Chiral Ti(IV) complexes of hexadentate Schiff bases as precatalysts for the asymmetric addition of TMSCN to aldehydes and the ring opening of cyclohexene oxide

Article abstract of DOI:10.1016/j.tetasy.2006.08.009

Chiral dinuclear titanium(IV) complexes (generated in situ from hexadentate Schiff bases and titanium tetra-isopropoxide) have been found to be more effective catalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes and the ring openin

Full text of DOI:10.1016/j.tetasy.2006.08.009

Tetrahedron: Asymmetry 17 (2006) 2328–2333
Chiral Ti(IV) complexes of hexadentate Schiff bases
as precatalysts for the asymmetric addition of TMSCN
to aldehydes and the ring opening of cyclohexene oxide
Yuri N. Belokon,a,* Denis Chusov,a Dmitry A. Borkin,a Lidia V. Yashkina,a
Andrey V. Dmitriev,a Dmitry Katayeva and Michael Northb
aA.N. Nesmeyanov Institute of Organo-Element Compounds, Russian Academy of Science, Vavilov 28, 117813 Moscow, Russia
bSchool of Natural Sciences, Bedson Building, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
Received 10 July 2006; accepted 11 August 2006
Available online 22 September 2006
Abstract—Chiral dinuclear titanium(IV) complexes (generated in situ from hexadentate Schiff bases and titanium tetra-isopropoxide)
have been found to be more effective catalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes and the ring opening
of cyclohexene oxide than their mononuclear analogues. The best results were obtained for benzaldehyde (86% enantiomeric excess) and
cyclohexene oxide (89% enantiomeric excess).
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
nism of the catalysis by the coordinatively saturated
systems incorporating an interaction of the bridging oxy-
gen atom with the aldehyde carbonyl group.5d We believed
that the use of formally unsaturated catalytically active
dinuclear complexes would broaden the scope of their
application whilst retaining the advantages of the dinuclear
catalysis.
The design and use of homo- and heterometallic poly-
nuclear chiral Lewis acid catalysts for asymmetric catalysis
is a rapidly developing area.1 A simple mixing of several
single-site chiral catalysts can be extremely successful, lead-
ing to efficient heterobimetallic catalysts, as was the case
with Shibasaki’s catalyst for Michael addition reactions.2
Nevertheless, the rational design of chiral ligands capable
of supporting two Lewis acid sites rigidly oriented in space
seems to be more straightforward. Trost’s dinuclear Zn-
catalysts for aldol condensations3 and mono and dinuclear
catalysts for asymmetric binaphthol synthesis4 are success-
ful examples of the latter approach.
Herein, we report on the use of chiral binuclear Ti com-
plexes of hexadentate Schiff bases of (S)-valinol and both
(S)- and (R)-binaphthol derived salicylaldehydes 1 and 2,
as precatalysts for the asymmetric addition of trimethylsilyl
cyanide to aldehydes and the ring opening of cyclohexene
oxide. The Schiff bases of biphenol derived salicylaldehyde
3, 2,4-di-tert-butylsalicylaldehyde 4 and salicyladehyde 5,
combined with (S)-valinol, were also prepared and tested
as catalysts for the addition of trimethylsilyl cyanide to
benzaldehyde, for comparison purposes.
Some of us have developed highly efficient homobinuclear
Ti based5a and heteronuclear Ti/V mixed5b chiral salen cat-
alysts for the asymmetric addition of trimethylsilyl cyanide
to aldehydes and ketones. Both catalytic metal sites were
held together in space by an oxygen atom bridge, which
was found to be necessary for the catalytic activity of the
binuclear system.5c Unfortunately, those complexes were
not effective for other asymmetric C–C bond forming reac-
tions. One reason for this seemed to be the specific mecha-
2. Results and discussion
The synthesis of both (S)- and (R)-2,20-diformyl-binaph-
thols and the corresponding 2,20-diformyl-biphenols was
achieved in three steps following the literature proce-
dures,6a,b as illustrated in Scheme 1 for ligand 2. Further
condensation of the aldehydes with (S)-valinol furnished
*
Corresponding author. Tel.: +7 495 135 6356; fax: +7 495 135 5085;
e-mail: yubel@ineos.ac.ru
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.08.009

Y. N. Belokon et al. / Tetrahedron: Asymmetry 17 (2006) 2328–2333
2329
OSiMe3
CN
O
+ Me3SiCN Ti(1-5), CH2Cl2, 4 h, 6 oC
NaH/ DMF /
MOMCl
R2
OH
OH
OMOM
OMOM
R1
R2
R1
Scheme 2. Addition of trimethylsilyl cyanide to carbonyl compounds
catalysed by the titanium complexes of ligands 1–5.
BuLi /
out for 4 h in CH2Cl2 at 6 ꢁC using 20 mol % of the Ti-
Schiff base complex. The concentration of the precatalyst
was varied from 8.0 · 10ꢀ2 to 9.0 · 10ꢀ3 M. Under these
conditions, all the reactions went to completion. The
results of these experiments are summarised in Table 1.
TMEDA /
DMF
CHO
CHO
OH
OH
OMOM
OMOM
HCl, THF
Table 1. Addition of trimethylsilyl cyanide to benzaldehyde catalysed by
the titanium complexes of ligands 1–5a
Run
Ligand
Complex concentration
Product ee (%)
(configuration)b
CHO
CHO
(M · 10ꢀ2
)
(S)-valinol
1
2
3
4
5
5
4
3
3
2
2
1
1
8.0
1.8
8.0
4.0
0.9
4.0
1.6
4.0
0.9
46 (S)9
27 (S)
19 (R)
28 (R)
2
Scheme 1. Synthesis of hexadentate ligand 2.
5
24 (R)
6c
7c
8
85–86 (R)
85–86 (R)
23 (S)
targets 1–3 (see Scheme 1). The model monomeric ligands 4
and 5 were prepared via a literature procedure.7 The prep-
aration of the titanium complexes was carried out in situ by
mixing ligands 1–5 with titanium tetra-isopropoxide in a
1:1 molar ratio of Ti/Schiff base moieties.
9
28 (S)
a Reaction conditions: 6 ꢁC in dichloromethane for 4 h, ligands 1–3/Ti
ratio = 1:2, ligands 4–5/Ti ratio = 1:1, 20 mol % of titanium tetra-iso-
propoxide relative to benzaldehyde.
b Formation of mandelonitrile trimethylsilyl ether was essentially quanti-
tative, Ee determination was achieved by GLC on a DP-TFA-c-cD
(32 m · 0.20 mm) column.
c Average of several experiments.
N
OH
OH
N
N
The results of runs 1–3 in Table 1 indicate a reversal of the
configuration of the product with the introduction of bulky
substituents in the salicylaldehyde moiety. Thus, ligand 5
derived from unsubstituted salicyclaldehyde predominantly
produces (S)-mandelonitrile trimethylsilyl ether, whilst
ligand 4 derived from 2,4-di-tert-butylsalicylaldehyde gen-
erates an excess of (R)-mandelonitrile trimethylsilyl ether.
OH
OH
OH
OH
OH
OH
N
2
The catalyst derived from ligand 3 also formed (R)-mand-
elonitrile trimethylsilyl ether (Table 1: runs 4 and 5). The
highest enantioselectivity was achieved with the catalyst
obtained from ligand 2 (Table 1: runs 6 and 7), which pro-
duced (R)-mandelonitrile trimethylsilyl ether with up to
86% enantiomeric excess. A catalyst derived from the dia-
stereomeric ligand 1 gave (S)-mandelonitrile trimethylsilyl
ether with a low enantiomeric excess (Table 1: runs 8 and
9). These results indicate that the configurations of both
the binaphthyl unit and the valinol groups have an influ-
ence on the enantioselectivity of the reaction, and the com-
bination of (R)-binaphthyl and (S)-valinol is optimal to
maximise the asymmetric induction.
1
tBu
N
OH
N
N
OH
tBu
OH
OH
OH
OH
4
N
OH
OH
3
5
In the case of the catalyst derived from ligand 5, a two-
fold decrease in the enantiomeric excess of the product
was observed when the reaction mixture was diluted
(Table 1: runs 1 and 2). However, no concentration depen-
dence of the asymmetric efficiency of the catalysts was
The catalytic activity of the complexes was tested using the
addition of trimethylsilyl cyanide to benzaldehyde8
(Scheme 2) as a model system. The reactions were carried

2330
Y. N. Belokon et al. / Tetrahedron: Asymmetry 17 (2006) 2328–2333
observed in the case of the titanium complexes of 3 (Table
1: runs 4 and 5), 2 (Table 1: runs 6 and 7) and 1 (Table 1:
runs 8 and 9). These data are consistent with a catalyti-
cally active dinuclear complex catalysing the reaction in
the case of the catalysts derived from ligands 1–3. In con-
trast, for the catalyst derived from ligand 5, there are no
catalytically active dinuclear complexes present in the
reaction solution, although the catalysis still requires
two metal ions. Therefore, the catalysis occurs by two
mononuclear complexes acting together and the catalytic
efficiency decreases as the concentration decreases. In
the case of catalysis by the titanium complex of ligand
4, the enantiomeric excess of the mandelonitrile trimethyl-
silyl ether was found to decrease significantly with time
(Fig. 1). No such effect was observed with the correspond-
ing reactions carried out using ligand 2. This observation
is also consistent with the formation of a single type of
catalytical active complexes in the case of ligand 2, but
a time dependent formation of a manifold of complexes
with differing catalytic activities in the case of the tita-
nium complex of ligand 4.
ing ligand 4 under similar reaction conditions (Table 1:
run 3).
Further optimisation of the reaction conditions proved
that neither decreasing nor increasing the reaction temper-
ature affected the enantioselectivity observed using the
catalyst derived from ligand 2. The addition of water or
phosphine oxide10 to the reaction mixture did, however,
lead to a significant decrease in both the activity and stereo-
selectivity of the catalyst. Under the optimal reaction
conditions, two other aldehydes and acetophenone were
also substrates for the reaction, although with a lower
enantioselectivity as shown in Table 3.
Table 3. The asymmetric addition of trimethylsilyl cyanide to carbonyl
compounds catalysed by ligand 2 and titanium tetra-isopropoxidea
R1
R2
Time (h)
Yieldd (%)
ee (%)
o-Cl–C6H4
(CH3)3C
C6H5
H
H
CH3
4
7
24
100
100
36
74b
27b,c
15b
a Reaction conditions: temperature +2 to +6 ꢁC, CH2Cl2, 2:1 ratio of
Ti(Oi-Pr)4 to 2, 20 mol % of Ti(Oi-Pr)4 with respect to carbonyl
compound.
b Ee determination was by GLC on a DP-TFA-c-cD column (32 m ·
0.20 mm).
100
80
60
40
20
0
c Ee determination was carried out on the O-acetyl derivative.11
d Determined by NMR analysis.
Whilst the asymmetric addition of trimethylsilyl cyanide to
aldehydes has been extensively studied, the corresponding
reaction between trimethylsilyl cyanide and a meso-epoxide
to form a b-hydroxy-nitrile has received only scant atten-
tion. A number of achiral catalysts12 for the ring opening
of epoxides by trimethylsilyl cyanide have been reported,
and it is known that the reaction can be complicated by
the competing formation of the corresponding isocyanide13
There are, however, only two previous reports of asymmet-
ric catalysts for the asymmetric ring opening of meso-epox-
ides by trimethylsilyl cyanide. Hoveyda reported the use of
titanium-based complexes,14 whilst Jacobsen has reported
the use of lanthanide(pybox) complexes.15
10
60
110
160
210
time (minutes)
Figure 1. Time dependence of the enantiomeric excess of mandelonitrile
trimethylsilyl ether formed using the titanium catalyst of ligand 2 (squares)
and ligand 4 (circles).
The ratio of titanium to ligand 2 greatly influenced the
enantiomeric excess of the mandelonitrile trimethylsilyl
ether, as shown by the data in Table 2. As expected for
the formation of a bimetallic complex, a titanium to ligand
ratio of 2:1 gave the highest enantioselectivity (Table 2, run
1). Decreasing the titanium to ligand ratio to 1:1 resulted in
a dramatic decrease in the enantiomeric excess of the prod-
uct (Table 2: runs 2–4). Significantly, under these condi-
tions, the enantiomeric excess of the product was around
20%, which is similar to that obtained using mononucleat-
The ring opening of cyclohexene oxide with trimethylsilyl
cyanide was also catalysed by the dinuclear titanium com-
plex derived from ligand 2 at a substrate to catalyst ratio of
10:1, as shown in Scheme 3. At 4 ꢁC in dichloromethane,
the b-hydroxy nitrile was obtained in a 60% yield after
1
72 h. The H and 13C NMR spectra of the product con-
firmed that the product was cyanide rather than the iso-
cyanide13 and the specific rotation and chiral GC of the
product corresponded to 89% enantiomeric excess. In con-
trast, the use of a 1:1 mixture of titanium tetra-isopropox-
ide and ligand 4 gave a racemic product for this reaction.
Table 2. The effect of changing the titanium to ligand 2 ratio on the
enantiomeric excess of the mandelonitrile trimethylsilyl ethera
Run
Ti(Oi-Pr)4/2
ee (%)
Ti(OiPr)4 / 2 (10 mol%),
CH2Cl2, 4 oC, 72 h
OSiMe3
1
2
3
4
2:1
1.2:1
1:1
0.8:1
86
49
15
24
+ Me SiCN
O
3
CN
a Experimental conditions were the same as for Table 1 except that the
concentration of 2 was kept at 1.8 · 10ꢀ2 M.
Scheme 3. Addition of trimethylsilyl cyanide to cyclohexene oxide
catalysed by the titanium complex of ligand 2.

Y. N. Belokon et al. / Tetrahedron: Asymmetry 17 (2006) 2328–2333
2331
3. Conclusions
2H), 7.14–7.26 (m, 6H), 7.35 (d, J 8.9 Hz, 2H), 7.58 (d,
J 9.0 Hz, 2H), 7.88 (d, J 8.1 Hz, 2H), 7.96 (d, J 9.0 Hz,
2H); 13C NMR (75 MHz, CDCl3) d 55.8, 95.1, 117.2,
121.2, 124.0, 125.5, 126.3, 127.8, 129.4, 129.8, 134.0, 152.6.
A new family of chiral Schiff base ligands has been con-
structed. When complexed to titanium to form binuclear
species, enantioselectivities of up to 86% have been
achieved in the asymmetric addition of trimethylsilyl cya-
nide to aldehydes. The ligands, which can form binuclear
complexes are significantly more enantioselective than pre-
viously reported similar ligands, which can only form
mononuclear complexes. The stereoselective ring opening
of a meso-epoxide with trimethylsilyl cyanide, catalysed
by the binuclear complex, is a novel extension of the cata-
lyst reactivity.
4.2.3.
(S)-2,20-Bis-(methoxymethoxy)-1,10-binaphthyl.6b
The title compound was prepared in the same way as the
(R)-enantiomer starting from (S)-BINOL.
4.3. Synthesis of dialdehydes
4.3.1. 3,30-Diformyl-2,20-bis(methoxymethoxy)biphenyl.6a
Prepared by the literature procedure6a in 57% yield as
colourless crystals. Rf = 0.13 (hexane/ethyl acetate 5:1);
1H NMR (300 MHz, CDCl3) d 3.15 (s, 6H), 4.81 (s, 4H),
7.37 (dd, J 0.9, 8.4 Hz, 2H), 7.67 (dd, J 1.8, 7.5 Hz, 2H),
7.93 (dd, J 1.8, 7.8 Hz, 2H), 10.43 (s, 2H); 13C NMR
(75 MHz, CDCl3) d 57.6, 101.2, 125.0, 129.2, 130.3,
132.7, 138.0, 158.2, 190.3.
4. Experimental
4.1. General
Optical rotations were measured on a Perkin–Elmer 241
polarimeter and specific rotations are reported as follows:
4.3.2. (R)-3,30-Diformyl-2,20-bis(methoxymethoxy)-1,10-bi-
naphthyl.6a Prepared by the literature procedure6a in
68% yield as white crystals. Rf = 0.17 (hexane/ethyl acetate
4:1); 1H NMR (300 MHz, CDCl3) d 2.87 (s, 6H), 4.69 (d, J
6.6 Hz, 2H), 4.73 (d, J 6.3 Hz, 2H), 7.22 (d, J 8.7 Hz, 2H),
7.42 (ddd, J 0.9, 7.5, 8.1 Hz, 2H), 7.52 (ddd, J 0.9, 6.9,
7.8 Hz, 2H), 8.08 (d, J 8.1 Hz, 2H), 8.62 (s, 2H), 10.55 (s,
2H); 13C NMR (75 MHz, CDCl3) d 57.0, 100.6, 125.9,
126.1, 126.3, 128.8, 129.6, 130.1, 130.3, 132.29, 136.7,
154.0, 190.6.
T
½aꢁk (concentration in g/100 mL, solvent). Enantiomeric
excesses were determined by HPLC analysis using a
Kromasil column (0.25 m · 46 mm) with UV detection at
254 nm or by GC analysis using a DP-TFA-c-cD column
(32 m · 0.20 mm).
1H NMR spectra were recorded on a Bruker Avance 300
(300 MHz) spectrometer and are reported in parts per mil-
lion using the solvent as the internal standard. The data are
reported as s = singlet, d = doublet, dd = double doublet,
t = triplet, q = quartet, m = multiplet, b = broad; coupling
constant(s) in Hertz, integration. Proton-decoupled 13C
NMR spectra were recorded on a Bruker Avance 300
(75.5 MHz) spectrometer and are reported in parts per mil-
lion using the solvent as an internal standard. The melting
points were determined in open capillary tubes and are
uncorrected. Elemental analyses were carried out by the
laboratory of Microanalysis of INEOS RAS.
4.3.3. (S)-3,30-Diformyl-2,20-bis(methoxymethoxy)-1,10-bi-
naphthyl.6a The title compound was prepared by the liter-
ature procedure6a as described for the (R)-enantiomer in
Section 4.3.2.
4.4. Deprotection of MOM-groups
4.4.1. 3,30-Diformyl-2,20-dihydroxy-1,10-biphenyl.6a Prep-
ared by the literature procedure6c in 88% yield as yellow
crystals. Rf = 0.26 (hexane/ethyl acetate 6:1); 1H NMR
(300 MHz, CDCl3) d 7.11–7.15 (m, 2H), 7.32–7.36 (m,
4H), 7.93–7.97 (m, 2H), 8.31 (s, 2H), 10.13 (s, 2H), 10.53
(s, 2H). Anal. Calcd for C14H10O4: C, 69.42; H, 4.16.
Found: C, 69.41; H, 4.11.
THF was freshly distilled from sodium/benzophenone un-
der argon. Dichloromethane was distilled under argon
˚
from P2O5 and dried over 3 A molecular sieves (7.4 g sieves
on 7 mL dichloromethane). Benzaldehyde was distilled in
vacuo under argon prior to use. All reagents were pur-
chased from Aldrich or Acros, and used without purifica-
tion unless otherwise stated.
4.4.2.
(R)-3,30-Diformyl-2,20-dihydroxy-1,10-binaphthyl.
Prepared by the literature procedure6c in a quantitative
4.2. Synthesis of methoxymethyl protected phenols
yield as yellow crystals. Rf = 0.35 (hexane/ethyl ace-
25
tate 4:1); Mp 285 ꢁC; ½aꢁD ¼ þ249:5 (c 0.8, CH2Cl2) {lit.6a
20
4.2.1. 2,20-Bis-(methoxymethoxy)biphenyl.6a Prepared by
½aꢁD ¼ ꢀ254 (c 0.3, CH2Cl2) for (S)-enantiomer}; 1H NMR
the literature procedure6a in 51% yield as a colourless oil.
(300 MHz, CDCl3)
d
7.11–7.15 (m, 2H), 7.32–
1
Rf = 0.4 (hexane/ethyl acetate 5:1); H NMR (300 MHz,
7.36 (m, 4H), 7.93–7.97 (m, 2H), 8.31 (s, 2H), 10.13
(s, 2H),10.53 (s, 2H). Ee = 98.8% determined by HPLC
analysis (Kromasil 0.46 cm · 25 cm, eluent hexane/iso-
propyl alcohol 100/4, 1 mL/min, UV detector 254 nm)
tR(major) = 22.8, tR(minor) = 20.8 min.
CDCl3) d 3.35 (s, 6H), 5.08 (s, 4H), 7.06–7.11 (m, 2H),
7.21–7.36 (m, 6H); 13C NMR (75 MHz, CDCl3) d 55.8,
95.2, 115.6, 121.8, 128.7, 131.53.
4.2.2.
(R)-2,20-Bis-(methoxymethoxy)-1,10-binaphthyl.6b
Prepared by the literature procedure6b in 85% yield as
4.4.3.
(S)-3,30-Diformyl-2,20-dihydroxy-1,10-binaphthyl.6a
colourless crystals. Rf = 0.17 (hexane/ethyl acetate 3:1);
Prepared by the literature procedure6c in quantitative yield as
25
25
1
½aꢁD ¼ þ98 (c 1, THF); H NMR (300 MHz, CDCl3) d
yellow crystals. ½aꢁD ¼ ꢀ267:0 (c 0.5, CH2Cl2) {lit.6a
20
3.15 (s, 6H), 4.98 (d, J 6.6 Hz, 2H), 5.09 (d, J 6.6 Hz,
½aꢁD ¼ ꢀ254 (c 0.3, CH2Cl2)}. Ee = 100% determined by

2332
Y. N. Belokon et al. / Tetrahedron: Asymmetry 17 (2006) 2328–2333
HPLC analysis (Kromasil 0.46 cm · 25 cm, eluent hexane/
iso-propyl alcohol 100/4, 1 mL/min, UV detector 254 nm)
tR(major) = 20.8, tR(minor) = 22.8.
Calcd for C20H33NO2: C, 75.19 H, 10.41, N, 4.38. Found:
C, 75.04; H, 10.41, N, 4.37.
4.5.5. (S)-2-(N-Salicylideneamino)-3-methyl-butan-1-ol 5.7
Prepared by a modification of the literature procedure.7
A solution of (S)-2-amino-3-methyl-1-butanol16 (0.10 g,
0.97 mmol) in ethanol (5 mL) and benzene (5 mL) was
added to salicylaldehyde (0.12 g, 0.98 mmol). The reaction
mixture was heated in a Dean–Stark apparatus for 10 h.
The solution was concentrated and the residue purified
by column chromatography on aluminium oxide eluting
with hexane/dichloromethane/ethanol (20:5:1) to give the
4.5. Synthesis of ligands
4.5.1. Compound 3. A solution of (S)-2-amino-3-methyl-
1-butanol16 (Ee = 96.6% determined by GC analysis of
the trifluoroacetyl derivative) (0.52 g, 5.0 mmol) in ethanol
(5 mL) and benzene (5 mL) was added to 3,30-diformyl-
2,20-dihydroxy-1,10-biphenyl (0.61 g, 2.5 mmol) and the
reaction mixture was heated in a Dean–Stark apparatus
for 10 h. The solution was concentrated and the residue
purified by column chromatography on aluminium oxide
eluting with hexane/dichloromethane/ethanol (20:5:1) to
title compound (0.19 g, 85%) as yellow crystals. Mp 104–
25
106 ꢁC; ½aꢁD ¼ ꢀ25:0 (c 0.8, MeOH) [lit.7 = ꢀ26.2 (c
1
1, MeOH)]; H NMR (300 MHz, CDCl3) d 0.95 (dd, J
give compound 3 (0.98 g, 95%) as yellow crystals.
4.2, 6.9 Hz, 6H), 1.45–1.70 (br s, 1H), 1.89–2.01 (m, 1H),
3.02–3.09 (m, 1H), 3.70–3.90 (m, 2H), 6.85–7.00 (m, 2H),
7.26–7.36 (m, 2H), 8.36 (s, 1H), 13.20–13.50 (br s, 1H).
Anal. Calcd for C12H17NO2: C, 69.54; H, 8.27; N, 6.76.
Found: C, 69.99; H, 7.80; N, 6.75.
25
½aꢁD ¼ ꢀ143:8 (c 1, MeOH); 1H NMR (CDCl3) d 0.93
(dd, J 6.6, 7.8 Hz, 12H), 1.86–1.91 (m, 2H), 3.05–3.10 (m,
2H), 3.76–3.82 (m, 4H), 6.96–7.04 (m, 2H), 7.34 (dd, J
1.8, 7.5 Hz, 2H), 7.44 (dd, J 1.8, 7.5 Hz, 2H), 8.43 (s,
2H), 14.00 (br s, 2H). Anal. Calcd for C24H32N2O4: C,
69.88; H, 7.82; N, 6.79. Found: C, 69.99; H, 7.80; N, 6.75.
4.6. Catalytic reactions
4.5.2. Compound 2. A solution of (S)-2-amino-3-methyl-
1-butanol16 (Ee = 96.6% determined by GC analysis of
the trifluoroacetyl derivative) (0.19 g, 1.8 mmol) in etha-
nol (5 mL) and benzene (5 mL) was added to (R)-3,30-di-
formyl-2,20-dihydroxy-1,10-binaphthyl (0.31 g, 0.91 mmol).
The reaction mixture was heated in a Dean–Stark appara-
tus for 10 h. The solution was concentrated and the resi-
due purified by column chromatography on aluminium
oxide eluting with hexane/dichloromethane/ethanol
(20:5:1), then the eluent was further purified by chroma-
4.6.1. Asymmetric cyanohydrin trimethylsilyl ether synthe-
sis. The following procedure using benzaldehyde is a rep-
resentative of that used with all carbonyl compounds:
Ti(Oi-Pr)4 (28 lL, 94 lmol) was added to a solution of
ligand (47 lmol) in dichloromethane (1 mL) (containing
0.00046 mass % H2O). The reaction mixture was stirred
for 2 h, then freshly distilled benzaldehyde (48 lL,
471 lmol) was added. The mixture was cooled to +1 ꢁC
and trimethylsilyl cyanide (100 lL, 750 lmol) was added.
The reaction was stirred at +1 to +6 ꢁC for 4 h, then the
solvent was evaporated and the residue purified by column
chromatography on silica gel eluting with hexane/ethyl
acetate (5:1) to give mandelonitrile trimethylsilyl ether.
tography on Sephadex LH-20 eluting with benzene to give
25
compound 2 (0.44 g, 95%) as a red solid. ½aꢁD ¼ ꢀ139:8 (c
1
1, CHCl3); H NMR (CDCl3) d 0.91 (dd, J 6.6, 7.8 Hz,
6H), 1.80–1.90 (m, 2H), 2.30–2.80 (br m, 2H), 3.00–
3.15 (m, 2H), 3.65–3.75 (m, 4H), 7.10–7.19 (m, 2H),
7.27–7.33 (m, 4H), 7.86–7.89 (m, 2H), 7.99 (s, 2H),
8.64 (s, 2H), 13.19 (s, 2H). Anal. Calcd for
C32H36N2O4: C, 74.97; H, 7.08, N, 5.46. Found: C,
75.04; H, 7.41, N, 5.26.
4.6.2. Asymmetric ring opening of cyclohexene oxide.
Ti(Oi-Pr)4 (23.3 lL, 78 lmol) was added to a solution of
ligands (39.0 lmol) in dichloromethane (1 mL) (containing
0.00046 mass % H2O). The reaction mixture was stirred for
2 h, then cyclohexene oxide (40 lL, 390 lmol) was added.
The reaction was cooled to +1 ꢁC and trimethylsilyl cya-
nide (80 lL, 600 lmol) was added. The reaction was stirred
in an ice bath for 4 h, then kept in a refrigerator for 20 h.
The solvent was evaporated and the residue purified by
column chromatography on silica gel eluting with hex-
4.5.3. Compound 1. The title compound was prepared as
described in Section 4.5.2 for compound 2, using (S)-3,30-
diformyl-2,20-dihydroxy-1,10-binaphthyl as the starting
25
material. ½aꢁD ¼ ꢀ163 (c 1, CHCl3).
4.5.4. (S)-2-(N-30,50-Di-tert-butylsalicylideneamino)-3-meth-
yl-butan-1-ol. A solution of (S)-2-amino-3-methyl-1-buta-
nol16 (0.10 g, 0.97 mmol) in ethanol (5 mL) and benzene
(5 mL) was added to 2,4-di-tert-butylsalicylaldehyde
(0.23 g, 0.97 mmol). The reaction mixture heated in a
Dean–Stark apparatus for 10 h. The solution was concen-
trated and the residue purified by column chromatography
on aluminium oxide eluting with hexane/dichloromethane/
ane/ethyl acetate (5:1) to give (1R,2S)-trans-2-hydroxy-
25
1-cyanocyclohexene in 60% yield as a viscous oil. ½aꢁD
¼
25
þ28:0 (c 0.4, CH2Cl2) {lit.,15 ½aꢁD ¼ ꢀ38:0 (c 4, CH2Cl2)
for the (1S,2R)-isomer}; 1H NMR (CDCl3) d 0.17 (s,
9H), 1.25–1.33 (m, 3H), 1.55–1.75 (m, 3H), 1.90–2.07 (m,
1H), 2.08–2.11 (m, 1H), 2.38–2.44 (m, 1H), 3.64–3.70 (m,
1H); 13C NMR (CDCl3) d 0.18, 23.3, 23.9, 28.2, 34.7,
37.7, 71.1, 121.6.
ethanol (20:5:1) to give the title compound (0.30 g, 86%)
25
as yellow crystals. ½aꢁD ¼ ꢀ33:3 (c 0.78, MeOH); 1H
Acknowledgements
NMR (300 MHz, CDCl3) d 0.97 (dd, J 3.9, 9.6 Hz 6H),
1.32 (s, 9H), 1.45 (s, 9H), 1.85–2.05 (m, 1H), 2.99–3.07
(m, 1H), 3.70–3.90 (m, 2H), 7.13 (d, J 2.4 Hz 1H), 7.40
(d, J 2.4 Hz 1H), 8.38 (s, 1H), 13.40–13.70 (br s, 1H). Anal.
We thank INTAS (05-1000008-7822) and RFBR (05-03-
32243a) for financial support. The use of the EPSRC’s

Y. N. Belokon et al. / Tetrahedron: Asymmetry 17 (2006) 2328–2333
2333
Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 2329–
2330; (c) DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2001,
3, 1641–1644.
Chemical Database Service at Daresbury is also gratefully
acknowledged.
7. Hayashi, M.; Miyamoto, Y.; Inoue, T.; Oguni, N. J. Org.
Chem. 1993, 58, 1515–1522.
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