Enantioselective trimethylsilylcyanation of aldehydes catalyzed by chiral lanthanoid alkoxides

Article abstract of DOI:10.1039/a802509f

The first example of enantioselective trimethylsilylcyanation of aldehydes catalyzed by chiral binaphthol and binaphthol-modified lanthanum alkoxides has been achieved, in which an obvious effect of substituents at the 3,3′-positions of BINOL on the enantioselectivity was observed and 3,3′-bis(methoxyethyl)-BINOL had the advantage over simple BINOL to give (S)-products in excellent yields with 73% ee.

Full text of DOI:10.1039/a802509f

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Enantioselective trimethylsilylcyanation of aldehydes catalyzed by
chiral lanthanoid alkoxides
Changtao Qian,* Chengjian Zhu and Taisheng Huang
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Fenglin Lu, Shanghai, 200032, China
The first example of enantioselective trimethylsilyl-
cyanation of aldehydes catalyzed by chiral binaphthol
and binaphthol-modified lanthanum alkoxides has been
achieved, in which an obvious effect of substituents at
the 3,3Ј-positions of BINOL on the enantioselectivity
was observed and 3,3Ј-bis(methoxyethyl)-BINOL had the
OH
OMOM
OMOM
a
OH
advantage over simple BINOL to give (S)-products in
excellent yields with 73% ee.
(S )-1
(S )-2
b
Lanthanide reagents have attracted much attention recently
because of their potential use in organic synthesis.1 Especially
of interest is their use in catalytic asymmetric reactions. There
are a few reports on successful catalytic asymmetric C᎐C
OMe
OMe
OH
bond forming reactions catalyzed by a lanthanide complex.2
OMOM
OMOM
OMOM
c
OMOM
Optically active cyanohydrins are an important class of
versatile intermediates in organic synthesis and hence much
effort has currently been directed towards the development of
OH
enantioselective catalysts for cyanosilylation of aldehydes.3
(S )-4
(S )-3
However, to the best of our knowledge, no chiral lanthanide
complex has yet been successfully applied to this asymmetric
d
reaction. Here we wish to report the first example of enantio-
selective trimethylsilylcyanation of aldehydes catalyzed by
chiral lanthanoid alkoxides.
OMe
OMe
OH
The readily obtainable (S)-BINOL 1, (S)-3,3Ј-bis(trimethyl-
silyl)-BINOL,4 (S)-3,3Ј-diphenyl-BINOL5 and a new chiral
OH
ligand, (S)-3,3Ј-bis(methoxyethyl)-BINOL 5 which we synthes-
ised, were chosen as chiral auxiliaries. (S)-3,3Ј-Bis(methoxy-
ethyl)-BINOL 5 was conveniently synthesized as a colorless
(S )-5
solid in a reasonable total yield (36.6%) from (S)-BINOL by
ring-opening of ethylene oxide with the dilithium salt of 2,
followed by sequential methylation of the hydroxy groups of
the resulting ring-opened product (3) with MeI, and demeth-
oxymethylation with a trace of HCl (Scheme 1).
Scheme
1
Preparation of (S)-3,3Ј-bis(methoxyethyl)-BINOL 5.
Reagents and conditions: a: (i) NaH, rt, (ii) ClCH2OCH3; b: (i) 3 equiv.
BunLi, (ii) ethylene oxide; c: NaH, MeI; d: trace HCl, MeOH, 60 ЊC.
Table 1 The effect of solvents on the enantioselectivity of the asym-
Treatment of (S)-BINOL with 1.5 equiv. of La(OBut)3 in
dichloromethane gave a clear solution containing a catalytically
active species for the asymmetric addition of trimethylsilyl
cyanide to benzaldehyde. The possible structure of the chiral
lanthanum catalyst is shown in Scheme 2. However, the enantio-
selectivity of the catalyst was low. Thus, use of 10 mol% of the
catalyst afforded (S)-mandelonitrile after 10 h at Ϫ78 ЊC with
only 27% ee (88% yield). The presence of a little La(OBut)3 in
the catalyst system was thought to be mainly responsible for the
lower enantioselectivity. In accord with this assumption, a
remarkable increase in the enantioselectivity was observed
when an improved catalyst preparation procedure6 was used,
which ensured that no trace amounts of La(OBut)3 remained.
Thus trimethylsilylcyanation of benzaldehyde in the presence
of 10 mol% of the improved catalyst gave (S)-mandelonitrile in
81% yield with 49% ee. The activity and enantioselectivity of
the catalyst could be adjusted for the reaction by tuning the
donor or acceptor ability of the solvents used. Tetrahydrofuran
gave a racemic product and dichloromethane proved to be
the most favourable solvent for the enantioselectivity of the
reaction (Table 1).
metric trimethylsilylcyanation of benzaldehydea (10 mol% catalyst)
Entry
Solvent
Time/h
Yield (%)
ee (%)b (confign.c)
1
2
3
4
CH2Cl2
CH2Cl2
THF
10
10
6
88
81
90
65
27d (S)
49 (S)
0
Toluene
10
40 (S)
a At Ϫ78 ЊC. b Determined by H NMR of the corresponding MTPA
esters. c Determined by comparison of optical rotations with literature
values.3b d A little La(OBut)3 may be present.
1
the conditions which had been optimized for the Me3SiCN
addition to benzaldehyde [eqn. (1)]. As summarized in Table 2,
OH
H
chiral lanthanum catalyst (10 mol%)
CH2Cl2, –78 °C, 10 h
(eqn. 1)
RCHO + Me3SiCN
CN
R
a variety of aldehydes including substituted aromatic and ali-
phatic aldehydes were silylcyanated in good to excellent yields
with modest enantioselectivity. The enantiomeric excesses were
determined by 1H NMR of the corresponding α-methoxy-
α-(trifluoromethyl)-phenylacetic esters (MTPA). We found that
Trimethylsilylcyanations of several aldehydes were investi-
gated in the presence of the various kinds of chiral ligands and
J. Chem. Soc., Perkin Trans. 1, 1998
2131

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Table 2 Enantioselective trimethylsilylcyanation of aldehydes catalyzed by different catalysts
R
Catalysta
Yield (%)
Ee (%)b (confign.c)
R
Catalysta
Yield (%)
Ee (%)b (confign.c)
Ph
I
II
III
IV
I
81
86
84
77
79
83
82
80
56
49 (S)
36 (S)
32 (S)
71 (S)
58 (S)
40 (S)
34 (S)
73 (S)
63 (S)
PhCH2CH2
I
II
III
IV
I
82
85
87
80
83
92
85
82
76
52 (S)
27 (S)
19 (S)
66 (S)
23 (S)
7 (S)
11 (S)
48 (S)
54 (S)
p-CH3C6H4
p-ClC6H4
II
II
III
IV
IV
III
IV
IV
p-CH3OC6H4
c-C6H11
a Catalysts were prepared according to the improved preparation procedure.6 b Ee value was determined by 1H NMR of the corresponding MTPA
ester. c Absolute configuration determined by comparison of the optical rotation with literature values.3b,3e
proved to be superior to simple bidentate BINOL to give
R
R
O
R
(S)-α-hydroxy nitriles in good yields with higher optical purities
(73% ee). Further studies on the asymmetric reaction are now
in progress in our research group.
*
R
R
R
R
O
OH
OH
O
O
O
O
CH2Cl2, rt, 12 h
La(OBut)3+
La
La
*
chiral lanthanum catalyst
References
R
Catalyst I: R = H
Catalyst II: R = SiMe3
Catalyst III: R = Ph
Catalyst IV: R = CH2CH2OCH3
1 For recent reviews, see: (a) G. A. Molander, Chem. Rev., 1992, 92, 29;
(b) H. B. Kagan and J. L. Nancy, Tetrahedron, 1986, 42, 6573.
2 (a) T. Yokomatsu, T. Yamagishi and S. Shibuya, Tetrahedron:
Asymmetry, 1993, 4, 1779; (b) H. Sasai, T. Arai and M. Shibasaki,
J. Am. Chem. Soc., 1994, 116, 1571; (c) S. Kobayashi and H. Ishitani,
J. Am. Chem. Soc., 1994, 116, 4083; (d) K. Uotsu, H. Sasai and
M. Shibasaki, Tetrahedron: Asymmetry, 1995, 6, 71; (e) H. Sasai,
S. Arai, Y. Tahara and M. Shibasaki, J. Org. Chem., 1995, 60, 6656;
( f ) F. Zhang, C. Yip and A. S. C. Chan, Tetrahedron: Asymmetry,
1996, 7, 2463; (g) I. E. Marko, G. R. Evan, P. Seres, I. Chelle and
Z. Janousek, Pure Appl. Chem., 1996, 68, 113.
3 (a) K. Narasaka, T. Yamada and H. Minamikawa, Chem. Lett., 1987,
2073; (b) H. Minamikawa, S. Hayakawa, T. Yamada, N. Iwasawa and
K. Narasaka, Bull. Chem. Soc. Jpn., 1988, 61, 4379; (c) M. Hayashi,
T. Matsuda and N. Oguni, J. Chem. Soc., Perkin Trans. 1, 1992, 3135;
(d) M. Hayashi, Y. Miyamoto, T. Inoue and N. Oguni, J. Org. Chem.,
1993, 58, 1515; (e) M. Hayashi, T. Inoue, Y. Miyamato and N. Oguni,
Tetrahedron, 1994, 50, 4385; ( f ) M. Hayashi, Y. Miyamoto, T. Inoue
and N. Oguni, J. Chem. Soc., Chem. Commun., 1991, 1752; (g) Y. Jiang,
X. Zhou, W. Hu, L. Wu and A. Mi, Tetrahedron: Asymmetry, 1995,
6, 405.
Scheme 2 Preparation of chiral lanthanum catalyst
the substituents of BINOL had a significant effect on the
enantioselectivity of the asymmetric trimethylsilylcyanation
of aldehydes. This is exemplified by a comparison of catalysts
I, II, III and IV. Sterically hindered ligands such as 3,3Ј-
bis(trimethylsilyl)-BINOL and 3,3Ј-diphenyl-BINOL produced
α-hydroxy nitriles with lower enantioselectivity than simple
BINOL 1. As expected, a remarkable increase in the enantio-
selectivity was achieved when the tetradentate ligand 5, (S)-
3,3Ј-bis(methoxyethyl)-BINOL, was applied. Chiral catalyst IV
afforded the products in 48–73% ee, which was higher than that
provided by simple BINOL (23–58%). Although the relation-
ship between the substituents of BINOL and the enantio-
selectivity is not completely clear at present, certain features
of the substituents seem to be responsible for the extent of
enantioselection. In general, sterically larger 3,3Ј-substituents
of BINOL induced a negative effect on the enantioselectivity of
the reaction, which was in sharp contrast with that in the case
of main-group and transition metals. We thought that this
should be related to the predominant electrostatic interaction
between lanthanide ion and ligand, which makes steric factors
extremely important in determining the reactivities and struc-
tures of lanthanide complexes. Because of the large radius of
the lanthanide ion, the enhanced steric hindrance of the ligand
would lengthen the M᎐O bonds of lanthanide oxides, make the
asymmetric space looser and as a result lead to reduced
asymmetric induction. On the other hand, coordination
between the oxygen atoms of ortho-substituents and lanthanum
ions was beneficial and produced a favorable steric environment
and improved the asymmetric induction; furthermore, the
coordination bond was indicated by the following two factors in
Catalyst IV. (i) C-O-C absorption frequency of substituents in
Catalyst IV appeared at 1097 cmϪ1, which was a shift of 9 cmϪ1
to low wavenumber relative to the corresponding absorption
(1106 cmϪ1) of the ligand; (ii) the 1H NMR signals of methoxy
groups of substituents in Catalyst IV appeared at 3.56 ppm,
which was 0.16 ppm downfield relative to the corresponding
resonance (3.40 ppm) of the ligand.7
4 P. J. Cox, W. Eang and V. Snieckus, Tetrahedron Lett., 1992, 33, 2253.
5 D. S. Lingenfelter, R. C. Helgeson and D. J. Cram, J. Org. Chem.,
1981, 46, 393.
6 An improved procedure for the preparation of chiral lanthanum
catalyst: a solution of (S)-BINOL (42.9 mg, 0.15 mmol) in CH2Cl2
was mixed with a solution of lanthanum tri-tert-butoxide (0.1 mmol)
in CH2Cl2 under Ar atmosphere in a 25 ml Schlenk flask. The mixture
was allowed to stir at room temperature for 12 h to give a yellow
solution. In order to remove the resulting ButOH completely and
ensure that all the lanthanum tri-tert-butoxide was consumed, the
solvent was removed under vacuum until a dry residue was obtained.
After the residue was dried at 50 ЊC under vacuum for 2 h, the desired
product was directly used as an asymmetric catalyst.
Representative procedure for trimethylsilylcyanation of aldehydes:
a solution of chiral binaphthol-modified lanthanum alkoxide (0.1
mmol) in dichloromethane (4 ml) was stirred for 30 min. The solution
was cooled to Ϫ78 ЊC and aldehyde (1.0 mmol) and trimethylsilyl
cyanide (1.2 mmol) were added. After stirring for 10 h at Ϫ78 ЊC
the reaction mixture was warmed to room temperature and was
quenched with 2 ml saturated aq. NH4Cl. The aqueous layer was
extracted with diethyl ether (3 × 2 ml). The combined organic layers
were dried, filtered and concentrated. The residue was treated with
1  aq. HCl in methanol, stirred for 30 min at room temp. and
solvent was removed by rotary evaporation. The adduct was purified
by column chromatography on silica gel to afford the pure desired
cyanohydrin product.
Enantioselectivities were determined by 1H NMR of the MTPA
esters.
7 B. Wang, D. Deng and C. Qian, New J. Chem., 1995, 19, 515.
In summary, we have achieved the first enantioselective
trimethylsilylcyanation of aldehydes catalysed by chiral lanthan-
oid alkoxides. Although the enantioselectivity of the present
reaction is modest, an obvious effect of substituents at the
3,3Ј-position of BINOL on the enantioselectivity was observed.
The tetradentate ligand (S)-3,3Ј-bis(methoxyethyl)-BINOL 5
Paper 8/02509F
Received 2nd April 1998
Accepted 29th May 1998
2132
J. Chem. Soc., Perkin Trans. 1, 1998