Chemistry Letters 2002
165
as follows; (yield/%, ee/% (configuration)), 4-ClC6H4CHO (62, 85
(R)), 4-CF3C6H4CHO (61, 87 (R)), ðEÞ-PhCH ¼ CHCHO (61, 69
(R)), PhCH2CH2CHO (49, 66 (R)), nC8H17CHO (40, 72 (R)). As a
result, it was proved that the present catalyst system efficiently
promoted the reaction not only of aromatic aldehydes but also of
aliphatic aldehydes to form the desired alcohols with good to high
ee.
Scheme 2.
Thus, asymmetric alkylation of aldehydes to give the
corresponding optically active secondary alcohols by using a new
ligand 4 combined with several metal alkoxides was developed. The
hypothesis that the reaction using 4 proceeded via the transition
state that possesses zinc chelated by sulfur and oxygen was
supported experimentally as the similar enantioselectivities were
observed with the use of various metal alkoxides. Other applications
and further studies on mechanism of the present reaction are now in
progress.
salt. Actually, (R)-6 was obtained with moderate enantioselectivity
(37% ee)when the reaction of diethylzinc with benzaldehyde was
carried out in the presence of a titanium alkoxide generated from
20 mol% of 4 with 20 mol% of Ti(OiPr)4 in refluxed toluene for 2 h
prior to use. After examining the solvents and the molar ratios of
Ti(OiPr)4 to 4, the desired (R)-6 was obtained with good ee (74%)at
0 ꢁC in a mixed solvent (o-xylene/hexane¼3/2)by using 20 mol%
of 4 and 10 mol% of Ti(OiPr)4.
Since there was a possibility for metal salts other than ziac
alkoxide of 4 also to be utilized for the asymmetric alkylation of
aldehydes,11 various commercially available metal salts were tried
in the enantioselective alkylation. It was then found that the reaction
using some kinds of metal alkoxides with 20 mol% of 4 at 0 ꢁC gave
good to high enantioselectivities as shown in Table 1.12
We dedicate this paper to Professor Teruaki Mukaiyama on the
celebration of his 75th birthday.
References and Notes
1
N. Oguni and T. Omi, Tetrahedron Lett., 25, 2823 (1984). See also, N. Oguni,
T. Omi, Y. Yamamoto, and A. Nakamura, Chem. Lett., 1983, 841.
Reviews: R. Noyori and M. Kitamura, in ‘‘Modern Synthetic Methods,’’ ed.
by R. Scheffold, Springer, Berlin (1989), Vol. 5, p. 172; R. Noyori and M.
Kitamura, Angew. Chem., Int. Ed. Engl., 30, 49 (1991); K. Soai and S. Niwa,
Chem. Rev., 92, 833 (1992); L. Pu and H.-B. Yu, Chem. Rev., 101, 757
(2001).
2
Table 1. Synthesis of optically active 6 using several alkoxides
Entry M(OiPr)n (mol%)Yield/%
ee/%
Configuration
1a
2b
3b
4b
5b
6c
7d
none
69
22
92 (91)e
S
B(OiPr)3 (10)52 (32)
Sc(OiPr)3 (20)58
Ge(OiPr)4 (20)44
Sn(OiPr)4 (20)42
Ti(OiPr)4 (10)41
Zr(OiPr)4 (10)68
R
R
R
R
R
R
e
3
Some zinc thiolates are known as effective catalysts. See, E. Rijnberg,
J. T. B. H. Jastrzebski, M. D. Janssen, J. Boersma, and G. van Koten,
Tetrahedron Lett., 35, 6521 (1994); K. Fitzpatrick, R. Hulst, and R. M.
Kellogg; Tetrahedron: Asymmetry, 6, 1861 (1995); A. L. Braga, H. R.
Appelt, P. H. Schneider, O. E. D. Rodrigues, C. C. Silveira, and L. A.
Wessjohann, Tetrahedron, 57, 3291 (2001).
89
90
90
74
90
4
5
T. Mukaiyama, H. Asanuma, I. Hachiya, T. Harada, and S. Kobayashi,
Chem. Lett., 1991, 1209.
K. Soai, A. Ookawa, K. Ogawa, and T. Kaba, J. Chem. Soc., Chem.
Commun., 1987, 467; K. Soai, A. Ookawa, T. Kaba, and K. Ogawa, J. Am.
Chem. Soc., 109, 7111 (1987).
aHexane was used as a solvent. bA mixture of toluene and hexane (3 : 2)
was usedasa solvent. cAmixtureof o-xyleneandhexane(3 : 2)wasused
as a solvent. dA mixture of mesitylene and hexane (3 : 2)was used as a
solvent. e20 mol% of B(OiPr)3 was used.
6
7
8
9
G. Vermeersch, J. Marko, N. Febvay-Garot, S. Caplain, A. Couture, and A.
Lablache-Combier, Tetrahedron, 34, 2453 (1978).
B. Sjoberg, Chem. Ber., 1941, 64; G. Claeson and H.-G. Jonsson, Arkiv for
´
¨
Kemi, 1966, 247; J. T. Wrobel and E. Hejchman, Synthesis, 1987, 452.
Next, the transition states that form ethanol were calculated by
the reaction of formaldehyde with dimethylzinc in the presence of
boron alkoxide generated from 8 and B(OMe)3 (See Figure 1) . It
was assumed that this complex was formed after the ligand
exchange between dimethylzinc and boron alkoxide of 8.13 In this
structure, zinc chelated by sulfur and oxygen was located inside the
complex, and migration of methyl group proceeded via 4-
membered ring transition structure. On the other hand, boron was
coordinated with oxygen in zinc alkoxide of 8 to form stable 4-
membered ring structure which included two oxygens and two
metallic species.
M. Yamakawa and R. Noyori, J. Am. Chem. Soc., 117, 6327 (1995); M.
Yamakawa and R. Noyori, Organometallics, 18, 128 (1999).
B. Goldfuss, M. Steigelmann, S. I. Khan, and K. N. Houk, J. Org. Chem., 65,
´
`
77 (2000), and references cited therein; J. Vazquez, M. A. Pericas, F.
Maseras, and A. Lledos, J. Org. Chem., 65, 7303 (2000), and references cited
´
therein. Recently, Norrby et al. found other transition states. See, T.
Ramussen and P. Norrby, J. Am. Chem. Soc., 123, 2464 (2001).
10 All calculations were performed at B3LYP/LAV3Pꢀꢀ(6-31Gꢀꢀ)//HF/3-21Gꢀ
level with the program package TITAN 1.0.1 of Schrodinger, Inc. and
¨
Wavefunction, Inc.
11 Some metal alkoxides of ((S)-pyrrolidin-2-yl)diphenylmethanol, an analo-
gue of 3, were utilized for enantioselective reduction of ketones with borane-
dimethyl sulfide complex. T. Yanagi, K. Kikuchi, H. Takeuchi, T. Ishikawa,
T. Nishimura, and T. Kamijo, Chem. Lett., 1999, 1203.
12
A typical experimental procedure is described for the reaction of
benzaldehyde with diethylzinc in the presence of 10 mol% of boron alkoxide
of 4; to a solution of 4 (56.4 mg, 0.209 mmol)in toluene (2.0 mL)was added
tri-i-propyl borate (0.025 mL, 0.11 mmol). The reaction mixture was
refluxed for 2 h, a solution of diethylzinc in hexane (1.0 M, 2.2 mL,
2.2 mmol)was added at À78 ꢁC. After the reaction mixture was stirred for
1 h, a solution of benzaldehyde (101.1 mg, 0.953 mmol)in toluene (1.2 mL)
was added at À78 ꢁC. The reaction mixture was stirred for 20 h at 0 ꢁC and
then 1 M hydrochloric acid was added. Usual work up and purification of the
mixture by TLC on silica gel afforded 68.8 mg (52%)of 1-phenylpropanol
(6) . R)(-6: HPLC (CHIRALCEL OD-H, iPrOH=hexane ¼ 1=39,
flow rate ¼ 0:5 mL/min): tR ¼ 21:2 min (96.0%), tR ¼ 24:4 min (4.0%).
Figure 1. Calculated transition structure forming ethanol by meth-
ylation of formaldehyde. Some hydrogens have been omitted for clarity.
Several examples of the synthesis of optically active secondary
alcohols via the reaction of the corresponding aldehydes with
diethylzinc using 20 mol% of 4 and 10 mol% of B(OiPr)3 are shown
13 Ohno and Kobayashi et al. and Seebach et al. suggested the structure of
complexes generated from their ligands, Ti(OiPr)4 and diethylzinc. See,
references sited in ref. 2.