Communications
Substrates 4g–i required over 2 days reaction time and
10–15 mol% of 1 to attain high conversion, yet reached
completion within 6-14 h with comparable levels of enantio-
selectivity using 2.5 mol% of 2e. Imides bearing benzyl
(4i),[10] MOM (methoxymethyl, 4l), or TBDPS (tert-butyldi-
phenylsilyl, 4m) ethers, ester (4k) as well as benzyl carbamate
(4n) also afforded the corresponding cyanation products with
high to very enantioselectivity within 6 to 8 h (Table 1).
More remarkably, conjugate cyanation of imides 6a–c,
which were completely unreactive with catalyst 1 or with the
heterobimetallic combination, was effective with 5 mol% of
either catalyst 2e or 3. Cinnamate derivative 6a was thus
converted into 7a in 65% yield and 95% ee after 3 daysꢀ
reaction time (Figure 3). Similarly, using 5 mol% of catalyst 3,
Figure 4. Plot of rate/[cat.] versus [cat.] for the conjugate cyanation of
4e catalyzed by 2e. kintra =y intercept=7.63 sꢀ1, kinter =slope=
3.55ꢀ10ꢀ6 m, r2 =0.9785.
cept, respectively) in the conjugate cyanation of imides.
Remarkably, the second-order pathway with the dinuclear
catalyst 2e is two orders of magnitude greater than the
second-order component of the reaction catalyzed by 1.[12]
A
similar phenomenon was observed in epoxide ring-opening
reactions catalyzed by dinuclear {(salen)Cr} complexes, and
may be attributed to enhanced Lewis acidity of the dinuclear
catalysts.[5]
We have developed covalently linked dinuclear {(salen)-
Al} complexes that catalyze the conjugate cyanation of a,b-
unsaturated imides with several orders of magnitude greater
reactivity than the mononuclear analogue 1 and with com-
parable enantioselectivity. Addition products that were
inaccessible with the original homobimetallic and heterobi-
metallic systems are now converted into the corresponding
cyanation products with high level of enantioselectivity.
Remarkably, the same dinuclear scaffolds have proven
optimal for epoxide ring-opening and conjugate cyanation
reactions, despite the use of different reactive metal centers
and the fundamentally distinct geometrical characteristics of
these transformations. We anticipate further applications of
these linked salen–metal catalyst systems to other reaction
classes.
Figure 3. Conjugate cyanation of less reactive a,b-unsaturated imides
catalyzed by 2e or 3. Reactions were carried out at 508C for 3 days on
a 0.5 mmol scale using 6.5 equivalents of TMSCN and iPrOH, and
0.6 m tert-butyl methyl ether.
product 7b was generated in 92% ee with concomitant
formation of a quaternary center, albeit in a modest 38%
yield.[11] The addition of cyanide to sorboyl imide 6c catalyzed
by 3 provided the 1,4-addition product 7c exculsively in 47%
yield and 95% ee. No trace of 1,6-addition product was
observed.
Received: September 27, 2007
Revised: December 12, 2007
Published online: January 24, 2008
Kinetic studies of the 1,4-cyanation reaction of imide 4e
catalyzed by 2e were carried out by monitoring initial rates of
product formation by H NMR spectroscopy. In contrast to
the purely second-order dependence observed with mono-
nuclear catalyst 1,[1] a two-term rate law consistent with the
participation of both intra- and intermolecular pathways was
considered [Eq. (1)].
Keywords: aluminum · asymmetric catalysis · cyanation ·
dinuclear complexes · kinetics
.
1
2
ð1Þ
rate ¼ kintra ½cat: þ kinter ½cat:
[4] Typically, 10–40 mol% of chiral ligand were used. Reaction time
ranged from 8 h to 6 days. See ref. [2b] for details. The second
generation of catalyst reported in ref. [2b] partially circumvents
these limitations.
Figure 4 shows a plot of rate/[cat.] versus [cat.] according
to equation (2). The linear correlation with a positive slope
rate=½cat: ¼ kintra þ kinter ½cat:
ð2Þ
and a nonzero intercept is consistent with a contribution of
both inter- and intramolecular pathways (slope and y inter-
1764
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 1762 –1765