for the dimerization of benzaldehyde to benzyl benzoate.
More recently, homoleptic lanthanide amides, M[N(SiMe3)2]3
(M ) Sc, Y, La), have been reported as highly active
catalysts for the Tischenko reaction, mediating the dimer-
ization of aromatic and aliphatic aldehydes to the carboxylic
esters with turnover frequencies (TOF) ranging from 2 to
1500 h-1.8 In this instance, the reaction mechanism has been
investigated and proposed to occur via the formation of an
intermediate lanthanide(III) alkoxide.8
Table 1. Dimerization of Benzaldehyde to Benzyl Benzoate
Catalyzed by 1 mol % of M{N(SiMe3)2}2(THF)2 in C6D6 at
Room Temperature
catalyst
TOF/h-1
NMR yield/%
We now present a preliminary report that the heteroleptic
calcium amide 1 and the readily synthesized homoleptic
alkaline earth amides 2a-c are competent precatalysts for
the dimerization of aldehydes to carboxylic esters (Scheme
1).
2a
2b
2c
52
41
1.6
97
78
86
An initial reaction between benzaldehyde and 10 mol %
of 1 was conducted on an NMR scale in C6D6. After 1 h at
room temperature, the production of benzyl benzoate was
observed as evidenced by the appearance of a characteristic
methylene singlet of the product at 5.21 ppm, with a
concomitant decrease in intensity of the aldehyde proton of
benzaldehyde. The reaction was complete within 2 h, and
benzyl benzoate was identified as the major volatile product
by NMR and GC-MS analysis. The reaction could be
repeated with 1 mol % of 1 with no loss of activity. In both
cases, the dimerization of benzaldehyde was accompanied
by the production of the protonated ligand ArNHC(Me)CHC-
(Me)NAr (Ar ) 2,6-diisopropylphenyl), observed in the 1H
NMR. This result suggested the catalytically active species
was not supported by the spectator ligand. On the basis of
this observation, a series of simple homoleptic alkaline earth
amides, M{N(SiMe3)2}2(THF)2 (M ) Ca, Sr, and Ba,
2a-c), were synthesized by metathesis of MI2 with 2 equiv
of KN(SiMe3)2 in THF, and their catalytic reaction with
benzaldehyde was investigated on an NMR scale. The results
of these experiments are presented in Table 1. Compounds
2a-c were found to be active catalysts for the dimerization
of benzaldehyde to benzyl benzoate. In all cases, the latter
was observed as the major product of the reaction. The
turnover frequency of the reaction decreases with increasing
ionic radius of the alkaline earth metal. This result is in stark
contrast to that observed in the lanthanide series, M{N-
(SiMe3)2}3 (M ) Sc, Y, La), for the same reaction where
turnover frequencies increase with increasing ionic radius.8
Indeed, although the reaction could be catalyzed by Ba-
{N(SiMe3)2}2(THF)2, 2c, turnover was markedly slow and
the reaction took several days to near completion.
Recent reports have shown that pretreated alkaline earth
oxides, MO (M ) Ca, Sr, Ba), may act as heterogeneous
catalysts for the Tischenko reaction with activities increasing
with the increasing basicity of the M-O bond (Sr > Ca .
Ba).9 To ascertain that the observed catalytic activity was
due to a homogeneous intermediate, and not hydrolysis
products, the reaction of benzaldehyde with 2a was carried
out following exposure of the catalyst to an aerobic
atmosphere. In these instances, no benzyl benzoate produc-
tion was observed.
The scope of the reaction was investigated, and a series
of aromatic, heteroaromatic, and aliphatic aldehydes were
allowed to react with 1-5 mol % of Ca{N(SiMe3)2}2(THF)2
2a. The reactions were performed on both an NMR and a
preparative scale (Table 2). In all cases, the preparative scale
yields paralleled those observed by NMR and the products
were isolated and fully characterized (see Supporting Infor-
mation). This study showed that 2a was an effective catalyst
for both the inter- and intramolecular Tischenko reaction,
with the rate of the latter exceeding that of the former. A
number of aromatic aldehydes and both enolizable and
nonenolizable aliphatic aldehydes are reactive substrates
giving the analogous dimeric esters in high yield. The
reactivity of enolizable aliphatic aldehydes with 2a under
these conditions is of particular note as the stoichiometric
reaction of Ca{N(SiMe3)2}2(THF)2 with acetophenone is
reported to give a high yield of the corresponding calcium
enolate, which has been isolated and characterized in the
solid state.10
The dimerization of more electron-rich aromatic aldehydes
with the calcium amide 2a proved unsuccessful. Indeed, the
attempted dimerization of N-methylindole-2-carboxaldehyde,
2-furfuraldehyde, and p-N,N-dimethylbenzaldehyde by 2a
were all ineffective, even at higher reaction temperatures and
catalyst loadings. Although it is feasible that heteroatom-
substituted substrates may inhibit catalytic turnover by
coordination to the electrophilic calcium center, treatment
of 2a with m-anisaldehyde gave an almost quantitative yield
of 3-methoxybenzyl 3-methoxybenzoate. In contrast, under
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Org. Lett., Vol. 9, No. 2, 2007