2d in 59, 77 and 87% yields, respectively (entries 1À3). The
use of primary amine such as aniline 2e resulted in the
major formation of the expected mono alkylated com-
pound 3e in 66% yield along with dialkylated amine in 6%
yield (entry 4). It is noteworthy, that longer reaction time
(24 h) increased the formation of the dialkylated amine
based on dealkylation/alkylation via the intervention of
hydrogen autotransfer process. Thus, an excess of alcohol
resulted in the formation of the dialkylated amine in 62%
yield along with 10% of monoalkylated amine (Scheme 1).
Table 1. Ruthenium-Catalyzed Reductive Amination of
Cinnamyl Alcohola
entry
1ab
additivesc
none
yieldd
1
2
3
4
5
6
7
8
1.2
1.4
1.6
1.8
2.0
1.2
1.2
1.2
41
44
none
none
48
Scheme 1. Amination via multi hydrogen transfer processes
none
62
none
61
i-PrOH (1)
HCO2H (1)
HCO2H (1.1)
36
75
98(82)e
a All reactions were carried out at 0.2 M concentration in toluene at
150 °C for 15 h under an inert atmosphere with 2a/cat. A in 1/0.025 molar
ratio. b Equivalent of 1a. c Equivalent of additive. d Yield determinated
by GC using n-tetradecane as internal standard. e Number in parenth-
eses is isolated yield.
Other alcohols were also evaluated. Interestingly, geraniol
1b which contains additional carbonÀcarbon double bond
was converted into amines 3fÀi in 57À65% isolated yield
(entries 5À8). Compounds 3fÀi are formed as major
products with only traces of the fully saturated products
(less than 10%) highlighting the high chemoselectivity of
the reduction process toward the initial allylic alcohol
carbonÀcarbon double bond.
describedin Table 1. Experiments were performedat 150 °C
with 2.5 mol % of precatalyst A7 for 15 h (Figure 1). The
role of cinnamyl alcohol 1a was first investigated and as
expected, 1a was not only a reactant but also played the
role of sacrificial hydrogen donor. Indeed, as shown in
entries 1À4 an excess of alcohol led to an increase of the
formation of saturated amine 3a leading to 62% GC yield
as the best result in the presence of 1.8 equivalent of 1a
(entry 4). Increasing the amount of alcohol did not im-
proved the yield and resulted in the formation of aldol
condensation side products (entry 5). To ensure better
results, additional hydrogen donors were then investi-
gated. Thus, the use of stoichiometric amount of i-PrOH
in the presence of 1.2 equiv of cinnamyl alcohol did not
improve the yield (entry 6 as compared to 1). Even worse,
the use of isopropanol as solvent afforded no conversion.
We then turned out our attention on formic acid as hydro-
gen donor. Remarkably, the use of equimolar amount of
formic acid resulted in complete consumption of N-ethy-
laniline 2a to afford 75% yield (entry 7). Further optimiza-
tion led to the use of a slight excess of formic acid to give
82% of isolated yield (entry 8). Other ruthenium sources
such as Shvo catalyst,8 [RuCl2(p-cymene)]29 afforded low-
er conversions and yields. With our best conditions in
hands, we further enlarged the scope of this transforma-
tion. Various amines and allylic alcohols were evaluated
(Table 2). Cinnamyl alcohol 1a was smoothly converted
to the expected saturated amines with secondary cyclic
amines such as piperidine 2b, pyrrolidine 2c and azepane
Scheme 2. Amination via Multi Hydrogen Transfer Processes
Similarly, good results were obtained with hex-2-en-1-ol
1c, crotyl alcohol 1d and isoprenol 1e affording alkylated
products in 48À82% yield (entries 9À14). Phytol 1f, a
linear diterpene featuring a terminal allylic alcohol func-
tionality was also efficiently converted into the corre-
sponding amine 3p from 2a (entry 15). We showed that
the reaction is only possible with amines as N-protected
carbamates and sulfonamides did not react. Taking into
account that several hydrogen processes occurred simul-
taneously, we undertook the challenging preparation -
of amines 3f starting from a mixture a substrates. After
(7) Sundararaju, B.; Tang, Z.; Achard, M.; Sharma, G. V. M.;
Toupet, L.; Bruneau, C. Adv. Synth. Catal. 2010, 352, 3141.
(8) Shvo, Y.; Czarkie, D.; Rahamim, Y. J. Am. Chem. Soc. 1986, 108,
7400.
(9) (a) Bennett, M. A.; Huang, T.-N.; Matheson, T. W.; Smith, A. K.
Inorg. Synth. 1982, 21, 74. (b) Bennett, M. A.; Smith, A. K. J. Chem.
Soc., Dalton Trans. 1974, 233.
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