Efficient asymmetric catalysis of chiral organoaluminum complex for enantioselective ene reactions of aldehydes

Article abstract of DOI:10.1016/j.tetlet.2004.04.052

Chiral organoaluminum complex 1 efficiently catalyzed the asymmetric hetero-ene reaction of commercially available 2-methoxypropene (2) with aldehydes under mild conditions to give the corresponding β-hydroxymethyl ketones 3 in good to excellent chemical

Full text of DOI:10.1016/j.tetlet.2004.04.052

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4481–4484
Efficient asymmetric catalysis of chiral organoaluminum
complex for enantioselective ene reactions of aldehydes
Takashi Ooi, Kohsuke Ohmatsu, Daisuke Uraguchi and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Received 22 March 2004; revised 7 April 2004; accepted 9 April 2004
This paper is dedicated to Professor Iwao Ojima on the occasion of his 60th birthday
Abstract—Chiral organoaluminum complex 1 efficiently catalyzed the asymmetric hetero-ene reaction of commercially available
2
-methoxypropene (2) with aldehydes under mild conditions to give the corresponding b-hydroxymethyl ketones 3 in good to
excellent chemical yields with high enantiomeric excesses. The asymmetric catalysis of 1 was further applied to the carbonyl addition
of methallylsilanes, where exclusive formation of the optically active allylic silanes 5 was achieved.
Ó 2004 Elsevier Ltd. All rights reserved.
The ene reaction involving a carbonyl compound as the
enophile, carbonyl-ene reaction, has been widely utilized
as an attractive tool for the stereocontrolled construc-
tion of a primary carbon framework of organic mole-
b-hydroxymethyl ketones 3 with high enantiomeric
purities (Scheme 1). Further application of the efficient
asymmetric catalysis of 1 to the ene-type carbonyl
addition of methallylsilanes is also reported.
1
cules. The synthetic potential of this methodology has
been further demonstrated by the recent extensive
development of the asymmetric variants based on the
The requisite chiral organoaluminum Lewis acid (R)-1
can be readily prepared in situ by the treatment of (R)-
2
0
0
use of chiral Lewis acid catalysts. Among these,
asymmetric hetero-ene reaction of aldehydes with
2,2 -bis(trifluoromethanesulfonylamino)-1,1 -binaphthyl
with 1 equiv of Me Al in CH Cl at refluxing tempera-
3
2
2
6
2
-methoxypropene (2) appears as a convenient yet reli-
ture for 1 h. An initial attempt was then made by
conducting the reaction of 3-phenylpropanal with 2
able bond-forming process, enabling the preparation of
various enantiomerically enriched b-hydroxymethyl
ketones from commercially available, easy-to-handle
reaction partners. Unfortunately, however, previous
studies on this subject have been strictly limited to two
examples, that is, the pioneering work of Carreira et al.
(2.1 equiv) in the presence of 5 mol % of (R)-1 in CH Cl2
2
at )78 °C; this revealed the complete consumption of the
starting aldehyde within 30 min and that the subsequent
acidic hydrolysis of the ene-product with 1 N HCl
afforded the corresponding b-hydroxymethyl ketone 3
3
using NOBIN-derived chiral titanium Lewis acid, and
an optically active tridentate Schiff base chromium(III)
[R ¼ Ph(CH
2 2
) ] in 95% isolated yield with 86% ee (entry
1 in Table 1). It is noteworthy that the catalyst loading
can be reduced to 2 mol % without substantial loss of the
enantioselectivity of the product 3 (entry 2).
complex-catalyzed reaction of 2 with mainly aromatic
4
aldehydes elegantly invented by Ruck and Jacobsen.
Here we wish to report our own contribution uncover-
ing the eminent catalytic activity of chiral organoalu-
Other selected examples summarized in Table 1 demon-
strate the scope and limitations of the present chiral
organoaluminum-catalyzed hetero-ene process. Gener-
ally, 5 mol % of (R)-1 with 2.1 equiv of 2 was sufficient
for the rapid bond formation. A high level of chiral
efficiency was attained in the reactions of unbranched
aliphatic aldehydes (entries 3 and 4), while certain
decrease of the chemical yield and the enantiomeric
excess was observed with the substrates having a-sub-
stituent (entries 5 and 6). The addition of 2 to various
5
minum complex 1 in the hetero-ene reaction of
aldehydes with 2, giving rise to the corresponding
Keywords: Aldehydes; Chiral organoaluminum complex; Ene reac-
tions; Methallylsilanes; 2-Methoxypropene.
*
Corresponding author. Tel./fax: +81-75-753-4041; e-mail: maruoka@
kuchem.kyoto-u.ac.jp
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.052

4482
T. Ooi et al. / Tetrahedron Letters 45 (2004) 4481–4484
O
OMe
OH OMe
OH
O
(
R)-1 (2—5 mol%)
1 N HCl
+
R
H
R
R
CH2Cl2, —78 °C
2
3
0.5—1.5 h
Tf
Tf
NH
N
Me3Al (1 equiv)
AlMe
CH2Cl2
reflux, 1 h
NH
N
Tf
Tf
(
R)-1
Scheme 1.
a
Table 1. Chiral organoaluminum Lewis acid (R)-1-catalyzed hetero-ene reaction of aldehydes with 2-methoxypropene (2)
O
OMe
OH
O
(
R)-1 (5 mol%) 1 N HCl
+
R
H
R
CH2Cl2, —78 °C
2
3
b
c
d
Entry
1
R
Reaction time (h)
% Yield
% Ee (config)
Ph(CH
Ph(CH
Ph(CH
2
2
2
)
)
)
2
2
4
0.5
1.5
0.5
0.5
1
95
91
90
83
63
78
95
93
91
84
86 (S)
84 (S)
80
e
2
3
4
5
6
7
8
9
CH
3
(CH
2
)
4
81
C
6
H
11
68 (S)
70
(Et)
Ph
2
CH
1
0.5
0.5
0.5
0.5
74 (S)
69
70
6 4
p-F–C H
a-Naph
2-Furyl
10
72
a
2 2
Unless otherwise specified, the reaction was carried out with 2.1 equiv of 2-methoxypropene (2) in the presence of 5 mol % of (R)-1 in CH Cl at
)
78 °C for the given reaction time.
b
c
Isolated yield.
Enantiomeric excess of 3 was determined by HPLC analysis using a chiral column with hexane–2-propanol as solvent.
d
e
9
Absolute configuration was established by comparison of optical rotation to known literature value.
With 2 mol % of (R)-1 and 2 was added over 1 h.
aromatic and hetero-aromatic aldehydes also proceeded
smoothly with good enantioselectivity (entries 7–10).
lable product in good yield with similar enantioselec-
tivity even in the reactions with triethyl- and
trimethylmethallylsilanes, respectively (entries 2 and 3).
This reaction profile is in contrast to the previously
reported chiral titanium complex-catalyzed addition
of trimethylmethallylsilane to methyl glyoxylate.
Although employment of the sterically more hindered
silyl substituents ruined the stereoselectivity (entries 4
The salient feature of the chiral organoaluminum catal-
yst 1 has been emphasized by its asymmetric catalysis in
the ene-type carbonyl addition of methallylsilanes
7
(
Scheme 2 and Table 2). For instance, treatment of
-phenylpropanal with tert-butyldimethylmethallyl-
silane (4, R ) under the influence of (R)-1 in
¼ t-BuMe
toluene at )78 °C for 1 h resulted in the exclusive for-
mation of the allylic silane 5 (R ) in 78%
¼ t-BuMe
yield, and the enantiomeric excess was determined to be
8% ee (entry 1 in Table 2). Particularly noteworthy is
3
3
2
2 2
and 5), we found that the use of CH Cl as solvent led to
a significant enhancement of the catalytic efficiency, by
which the desired 5 was obtained in excellent chemical
yield regardless of the steric demand of the silyl group
on 4, and the optimal enantioselectivity reached 80% ee
3
2
6
8
that the ene-type adduct 5 was obtained as a sole iso-
(entries 6–8).
OH
OSiR3
CHO
(
R)-1 (10 mol%)
Ph
SiR3
+
+
Ph
Ph
solvent
SiR3
5
6
—
78 °C, 1 h
4
Scheme 2.

T. Ooi et al. / Tetrahedron Letters 45 (2004) 4481–4484
4483
a
Table 2. Selective ene-type carbonyl addition of methallylsilanes to 3-phenylpropanal catalyzed by (R)-1
b
c
Entry
R
3
(4)
t-BuMe
Et
Me
t-BuPh
i-Pr
t-BuMe
t-BuPh
i-Pr
Solvent
Toluene
% Yield of 5
% Ee of 5
1
2
3
4
5
6
7
8
2
78
83
69
79
63
91
99
90
68
69
67
54
61
80
63
74
3
3
2
3
2
2 2
CH Cl
2
3
a
b
c
The reaction was performed with 2.1 equiv of methallylsilane 4 in the presence of 10 mol % of (R)-1 in the given solvent at )78 °C for 1 h.
Isolated yield.
Enantiomeric excess was determined by HPLC analysis using a chiral column with hexane–2-propanol as solvent, and absolute configuration was
1
assigned by the correlation of the HPLC retention time with that reported after desilylation.
0
In summary, chiral organoaluminum complex (R)-1
0
PhCH ),
2
C(OH)CH
C(OH)CH
2.18
(1H,
dd,
J ¼ 14:0,
3.2 Hz,
derived from (R)-2,2 -bis(trifluoromethanesulfonyl-
0
2
2
C@C), 2.05 (1H, dd, J ¼ 14:0, 9.5 Hz,
amino)-1,1 -binaphthyl and Me
3
Al was found to display
C@C), 1.92 (1H, s, OH), 1.75–1.85 (2H, m,
high catalytic and chiral efficiency in the asymmetric
hetero-ene reaction of commercially available 2-meth-
oxypropene (2) with aldehydes under mild conditions.
Examination of the substrate generality revealed the
scope and limitations of this system. The characteristic
feature of the asymmetric catalysis of 1 has also been
demonstrated by achieving the exclusive ene-type addi-
tions of methallylsilanes 4 to 3-phenylpropanal with
good to high enantioselectivities. Further investigations
of the unique reactivity and selectivity of this excep-
tionally Lewis acidic chiral organoaluminum catalyst
are now underway in our laboratory.
PhCCH ), 1.59 (1H, d, J ¼ 13:3 Hz, C@CCH Si), 1.48
2
2
t
(1H, d, J ¼ 13:3 Hz, C@CCH
2
Si), 0.91 (9H, s, Si Bu),
13
)0.02 (6H, s, SiMe ); C NMR (100 MHz, CDCl ) d
2
3
144.6, 142.0, 128.3, 128.2, 125.6, 110.7, 67.9, 46.5, 38.5,
32.0, 26.3, 22.0, 16.6, )5.9, )6.3; IR (neat) 3364, 2926,
2854, 1630, 1454, 1362, 1250, 1153, 1051, 835, 746,
ꢁ
1
698 cm . HRMS (ESI-TOF) Calcd for C19
H
32ONaSi
þ
([M+Na] ): 327.2110. Found: 327.2115. HPLC condi-
tions: Daicel Chiralcel OD-H, hexane/i-PrOH ¼ 30:1,
flow rate ¼ 0.5 mL/min, k ¼ 254 nm, retention time:
12.8 min (major), 22.5 min (minor).
Typical experimental procedure is as follows (entry 1 in
0
Table 1): To a solution of (R)-2,2 -bis(trifluoro-
0
Acknowledgements
methanesulfonylamino)-1,1 -binaphthyl (27.4 mg, 0.05
mmol) in freshly distilled CH Cl (5 mL) was added a
2
2
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. D.U. is
grateful to the Japan Society for the Promotion of
Science for Young Scientists for a Research Fellowship.
1
0
M hexane solution of trimethylaluminum (50 lL,
.05 mmol) at room temperature under argon atmo-
sphere and the mixture was refluxed for 1 h. The
resulting solution was cooled to )78 °C and 3-phenyl-
propanal (132 lL, 1.0 mmol) was added followed by the
dropwise introduction of 2-methoxypropene (2, 201 lL,
2
.1 mmol). The reaction mixture was stirred at )78 °C
for 0.5 h and then poured into 1 N HCl at 0 °C. After
being stirred for 0.5 h at the same temperature, extrac-
tive workup was performed with ether. The organic
extracts were washed with brine and dried over anhy-
References and notes
1
2
. For reviews, see: (a) Snider, B. B. Acc. Chem. Res. 1980,
3, 426; (b) Whitesell, J. K. Acc. Chem. Res. 1985, 18, 280;
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1
(
2 4
drous Na SO . Evaporation of solvents and purification
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Chapter 8C.
3
sponding b-hydroxymethyl ketone 3 [R ¼ Ph(CH
2 2
) ]
(
183.3 mg, 0.95 mmol, 95% yield) as colorless oil. The
enantiomeric excess was determined to be 86% ee by
chiral HPLC analysis [Daicel Chiralpak AD-H, hexane/
i-PrOH ¼ 10:1, flow rate ¼ 0.5 mL/min, k ¼ 254 nm,
retention time: 17.6 min (S), 19.6 min (R)].
3
4
5
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1
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The ene-type addition of methallylsilanes to 3-phenyl-
propanal was conducted in a similar manner as
described above. Characterization of allylic silane 5
2
3
0
(
CHCl
R
3
¼ t-BuMe
2
) is representative; ½aꢀ )30.70 (c 1.05,
D
, 80% ee); H NMR (400 MHz, CDCl
1
3
3
) d 7.19–
6
. We confirmed nearly quantitative formation of (R)-1
1
7
CHOH), 2.66–2.76 (1H, m, PhCH
.33 (5H, m, Ph), 4.74 (2H, s, C@CH ), 3.76 (1H, br s,
under this condition by H NMR analysis. For the
original preparative conditions, see: Noyori, R.;
2
2
), 2.78–2.88 (1H, m,

4
484
T. Ooi et al. / Tetrahedron Letters 45 (2004) 4481–4484
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1
sen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
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2
2