Catalytic asymmetric methallylation and propargylation of aldehydes with bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide

Article abstract of DOI:10.1016/S0957-4166(03)00247-7

New and highly efficient enantioselective methallylation and propargylation of achiral aldehydes with methallyltributyltin and allenyltributyltin, respectively, can be achieved with high enantioselectivity under the influence of chiral bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as catalyst.

Full text of DOI:10.1016/S0957-4166(03)00247-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1603–1605
Catalytic asymmetric methallylation and propargylation of
aldehydes with bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide
Shunsuke Konishi, Hideo Hanawa and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan
Received 21 February 2003; accepted 13 March 2003
Abstract—New and highly efficient enantioselective methallylation and propargylation of achiral aldehydes with methallyl-
tributyltin and allenyltributyltin, respectively, can be achieved with high enantioselectivity under the influence of chiral
bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as catalyst. © 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
ation of aldehydes using allenyltributyltin, presumably
due to its low reactivity and regiochemical problems.6
The enantioselective methallylation and propargylation
of achiral aldehydes are important asymmetric transfor-
mations in organic synthesis,1 and subsequent oxidative
cleavage of the methallyl moiety and Hg(II)-promoted
hydrolysis of the propargyl moiety provide optically
active aldol products (Scheme 1), which are equivalent
to those of asymmetric crossed aldol reactions between
aldehydes and the enolate of acetone. In contrast to the
numerous examples of catalytic asymmetric allylation
of prochiral aldehydes with allyltributyltin,2 the corre-
sponding asymmetric methallylation and propargyla-
tion are rather difficult.3,4 Indeed, compared to the
allylic system, both reactivity and enantioselectivity in
the catalytic asymmetric methallylation using ordinary
chiral Lewis acid catalysts and methallyltributyltin were
somewhat low, and did not exhibit broad applicability.5
In addition, such transformations required longer reac-
tion times at low temperature. Moreover, there have
been few reports on the catalytic asymmetric propargyl-
2. Results
The requisite binaphthyl-modified bis-Ti(IV) oxide
(S,S)-1 was synthesized starting from triisopropoxytita-
nium chloride, (PriO)3TiCl as described previously.7,8
Thus, reaction of (PriO)3TiCl (2 equiv.) with silver(I)
oxide in CH2Cl2 at room temperature for 5 h gave rise
to bis(triisopropoxy)titanium oxide, which was further
treated with (S)-binaphthol (2 equiv.) at room tempera-
ture for 2 h to produce bis(((S)-binaphthoxy)(isoprop-
oxy)titanium) oxide (S,S)-1. Reaction of hydrocin-
namaldehyde
3
(R=CH2CH2Ph) with methallyl-
tributyltin (1.1 equiv.) under the influence of in situ
generated chiral bis-Ti(IV) oxide (S,S)-1 (10 mol%) in
CH2Cl2 at 0°C for 30 min afforded 5-methyl-1-phenyl-
5-hexen-3-ol 4 (R=CH2CH2Ph) in 63% yield with 94%
ee.9 The absolute configuration of the homomethallylic
alcohol was determined to be (R) by correlation with
an authentic sample.3b It should be noted that both the
reaction rate and the enantioselectivity of the methallyl-
ation are greatly lowered (e.g. 13% and 47% ee for
hydrocinnamaldehyde) under similar reaction condi-
tions with a chiral mono-Ti(IV) catalyst 2 (20 mol%),
which is derived from Ti(OPri)4 and (S)-binaphthol
according to the literature procedure.10
Other selected examples are listed in Table 1. Several
characteristic features of the present methallylation fol-
low: (1) the chiral bis-Ti(IV) oxide (S,S)-1 is applicable
to various types of aldehydes and exhibits uniformly
high asymmetric induction as well as high chemical
Scheme 1.
* Corresponding author.
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00247-7

1604
S. Konishi et al. / Tetrahedron: Asymmetry 14 (2003) 1603–1605
Table 1. Asymmetric methallylation of aldehydes with methallyltributyltin catalyzed by chiral bis-Ti(IV) oxide (S,S)-1a
Entry
Aldehyde
Ti catalyst (mol%)
Reaction time (h)
% Yieldb
% eec (config.)d
1
2
3
4
5
6
7
8
9
PhCH2CH2CHO
PhCHꢀCHCHO
PhCHO
1 (10)
2 (20)
1 (10)
2 (20)
1 (10)
2 (20)
1 (10)
2 (20)
1 (10)
0.5
0.5
2
63
13
90
32
94
31
88
45
87
94 (R)
47 (R)
94 (S)
85 (S)
95 (S)
72 (S)
91 (S)
79 (S)
92
2
0.5
0.5
2
2
20
Furfural
CH3(CH2)6CHO
a Unless otherwise noted, the reaction of aldehyde and Bu3SnCH2C(Me)ꢀCH2 (1.1 equiv.) was carried out in the presence of chiral bis-Ti(IV) oxide
(S,S)-1 or chiral mono-Ti(IV) 2 in CH2Cl2 (0.33 M) at 0°C under the given reaction time.
b Isolated yield.
c Determined by HPLC analysis using Chiralcel OD, OD-H and OB-H.
d Determined by comparison of the sign of the specific rotation with reported values. See Ref. 3b.
substrate. Selected results are summarized in Table 2,
which clearly shows a high dilution effect in correlating
the enantiopurity of methallylation products 4 (R=
CH2CH2Ph, CH=CHPh).
yield. (2) The use of TiꢁOꢁTi unit in the chiral bis-
Ti(IV) catalyst (S,S)-1 toward aldehyde carbonyls
strongly accelerates the rate of methallylation com-
pared to the corresponding mono-Ti(IV) catalyst 2. (3)
The absolute configuration of the homomethallylic
alcohol 4 is predictable based on the use of either
(S,S)-1 or (R,R)-1 (Scheme 2).
The present asymmetric approach can also be applied
to the asymmetric propargylation of aldehydes with
allenyltributyltin in the presence of chiral bis-Ti(IV)
catalyst (S,S)-1 as shown in Table 3.
Acknowledgements
This work was supported by a Grant-in-Aid for Scien-
tific Research (No. 13853003) from the Ministry of
Education, Culture, Sports, Science and Technology,
Japan. H.H. thanks the Japan Society for the Promo-
tion of Science for Young Scientists for Research
Fellowships.
Scheme 2.
We further examined the reaction conditions of the
asymmetric methallylation of aldehydes with (S,S)-1,
and found some effect with the concentration of the
Table 2. Dilution effects of aldehyde substrate on the asymmetric methallylation of aldehydes with methallyltributyltin
catalyzed by chiral bis-Ti(IV) oxide (S,S)-1a
Entry
Aldehyde
Concentration of substrate (M)
Reaction conditions (°C, h)
% Yieldb
% eec (config)
1
2
3
4
5
6
7
PhCH2CH2CHO
1.33
0.67
0.33
0.17
0.083
0.33
0.083
−20, 2
0, 2
0, 0.75
0, 2
0, 5
0, 2
76
76
80
73
77
90
90
82 (R)
93 (R)
94 (R)
94 (R)
96 (R)
94 (S)
96 (S)
PhCHꢀCHCHO
0, 11
a The reaction of aldehyde and Bu3SnCH2C(Me)ꢀCH2 (1.1 equiv.) was carried out in the presence of chiral bis-Ti(IV) oxide (S,S)-1 (10 mol%)
in CH2Cl2 under the given reaction condition.
b Isolated yield.
c Determined by HPLC analysis using Chiralcel OD, OD-H and OB-H.

S. Konishi et al. / Tetrahedron: Asymmetry 14 (2003) 1603–1605
1605
Table 3. Asymmetric propargylation of aldehydes with allenyltributyltin catalyzed by chiral bis-Ti(IV) oxide (S,S)-1a
Entry
Aldehyde
Ti catalyst (mol%)
Reaction conditions (°C, h)
% Yieldb (ratio)c
% eed (config)e
1
2
3
4
PhCH2CH2CHO
PhCHO
1 (10)
1 (10)f
1 (10)
1 (20)f
0, 18
0, 18; 25, 6
0, 18
50 (10:1)
64 (15:1)
28 (10:1)
69 (10:1)
92 (R)
92 (R)
95 (S)
92 (S)
0, 18; 25, 6
a Unless otherwise noted, the reaction of aldehyde and Bu3SnCHꢀCꢀCH2 (1.1 equiv.) was carried out in the presence of chiral bis-Ti(IV) oxide
(S,S)-1 in CH2Cl2 (0.33 M) under the given reaction condition.
b Isolated yield.
c Isomeric ratio of homopropargyl alcohol 5 and homoallenyl alcohol 6.
d Determined for major 5 by HPLC analysis using Chiralcel OD, OD-H and AD-H.
e Determined by comparison of the sign of specific rotation with reported values. See Ref. 4b.
f Use of excess Bu3SnCHꢀCꢀCH2 (3 equiv.).
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