Chiral phenoxyimino-amido aluminum complexes for the asymmetric cyanation of aldehydes

Article abstract of DOI:10.1039/c3dt53292e

The reactivity of triethylaluminum towards salicylaldimine sulfonamides was probed, affording well-defined complexes through consecutive protonolysis of two Al-C bonds by the proligand. These complexes, when combined with an achiral anilinic N-oxide, catalyze the asymmetric addition of trimethylsilylcyanide to a wide range of aldehydes, with good activity and enantioselectivity (up to 91% ee). Insertion of the benzaldehyde substrate into the Al-N amido bond was observed, bringing elements for discussion around the nature of the actual active species.

Full text of DOI:10.1039/c3dt53292e

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PAPER
Chiral phenoxyimino-amido aluminum complexes
for the asymmetric cyanation of aldehydes†
J. Ternel,a,b F. Agbossou-Niedercorn*a,b and R. M. Gauvin*a,b
Cite this: Dalton Trans., 2014, 43,
4530
The reactivity of triethylaluminum towards salicylaldimine sulfonamides was probed, affording well-
defined complexes through consecutive protonolysis of two Al–C bonds by the proligand. These com-
plexes, when combined with an achiral anilinic N-oxide, catalyze the asymmetric addition of trimethyl-
silylcyanide to a wide range of aldehydes, with good activity and enantioselectivity (up to 91% ee).
Insertion of the benzaldehyde substrate into the Al–N amido bond was observed, bringing elements for
discussion around the nature of the actual active species.
Received 21st November 2013,
Accepted 17th December 2013
DOI: 10.1039/c3dt53292e
www.rsc.org/dalton
Inspired by the successful use of cyanosilylation (pre)-cata-
lysts bearing C1 chiral inducers as reported by Oguni (phenoxy-
Introduction
The addition of a cyanide source to a carbonyl compound in imine ligands)8 and Choi (N-sulfonyl derivatives of
order to form enantiomerically pure cyanohydrins is one of aminoalcohols),9 we have recently reported the successful
the most popular carbon–carbon bond forming reactions in application of salicylaldimine sulfonamides10 (that can be
organic synthesis.1 Optically active cyanohydrins and their viewed as chiral C1-symmetric hemisalen ligands, 1a–j, Fig. 1)
derivatives are important intermediates for the preparation of as efficient chiral inducers in asymmetric cyanation of
a variety of valuable classes of chiral compounds. Due to their aldehydes.11
importance, much effort has been devoted to the design and
These proligands react with AlEt2Cl to afford chiral phenoxy-
development of efficient chiral catalysts,2 a significant class imine Al(III) complexes featuring a sulfonamide moiety, that is,
composed of chiral metal species. Among them, chiral salen with a free NH functionality. Depending on the reaction stoi-
complexes are the most widely studied, thanks to the versatility chiometry, one can introduce one or two of these ligands in
and ease of tuning of the salen framework.3
the aluminum coordination sphere (see Fig. 2). The corres-
Furthermore, the concept of bifunctional catalysis has been ponding complexes 2a–j and 3a–j, respectively of C1 or C2
successfully applied to asymmetric reactions. It consists, for symmetry, efficiently catalyze asymmetric addition of
example, of catalytic systems composed of Lewis acid/Lewis
base moieties able to simultaneously activate both an electro-
phile and a nucleophile, respectively.4 The efficiency of this
dual activation, i.e. a metal-based Lewis acid/Lewis base, relies
on enhanced reactivity and higher control of the transition
structure with respect to the catalyst pair. Indeed, this dual
activation concept has been successfully applied to the asym-
metric cyanosilylation of carbonyl derivatives.5 Kim6 and
Zhou7 demonstrated that salen–Al complexes were able to
mediate this reaction efficiently, provided that a phosphine
oxide co-catalyst was used.
aUniversité Lille Nord de France, France
bUCCS, UMR CNRS 8181, Cité Scientifique, BP 90108, 59652 Villeneuve d’Ascq
Cedex, France. E-mail: francine.agbossou@ensc-lille.fr, regis-gauvin@ensc-lille.fr;
Fax: +33(0)320436585; Tel: +33(0)320436754
†Electronic supplementary information (ESI) available: Additional spectroscopic
Fig. 1 Phenoxyimino-sulfonamide proligands used in the present
data. See DOI: 10.1039/c3dt53292e
study.
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Fig. 2 Reactivity of ligands 1a–j toward AlEt2Cl.
Fig. 3 1H NMR monitoring of the reaction between AlEt3 and 1a
(1 : 1 molar ratio, C6D6, 300 MHz, 297 K): after 2 hours of reaction at
room temperature (bottom) and after 24 hours of heating at 40 °C (top).
trimethylsilylcyanide to a broad range of aldehydes with high
yields and good to excellent enantioselectivities (up to 97% ee)
in the presence of a Lewis base as a co-catalyst. From these
elements, as variation of the chiral ligand’s structure leads to
significant progress of the catalytic performances, an attractive
option for further improvement of the system is the variation
of the non-chiral ancillary ligands, which can easily be probed
by switching the aluminum precursor. We present, in this con-
tribution, the reactivity of the phenoxyimine sulfonamides
toward triethylaluminum along with the reactivity of the result-
ing chiral complexes in enantioselective silylcyanation of
aldehydes.
1
the final complex. Given the H NMR characteristic of the 4a–j
complexes described below, one can postulate that the inter-
mediate compound was the bis-ethyl derivative 5a (Fig. 4),
which afforded the mono-ethyl complex 4a after reaction of
the N–H with an aluminum ethyl fragment. Such phenoxy-
imine bis-alkyl aluminum species have been described by
several authors, and were successfully used, mostly in polymer-
ization catalysis.13
Next, on a preparative scale, reaction of an equimolar
amount of 1a and AlEt3 in toluene at 40 °C for 24 hours
afforded the corresponding Al(III) complex 4a as a pale yellow
solid in 89% isolated yield. This complex was characterized by
1H and 13C NMR, infrared spectroscopy, and elemental analy-
sis. In the 1H NMR spectrum, the AlEt group was evidenced by
signals at 0.7 (multiplet, Al–CH2) and 1.6 ppm (triplet, CH3),
while the coordinated phenoxyimino ligand gave rise most par-
ticularly to two multiplets at 3.1 and 3.2 ppm (CH–N), and two
singlets accounting for the t-butyl protons (1.5 and 1.8 ppm).
In the 13C NMR spectrum, the coordinated imine carbon reso-
nates at 164.0 ppm and the phenolic C–O at 161.2 ppm. The
Results and discussion
Chiral aluminum complex synthesis
We have demonstrated in the preceding communication that
ligands 1a–j reacted at room temperature to afford complexes
2a–j and 3a–j, which bear chloro aluminum and ethyl chloro
aluminum moieties, respectively, along with sulfonamide N–H
functionalities as mixtures of two isomers. Here, the reactivity
of readily available triethylaluminum toward proligand 1a was
probed to explore the synthesis of the related chiral Lewis acid.
Thus, the reaction of an equimolar ratio of triethylaluminum
and proligand 1a in C6D6 at room temperature afforded within
minutes a mixture of complexes, as shown by 1H NMR (Fig. 3).
Reaction of aluminum-ethyl groups was evidenced by the pres-
ence of the ethane signal at 0.80 ppm.12 No trace of the pheno-
lic proton (13.0 ppm for 1a) was observed, indicating a fast
reaction with the aluminum alkyl. Furthermore, the chiral
ligand was exhibiting a doublet at 4.70 ppm (2JH–H = 6.3 Hz)
attributed to the sulfonamide NH proton, and two sets of
multiplets in the 3.5–2.5 ppm range characteristic of cyclohexyl
CH–N protons. Heating this reaction mixture at 40 °C for
1
24 hours led to simplification of the H NMR spectrum, as a
single set of chiral ligand’s signals was observed, consistent
with the presence of a single C1-symmetric species in solution.
Most particularly, the N–H signal was no longer observed in Fig. 4 Preparation of Al(III) complexes.
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infrared spectrum displays a ν(CvN) band at 1628 cm−1 and
confirms the absence of NH functionality. Despite repeated
efforts, we did not succeed in isolating single crystals suitable
for X-ray diffraction studies. However, based on the related
work from Wu et al., the geometry around the aluminum
center is most probably a distorted square pyramid with the
ethyl group at the axial position, the nitrogen and oxygen
atoms occupying the basal positions.14 The analogous
complex 4h, which was also synthesized on a preparative scale
and isolated in 82% yield, features similar spectroscopic
characteristics.
Table 2 Influence of the co-catalyst on benzaldehyde silylcyanationa
Co-catalyst
Entry (mol%)
Time to full
Conv. at
eeb
conversionb (h) 2 hoursb (%) (%) Config.
1
2
3
4
—
>24
18
>24
<5
15
5
0
80
16
11
—
R
R
DMNO (1.5)
Ph3PO (10)
Ph2HPO (10) >24
5
R
a 1a : AlEt3 (1 : 1; 2 mol%), −20 °C, TMSCN (1.5 eq.), [PhCHO] = 0.66 M.
b From GC analysis on Chirasil DEX CB.
(DMNO) as a co-catalyst afforded promising results under opti-
mized experimental conditions, i.e. 2 mol% 4a, 1.5 mol%
DMNO, 0.66 M of benzaldehyde in CH2Cl2, −20 °C, and
1.5 eq. of TMSCN. Very interestingly, similar results were
obtained for isolated and in situ-prepared catalytic systems,
where the organoaluminum species was reacted with the pro-
ligand at 40 °C for 24 hours. This is relevant to mention, as it
was demonstrated that the chemistry of the related salen
based catalytic systems, which were generated in situ, was
indeed complex, leading to unexpected species.15 In the
present case, this validates a catalytic approach implying the
use of a proligand without the need to isolate its complex.
As shown in Table 3, under the optimal conditions, this
highly efficient catalytic system converted a wide range of aro-
matic aldehydes with moderate to good asymmetric induction.
Indeed, in the presence of 2 mol% of 4a and 1.5 mol% of
DMNO, benzaldehyde was converted into O-silyl mandelo-
nitrile in 15% yield in 2 hours at −20 °C with 80% ee
(R isomer, entry 1). 18 hours were required to reach full sub-
strate conversion. No change in the amplitude of enantio-
selectivity was observed over the course of the reaction. The
presence of an electron donating group on the substrate
induced the formation of the silylated cyanohydrins with good
levels of enantioselectivity (Table 3, entries 2–4; 70–90% ee)
while an electron withdrawing moiety on the substrate
As we intended to screen the efficiency of the series of pro-
ligands 1a–f in combination with triethylaluminum in asym-
metric silylcyanation of aldehydes, we studied the in situ
preparation of the corresponding chiral aluminum ethyl
derivatives by NMR monitoring. As was observed in the case of
1a, these reactions proceeded cleanly to quantitative formation
of the expected species, after 24 hours of heating at 40 °C.
1
Selected H and 13C NMR data for a range of complexes gene-
rated from different proligands are presented in Table 1.
In order to extend the scope of these aluminum-based cata-
lysts, we attempted to convert the previously reported complex
3a, as a mixture of two isomers, into the corresponding phe-
noxyimino-amido chloro aluminum derivative using the same
procedure as for the synthesis of 4a (prolonged heating in
toluene). Unfortunately, the reaction proved to be non-selec-
tive, affording a mixture of complexes. Most particularly, in the
1H NMR spectrum, the CH–N region comprises three main
sets of signals, corresponding to unreacted 3a (10%), complex
2a (that bears two chiral ligands, 45%) and the expected amido
complex (45%). Assignment of the latter was based on the 3.3
and 3.15 ppm signals that are close to those of the amido ethyl
complex 4a. Further attempts did not allow isolating the
desired amido aluminum complex in pure form.
Catalytic studies
The catalytic performances of 4a were first probed in benz-
aldehyde silylcyanation. As reported in our preliminary com-
munication on the related phenoxyimino complexes 2a–j and
3a–j,11 the presence of a co-catalyst exerted an important influ-
ence on the stereoselectivity outcome of the reaction. The
results summarised in Table 2 show that here, in the absence
of a Lewis base as a co-catalyst, no asymmetric induction
could be achieved at all. Use of N,N-dimethylaniline N-oxide
Table 3 Enantioselective cyanosilylation of aldehydes catalyzed by
complex 4aa
Time to full
Conv. at
eeb
Entry
R
conversionb [h] 2 hoursb [%] [%] Config.
Table 1 Selected 1H and 13C NMR data for some complexes 4 (C6D6,
297 K)
1
2
3
4
5
6
7
8
9
Ph
o-MeC6H4
p-MeC6H4
18
18
22
15
15
12
10
10
12
100
65
80
90
77
70
68
72
0
R
R
R
R
S
1H NMR
13C NMR
o-OMeC6H4 >24
Complex
CHNv
CHNS
NvCH
CHNv
CHNS
NvCH
p-ClC6H4
p-CF3C6H4
2-C5H4N
3-C5H4N
C6H13
>24
22
2
4
2
S
—
—
S
4a
3.1
3.0
3.0
3.0
3.2
3.2
3.1
3.2
7.9
7.7
8.1
8.2
66.0
67.5
67.1
71.5
60.2
61.2
60.8
57.8
164.0
165.1
163.8
173.5
0
25
4b
4c
99
4ha
a 4a (2 mol%), DMNO (1.5 mol%), −20 °C, TMSCN (1.5 eq.), [substrate]
= 0.66 M in CH2Cl2. b From GC analysis on Chirasil DEX CB.
a CD2Cl2, 297 K.
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induced the formation of the silylated cyanohydrins with only 2 hours and selectivity up to 91% ee. About camphoryl sulfonyl
moderate selectivities (Table 3, entries 5 and 6; 68–72% ee) derivatives (Table 4, entries 9 and 10), activity and selectivity
and with opposite configuration. The change in the major were highly dependent on the camphoryl enantiomer linked to
isomer configuration indicates that electronic effects play an the (R,R) diaminocyclohexyl ligand framework. Thus, the Al
important role in the enantiodiscriminating step of the reac- complex bearing the (R)-camphoryl substituted ligand was par-
tion. Heteroaromatic aldehydes are more efficiently converted, ticularly unreactive and non-selective while the use of the (S)-
but without asymmetric induction (Table 3, entries 7 and 8). camphoryl substituted moiety led to up to 58% of enantio-
Most noteworthy, in the case of ortho-pyridylcarboxaldehyde, a meric excess. This probably results from quite different stereo-
fast reaction rate was observed, most probably due to preferen- electronic environments of the aluminum center while
tial substrate binding onto the Al center via pyridine coordi- applying camphoryl modified ligands. Consequently, the cata-
nation. However, this obviously generated a transition state lyst performances are somehow inhibited in the case of both
that does not lead to any significant chirality transfer from the cyclohexyldiamine and camphoryl configuration combi-
chiral catalyst. In the case of cyclohexanecarboxaldehyde, fast nations, one exhibiting nonetheless a match situation even if
conversion was observed, with poor enantioselectivity transfer significantly less active (Table 4, entry 10).
(Table 3, entry 9).
After having probed the effect of sulfonamide moieties and
The stereoelectronic properties of the ligand framework of the salicylaldehyde substituents, the impact of the chiral
were then tuned (Table 4). Substituents at the R2 position backbone on catalytic performances was studied (Table 5).
affected strongly the activity of the corresponding catalyst but Indeed, systems based on ligands derived from (R,R)-1,2-diphe-
had little effect on the ee values. For example, introduction of nylethylenediamine exhibited lesser performances. In all
the electron withdrawing nitro group at that position allows cases, a decrease in both activity and selectivity was observed
for higher activity and slightly higher enantioselectivity (Table 3, entries 1–3). However, trends similar to cyclohexane-
(Table 4, entry 2 vs. 1). Indeed, in the case of benzaldehyde as diamine-based systems were obtained: a nitro group in R2
a substrate, the use of a catalyst based on a ligand containing position in the salicylaldehyde moiety and a m-nosyl group as
a salicylaldehyde residue bearing a nitro group as the R2 sub- a sulfonamide substituent are both beneficial in terms of
stituent and a p-tolyl sulfonamide on the cyclohexyl moiety led selectivity. However, the role of the sulfonamide substituent is
to the formation of a silylated product with 60% conversion subtle: the m-nosyl group affords the opposite major enantio-
after 2 hours (vs. 15% with t-Bu as the R2 group) and an mer as compared to its p-tolyl analogue. This was not observed
enantioselectivity up to 84% (vs. 80% with t-Bu as the R2 in the case of the more rigid systems involving proligand 1a–j.
group). This contrasts with the observation of Belokon and co- Here, the flexibility on the ethylenediamine backbone affects
workers,3 who reported a decrease of selectivity upon introduc- the structure of the catalytic intermediate responsible for the
tion of NO2 in R2 position. Concerning the sulfonamide enantiodiscriminating step, which translates into markedly
moiety, several combinations were used and the framework different selectivity.
derived from m-nosyl (m-NO2-C6H4SO2) proved to be the most
Our catalytic results compare well to those obtained with
effective. Thus, the catalyst derived from ligand 1h, containing salen-based systems, such as the one developed by Kim6 and
a m-nosyl group and a salicylaldehyde bearing a nitro group in by Zhou.7 These require 1 mol% of catalyst loading but also a
R2 position, exhibited the best catalytic performances (Table 4, significant amount of a co-catalyst (10 mol%) to convert alde-
entry 8). In this case, benzaldehyde was converted into the hydes with good activity and ee values (up to 92% ee, in
corresponding silyl cyano ether with a total conversion in
Table 5 Influence of the ligand’s backbone on benzaldehyde
silylcyanationa
Table 4 Influence of the ligand structure on benzaldehyde
silylcyanationa
Time to full
Conv. at
eeb
[%]
Entry
L
conversionb [h]
2 hoursb [%]
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
18
2
15
60
20
10
18
30
20
100
15
9
80
84
54
55
70
83
68
91
0
14
>24
16
12
14
2
Time to full
Conv. at
eeb
(%)
Entry
L
conversionb (h)
2 hoursb (%)
Config.
1
2
3
1k
1l
1m
9
21
32
15
60
20
65
73
85
S
S
R
18
>24
10
1j
58
a (1a–j) : AlEt3 (1 : 1; 2 mol%), N-oxide (1.5 mol%), −20 °C, TMSCN (1.5 a (1k–m) : AlEt3 (1 : 1; 2 mol%), N-oxide (1.5 mol%), −20 °C, TMSCN
eq.), [benzaldehyde] = 0.66 M in CH2Cl2. b From GC analysis on (1.5 eq.), [benzaldehyde] = 0.66 M in CH2Cl2. b GC analysis on Chirasil
Chirasil DEX CB; the major isomer is of R configuration.
DEX CB.
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12–16 h). The catalysts developed here with an aluminum ligand on each metal center, two bridging benzaldehydes, and
center accommodating a tridentate hemisalen moiety with a no ethyl group. Aluminum is thus pentacoordinated. Alumi-
N-sulfonamido group proved to be easily tunable and thus num being at the (III) oxidation state, this implies a dicationic
allowed fast optimization to achieve very good catalytic per- structure, the nature of expected anions not being determined
formances for a broad range of aldehydes. However, the sulfo- due to poor crystal quality. The chiral ligand resulted from the
namide moiety does not, most probably, act as an efficient insertion of a benzaldehyde into the Al–N sigma bond, gener-
intramolecular co-catalyst (Lewis base) as the cyanation of ating a O-coordinated hemiaminal group. The chiral ligand in
benzaldehyde was very sluggish with no asymmetric induction this case is of the (O,N,O) type compared to the (O,N,N) phe-
without an external assistance (Table 1, entry 1). Indeed, our noxyimino-amido entity initially present on the aluminum
system requires the use of an external base to enforce high moiety. This type of reactivity was previously reported by
levels of stereoselection.
Mimoun and Floriani, in the course of their studies on ketone
Attempts were made to provide further understanding of reduction mediated by zinc-based systems.16 The implication
the complex catalytic system described above. On the one of this observation for the catalytic systems described above
hand, addition of benzaldehyde (1 equivalent) to complex 4a will require further specific studies, but this emphasizes the
induced immediate change of the solution’s color from pale to peculiarity of the herein described (pre)catalysts.
deep yellow. However, this did not lead to any significant
change on the 1H NMR spectrum. On the other hand, addition
of DMNO (1 equivalent) significantly perturbed the spectrum:
featureless signals are observed, among which one can dis-
Conclusions
tinguish signals due to the coordinated DMNO methyl groups In summary, we have described here how modification of the
(3.8 and 4.0 ppm, to be compared to 3.6 ppm for free DMNO). aluminum precursor affects the coordination chemistry of phe-
This may be expected from coordination of this base on the noxyimine sulfonamide ligands. In contrast with the related
chiral Lewis acidic Al center, generating diastereotopic methyl AlEt2Cl chemistry, AlEt3 affords chiral amido species that
groups. However, further understanding is still out of reach. proved to be efficient catalysts for aldehyde silylcyanation in
Further, reaction of 4a with TMSCN and benzaldehyde in combination with an external Lewis base. Some elements indi-
benzene afforded colorless crystals, which proved to be of poor cate that the amido functionality may not be innocent and
quality but amenable to X-ray diffraction study. If refining the could play a role in the modification of the chiral aluminum
structure was not possible due to significant thermal agitation coordination sphere.
in the crystal even at low temperature, the coordination
scheme of the compound could be assessed and presented a
most peculiar structural pattern (Fig. 5). The species consisted
of a dinuclear assembly of C2 symmetry, bearing a chiral
Experimental
Materials and methods
All the experiments (except proligands synthesis) have been
carried out under an inert atmosphere using conventional
Schlenk techniques or in an argon-filled glove-box. All reagents
and solvents were of commercial grade and purified prior to
use when necessary. 1H and 13C NMR were acquired on a
Bruker AC300 instrument. Chemical shifts are measured rela-
tive to residual solvent peaks as an internal standard set to δ =
7.26 ppm and δ = 77.1 ppm (CDCl3) for 1H and 13C, respect-
ively. Enantiomeric excesses were determined with a Shimadzu
instrument (Chirasil-DEX CB, 25 m × 0.25 mm column). Absol-
ute configurations were determined by comparing the known
order of elution of the two enantiomers or the sign of optical
rotation with literature data.17 Infrared spectra were recorded
on a Nicolet 6700 FTIR. Elemental analyses were conducted
using a VarioMIRO Superuser automatic analyser in the UCCS,
or in London Metropolitan University Services. All substrates,
TMSCN, substituted salicylaldehydes and (1R,2R)-diamines
were purchased from Acros, Aldrich, and Fluka, and were used
without further purification. DMNO was synthesized according
to the procedure described in the literature.18 Solvents and
substrates were purified by conventional methods. CAUTION:
Fig. 5 Ball and stick representation of the molecular connectivity of the
species resulting from the reaction of 4a, SiMe3CN and PhCHO (black:
SiMe3CN is a highly toxic chemical and should be handled
with care using appropriate precautions.
aluminum; red: oxygen; pink: nitrogen; blue: carbon; yellow: sulfur;
hydrogen atoms not depicted).
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Preparation of ligands 1a–m. To a solution of the selected 23.8 (CH2), 21.1 (Ar–CH3), 10.2 (CH3–CH2–Al), 0.3 (broad,
aminosulfonamide (1 mmol) in dichloromethane (5 ml), a CH3–CH2–Al). IR (KBr, cm−1): ν = 2985 (ν(sp3-CH)), 1628
mixture of the selected salicylaldehyde derivative (1 mmol) in (νCvN). Anal. calculated for C30H43AlN2O3S (538.72 g mol−1):
dichloromethane (3 ml) was added at room temperature. The C 66.88; H 8.05; N 5.20; found C 66.32; H 7.96; N 5.17.
mixture was stirred overnight. MgSO4 was then added; the
Complex 4h. To a stirred solution of 1h (0.558 g, 1 mmol) in
mixture was filtered and evaporated to dryness. After crystalli- dry dichloromethane (20 mL) was added dropwise a solution
zation in ethanol, yellow crystals were obtained. Proligands 1a– of triethylaluminum (0.114 g, 1 mmol) at room temperature
j were described in a previous communication.11
under a nitrogen atmosphere. The resulting mixture was
1
1l: Yield = 96%. H NMR (CDCl3, 300 MHz, δ ppm): 14.54 stirred for 24 hours at 40 °C. After removal of the solvent, the
(s, 1H, OH), 8.25 (s, 1H, CHvN), 8.24 (d, 3J = 2.7 Hz, 1H, orange crude product was recrystallized from dry pentane
H
ArOH), 7.95 (d, 4J = 2.7 Hz, 1H, HArOH), 7.45 (d, 3J = 8.2 Hz, (50 mL) to afford complex 4h as an orange solid. Yield = 82%.
3
2H, Hp-Tol), 7.20–7.05 (m, 10H, HAr), 7.02 (d, J = 8.2 Hz, 2H, 1H NMR (CD2Cl2, 300 MHz, δ ppm): 8.47 (t, 4J = 1.9 Hz, 1H,
3
3
3
H
p-Tol), 5.51 (d, J = 7.5 Hz, 1H, NH), 4.81 (dd, J = 7.5 Hz, J = H m-Nosyl), 8.19 (s, 1H, CHvN), 8.16–7.90 (m, 5H, H ArO and
3
6.6 Hz, 1H, CH–N), 4.53 (d, J = 6.6 Hz, 1H, CH–NH), 2.29 (s, m-Nosyl), 7.45–7.32 (m, 1H, H m-Nosyl), 3.18 (m, 2 H, CH–N),
3H, CH3), 1.43 (s, 9H, t-Bu). 13C NMR (CDCl3, 75 MHz, δ ppm): 2.98 (m, 2H, CH–NSO2), 1.31 (s, 9H, t-Bu), 1.82–1.18 (m, 8H,
166.4 (CHvN), 166.0 (C–OH), 143.1, 139.3, 139.0, 137.4, 137.0, CH2), 0.67 (t, 3H, 3J = 6.3 Hz, CH3–CH2), 0.35 (m, 2H,
136.8, 129.3, 128.6, 128.2, 127.8, 127.6, 127.4, 126.8, 126.3, CH2–CH3). 13C NMR (CD2Cl2, 75 MHz, δ ppm): 173.5 (CHvN),
125.3, 117.2, 107.5 (CAr), 78.1 (CH–N), 63.4 (CH–NH), 35.3, 160.5 (C–OAl), 147.9 (C–NO2), 143.0 (Cq Ar), 137.4 (Cq Ar),
29.0, 21.4. IR (KBr): ν = 3283 (νN–H), 3062 (νCsp2–H), 3032 137.3 (Cq Ar), 132.9 (CH Ar), 129.6 (CH Ar), 126.3 (CH Ar),
(νCsp2–H), 2957 (νO–H), 1626 (νCvN), 1320, 1290, 1160, 125.2 (CH Ar), 121.9 (CH Ar), 121.5 (CH Ar), 117.2 (Cq Ar), 71.5
1059 cm−1. Anal. calculated for C32H33N3O5S (571.69 g mol−1): (C–NvC), 57.8 (CH–NSO2), 35.1 (C(CH3)3), 34.5 (C(CH3)3), 33.9
C 67.23; H 5.82; N 7.35; S 5.61; found C 67.38; H 5.87; N 7.47; (CH2CH–N), 31.2 (CH2CH–N), 29.4 (C(CH3)3), 29.1 (C(CH3)3),
S 5.29.
23.7 (CH2), 23.2 (CH2), 8.1 (CH3–CH2–Al), 0.7 (broad, CH3–
1
1m: Yield = 93%. H NMR (CDCl3, 300 MHz, δ ppm): 14.54 CH2–Al).
(s, 1H, OH), 8.27 (s, 1H, CHvN), 8.20 (d, 3J = 2.4 Hz, 1H,
General procedure for catalyzed asymmetric cyanosilylation
H
H
m-Nosyl), 8.01 (s, 1H, Hm-Nosyl), 7.95 (d, 3J = 8.4 Hz, 1H, of aldehydes in the presence of synthesized aluminium com-
m-Nosyl), 7.43 (t, J = 7.7 Hz, 1H, Hm-Nosyl), 7.22–7.05 (m, 11H, plexes. A mixture of the selected aluminium complex
3
3
HAr), 6.91 (s, 1H, HArOH), 5.72 (d, J = 7.5 Hz, 1H, NH), 4.93 (t, (0.02 mmol), benzaldehyde (0.1 ml, 1 mmol), and dry dichloro-
3J = 6.9 Hz, 1H, CH–NvC), 4.66 (d, 3J = 6.6 Hz, 1H, CH– methane (1.5 mL) was stirred for 0.5 h at room temperature
NHSO2), 1.43 (s, 9H, t-Bu). 13C NMR (CDCl3, 75 MHz, δ ppm): under a nitrogen atmosphere. To the mixture was added
166.9 (CHvN), 165.9 (C–OH), 147.7, 142.0, 139.5, 139.2, 137.2, N,N-dimethylaniline N-oxide (0.015 mmol) and the resulting
136.2, 132.2, 129.9, 128.8, 128.4, 128.3, 128.2, 127.4, 127.3, 126.6, medium was stirred for another 0.5 h at the same temperature.
126.4, 125.6, 122.3, 117.2 (CAr), 77.9 (CH–N), 63.6 (CH–NH), 35.3, Then, the mixture was stirred at −20 °C and then tri-
28.9. IR (KBr): ν = 3301 (νN–H), 3063 (νCsp2–H), 3033 (νCsp2–H), methylsilylcyanide (0.2 ml, 1.5 mmol) was added with a
2962 (νO–H), 1622 (νCvN), 1354, 1290, 1166, 1051 cm−1. Anal. syringe. After stirring for 2–24 h at this temperature, the crude
calculated for C31H30N4O7S (602.66 g mol−1): C 61.78; H 5.02; reaction mixture was concentrated under reduced pressure
N 9.30; S 5.32; found C 61.50; H 5.12; N 9.30; S 4.80.
and purified through silica gel column chromatography
Complex 4a. To a stirred solution of (R,R)-1a (0.485 g, (200–300 mesh, gradient of petroleum ether–ethyl acetate) to
1 mmol) in dry dichloromethane (20 mL) was added dropwise yield the silylated cyanohydrin which was used for further
a solution of triethylaluminum (0.114 g, 1 mmol) at room chiral GC analysis.
temperature under a nitrogen atmosphere. The resulting
mixture was stirred for another 24 hours at 40 °C. After of aldehydes in the presence of in situ generated catalysts. A
removal of the solvent, the crude product was recrystallized mixture of selected ligand (0.02 mmol) and AlEt3
General procedure for catalyzed asymmetric cyanosilylation
1
from dry toluene (5 mL) to afford complex 4a as a yellow solid. (0.02 mmol) in dry dichloromethane (1 ml) was stirred over-
Yield = 89%. 1H NMR (C6D6, 300 MHz, δ ppm): 8.19 (d, 3J = night at 40 °C. Then, benzaldehyde (0.1 ml, 1 mmol) was
3
7.9 Hz, 2H, H p-Tol), 7.87 (d, J = 2.0 Hz, 1H, H ArO), 7.55 (s, added and stirred for 0.5 h at room temperature under a nitro-
1H, CHvN), 7.16 (d, 3J = 2.0 Hz, 1H, H ArO), 6.90 (d, 3J = gen atmosphere. To the mixture was added N,N-dimethyl-
7.9 Hz, 2H, H p-Tol), 3.29–3.16 (m, 1H, CH–NvC), 3.15–3.02 aniline N-oxide (0.015 mmol) and the resulting mixture was
(m, 1H, CH–NSO2), 1.98 (s, 3H, CH3), 1.84 (s, 9H, t-Bu), 1.61 stirred for another 0.5 h at the same temperature. Then, the
(m, 3H, CH2–CH3, 1.49 (s, 9H, t-Bu), 1.24–0.82 (m, 8H, CH2), mixture was stirred at −20 °C and trimethylsilylcyanide
0.73 (m, 2H, CH3–CH2–Al). 13C NMR (C6D6, 75 MHz, δ ppm): (0.2 ml, 1.5 mmol) was added with a syringe. After stirring for
164.0 (CHvN), 161.2 (C–O–Al), 142.7 (Cq Ar), 141.6 (Cq Ar), 2–24 h at this temperature, the mixture was concentrated
139.9 (Cq Ar), 139.0 (Cq Ar), 130.5 (CH Ar), 129.6 (CH p-Tol), under reduced pressure and purified through silica gel
127.7 (CH Ar), 127.2 (CH p-Tol), 119.5 (Cq Ar), 66.0 (CH–NvC), column chromatography (200–300 mesh, gradient of pet-
60.2 (CH–NSO2), 35.9 (C(CH3)3), 34.2 (C(CH3)3), 32.9 (CH2CH– roleum ether–ethyl acetate) to yield the silylated cyanohydrin
N), 31.6 (C(CH3)3), 29.8 (C(CH3)3), 25.8 (CH2CH–N), 24.0 (CH2), which was used for further chiral GC analysis.
This journal is © The Royal Society of Chemistry 2014
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Dalton Transactions
M. Kanai, W. Du, D. P. Curran and M. Shibasaki, J. Am.
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Acknowledgements
The authors are grateful to the French Ministry of Higher Edu-
cation and Research (PhD grant to JT) and CNRS for funding
this research. We are grateful to Pascal Roussel and Frédéric
Capet for their attempts at resolution of X-ray diffraction data
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4536 | Dalton Trans., 2014, 43, 4530–4536
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