1.99–2.11 (m, 1H; Me2CH), 3.89–3.91
(m, 3H; 1-H and 1’-CH2), 4.71 (dd, J=6.6, 1.5 Hz, 2H; 4-CH2), 5.26 (dd,
J=13.1, 6.6 Hz, 1H; 2-H), 6.14–6.24 (m, 1H; 2’-H), 6.42–6.48 (m, 1H; 3’-
H), 7.17–7.34 ppm (m, 5H; Ph); 13C NMR (67.8 MHz, CDCl3, 328 K): d=
19.7, 20.6, 28.6 (3C), 30.9, 47.8, 62.9, 75.7, 79.7, 90.0, 126.2 (2C), 127.2,
127.3, 128.1 (2C), 131.4, 137.2, 155.4, 209.2 ppm; IR (KBr): n˜ =1955 (C=
C=C), 1693 cmÀ1 (C=O); MS (FAB): m/z (%): 328 (23) [M++H], 272
(100); HRMS (FAB): calcd for C21H30NO2 [M++H]: 328.2277; found:
328.2269.
N-[(1S)-1-Isobutylbuta-2,3-dienyl]-2,4,6-trimethyl-N-[(E)-3-phenyl-2-pro-
penyl]phenylsulfonamide (10b): By using a procedure identical to that
described for the synthesis of 10a, amino allene 9b (200 mg, 0.651 mmol)
was converted into allenene 10b (263 mg, 95%). Colorless oil; [a]D27
=
À39.2 (c=3.00, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.74 (d, J=
6.1 Hz, 3H; CMe), 0.78 (d, J=6.1 Hz, 3H; CMe), 1.43–1.49 (m, 1H;
Me2CH), 1.56–1.61 (m, 2H; Me2CHCH2), 2.23 (s, 3H; PhCH3), 2.63 (s,
6H; 2ꢂPhCH3), 3.91 (dd, J=17.0, 6.7 Hz, 1H; 1’-CHH), 4.00 (dd, J=
17.0, 6.7 Hz, 1H; 1’-CHH), 4.31–4.35 (m, 1H; 1-H), 4.73–4.80 (m, 2H; 4-
CH2), 5.29 (dt, J=6.1, 6.1 Hz, 1H; 2-H), 6.01 (dt, J=15.9, 6.7 Hz, 1H; 2’-
H), 6.33 (d, J=15.9 Hz, 1H; 3’-H), 6.90 (s, 2H; Ph), 7.05–7.29 ppm (m,
5H; Ph); 13C NMR (67.8 MHz, CDCl3): d=20.9, 22.1, 22.6, 23.1 (2C),
24.7, 41.6, 45.3, 53.5, 77.0, 90.5, 126.2 (2C), 127.0, 127.4, 128.3 (2C), 131.6,
131.8 (2C), 133.3, 136.5, 140.1 (2C), 142.3, 208.7 ppm; IR (KBr): n˜ =1954
(C=C=C), 1319 (SO2N), 1153 cmÀ1 (SO2N); MS (FAB): m/z (%): 424
(14) [M++H], 117 (100); HRMS (FAB): calcd for C26H34NO2S [M++H]:
424.2310; found: 424.2308.
N-[(1S)-1-(Isopropyl)buta-2,3-dienyl]-2,4,6-trimethyl-N-[(Z)-3-phenyl-2-
propenyl]phenylsulfonamide ((Z)-10a): By using a procedure similar to
that described for the synthesis of 10a, amino allene 9a (200 mg,
0.682 mmol) was converted into, in the order of elution, (Z)-10a (107 mg,
39%) and (E)-10a (18 mg, 6%), by use of (Z)-cinnamyl bromide
(268 mg, 1.36 mmol). Compound (Z)-10a: Colorless oil; [a]2D5 =À16.7
(c=0.425, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.82 (d, J=6.6 Hz,
3H; CMe), 0.87 (d, J=6.6 Hz, 3H; CMe), 1.62–1.74 (m, 1H; Me2CH),
2.30 (s, 3H; PhCH3), 2.58 (s, 6H; 2ꢂPhCH3), 3.79–3.86 (m, 1H; 1-H),
4.07 (ddd, J=17.4, 6.0, 2.1 Hz, 1H; 1’-CHH), 4.21 (ddd, J=17.4, 6.0,
2.1 Hz, 1H; 1’-CHH), 4.46 (ddd, J=11.4, 6.6, 1.5 Hz, 1H; 4-CHH), 4.61
(ddd, J=11.4, 6.6, 1.5 Hz, 1H; 4-CHH), 5.08 (ddd, J=6.6, 6.6, 6.6 Hz,
1H; 2-H), 5.67 (ddd, J=11.7, 6.0, 6.0 Hz, 1H; 2’-H), 6.34 (d, J=11.7 Hz,
1H; 3’-H), 6.91 (s, 2H; Ph), 7.12–7.36 ppm (m, 5H; Ph); 13C NMR
(75.5 MHz, CDCl3): d=20.2, 20.6, 20.9, 23.3 (2C), 30.2, 41.4, 63.1, 76.0,
88.6, 127.1, 128.2 (2C), 128.8 (2C), 129.7, 130.2, 132.0 (2C), 133.6, 136.4,
140.1 (2C), 142.2, 209.2 ppm; IR (KBr): n˜ =1956 (C=C=C), 1323 (SO2N),
1157 cmÀ1 (SO2N).
N-[(1S)-1-Benzylbuta-2,3-dienyl]-2,4,6-trimethyl-N-[(E)-3-phenyl-2-pro-
penyl]phenylsulfonamide (10c): By using a procedure identical to that
described for the synthesis of 10a, amino allene 9c (250 mg, 0.732 mmol)
was converted into allenene 10c (338 mg, 99%). Colorless oil; [a]D28
=
À95.0 (c=1.38, CHCl3); 1H NMR (500 MHz, CDCl3): d=2.23 (s, 1H;
PhCH3), 2.64 (s, 6H; 2ꢂPhCH3), 2.96–3.05 (m, 2H; PhCH2), 4.03–4.13
(m, 2H; 1’-CH2), 4.56–4.59 (m, 1H; 1-H), 4.77–4.79 (m, 2H; 4-CH2), 5.35
(dt, J=6.7, 6.7 Hz, 1H; 2-H), 6.07 (dt, J=15.9, 6.7 Hz, 1H; 2’-H), 6.41
(d, J=15.9 Hz, 1H; 3’-H), 6.83 (s, 2H; Ph), 7.00–7.31 ppm (m, 10H; Ph);
13C NMR (67.8 MHz, CDCl3): d=20.9, 22.9 (2C), 39.2, 45.7, 56.9, 77.7,
90.0, 126.2, 126.3 (2C), 126.9, 127.5, 128.1 (2C), 128.4 (2C), 129.1 (2C),
131.9 (3C), 132.9, 136.5, 138.0, 140.3 (2C), 142.3, 209.0 ppm; IR (KBr):
n˜ =1954 (C=C=C), 1317 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB): m/z
(%): 458 (14) [M++H], 117 (100); HRMS (FAB): calcd for C29H32NO2S
[M++H]: 458.2154; found: 458.2162.
N-[(1S)-1-(2-Isopropyl)buta-2,3-dienyl]-2,4,6-trimethyl-N-(3-methyl-2-bu-
tenyl)phenylsulfonamide (11): By using a procedure similar to that de-
scribed for the synthesis of 10a, amino allene 9a (200 mg, 0.682 mmol)
was converted into allenene 11 (250 mg, 99%) by use of 4-bromo-2-
methylbut-2-ene. Colorless oil; [a]2D3 =À20.4 (c=0.89, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.89 (d, J=6.1 Hz, 3H; CMe), 0.90 (d, J=6.1 Hz,
3H; CMe), 1.58 (m, 6H; 2ꢂCMe), 1.81–1.89 (m, 1H; Me2CH), 2.28 (s,
3H; PhCH3), 2.61 (s, 6H; 2ꢂPhCH3), 3.76–3.86 (m, 3H; 1-H and 1’-
CH2), 4.66–4.72 (m, 2H; 4-CH2), 5.10 (t, J=6.7 Hz, 1H; 2’-H), 5.18 (dt,
J=6.7, 6.7 Hz, 1H; 2-H), 6.91 ppm (s, 2H; Ph); 13C NMR (75.5 MHz,
CDCl3): d=17.7, 20.1, 20.8, 20.9, 23.2 (2C), 25.6, 30.6, 41.6, 63.1, 75.9,
88.9, 122.0, 131.8 (2C), 133.4 (2C), 134.0, 140.1 (2C), 142.0, 209.1 ppm; IR
(KBr): n˜ =1956 (C=C=C), 1323 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB):
m/z (%): 362 (16) [M++H], 119 (100); HRMS (FAB): calcd for
C21H32NO2S [M++H]: 362.2154; found: 362.2134.
N-[(1S)-1-(tert-Butyl)buta-2,3-dienyl]-2,4,6-trimethyl-N-[(E)-3-phenyl-2-
propenyl]phenylsulfonamide (10d): By using a procedure identical to
that described for the synthesis of 10a, amino allene 9d (200 mg,
0.651 mmol) was converted into allenene 10d (227 mg, 82%). Colorless
crystals; m.p. 86–888C; [a]2D1 =+77.0 (c=0.865, CHCl3); 1H NMR
(270 MHz, CDCl3): d=1.01 (s, 9H; 3ꢂCMe), 2.16 (s, 3H; PhCH3), 2.61
(s, 6H; 2ꢂPhCH3), 4.01 (dd, J=17.0, 7.1 Hz, 1H; 1’-CHH), 4.11 (dd, J=
17.0, 5.8 Hz, 1H; 1’-CHH), 4.27 (dt, J=8.9, 1.6 Hz, 1H; 1-H), 4.69 (dd,
J=6.8, 1.6 Hz, 2H; 4-CH2), 5.32 (dt, J=8.9, 6.8 Hz, 1H; 2-H), 5.92 (ddd,
J=16.0, 7.1, 5.8 Hz, 1H; 2’-H), 6.83 (s, 2H; Ph), 7.09–7.27 ppm (m, 5H;
Ph); 13C NMR (67.8 MHz, CDCl3): d=20.8, 23.5 (2C), 28.1 (2C), 37.3,
47.2, 65.9, 75.5, 86.6, 126.2 (2C), 126.9, 127.3, 128.2 (2C), 130.9, 131.8
3734
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3728 – 3741

Cyclization of Allenenes
FULL PAPER
N-[(1R)-Cyclohex-2-en-1-yl]-N-[(1R)-1-isopropylbuta-2,3-dienyl]-2,4,6-
trimethylphenylsulfonamide (12a) and its [(1S)-cyclohex-2-en-1-yl]
isomer (13a): By using a procedure similar to that described for the syn-
thesis of 10a, amino allene 9a (400 mg, 1.36 mmol) was converted into,
in the order of elution, 12a (159 mg, 31%) and 13a (178 mg, 35%) by
use of racemic 3-bromocyclohexene.
Compound 12a: Colorless oil; [a]2D4 =À11.9 (c=2.75, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.80 (d, J=6.7 Hz, 3H; CMe), 0.84 (d, J=6.7 Hz,
3H; CMe), 1.45–2.08 (m, 7H; Me2CH, 4’-CH2, 5’-CH2, and 6’-CH2), 2.27
(s, 3H; PhCH3), 2.64 (s, 6H; 2ꢂPhCH3), 3.55 (dd, J=9.8, 9.2 Hz, 1H; 1-
H), 4.10 (m, 1H; 1’-H), 4.66–4.74 (m, 2H; 4-CH2), 5.54 (dt, J=8.5,
6.7 Hz, 1H; 2-H), 5.62 (d, J=10.4 Hz, 1H; 2’-H), 5.69–5.72 (m, 1H; 3’-
H), 6.91 ppm (s, 2H; Ph); 13C NMR (67.8 MHz, CDCl3): d=20.7, 21.0,
21.3, 23.0, 23.3 (2C), 24.6, 29.0, 31.6, 55.5, 64.1, 75.5, 90.5, 129.3, 130.2,
131.9 (2C), 134.1, 140.0 (2C), 142.1, 208.7 ppm; IR (KBr): n˜ =1956 (C=
C=C), 1319 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 374 (28)
[M++H], 119 (100); HRMS (FAB): calcd for C22H31NO2S [M++H]
374.2154; found: 374.2145.
Compound 13a: Colorless crystals; m.p. 63–658C; [a]2D5 =À73.8 (c=2.94,
CHCl3); 1H NMR (500 MHz, CDCl3): d=0.75 (d, J=6.7 Hz, 3H; CMe),
0.84 (d, J=6.7 Hz, 3H; CMe), 1.49–2.32 (m, 7H; Me2CH, 4’-CH2, 5’-CH2,
and 6’-CH2), 2.29 (s, 3H; PhCH3), 2.68 (s, 6H; 2ꢂPhCH3), 3.38 (dd, J=
9.2, 9.2 Hz, 1H; 1-H), 3.98 (m, 1H; 1’-H), 4.73 (dd, J=11.0, 6.7 Hz, 1H;
4-CHH), 4.77 (dd, J=11.0, 6.7 Hz, 1H; 4-CHH), 5.53 (ddd, J=8.5, 6.7,
6.7 Hz, 1H; 2-H), 5.73–5.75 (m, 1H; 3’-H), 5.95 (d, J=10.4 Hz, 1H; 2’-
H), 6.95 ppm (s, 2H; Ph); 13C NMR (67.8 MHz, CDCl3): d=20.5, 21.0
(2C), 23.1, 23.3 (2C), 24.6, 29.7, 31.1, 55.6, 64.0, 75.6, 89.5, 129.0, 129.5,
131.8 (2C), 133.3, 140.4 (2C), 142.2, 209.0 ppm; IR (KBr): n˜ =1956 (C=
C=C), 1317 (SO2N), 1155 cmÀ1 (SO2N); elemental analysis calcd (%) for
C22H31NO2S: C 70.74, H 8.36, N 3.75; found: C 70.70, H 8.31, N 3.75.
Compound 13c: Colorless oil; [a]2D5 =À5.91 (c=1.11, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.60–0.68 (m, 1H; CH), 0.69 (d, J=6.1 Hz, 3H;
CMe), 0.83 (d, J=6.7 Hz, 3H; CMe), 1.42–2.26 (m, 8H; 8ꢂCH), 2.23 (s,
3H; PhCH3), 2.67 (s, 6H; 2ꢂPhCH3), 3.50 (dd, J=9.2, 9.2 Hz, 1H; 1-H),
4.00–4.05 (m, 1H; 1’-H), 4.69–4.77 (m, 2H; 4-CH2), 5.52 (ddd, J=8.5, 6.7,
6.7 Hz, 1H; 2-H), 5.72–5.77 (m, 1H; CH=CH), 5.95 (d, J=10.4 Hz, 1H;
CH=CH), 6.92 ppm (s, 2H; Ph); 13C NMR (67.8 MHz, CDCl3): d=11.4,
16.7, 21.0, 23.1, 23.2 (2C), 24.6, 26.2, 29.6, 37.8, 55.8, 62.9, 75.4, 89.4,
129.1, 129.6, 131.8 (2C), 133.5, 140.4 (2C), 142.2, 209.1 ppm; IR (KBr):
n˜ =1956 (C=C=C), 1317 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z
(%): 388 (100) [M++H]; HRMS (FAB): calcd for C23H34NO2S [M++H]:
388.2310; found: 388.2314.
(3R,4S,7R)-5-Aza-4-isopropyl-7-methyl-2-methylene-5-(2,4,6-trimethyl-
phenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (19): A stirred
mixture of allenene 18 (50.0 mg, 0.144 mmol), [Pd(PPh3)4] (16.2 mg,
0.014 mmol), iodobenzene (0.065 mL, 0.584 mmol), and K2CO3 (80.7 mg,
0.584 mmol) in dioxane (3 mL) was heated under reflux for 36 h. Water
was added to the mixture, and it was extracted with Et2O. The extract
was washed with water and brine, and dried over MgSO4. The filtrate
was concentrated under reduced pressure to leave an oily residue, which
was purified by flash chromatography over silica gel with n-hexane/
EtOAc (50:1) to give 19 (2.8 mg, 5%) and recovered starting material
(15.8 mg, 32%). Compound 19: Colorless oil; [a]2D3 =À71.9 (c=0.69,
CHCl3); 1H NMR (500 MHz, CDCl3): d=0.63 (d, J=7.3 Hz, 3H; CMe),
0.76 (d, J=6.7 Hz, 3H; CMe), 0.89 (s, 3H; CMe), 1.78–1.84 (m, 1H;
Me2CH), 2.30 (s, 3H; PhCH3), 2.64 (d, J=9.2 Hz, 1H; 3-H), 2.66 (s, 6H;
2ꢂPhCH3), 2.81 (d, J=15.9 Hz, 1H; 8-CHH), 2.90 (d, J=15.9 Hz, 1H; 8-
CHH), 3.09 (d, J=10.4 Hz, 1H; 6-CHH), 4.20 (d, J=10.4 Hz, 1H; 6-
CHH), 4.32 (dd, J=9.2, 3.1 Hz, 1H; 4-H), 5.02 (d, J=1.8 Hz, 1H; C=
CHH), 5.60 (d, J=1.8 Hz, 1H; C=CHH), 6.93 (s, 2H; Ph), 7.13 (d, J=
7.3 Hz, 1H; Ph), 7.18–7.24 (m, 2H; Ph), 7.57 ppm (dd, J=7.9, 1.2 Hz,
1H; Ph); 13C NMR (67.8 MHz, CDCl3): d=17.4, 17.8, 19.2, 21.0, 23.1
(2C), 31.5, 41.1, 41.3, 52.0, 62.8, 63.9, 108.4, 124.9, 126.0, 128.0, 130.0,
131.8 (2C), 134.7, 136.1, 136.4, 138.7 (2C), 141.6, 142.5 ppm; IR (KBr):
n˜ =1324 (SO2N), 1147 cmÀ1 (SO2N); MS (FAB): m/z (%): 424 (100) [M+
+H]; HRMS (FAB): calcd for C26H34NO2S [M++H]: 424.2310; found:
424.2332.
N-[(1R)-Cyclohex-2-en-1-yl]-N-[(1R)-1-isobutylbuta-2,3-dienyl]-2,4,6-tri-
methylphenylsulfonamide (12b) and its [(1S)-cyclohex-2-en-1-yl] isomer
(13b): By using a procedure similar to that described for the synthesis of
10a, amino allene 9b (300 mg, 0.976 mmol) was converted into an insepa-
rable mixture of 12b and 13b (1:1; 347 mg, 92%) by use of racemic 3-
bromocyclohexene. Colorless oil; 1H NMR (300 MHz, CDCl3): d=0.71
(d, J=6.3 Hz, 3H; CMe), 0.72 (d, J=6.0 Hz, 3H; 3ꢂCH), 1.81–2.05 (m,
6H; 6ꢂCH), 2.29 (s, 3H; PhCH3), 2.67 (s, 6H; 2ꢂPhCH3), 3.86–3.93 (m,
1H; NCH), 3.98–4.01 (m, 1H; NCH), 4.74 (dd, J=6.9, 3.6 Hz, 2H; 4-
CH2), 5.55 (dt, J=6.9, 6.9 Hz, 1H; 2-H), 5.66–5.86 (m, 2H; 2ꢂC=CH),
6.93 ppm (s, 2H; Ph); 13C NMR (75.5 MHz, CDCl3): d=20.9, 21.1 (0.5C),
21.3 (0.5C), 22.5 (0.5C), 22.6 (0.5C), 22.90, 22.93, 23.0 (0.5C), 23.3 (0.5C),
24.5, 25.1 (0.5C), 25.4 (0.5C), 28.7 (0.5C), 29.3 (0.5C), 43.2 (0.5C), 43.6
(0.5C), 55.0 (0.5C), 55.2 (0.5C), 55.3 (0.5C), 55.5 (0.5C), 75.9 (0.5C), 76.0
(0.5C), 91.4 (0.5C), 91.8 (0.5C), 129.3 (0.5C), 129.4 (0.5C), 129.9 (0.5C),
130.6 (0.5C), 131.9 (2C), 133.3 (0.5C), 133.6 (0.5C), 140.4, 140.5, 142.37
(0.5C), 142.41 (0.5C), 208.5 (0.5C), 208.6 ppm (0.5C); IR (KBr): n˜ =1953
(C=C=C), 1315 (SO2N), 1157 cmÀ1 (SO2N); MS (FAB): m/z (%): 388
(38) [M++H], 268 (100), 119 (100); HRMS (FAB): calcd for C23H34NO2S
[M++H]: 388.2310; found: 388.2308.
General procedure for the palladium(0)-catalyzed tandem cyclization
(3S,4S,7R,8S)-5-Aza-4-isopropyl-2-methylene-8-phenyl-5-(2,4,6-trimethyl-
phenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (20a) and its
(3S,4S,7S,8S) isomer (21a, Table 1, entry 1): A stirred mixture of allenene
10a (100 mg, 0.244 mmol), [Pd(PPh3)4] (27.7 mg, 0.024 mmol), iodoben-
zene (0.055 mL, 0.488 mmol), and K2CO3 (67.4 mg, 0.488 mmol) in diox-
ane (3 mL) was heated under reflux for 7.5 h. Water was added to the
mixture and it was extracted with Et2O. The extract was washed with
water and brine, and dried over MgSO4. The filtrate was concentrated
under reduced pressure to leave an oily residue, which was purified by
flash chromatography over silica gel with n-hexane/EtOAc (50:1) to give,
in the order of elution, 20a (48.4 mg, 41%) and 21a (12.4 mg, 10%).
Compound 20a: Colorless oil; [a]2D5 =+12.0 (c=1.33, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.90 (d, J=7.3 Hz, 3H; CMe), 0.92 (d, J=7.3 Hz,
3H; CMe), 2.02–2.16 (m, 1H; Me2CH), 2.26 (s, 3H; PhCH3), 2.33–2.41
(m, 1H; 7-H), 2.53 (s, 6H; 2ꢂPhCH3), 2.64–2.68 (m, 1H; 3-H), 2.77 (dd,
J=11.6, 11.6 Hz, 1H; 6-CHH), 3.47 (dd, J=11.6, 6.1 Hz, 1H; 6-CHH),
3.88 (d, J=11.6 Hz, 1H; 8-H), 4.45 (dd, J=7.9, 4.3 Hz, 1H; 4-H), 5.11 (s,
1H; C=CHH), 5.57 (s, 1H; C=CHH), 6.79–7.61 (m, 9H; Ph), 6.87 ppm
(s, 2H; Ph); 13C NMR (75.5 MHz, CDCl3): d=17.3, 19.4, 20.9, 22.9 (2C),
32.6, 48.4, 51.5, 51.9, 53.2, 64.1, 106.0, 125.4, 126.5, 126.9, 128.1, 128.5
(2C), 128.7 (2C), 129.8, 131.9 (2C), 133.1, 136.7, 139.5, 140.1 (2C), 142.3,
143.9, 145.4 ppm; IR (KBr): n˜ =1315 (SO2N), 1153 cmÀ1 (SO2N); MS
(FAB): m/z (%): 486 (100) [M++H]; HRMS (FAB): calcd for
C31H36NO2S [M++H]: 486.2467; found: 486.2471.
N-[(1R)-Cyclohex-2-en-1-yl]-N-{(1S)-1-[(1S)-1-methylpropyl]buta-2,3-
dienyl}-2,4,6-trimethylphenylsulfonamide (12c) and its N-[(1S)-cyclohex-
2-en-1-yl] isomer (13c): By using a procedure similar to that described
for the synthesis of 10a, amino allene 9a (100 mg, 0.325 mmol) was con-
verted into, in the order of elution, 12c (23.4 mg, 19%) and 13c
(28.4 mg, 23%) by use of racemic 3-bromocyclohexene.
Compound 12c: Colorless crystals; m.p. 76–788C (n-hexane/Et2O);
[a]2D3 =+3.38 (c=0.87, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.64 (t,
J=7.3 Hz, 3H; CMe), 0.73–0.76 (m, 1H; CH), 0.84 (d, J=6.7 Hz, 3H;
CMe), 1.52–2.07 (m, 8H; 8ꢂCH), 2.23 (s, 3H; PhCH3), 2.65 (s, 6H; 2ꢂ
PhCH3), 3.64 (dd, J=9.8, 9.2 Hz, 1H; 1-H), 4.19–4.22 (m, 1H; 1’-H),
4.67–4.75 (m, 2H; 4-CH2), 5.57–5.76 (m, 2H; 2’-H and 3’-H), 5.73–5.77
(m, 1H; 2-H), 6.93 ppm (s, 2H; Ph); 13C NMR (67.8 MHz, CDCl3): d=
11.5, 17.0, 21.0, 23.0, 23.3 (2C), 24.7, 26.5, 29.2, 38.1, 56.0, 63.2, 75.2, 90.6,
129.8 (2C), 131.9 (2C), 134.6, 139.9 (2C), 142.0, 208.8 ppm; IR (KBr): n˜ =
1956 (C=C=C), 1319 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z (%):
388 (100) [M++H]; HRMS (FAB): calcd for C23H34NO2S [M++H]:
388.2310; found: 388.2328.
Compound 21a: Colorless crystals; [a]2D4 =À1.05 (c=1.39, CHCl3);
1H NMR (500 MHz, CDCl3): d=0.81 (d, J=7.3 Hz, 3H; CMe), 0.92 (d,
J=7.3 Hz, 3H; CMe), 2.00–2.04 (m, 1H; Me2CH), 2.28 (s, 3H; PhCH3),
2.52 (s, 6H; 2ꢂPhCH3), 2.81 (ddd, J=12.8, 6.1, 6.1 Hz, 1H; 7-H), 3.07–
3.09 (m, 1H; 3-H), 3.22 (dd, J=9.8, 6.1 Hz, 1H; 6-CHH), 3.36 (dd, J=
9.8, 6.1 Hz, 1H; 6-CHH), 3.96–3.99 (m, 2H; 4-H and 8-H), 5.11 (s, 1H;
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3735

H. Ohno, T. Tanaka et al.
C=CHH), 5.58 (s, 1H; C=CHH), 6.86 (s, 2H; Ph), 7.01–7.50 ppm (m,
9H; Ph); 13C NMR (67.8 MHz, CDCl3): d=17.1, 19.8, 21.0, 23.2 (2C),
32.0, 44.1, 45.2, 46.2, 52.9, 72.1, 113.1, 125.0, 126.3, 126.9, 128.1, 128.4
(4C), 129.5, 131.7 (2C), 133.9, 134.8, 136.7, 139.4 (2C), 141.8, 143.7,
144.9 ppm; IR (KBr): n˜ =1317 (SO2N), 1157 cmÀ1 (SO2N); MS (FAB):
m/z (%): 486 (70) [M++H], 442 (100); HRMS (FAB): calcd for
C31H36NO2S [M++H]: 486.2467; found: 486.2459.
4-H), 5.00 (s, 1H; C=CHH), 5.47 (s, 1H; C=CHH), 6.38 (d, J=2.4 Hz,
1H; Ph), 6.77 (dd, J=8.5, 2.4 Hz, 1H; Ph), 6.86 (s, 2H; Ph), 7.03 (d, J=
7.3 Hz, 2H; Ph), 7.17–7.26 (m, 3H; Ph), 7.44 ppm (d, J=8.5 Hz, 1H;
Ph); 13C NMR (75.5 MHz, CDCl3): d=17.1, 19.6, 20.9, 23.1 (2C), 31.9,
44.0, 45.0, 46.4, 52.9, 55.2, 72.4, 111.2, 113.4, 114.1, 126.4, 126.5, 127.7,
128.5 (5C), 131.8 (2C), 134.1, 138.1, 139.6 (2C), 141.9, 143.7, 144.4 ppm;
IR (KBr): n˜ =1315 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 516
(53) [M++H], 136 (100); HRMS (FAB): calcd for C32H38NO3S [M++H]:
516.2572; found: 516.2571.
(3S,4S,7R,8S)-5-Aza-4-isopropyl-11-methyl-2-methylene-8-phenyl-5-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(20b) and its (3S,4S,7S,8S) isomer (21b) (Table 1, entry 2): By using a
procedure similar to that described for the synthesis of 20a and 21a, alle-
nene 10a (80.0 mg, 0.195 mmol) was converted into, in the order of elu-
tion, 20b (35.9 mg, 37%) and 21b (18.0 mg, 18%), by use of 4-iodo-
toluene.
Compound 20b: Colorless oil; [a]2D4 =À6.03 (c=1.29, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.89 (d, J=7.3 Hz, 3H; CMe), 0.91 (d, J=7.3 Hz,
3H; CMe), 1.99–2.06 (m, 1H; Me2CH), 2.17 (s, 3H; PhCH3), 2.27 (s, 3H;
PhCH3), 2.34 (dddd, J=11.6, 11.6, 11.0, 6.1 Hz, 1H; 7-H), 2.53 (s, 6H; 2ꢂ
PhCH3), 2.60–2.65 (m, 1H; 3-H), 2.75 (dd, J=11.6, 11.6 Hz, 1H; 6-
CHH), 3.44 (dd, J=11.6, 6.1 Hz, 1H; 6-CHH), 3.83 (d, J=11.0 Hz, 1H;
8-H), 4.43 (dd, J=7.9, 4.3 Hz, 1H; 4-H), 5.05 (d, J=1.8 Hz, 1H; C=
CHH), 5.51 (d, J=1.8 Hz, 1H; C=CHH), 6.59 (s, 1H; Ph), 6.87 (s, 2H;
Ph), 7.01 (d, J=7.9 Hz, 1H; Ph), 7.06 (d, J=6.7 Hz, 2H; Ph), 7.22–7.29
(m, 3H; Ph), 7.50 ppm (d, J=7.9 Hz, 1H; Ph); 13C NMR (67.8 MHz,
CDCl3): d=17.4, 19.5, 21.0, 21.2, 23.0 (2C), 32.6, 48.5, 51.4, 52.0, 53.2,
64.2, 105.1, 125.2, 126.7, 127.4, 128.4 (2C), 128.6 (2C), 130.1, 131.8 (2C),
133.0, 134.0, 137.9, 139.2, 139.9 (2C), 142.2, 143.8, 145.1 ppm; IR (KBr):
n˜ =1315 (SO2N), 1153 cmÀ1 (SO2N); MS (FAB): m/z (%): 500 (98) [M+
+H], 456 (100); HRMS (FAB): calcd for C32H38NO2S [M++H]:
500.2623; found: 500.2635.
(3S,4S,7R,8S)-5-Aza-4-isopropyl-10-methoxy-2-methylene-8-phenyl-5-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(20da) and (3S,4S,7R,8S)-5-aza-4-isopropyl-12-methoxy-2-methylene-8-
phenyl-5-(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-
1(9),10,12-triene (20db) (Table 1, entry 4): By using a procedure similar
to that described for the synthesis of 20a and 21a, allenene 10a (213 mg,
0.520 mmol) was converted into 20da (50.0 mg, 19%) and 20db (45.0 mg,
17%) by use of 3-iodoanisole.
Compound 20da: Colorless powder; m.p. 163–1658C; [a]2D3 =+6.70 (c=
1.035, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.88 (d, J=6.2 Hz, 3H;
CMe), 0.91 (d, J=6.9 Hz, 3H; CMe), 2.01–2.04 (m, 1H; Me2CH), 2.27 (s,
3H; PhCH3), 2.27–2.40 (m, 1H; 7-H), 2.53 (s, 6H; 2ꢂPhCH3), 2.62–2.70
(m, 1H; 3-H), 2.77 (dd, J=11.8, 11.8 Hz, 1H; 6-CHH), 3.45 (dd, J=11.8,
6.2 Hz, 1H; 6-CHH), 3.81 (s, 3H; OMe), 3.82 (d, J=8.7 Hz, 1H; 8-H),
4.44 (dd, J=8.1, 4.4 Hz, 1H; 4-H), 5.12 (d, J=1.2 Hz, 1H; C=CHH), 5.56
(d, J=1.2 Hz, 1H; C=CHH), 6.70 (s, 2H; Ar), 6.88 (s, 2H; Ar), 7.05 (d,
J=8.1 Hz, 2H; Ar), 7.11 (s, 1H; Ar), 7.22–7.30 ppm (m, 3H; Ar);
13C NMR (75.5 MHz, CDCl3): d=17.2, 19.5, 20.9, 22.9 (2C), 32.5, 48.3,
50.8, 52.2, 53.1, 55.3, 64.0, 106.2, 109.7, 114.5, 126.8, 128.4 (2C), 128.7
(2C), 130.9, 131.9 (3C), 133.0, 137.8, 140.0 (2C), 142.4, 144.0, 145.4,
158.0 ppm; IR (KBr): n˜ =1311 (SO2N), 1153 cmÀ1 (SO2N); MS (FAB):
m/z (%): 516 (86) [M++H], 472 (100); HRMS (FAB): calcd for
C32H38NO3S [M++H]: 516.2572; found: 516.2550.
Compound 20db: Colorless powder; m.p. 202–2048C; [a]2D2 =À27.5 (c=
1.01, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.85 (d, J=7.5 Hz, 3H;
CMe), 0.88 (d, J=7.5 Hz, 3H; CMe), 1.99–2.18 (m, 2H; Me2CH and 7-
H), 2.27 (s, 3H; PhCH3), 2.49 (s, 6H; 2ꢂPhCH3), 2.48–2.57 (m, 1H; 3-
H), 2.85 (dd, J=11.8, 11.2 Hz, 1H; 6-CHH), 3.31 (s, 3H; OMe), 3.61 (dd,
J=11.8, 6.2 Hz, 1H; 6-CHH), 3.91 (d, J=10.6 Hz, 1H; 8-H), 4.37 (dd,
J=8.1, 4.4 Hz, 1H; 4-H), 5.10 (s, 1H; C=CHH), 5.57 (s, 1H; C=CHH),
6.72 (dd, J=6.9, 2.5 Hz, 1H; Ar), 6.87 (s, 2H; Ar), 6.91 (d, J=6.9 Hz,
2H; Ar), 7.08–7.24 ppm (m, 5H; Ar); 13C NMR (75.5 MHz, CDCl3): d=
16.8, 19.6, 20.9, 22.8 (2C), 32.3, 47.2, 47.3, 53.2, 53.3, 55.3, 63.5, 105.7,
111.3, 118.3, 125.5, 126.5 (2C), 127.6, 128.0 (2C), 128.2, 131.9 (2C), 133.0,
139.6, 140.0 (2C), 142.3, 146.0, 146.6, 158.1 ppm; IR (KBr): n˜ =1313
(SO2N), 1153 cmÀ1 (SO2N); MS (FAB): m/z (%): 516 (99) [M++H], 472
(100); HRMS (FAB): calcd for C32H38NO3S [M++H]: 516.2572; found:
516.2567.
Compound 21b: Colorless oil; 1H NMR (500 MHz, CDCl3): d=0.79 (d,
J=6.7 Hz, 3H; CMe), 0.90 (d, J=6.7 Hz, 3H; CMe), 1.96–2.02 (m, 1H;
Me2CH), 2.22 (s, 3H; PhCH3), 2.28 (s, 3H; PhCH3), 2.52 (s, 6H; 2ꢂ
PhCH3), 2.76–2.81 (m, 1H; 7-H), 3.04–3.06 (m, 1H; 3-H), 3.21 (dd, J=
9.8, 6.7 Hz, 1H; 6-CHH), 3.36 (dd, J=9.8, 6.7 Hz, 1H; 6-CHH), 3.93 (d,
J=5.5 Hz, 1H; 8-H), 3.96 (dd, J=4.3, 4.3 Hz, 1H; 4-H), 5.04 (s, 1H; C=
CHH), 5.54 (s, 1H; C=CHH), 6.68 (s, 1H; Ph), 6.85 (s, 2H; Ph), 7.03 (d,
J=6.7 Hz, 2H; Ph), 7.17–7.29 (m, 4H; Ph), 7.39 ppm (d, J=7.9 Hz, 1H;
Ph).
(3S,4S,7R,8S)-5-Aza-4-isopropyl-11-methoxy-2-methylene-8-phenyl-5-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(20c) and its (3S,4S,7S,8S) isomer (21c) (Table 1, entry 3): By using a
procedure similar to that described for the synthesis of 20a and 21a, alle-
nene 10a (80.0 mg, 0.195 mmol) was converted into, in the order of elu-
tion, 20c (43.8 mg, 43%) and 21c (20.4 mg, 20%), by use of 4-iodo-
anisole.
Compound 20c: Colorless crystals; m.p. 185–1878C; [a]2D3 =À14.7 (c=
0.38, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.90 (d, J=7.3 Hz, 3H;
CMe), 0.91 (d, J=7.3 Hz, 3H; CMe), 2.00–2.06 (m, 1H; Me2CH), 2.27 (s,
3H; PhCH3), 2.36 (dddd, J=11.6, 11.6, 11.6, 6.1 Hz, 1H; 7-H), 2.53 (s,
6H; 2ꢂPhCH3), 2.61–2.65 (m, 1H; 3-H), 2.75 (dd, J=11.6, 11.6 Hz, 1H;
6-CHH), 3.44 (dd, J=11.6, 6.1 Hz, 1H; 6-CHH), 3.62 (s, 3H; OMe), 3.83
(d, J=11.6 Hz, 1H; 8-H), 4.43 (dd, J=7.9, 4.3 Hz, 1H; 4-H), 5.00 (s, 1H;
C=CHH), 5.44 (s, 1H; C=CHH), 6.29 (d, J=2.4 Hz, 1H; Ph), 6.76 (dd,
J=9.2, 2.4 Hz, 1H; Ph), 6.87 (s, 2H; Ph), 7.06 (d, J=7.3 Hz, 2H; Ph),
7.21–7.28 (m, 3H; Ph), 7.55 ppm (d, J=9.2 Hz, 1H; Ph); 13C NMR
(67.8 MHz, CDCl3): d=17.4, 19.5, 21.0, 23.0 (2C), 32.6, 48.5, 51.6, 51.7,
53.2, 55.2, 64.1, 104.3, 112.4, 114.5, 126.5, 126.9, 128.4 (2C), 128.6 (2C),
129.6, 131.8 (2C), 132.9, 139.9 (2C), 140.9, 142.2, 143.4, 144.7, 159.2 ppm;
IR (KBr): n˜ =1313 (SO2N), 1153 cmÀ1 (SO2N); MS (FAB): m/z (%): 516
(70) [M++H], 472 (100); HRMS (FAB): calcd C32H38NO3S [M++H]:
516.2572; found: 516.2572.
(3S,4S,7R,8S)-5-Aza-4-isopropyl-13-methoxy-2-methylene-8-phenyl-5-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(20e), its (3S,4S,7S,8S) isomer (21e) (Table 1, entry 5), and (2S,3S)-4-
[(Z)-benzylidene]-2-isopropyl-3-[1-(2-methoxyphenyl)vinyl]-1-(2,4,6-tri-
methylphenylsulfonyl)pyrrolidine (58):[25] By using a procedure similar to
that described for the synthesis of 20a and 21a, allenene 10a (100 mg,
0.244 mmol) was converted into 20e (45.2 mg, 36%), 21e (3 mg, 2%),
and 58 (18.0 mg, 14%) by use of 2-iodoanisole.
Compound 20e: Colorless powder; m.p. 221–2228C; [a]2D3 =+24.0 (c=
1.06, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.86 (d, J=6.9 Hz, 3H;
CMe), 0.92 (d, J=7.5 Hz, 3H; CMe), 1.97–2.05 (m, 1H; Me2CH), 2.27 (s,
3H; PhCH3), 2.27–2.41 (m, 1H; 7-H), 2.53 (s, 6H; 2ꢂPhCH3), 2.53–2.59
(m, 1H; 3-H), 2.77 (dd, J=11.8, 11.2 Hz, 1H; 6-CHH), 3.54 (dd, J=11.2,
5.6 Hz, 1H; 6-CHH), 3.85 (s, 3H; OMe), 3.88 (d, J=11.2 Hz, 1H; 8-H),
4.48 (dd, J=8.1, 3.8 Hz, 1H; 4-H), 5.46 (s, 1H; C=CHH), 6.04 (s, 1H; C=
CHH), 6.44 (d, J=7.5 Hz, 1H; Ar), 6.78 (d, J=8.1 Hz, 1H; Ar), 6.88 (s,
2H; Ar), 7.00–7.07 (m, 3H; Ar), 7.19–7.29 ppm (m, 3H; Ar); 13C NMR
(75.5 MHz, CDCl3): d=17.2, 19.5, 20.9, 22.9 (2C), 32.3, 49.5, 52.0, 52.2,
53.8, 55.6, 63.5, 109.3, 111.8, 122.6, 126.2, 126.7, 127.8, 128.4 (2C), 128.6
(2C), 131.9 (2C), 133.2, 139.7, 140.0 (2C), 141.7, 142.3, 144.6, 157.5 ppm;
IR (KBr): n˜ =1309 (SO2N), 1153 cmÀ1 (SO2N); elemental analysis calcd
Compound 21c: Colorless oil; [a]2D2 =À5.45 (c=1.05, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.80 (d, J=7.3 Hz, 3H; CMe), 0.90 (d, J=7.3 Hz,
3H; CMe), 1.97–2.03 (m, 1H; Me2CH), 2.28 (s, 3H; PhCH3), 2.53 (s, 6H;
2ꢂPhCH3), 2.76–2.81 (m, 1H; 7-H), 3.02–3.05 (m, 1H; 3-H), 3.23 (dd,
J=9.8, 6.1 Hz, 1H; 6-CHH), 3.37 (dd, J=9.8, 6.7 Hz, 1H; 6-CHH), 3.69
(s, 3H; OMe), 3.94 (d, J=5.5 Hz, 1H; 8-H), 3.96 (dd, J=4.3, 4.3 Hz, 1H;
3736
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3728 – 3741

Cyclization of Allenenes
FULL PAPER
(%) for C32H37NO3S: C 74.53, H 7.23, N 2.72; found: C 74.38, H 7.27, N
2.74.
133.9, 138.0, 139.8 (2C), 142.0, 143.2, 143.8, 159.5 ppm; IR (KBr): n˜ =
1313 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 530 (100) [M+
+H]; HRMS (FAB): calcd for C33H40NO3S [M++H]: 530.2729; found:
530.2727.
Compound 58: Colorless oil; [a]2D2 =À102 (c=1.165, CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.41 (d, J=6.9 Hz, 3H; CMe), 0.68 (d, J=6.9 Hz,
3H; CMe), 1.62–1.70 (m, 1H; Me2CH), 2.30 (s, 3H; PhCH3), 2.62 (s, 6H;
2ꢂPhCH3), 3.59 (d, J=3.7 Hz, 1H; 2-H), 3.87 (s, 3H; OMe), 4.00 (s, 1H;
3-H), 4.32 (d, J=15.0 Hz, 1H; 5-CHH), 4.62 (d, J=15.0 Hz, 1H; 5-
CHH), 5.10 (s, 1H; C=CHH), 5.20 (s, 1H; C=CHH), 6.49 (s, 1H; C=
CHPh), 6.87 (dd, J=8.1, 7.5 Hz, 2H; Ar), 6.93 (s, 2H; Ar), 7.07 (d, J=
7.5 Hz, 1H; Ar), 7.21–7.40 ppm (m, 6H; Ar); 13C NMR (75.5 MHz,
CDCl3): d=16.3, 18.7, 20.9, 23.1 (2C), 32.2, 50.8, 51.4, 55.3, 67.4, 110.1,
115.2, 120.5, 125.5, 126.9, 128.2 (2C), 128.5 (2C), 128.9, 130.8, 131.7 (2C),
131.8, 133.5, 136.9, 139.8, 140.1 (2C), 142.3, 150.1, 156.0 ppm; IR (KBr):
n˜ =1319 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB): m/z (%): 516 (97) [M+
+H], 472 (100); HRMS (FAB): calcd for C32H38NO3S [M++H]:
516.2572; found: 516.2584.
Compound 23b: Colorless crystals; m.p. 163–1658C (n-hexane/EtOAc);
[a]2D0 =À11.3 (c=1.03, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.82 (d,
J=6.7 Hz, 3H; CMe), 0.84 (d, J=6.7 Hz, 3H; CMe), 1.38–1.50 (m, 2H;
1’-CH2), 1.69–1.75 (m, 1H; 2’-H), 2.27 (s, 3H; PhCH3), 2.33–2.40 (m, 1H;
7-H), 2.47–2.52 (m, 1H; 3-H), 2.55 (s, 6H; 2ꢂPhCH3), 2.85 (dd, J=11.6,
11.6 Hz, 1H; 6-CHH), 3.52 (dd, J=11.6, 5.5 Hz, 1H; 6-CHH), 3.62 (s,
3H; OMe), 3.80 (d, J=11.0 Hz, 1H; 8-H), 4.37 (ddd, J=7.9, 6.1, 6.1 Hz,
1H; 4-H), 4.94 (s, 1H; C=CHH), 5.44 (s, 1H; C=CHH), 6.28 (d, J=
2.4 Hz, 1H; 10-H), 6.76 (dd, J=8.5, 2.4 Hz, 1H; 12-H), 6.89 (s, 2H; Ph),
7.06–7.07 (m, 2H; Ph), 7.22–7.29 (m, 3H; Ph), 7.57 ppm (d, J=8.5 Hz,
1H; 13-H); 13C NMR (67.8 MHz, CDCl3): d=21.0, 23.0 (2C), 23.3, 23.4,
24.3, 46.0, 51.3, 51.8, 52.2, 54.9, 55.2, 59.1, 103.6, 112.5, 114.5, 126.3, 126.9,
128.5 (2C), 128.6 (2C), 129.0, 131.8 (2C), 133.2, 140.0 (2C), 140.9, 142.2,
143.4, 144.1, 159.3 ppm; IR (KBr): n˜ =1319 (SO2N), 1155 cmÀ1 (SO2N);
MS (FAB): m/z (%): 530 (87) [M++H], 472 (100); HRMS (FAB): calcd
for C33H40NO3S [M++H]: 530.2729; found: 530.2736.
(3S,4S,7R,8S)-5-Aza-4-isobutyl-2-methylene-8-phenyl-5-(2,4,6-trimethyl-
phenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (22a) and its
(3S,4S,7S,8S) isomer (23a) (Table 1, entry 6): By using a procedure iden-
tical to that described for the synthesis of 20a and 21a, allenene 10b
(150 mg, 0.354 mmol) was converted into, in the order of elution, 22a
(38.0 mg, 21%) and 23a (25.0 mg, 14%).
Compound 22a: Colorless oil; [a]2D8 =+14.9 (c=1.22, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.82 (d, J=6.7 Hz, 3H; CMe), 0.83 (d, J=6.7 Hz,
3H; CMe), 1.25–1.49 (m, 2H; Me2CHCH2), 1.68–1.74 (m, 1H; Me2CH),
2.27 (s, 3H; PhCH3), 2.34–2.43 (m, 1H; 7-H), 2.51–2.54 (m, 1H; 3-H),
2.55 (s, 6H; 2ꢂPhCH3), 2.87 (dd, J=12.2, 11.6 Hz, 1H; 6-CHH), 3.55
(dd, J=12.2, 6.1 Hz, 1H; 6-CHH), 3.85 (d, J=11.0 Hz, 1H; 8-H), 4.38
(ddd, J=6.7, 6.7, 6.7 Hz, 1H; 4-H), 5.06 (d, J=1.8 Hz, 1H; C=CHH),
5.58 (d, J=1.8 Hz, 1H; C=CHH), 6.77–7.64 (m, 9H; Ph), 6.89 ppm (s,
2H; Ph); 13C NMR (75.5 MHz, CDCl3): d=20.9, 22.9 (2C), 23.2, 23.4,
24.2, 45.9, 51.4, 51.6, 52.2, 54.8, 59.1, 105.5, 125.1, 126.6, 126.9, 128.2,
128.6 (2C), 128.7 (2C), 129.8, 131.9 (2C), 133.3, 136.1, 139.5, 140.1 (2C),
142.3, 143.8, 144.7 ppm; IR (KBr): n˜ =1313 (SO2N), 1153 cmÀ1 (SO2N);
MS (FAB): m/z (%): 500 (100) [M++H]; HRMS (FAB): calcd for
C32H38NO2S [M++H]: 500.2623; found: 500.2626.
Compound 23a: Colorless solid; [a]2D8 =À5.78 (c=1.88, CHCl3);
1H NMR (500 MHz, CDCl3): d=0.77 (d, J=6.1 Hz, 3H; CMe), 0.80 (d,
J=6.1 Hz, 3H; CMe), 1.37–1.48 (m, 2H; Me2CHCH2), 1.57–1.62 (m, 1H;
Me2CH), 2.27 (s, 3H; PhCH3), 2.53 (s, 6H; 2ꢂPhCH3), 2.82–2.87 (m, 1H;
7-H), 2.93–2.95 (m, 1H; 3-H), 3.10 (dd, J=9.8, 6.1 Hz, 1H; 6-CHH), 3.38
(dd, J=9.8, 6.7 Hz, 1H; 6-CHH), 3.97–4.02 (m, 2H; 4-H and 8-H), 5.13
(s, 1H; C=CHH), 5.65 (s, 1H; C=CHH), 6.86 (s, 2H; Ph), 6.87–7.55 ppm
(m, 9H; Ph); 13C NMR (67.8 MHz, CDCl3): d=21.0, 21.7, 23.2 (2C), 23.8,
25.4, 44.1 (2C), 46.3, 48.5, 51.2, 65.6, 112.8, 124.7, 126.4, 126.9, 128.1,
128.4 (2C), 129.7, 131.6 (4C), 133.7, 134.5, 136.5, 139.7 (2C), 141.9, 143.7,
143.8 ppm; IR (KBr): n˜ =1315 (SO2N), 1157 cmÀ1 (SO2N); MS (FAB): m/
z (%): 500 (80) [M++H], 91 (100); HRMS (FAB): calcd for C32H38NO2S
[M++H]: 500.2623; found: 500.2621.
(3S,4S,7R,8S)-5-Aza-4-benzyl-2-methylene-8-phenyl-5-(2,4,6-trimethyl-
phenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (24) and its
(3S,4S,7S,8S) isomer (25) (Table 1, entry 8): By using a procedure identi-
cal to that described for the synthesis of 20a and 21a, allenene 10c
(150 mg, 0.328 mmol) was converted into, in the order of elution, 24
(52.6 mg, 30%) and 25 (42.7 mg, 24%).
Compound 24: Colorless oil; [a]2D8 =+32.7 (c=2.00, CHCl3); 1H NMR
(500 MHz, CDCl3): d=2.22–2.32 (m, 1H; 7-H), 2.29 (s, 3H; PhCH3),
2.56–2.65 (m, 1H; 3-H), 2.62 (s, 6H; 2ꢂPhCH3), 2.70 (dd, J=11.6,
À
11.6 Hz, 1H; 6-CHH), 2.88 (dd, J=13.4, 6.7 Hz, 1H; Ph CHH), 2.95
À
(dd, J=13.4, 6.1 Hz, 1H; Ph CHH), 3.63 (dd, J=11.6, 6.1 Hz, 1H; 6-
CHH), 3.70 (d, J=11.0 Hz, 1H; 8-H), 4.51–4.54 (m, 1H; 4-H), 4.58 (d,
J=1.8 Hz, 1H; C=CHH), 5.38 (d, J=1.8 Hz, 1H; C=CHH), 6.71–
7.54 ppm (m, 16H; Ph); 13C NMR (75.5 MHz, CDCl3): d=20.9, 23.2
(2C), 40.6, 50.9, 51.2, 51.6, 52.7, 61.7, 106.1, 125.0, 126.5 (2C), 126.9,
128.1, 128.3 (2C), 128.5 (2C), 128.7 (2C), 129.8, 130.0 (2C), 132.1 (2C),
133.5, 135.7, 137.0, 139.3, 139.9 (2C), 142.6, 143.4, 143.7 ppm; IR (KBr):
n˜ =1311 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB): m/z (%): 534 (20) [M+
+H], 136 (100); HRMS (FAB): calcd for C35H36NO2S [M++H]: 534.2467;
found: 534.2470.
Compound 25: Colorless oil; [a]2D8 =+6.35 (c=1.81, CHCl3); 1H NMR
(500 MHz, CDCl3): d=2.28 (s, 3H; PhCH3), 2.57 (s, 6H; 2ꢂPhCH3),
À
2.70–2.77 (m, 2H; Ph CHH and 7-H), 2.97–2.99 (m, 1H; 3-H), 3.07 (dd,
À
J=14.0, 3.7 Hz, 1H; Ph CHH), 3.11 (dd, J=9.8, 6.1 Hz, 1H; 6-CHH),
3.34 (dd, J=9.8, 6.7 Hz, 1H; 6-CHH), 3.92 (d, J=6.1 Hz, 1H; 8-H), 4.25
(ddd, J=7.9, 3.7, 3.7 Hz, 1H; 4-H), 4.61 (d, J=1.2 Hz, 1H; C=CHH),
5.43 (s, 1H; C=CHH), 6.65–7.44 ppm (m, 16H; Ph); 13C NMR
(75.5 MHz, CDCl3): d=20.9, 23.2 (2C), 40.7, 43.6, 45.9, 46.2, 51.7, 68.3,
113.0, 124.8, 126.4 (2C), 127.0, 128.1, 128.4 (4C), 128.5 (2C), 129.6 (2C),
129.7, 131.9 (2C), 133.7, 134.4, 136.5, 137.9, 139.8 (2C), 142.2, 143.0,
143.7 ppm; IR (KBr): n˜ =1317 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB):
m/z (%): 534 (70) [M++H], 442 (100); HRMS (FAB): calcd for
C35H36NO2S [M++H]: 534.2467; found: 534.2457.
(3S,4S,7R,8S)-5-Aza-4-isobutyl-11-methoxy-2-methylene-8-phenyl-5-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(22b) and its (3S,4S,7S,8S) isomer (23b) (Table 1, entry 7): By using a
procedure identical to that described for the synthesis of 20a and 21a, al-
lenene 10b (122 mg, 0.288 mmol) was converted into, in the order of elu-
tion, 22b (48.0 mg, 32%) and 23b (54.7 mg, 36%), by use of 4-iodo-
anisole.
(3S,4R,7R,8S)-5-Aza-4-(tert-butyl)-2-methylene-8-phenyl-5-(2,4,6-trime-
thylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (26) and its
(3S,4R,7S,8S) isomer (27) (Table 1, entry 9): By using a procedure identi-
cal to that described for the synthesis of 20a and 21a, allenene 10d
(45.0 mg, 0.106 mmol) was converted into, in the order of elution, 26
(18.0 mg, 34%) and 27 (3.6 mg, 7%).
Compound 26: Colorless oil; [a]2D3 =+31.9 (c=1.62, CHCl3); 1H NMR
(500 MHz, CDCl3): d=0.97 (s, 3H; CMe3), 2.24 (s, 3H; PhCH3), 2.24–
2.34 (m, 1H; 7-H), 2.50 (s, 6H; 2ꢂPhCH3), 2.69 (dd, J=12.2, 7.3 Hz, 1H;
3-H), 2.75 (dd, J=12.2, 12.2 Hz, 1H; 6-CHH), 3.30 (dd, J=12.2, 6.1 Hz,
1H; 6-CHH), 3.87 (d, J=11.6 Hz, 1H; 8-H), 4.40 (d, J=7.3 Hz, 1H; 4-
H), 5.19 (s, 1H; C=CHH), 5.61 (s, 1H; C=CHH), 6.79 (d, J=7.9 Hz, 1H;
Ph), 6.82 (s, 2H; Ph), 6.97–6.98 (m, 2H; Ph), 7.10 (t, J=7.3 Hz, 1H; Ph),
7.18–7.25 (m, 4H; Ph), 7.62 ppm (d, J=7.9 Hz, 1H; Ph); 13C NMR
(75.5 MHz, CDCl3): d=20.9, 23.3 (2C), 27.2 (3C), 36,4, 50.0, 51.5, 52.0,
Compound 22b: Colorless crystals; m.p. 145–1488C (n-hexane/EtOAc);
[a]2D0 =À0.92 (c=1.00, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.76 (d,
J=6.1 Hz, 3H; CMe), 0.79 (d, J=6.7 Hz, 3H; CMe), 1.35–1.45 (m, 2H;
1’-CH2), 1.48–1.70 (m, 1H; 2’-H), 2.28 (s, 3H; PhCH3), 2.53 (s, 6H; 2ꢂ
PhCH3), 2.79–2.86 (m, 1H; 7-H), 2.88–2.92 (m, 1H; 3-H), 3.11 (dd, J=
9.8, 6.1 Hz, 1H; 6-CHH), 3.38 (dd, J=9.8, 6.7 Hz, 1H; 6-CHH), 3.68 (s,
3H; OMe), 3.92–4.00 (m, 2H; 4-H and 8-H), 5.01 (s, 1H; C=CHH), 5.54
(s, 1H; C=CHH), 6.38 (d, J=2.4 Hz, 1H; 10-H), 6.77 (dd, J=8.5, 2.4 Hz,
1H; 12-H), 6.87 (s, 2H; Ph), 7.03–7.04 (m, 2H; Ph), 7.17–7.26 (m, 3H;
Ph), 7.49 ppm (d, J=8.5 Hz, 1H; 13-H); 13C NMR (75.5 MHz, CDCl3):
d=20.9, 21.6, 23.0 (2C), 23.7, 25.3, 43.97, 44.00, 46.4, 48.4, 51.2, 55.1, 65.7,
110.8, 113.5, 114.2, 126.2, 126.5, 127.4, 128.5 (2C), 128.5 (2C), 131.7 (2C),
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3737

H. Ohno, T. Tanaka et al.
53.5, 68.1, 105.9, 125.6, 126.5, 126.8, 128.0, 128.5 (2C), 128.6 (2C), 129.9,
131.9 (2C), 133.0, 137.0, 139.6, 140.1 (2C), 142.2, 143.9, 145.4 ppm; IR
(KBr): n˜ =1309 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 500
(100) [M++H]; HRMS (FAB): calcd for C32H38NO2S [M++H]: 500.2623;
found: 500.2591.
Compound 27: Colorless oil; 1H NMR (500 MHz, CDCl3): d=0.93 (s,
3H; CMe3), 2.26 (s, 3H; PhCH3), 2.48 (s, 6H; 2ꢂPhCH3), 2.99–3.05 (m,
1H; 7-H), 3.19 (dd, J=11.0, 6.1 Hz, 1H; 6-CHH), 3.22–3.24 (m, 1H; 3-
H), 3.37 (dd, J=11.0, 8.5 Hz, 1H; 6-CHH), 3.80 (d, J=6.7 Hz, 1H; 8-H),
4.14 (s, 1H; 4-H), 5.22 (s, 1H; C=CHH), 5.58 (s, 1H; C=CHH), 6.75 (d,
J=7.3 Hz, 1H; Ph), 6.81 (s, 2H; Ph), 6.95 (d, J=7.9 Hz, 2H; Ph), 7.10 (t,
J=7.3 Hz, 1H; Ph), 7.19–7.26 (m, 4H; Ph), 7.47 ppm (d, J=7.9 Hz, 1H;
Ph).
71.1, 77.1, 79.1, 112.3, 125.0, 126.4, 127.1, 128.2, 128.4 (2C), 128.5 (2C),
129.9, 135.8, 137.0, 144.3, 145.8, 155.0 ppm; IR (KBr): n˜ =1691 cmÀ1 (C=
O); MS (FAB): m/z (%): 404 (8) [M++H], 348 (100); HRMS (FAB):
calcd for C27H34NO2 [M++H]: 404.2590; found: 404.2607.
Compound 31: Colorless oil; [a]2D4 =À7.14 (c=1.47, CHCl3); 1H NMR
(500 MHz, CDCl3, 333 K): d=0.92 (d, J=6.9 Hz, 3H; CMe), 0.95 (d, J=
6.9 Hz, 3H; CMe), 1.40–1.44 (m, 9H; CMe3), 2.12–2.20 (m, 1H; 7-H),
2.40–2.66 (brs, 2H; Me2CH and 3-H), 2.90 (dd, J=11.1, 11.1 Hz, 1H; 6-
CHH), 3.60–3.80 (brs, 1H; 6-CHH), 3.98 (d, J=11.1 Hz, 1H; 8-H), 4.13–
4.21 (brs, 1H; 4-H), 5.08 (s, 1H; C=CHH), 5.55 (d, J=1.8 Hz, 1H; C=
CHH), 6.81 (d, J=7.5 Hz, 1H; Ph), 7.08–7.30 (m, 7H; Ph), 7.59–
7.61 ppm (m, 1H; Ph); 13C NMR (67.8 MHz, CDCl3, 333 K): d=17.5,
19.4, 28.7 (3C), 29.8, 48.7, 51.3, 52.1, 62.4, 77.2, 79.4, 105.5, 125.3, 126.4,
126.8, 128.0, 128.6 (4C), 130.0, 137.0, 139.7, 144.4, 146.3, 154.5 ppm; IR
(KBr): n˜ =1693 cmÀ1 (C=O); MS (FAB): m/z (%): 404 (6) [M++H], 348
(100); HRMS (FAB): calcd for C27H34NO2 [M++H]: 404.2590; found:
404.2590.
(3S,4S,7R,8S)-5-Aza-11-methoxy-2-methylene-4-[(1S)-1-methylpropyl]-8-
phenyl-5-(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-
1(9),10,12-triene (28) and its (3S,4S,7S,8S) isomer (29) (Table 1,
entry 10): By using a procedure identical to that described for the synthe-
sis of 20a and 21a, allenene 10e (141 mg, 0.332 mmol) was converted
into, in the order of elution, 28 (60.4 mg, 34%) and 29 (53.9 mg, 31%),
by use of 4-iodoanisole.
(3S,4S,7S)-5-Aza-4-isopropyl-8,8-dimethyl-2-methylene-5-(2,4,6-trimethyl-
phenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (32a) (Table 1,
entry 12): By using a procedure identical to that described for the synthe-
sis of 20a and 21a, allenene 11 (40.0 mg, 0.110 mmol) was converted into
32a (20.1 mg, 42%). Colorless oil; [a]2D2 =À42.9 (c=2.86, CHCl3);
1H NMR (500 MHz, CDCl3): d=0.88 (d, J=6.7 Hz, 3H; CMe), 0.88 (d,
J=6.7 Hz, 3H; CMe), 1.21 (s, 3H; CMe), 1.34 (s, 3H; CMe), 2.04–2.17
(m, 2H; Me2CH and 7-H), 2.30 (s, 3H; PhCH3), 2.69 (s, 6H; 2ꢂPhCH3),
2.67–2.71 (m, 1H; 3-H), 2.96 (dd, J=11.6, 11.6 Hz, 1H; 6-CHH), 3.72
(dd, J=11.6, 6.7 Hz, 1H; 6-CHH), 4.41 (dd, J=7.3, 4.3 Hz, 1H; 4-H),
5.06 (d, J=1.8 Hz, 1H; C=CHH), 5.47 (d, J=1.8 Hz, 1H; C=CHH), 6.96
(s, 2H; Ph), 7.16–7.19 (m, 1H; Ph), 7.26–7.29 (m, 1H; Ph), 7.33–7.35 (m,
1H; Ph), 7.52–7.54 ppm (m, 1H; Ph); 13C NMR (75.5 MHz, CDCl3): d=
17.3, 19.4, 20.9, 23.1 (2C), 25.2, 30.2, 32.8, 37.1, 43.2, 49.2, 53.6, 63.9,
105.4, 125.6, 126.2, 126.6, 128.4, 131.9 (2C), 133.3, 135.2, 140.1 (2C),
142.4, 145.7, 146.4 ppm; IR (KBr): n˜ =1315 (SO2N), 1153 cmÀ1 (SO2N);
MS (FAB): m/z (%): 438 (100) [M++H]; HRMS (FAB): calcd for
C27H36NO2S [M++H]: 438.2467; found: 438.2468.
Compound 28: Colorless crystals; m.p. 105–1088C (n-hexane/Et2O);
[a]1D9 =+13.3 (c=0.95, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.76 (d,
J=6.7 Hz, 3H; CMe), 0.79 (t, J=7.3 Hz, 3H; CMe), 1.10–1.17 (m, 1H;
2’-CHH), 1.36–1.42 (m, 1H; 2’-CHH), 1.59–1.63 (m, 1H; 1’-H), 2.28 (s,
3H; PhCH3), 2.54 (s, 6H; 2ꢂPhCH3), 2.74–2.79 (m, 1H; 7-H), 3.05 (dd,
J=6.1, 5.5 Hz, 1H; 3-H), 3.32–3.40 (m, 2H; 6-CH2), 3.69 (s, 3H; OMe),
3.98 (d, J=6.1 Hz, 1H; 8-H), 4.02 (dd, J=5.5, 3.7 Hz, 1H; 4-H), 4.98 (s,
1H; C=CHH), 5.45 (s, 1H; C=CHH), 6.39 (d, J=2.4 Hz, 1H; 10-H), 6.77
(dd, J=8.5, 2.4 Hz, 1H; 12-H), 6.87 (s, 2H; Ph), 7.04–7.07 (m, 2H; Ph),
7.18–7.26 (m, 3H; Ph), 7.45 ppm (d, J=8.5 Hz, 1H; 13-H); 13C NMR
(67.8 MHz, CDCl3): d=12.5, 14.2, 21.0, 23.1 (2C), 27.0, 38.9, 44.5, 45.5,
46.5, 53.2, 55.2, 70.3, 111.3, 113.4, 114.1, 126.3, 126.4, 127.5, 128.4 (2C),
128.5 (2C), 131.6 (2C), 134.2, 138.1, 139.4 (2C), 141.8, 143.9, 144.3,
159.4 ppm; IR (KBr): n˜ =1317 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB):
m/z (%): 530 (46) [M++H], 472 (100); HRMS (FAB): calcd for
C33H40NO3S [M++H]: 530.2729; found: 530.2715.
(3S,4S,7S)-5-Aza-4-isopropyl-11-methoxy-8,8-dimethyl-2-methylene-5-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(32b) (Table 1, entry 13): By using a procedure identical to that de-
scribed for the synthesis of 20a and 21a, allenene 11 (50.0 mg,
0.138 mmol) was converted into 32b (29.0 mg, 45%) by use of 4-iodoani-
sole. Colorless oil; [a]D20 =À49.2 (c=0.92, CHCl3); 1H NMR (500 MHz,
CDCl3): d=0.876 (d, J=6.7 Hz, 3H; CMe), 0.882 (d, J=6.7 Hz, 3H;
CMe), 1.20 (s, 3H; CMe), 1.32 (s, 3H; CMe), 2.02–2.15 (m, 2H; Me2CH
and 7-H), 2.30 (s, 3H; PhCH3), 2.64–2.71 (m, 1H; 3-H), 2.69 (s, 6H; 2ꢂ
PhCH3), 2.95 (dd, J=11.6, 11.6 Hz, 1H; 6-CHH), 3.70 (dd, J=11.6,
6.7 Hz, 1H; 6-CHH), 3.81 (s, 3H; OMe), 4.39 (dd, J=7.3, 4.3 Hz, 1H; 4-
H), 4.94 (d, J=1.2 Hz, 1H; C=CHH), 5.34 (d, J=1.8 Hz, 1H; C=CHH),
6.75 (dd, J=8.5, 2.4 Hz, 1H; Ph), 6.85 (d, J=2.4 Hz, 1H; Ph), 6.96 (s,
2H; Ph), 7.48 ppm (d, J=8.5 Hz, 1H; Ph); 13C NMR (75.5 MHz, CDCl3):
d=17.4, 19.3, 20.9, 23.1 (2C), 25.1, 30.2, 32.9, 37.2, 43.3, 49.2, 53.5, 55.3,
63.9, 103.7, 111.8, 111.9, 126.8, 128.2, 131.9 (2C), 133.3, 140.1 (2C), 142.4,
145.8, 147.3, 159.7 ppm; IR (KBr): n˜ =1367 (NSO2), 1153 cmÀ1 (NSO2);
MS (FAB): m/z (%): 468 (80) [M++H], 424 (100); HRMS (FAB): calcd
for C28H38NO3S [M++H]: 468.2572; found: 468.2580.
Compound 29: Colorless crystals; m.p. 167–1698C (n-hexane/Et2O);
[a]2D2 =À7.47 (c=1.15, CHCl3); 1H NMR (500 MHz, CDCl3): d=0.84 (t,
J=7.3 Hz, 3H; CMe), 0.86 (d, J=6.7 Hz, 3H; CMe), 0.98–1.08 (m, 1H;
2’-CHH), 1.47–1.56 (m, 1H; 2’-CHH), 1.69–1.72 (m, 1H; 1’-H), 2.27 (s,
3H; PhCH3), 2.32–2.41 (m, 1H; 7-H), 2.54 (s, 6H; 2ꢂPhCH3), 2.64 (dd,
J=12.2, 7.9 Hz, 1H; 3-H), 2.77 (dd, J=12.2, 11.6 Hz, 1H; 6-CHH), 3.47
(dd, J=11.6, 6.1 Hz, 1H; 6-CHH), 3.62 (s, 3H; OMe), 3.84 (d, J=
12.2 Hz, 1H; 8-H), 4.44 (dd, J=7.9, 4.3 Hz, 1H; 4-H), 5.01 (s, 1H; C=
CHH), 5.41 (s, 1H; C=CHH), 6.29 (d, J=1.8 Hz, 1H; 10-H), 6.76 (dd,
J=9.2, 1.8 Hz, 1H; 12-H), 6.88 (s, 2H; Ph), 7.05–7.07 (m, 2H; Ph), 7.21–
7.28 (m, 3H; Ph), 7.53 ppm (d, J=9.2 Hz, 1H; 13-H); 13C NMR
(67.8 MHz, CDCl3): d=12.4, 14.0, 21.0, 23.0 (2C), 26.4, 39.8, 48.5, 51.7,
52.1, 53.1, 55.2, 63.6, 104.2, 112.4, 114.5, 126.6, 126.9, 128.4 (2C), 128.6
(2C), 129.8, 131.8 (2C), 132.9, 140.0 (2C), 140.9, 142.3, 143.5, 145.0,
159.2 ppm; IR (KBr): n˜ =1309 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB):
m/z (%): 530 (87) [M++H], 472 (100); HRMS (FAB): calcd for
C33H40NO3S [M++H]: 530.2729; found: 530.2736.
(3S,4S,7R,8S)-5-Aza-5-(tert-butoxycarbonyl)-4-isopropyl-2-methylene-8-
phenyltricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(30)
and
its
(3S,4S,7R,8R)-5-Aza-4-isopropyl-2-methylene-8-phenyl-5-(2,4,6-trime-
thylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (33): By
using a procedure identical to that described for the synthesis of 20a and
21a, allenene (Z)-10a (50.0 mg, 0.122 mmol) was converted into, in the
order of elution, 20a (9.3 mg, 16%) and 33 (15.2 mg, 26%).
(3S,4S,7S,8S) isomer (31) (Table 1, entry 11): By using a procedure iden-
tical to that described for the synthesis of 20a and 21a, allenene 10 f
(45.2 mg, 0.138 mmol) was converted into, in the order of elution, 30
(8.7 mg, 16%) and 31 (19.4 mg, 35%).
Compound 33: Colorless oil; 1H NMR (500 MHz, CDCl3): d=0.53 (d,
J=6.7 Hz, 3H; CMe), 0.74 (d, J=6.7 Hz, 3H; CMe), 1.86–1.92 (m, 1H;
Me2CH), 2.20 (dd, J=12.2, 11.6 Hz, 1H; 6-CHH), 2.29 (s, 3H; PhCH3),
2.49–2.56 (m, 1H; 7-H), 2.63 (s, 6H; 2ꢂPhCH3), 2.79 (dd, J=12.8,
7.3 Hz, 1H; 3-H), 3.61 (dd, J=11.6, 6.1 Hz, 1H; 6-CHH), 4.31 (dd, J=
7.3, 4.3 Hz, 1H; 4-H), 4.45 (d, J=5.5 Hz, 1H; 8-H), 5.12 (d, J=1.8 Hz,
1H; C=CHH), 5.62 (d, J=1.8 Hz, 1H; C=CHH), 6.90 (d, J=6.7 Hz, 2H;
Ph), 6.93 (s, 2H; Ph), 6.98 (d, J=7.3 Hz, 1H; Ph), 7.17–7.25 (m, 5H; Ph),
7.70 ppm (d, J=7.3 Hz, 1H; Ph); 13C NMR (67.8 MHz, CDCl3): d=17.3,
Compound 30: Colorless oil; [a]2D4 =À17.9 (c=1.40, CHCl3); 1H NMR
(500 MHz, CDCl3, 328 K): d=0.93 (d, J=6.6 Hz, 3H; CMe), 0.95 (d, J=
6.9 Hz, 3H; CMe), 1.36 (s, 9H; CMe3), 1.97–2.09 (brs, 1H; Me2CH),
2.81–2.90 (m, 1H; 7-H), 2.99–3.01 (m, 1H; 3-H), 3.28–3.29 (brs, 1H; 6-
CHH), 3.40 (dd, J=11.4, 7.5 Hz, 1H; 6-CHH), 3.75–3.77 (brs, 1H; 4-H),
3.93 (d, J=4.5 Hz, 1H; 8-H), 5.10 (s, 1H; C=CHH), 5.56 (s, 1H; C=
CHH), 6.96 (d, J=7.2 Hz, 1H; Ph), 7.05 (d, J=6.9 Hz, 2H; Ph), 7.14–
7.28 (m, 5H; Ph), 7.54 ppm (dd, J=7.5, 1.2 Hz, 1H; Ph); 13C NMR
(75.5 MHz, CDCl3, 328 K): d=18.9, 19.3, 28.5 (3C), 31.8, 44.1, 47.5, 51.5,
3738
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3728 – 3741

Cyclization of Allenenes
FULL PAPER
19.2, 21.1, 23.1 (2C), 32.9, 41.2, 46.5, 46.7, 51.0, 63.5, 106.4, 125.0, 126.6,
126.7, 128.0 (2C), 128.3, 129.8 (2C), 131.0, 131.8 (2C), 133.1, 136.3, 138.2,
140.0 (2C), 141.0, 142.3, 144.9 ppm; IR (KBr): n˜ =1315 (SO2N),
1153 cmÀ1 (SO2N).
1H; 9-H), 2.74–2.82 (m, 2H; 1-H and 10-CHH), 3.39 (dd, J=11.8,
5.6 Hz, 1H; 10-CHH), 3.75 (d, J=11.2 Hz, 1H; 8-H), 4.38 (dd, J=8.1,
4.4 Hz, 1H; 12-H), 4.93 (s, 1H; C=CHH), 5.35 (s, 1H; C=CHH), 6.38 (d,
J=5.0 Hz, 1H; Ar), 6.87 (s, 2H; Ar), 7.01 (d, J=5.0 Hz, 1H; Ar), 7.08
(d, J=7.5 Hz, 2H; Ar), 7.23–7.30 ppm (m, 3H; Ar); 13C NMR
(75.5 MHz, CDCl3): d=18.0, 19.0, 20.9, 22.9 (2C), 33.0, 48.4, 49.4, 52.1,
52.4, 64.0, 105.4, 124.0, 127.1, 127.8 (2C), 127.9, 128.6 (2C), 131.9 (2C),
132.9, 138.8, 140.1 (2C), 140.4, 141.2, 142.4 ppm (2C); IR (KBr): n˜ =1313
(SO2N), 1151 cmÀ1 (SO2N); MS (FAB): m/z (%): 492 (58) [M++H], 307
(100); HRMS (FAB): calcd for C29H34NO2S2 [M++H]: 492.2031; found:
492.2061.
Compound 57a: Pale-yellow oil; [a]2D3 =+7.83 (c=1.06, CHCl3);
1H NMR (300 MHz, CDCl3): d=0.71 (d, J=6.9 Hz, 3H; CMe), 0.86 (d,
J=6.9 Hz, 3H; CMe), 1.92–1.99 (m, 1H; Me2CH), 2.29 (s, 3H; PhCH3),
2.60 (s, 6H; 2ꢂPhCH3), 2.89–3.07 (m, 1H; 9-H), 3.11 (dd, J=6.9, 6.2 Hz,
1H; 1-H), 3.25 (dd, J=10.0, 5.0 Hz, 1H; 10-CHH), 3.79 (dd, J=10.0,
3.7 Hz, 1H; 10-CHH), 4.01–4.05 (m, 2H; 8-H and 12-H), 4.98 (s, 1H; C=
CHH), 5.46 (s, 1H; C=CHH), 6.43 (d, J=5.0 Hz, 1H; Ar), 6.91 (s, 2H;
Ar), 7.04 (d, J=5.0 Hz, 1H; Ar), 7.15–7.18 (m, 2H; Ar), 7.18–7.30 ppm
(m, 3H; Ar); 13C NMR (75.5 MHz, CDCl3): d=17.8, 18.6, 20.9, 22.9 (2C),
30.9, 42.3, 45.9, 46.8, 53.4, 69.4, 110.7, 124.2, 126.7, 128.6 (3C), 128.7 (2C),
131.8 (2C), 135.4, 135.5, 138.3, 138.8, 139.3 (2C), 142.0, 144.1 ppm; IR
(KBr): n˜ =1315 (SO2N), 1155 cmÀ1 (SO2N); MS (FAB): m/z (%): 492
(100) [M++H]; HRMS (FAB): calcd for C29H34NO2S2 [M++H]:
492.2031; found: 492.2037.
(1S,9S,10S,12R,16R)-11-Aza-10-isopropyl-8-methylene-11-(2,4,6-trimeth-
ylphenylsulfonyl)tetracyclo[7.6.1.02,7.012,16]hexadeca-2(3),4,6-triene (34a):
By using a procedure identical to that described for the synthesis of 20a
and 21a, allenene 12a (80 mg, 0.214 mmol) was converted into 34a
1
(47.0 mg, 49%). Colorless solid; [a]2D8 =À12.9 (c=1.59, CHCl3); H NMR
(500 MHz, CDCl3): d=1.01 (d, J=6.7 Hz, 3H; CMe), 1.03 (d, J=6.7 Hz,
3H; CMe), 1.19–1.40 (m, 3H; 3ꢂCH), 1.47–1.48 (m, 1H; CH), 1.65–1.68
(m, 1H; CH), 1.88–1.91 (m, 1H; CH), 2.17–2.22 (m, 1H; Me2CH), 2.31
(s, 3H; PhCH3), 2.31–2.36 (m, 1H; 16-H), 2.70 (s, 6H; 2ꢂPhCH3), 2.84
(dd, J=13.4, 8.5, Hz, 1H; 9-H), 3.01 (ddd, J=11.6, 6.1, 6.1 Hz, 1H; 1-H),
3.67 (ddd J=13.4, 6.7, 6.7 Hz, 1H; 12-H), 4.35 (dd, J=8.5, 4.9 Hz, 1H;
10-H), 5.11 (d, J=1.8 Hz, 1H; C=CHH), 5.41 (d, J=1.8 Hz, 1H; C=
CHH), 6.95 (s, 2H; Ph), 7.13–7.52 ppm (m, 4H; Ph); 13C NMR
(67.8 MHz, CDCl3): d=18.7, 21.1 (2C), 23.2 (2C), 23.8, 28.5, 30.7, 32.7,
38.9, 40.9, 45.9, 58.7, 64.8, 107.1, 125.6, 126.2, 127.9, 128.7, 131.8 (3C),
132.6, 136.1, 140.3 (2C), 142.4, 146.8 ppm; IR (KBr): n˜ =1306 (SO2N),
1149 cmÀ1 (SO2N); MS (FAB): m/z (%): 450 (100) [M++H]; HRMS
(FAB): calcd for C28H36NO2S [M++H]: 450.2467; found: 450.2470.
(1S,9S,10S,12R,16R)-11-Aza-10-isobutyl-8-methylene-11-(2,4,6-trimethyl-
phenylsulfonyl)tetracyclo[7.6.1.02,7.012,16]hexadeca-2(3),4,6-triene
(34b):
By using a procedure identical to that described for the synthesis of 20a
and 21a, diastereomixture of allenene 12b and 13b (1:1; 80 mg,
a
(1S,2S,9S,10S)-11-Aza-10-isopropyl-8-methylene-4-oxa-2-phenyl-11-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.3.0.03,7]dodeca-3(7),5-diene
(56b) (Table 2, entry 2): By using a procedure similar to that described
for the synthesis of 20a and 21a, allenene 10a (158 mg, 0.386 mmol) was
converted into 56b (56.3 mg, 31%) by use of 3-bromofuran. Colorless
oil; [a]2D0 =+24.2 (c=1.04, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.94
(d, J=7.5 Hz, 6H; 2ꢂCMe), 1.96–2.05 (m, 1H; Me2CH), 2.27 (s, 3H;
PhCH3), 2.41–2.53 (m, 1H; 1-H), 2.51 (s, 6H; 2ꢂPhCH3), 2.51–2.74 (m,
1H; 9-H), 2.82 (dd, J=12.5, 11.8 Hz, 1H; 12-CHH), 3.44 (dd, J=11.8,
5.6 Hz, 1H; 12-CHH), 3.86 (d, J=10.6 Hz, 1H; 2-H), 4.37 (dd, J=8.1,
4.4 Hz, 1H; 10-H), 4.92 (s, 1H; C=CHH), 5.21 (s, 1H; C=CHH), 6.49 (d,
J=1.9 Hz, 1H; Ar), 6.87 (s, 2H; Ar), 7.04 (d, J=8.1 Hz, 2H; Ar), 7.22–
7.30 ppm (m, 4H; Ar); 13C NMR (75.5 MHz, CDCl3): d=18.2, 18.9, 20.9,
22.9 (2C), 33.0, 46.5, 49.4, 51.7, 52.4, 63.6, 105.1, 106.9, 122.8, 127.4, 127.7
(2C), 128.7 (2C), 131.9 (2C), 132.9, 138.5, 139.4, 140.2 (2C), 142.4, 142.9,
152.9 ppm; IR (KBr): n˜ =1313 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB):
m/z (%): 476 (96) [M++H], 432 (100); HRMS (FAB): calcd for
C29H34NO3S [M++H]: 476.2259; found: 476.2253.
0.206 mmol) was converted into 34b (24.3 mg, 51% based on 12b). Col-
orless oil; [a]2D4 =À6.02 (c=1.40, CHCl3); 1H NMR (500 MHz, CDCl3):
d=0.83 (d, J=6.7 Hz, 3H; CMe), 0.88 (d, J=6.7 Hz, 3H; CMe), 1.20–
1.38 (m, 3H; 3ꢂCH), 1.46–1.69 (m, 4H; 4ꢂCH), 1.81–1.90 (m, 2H; 2ꢂ
CH), 2.32 (s, 3H; PhCH3), 2.35–2.40 (m, 1H; 16-H), 2.71 (s, 6H; 2ꢂ
PhCH3), 2.74–2.78 (m, 1H; 9-H), 3.04 (ddd, J=11.6, 6.1, 5.5 Hz, 1H; 1-
H), 3.76–3.80 (m, 1H; 12-H), 4.24 (ddd, J=11.0, 11.0, 4.8 Hz, 1H; 10-H),
5.02 (d, J=1.8 Hz, 1H; C=CHH), 5.44 (d, J=1.8 Hz, 1H; C=CHH), 6.96
(s, 2H; Ph), 7.14 (d, J=7.3 Hz, 1H; Ph), 7.18 (dd, J=7.3, 7.3 Hz, 1H;
Ph), 7.23 (dd, J=7.3, 7.3 Hz, 1H; Ph), 7.56 ppm (d, J=7.3 Hz, 1H; Ph);
13C NMR (75.5 MHz, CDCl3): d=21.0, 22.8, 23.1 (2C), 23.7, 23.8, 24.5,
29.0, 30.3, 38.8, 45.8, 46.9, 48.8, 58.3, 58.6, 105.7, 125.4, 126.4, 128.1, 129.0,
131.9 (3C), 132.5, 135.3, 140.6 (2C), 142.6, 146.3 ppm; IR (KBr): n˜ =1301
(SO2N), 1157 cmÀ1 (SO2N); MS (FAB): m/z (%): 464 (100) [M++H];
HRMS (FAB): calcd for C29H38NO2S [M++H]: 464.2623; found:
464.2612.
(1S,9S,10S,12R,16R)-11-Aza-8-methylene-10-[(1S)-1-methylpropyl]-5-
(2,4,6-trimethylphenylsulfonyl)tetracyclo[7.6.1.02,7.012,16]hexadeca-2(3),4,6-
triene (34c): By using a procedure identical to that described for the syn-
thesis of 20a and 21a, allenene 12c (39.3 mg, 0.101 mmol) was converted
into 34c (28.4 mg, 61%). Colorless oil; [a]2D4 =À17.2 (c=0.72, CHCl3);
1H NMR (500 MHz, CDCl3): d=0.88 (t, J=7.3 Hz, 3H; CMe), 0.97 (d,
J=6.7 Hz, 3H; CMe), 1.02–1.68 (m, 7H; 7ꢂCH), 1.86–1.91 (m, 2H;
CH2), 2.31 (s, 3H; PhCH3), 2.32–2.37 (m, 1H; 16-H), 2.70 (s, 6H; 2ꢂ
PhCH3), 2.82–2.87 (m, 1H; 9-H), 2.99–3.04 (m, 1H; 1-H), 3.70 (ddd, J=
11.6, 5.5, 5.5 Hz, 1H; 12-H), 4.35 (dd, J=8.5, 4.3 Hz, 1H; 10-H), 5.11 (s,
1H; C=CHH), 5.38 (s, 1H; C=CHH), 6.95 (s, 2H; Ph), 7.13–7.26 (m, 3H;
Ph), 7.49 ppm (d, J=7.3 Hz, 1H; Ph); 13C NMR (67.8 MHz, CDCl3): d=
12.6, 14.6, 21.0, 23.1 (2C), 23.7, 27.4, 28.6, 30.8, 38.8, 39.4, 40.8, 46.0, 58.4,
64.4, 107.1, 125.5, 126.1, 127.8, 128.5, 131.7 (3C), 136.2, 140.1, 140.2 (2C),
142.3, 146.9 ppm; IR (KBr): n˜ =1307 (SO2N), 1151 cmÀ1 (SO2N); MS
(FAB): m/z (%): 464 (100) [M++H]; HRMS (FAB): calcd for
C29H38NO2S [M++H]: 464.2623; found: 464.2622.
(10S,11R,14S,15S)-5,13-Diaza-14-isopropyl-5-methyl-16-methylene-10-
phenyl-13-(2,4,6-trimethylphenylsulfonyl)tetracyclo[7.7.0.02,6.011,15]hexa-
deca-1(9),2(6),3,7-tetraene (56c) and its (10S,11S,14S,15S) isomer (57c)
(Table 2, entry 3): By using a procedure similar to that described for the
synthesis of 20a and 21a, allenene 10a (150 mg, 0.366 mmol) was con-
verted into 56c (84.3 mg, 43%) and 57c (12.2 mg, 6%) by use of 4-
bromo-1-methylindole.
Compound 56c: Colorless powder; m.p. 223–2258C; [a]2D0 =+65.3 (c=
1.005, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.87 (d, J=6.9 Hz, 3H;
CMe), 0.95 (d, J=6.9 Hz, 3H; CMe), 2.03–2.08 (m, 1H; Me2CH), 2.27 (s,
3H; PhCH3), 2.37–2.46 (m, 1H; 11-H), 2.54 (s, 6H; 2ꢂPhCH3), 2.73 (dd,
J=11.8, 8.7 Hz, 1H; 15-H), 2.84 (dd, J=11.8, 11.2 Hz, 1H; 12-CHH),
3.57 (dd, J=11.8, 6.2 Hz, 1H; 12-CHH), 3.75 (s, 3H; CMe), 4.00 (d, J=
10.6 Hz, 1H; 10-H), 4.52 (dd, J=8.7, 4.4 Hz, 1H; 14-H), 5.43 (s, 1H; C=
CHH), 5.84 (s, 1H; C=CHH), 6.68 (d, J=8.1 Hz, 1H; Ar), 6.83 (d, J=
3.1 Hz, 1H; Ar), 6.88 (s, 2H; Ar), 7.07–7.11 (m, 4H; Ar), 7.21–7.27 ppm
(m, 3H; Ar); 13C NMR (75.5 MHz, CDCl3): d=16.8, 19.7, 20.9, 22.9 (2C),
32.3, 32.9, 48.8, 51.6, 53.5, 53.6, 63.5, 101.3, 108.6, 109.3, 123.7, 125.2,
126.6, 128.5 (2C), 128.6 (2C), 129.1, 130.0, 130.7, 131.9 (2C), 133.3, 135.8,
140.0 (2C), 142.2, 145.1, 145.4 ppm; IR (KBr): n˜ =1311 (SO2N),
1151 cmÀ1 (SO2N); MS (FAB): m/z (%): 539 (100) [M++H]; HRMS
(FAB): calcd for C34H39N2O2S [M++H]: 539.2732; found: 539.2744.
(1S,8S,9R,12S)-11-Aza-12-isopropyl-2-methylene-8-phenyl-4-thia-11-
(2,4,6-trimethylphenylsulfonyl)tricyclo[7.3.0.03,7]dodeca-3(7),5-diene
(56a) and its (1S,8S,9S,12S) isomer (57a) (Table 2, entry 1): By using a
procedure similar to that described for the synthesis of 20a and 21a, alle-
nene 10a (155 mg, 0.378 mmol) was converted into 56a (88.1 mg, 47%)
and 57a (23.0 mg, 12%) by use of 2-bromothiophene.
Compound 56a: Colorless oil; [a]2D5 =+7.63 (c=1.04, CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.94 (d, J=6.9 Hz, 6H; 2ꢂCMe), 1.99–2.04 (m,
1H; Me2CH), 2.26 (s, 3H; PhCH3), 2.52 (s, 6H; 2ꢂPhCH3), 2.52–2.60 (m,
Compound 57c: Pale-yellow powder; m.p. 194–1968C; [a]2D5 =À15.7 (c=
0.735, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.84 (d, J=6.9 Hz, 3H;
CMe), 0.95 (d, J=6.9 Hz, 3H; CMe), 2.04–2.13 (m, 1H; Me2CH), 2.23 (s,
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3739

H. Ohno, T. Tanaka et al.
3H; PhCH3), 2.44 (s, 6H; 2ꢂPhCH3), 2.86–2.90 (m, 1H; 11-H), 3.12–3.22
(m, 2H; 12-CHH and 15-H), 3.44 (dd, J=10.0, 6.9 Hz, 1H; 12-CHH),
3.79 (s, 3H; NMe), 3.98–4.03 (m, 2H; 10-H and 14-H), 5.34 (s, 1H; C=
CHH), 5.79 (s, 1H; C=CHH), 6.74 (s, 2H; Ar), 6.70–6.90 (m, 2H; Ar),
7.00–7.28 ppm (m, 7H; Ar); 13C NMR (75.5 MHz, CDCl3): d=16.5, 19.8,
20.9, 23.1 (2C), 32.0, 32.9, 45.7, 45.8, 47.1, 53.3, 72.1, 101.3, 109.2, 114.7,
123.6, 125.2, 126.1, 127.2, 127.5, 128.3 (2C), 128.5 (2C), 129.0, 131.6 (2C),
134.0, 136.2, 139.5 (2C), 141.5, 144.5, 144.9 ppm; IR (KBr): n˜ =1317
(SO2N), 1153 cmÀ1 (SO2N); MS (FAB): m/z (%): 539 (100) [M++H];
HRMS (FAB): calcd for C34H39N2O2S [M++H]: 539.2732; found:
539.2744.
7-H), 2.70–2.78 (m, 1H; 3-H), 2.81 (dd, J=11.8, 11.8 Hz, 1H; 6-CHH),
3.48 (dd, J=11.8, 5.6 Hz, 1H; 6-CHH), 4.06 (d, J=11.2 Hz, 1H; 8-H),
4.48 (dd, J=8.1, 4.4 Hz, 1H; 4-H), 5.39 (d, J=1.9 Hz, 1H; C=CHH), 6.39
(d, J=1.9 Hz, 1H; C=CHH), 6.89 (s, 2H; Ar), 7.01 (d, J=8.1 Hz, 2H;
Ar), 7.24–7.30 (m, 3H; Ar), 8.38 (d, J=1.9 Hz, 1H; Ar), 8.40 ppm (d, J=
1.9 Hz, 1H; Ar); 13C NMR (75.5 MHz, CDCl3): d=17.6, 19.3, 20.9, 22.8
(2C), 32.7, 47.7, 50.2, 52.7 (2C), 64.3, 112.4, 127.2, 128.4 (2C), 128.8 (2C),
131.9 (2C), 132.7, 140.2 (2C), 141.7, 142.2, 142.6, 142.8, 143.6, 148.9,
153.6 ppm; IR (KBr): n˜ =1315 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB):
m/z (%): 488 (41) [M++H], 307 (100); HRMS (FAB): calcd for
C29H34N3O2S [M++H]: 488.2372; found: 488.2353.
(10S,11S,14S,15S)-13-Aza-14-isopropyl-16-methylene-10-phenyl-8-thia-13-
(2,4,6-trimethylphenylsulfonyl)tetracyclo[7.7.0.02,7.011,15]hexadeca-
1(9),2(7),3,5-tetraene (56d) (Table 2, entry 4): By using a procedure simi-
lar to that described for the synthesis of 20a and 21a, allenene 10a
(150 mg, 0.366 mmol) was converted into 56d (90.0 mg, 45%) by use of
3-bromobenzothiophene. Colorless powder; m.p. 201–2028C; [a]D25
=
Acknowledgements
+75.8 (c=1.015, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.92 (d, J=
6.9 Hz, 3H; CMe), 0.97 (d, J=7.5 Hz, 3H; CMe), 2.03–2.10 (m, 1H;
Me2CH), 2.28 (s, 3H; PhCH3), 2.56 (s, 6H; 2ꢂPhCH3), 2.62–2.73 (m, 1H;
11-H), 2.80–2.89 (m, 2H; 12-CHH and 15-H), 3.55 (dd, J=11.8, 5.6 Hz,
1H; 12-CHH), 4.05 (d, J=10.6 Hz, 1H; 10-H), 4.52 (dd, J=8.1, 4.4 Hz,
1H; 14-H), 5.38 (s, 1H; C=CHH), 5.77 (s, 1H; C=CHH), 6.90 (s, 2H;
Ar), 7.17–7.22 (m, 2H; Ar), 7.28–7.33 (m, 4H; Ar), 7.38 (m, 1H; Ar),
7.68 (d, J=8.1 Hz, 1H; Ar), 8.10 ppm (d, J=8.1 Hz, 1H; Ar); 13C NMR
(75.5 MHz, CDCl3): d=17.3, 19.4, 20.9, 22.9 (2C), 32.6, 49.3, 49.8, 52.6,
53.2, 62.9, 107.6, 122.7, 122.9, 124.2, 124.5, 127.7, 127.9 (2C), 128.8 (2C),
131.9 (2C), 132.2, 133.0, 136.7, 140.1 (2C), 140.3, 140.9, 142.1, 142.5,
145.0 ppm; IR (KBr): n˜ =1313 (SO2N), 1151 cmÀ1 (SO2N); MS (FAB):
m/z (%): 542 (55) [M++H], 136 (100); HRMS (FAB): calcd
C33H36NO2S2 [M++H]: 542.2187; found: 542.2205.
We thank Dr. S. Aoki, Graduate School of Pharmaceutical Sciences,
Osaka University, for NMR analyses. This work was supported by the
Grant-in-Aid for Encouragement of Young Scientists from the Ministry
of Education, Culture, Sports, Science, and Technology of Japan, and the
Mitsubishi Chemical Corporation Fund.
[1] a) M. Catellani, G. P. Chiusoli, C. Castagnoli, J. Organomet. Chem.
1991, 407, c30–33; b) M. Burwood, B. Davies, I. Dꢃaz, R. Grigg, P.
Molina, V. Sridharan, M. Hughes, Tetrahedron Lett. 1995, 36, 9053–
9056; c) M. A. Campo, R. C. Larock, J. Am. Chem. Soc. 2002, 124,
14326–14327; d) For a review on the organopalladium(iv) chemis-
try, see: A. J. Canty, Acc. Chem. Res. 1992, 25, 83–90.
[2] a) D. E. Ames, D. Bull, Tetrahedron 1982, 38, 383–387; b) J. J. Gon-
zꢄlez, N. Garcꢃa, B. Gꢅmez-Lor, A. M. Echavarren, J. Org. Chem.
1997, 62, 1286–1291; c) S. Pivsa-Art, T. Satoh, Y. Kawamura, M.
Miura, M. Nomura, Bull. Chem. Soc. Jpn. 1998, 71, 467–473; d) C.-
H. Park, V. Ryabova, I. V. Seregin, A. W. Sromek, V. Gevorgyan,
Org. Lett. 2004, 6, 1159–1162.
(2S,3R,6S,7S)-5,10-Diaza-6-isopropyl-8-methylene-2-phenyl-5-(2,4,6-tri-
methylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene
(56e)
(2S,3S)-4-[(Z)-benzylidene]-2-isopropyl-3-[1-(2-pyridyl)vinyl]-1-
and
(2,4,6-trimethylphenylsulfonyl)pyrrolidine (59) (Table 2, entry 5): By
using a procedure similar to that described for the synthesis of 20a and
21a, allenene 10a (100 mg, 0.244 mmol) was converted into 56e (57.8 mg,
49%) and 59 (12.5 mg, 11%) by use of 2-iodopyridine.
[3] a) R. Grigg, V. Savic, V. Tambyrajah, Tetrahedron Lett. 2000, 41,
3003–3006; b) C. C. Hughes, D. Trauner, Angew. Chem. 2002, 114,
1639–1642; Angew. Chem. Int. Ed. 2002, 41, 1569–1572; c) E. J.
Hennessy, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125, 12084–
12085; d) B. Sezen, D. Sames, J. Am. Chem. Soc. 2003, 125, 10580–
10585; e) B. S. Lane, D. Sames, Org. Lett. 2004, 6, 2897–2900.
[4] a) D. E. Ames, A. Opalko, Tetrahedron 1984, 40, 1919–1925; b) J. E.
Rice, Z.-W. Cai, J. Org. Chem. 1993, 58, 1415–1424; c) S. Pogodin,
P. U. Biedermann, I. Agranat, J. Org. Chem. 1997, 62, 2285–2287;
d) T. Iwaki, A. Yasuhara, T. Sakamoto, J. Chem. Soc. Perkin Trans. 1
1999, 1505–1510; e) T. Harayama, H. Yasuda, T. Akiyama, Y. Take-
uchi, H. Abe, Chem. Pharm. Bull. 2000, 48, 861–864; f) T. Haraya-
ma, H. Akamatsu, K. Okamura, T. Miyagoe, T. Akiyama, H. Abe,
Y. Takeuchi, J. Chem. Soc. Perkin Trans. 1 2001, 523–528; g) M. A.
Campo, Q. Huang, T. Yao, Q. Tian, R. C. Larock, J. Am. Chem. Soc.
2003, 125, 11506–11507; h) L.-C. Campeau, M. Parisien, M. Leb-
lanc, K. Fagnou, J. Am. Chem. Soc. 2004, 126, 9186–9187.
Compound 56e: Colorless oil; [a]2D6 =+41.7 (c=1.04, CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.91 (d, J=6.9 Hz, 3H; CMe), 0.94 (d, J=7.5 Hz,
3H; CMe), 2.00–2.07 (m, 1H; Me2CH), 2.27 (s, 3H; PhCH3), 2.40–2.54
(m, 1H; 3-H), 2.54 (s, 6H; 2ꢂPhCH3), 2.60 (m, 1H; 7-H), 2.77 (dd, J=
11.8, 11.8 Hz, 1H; 4-CHH), 3.46 (dd, J=11.8, 5.6 Hz, 1H; 4-CHH), 3.88
(d, J=11.2 Hz, 1H; 2-H), 4.46 (dd, J=8.1, 4.5 Hz, 1H; 6-H), 5.29 (s, 1H;
C=CHH), 6.34 (s, 1H; C=CHH), 6.89 (s, 2H; Ar), 7.01–7.10 (m, 4H;
Ar), 7.12–7.31 (m, 3H; Ar), 8.46 ppm (d, J=3.7 Hz, 1H; Ar); 13C NMR
(75.5 MHz, CDCl3): d=17.5, 19.3, 20.9, 22.9 (2C), 32.6, 48.2, 50.1, 50.6,
52.8, 64.6, 110.6, 122.7, 127.3, 128.4 (2C), 128.9 (2C), 131.9 (2C), 132.9,
134.6, 137.7, 140.1 (2C), 142.4, 142.5, 144.5, 147.7, 153.1 ppm; IR (KBr):
n˜ =1315 (SO2N), 1153 cmÀ1 (SO2N); MS (FAB): m/z (%): 487 (100) [M+
+H]; HRMS (FAB): calcd for C30H35N2O2S [M++H]: 487.2419; found:
487.2407.
Compound 59: Colorless oil; 1H NMR (300 MHz, CDCl3): d=0.67 (d,
J=7.5 Hz, 3H; CMe), 0.79 (d, J=6.9 Hz, 3H; CMe), 1.71–1.85 (m, 1H;
Me2CH), 2.29 (s, 3H; CMe), 2.54 (s, 6H; 2ꢂCMe), 3.59 (d, J=4.5 Hz,
1H; 2-H), 4.30 (d, J=15.0 Hz, 1H; 5-CHH), 4.43 (s, 1H; 3-H), 4.64 (d,
J=15.0 Hz, 1H; 5-CHH), 5.28 (s, 1H; C=CHH), 5.56 (s, 1H; C=CHH),
6.52 (s, 1H; C=CHPh), 6.90 (s, 2H; Ar), 6.93 (m, 1H; Ar), 7.17–7.27 (m,
3H; Ar), 7.37 (m, 2H; Ar), 7.49 (d, J=8.1 Hz, 1H; Ar), 7.65 (t, J=
6.5 Hz, 1H; Ar), 8.57 ppm (d, J=3.0 Hz, 1H; Ar).
[5] a) R. C. Larock, Q. Tian, J. Org. Chem. 1998, 63, 2002–2009; b) Q.
Tian, R. C. Larock, Org. Lett. 2000, 2, 3329–3332.
[6] a) M. Catellani, G. P. Chiusoli, J. Organomet. Chem. 1985, 286, c13–
16; b) G. Dyker, Angew. Chem. 1992, 104, 1079; Angew. Chem. Int.
Ed. Engl. 1992, 31, 1023–1025; c) M. Catellani, F. Frignani, A. Ran-
goni, Angew. Chem. 1997, 109, 142–145; Angew. Chem. Int. Ed.
Engl. 1997, 36, 119–122.
(3S,4S,7S,8S)-5,10,13-Triaza-4-isopropyl-2-methylene-8-phenyl-5-(2,4,6-
trimethylphenylsulfonyl)tricyclo[7.4.0.03,7]trideca-1(9),10,12-triene (56 f)
(Table 2, entry 6): By using a procedure similar to that described for the
synthesis of 20a and 21a, allenene 10a (150 mg, 0.366 mmol) was con-
verted into 56 f (110 mg, 62%) by use of iodopyrazine. Colorless oil;
[7] a) O. Reiser, M. Weber, A. de Meijere, Angew. Chem. 1989, 101,
1079; Angew. Chem. Int. Ed. Engl. 1989, 28, 1037–1038; b) P. Mau-
leꢅn, A. A. NfflÇez, I. Alonso, J. C. Carretero, Chem. Eur. J. 2003, 9,
1511–1520.
[8] a) R. Grigg, P. Fretwell, C. Meerholtz, V. Sridharan, Tetrahedron
1994, 50, 359–370; b) D. Brown, R. Grigg, V. Sridharan, V. Tambyr-
ajah, Tetrahedron Lett. 1995, 36, 8137–8140; c) R. Grigg, V. Logana-
than, V. Sridharan, Tetrahedron Lett. 1996, 37, 3399–3402.
1
[a]2D4 =+85.3 (c=1.035, CHCl3); H NMR (300 MHz, CDCl3): d=0.94 (d,
J=6.9 Hz, 3H; CMe), 0.95 (d, J=6.9 Hz, 3H; CMe), 2.03–2.10 (m, 1H;
Me2CH), 2.28 (s, 3H; PhCH3), 2.54 (s, 6H; 2ꢂPhCH3), 2.50–2.58 (m, 1H;
3740
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3728 – 3741

Cyclization of Allenenes
FULL PAPER
[9] F. Teply, I. G. Starꢄ, I. Stary, A. Kollꢄrovic, D. Saman, P. Fiedler, Tet-
rahedron 2002, 58, 9007–9018.
[19] a) H. Ohno, A. Toda, S. Oishi, T. Tanaka, Y. Takemoto, N. Fujii, T.
Ibuka, Tetrahedron Lett. 2000, 41, 5131–5134; b) H. Ohno, K. Miya-
mura, T. Tanaka, S. Oishi, A. Toda, Y. Takemoto, N. Fujii, T. Ibuka,
J. Org. Chem. 2002, 67, 1359–1367.
[20] F. A. Davis, R. T. Reddy, J. Org. Chem. 1992, 57, 2599–2606.
[21] As separation of 12b and 13b was extremely difficult, an almost 1:1
diastereomixture of 12b and 13b was used directly for the palladi-
um-catalyzed cyclization without further purification. Other diastereo-
mixtures (12a/13a and 12c/13c) were readily separated by flash
column chromatography.
[10] For recent reviews, see: a) R. Zimmer, C. U. Dinesh, E. Nandanan,
F. A. Khan, Chem. Rev. 2000, 100, 3067–3125; b) A. S. K. Hashmi,
Angew. Chem. 2000, 112, 3737–3740; Angew. Chem. Int. Ed. 2000,
39, 3590–3593; c) G. Balme, D. Bouyssi, T. Lomberget, N. Monteiro,
Synthesis 2003, 2115; d) T. Mandai in Modern Allene Chemistry,
Vol. 2 (Eds.: A. S. K. Hashmi, N. Krause), Wiley-VCH, Weinheim,
2004, pp. 925–972.
[11] For pioneering works, see: a) R. C. Larock, N. G. Berrios-PeÇa,
C. A. Fried, J. Org. Chem. 1991, 56, 2615–2617; b) I. W. Davies,
D. I. C. Scopes, T. Gallagher, Synlett 1993, 85; c) For a recent review,
see: R. W. Bates, V. Satcharoen, Chem. Soc. Rev. 2002, 31, 12–21.
[12] For some recent examples: a) H. Ohno, A. Toda, Y. Miwa, T. Taga,
E. Osawa, Y. Yamaoka, N. Fujii, T. Ibuka, J. Org. Chem. 1999, 64,
2992–2993; b) S. Ma, S. Zhao, J. Am. Chem. Soc. 1999, 121, 7943–
7944; c) S. K. Kang, K.-J. Kim, Org. Lett. 2001, 3, 511–514; d) H.
Ohno, M. Anzai, A. Toda, S. Ohishi, N. Fujii, T. Tanaka, Y. Takemo-
to, T. Ibuka, J. Org. Chem. 2001, 66, 4904–4914; e) H. Ohno, Yaku-
gaku Zasshi 2001, 121, 733–741; f) K. Hiroi, Y. Hiratsuka, K. Wata-
nabe, I. Abe, F. Kato, M. Hiroi, Tetrahedron: Asymmetry 2002, 13,
1351–1353; g) H. Ohno, H. Hamaguchi, M. Ohata, T. Tanaka,
Angew. Chem. 2003, 115, 1791–1795; Angew. Chem. Int. Ed. 2003,
42, 1749–1753; h) H. Ohno, H. Hamaguchi, M. Ohata, S. Kosaka, T.
Tanaka, J. Am. Chem. Soc. 2004, 126, 8744–8754.
[22] R. F. Heck, Acc. Chem. Res. 1979, 12, 146–151.
[23] Although the syn-b elimination generally predominates, a base-in-
duced anti elimination by an E2 mechanism can occur in limited
cases. See, for examples: a) J. M. Takacs, E. C. Lawson, F. Clement,
J. Am. Chem. Soc. 1997, 119, 5956–5957; b) I. Schwarz, M. Braun,
Chem. Eur. J. 1999, 5, 2300–2305, and references therein.
[24] The reaction with iodobenzene bearing an electron-withdrawing
substitutent has not been examined, because, in our previous study
of pyrrolidine formation, the reaction with 1-iodo-4-nitrobenzene af-
forded a lower yield of the corresponding pyrrolidine (36%).[16b]
[25] For example, in the reaction of allenene 10a with 2-iodoanisole
(Table 1, entry 5), 14% of the b-elimination product 58 was isolated.
In other cases, the yields of this type of elimination product were
lower (<5%) and isolation of these compounds was difficult.
[13] a) S.-K. Kang, T.-G. Baik, A. N. Kulak, Y.-H. Ha, Y. Lim, J. Park, J.
Am. Chem. Soc. 2000, 122, 11529–11530; b) S. Shin, T. V. RajanBa-
bu, J. Am. Chem. Soc. 2001, 123, 8416–8417.
[14] a) J. Lçfstedt, J. FranzØn, J.-E. Bꢀckvall, J. Org. Chem. 2001, 66,
8015–8025; b) J. FranzØn, J. Lçfstedt, I. Dorange, J.-E. Bꢀckvall, J.
Am. Chem. Soc. 2002, 124, 11246–11247; c) I. Dorange, J. Lçfstedt,
K. Nꢀrhi, J. FranzØn, J.-E. Bꢀckvall, Chem. Eur. J. 2003, 9, 3445–
3449; d) J. FranzØn, J.-E. Bꢀckvall, J. Am. Chem. Soc. 2003, 125,
6056–6057; e) J. FranzØn, J. Lçfstedt, J. Falk, J.-E. Bꢀckvall, J. Am.
Chem. Soc. 2003, 125, 14140–14148.
[15] For related palladium-catalyzed cyclization reactions of allenynes,
see: a) C. H. Oh, S. H. Jung, C. Y. Rhim, Tetrahedron Lett. 2001, 42,
8669–8671; b) C. H. Oh, S. H. Jung, D. I. Park, J. H. Choi, Tetrahe-
dron Lett. 2004, 45, 2499–2502.
[26] For related stereomutations of the palladium(ii) intermediate in the
carbopalladation onto an aryl ring, see: a) R. Grigg, V. Sridharan, P.
Stevenson, S. Sukirthalingam, T. Worakun, Tetrahedron 1990, 46,
4003–4018; b) M. S. McClure, B. Glover, E. McSorley, A. Millar,
M. H. Osterhout, F. Roschangar, Org. Lett. 2001, 3, 1677–1680.
[27] For a related isomerization of a trans-organopalladium complex to
the cis isomer through the h3–h1–h3 mechanism, see: a) T. Nishi-
mura, K. Ohe, S. Uemura, J. Am. Chem. Soc. 1999, 121, 2645–2646;
b) T. Nishimura, K. Ohe, S. Uemura, J. Org. Chem. 2001, 66, 1455–
1465.
[28] a) M. Toyota, A. Ilangovan, R. Okamoto, T. Masaki, M. Arakawa,
M. Ihara, Org. Lett. 2002, 4, 4293–4296; b) B. Glover, K. A. Harvey,
B. Liu, M. J. Sharp, M. F. Tymoschenko, Org. Lett. 2003, 5, 301–304;
c) B. Sezen, D. Sames, J. Am. Chem. Soc. 2003, 125, 5274–5275; see
also ref. [3c].
[16] a) H. Ohno, Y. Takeoka, K. Miyamura, Y. Kadoh, T. Tanaka, Org.
Lett. 2003, 5, 4763–4766; b) H. Ohno, Y. Takeoka, Y. Kadoh, K.
Miyamura, T. Tanaka, J. Org. Chem. 2004, 69, 4541–4544.
[17] a) A palladium(ii)-catalyzed domino cyclization of allenynes in the
presence of LiBr under oxygen at atmospheric pressure was recently
reported: B. Alcaide, P. Almendros, C. Aragoncillo, Chem. Eur. J.
2002, 8, 1719–1729; b) Yamamoto and co-workers reported that pal-
ladium-catalyzed carbonylative tandem cyclization of an allenene
that contains an allyl acetate moiety in the presence of carbon mon-
oxide afforded the tetracyclic product in a 22% yield, although it is
only an isolated example: T. Doi, A. Yanagisawa, S. Nakanishi, K.
Yamamoto, T. Takahashi, J. Org. Chem. 1996, 61, 2602–2603.
[18] For a preliminary communication, see: H. Ohno, K. Miyamura, Y.
Takeoka, T. Tanaka, Angew. Chem. 2003, 115, 2751–2754; Angew.
Chem. Int. Ed. 2003, 42, 2647–2650.
Received: January 15, 2005
Published online: April 7, 2005
Chem. Eur. J. 2005, 11, 3728 – 3741
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3741