Iridium complex-catalyzed enantioselective intramolecular [4+2] cycloaddition of dieneynes

Article abstract of DOI:10.1055/s-2002-34217

A catalytic and highly enantioselective intramolecular [4+2] cycloaddition of dieneynes was achieved by use of chiral iridium complex prepared in situ from [IrCl(cod)]₂ and BDPP [2,4-bis(diphenylphosphino)pentane]. The reaction proceeded in refluxed tert-butyl acetate to give chiral cyclohexa-1,4-dienes in very high enantiomeric excess.

Full text of DOI:10.1055/s-2002-34217

LETTER
1681
Iridium Complex-Catalyzed Enantioselective Intramolecular
[
4+2] Cycloaddition of Dieneynes
I
T
ridium Comple
a
x-Catalyze
k
d
Enantiosel
a
ective Cycl
n
oaddition ori Shibata,* Koji Takasaku, Yuri Takesue, Naohito Hirata, Kentaro Takagi
Department of Chemistry, Faculty of Science, Okayama University, Tsushima, Okayama 700-8530, Japan
E-mail: tshibata@cc.okayama-u.ac.jp
Received 2 August 2002
intramolecular [4+2] cycloadditions have used dienes
having a methyl substituent on their terminal, which are
Abstract: A catalytic and highly enantioselective intramolecular
4+2] cycloaddition of dieneynes was achieved by use of chiral iri-
dium complex prepared in situ from [IrCl(cod)] and BDPP [2,4-
[
derived from sorbic alcohol (hexa-2,4-dien-1-ol) except
2
bis(diphenylphosphino)pentane]. The reaction proceeded in re- limited examples.4
a,c,6b
Moreover, no enantioselective in-
fluxed tert-butyl acetate to give chiral cyclohexa-1,4-dienes in very tramolecular [4+2] cycloadditions have been reported us-
high enantiomeric excess.
ing unsubstituted dienes derived from penta-2,4-dien-1-ol
Key words: catalysis, chiral auxiliaries, cycloadditions, Diels– as far as we know.
Alder reactions, Iridium
In the presence of 10 mol% catalyst, the [4+2] cycloaddi-
tion of dieneyne 1a was examined at 90 °C (Table 1).
Both iridium complexes provided cyclohexa-1,4-diene 2a
Enantioselective [4+2] cycloaddition is the most reliable
and a common protocol for the construction of chiral 6-
membered ring systems. In particular, chiral Lewis acid
promoted [4+2] cycloaddition (Diels–Alder reaction) is
in ca. 70% yield (entries 1 and 2). Other penta-2,4-dienyl
propargyl ether 1b,c were also transformed into the corre-
sponding bicyclic products 2b,c (entries 3–6). Along with
the formation of 2a–c, aromatized products 3a–c were
also generated in each reaction (5–15%). Penta-2,4-die-
nylpropargylamine 1d was found to be a good substrate
and 2d was obtained in high yield without the formation
of 3d even for prolonged reaction time (entries 7 and 8).
1
comprehensively examined and development of highly
2
efficient catalysts is still an intriguing topic. The coordi-
nation of heteroatoms of activated dienophiles (alkenes)
to chiral Lewis acids realized enantioselective Diels–
Alder reactions. Therefore functional groups like carbon-
yl moiety adjacent to alkene play a pivotal role for asym- Table 1. Ir Complex-Catalyzed [4+2] Cycloadditiona
metric induction. On the other hand, the transition metal
IrCl(CO)(PPh
or IrCl(cod)(dppp) (cat. B)
3
)
2
(cat. A)
R
R
complex-catalyzed cycloaddition of unactivated sub-
strates possessing no heteroatoms proceeds smoothly be-
cause direct coordination of reaction sites like alkynes,
alkenes, and dienes to the transition metal promotes the
formation of metallacycle, an intermediate of cycloaddi-
R
(10 mol%)
Z
Z
+
Z
toluene, 90 °C
1
2
3
En- R
try
Z
1
Catalyst Time Yield
Yield
of 3/%
3
tion. Actually, intramolecular [4+2] cycloadditions of di-
/h
of 2/%
4
eneynes or trienes catalyzed by transition metal (e.g. Ni,
5
6
1
2
3
4
5
6
7
C H
O
O
O
O
O
O
1a
1a
1b
1b
1c
1c
A
B
A
B
A
B
A
B
19
11
30
15
23
10
96
53
71 (2a)
68 (2a)
4 (3a)
8 (3a)
Pd, and Rh ) complexes have been reported. Enantiose-
lective [4+2] cycloadditions were also realized by chiral
cationic rhodium complexes, which were prepared in situ
6
5
5
C H
6
7
from Rh(I), chiral phosphine, and Ag(I) salt.
4-MeOC
6
H
4
4
71 (2b) 15 (3b)
We recently found that iridium-phosphine complexes are
efficient catalysts for [2+2+1] cycloadditions (carbonyla-
4-MeOC H
68 (2b)
71 (2c)
65 (2c)
70 (2d)
80 (2d)
7 (3b)
6
8
4-ClC
6
H
4
4
15 (3c)
tive alkyne-alkyne and enantioselective carbonylative
9
10
alkyne-alkene couplings ). We report here that an iridi-
um-chiral phosphine complex catalyzes an enantioselec-
tive intramolecular [4+2] cycloaddition of dieneynes to
give chiral bicyclic products in high enantiomeric excess.
4-ClC H
7 (3c)
6
C H
NTs 1d
NTs 1d
-
-
6
5
5
8
C H
6
At first, we examined non-asymmetric cycloaddition us-
ing Vaska’s complex and IrCl(cod)(dppp) which was used
in [2+2+1] cycloadditions. We chose dieneynes 1 pos-
a
dppp: 1,3-Bis(diphenylphosphino)propane.
8
sessing an unsubstituted diene because most of reported We further studied an enantioselective reaction using
chiral iridium complexes (Table 2). Dieneyne 1a was sub-
mitted to [4+2] cycloaddition in the presence of a chiral
Synlett 2002, No. 10, Print: 01 10 2002.
catalyst which was prepared in situ from [IrCl(cod)] and
2
Art Id.1437-2096,E;2002,0,10,1681,1682,ftx,en;U05102ST.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
9
tolBINAP. 2a was obtained in moderate ee (entry 1).
©

1
682
T. Shibata et al.
LETTER
Next, we examined Me-DUPHOS and DIOP, which are In summary, we developed the first example of iridium
efficient chiral ligands for cationic Rh complex-catalyzed complex-catalyzed [4+2] cycloaddition. Highly enantio-
7
b,c
enantioselective [4+2] cycloadditions.
However, the selective intramolecular reaction of dieneynes with an un-
results were poorer than those of tolBINAP in both yield substituted diene moiety proceeded using an Ir-chiral
and ee (entries 2,3). When we chose BDPP as a chiral diphosphine complex to give chiral cyclohexa-1,4-dienes
ligand, dieneyne 1a was consumed within 2 hours and the in up to 98% ee.
ee of obtained 2a significantly increased to 78% (entry 4).
After screening of various solvents, ethyl acetate was
proved to be the best one and the ee reached over 90% (en-
Acknowledgement
tries 4–7). In order to shorten the reaction time, other ace- This research was supported by a Grant-in-Aid for Scientific Rese-
arch on Priority Areas (A) ‘Exploitation of Multi-Element Cyclic
tates having higher boiling points were examined as
Molecules’ from the Ministry of Education, Culture, Sports, Sci-
ence and Technology, Japan.
solvent (entries 8–9). As a result, the reaction proceeded
smoothly to give 2a with 95% ee in tert-butyl acetate (bp:
1
1
9
6 °C). When [RhCl(cod)] was used in place of
2
[
IrCl(cod)] under the same reaction conditions, 2a with References
2
only 4% ee was obtained in 80%. These results imply that
the iridium complex realized the highly enantioselective
(
1) (a) Evans, D. A.; Johnson, J. S. In Comprehensive
Asymmetric Catalysis, Vol. 3; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer: Berlin, 1999, 1177.
(b) Maruoka, K. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; Wilely-VCH: New York, 2000, 467.
[
4+2] cycloaddition of 1a. Highly enantiomerically en-
riched 2b,c were obtained in good yield from 1b,c (entries
1
0 and 11). Dieneyne 1d was also transformed into 2d in
1
2
(2) Corey, E. J.; Shibata, T.; Lee, T. W. J. Am. Chem. Soc. 2002,
24, 3808.
very high ee within 1 hour (entry 12).
1
(
(
3) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49.
4) (a) Wender, P. A.; Jenkins, T. E. J. Am. Chem. Soc. 1989,
Table 2. Ir Complex-Catalyzed Enantioselective [4+2] Cycloaddi-
tion
111, 6432. (b) Wender, P. A.; Smith, T. E. J. Org. Chem.
R
1995, 60, 2962. (c) Wender, P. A.; Smith, T. E. J. Org.
[
IrCl(cod)]2+ 2diphosphine
10 mol%)
Chem. 1996, 61, 824.
R
(
(
5) (a) Mandai, T.; Suzuki, S.; Ikawa, A.; Murakami, T.;
Kawada, M.; Tsuji, J. Tetrahedron Lett. 1991, 32, 7687.
(b) van Boxtel, L. J.; Körbe, S.; Noltemeyer, M.; de Meijere,
A. Eur. J. Org. Chem. 2001, 2283.
Z
Z
*
2
1
En-
try
1
Diphosphinea
Solventb
Time Yield
/h /%
ee
/%
(
6) (a) Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T. J.
Am. Chem. Soc. 1990, 112, 4965. (b) Wender, P. A.;
Jenkins, T. E.; Suzuki, S. J. Am. Chem. Soc. 1995, 117,
1
2
3
4
5
6
7
8
9
1a (S)-tolBINAP
Toluene
5
63 (2a) 68
36 (2a) 60
37 (2a) 24
58 (2a) 78
47 (2a) 49
33 (2a) 83
60 (2a) 92
56 (2a) 94
64 (2a) 95
73 (2b) 98
73 (2c) 94
67 (2d) 97
1843. (c) Gilbertson, S. R.; Hoge, G. S. Tetrahedron Lett.
1998, 39, 2075. (d) Wang, B.; Cao, P.; Zhang, X.
1a (S,S)-Me-DUPHOS Toluene
8
8
Tetrahedron Lett. 2000, 41, 8041.
(7) (a) McKinstry, L.; Livinghouse, T. Tetrahedron 1994, 50,
145. (b) O’Mahony, D. J. R.; Belanger, D. B.; Livinghouse,
1a (S,S)-DIOP
1a (S,S)-BDPP
1a (S,S)-BDPP
1a (S,S)-BDPP
1a (S,S)-BDPP
1a (S,S)-BDPP
1a (S,S)-BDPP
1b (S,S)-BDPP
1c (S,S)-BDPP
1d (S,S)-BDPP
Toluene
Toluene
6
2
T. Synlett 1998, 443. (c) Gilbertson, S. R.; Hoge, G. S.;
Genov, D. G. J. Org. Chem. 1998, 63, 10077. (d)Heath, H.;
Wolfe, B.; Livinghouse, T.; Bae, S. K. Synthesis 2001, 2341.
8) Shibata, T.; Yamashita, K.; Ishida, H.; Takagi, K. Org. Lett.
CH CN
15
14
20
5
3
(
DME
2001, 3, 1217.
AcOEt
(9) Shibata, T.; Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852.
10) Iridium complex-catalyzed [5+1] cycloaddition has been
reported: Murakami, M.; Itami, K.; Ubukata, M.; Tsuji, I.;
Ito, Y. J. Org. Chem. 1998, 63, 4.
11) A typical experimental procedure is as follows (Table 2,
entry 9): Stirring of (S,S)-BDPP (17.6 mg, 0.04 mmol) and
(
AcO-i-Pr
AcO-t-Bu
AcO-t-Bu
AcO-t-Bu
AcO-t-Bu
2
(
1
1
0
1
2
1
[
IrCl(cod)] (13.4 mg, 0.02 mmol) in t-BuOAc (1 mL) at
2
1
40 °C under argon gave a light yellow solution. After
addition of a t-BuOAc solution (1 mL) of dieneyne 1a (40.7
mg, 0.205 mmol), the solution was refluxed for 2 h. Solvent
was removed under a reduced pressure, then the resulting
crude products were purified by thin layer chromatography.
Pure 2a was obtained (26.0 mg, 0.131 mmol, 64% yield) and
the ee was determined to be 95% by HPLC analysis using a
chiral column.
1
1
a
tolBINAP: 2,2 -Bis(di-p-tolylphosphino)-1,1 -binaphthyl, Me-
DUPHOS: 1,2-Bis(2,5-dimethylphospholano)benzene. DIOP:
O-Isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane,
BDPP: 2,4-Bis(diphenylphosphino)pentane.
b
In toluene, the reaction was performed at 90 °C. In other solvents,
(
12) Aromatized products 3a–d were also generated (entries 9–
the reaction was performed under refluxed conditions.
12).
Synlett 2002, No. 10, 1681–1682 ISSN 0936-5214 © Thieme Stuttgart · New York