Rhodium-catalyzed asymmetric 1,4-addition of aryltitanium reagents generating chiral titanium enolates: Isolation as silyl enol ethers

Article abstract of DOI:10.1021/ja027663w

The addition of aryltitanium triisopropoxide (ArTi(OPr-i )₃) to α,β-unsaturated ketones proceeded with high enantioselectivity (94-99.8% ee) in the presence of 3 mol % of [Rh(OH)((S )-binap)]₂ in THF at 20 °C to give high yields of t

Full text of DOI:10.1021/ja027663w

Published on Web 09/18/2002
Rhodium-Catalyzed Asymmetric 1,4-Addition of Aryltitanium Reagents
Generating Chiral Titanium Enolates: Isolation as Silyl Enol Ethers
Tamio Hayashi,* Norihito Tokunaga, Kazuhiro Yoshida, and Jin Wook Han
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received July 12, 2002
Scheme 1
A growing attention has been paid to rhodium-catalyzed addition
of organoboronic acids to alkenes1 and alkynes2 and its application
to catalytic asymmetric synthesis.3,4,5 Recently it has been reported
that some organosilicon compounds can participate in the rhodium-
catalyzed reaction.6 The catalytic cycle has been revealed for the
asymmetric 1,4-addition of arylboronic acids to R,â-unsaturated
ketones catalyzed by a rhodium-binap complex.7 One of the key
steps is the hydrolysis of an (oxa-π-allyl)rhodium intermediate
giving a â-arylated ketone and a hydroxorhodium species. It follows
that the reaction must be carried out in the presence of water or a
proton source, and as a result, the 1,4-addition products are obtained
not as boron enolates but as the hydrolyzed products. It would be
better to isolate chiral metal enolates generated regiospecifically
by the rhodium-catalyzed asymmetric 1,4-addition and to use them
for further transformations.8,9 We found that the use of aryltitanium
triisopropoxides (ArTi(OPr-i)3) as arylating reagents for the rhodium-
catalyzed asymmetric 1,4-addition in nonprotic solvent realizes the
formation of titanium enolates as the 1,4-addition products which
Table 1. Asymmetric 1,4-Addition of Aryltitanium Triisopropoxide
2 to Enone 1 Catalyzed by [Rh(OH)((S)-binap)]2; Isolation as Silyl
Enol Ether 5a
are versatile intermediates for the synthesis of enantiomerically
enriched compounds by the reaction with electrophiles.
enone
1
ArTi(OPr-i)3
silyl ether 5
yield (%)c
%eeof 4b
(config)
The reaction of 2-cyclohexenone (1a) with PhTi(OPr-i)310,11 (2m)
entry
2
7
in the presence of 3 mol % of [Rh(OH)((S)-binap)]2 in THF-d8
1
2
3
4
1a
1a
1a
1a
1b
1c
1d
1e
2m
2n
2o
5am
5an
5ao
5ap
5bm
5cm
5dmh
5emi
84
68
84
63
62f
89
77
84
99.5
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(R)
was monitored by 1H NMR at 20 °C. Within 10 min, the 1H
resonances for the enone 1a disappeared and were replaced by new
signals attributable to titanium enolate 3am.12,13 On addition of
methanol, protonolysis of the enolate took place to give a high yield
(85%) of 3-phenylcyclohexanone (4am), which is an S isomer of
99.5% ee. Attempts to isolate the enolate as a silyl enol ether by
silylation of the titanium enolate 3am with a chlorotrialkylsilane
were not successful. We found that addition of lithium isopropoxide
to titanium enolate 3am in THF followed by silylation of the
resulting titanate14 with chlorotrimethylsilane leads to silyl enol ether
5am in a high yield (84%).15 The results obtained for the rhodium-
catalyzed asymmetric 1,4-addition of aryltitanium reagents 2m-p
to R,â-unsaturated ketones 1a-e, which was carried out in THF at
20 °C (Scheme 1), are summarized in Table 1. The asymmetric
1,4-addition products were isolated as trimethylsilyl enol ethers 5
after the silylation by way of the titanates generated by the addition
of lithium isopropoxide to titanium enolates 3.
99.0
99.8
94
99.8
98
2pd
2m
2m
2m
2m
5e
6g
7
99.8
97
8
a
The rhodium-catalyzed 1,4-addition was carried out with enone 1 (1.00
mmol) and ArTi(OPr-i)3 2 (1.60 mmol) in 5.0 mL of THF in the presence
of 3 mol % (Rh) of [Rh(OH)((S)-binap)]2 at 20 °C for 1 h. To the reaction
b
mixture, were added LiOPr-i (1.60 mmol) and ClSiMe3 (2.00 mmol).
Determined by HPLC analysis of ketone 4 with chiral stationary phase
columns (Chiralcel OD-H (4am, 4ap, 4cm, 4dm, 4em), AD (4an, 4ao),
c
d
and OB-H (4bm)).
Isolated yield by bulb-to-bulb distillation.
2-MeC6H4Ti(OPr-i)3 (2p) was generated in situ from 2-MeC6H4Li and
e
f
ClTi(OPr-i)3. Reaction for 5 min. Contaminated with ca. 6% of 4bm
g
h
(hydrolyzed product). Reaction for 15 min. A mixture of E and Z
isomers (10/9). A mixture of E and Z isomers (10/11).
i
1,4-addition, giving the corresponding silyl enol ethers 5dm and
5em with high enantioselectivity (entries 7-8).
The asymmetric 1,4-addition forming a chiral titanium enolate
was also successful with the titanium reagents containing 4-sub-
stituted phenyl (ArTi(OPr-i)3, 2n,o) (entries 2-3). They gave the
corresponding silyl enol ethers 5an and 5ao with over 99%
enantioselectivity. The catalytic asymmetric titanium enolate forma-
tion also proceeded with high enantioselectivity for 2-cyclopen-
tenone (1b) and 2-cycloheptenone (1c) (entries 5-6). Linear R,â-
unsaturated ketones 1d and 1e are good substrates for the present
Although the silyl enol ethers such as those isolated here are
well-documented to be very useful as synthetic intermediates16
which are readily converted into various kinds of enantiomerically
enriched compounds, the titanium enolates generated by the
rhodium-catalyzed asymmetric 1,4-addition can be used, not by way
of the silyl enol ethers, for alkylation with alkyl halides (Scheme
2). Thus, the titanium enolate 3am was allowed to react with lithium
isopropoxide and allyl bromide to give 82% yield of (2R,3S)-trans-
3-phenyl-2-allylcyclohexanone (6) as a single diastereomeric isomer,
whose enantiomeric purity is over 99%. In the reaction of the enol
* To whom correspondence should be addressed. E-mail: thayashi@kuchem.kyoto-
u.ac.jp.
9
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J. AM. CHEM. SOC. 2002, 124, 12102-12103
10.1021/ja027663w CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2 a
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Scheme 3
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31P NMR studies showed that addition of the phenyltitanium
reagent PhTi(OPr-i)3 (2m) to the (oxa-π-allyl)((S)-binap)rhodium
complex 97,18 in the presence of triphenylphosphine in THF
generated the phenylrhodium complex coordinated with (S)-binap
and triphenylphosphine 10.7 Protonolysis of the resulting THF
solution with methanol gave a high yield of (S)-3-phenylcyclohex-
anone (4am) (Scheme 3). These results indicate that the catalytic
cycle of the present 1,4-addition consists of two steps (Scheme 4):
One is transmetalation of the aryl group from titanium to the (oxa-
π-allyl)rhodium intermediate, forming an arylrhodium species and
the titanium enolate. The other is insertion of an enone into the
arylrhodium species, forming the (oxa-π-allyl)rhodium complex,
this step having been established during our studies on the rhodium-
catalyzed 1,4-addition of arylboronic acids.7
To summarize, the rhodium-catalyzed asymmetric 1,4-addition
forming chiral titanium enolates with high enantioselectivity was
realized for the first time by the use of ArTi(OPr-i)3. The chiral
titanium enolates can be isolated as silyl enol ethers by way of
titanate-type enolates generated by the addition of lithium isopro-
poxide to the titanium enolates. The catalytic cycle has been
established by a stoichiometric reaction of an (oxa-π-allyl)rhodium
complex.
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(12) 1H NMR (THF-d8): δ 1.27 (br d, J ) 5.5 Hz, 18H), 1.37-1.49 (br m,
1H), 1.60-1.72 (br m, 1H), 1.74-1.86 (br m, 1H), 1.86-2.00 (br m,
1H), 2.14-2.43 (br m, 2H), 3.47-3.58 (br m, 1H), 4.38-4.75 (br m,
3H), 4.91-5.11 (br m, 1H), 7.11 (t, J ) 7.2 Hz, 1H), 7.21 (t, J ) 7.2 Hz,
2H), 7.25 (d, J ) 7.2 Hz, 2H).
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of chlorotrimethylsilane giving silyl enol ethers has been reported: Arai,
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Acknowledgment. This work was supported in part by a Grant-
in-Aid for Scientific Research from the Ministry of Education,
Science, Sports, and Culture, Japan. K.Y. thanks the Japan Society
for the Promotion of Science for the award of a fellowship for
graduate students.
(17) Contaminated with ca. 8% of its isomer.
(18) The (oxa-π-allyl)rhodium complex 8 was generated in the NMR sample
tube by addition of 2-cyclohexenone to phenylrhodium 9 (ref 7).
Supporting Information Available: Experimental procedures and
spectroscopic and analytical data for the products (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA027663W
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J. AM. CHEM. SOC. VOL. 124, NO. 41, 2002 12103