Iridium complex-catalyzed highly enantio- and diastereoselective [2+2+2] cycloaddition for the synthesis of axially chiral teraryl compounds

Article abstract of DOI:10.1021/ja048131d

An asymmetric [2+2+2] cycloaddition of an α,ω-diyne, possessing ortho-substituted aryl groups on its terminus, and a monoalkyne with oxygen functionalities gave various axially chiral teraryl compounds. The coupling proceeded with extremely high enantio-

Full text of DOI:10.1021/ja048131d

Published on Web 06/17/2004
Iridium Complex-Catalyzed Highly Enantio- and Diastereoselective [2+2+2]
Cycloaddition for the Synthesis of Axially Chiral Teraryl Compounds
Takanori Shibata,*,† Takayoshi Fujimoto,‡ Kazuhisa Yokota,‡ and Kentaro Takagi‡
Department of Chemistry, School of Science and Engineering, Waseda UniVersity, Shinjuku,
Tokyo 169-8555, Japan, and Department of Chemistry, Faculty of Science, Okayama UniVersity,
Tsushima, Okayama, 700-8530, Japan
Received April 1, 2004; E-mail: tshibata@waseda.jp
Scheme 1. Synthesis of Axially Chiral Teraryl Compound by
[2+2+2] Cycloaddition
An axially chiral biaryl is an important structure among chiral
ligands, and many catalytic and highly enantioselective reactions
have been achieved by using axially chiral biaryl compounds
possessing C2 symmetry, as represented by BINOL and BINAP.1
While various methods have been reported for the synthesis of
axially chiral biaryl components, including optical resolution of
racemic compounds and diastereoselective reactions using a stoi-
chiometric amount of chiral auxiliaries, practical examples of the
catalytic synthesis of axially chiral biaryls are limited. Hayashi and
Ito reported a pioneering work on asymmetric Kumada coupling
using a chiral nickel catalyst for the synthesis of 1,1′-binaphthyl
compounds.2 Hayashi further reported an enantioposition-selective
cross-coupling using a chiral palladium catalyst3 and an asymmetric
Kumada coupling of dinaphthothiophene based on the concept of
dynamic kinetic resolution.4 Asymmetric Suzuki coupling using a
chiral palladium catalyst is another approach for the catalytic
synthesis of axially chiral biaryls.5 Oxidative coupling of 2-naphthol
derivatives has also been reported for the synthesis of BINOL
derivatives using chiral copper6 or oxovanadium complexes.7,8
However, all of these procedures involve the asymmetric coupling
of aryl compounds.9
Table 1. Asymmetric [2+2+2] Cycloaddition Using Chiral Iridium
Complexes
We report here an asymmetric [2+2+2] cycloaddition of an R,ω-
diyne and monoalkynes as a new approach for obtaining axially
chiral compounds possessing C2 symmetry.10,11 [2+2+2] Cycload-
dition is a common protocol for the synthesis of substituted aromatic
compounds, and various transition metal complexes, including those
of cobalt, rhodium, and palladium, have been reported to be efficient
catalysts.12 We considered that the cycloaddition of an R,ω-diyne,
possessing ortho-substituted aryls on its terminus, and a disubstituted
alkyne would give an axially chiral teraryl compound due to steric
hindrance between R1 and R2 (Scheme 1).13
entry
ligand
X/mol% time/h yield/%
dl/meso
ee/%
1
2
3
4
5
6
7
8
(S)-BINAP
(S,S)-BDPP
10
10
10
10
10
5
4
6
1
1
1
1
1
3
31
39
83
75
88
83
89
84
60/40
45/55 51
>95/5
>95/5
>95/5
>95/5
>95/5
98/2
6
(S,S)-MeDUPHOS
(S,S)-EtDUPHOS
(R,R)-MeDUPHOS
(S,S)-MeDUPHOS
(S,S)-MeDUPHOS
(S,S)-MeDUPHOS
99.6
99.8
99.6a
99.0
99.3
99.1
2
0.5
a An opposite enantiomer to the above structure of 3aa was obtained.
We have previously reported an iridium complex-catalyzed
[2+2+1] cycloaddition of an R,ω-diyne and carbon monoxide. As
a minor product of this reaction, we obtained a polysubstituted
benzene, which resulted from the [2+2+2] cycloaddition of the
R,ω-diyne itself.14a We anticipated that iridium complexes would
show high catalytic activity in [2+2+2] cycloaddition for the
synthesis of a congested polyaryl compound, and examined the
cross-coupling of propargyl ether possessing naphthyl groups 1a
and methyl-protected 2-butyne-1,4-diol 2a using an Ir-dppp com-
plex.14,15 As a result, teraryl 3aa was obtained as a mixture of dl
and meso isomers, and the dl isomer was resolved by HPLC using
a chiral column.
(entry 1). BDPP gave moderate enantioselectivity, but the diaste-
reoselectivity was low (entry 2). We found that MeDUPHOS (1,2-
bis-(2,5-dimethylphospholano)benzene) gave the best results: the
meso isomer could not be detected in the NMR spectrum, and the
enantioselectivity exceeded 99% (entry 3). EtDUPHOS gave almost
the same results (entry 4), and (R,R)-MeDUPHOS provided the
opposite enantiomer (entry 5).16 No decrease in selectivity was
observed upon lowering the amount of catalyst to 2 mol %, and a
high ee of 99.1% was achieved, even with 0.5 mol % catalyst
(entries 6-8).
The asymmetric [2+2+2] cycloaddition of various R,ω-diynes
and protected 2-butyne-1,4-diols (3 equiv) was examined using
the Ir-MeDUPHOS catalyst, and extremely high enantio- and
diastereoselectivities were achieved in each reaction (Table 2). THP-
and TBS-protected diols 2b,c were also good coupling part-
ners, and the ee was extremely high after deprotection to diol 4a
Next, we investigated the reaction conditions for asymmetric
coupling (Table 1): while BINAP was the first choice as a chiral
ligand, both the yield and the enantioselectivity of 3aa were low
† Waseda University.
‡ Okayama University.
9
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J. AM. CHEM. SOC. 2004, 126, 8382-8383
10.1021/ja048131d CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Asymmetric [2+2+2] Cycloaddition of Various
R,ω-Diynes and Monoalkynes
In conclusion, we have reported an asymmetric [2+2+2]
cycloaddition of diynes and alkynes with oxygen functionalities.
This reaction proceeds with extremely high enantio- and diaste-
reoselectivity to give various axially chiral compounds. The present
procedure provides access to a new chiral pool of diol compounds
possessing C2 symmetry.
a
entry
Ar
Z
diyne
R
yield/%
ee/%
1
2
3
4
5
6
1-naphthyl
1-naphthyl
1-naphthyl
2-MeC6H4
2-Cl C6H4
4-MeO-1-
naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
1-naphthyl
O
O
O
O
O
O
1a
1a
1a
1b
1c
1d
THP
TBS
76 (4a)b
74 (3ac)
99.5b
99.5c
98.5
99.6
97.7
99.4
MOM 76 (3ad)d
Me
Me
Me
85 (3ba)
85 (3ca)
72 (3da)
Acknowledgment. The authors thank Masaya Hirase for his
experimental assistance. This research was supported by a Grant-
in-Aid for Scientific Research on Priority Areas (A) “Exploitation
of Multi-Element Cyclic Molecules” from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan.
7
8
9
10
11
NTs
NTs
1e
1e
1f
1g
1g
Me
THP
Me
Me
TBS
92 (3ea)
97 (4e)b
77 (3fa)
96 (3ga)
77 (3gc)e
99.4
99.1b
>99.8
>99.8
98.6c
C(CO2Et)2
CH2
CH2
Supporting Information Available: Experimental details and
spectral data for R,ω-diynes and products. This material is available
free of charge via the Internet at http://pubs.acs.org.
a Only dl isomer was detected by NMR spectrum, except entries 3 and
11. b Yield and ee were determined as diol 4a or 4e after deprotection using
PPTS in EtOH. c Ee was determined as diol 4a or 4g after deprotection
using TBAF in THF. d dl/meso) 93/7. e dl/meso ) 91/9.
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Supporting Information).
The present asymmetric [2+2+2] cycloaddition was applied to
the unsymmetrical diyne 6, and the chiral biaryl compound 7 was
obtained (eq 2). In this reaction, EtDUPHOS gave a significantly
better enantioselectivity than MeDUPHOS.
JA048131D
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J. AM. CHEM. SOC. VOL. 126, NO. 27, 2004 8383