Enantioselective intramolecular [2+2+2] cycloaddition of dienynes for the construction of adjacent three chiral centers

Article abstract of DOI:10.1055/s-0029-1219815

A chiral rhodium catalyst realized the first intramolecular [2+2+2] cycloaddition of yne-ene-enes, and chiral multicyclic cyclohexenes with adjacent three chiral centers were afforded with high to excellent ee. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1219815

LETTER
1235
Enantioselective Intramolecular [2+2+2] Cycloaddition of Dienynes for the
Construction of Adjacent Three Chiral Centers
Intramolecular
[
a
2+2+2] Cy
k
cloadditiono
a
f
Dienynesnori Shibata,* Mayumi Otomo, Kohei Endo
Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University,
Okubo, Shinjuku, Tokyo 169-8555, Japan
Fax +81(3)52868098; E-mail: tshibata@waseda.jp
Received 13 February 2010
BINAP, dienyne 1a was completely consumed within 2
Abstract: A chiral rhodium catalyst realized the first intramolecu-
lar [2+2+2] cycloaddition of yne–ene–enes, and chiral multicyclic
cyclohexenes with adjacent three chiral centers were afforded with
high to excellent ee.
hours at room temperature, and the desired tricyclic prod-
uct 2a was obtained in good yield with high ee, however,
the mixture of ene type product 2a¢ and its isomerized
product 2a¢¢ was also obtained in significant yield (entry
1). After screening several BINAP derivatives, H8-
BINAP gave the best results but the b-elimination could
not be completely restrained (entries 2–5).14
Key words: catalysis, chirality, cycloaddition, rhodium, multi-
cyclic
Intramolecular reaction of substrates with multi-reaction
sites is synthetically very important because it realizes the
construction of multicyclic skeleton in one-pot with com-
plete regioselectivity. Actually, transition-metal-
catalyzed intramolecular [2+2+2] cycloaddition of unsat-
urated motifs, such as alkyne and alkene, has been com-
prehensively studied, and various types of reactions were
reported1 including asymmetric variants.2 Especially,
enantioselective cycloaddition of triynes was used for the
construction of helical,3 axial,4 and planar chiralities.5 In
the cycloaddition of enediynes, palladium-catalyzed reac-
tions of yne–yne–enes and yne–ene–ynes were reported,6
and chiral rhodium-catalyzed enantioselective reaction of
yne–ene–ynes was also reported.7 On the contrary, as for
the cycloaddition of dienynes (Scheme 1), ruthenium-
catalyzed8 and chiral rhodium-catalyzed reactions9 of
ene–yne–enes (type A) were reported, however, the cy-
cloaddition of yne–ene–enes (type B) was not reported.
The transformation of yne–ene–enes into tricyclic cyclo-
hexenes was realized by palladium-catalyzed cycloi-
somerization along with thermal Diels–Alder reaction10
and radical cyclization,11 but no asymmetric variant was
reported.12
type A
[2+2+2]
type B
[2+2+2]
Scheme 1 [2+2+2] Cycloadditions of ene–yne–ene and yne–ene–
ene
H
Z
β
Z
Z
Z'
*
*
*
M
*
E
M
Z'
– M
*
Z'
R
R
R
Scheme 2 Generation of adjacent three chiral centers
Under the optimal reaction conditions, we examined sev-
eral dienynes (Table 2). In place of nitrogen tether, carbon
and oxygen tethers could be introduced into the enyne
moiety (entries 1 and 2). Especially, carbon-tethered di-
enyne 1b was a good substrate, and the corresponding tri-
cyclic product 2b was selectively obtained with excellent
ee. As a substituent on the alkyne terminus, phenyl group
was also possible and chiral cyclohexenes 2d and 2e were
obtained in high ee (entries 3 and 4).15 On the contrary,
We examined an intramolecular [2+2+2] cycloaddition of
yne–ene–enes: oxidative coupling of enyne moiety, which
is more active than diene moiety, proceeds with a metal
catalyst, and the following alkene insertion provides a tri-
cyclic cyclohexene with adjacent three chiral centers
(Scheme 2). The most expected side reaction is the b-
hydrogen elimination from the metallacyclopentene inter-
mediate, which gives the ene-type product.13
We chose dienyne 1a with two nitrogen tethers as a model when carbon and oxygen tethers were introduced into the
substrate and submitted to the reaction using rhodium- diene moiety, the corresponding [2+2+2] cycloadducts
chiral diphosphine ligand (Table 1). In the case of could not be obtained (entries 5 and 6).16
We next examined o-phenylene-tethered dienynes under
the same reaction conditions (Scheme 3). In the reaction
SYNLETT 2010, No. 8, pp 1235–1238
x
x.
x
x.
2
0
1
0
of phenyl-substituted substrate 1h, almost perfect enantio-
Advanced online publication: 09.04.2010
DOI: 10.1055/s-0029-1219815; Art ID: U00910ST
© Georg Thieme Verlag Stuttgart · New York

1236
T. Shibata et al.
LETTER
Table 1 Screening of Chiral Ligands for Cycloaddition of Dienyne 1a
TsN
[Rh(cod)2]BF4 + ligand
TsN
NTs
*
*
(10 mol%)
*
DCE
NTs
Me
Me
2a
1a
Ts
N
Ts
N
TsN
TsN
Me
Me
2a"
2a'
Entry
Chiral liganda
BINAP
Temp (°C)
Time (h)
Yield of 2a (%) ee of 2a (%)
Yield of 2a¢ + 2a¢¢ (%)
1
2
3
4
5
r.t.
60
r.t.
80
r.t.
2
4
72
63
74
55
64
80
77
19
37
13
25
24
tolBINAP
H8-BINAP
DM-H8-BINAP
SEGPHOS
0.5
5
87
–68
46
24
a H8-BINAP: bis(diphenylphospino)-5,5¢,6,6¢,7,7¢,8,8¢-octahydro-1,1¢-binaphthyl, DM-H8-BINAP: bis[di-(3,5-xylyl)phosphino]-
5,5¢,6,6¢,7,7¢,8,8¢-octahydro-1,1¢-binaphthyl, SEGPHOS: 5,5¢-bis(diphenylphosphino)-4,4¢-bi-1,3-benzodioxole. S-Isomers were used except
DM-H8-BINAP.
Table 2 Examination of Dienynes with Various Tethers
Z
Z'
[Rh(cod)2]BF4 + (S)-H8-BINAP
(10 mol%)
Z
*
*
*
DCE
Z'
R
R
2b–g
1b–g
Entry
Z
Z¢
R
Temp, time
r.t., 1 h
Yield (%)
79 (2b)
54 (2c)
54 (2d)
55 (2e)
–
ee (%)
95
73
86
92
–
a
1
NTs
NTs
NTs
NTs
CE2
O
Me
Me
Ph
1b
1c
1d
1e
1f
2
40 °C, 24 h
80 °C, 15 min
80 °C, 30 min
80 °C, 24 h
r.t., 2 h
3
NTs
a
4
CE2
NTs
NTs
Ph
a
5
CE2
Me
Me
6
O
1g
–
–
a E = CO2Me
selectivity was achieved, and its absolute configuration
was determined by X-ray diffraction (Figure 1).17
TsN
*
*
[Rh(cod)2]BF4 + (S)-H8-BINAP
(10 mol%)
TsN
We examined ester-tethered dienyne 1i, which never un-
dergoes cycloisomerization by b-elimination, but almost
no reaction proceeded (Figure 2). In the case of dienynes
1j and 1k, which have 1,1- and 1,2-disubstituted alkene
moiety, respectively, cycloisomerization predominantly
proceeded.
*
DCE, 40 °C, 48 h
Ph
2h
65%, 99% ee
Ph
1h
Scheme 3 Reaction of o-phenylene-tethered dienyne 1h
Synlett 2010, No. 8, 1235–1238 © Thieme Stuttgart · New York

LETTER
Intramolecular [2+2+2] Cycloaddition of Dienynes
1237
Under an atmosphere of argon, H8-BINAP (6.3 mg, 0.010 mmol)
and [Rh(cod)2]BF4 (4.1 mg, 0.010 mmol) were stirred in CH2Cl2
(0.75 mL). While stirring the solution at r.t., hydrogen gas was in-
troduced to the flask, and the solution was further stirred for 30 min
at r.t. After removal of the solvent and hydrogen under reduced
pressure, argon gas was introduced. DCE (0.25 mL) was added to
the flask, and the solution was stirred at r.t. to give a mars yellow
solution. Then, a dienyne (0.10 mmol) in DCE (0.75 mL) were add-
ed to the solution, and the mixture was stirred at the appropriate
temperature. After completion of the reaction, the solvent was re-
moved under reduced pressure, and the crude products were puri-
fied by TLC to give a chiral cycloadduct. The ee was determined by
HPLC analysis using a chiral column.
4-Methyl-2,7-bis(p-toluenesulfonyl)-1,3,5,6,8,8a,8b,-hepta-
hydro-2,7-diaza-as-indacene (2a)
White solid (mp 191 °C). IR (KBr): 1337, 1155, 820, 663 cm–1. 1H
NMR (400 MHz, CDCl3): d = 1.49 (s, 3 H), 1.53–1.66 (m, 2 H), 1.81
(d, J = 18.6 Hz, 1 H), 2.04 (dd, J = 6.4, 18.6 Hz, 1 H), 2.24–2.32 (m,
1 H), 2.35 (dd, J = 8.1, 8.8 Hz, 1 H), 2.43 (s, 3 H), 2.48 (s, 3 H), 2.74
(dd, J = 9.1, 10.4 Hz, 1 H), 3.20 (d, J = 10.4 Hz, 1 H), 3.31 (dd,
J = 4.6, 10.4 Hz, 1 H), 3.46 (dd, J = 9.1, 10.4 Hz, 1 H), 3.54 (dd,
J = 8.1, 8.8 Hz, 1 H), 3.55 (d, J = 13.2 Hz, 1 H), 3.83 (d, J = 13.2
Hz, 1 H), 7.30–7.38 (m, 4 H), 7.65–7.72 (m, 4 H). 13C NMR (100
MHz, CDCl3): d = 19.0, 21.5, 21.5, 29.9, 35.8, 37.8, 38.6, 49.7,
51.2, 52.8, 53.5, 123.9, 127.1, 127.3, 127.6, 129.7, 129.8, 132.9,
133.5, 143.6, 144.0. HRMS–FAB (positive): m/z calcd for
Figure 1 ORTEP diagram of cycloadduct 2h
Me
O
O
TsN
Me
Me
TsN
Me
18
C25H31N2O4S2: 487.1725 [M + 1]+; found: 487.1724 [M + 1]+; [a]D
NTs
NTs
NTs
Me
17.4 (c 1.02, CHCl3, 87% ee). The ee was determined by HPLC
analysis using a chiral column [Daicel Chiralpak IA-H: 4 × 250
mm, 254 nm UV detector, r.t., eluent: 50% CH2Cl2 in hexane, flow
rate: 1.0 mL/min; tR (minor isomer) = 10 min; tR (major isomer) =
12 min].
1i
1j
1k
Figure 2 Inappropriate substrates
On the contrary, yne–ene–diene system was available
(Scheme 4). Trienyne 1l possessing active conjugate di-
ene moiety was transformed into tricyclic compound 2l in
98% ee using Rh-BINAP catalyst, which means chiral
5,6,7-tricyclic ring system was constructed in one pot
along with excellent enantioselectivity.
2,2-Bis(methoxycarbonyl)-4-methyl-7-(p-toluenesulfonyl)-
1,3,5,6,8,8a,8b-heptahydro-7-aza-as-indacene (2b)
1
Colorless oil. IR (neat) 1734, 1344, 1161, 665, 594, 550 cm–1. H
NMR (400 MHz, CDCl3): d = 1.23 (s, 3 H), 1.64–1.85 (m, 3 H),
1.85–1.97 (m, 1 H), 2.07 (dd, J = 7.6, 15.4 Hz, 1 H), 2.16–2.29 (m,
1 H), 2.44 (s, 3 H), 2.52 (dd, J = 7.6, 15.4 Hz, 1 H), 2.75–2.90 (m,
2 H), 2.97 (d, J = 17.2 Hz, 1 H), 3.25–3.37 (m, 2 H), 3.44 (dd,
J = 8.8, 9.0 Hz, 1 H), 3.71 (s, 3 H), 3.74 (s, 3 H), 7.32 (d, J = 8.2 Hz,
2 H), 7.71 (d, J = 8.2 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d =
19.1, 21.5, 30.5, 36.3, 37.2, 38.5, 40.3, 41.8, 51.7, 52.8, 52.8, 52.9,
58.0, 123.5, 127.3, 129.7, 131.2, 134.2, 143.3, 172.1, 172.4.
HRMS–FAB (positive): m/z calcd for C23H30NO6S: 448.1794 [M +
1]+; found: 448.1792 [M + 1]+; [a]D27 40.1 (c 1.60, CHCl3, 95% ee).
The ee was determined by HPLC analysis using a chiral column
[Daicel Chiralpak AD-H: 4 × 250 mm, 254 nm UV detector, r.t.,
eluent: 20% 2-PrOH in hexane, flow rate: 1.0 mL/min; tR (minor
isomer) = 12 min; tR (major isomer) = 18 min].
Ts
N
TsN
Me
[Rh(cod)2]BF4 + (S)-BINAP
(10 mol%)
*
*
NTs
DCE, 60 °C, 2 h
*
NTs
Me
1l
2l
65%, 98% ee
4-Methyl-7-(p-toluenesulfonyl)-1,3,5,6,8,8a,8b-heptahydro-7-
aza-2-oxa-as-indacene (2c)
Scheme 4 Reaction of yne–ene–diene 1l
Colorless oil. IR (neat): 1342, 1165, 661, 594, 550 cm–1. 1H NMR
(400 MHz, CDCl3): d = 1.55 (s, 3 H), 1.72–1.81 (m, 1 H), 1.83–1.90
(m, 2 H), 2.08–2.20 (m, 1 H), 2.29–2.40 (m, 1 H), 2.44 (s, 3 H), 2.85
(dd, J = 9.1, 10.4 Hz, 1 H), 3.14 (dd, J = 7.8, 8.8 Hz, 1 H), 3.24 (d,
J = 9.8 Hz, 1 H), 3.37 (dd, J = 5.2, 9.8 Hz, 1 H), 3.50 (dd, J = 9.1,
10.4 Hz, 1 H), 4.04 (dd, J = 7.8, 8.8 Hz, 1 H), 4.27 (d, J = 1.2 Hz, 2
H), 7.33 (d, J = 8.4 Hz, 2 H), 7.72 (d, J = 8.4 Hz, 2 H). 13C NMR
(100 MHz, CDCl3): d = 19.1, 21.5, 30.4, 36.3, 38.4, 39.1, 51.5, 53.2,
69.2, 73.7, 121.6, 127.3, 129.7, 131.2, 134.1, 143.5. HRMS–FAB
(positive): m/z calcd for C18H24NO3S: 334.1477 [M + 1]+; found:
In conclusion, we developed an enantioselective [2+2+2]
cycloaddition of dienynes using a chiral rhodium-catalyst.
The present reaction is the first example of intramolecular
cycloaddition of yne–ene–ene system, and multicyclic cy-
clohexenes with adjacent three chiral centers were ob-
tained with good to excellent enantioselectivity. It is
noteworthy that a chiral 5,6,7-tricyclic ring system could
be constructed in one pot in the reaction of trienyne.
19
334.1490 [M + 1]+; [a]D 7.22 (c 0.420, CHCl3, 73% ee). The ee
was determined by HPLC analysis using a chiral column [Daicel
Chiralpak OD-H: 4 × 250 mm, 254 nm UV detector, r.t., eluent:
20% 2-PrOH in hexane, flow rate: 1.0 mL/min; tR (minor isomer) =
14 min; tR (major isomer) = 21 min].
Synlett 2010, No. 8, 1235–1238 © Thieme Stuttgart · New York

1238
T. Shibata et al.
LETTER
4-Phenyl-2,7-bis(p-toluenesulfonyl)-1,3,5,6,8,8a,8b,-hepta-
hydro-2,7-diaza-as-indacene (2d)
7.64–7.74 (m, 4 H). 13C NMR (125 MHz, CDCl3): d = 21.6, 21.9,
36.3, 39.5, 40.6, 44.6, 49.9, 51.5, 52.5, 53.1, 127.4, 128.0, 128.4,
129.8, 129.9, 130.4, 130.8, 131.9, 134.2, 143.7, 143.9 (a pair of
peaks at the aliphatic region and a pair of peaks at the aromatic re-
gion are overlapped). HRMS–FAB (positive): m/z calcd for
Colorless solid (mp 170 °C). IR (KBr): 1344, 1159, 665, 550 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.82–1.93 (m, 1 H), 1.98–2.16 (m,
2 H), 2.34–2.53 (m, 1 H), 2.43 (s, 3 H), 2.47 (s, 3 H), 2.55–2.70 (m,
2 H), 2.93 (dd, J = 9.0, 9.7 Hz, 1 H), 3.23 (dd, J = 3.4, 10.0 Hz, 1
H), 3.32 (dd, J = 3.4, 10.0 Hz, 1 H), 3.42 (dd, J = 9.0, 9.7 Hz, 1 H),
3.53–3.70 (m, 2 H), 3.98 (d, J = 15.6 Hz, 1 H), 7.00–7.07 (m, 2 H),
7.22–7.34 (m, 5 H), 7.37 (d, J = 8.2 Hz, 2 H), 7.63 (d, J = 8.2 Hz, 2
H), 7.72 (d, J = 8.2 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 21.5,
21.6, 30.4, 36.3, 39.4, 50.6, 51.7, 52.8, 53.0, 126.9, 127.3, 127.4,
127.6, 128.5, 129.6, 129.7, 129.8, 131.2, 133.4, 140.0, 143.7, 144.0
(a pair of peaks at the aromatic region is overlapped). HRMS–FAB
(positive): m/z calcd for C30H33N2O4S2: 549.1881 [M + 1]+; found:
17
C27H33N2O4S2: 513.1881 [M + 1]+; found: 513.1885 [M + 1]+; [a]D
–15.9 (c 1.00, CHCl3, 98% ee). The ee was determined by HPLC
analysis using a chiral column [Daicel Chiralpak Doubly-arrayed
IC-H: 4 × 250 mm, 254nm UV detector, r.t., eluent: 80% CH2Cl2 in
hexane, flow rate: 0.5 mL/min; tR (minor isomer) = 48 min; tR (ma-
jor isomer) = 58 min].
Acknowledgment
549.1881 [M + 1]+; [a]D 5.95 (c 0.740, CHCl3, 86% ee). The ee
18
This research was supported by a Grant-in-Aid for Scientific Rese-
arch from the Ministry of Education, Culture, Sports, Science, and
Technology, Japan. We also thank Takasago International Corp. for
the gift of H8-BINAP, DM-H8-BINAP, and SEGPHOS.
was determined by HPLC analysis using a chiral column [Daicel
Chiralpak IA-H: 4 × 250 mm, 254 nm UV detector, r.t., eluent: 50%
CH2Cl2 in hexane, flow rate: 1.0 mL/min; tR (minor isomer) = 7.7
min; tR (major isomer) = 8.2 min].
2,2-Bis(methoxycarbonyl)-4-phenyl-7-(p-toluenesulfonyl)-
1,3,5,6,8,8a,8b-heptahydro-7-aza-as-indacene (2e)
Reference and Notes
Colorless oil. IR (neat): 1734, 1344, 1163, 665, 590, 550 cm–1. 1H
NMR (400 MHz, CDCl3): d = 1.87 (dd, J = 10.4, 12.8 Hz, 1 H),
1.92–2.02 (m, 1 H), 2.05–2.25 (m, 2 H), 2.30–2.42 (m, 1 H), 2.45
(s, 3 H), 2.53–2.62 (m, 2 H), 2.88 (d, J = 17.4 Hz, 1 H), 2.97 (dd,
J = 8.6, 9.4 Hz, 1 H), 3.10 (d, J = 17.4 Hz, 1 H), 3.24 (dd, J = 4.5,
9.6 Hz, 1 H), 3.36 (dd, J = 4.5, 9.6 Hz, 1 H), 3.42 (dd, J = 8.6, 9.4
Hz, 1 H), 3.66 (s, 3 H), 3.72 (s, 3 H), 7.14–7.24 (m, 3 H), 7.27–7.38
(m, 4 H), 7.70–7.76 (m, 2 H). 13C NMR (100 MHz, CDCl3): d =
21.5, 31.5, 37.1, 38.4, 39.7, 40.5, 42.3, 52.4, 52.8, 52.9, 53.1, 58.7,
126.7, 127.4, 127.6, 128.2, 129.4, 129.7, 133.4, 135.9, 141.4, 143.5,
171.9, 172.0. HRMS–FAB (positive): m/z calcd for C28H32NO6S:
510.1950 [M + 1]+; found: 510.1924 [M + 1]+; [a]D28 41.1 (c 1.21,
CHCl3, 92% ee). The ee was determined by HPLC analysis using a
chiral column [Daicel Chiralpak IB-H: 4 × 250 mm, 254 nm UV
detector, r.t., eluent: 20% 2-PrOH in hexane, flow rate: 1.0 mL/min;
tR (minor isomer) = 15 min; tR (major isomer) = 16 min].
(1) Reviews: (a) Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503.
(b) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org.
Chem. 2005, 4741. (c) Chopade, P. R.; Louie, J. Adv. Synth.
Catal. 2006, 348, 2307.
(2) (a) Shibata, T.; Tsuchikama, K. Org. Biomol. Chem. 2008,
1317. (b) Tanaka, K. Chem. Asian J. 2009, 4, 508.
(3) Stará, I. G.; Starý, I.; Kollárovič, A.; Teplý, F.; Vyskočil, Š.;
Šaman, D. Tetrahedron Lett. 1999, 40, 1993.
(4) Shibata, T.; Tsuchikama, K.; Otsuka, M. Tetrahedron:
Asymmetry 2006, 17, 614.
(5) Tanaka, K.; Sagae, H.; Toyoda, K.; Noguchi, K.; Hirano, M.
J. Am. Chem. Soc. 2007, 129, 1522.
(6) Yamamoto, Y.; Kuwabara, S.; Ando, Y.; Nagata, H.;
Nishiyama, H.; Itoh, K. J. Org. Chem. 2004, 69, 6697.
(7) (a) Shibata, T.; Kurokawa, H.; Kanda, K. J. Org. Chem.
2007, 72, 6521. (b) Tanaka, K.; Nishida, G.; Sagae, H.;
Hirano, M. Synlett 2007, 1426.
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7730.
(9) Sagae, H.; Noguchi, K.; Hirano, M.; Tanaka, K. Chem.
Commun. 2008, 3804.
(10) (a) Trost, B. M. Acc. Chem. Res. 1990, 23, 34. (b) Trost,
B. M.; Tanoury, G. J.; Lautens, M.; Chan, C.; MacPherson,
D. T. J. Am. Chem. Soc. 1994, 116, 4255.
(11) Spino, C.; Barriault, N. J. Org. Chem. 1999, 64, 5292.
(12) Cycloisomerization of yne–ene–enes for the construction of
polycyclic system, see: Chatani, N.; Kataoka, K.; Murai, S.
J. Am. Chem. Soc. 1998, 120, 9104.
(13) Enantioselective ene-type reaction of 1,6-enynes with Z-
olefinic moiety using chiral Rh catalysts, see: (a) Cao, P.;
Zhang, X. Angew. Chem. Int. Ed. 2000, 39, 4104. (b) Lei,
A.; He, M.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 8198.
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Chem. Int. Ed. 2002, 41, 4526.
(14) The counter anion of the Rh catalyst did not affect the yield
of 2a and its ee (BF4: 74%, 87% ee, OTf: 69%, 86% ee).
(15) The ene-type products and their isomerized products were
also formed in each entry.
(16) The reaction of carbon-tethered dienyne 1f did not
proceeded even at 80 °C. Oxygen-tethered dienyne 1g was
promptly consumed at r.t. but ene-type products were
formed and no cycloadduct could be detected.
(17) Based on Scheme 2, the absolute configuration of the
tricyclic product would be determined at the formation of the
bicyclic metallacyclopentene, which is the same interme-
diate as that of [2+2+2] cycloaddition of enediynes, see ref. 7a.
5-Phenyl-2-(p-toluenesulfonyl)-1,3,3a,4,10,10a,10b-heptahydro-
2-aza-cyclopenta[a]fluorene (2h)
Colorless crystals (mp 143 °C). IR (KBr): 1340, 1165, 667, 594,
1
546 cm–1. H NMR (400 MHz, CDCl3): d = 2.10–2.25 (m, 1 H),
2.30–2.58 (m, 8 H), 2.63 (dd, J = 7.6, 16.0 Hz, 1 H), 3.01–3.12 (m,
2 H), 3.30–3.55 (m, 2 H), 6.53 (d, J = 8.0 Hz, 1 H), 6.83 (dd, J = 7.2,
7.2 Hz, 1 H), 7.06 (dd, J = 7.2, 7.2 Hz, 1 H), 7.13–7.25 (m, 3 H),
7.27–7.45 (m, 5 H), 7.75 (d, J = 8.4 Hz, 2 H). 13C NMR (100 MHz,
CDCl3): d = 21.5, 34.3, 36.5, 36.9, 41.5, 42.8, 52.6, 53.0, 123.5,
124.8, 126.1, 127.1, 127.4, 127.5, 128.0, 128.2, 128.7, 129.6, 130.1,
137.8, 142.1, 143.5 (two pairs of peaks at the aromatic region are
overlapped). HRMS–FAB (positive): m/z calcd for C28H28NO2S:
442.1840 [M + 1]+; found: 442.1848 [M + 1]+; [a]D29 34.2 (c 0.655,
CHCl3, 99% ee). The ee was determined by HPLC analysis using a
chiral column [Daicel Chiralpak OD-H: 4 × 250 mm, 254 nm UV
detector, r.t., eluent: 20% 2-PrOH in hexane, flow rate: 1.0 mL/min;
tR (minor isomer) = 15 min; tR (major isomer) = 17 min]. Crystal
data for C28H27NO2S, M = 441.59, orthorhombic, space group
P212121 (no. 19), a = 7.8895(8) Å, b = 15.3909(16) Å,
c = 19.578(2) Å, V = 2377.3(4) Å3, T = 193 K, Z = 4, m(Cu-
Ka) = 13.943 cm–1; number of reflections measured: total 27727
and unique 4362 (Rint = 0.085), R1 = 0.0411, wR2 = 0.0946, Flack
parameter (Friedel pairs = 1863) 0.03(2). CCDC 762243.
4-Methyl-2,9-bis(p-toluenesulfonyl)-1,3,5,5a,8,10,10a,10b-octa-
hydro-2,9-diaza-cyclohepta[g]indene (2l)
Colorless oil. IR (neat): 1344, 1163, 665, 548 cm–1. 1H NMR (500
MHz, CDCl3): d = 1.49 (s, 3 H), 2.09–2.19 (m, 1 H), 2.43 (s, 3 H),
2.46 (s, 3 H), 2.65–2.87 (m, 4 H), 2.90–2.97 (m, 1 H), 2.98–3.04 (m,
1 H), 3.15–3.24 (m, 2 H), 3.31–3.42 (m, 3 H), 3.91 (d, J = 13.6 Hz,
1 H), 5.01–5.12 (m, 1 H), 5.62–5.72 (m, 1 H), 7.29–7.38 (m, 4 H),
Synlett 2010, No. 8, 1235–1238 © Thieme Stuttgart · New York

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