Angewandte
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spectroscopy) for tertiary amides in the presence of compet-
catalyzed hydrosilylation based on the following observations.
ing groups like ketones (Table 3, entry 8, 14, and 15), esters
(Table, entry 7, 17, and 18), aldimines (Table 3, entry 19), and
isocyanates (Table 3, entry 20). The catalytic activity was not
affected even in the presence of alcohol (Table 3, entry 21).
However an excess of silane (4 equiv) was necessary since
First, the least basic substrate is reduced with the fastest rate,
following the order ester> ketone > aldehyde. This was also
observed by Beller and co-workers in their zinc-catalyzed
amide reduction, in which the less nucleophilic substrate
experienced faster reduction.[5r] Secondly, the experimentally
derived rate law for the hydrosilylation of ketone by B(C6F5)3
silane–alcohol dehydrogenative coupling also took place.[10]
A
few limitations were discovered. Aldehydes were not toler-
ated, since PhCHO was preferentially reduced under similar
conditions in the presence of one equivalent of DMA
(Table 3, entry 16). Substrates like 1,1,3,3,-tetramethylurea
(Table 3, entry 12) and N-methyldiacetamide (Table 3,
entry 13) were inert under these conditions. An equivalent
amount of pyridine completely shut down the catalysis
(Table 3, entry 22), whereas thiophene did not inhibit the
reaction (Table 3, entry 23). Catalyst loading as low as
1 mol% also resulted in full conversion in the reduction of
N,N-dimethylbenzamide (DMB, 1 mmol scale) with PhMe-
SiH2 within 18 h at room temperature. TMDS worked equally
well for all these substrates. For several of them, the product
amines were isolated on a mmol scale.
shows an inverse dependence on [substrate], which indicates
[20a]
À
the necessity of free B(C6F5)3 for activating the Si H.
A Lewis acid/base type interaction in the case of BPh3 and
1
DMA was clearly evident. The H and 13C NMR resonances
of a 1:1 mixture in [D2]DCM are noticeably shifted from their
individual spectra. The 11B resonance of BPh3 shifted from
d = 67.5 to 38.5 ppm (see the Supporting Information). No
such shift in NMR resonances was detected in 1:1 or 1:10
mixtures of BPh3 with either acetophenone or ethyl acetate.
The order of basicity of carbonyl ligands toward B(C6F5)3
follows the trend amide > aldehyde > ketone > ester.[19] This
probably explains the chemoselectivity observed for BPh3,
since the weaker and selective interaction with the amides
appears to be critical. In contrast, an opposite reactivity trend
compared to that found for B(C6F5)3 was observed with the
BPh3 catalyst. As evident from Table 3 (entry 3 to 7), the less
nucleophilic amides are reduced at a slower rate. Further-
more, preliminary kinetic experiments showed that an
increase in [substrate]ini led to a higher reaction rate instead
of slowing it down. These observations are not in agreement
with the silane activation route, where the catalyst–substrate
interaction is deleterious. Additionally, the rate increased
with an increase in [PhMeSiH2]ini. Reduction with PhMeSiH2
was also faster than with PhMeSiD2 (see the Supporting
Information).
The a,b-unsaturated enamide N,N-dimethylacrylamide
=
was hydrosilylated at the C C double bond (Scheme 1). A
The reduction of amides to amines is fundamentally
different from that of carbonyls and esters. Based on these
preliminary results, we propose a carbonyl activation route
(Scheme 2) that takes into account the experimental findings.
The proposed mechanism for this apparently two-step
reduction involves O-silyl hemiaminal and iminium species
as intermediates. A similar pathway has been postulated
before for Zn,[5r] Fe,[5b] and In[5t] catalysts, as well as for the
classical reduction with LiAlH4.[21] Further in-depth kinetic
Scheme 1. BPh3-catalyzed reductive a-silylation of conjugated amides
with terminal and internal olefinic double bonds.
fast 1,4-hydrosilylation was followed by a slower silyl group
migration to afford the a-silyl amide as an 1:1 mixture of two
diastereomers. N,N-diethyl-3-phenylacrylamide containing an
internal double bond was also a-silylated in similar fashion.
The a,b-conjugated ester ethyl cinnamate remained inert
even after prolonged heating at 608C. The silyl migration step
has previously been catalyzed by aluminium[16] and lanthanide
complexes.[17] During our study, Chang and Kim reported
similar results using B(C6F5)3 as the catalyst, which reduces
both conjugated esters and amides.[18] Additionally, this study
postulated that silylium ions may possibly be generated
during the migration.
Stronger Lewis acidic boranes usually interact with
[19]
=
carbonyls (C O) rather than hydrosilanes.
Evidence for
À
a borane to Si H interaction has been obtained only under
special circumstances.[20] Piers and co-workers reported that
À
a B(C6F5)3···H Si interaction is fast on the reaction timescale
and that carbonyl hydrosilylation by this catalyst actually
follows a silane activation mechanism.[20a] An alternative
carbonyl activation route was discarded for the B(C6F5)3-
Scheme 2. Proposed mechanism for BPh3-catalyzed hydrosilylative
reduction of tertiary amides to amines following a carbonyl activation
pathway.
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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