Mizuta et al.
TABLE 1. Reductive Alkylation of 1a with 2a and 3 to
seems to be necessary to reduce the resulting enamine.
In this reaction, water, generated in the enamine forma-
tion from amine and aldehyde, would play an important
role as a hydrogen source as discussed later. Additionally,
it is worth noting that no reduction of aldehyde 2a
occurred during the reaction. The enamine formed in situ
from secondary amine and aldehyde could be reduced
with complete selectivity.
4
1
aa in the Presence of an Ir or Rh Catalyst (mol ratio of
a
a:2a:3 ) 1:1:1)
run
catalystb
yield (%)
1
2
3
4
5
6
7
[IrCl(cod)]2
[IrCl(coe)2]2
[Ir(cod)2]BF4
[Cp*IrCl2]2
IrCl(CO)(PPh3)2
[RhCl(cod)]2
IrCl3
98
83
79
27
29
19
44
99
c
8
IrCl3
a
1
a (1 mmol) was allowed to react with 2a (1 mmol) and 3 (1
mmol) in the presence of catalyst (0.01 mmol - Ir or Rh) in 1,4-
b
dioxane (2 mL) at 75 °C for 8 h. cod, 1,5-cyclooctadienyl; coe,
c
cyclooctenyl; Cp*, 1,2,3,4-tetramethylcyclopentadienyl. Reaction
was run in toluene (1 mL) at 110 °C for 15 h.
7
et al. Quite recently, Fujita and Yamaguchi established
the N-alkylation of primary and secondary amines with
alcohols catalyzed by [Cp*IrCl
]
2 2
in the presence of a base
Among the iridium complexes examined, [IrCl(cod)]
was found to be the best catalyst, followed by [IrCl(coe)
and a cationic complex such as [Ir(cod) ]BF
Cl ] and the Vaska complex were inert (runs 1-5). A
2
8
such as K
2
CO
3
.
2 2
]
During the course of our studies on the iridium-
2
4
, but [Cp*Ir-
9
catalyzed organic syntheses, we have disclosed the
2 2
rhodium complex such as [RhCl(cod)]
2
had difficulty
chemoselective transfer hydrogenation of R,â-unsaturated
ketones to saturated ketones using 2-propanol as a
catalyzing the reductive alkylation of 1a with 2a and 3
(
3
run 6). Surprisingly, it was found that IrCl , which is a
2 2 3
hydrogen donor catalyzed by the [IrCl(cod)] /dppp/Cs CO
9c
starting material for the preparation of [IrCl(cod)]2
system (dppp: diphenylphosphinopropane). In addition,
the R-alkylation of ketones with alcohols without employ-
ment of any solvents has been successfully achieved by
the use of a similar catalytic system.9b These reactions
are thought to proceed through an iridium-hydride [Ir-
H] (or iridium-dihydride [H-Ir-H]) generated in situ
complex, was also an efficient catalyst for the present
reaction. When 1a was allowed to react with 2a and 3 in
the presence of a catalytic amount of IrCl (mol. ratio of
3
1
3
a:2a:3:IrCl ) 1:1:1:0.01) at 110 °C for 15 h, 4 was
obtained in excellent yield (run 8). This is the first
example of the Ir-catalyzed reductive alkylation of sec-
from [IrCl(cod)]
species. Now, we have considered that the [Ir-H] species
could be generated by allowing [IrCl(cod)] to react with
2
, alcohol, and a base as a key catalytic
3
ondary amine with aldehyde and Et SiH.
Table 2 summarizes the reductive alkylation of various
secondary amines with aldehydes and 3 under the
2
influence of [IrCl(cod)] . These reactions were performed
2
organosilanes. Here, we would like to report the reductive
alkylation of secondary amine with aldehyde and tri-
ethylsilane in the presence of a catalytic amount of an
iridium compound by using a 1:1:1 mixture of amine,
by the use of a 1:1:1 molar ratio of amine:aldehyde:3 to
furnish the corresponding tertiary amines in good yields.
Unfortunately, the reductive alkylation of primary amine
was difficult to carry out with selectivity, because a part
of the secondary amines formed was further reacted
under these reaction conditions. Almost no reaction
occurred by using ketone in place of aldehyde in the
present reaction.
Next, we examined the reductive alkylation with
polymethylhydrosiloxane (PMHS, 5) as a reducing re-
agent. It is known that use of PMHS is advantageous as
a cheap, easy-to-handle, and environmentally friendly
3
aldehyde, and Et SiH.
Results
The reductive alkylation of dibutylamine (1a) with
butyraldehyde (2a) and triethylsilane (3) was selected as
a model reaction and was examined under the influence
of several Ir and Rh catalysts (eq 1, Table 1). The reaction
of 1a with 2a and 3 in 1,4-dioxane at 75 °C for 8 h
2
catalyzed by [IrCl(cod)] afforded tributylamine (4aa) in
reagent for reduction of organic functional groups, be-
cause it could be removed with ease.5
d,10
Treatment of
1a (1 mmol) with 2a (1 mmol) and 5 (0.05 mmol, about
1.4 equiv of hydride) in the presence of [IrCl(cod)] (0.005
2
-7
mmol) in THF at 50 °C gave 4aa in 99% yield (Scheme
1). It is interesting that the reaction was also promoted
by IrCl , forming 4aa in 91% yield. On the basis of these
3
results, several amines were alkylated with aldehydes
and 5 (Table 3). Except for the reaction of 1f with 2a,
tertiary amines were obtained in excellent yields. Be-
cause a polymer derived from PMHS was dissolved in
(
7) Hansen, M. C.; Buchwald, S. L. Org. Lett. 2000, 2, 713.
8) Fujita, K.-I.; Li, Z.; Ozeki, N.; Yamaguchi, R. Tetrahedron Lett.
(
2
003, 44, 2687. We recently reported R-alkylation of ketones with
alcohols catalyzed by [IrCl(cod)]
9b
2
.
(
9) (a) Ishii, Y.; Sakaguchi, S. Bull. Chem. Soc. Jpn. 2004, 77, 909.
(10) Review: Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem.
Soc., Perkin Trans. 1 1999, 3381. For recent papers, see: (a) Dumond,
Y. R.; Gum, A. G. Angew. Chem., Int. Ed. 2003, 42, 4789. (b) Czekelius,
C.; Carreira, E. M. Angew. Chem., Int. Ed. 2003, 42, 4793.
(
b) Taguchi, K.; Nakagawa, H.; Hirabayashi, T.; Sakaguchi, S.; Ishii,
Y. J. Am. Chem. Soc. 2004, 126, 72. (c) Sakaguchi, S.; Yamaga, T.;
Ishii, Y. J. Org. Chem. 2001, 66, 4710.
2196 J. Org. Chem., Vol. 70, No. 6, 2005