1830
T. Matsumura, M. Nakada / Tetrahedron Letters 55 (2014) 1829–1834
Table 2
limited reports on DRA using organosilane as a reducing reagent.
Organosilanes such as triethylsilane (TESH), in the presence of acid
catalysts, are mild and useful reagent systems for reduction. How-
ever, trifluoroacetic acid (TFA)/TESH22 is not compatible with acid
labile functional groups. The use of TiCl4/organosilane23 is limited
R3SiH (3.0 equiv)
BiCl3 (10 mol%)
Ph
Ph
Ph
O
Ph
Ph
N
N
H
+
Ph
H
solvent, rt, 23 h
24
to aromatic aldehydes. Bu2SnCl2/PhSiH3 is toxic, Ti(OiPr)4/poly-
Entry
Organosilane
Solvent
Yielda (%)
methylhydrosiloxane (PMHS)25 is water-sensitive, and organosi-
lane with a hydrio-iridium complex26 is not compatible with
substrates containing reducible functionalities. Hence, the devel-
opment of improved methods using organosilanes is still antici-
pated. We herein report DRA using TESH and catalytic
bismuth(III) chloride (BiCl3).
1
2
3
4
5
6
7
Et3SiH
Et3SiH
Et3SiH
Et3SiH
Et3SiH
Et3SiH
Et3SiH
Ph3SiH
(EtO)3SiH
PhMe2SiH
Et2SiH2
Ph2SiH2
PhMeSiH2
PhSiH3
CH3CN
Toluene
Et2O
CH2Cl2
THF
99
Trace
Trace
NR
NR
NR
NR
NR
NR
71
DMF
DMSO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
The preparation of aryl- and diarylamine derivatives is impor-
tant in research on structure–activity relationships. The DRA of
aryl- and diarylamines is a rational approach from the standpoint
described above, and DRAs, which use organosilane and a catalytic
amount of Ga(OTf)327 or InCl3,28 have also been reported. However,
both reagents are relatively expensive, and in the latter system, the
unsaturated carbonyl compounds are potentially reduced.29 More-
over, it has been reported that In(III) results in teratogenicity in
rats.30
8
9
10
11
12
13
14
72
42
95
97b
a
Isolated yield.
The reaction required 7 h to be completed.
b
It has been reported that diarylamines are included in many
biologically active and pharmaceutically relevant compounds,31
as well as new materials,32 but DRAs of aldehydes and diphenyl-
amine have been limited. Therefore, we started to screen various
Lewis acids as a catalyst for the DRA of benzaldehyde and
diphenylamine using TESH and Lewis acid.33
disadvantages, as described above. Consequently, the results listed
in Table 1 indicate that the use of BiCl3 (10 mol %) is the most effec-
tive and practical for the DRA of benzaldehyde and diphenylamine
using TESH.
To the best of our knowledge, DRA using organosilanes and cat-
alytic Bi(III) has never been reported. In addition, Bi(III) has been
used as an efficient green catalyst because of its many advantages,
including its easy handling, low cost, nontoxic nature, and mild Le-
wis acid activity.34 Hence, we decided to study DRA using organo-
silanes and BiCl3.
The DRA was examined using a 1:1 ratio of benzaldehyde and
diphenylamine in the presence of 3.0 equiv of TESH and 10 mol %
Lewis acid in acetonitrile at room temperature (Table 1). TiCl4
(59%, entry 1) and SnCl4 (68%, entry 2) afforded the product in good
yields. SbCl5 (entry 3), ZnCl2 (entry 4), PbCl2 (entry 5), and
CeCl3Á7H2O (entry 6) did not afford any product, and YCl3Á6H2O
was almost ineffective (10%, entry 7). The yields in the reactions
with Bi(III) were high, except BiF3 (0%, entry 8). The yield was
99% when 10 mol % of BiCl3 was used (entry 9), and use of the
reduced amount (5 mol %) reduced the yield to 34% (entry 10).
The yields when BiBr3 and BiI3 were used were 79% (entry 11)
and 81% (entry 12), respectively. Interestingly, Bi(OTf)3 (74%, entry
13), which is known to be a strong Lewis acid, was less effective
than the other Bi(III) reagents (entries 9, 11, 12). The DRA catalyzed
The reaction conditions for DRA using BiCl3 were examined
(Table 2). The DRAs of benzaldehyde and diphenylamine using
TESH in various solvents were screened. Trace amounts of the
product were obtained in toluene (entry 2) and diethyl ether (entry
3), but no reactions occurred in dichloromethane (entry 4), THF
(entry 5), DMF (entry 6), and DMSO (entry 7). Reactions with some
organosilanes were also examined, but no reaction occurred with
Ph3SiH (entry 8) and (EtO)3SiH (entry 9). The reactions with
PhMe2SiH (entry 10), Et2SiH2 (entry 11), Ph2SiH2 (entry 12), PhM-
eSiH2 (entry 13), and PhSiH3 (entry 14) afforded the product in
yields of 71%, 72%, 42%, 95%, and 97%, respectively. The results
listed in Table 2 indicate that the DRA of benzaldehyde and diphe-
nylamine exhibited the best performance when TESH or PhSiH3 in
the presence of catalytic BiCl3 in acetonitrile as the solvent was
used.
The DRAs of various aldehydes and ketones using TESH and
BiCl3 were examined, as summarized in Table 3. The substituent
effect of substrates was observed in the DRAs of arylaldehydes
with diphenylamine (Table 3). The yield was reduced in the DRAs
of o-chlorobenzaldehyde (entry 2) and o-ethynylbenzaldehyde
(entry 3), which can be attributed to the steric hindrance suffered
from the o-substituent. The yield in the DRA of p-nitrobenzalde-
hyde (entry 4) was 90%, while that of p-methoxybenzaldehyde
(entry 5) decreased to 35% and the starting material remained. This
difference can be explained by the electronic effect of the substitu-
ent, that is the electron-donating p-substituent deactivated the
benzaldehyde. This electronic effect well explains the DRA of
3,4,5-trimethoxybenzaldehyde (entry 6) in which the product
was formed with a low yield and the starting material remained
again.
28
by InCl3 proceeded faster and afforded the product with 95%
yield (entry 14); however, InCl3 is relatively expensive and has
Table 1
Et3SiH (3.0 equiv)
catalyst (10 mol%)
Ph
Ph
Ph
O
Ph
Ph
N
N
H
+
Ph
H
CH3CN, rt
Entry
Catalyst
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
TiCl4
SnCl4
SbCl5
ZnCl2
PbCl2
CeCl3Á7H2O
YCl3Á6H2O
BiF3
BiCl3
BiCl3
BiBr3
BiI3
23
23
23
23
23
13
13
13
13
13
13
13
13
10
59
68
9
NR
NR
NR
10
NR
99
34
79
81
74
95
9
10b
11
12
13
14
Bi(OTf)3
InCl3
The above substituent effect is consistent with a reaction mech-
anism via the formation of iminium by the nucleophilic attack of
diphenylamine to aldehyde and the subsequent reduction of the
imine. Chloride, nitro group, and alkyne, which are reducible
a
Isolated yield.
BiCl3 (5 mol %) was used.
b