Novel asymmetric alkylation of aromatic aldehydes with triethylaluminum catalyzed by titanium·(1,1'-bi-2-naphthol) and titanium·(5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol) complexes

Full text of DOI:10.1021/ja970135d

4080
J. Am. Chem. Soc. 1997, 119, 4080-4081
triethylaluminum to aldehydes. Recently, Cai et al. at Merck7
found that binaphthol forms an inclusion complex with N-
benzylcinchonidinium chloride in acetonitrile and the (R)-
BINOL complex precipitated from the solution to give 99%
yield and 96% ee of the desired isomer. The (S)-BINOL was
found to stay in the acetonitrile solution and gave the enantiomer
in 99% yield and 99% ee. The development of this finding is
expected to provide excellent technology for the economic
production of (S)- or (R)-1,1′-bi-2-naphthol ((S)- or (R)-BINOL)
and consequently will provide an excellent opportunity for the
exploitation of (S)- and (R)-BINOL and their derivatives as
readily available and potentially low-cost chiral auxiliaries for
asymmetric synthesis. In this respect, it is of great interest to
examine the effect of (S)- or (R)-BINOL and their derivatives
in asymmetric catalysis such as the enantioselective addition
of triethylaluminum to aldehydes. With this background in
mind, we started a study of the triethylaluminum addition with
Novel Asymmetric Alkylation of Aromatic
Aldehydes with Triethylaluminum Catalyzed by
Titanium‚(1,1′-bi-2-naphthol) and
Titanium‚(5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-
bi-2-naphthol) Complexes
Albert S. C. Chan,* Fu-Yao Zhang, and Chiu-Wing Yip
Union Laboratory of Asymmetric Synthesis and
Department of Applied Biology and Chemical Technology
The Hong Kong Polytechnic UniVersity, Hong Kong
ReceiVed January 16, 1997
The catalytic asymmetric carbon-carbon bond formation is
8
BINOL and 5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-bi-2-naphthol (H8-
BINOL) as chiral auxiliaries.
one of the most actively pursued areas of research in the field
of asymmetric catalysis.1 Over the past 10 years, the catalytic
addition of diethylzinc to aldehydes as a route to chiral alcohols
has attracted much attention.2 Since many chiral alcohols are
highly valuable intermediates for the manufacturing of chiral
pharmaceuticals and agricultural products, the development of
highly effective systems for the alkylation of aldehydes is not
only of interest to the academic world but also of substantial
interest to industrial scientists. Recently, several highly enan-
tioselective catalysts for these reactions have been reported in
3
the literature. Similarly the catalytic asymmetric alkylation of
The preliminary results were found to be highly encouraging.
By using a catalyst conveniently prepared in situ from Ti(O-i-
Pr)4 and (R)-BINOL or (S)-H8-BINOL, a variety of arylalde-
hydes were smoothly alkylated to the corresponding alkylated
alcohols. When suitable conditions are chosen, side reactions
such as the reduction of the aldehydes to primary alcohols
aldehydes with alkylboranes, organotin compounds, and Grig-
nard reagents also have attracted interest.2
b,4
From a broader
perspective, the catalytic asymmetric alkylation of aldehydes
with trialkylaluminum compounds should be of particularly high
scientific and commercial interest.
(
which often took place in the diethylzinc addition reactions)
could be reduced to minimum and quantitative yields of the
alkylation products were frequently achieved.
Trialkylaluminum compounds are economically prepared in
5
industrial scale from aluminum hydride and olefins. The
successful alkylation of this type will certainly open up a new
area for active research. Mukaiyama et al. found that when an
aldehyde reacted with allyldialkylaluminum in the presence of
stannous triflate and a chiral bidentate diamine, the aldehyde
could be allylated and gave secondary homoallyl alcohols with
up to 84% ee (enantiomeric excess).6 In this paper, we report
the first example of the enantioselective catalytic alkylation of
aldehydes with triethylaluminum.
In THF solvent and at 0 °C, benzaldehyde was alkylated to
give 1-phenyl-1-propanol quantitatively, and 81% ee was
obtained when (R)-BINOL was used as the chiral ligand. When
(S)-H8-BINOL was used as the chiral auxiliary, the enantiose-
lectivity of the catalytic reaction improved. Under otherwise
identical conditions, the ee for the 1-phenyl-1-propanol product
was found to be 96.4% when a catalyst prepared in situ from
Ti(O-i-Pr)4 and (S)-H8-BINOL was used. This reaction was
found to be general and of high yields for a variety of aromatic
aldehydes. The aldehydes shown below (1-9) have been tested,
Since titanium chiral alkoxide complexes have been found
to be highly enantioselective in the asymmetric addition of
diethylzinc to aldehydes,3 our initial effort was focused on the
use of this class of complexes as catalyst for the addition of
a
(
1) For recent review, see: Noyori, R. Asymmetric Catalysis in Organic
(7) Cai, D.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Tetrahedron
Lett. 1995, 36, 7991.
Synthesis; Wiley: New York, 1994.
(
2) For recent reviews, see: (a) Noyori, R. Asymmetric Catalysis in
(8) Cram, D. J.; Helgeson, R. C.; Peacock, S. C.; Kaplan, L. J.; Domeier,
L. A.; Moreau, P.; Koga, K.; Mayer, J. M.; Chao, Y.; Siegel, M. G.;
Hoffman, D. H.; Sogah, G. D. Y. J. Org. Chem. 1978, 43, 1930.
(9) A typical procedure for the experiment is as follows. Titanium
tetraisopropoxide (60 µL, 0.175 mmol) was added to a solution of (R)-
binaphthol (7.0 mg, 0.025 mmol) in 1.0 mL of THF at ambient temperature,
and the solution was stirred with a magnetic stirrer for 10 min. A solution
of triethylaluminum in toluene (0.375 mL of a 1.0 M solution, 0.375 mmol)
was added to the catalyst solution, and the mixed solution continued to stir
at ambient temperature for 30 min. The solution was cooled to 0 °C, and
benzaldehyde (13 µL, 0.125 mmol) was added. The final solution was stirred
at 0 °C for 5 h. The reaction was quenched sequentially with 1.0 mL of
water and 0.5 mL of 2 N hydrochloric acid solution, and the product was
extracted with 2.0 mL of ethyl acetate. The organic extract was dried over
MgSO4 and analyzed by GLC with a Chrompack CD-Chirasil-DEX-CB
capillary column.
Organic Synthesis; Wiley: New York, 1994; pp 260-278. (b) Noyori, R.;
Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49.
(
3) (a) Schmidt, B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1991, 30,
1
321 and references therein. (b) Noyori, R.; Suga, S.; Kawai, K.; Okada,
S.; Kitamura, M.; Oguni, N.; Hayashi, M.; Kaneko, T.; Matsuda, Y. J.
Organomet. Chem. 1990, 382, 19. (c) Soai, K.; OoKawa, A.; Kaba, T.;
Ogawa, K. J. Am. Chem. Soc. 1987, 109, 7111. (d) Kitajima, H.; Ito, K.;
Katsuki, T. Chem. Lett. 1996, 343.
(
4) (a) Corey, E. J.; Cimprich, K. A. J. Am. Chem. Soc. 1994, 116, 3151.
b) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi,
A. J. Am. Chem. Soc. 1993, 115, 7001.
5) Cotton, F. A.; Wilkinson, G. AdVanced Inorganic Chemistry, 4th ed.;
Wiley: New York, 1980; p 342.
6) Mukaiyama, T.; Minowa, N.; Oriyama, T.; Narasaka, K. Chem. Lett.
986, 97.
(
(
(
1
S0002-7863(97)00135-2 CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 17, 1997 4081
Table 1. Asymmetric Addition of Triethylaluminum to
Arylaldehydes
meta- and para-substituents on the aromatic aldehydes had less
effect on the enantioselectivity for the alcohol products. These
results are consistent with the expectation that the electronic
effects from the starting materials are less significant as
compared with the steric hindrance effect in influencing the
enantioselectivity of the reaction. An analysis of the results
from entries 1, 7, 9, 11, and 13 indicated that, for the
(R)-BINOL/Ti(O-i-Pr)4 system, the electron withdrawing para-
substituents had little influence on the enantioselectivity while
electron-donating para-substituents had a small negative effect.
For meta-substituted benzaldehydes, an electron-withdrawing
substituent on the phenyl ring was found to increase the
enantioselectivity while an electron-donating substituent was
found to lower the enantioselectivity for the desired products
(entries 1, 15, and 17). For the (S)-H8-BINOL/Ti(O-i-Pr)4
system, the effects of the substituents were less significant, partly
because all of the ee values were already quite high.
a-c
convsn selectivity ee
entry aldehyde
ligand
(%)
(%)
(%) confign
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
1
1
2
2
3
3
4
4
5
5
6
6
7
7
8
8
9
9
(R)-BINOL
100
100
100
93.3
100
91.6
100
98.2
100
100
100
85.3
100
80.2
100
100
100
100
100
81
96.4
52
91
62
90.6
77.8
94.4
81
90.1
75.8
93
R
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
(S)-H
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
(R)-BINOL
(S)-H -BINOL
8
-BINOL 100
91.3
95.8
95.1
95.8
91.7
97.6
92.9
59
85.0
92.1
93
97.9
97.2
97.6
93.1
98.9
8
8
8
1
1
1
1
1
1
1
1
1
8
8
d
67
92.8d
85.6
94.4
8
When trimethylaluminum was used as alkylating agent, the
chemical selectivities were still quantitative and the expected
1-arylethanols were obtained after hydrolysis. However, the
ee values of the alcohols were found to be lower. For example,
when benzaldehyde was allowed to react with trimethylalumi-
num under otherwise identical conditions as in entry 2 of Table
8
71.4d
R
S
94.1d
8
a
A detailed experimental procedure is shown in ref 9. b Ligand/Ti(O-
/AlEt /substrate ) 0.2:1.4:3.0:1; solvent ) THF; reaction tem-
i-Pr)
4
3
c
perature ) 0 °C; reaction time ) 5 h. Except as noted, the ee values
were determined by chiral GLC with a Chrompack CD-Chirasil-DEX-
CB capillary column, and the sense of chirality was based on the
comparison of the direction of optical rotation (and GLC trace) of the
products with known compounds of the same or similar structures.
1
, the sec-phenethyl alcohol product was found to be of 53%
ee (91% conversion; 100% chemical selectivity). The ee values
for the methylation of other aldehydes under identical conditions
were as follows: p-fluorobenzaldehyde, 44.8% ee; p-chloroben-
zaldehyde, 43.0% ee; p-fluorobenzaldehyde, 44.8% ee; p-
methylbenzaldehyde, 42.1% ee; p-methoxybenzaldehyde, 42.7%
ee (100% chemical yields were obtained in all of these cases).
The lower ee values were probably due to the mismatch of the
catalysts and the alkylating agent. Since there are many chiral
catalysts available, as reported in the literature, further study
of this reaction with other catalysts should be of significant
interest. When triisobutylaluminum was allowed to react with
arylaldehydes under these conditions, only reduction products
were obtained. For example, the reaction of benzaldehyde with
triisobutylaluminum gave benzyl alcohol exclusively. The use
of triisobutylaluminum as a reducing agent is well established.10
Further exploration of this new asymmetric alkylation reaction
with other aluminum alkyls and other types of chiral catalyst is
in progress.
d
Determined by HPLC with a Chiralcel-OD column from Daicel.
and the representative data of the addition reaction are sum-
marized in Table 1.
These results clearly indicate the high potential of this new
chemistry which, we believe, can be applied to the synthesis of
a variety of chiral alcohols from low-cost raw materials.
Several interesting features can be noted from Table 1. While
the (R)-BINOL/Ti(O-i-Pr)4 system provided good yields of
chiral alcohols in moderate to good ee values, the (S)-H8-
BINOL/Ti(O-i-Pr)4 system gave quantitative yields of the
desired alcohols in excellent ee values (>90%) in the reaction
from all of the aromatic aldehydes tested. A comparison of
the experimental results from entries 1-6 (Table 1) revealed
the detrimental effect on enantioselectivity by ortho-substituents
on benzaldehyde. This was probably due to the strong steric
hindrance effect of the ortho-substituent which significantly
weakened the coordination of the aldehyde and consequently
lowered the enantioselectivity of the reaction. In comparison,
In conclusion, we have developed a new, highly efficient
method for the production of chiral alcohols from aldehydes
and triethylaluminum using catalysts which can be conveniently
prepared from commercially available or easily prepared
reagents. This study opens up a new frontier for the develop-
ment of more efficient synthetic methods. A more detailed
study of this new class of reaction with different kinds of
catalysts is underway.
Acknowledgment. We thank the Hong Kong Research Grant
Council for financial support of this study.
JA970135D
(
10) Tolstikov, G. A.; Akbutina, F. A.; Adler, M. E.; Sidorov, N. N.;
Kuchin, A. V.; Miftakhov, M. S. Zh. Org. Khim. 1988, 24, 2622.