Chiral Ti(IV) complexes of hexadentate Schiff bases as precatalysts for aldehyde allylation: unusual additive effect of trimethylsilyl chloride

Article abstract of DOI:10.1016/j.tetasy.2008.01.035

Chiral dinuclear titanium(IV) complexes have been found to be more effective catalysts for the asymmetric allylation of p-nitrobenzaldehyde than their mononuclear analogues. The addition of trimethylsilyl chloride to the reaction mixture decreases the rate of the background reaction and increases the yield of the reaction catalysed by the dinuclear complex.

Full text of DOI:10.1016/j.tetasy.2008.01.035

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 459–466
Chiral Ti(IV) complexes of hexadentate Schiff bases as
precatalysts for aldehyde allylation: unusual additive effect of
trimethylsilyl chloride
Yuri N. Belokon,a,* Denis Chusov,a Dmitry A. Borkin,a Lidia V. Yashkina,a Pavel Bolotov,a
Tatiana Skrupskayaa and Michael Northb
aA.N. Nesmeyanov Institute of Organo-Element Compounds, Russian Academy of Science, 119991 Vavilov 28, Moscow, Russia
bSchool of Natural Sciences and University Research Centre in Catalysis and Intensified Processing, Bedson Building,
University of Newcastle, Newcastle Upon Tyne NE1 7RU, UK
Received 5 December 2007; accepted 29 January 2008
Abstract—Chiral dinuclear titanium(IV) complexes have been found to be more effective catalysts for the asymmetric allylation of p-
nitrobenzaldehyde than their mononuclear analogues. The addition of trimethylsilyl chloride to the reaction mixture decreases the rate
of the background reaction and increases the yield of the reaction catalysed by the dinuclear complex.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
by Maruoka and co-workers3 Previously, we described
the use of chiral bis-(salen)Ti-l-O complexes as highly effi-
cient catalysts for aldehyde cyanation.4a The kinetics of
this reaction clearly indicated the presence of two titanium
ions in the transition state of the reaction.4b The important
feature, responsible for the catalytic activity of the com-
plexes, was the presence of an oxygen bridge in the com-
plex.4c The importance of oxygen bridges for the activity
of (S)-binaphthoxytitanium complexes in the catalytic ally-
lation of aldehydes was also established by Maruoka and
co-workers3c Recently, we described the synthesis of new
hexadentate Schiff bases, their chiral binuclear complexes
with titanium(IV), and their use as precatalysts for the
asymmetric addition of trimethylsilylcyanide to aldehydes.5
An important feature of this system was a cooperative
interaction of the two oxygen-atom-bridged titanium ions.
Amongst other details, the system differed from the previ-
ously studied titanium(salen) complexes by the additional
rigidity imposed by the hexadentate framework of its
ligand.
Asymmetric allylation of aldehydes constitutes as a very
important, enantioselective C–C bond forming reaction in
a series of total syntheses.1a,b This explains why the asym-
metric allylation of aldehydes remains one of the most
important and fundamental carbonyl addition reactions
in organic synthesis. Naturally, catalytic versions of the
reaction remain the most useful.2 Unfortunately, these
reactions are usually conducted at low temperatures and
take several days to obtain reasonable chemical yields
and enantiomeric purities with some substrates. Thus, an
improvement to the asymmetric catalytic systems is still
required.
The development of chiral polynuclear complexes of metals
as precatalysts for asymmetric conversions is a rapidly
growing and promising field of catalyst research.1c,d The
potential advantages of their use are the expected enthalpy
and entropy gains in the transition state of binuclear catal-
ysed reactions, compared to the corresponding mononu-
clear catalysts. Recently, a series of chiral dinuclear
catalysts for the allylation of aldehydes were elaborated
Herein, we report the asymmetric allylation of aldehydes
promoted by hexadentate Schiff base derived binuclear tita-
nium complexes and show that the addition of trimethyl-
silyl chloride to the reaction mixture increases the yield
of the reaction product and its enantiomeric purity. We
postulate that the dissociation of the product from the
*
Corresponding author. Tel.: +7 495 135 6356; fax: +7 495 135 5085;
e-mail: yubel@ineos.ac.ru
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.01.035

460
Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
catalytic entity may be the rate limiting step of the cataly-
sed reactions.
N
N
Ti
O
Ti
O
OiPr
OiPr
O
O
OiPr
OiPr
O
O
2. Results and discussion
O
O
Ti
N
O
Ti
N
O
Ligands 1–3 were prepared as described earlier from the
corresponding racemic and enantiomerically pure binaph-
thols.5,6 Precatalysts 4–8 were prepared in situ by mixing
the corresponding ligands with 2 equiv of titanium isoprop-
oxide. The 1H NMR spectra of the resulting mixtures after
solvent removal indicated the presence of two isopropoxyl
groups for each ligand, which in turn implied the existence
of one oxygen atom bridge linking two titanium atoms.
(Ra,S ,S)-5
(Sa,S ,S)-6
N
Ti
O
N
O
O
OiPr
OiPr
The addition of allyltributyltin to benzaldehyde and p-
nitrobenzaldehyde in CH2Cl2 at ambient temperature
(Scheme 1) was studied as a model reaction. Precatalysts
4 (20 mol % of Ti(OiPr)4 with respect to the carbonyl com-
pound) produced the final product in a low yield (47%) and
ee (8%) after 24 h (Table 1, entry 1). Clearly, under the
experimental conditions, they did not show any significant
catalytic activity, as a blank control reaction produced
almost the same yield of product (45%) after 24 h (Table
1, entry 2).
O
OH
+ Ti(OiPr)4
OH
Ti
N
O
8
(Ra,R,R )-7
N
Cl
O
Ti
O
O
Cl
Cl
The catalytic activity of the mixture of diastereoisomeric
complexes 4 was greatly promoted by the addition of tri-
O
Ti
N
Cl
9
N
N
OH
OH
OH
OH
OH
OH
OH
OH
HO
CHO
1). catalyst, CH2Cl2
2). KF, MeOH
N
N
+
X = H, NO2
SnBu3
(Ra,S,S+Sa,S,S)-1
(Sa,S,S)-2
X
Scheme 1. Addition of tributylallyltin to aldehydes.
X
N
N
OH
OH
OH
methylsilyl chloride (Table 1, entries 4–10). Increasing the
amount of trimethylsilyl chloride up to a fivefold ratio rel-
ative to the aldehyde increased both the chemical yield of
the product and its enantiomeric excess (Table 1, entries
1, 4–9). The further addition of trimethylsilyl chloride up
to 10 equiv had a negative effect on the enantioselectivity
of the reaction (Table 1, entry 10).
OH
OH
OH
OH
OH
N
N
(Ra,R,R)-ent-2
(Ra,S,S)-3
A comparison of entries 11 and 12 in Table 1 indicates that
both the catalytic activity and the asymmetry inducing abil-
ity of complex 6 were much greater than those of complex
5. Thus, it was complex 6 which was responsible for the
overall catalytic activity of the mixture of precatalysts 5
and 6.
N
N
OH
OH
OH
OH
OH
OH
+
OH
OH
N
N
Under the optimal conditions, the use of precatalyst 7 led
to the formation of (R)-product, as expected, with 96%
chemical yield and 70% ee after 1.5 h (Table 1, entry 20).
+ 4Ti(OiPr)4
4

Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
Table 1. Addition of allyltributyltin to aldehydes catalysed by the titanium complexes 4–9a
461
Entry
Catalyst
R
TMSClb
Temperature
Time (h)
Yieldc (%)
eed (%)
1
2
3
4
5
6
7
8
9
10
11
12
13e
14e
15f
16g
17h
18
19
20
21
22i
23
24j
25j
4
—
—
4
4
4
4
4
4
4
5
6
4
4
4
4
8
7
7
7
7
6
6
9
9
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
p-NO2
H
0
0
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
ꢀ20
0
24
24
24
2.5
24
24
4.5
1.5
1.5
1.5
24
2.5
2.5
2.5
2
47
45
22
79
53
61
78
87
88
82
65
94
30
36
87
90
91
87
81
96
85
94
84
33
57
8 (S)
0
0
2.1
2.1
0.8
1.0
1.5
3.0
5.0
10.0
5.0
5.0
0
5.0
5.0
5.0
5.0
2.1
2.1
2.1
2.1
5.0
5.0
0
50 (S)
50 (S)
43 (S)
38 (S)
63 (S)
65 (S)
55 (S)
3 (S)
70 (S)
2 (S)
7 (S)
40 (S)
56 (S)
11 (R)
43 (R)
57 (R)
70 (R)
58 (R)
74 (S)
67 (S)
8 (S)
1
18
24
5
1.5
1.5
1
8
24
24
20
40
20
20
20
20
p-NO2
p-NO2
2.0
2 (S)
a To a solution of the catalyst (0.025 mmol, 20 mol % of titanium with respect to aldehyde) were added 1 equiv of p-nitrobenzaldehyde (0.250 mmol) and
1.5 equiv of tributylallyltin (0.333 mmol) and additive.
b The number of equivalents of trimethylsilyl chloride with respect to the aldehyde.
c Isolated yield after removing tin and purification by chromatography.
d The enantiomeric excess was determined by HPLC.
e 1.2 equiv of Hu¨nigs base was added.
f The amount of ligand used was 5 mol % and titanium isopropoxide was 10 mol %.
g The amount of ligand used was 20 mol % and titanium isopropoxide was 40 mol %.
h The amount of ligand 8 was 20 mol % and titanium isopropoxide was 20 mol %.
i
˚
3 A molecular sieves were added to the reaction mixture.
j To a solution of the ligand (10 mol % with respect to aldehyde) were added 4 equiv of potassium tert-butoxide and 2 equiv of titanium tetrachloride. The
precipitate was removed and washed with dichloromethane. The solvent was removed on a rotary evaporator and the catalyst was redissolved in dry
dichloromethane.
The use of 1.2 equiv of Hunigs base as an additive instead
¨
Another possible source of the allyl group was trimethylall-
ylsilane (Scheme 2). In this case, the background reaction
between p-nitrobenzaldehyde and trimethylallylsilane was
not detected (Table 2, entry 1) even in the presence of tri-
methylsilyl chloride (Table 2, entry 2). Precatalyst 4 (mix-
ture of complexes 5 and 6) was not active at a loading of
10 mol % at room temperature (Table 2, entry 3), but the
addition of 1.2 equiv of trimethylsilyl chloride to complex
4 facilitated the reaction and the final product was obtained
in 91% chemical yield and 51% ee after 24 h (Table 2, entry
4).
of trimethylsilyl chloride, or with trimethylsilyl chloride,
had a harmful effect on the performance of the catalytic
system, as the chemical yield was only 30% after 2.5 h
and the product was virtually racemic (Table 1, entries 13
and 14). A twofold decrease or increase of the precatalyst
concentration led to some reduction in the enantiomeric
purity of the product (Table 1, entries 15 and 16).
Under the optimal conditions, complex 8, a monomeric
analogue of bimetallic complexes 5 and 6, had a low cata-
lytic activity and asymmetry inducing ability, forming the
(R)-allylic alcohol with only 11% ee (Table 1, entry 17).
Significantly, the configuration of the alcohol was the
opposite of that generated with either complex 5 or 6.
The dependence of the ee of the product on the ratio of tri-
methylsilyl chloride to benzaldehyde was the opposite to
that observed in the tributylallyltin reaction (Table 2). In
this case, the optimal amount was 1.2 equiv of trimethyl-
silyl chloride with respect to the aldehyde (Table 2, entry
4). Further increase in the amount of the additive led to
the ee values falling steadily (Table 2, entries 4–7), though
the relative reactivity of precatalysts 5 and 6 stayed the
same. Thus, precatalyst 5 was less catalytically active than
complex 6 and produced only racemic product even under
optimal conditions (Table 2, entry 8), whilst precatalyst 6
The temperature dependence of the asymmetric induction
was at its optimum at 20 °C (Table 1, entries 18–21). The
asymmetric induction was almost insensitive to the pres-
ence or absence of a nitro-group in the benzaldehyde
molecule, as entries 23 and 12 testified. The addition of
molecular sieves to the reaction mixture led to an increase
in the asymmetric induction to 74% (Table 1, entry 22).

462
Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
HO
CHO
NO2
1) catalyst, CH2Cl2
2) KF, MeOH
+
SiMe3
OiPr
O
iPrO
OiPr
O
iPrO
O
O
H2O
(- 2 iPrOH)
N Ti
Ti N
NO2
N
Ti
Ti N
O
iPrO
OiPr
iPr
iPr
iPr
iPr
Scheme 2. Addition of trimethylallylsilane to p-nitrobenzaldehyde.
O
O
O
O
2 TMSCl
(- 2 TMSOiPr)
produced the product with a chemical yield of 87% and
with 60% ee after 24 h (Table 2, entry 9).
O
O
Cl
Cl
O
Table 2. Addition of allyltrimethylsilane to p-nitrobenzaldehyde catalysed
by the titanium complexes 4–6a
N
Ti
Ti
O
N
iPr
iPr
O
O
Cl
TMSClb
Time (h)
Yieldc (%)
eed (%)
O
Entry
Catalyst
N Ti
O
Ti
O
N
O
iPr
iPr
1
2
3
4
5
6
7
8
9
—
—
4
—
1.2
—
1.2
3.0
5.0
10.0
1.2
1.2
24
24
24
24
24
24
24
24
24
0
0
0
91
81
87
88
33
87
0
0
0
Cl
Scheme 3. Generation of probable catalytic species.
4
51 (S)
37 (S)
30 (S)
27 (S)
0
4
4
4
In spite of all the progress in the field of dinuclear catalysis,
particularly as applied to Lewis acid catalysis, there seems
to be an inherent obstacle to catalyst turnover. For exam-
ple, nucleophilic addition to aldehydes should be greatly
accelerated by simultaneous coordination of their carbonyl
group to both metal ions. However, the alkoxide product
of the nucleophilic addition will also be stabilised in the
same way. As a result, the rate of product dissociation from
the dinuclear centre may become the rate limiting step of
the whole process and even cause the formation of the final
product to be slowed down, relative to catalysis by the cor-
responding mononuclear catalyst.
5
6
60 (S)
a To a solution of the catalyst (0.025 mmol, 20 mol % of titanium with
respect to aldehyde) were added 1 equiv of p-nitrobenzaldehyde
(0.250 mmol) and 1.5 equiv of tributylallyltin (0.333 mmol) and additive.
b The number of equivalents of trimethylsilyl chloride with respect to the
aldehyde.
c Isolated yield after purification by chromatography.
d The enantiomeric excess was determined by HPLC.
Precatalyst 9 generated from titanium tetrachloride and
ligand 4 had a low catalytic activity (Table 1, entries 24
and 25). The addition of 2 equiv of trimethylsilyl chloride
to precatalyst 9 after 24 h gave only a 57% yield of the race-
mic alcohol. Thus, clearly, the function of trimethylsilyl
chloride was not to convert complexes 5 or 6 into their cor-
responding chloride forms with the complete elimination of
any remaining Ti–O bonds. Most likely, the real catalyti-
cally active species is an oxygen-bridged bimetallic titanium
complex, where isopropoxy-groups were substituted with
chloride anions (Scheme 3). The increase in the reaction
enantioselectivity as the amount of trimethylsilyl chloride
was increased may be rationalised by the accompanied in-
crease of the number of chloride ions at the Ti-centres.
3. Conclusions
In conclusion, we have shown that binuclear catalysts are
much more active than mononuclear ones in the allylation
of aldehydes. In addition, we found an unusual effect of tri-
methylsilyl chloride addition on the effectiveness of the
allylation of aldehydes with both allyltributyltin and tri-
methylallylsilane. Despite its modest enantioselectivity,
the reaction can be brought to completion (94% isolated
yield) after 1 h at a room temperature. Ongoing work is
aimed at modifying the structure of the chiral ligand to
provide higher enantioselectivities with the same reaction
rate at room temperature.
However, the most important function of the trimethylsilyl
chloride seems to be increasing the reaction rate in both
catalytic versions of allylation (see Table 1, entries 1 vs 4
and Table 2, entries 3 vs 4). This phenomenon can be
rationalised by assuming that in the case of both allylating
agents, the catalytic species formed in solution were similar
and that the decomposition of a highly stable intermediate
complex formed from allyl alcoholate and two titanium
ions represents the rate limiting step of the catalytic cycle.
Thus, the silylation step, regenerating the initial catalytic
species, will be the rate limiting one in the whole catalytic
sequence (Scheme 4).
4. Experimental
4.1. General
Specific rotations were measured on a Perkin–Elmer 241
T
polarimeter and are reported as follows: ½aꢁk (concentration
in g/100 mL, solvent). Enantiomeric excesses were deter-
mined by HPLC analysis using a Kromasil column
(0.25 m ꢂ 46 mm) with UV detection at 254 nm.

Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
463
R
O
O
Cl
N
Ti
Ti
N
OSiMe3
Me3SiCl
RCHO
Cl
O
iPr
iPr
O
O
R
R
O
O
O
O
O
O
Cl
Cl
O
N
Ti
Ti N
N
Ti
Ti N
Cl
O
iPr
iPr
iPr
iPr
O
O
O
O
SnBu3
Bu3SnCl
R
SnBu3
O
Cl
O
O
N
Ti
Ti N
Cl
O
iPr
iPr
O
O
Scheme 4. Probable mechanism of aldehyde allylation.
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 internal standard. Data are re-
ported 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. Melting
points were determined in open capillary tubes and are
uncorrected. Elemental analyses were carried out by the
laboratory of Microanalysis of INEOS RAS.
water (ꢂ4), satd NaHCO3, brine and dried over Na2SO4.
The solvent was removed under reduced pressure at room
temperature and the residue was purified by short column
chromatography on silica gel, eluting first with hexane
and then with ethyl acetate to give the title compound as
colourless crystals. Isolated yield 85%. Rf = 0.39 (hexane/
25
ethyl acetate 3:1); ½aꢁD ¼ þ98 (c 1, THF); 1H NMR
(300 MHz, CDCl3) d 3.15 (s, 6H), 4.98 (d, J 6.6 Hz, 2H),
5.09 (d, J 6.6 Hz, 2H), 7.40–7.26 (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.
THF was freshly distilled from sodium/benzophenone un-
der argon. Dichloromethane was distilled under argon
from P2O5 and dried over 3 A molecular sieves (1 g sieves
for 1 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.
4.2.2.
(S)-2,20-Bis-(methoxymethoxy)-1,10-binaphthalene.
˚
The title compound was prepared in the same way as the
corresponding (R)-enantiomer, using (S)-BINOL as the
starting material.
4.2.3.
rac-2,20-Bis-(methoxymethoxy)-1,10-binaphthalene.
The title compound was prepared in the same way as the
corresponding (R)-enantiomer, using rac-BINOL as the
starting material.
4.2. Synthesis of methoxymethyl protected binaphthols
4.2.1. (R)-2,20-Bis-(methoxymethoxy)-1,10-binaphthalene.6b
A solution of (R)-BINOL (2.40 g, 8.4 mmol) in DMF
(20 mL) was added to a stirred suspension of sodium hy-
dride (60% suspension in mineral oil, 2.36 g, 59 mmol) in
DMF (20 mL) at 0 °C. After stirring for 10 min, methoxy-
methyl chloride (2.5 mL, 33.3 mmol) was added, and the
reaction was then stirred for 50 min at 0 °C and 3 h at
room temperature. The reaction mixture was quenched
with water (250 mL) and extracted with diethyl ether
(3 ꢂ 40 mL). The combined extracts were washed with
4.3. Synthesis of dialdehydes
4.3.1. (R)-3,30-Diformyl-2,20-bis(methoxymethoxy)-1,10-bin-
aphthalene. n-Butyllithium (2.5 M in hexane, 9.0 mL,
22 mmol) was added to a solution of (R)-2,20-bis(methoxy-
methyl)-1,10-binaphthalene (2.46 g, 6.6 mmol) in ether
(100 mL) under an argon atmosphere at ꢀ78 °C. The mix-
ture was stirred for 2 h at room temperature, which pro-
duced a grey suspension, after which the reaction was

464
Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
cooled to 0 °C and DMF (1.85 mL, 24 mmol) was added.
The reaction was allowed to warm to room temperature
and stirred for 16 h. Saturated NH4Cl (50 mL) was then
added to quench the reaction. The organic layer was sepa-
rated, and the aqueous phase was extracted with ethyl ace-
tate (3 ꢂ 50 mL). The combined organic phases were
washed with water and brine and dried over Na2SO4.
The solvent was removed in vacuo and the residue purified
by column chromatography on silica gel eluting with hex-
ane/ethyl acetate (4:1) to give (R)-3,30-diformyl-2,20-bis
(methoxymethyl)-1,10-binaphthalene as white crystals. Iso-
lated yield, 57% (lit.6a sticky yellow oil). Rf = 0.17 (hexane/
propyl alcohol 100/4, 1 mL/min, UV detector 254 nm) Rt
(major)= 20.81 min, Rt (minor)= 22.79 min.
4.4.3. rac-3,30-Diformyl-2,20-dihydroxy-1,10-binaphthalene.
The title compound was prepared in the same way as the
corresponding (R)-enantiomer using rac-3,30-diformyl-
2,20-bis-(methoxymethoxy)-1,10-binaphthalene as the start-
ing material.
4.5. Synthesis of aminoalcohols
4.5.1. (S)-2-Amino-3-methyl-1-butanol. To a suspension
of lithium aluminium hydride (5 g, 0.131 mol) under an
argon atmosphere in dry THF (100 mL) at room tempera-
ture was carefully added L-valine (10 g, 0.085 mol) in 20
portions. The reaction mixture was refluxed for 16 h and
after cooling was poured into diethyl ether (or methyl-
tert-butyl ether) (100 mL). To the ether layer was slowly
added water (15 mL), followed by 15% aqueous sodium
hydroxide solution (15 mL) and water (45 mL). The solu-
tion was filtered, and the precipitate was washed twice with
ether (50 mL). The organic layers were combined and dried
over anhydrous Na2SO4. After distillation in vacuo, the
title compound (6.6 g, 0.064 mol, 75%) was obtained. It is
best to switch off the water in the condenser of the distilla-
1
ethyl acetate 4:1); H 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), 7.42–7.50 (m, 2H), 7.52–7.60 (m, 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.
4.3.2. (S)-3,30-Diformyl-2,20-bis(methoxymethoxy)-1,10-bi-
naphthalene. The title compound was prepared in the
same way as the corresponding (R)-enantiomer using (S)-
2,20-bis(methoxymethyl)-1,10-binaphthalene as the starting
material.
tion apparatus when (S)-2-amino-3-methyl-1-butanol
25
4.3.3. rac-3,30-Diformyl-2,20-bis(methoxymethoxy)-1,10-bin-
aphthalene. The title compound was prepared in the same
way as the corresponding (R)-enantiomer using rac-2,
20-bis(methoxymethyl)-1,10-binaphthalene as the starting
material.
begins to distil. ½aꢁD ¼ þ17 (c 11.5, ethanol). 1H NMR
(300 MHz, CDCl3) d 0.91 (d, J 4.9 Hz, 3H), 0.93 (d, J 4.9
Hz, 3H), 1.60–1.73 (m, 1H), 1.90–2.50 (br s, 3H), 2.83–
2.92 (m, 1H), 3.21 (dd, J 10.6, 8.0 Hz, 1H), 3.53 (dd, J
10.6, 3.7 Hz, 1H).
4.4. Deprotection of MOM-groups
4.5.2. (R)-2-Amino-3-methyl-1-butanol. The title com-
pound was prepared in the same way as the corresponding
(S)-enantiomer using (R)-valine as the starting material.
4.4.1. (R)-3,30-Diformyl-2,20-dihydroxy-1,10-binaphthalene.6c
(R)-3,30-diformyl-2,20-bis(methoxymethoxy)-1,10-binaphtha-
lene (1.17 g, 2.72 mmol) was dissolved in THF (20 mL). The
solution was cooled in an ice bath, and then 12 M hydrochlo-
ric acid (10 mL) was added over 5 min. The ice bath was
removed and the reaction mixture was stirred for 3 h at room
temperature. The solution was extracted with ethyl acetate
(7 ꢂ 20 mL), the combined extracts were washed with water,
satd NaHCO3, brine and dried over Na2SO4. The solvent
was evaporated to give the title compound (0.93 g, 100%)
as yellow crystals. To produce dialdehyde with good elemen-
tal analysis, the product was purified by chromatography on
4.6. Synthesis of ligands
4.6.1. Compound 3. A solution of (S)-2-amino-3-methyl-1-
butanol (0.19 g, 1.8 mmol) in ethanol (5 mL) and benzene
(5 mL) was added to (R)-3,30-diformyl-2,20-dihydroxy-
1,10-binaphthyl (0.31 g, 0.91 mmol). The reaction mixture
was heated in a Dean–Stark apparatus for 10 h. The solu-
tion was concentrated and the residue purified by short
column chromatography on aluminium oxide eluting with
hexane/dichloromethane/ethanol (20:5:1), then the eluent
was further purified by chromatography on Sephadex
Sephadex LH-20 (eluent THF). Rf = 0.35 (hexane/ethyl ace-
25
tate 4:1); mp 285 °C; ½aꢁD ¼ þ249:5 (c 0.8, CH2C2) {lit.7
LH-20 eluting with dry benzene to give compound 2
20
25
½aꢁD ¼ þ248 (c 0.5, CH2Cl2)}; 1H NMR (300 MHz, CDCl3)
(0.44 g, 95%) as a red solid. ½aꢁD ¼ ꢀ139:8 (c 1, CHCl3);
d 7.10–7.15 (m, 2H), 7.30–7.37 (m, 4H), 7.90–7.95 (m, 2H),
8.30 (s, 2H), 10.12 (s, 2H), 10.52 (s, 2H). ee >99.9% deter-
mined by HPLC analysis (Kromasil 0.46 cm ꢂ 25 cm, eluent
hexane/iso-propyl alcohol 100/4, 1 mL/min, UV detector
254 nm) Rt (major) = 22.79 min, Rt (minor) = 20.81 min.
1H NMR (CDCl3) d 0.92 (d, J 7.0 Hz, 3H), 0.95 (d, J
7.2 Hz, 3H), 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); 13C NMR (75 MHz, CDCl3) d
18.9, 19.6, 30.0, 64.1, 77.8, 116.5, 120.7, 123.2, 124.9,
127.5, 128.2, 128.8, 133.4, 135.1, 154.6, 165.9. Anal. Calcd
for C32H36N2O4: C, 74.97; H, 7.08; N, 5.46. Found: C,
75.03; H, 7.40; N, 5.27.
4.4.2. (S)-3,30-Diformyl-2,20-dihydroxy-1,10-binaphthalene.
The title compound was prepared in the same way as the
corresponding (R)-enantiomer using (S)-3,30-diformyl-
2,20-bis-(methoxymethoxy)-1,10-binaphthalene as the start-
25
20
ing material. ½aꢁD ¼ ꢀ267:0 (c 0.5, CH2Cl2) {lit.6b ½aꢁD
¼
4.6.2. Compound 2. The title compound was prepared as
described in Section 4.6.1 for compound 3, using (S)-3,30-
diformyl-2,20-dihydroxy-1,10-binaphthyl as the starting
ꢀ254 (c 0.3, CH2Cl2)}. ee >99.9% determined by HPLC
analysis (Kromasil 0.46 cm ꢂ 25 cm, eluent hexane/iso-

Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
465
25
1
material. Yield 95%. ½aꢁD ¼ ꢀ163 (c 1, CHCl3). H NMR
and to the residue was added a saturated solution of potas-
sium fluoride in methanol (5 mL). After 20 min, dichloro-
methane (20 mL) was added. The resulting precipitate
was filtered off, the solution was evaporated and the prod-
uct was purified by preparative-scale chromatography
(Rf = 0.3, CH2Cl2).
(CDCl3) d 0.92 (d, J 7.0 Hz, 3H), 0.95 (d, J 7.2 Hz, 3H),
1.56 (br m, 2H), 1.89–1.91 (m, 2H), 3.09–3.14 (m, 2H),
3.70–3.86 (m, 4H), 7.19–7.22 (m, 2H), 7.29–7.36 (m, 4H),
7.87–7.90 (m, 2H), 8.00 (s, 2H), 8.64 (s, 2H), 12.95 (s,
2H). Anal. Calcd for C32H36N2O4: C, 74.97; H, 7.08; N,
5.46. Found: C, 74.91; H, 6.99; N, 5.28.
4.7.2. (S)-(ꢀ)-1-(4-Nitrophenyl)-but-3-en-1-ol. 1H NMR
(CDCl3) d 2.19 (br s, 1H), 2.42–2.49 (m, 1H), 2.54–2.60
(m, 1H), 4.86 (dd, J 8.0, 4.6 Hz, 1H), 5.17–5.22 (m, 2H),
5.74–5.84 (m, 1H), 7.54 (d, J 8.6, 2H), 8.21 (d, J 8.6,
2H). HPLC Daicel AS-H, hexane/iso-propanol 98:2
4.6.3. Compound ent-2. The title compound was prepared
as described in Section 4.6.1 for compound 3, using (R)-
3,30-diformyl-2,20-dihydroxy-1,10-binaphthyl and (R)-2-
amino-3-methyl-1-butanol as the starting material. Yield
25
94%. ½aꢁD ¼ þ163 (c 1, CHCl3). 13C NMR (75 MHz,
(Rt[(R)-enantiomer] = 44.5 min,
Rt[(S)-enantiomer] =
25
47 min); ½aꢁD ¼ ꢀ35:7 (c 0.5, CHCl3) for 74% ee {lit.8
CDCl3) d 18.9, 19.7, 30.2, 64.4, 78.3, 116.5, 120.8, 123.4,
124.8, 127.6, 128.4, 129.0, 133.8, 135.2, 154.7, 166.1. Anal.
Calcd for C32H36N2O4: C, 74.97; H, 7.08; N, 5.46. Found:
C, 75.01; H, 7.15; N, 5.50.
25
½aꢁD ¼ ꢀ33:2 (c 0.5, CHCl3) for 65% ee}.
4.7.3. (S)-(ꢀ)-1-Phenyl-but-3-en-1-ol. 1H NMR (CDCl3)
d 2.06 (br s, 1H), 2.48–2.56 (m, 2H), 4.77 (dd, J 7.7, 5.2
Hz, 1H), 5.15–5.22 (m, 2H), 5.79–5.89 (m, 1H), 7.28–7.39
(m, 5H). HPLC Daicel OD-H, hexane/iso-propanol 98:2
4.6.4. Compound 1. The title compound was prepared as
described in Section 4.6.1 for compound 3, using rac-3,30-
diformyl-2,20-dihydroxy-1,10-binaphthyl as the starting
(Rt[(R)-enantiomer] = 15.7 min,
Rt[(S)-enantiomer] =
25
material. ½aꢁD ¼ ꢀ14:6 (c 1, CHCl3). 13C NMR (75 MHz,
25
19.9 min); ½aꢁD ¼ ꢀ44:6 (c 1.05, CHCl3) for 67% ee {lit.8
25
CDCl3) d 18.7, 18.8, 19.5, 19.6, 29.9, 30.0, 64.1, 64.2,
77.9, 78.1, 116.4, 116.5, 120.7, 120.8, 123.2, 123.3, 124.7,
124.8, 127.5, 128.2, 128.4, 128.8, 128.9, 133.4, 133.7,
135.1, 154.6, 165.9, 166.0. Anal. Calcd for C32H36N2O4:
C, 74.97; H, 7.08; N, 5.46. Found: C, 75.04; H, 7.41; N,
5.26.
½aꢁD ¼ ꢀ61:2 (c 1.05, CHCl3) for 92% ee}.
4.7.4. Typical procedure with allyltrimethylsilane.
Ti(OiPr)4 (15 lL, 0.05 mmol) was added to a solution of li-
gand (0.025 mmol) in dichloromethane (0.125 mL). The
solution changed colour from yellow to orange. After stir-
ring for 20 min, the solvent was evaporated. A solution of
p-nitrobenzaldehyde (38 mg, 0.25 mmol) in dry dichloro-
methane (0.125 mL) was added to the reaction mixture.
Subsequently, allyltrimethylsilane (59.6 lL, 0.375 mmol)
was added followed (optionally) by the appropriate addi-
tive. The solution colour changed to deep red. The reaction
mixture was stirred for 24 h. The reaction could be moni-
tored by TLC (SiO2 on aluminium plates, CH2Cl2). When
the reaction was complete, solvent was evaporated and a
saturated solution of potassium fluoride in methanol
(5 mL) was added. After 20 min, dichloromethane
(20 mL) was added. The resulting precipitate was filtered
off, the solution was evaporated and the product was puri-
fied by preparative-scale chromatography (Rf = 0.3,
CH2Cl2).
4.6.5. (S)-2-(N-30,50-Di-tert-butylsalicylideneamino)-3-methyl-
butan-1-ol. A solution of (S)-2-amino-3-methyl-1-butanol
(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 concentrated and
the residue purified by column chromatography on alumin-
ium oxide eluting with hexane/dichloromethane/ethanol
(20:5:1) to give the title compound (0.30 g, 86%) as yellow
25
crystals. ½aꢁD ¼ ꢀ33:3 (c 0.78, MeOH); 1H NMR
(300 MHz, CDCl3) d 1.02 (d, J 4.1 Hz, 3H), 1.04 (d, J
4.1 Hz, 3H), 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. Calcd for C20H33NO2: C, 75.19; H, 10.41;
N, 4.38. Found: C, 75.04; H, 10.41; N, 4.37.
Acknowledgements
4.7. Catalytic reactions
The authors thank INTAS (05-1000008-7822) and RFBR
(05-03-32243a) for financial support.
4.7.1. Asymmetric allylation reactions
4.7.1.1. Typical procedure with allyltributyltin.
Ti(OiPr)4 (15 lL, 0.05 mmol) was added to a solution of
ligand (0.025 mmol) in dichloromethane (0.125 mL). The
solution changed colour from yellow to orange. After stir-
ring for 20 min, the solvent was evaporated. A solution of
p-nitrobenzaldehyde (38 mg, 0.25 mmol) in dry dichloro-
methane (0.125 mL) was added to the reaction mixture.
Allyltributyltin (0.117 mL, 0.375 mmol) was then added
followed (optionally) by the appropriate additive. The
solution colour changed to deep red. The reaction mixture
was stirred for the required time. The reaction could be
monitored by TLC (SiO2 on aluminium plates, CH2Cl2).
When the reaction was complete, solvent was evaporated
References
1. (a) Furstner, A.; Langemann, K. J. Am. Chem. Soc. 1997, 119,
9130; (b) Meng, D.; Su, D.-S.; Balog, A.; Bertinato, P.;
Sorensen, E. J.; Danishefsky, S. J.; Zheng, Y.-H.; Chou, T.-C.;
He, L.; Horwitz, S. B. J. Am. Chem. Soc. 1997, 119, 2733; (c)
Shibasaki, M.; Kanai, M.; Matsunaga, S. Aldrichim. Acta
2006, 39, 31; (d) Ma, J.-A.; Cahard, D. Angew. Chem., Int. Ed.
2004, 43, 4566.
2. (a) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763; (b)
Duthaler, R. O.; Hafner, A. Chem. Rev. 1992, 92, 807; (c)

466
Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 459–466
Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207; (d)
3. (a) Kii, S.; Maruoka, K. Chirality 2003, 15, 68; (b) Kii, S.;
Maruoka, K. Tetrahedron Lett. 2001, 42, 1935; (c) Hanawa,
H.; Kii, S.; Asao, N.; Maruoka, K. Tetrahedron Lett. 2000, 41,
5543; (d) Hanawa, H.; Hashimoto, T.; Maruoka, K. J. Am.
Chem. Soc. 2003, 125, 1708.
4. (a) Belokon, Yu. N.; Caveda-Cepas, S.; Green, B.; Ikonnikov,
N. S.; Khrustalev, V. N.; Larichev, V. S.; Moscalenko, M. A.;
North, M.; Orizu, C.; Tararov, V. I.; Tasinazzo, M.; Timo-
feeva, G. I.; Yashkina, L. V. J. Am. Chem. Soc. 1999, 121,
3968; (b) Belokon, Y. N.; Blacker, A. J.; Carta, P.; Clutter-
buck, L. A.; North, M. Tetrahedron 2004, 60, 10433; (c)
Belokon, Y. N.; Carta, P.; Gutnov, A. V.; Maleev, V.;
Moskalenko, M. A.; Yashkina, L. V.; Ikonnikov, N. S.;
Voskoboev, N. V.; Khrustalev, V. N.; North, M. Helv. Chim.
Acta 2002, 85, 3301.
5. Belokon, Y. N.; Chusov, D.; Borkin, D. A.; Yashkina, L. V.;
Dmitriev, A. V.; Katayev, D.; North, M. Tetrahedron:
Asymmetry 2006, 17, 2328.
6. (a) Zhang, H.-C.; Huang, W.-S.; Pu, L. J. Org. Chem. 2001, 66,
481; (b) Bougauchi, M.; Watanabe, S.; Arai, T.; Sasai, H.;
Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 2329; (c)
DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2001, 3, 1641.
7. Brunner, H.; Goldbrunner, J. Chem. Ber. 1989, 122, 2005.
8. Malkov, A. V.; Orsini, M.; Pernazza, D.; Muir, K. W.; Langer,
V.; Meghani, P.; Kocovsky, P. Org. Lett. 2002, 4, 1047.
Wang, Z.; Wang, D.; Sui, X. Chem. Commun. 1996, 2261; (e)
Kinnaird, J. W. A.; Yee, Ng P.; Kubota, K.; Wang, X.;
Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920; (f) Kubota,
K.; Leighton, J. L. Angew. Chem., Int. Ed. 2003, 42, 946; (g)
Yu, C.-M.; Choi, H.-S.; Jung, W.-H.; Kim, H.-J.; Shin, J.
Chem. Commun. 1997, 761; (h) Denmark, S. E.; Almstead, N.
G. J. Org. Chem. 1994, 59, 5130; (i) Motoyama, Y.; Okano,
M.; Narusawa, H.; Makihara, N.; Aoki, K.; Nishiyama, H.
Organometallics 2001, 20, 1580; (j) Ishihara, K.; Mouri, M.;
Gao, Q.; Maruyama, T.; Furuta, K.; Yamamoto, H. J. Am.
Chem. Soc. 1993, 115, 11490; (k) Marshall, J. A.; Palovich, M.
R. J. Org. Chem. 1998, 63, 4381; (l) Keck, G. E.; Yu, T. Org.
Lett. 1999, 1, 289; (m) Faller, J. W.; Sams, D. W. I.; Liu, X. J.
Am. Chem. Soc. 1996, 118, 1217; (n) Pignataro, L.; Benaglia,
M.; Annunziata, R.; Cinquini, M.; Cozzi, F. J. Org. Chem.
2006, 71, 1458; (o) Chelucci, G.; Belmonte, N.; Benaglia, M.;
Pignataro, L. Tetrahedron Lett. 2007, 48, 4037; (p) Takeuchi,
K.; Takeda, T.; Fujimoto, T.; Yamamoto, I. Tetrahedron 2007,
63, 5319; (q) Corey, E. J.; Lee, T. W. Chem. Commun. 2001,
1321; (r) Corey, E. J.; Barnes-Seeman, D.; Lee, T. W.
Tetrahedron Lett. 1997, 38, 1699; (s) Corey, E. J.; Rohde, J.
J. Tetrahedron Lett. 1997, 38, 37; (t) Corey, E. J.; Yu, C.-M.;
Kim, S. S. J. Am. Chem. Soc. 1989, 111, 5495; (u) Brown, H.
C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 209.