M. North, C. Williamson / Tetrahedron Letters 50 (2009) 3249–3252
3251
OSiMe3
-1.2
-1.4
-1.6
-1.8
-2
OSiMe3
Time (min)
600
Ph3P
0
200
400
Ph3PO + Me3SiCN
Ph
CN
N
C
rate
determining
step
Al(salen)
(salen)Al
O
O
1
y = -0.0015x - 1.3097
R² = 0.9886
Ph
CN
Al(salen)
C
(salen)Al
O
Ph3P
O
SiMe3
-2.2
6
N
PhCHO
O Al(salen)
Figure 1. First-order kinetics plot for the addition of trimethylsilyl cyanide to
benzaldehyde at 0 °C catalysed by complex (2 mol %) in dichloromethane.
[PhCHO]0 = 0.26 M, [Me3SiCN]0 = 0.26 M, [1] = 0.0051 M, [Ph3PO] = 0.025 M.
PPh3
1
O
(salen)Al
SiMe3
4
O
C
N
is given by: kobs = k[1]x[Ph3PO]y. Hence, carrying out reactions at
various concentrations of complex 1 and triphenylphosphine oxide
allows the order with respect to each of these components to be
determined. Figure 2 shows the results of experiments carried
out at different concentrations of catalyst 1 and triphenylphos-
phine oxide, and clearly indicates that the reaction is first order
with respect to both these components.
OSiMe3
Ph
H
P
Ph3
5
Scheme 2. Possible catalytic cycle consistent with the kinetics results.
be accomplished6 using triethoxyaluminium rather than highly
pyrophoric diethylaluminium chloride.
Thus, the full rate equation can be deduced as rate =
k[1][Ph3PO][Me3SiCN]. A possible catalytic cycle consistent with
these rate data is shown in Scheme 2. In this catalytic cycle, the tri-
methylsilyl cyanide is first activated by the triphenylphosphine
oxide as previously reported,19 and then complexes to catalyst 1
to form adduct 4 in the rate-determining step of the catalytic cycle.
Coordination of benzaldehyde to the second metal ion of adduct 4
gives 5, which is set up to undergo intramolecular transfer of cya-
nide to the Lewis acid-activated aldehyde, forming complex 6 and
establishing the new stereocentre within the chiral environment of
the bimetallic salen complex. Transfer of a trimethylsilyl group to
the aluminium-bound cyanohydrin releases the cyanohydrin tri-
methylsilyl ether and regenerates complex 1 and triphenylphos-
phine oxide.
In conclusion, we have shown that in the presence of triphenyl-
phosphine oxide, aluminium complex 1 is an effective catalyst for
the asymmetric addition of trimethylsilyl cyanide to aldehydes.
The enantioselectivities obtained using catalyst 1 are comparable
to those obtained using mononuclear (salen)AlCl complexes,15b,c,f
but the synthesis of complex 1 from the chiral salen ligand can
Acknowledgement
The authors thank the EPSRC for a studentship (to C.W.).
References and notes
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0.008
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1
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Figure 2. Plot of kobs against [1] (open squares) and [Ph3PO] (filled diamonds) for
the addition of trimethylsilyl cyanide to benzaldehyde at 0 °C catalysed by complex
1 in dichloromethane. [PhCHO]0 = 0.26 M, [Me3SiCN]0 = 0.26 M (filled diamonds) or
0.42 M (open squares), [Ph3PO] = 0.025 M (open squares), [1] = 0.0051 M (filled
diamonds).