ACS Catalysis
Letter
a
line (1a) and CO has been explored using a variety of
organocatalysts able to form adducts with CO2 or promote its
Table 1. Catalyst Screening for the Coupling of 1a to 2a
2
11
reduction, such as guanidines, amidines, N-heterocyclic
3
a,b,5f,g,12
carbenes (NHCs), and phosphorus bases.
Using
1
0 mol% of the NHC ItBu, CO undergoes hydrosilylation
2
in the presence of N-methylaniline (1a) in CH CN, and after
3
2
2
.5 h at 80 °C, 76% of 1a was converted to the expected aminal
a in 47% yield (Scheme 2). Nonetheless, methylamine 3a is
Scheme 2. Formation of Aminal 2a via CO Hydrosilylation
2
entry catalyst (mol%) reductant time (h) yield 2a (%) yield 3a (%)
1
2
3
4
5
6
7
8
9
ItBu (10)
IPr (10)
PhSiH3
PhSiH3
2.5
4.5
2.5
4.5
2.5
2.5
3.0
7.0
96
52
79
71
78
93
93
91
92
5
18
3
0
0
4
7
6
6
0
0
0
0
0
VBMe (10)
Me-TBD (10)
DBU (10)
TBD (10)
TBD (5)
TBD (1)
TBD (5)
TBD (5)
TBD (5)
TBD (5)
TBD (5)
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
also produced at a similar rate and reaches 25% yield.
Interestingly, after prolonged reaction time (24 h) methylamine
3
a is formed as the main nitrogen product (>95%), indicating
that the aminal is an intermediate in the formation of 3a and0
that the catalyst is unable to prevent over-reduction of the C
PhSiH3
carbon center in 2a. Reducing the quantity of CO in the
2
PMHS
reaction vessel to ca. 1 equiv per amine somewhat improves the
1
0
TMDS
96
0
2
a/3a ratio of the reaction from 1.9 to 2.9 (Scheme 2).
Although encouraging, these results stress the need for a
b
1
1
PhSiH3
PhSiH3
PhSiH3
48
5
c
1
2
48
7
catalyst having a balanced reactivity in CO hydrosilylation, to
2
d
1
3
19
26
avoid the methylation of the amine. While IPr, Verkade’s base
Me
a
VB or guanidine Me-TBD enables the formation of 2a in up
Reaction conditions: NMR tube (2.5 mL), catalyst, amine (0.10
mmol), hydrosilane (6 eq. “Si−H”), solvent (0.30 mL), CO (1 bar).
Yields determined by H NMR with Ph CH as internal standard. In
to 79% yield, the best activities and selectivities were obtained
with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-
triazabicyclo[4.4.0]dec-5-ene (TBD) as catalysts for which
the reaction was complete after 2.5 h, yielding 93% of the
desired aminal 2a and 3a as side-product (7%) (Entries 2−6,
Table 1). As expected, no reaction occurred after 24 h in the
2
1
b
2
2
c
d
toluene-d . In THF-d . At RT.
8
8
grown from the crude mixture confirmed the presence of the
untouched carbonyl group and, hence, the ability of the catalyst
to avoid over-reduction (Figure 1).
absence of CO or catalyst. Importantly, with a low catalyst
2
In order to widen the scope of aminal compounds available
from the present methodology, the influence of the substituent
on the nitrogen atom has been investigated. N-ethylaniline (1l)
and N-allylaniline (1m) were converted in good 73% and 77%
yields to 2l and 2m, respectively. The bulky N-benzylaniline
gave the desired product 2o in 94% after 2 h at 80 °C. N,N-
diphenylaniline only furnished 24% of 2n after 21 h,
presumably because of its poor nucleophilicity. Cyclic amines
such as indoline (1p) and 1,2,3,4-tetrahydroquinoline (1q)
were converted to their aminal analogues 2p and 2q in good
70% and 87% yields. The reaction is also viable with secondary
heteroaromatic amines: the formation of 2s from 2-methyl-
aminopyridine was accomplished quantitatively, and 2s was
isolated in 88% yield after removal of the siloxanes byproducts.
In contrast, the reaction with 4-methylaminopyridine resulted
in the formation of the corresponding formamide as a major
product (85%), and only 14% of the aminal 2t were observed.
Naturally, the formation of the heterocycle is favored over an
intermolecular reaction for diamino substrates, thus providing
2r and 2u with excellent 88 and 95% yield, respectively.
However, starting from an aliphatic amine such as morpholine,
only the corresponding formamide was yielded, and no trace of
1
the aminal product could be detected by H NMR. This
aminals is also chemoselective and oxidizing groups such as a
nitrile or ketone are tolerated, as exemplified in the formation
of 2j (95% yield) and 2k (98% yield). Indeed, crystals of 2k
observation may be due to the stronger nucleophilicity of
aliphatic amines, which facilitates the production of a
formamide that is unproductive in the formation of aminals.
3
984
ACS Catal. 2015, 5, 3983−3987