CHEMCATCHEM
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DOI: 10.1002/cctc.201300477
A Widely Applicable Regioselective Aerobic a-Cyanation of
Tertiary Amines Heterogeneously Catalyzed by Manganese
Oxides
Kazuya Yamaguchi, Ye Wang, and Noritaka Mizuno*[a]
a-Amino nitriles are an important class of compounds and
have been utilized as versatile synthetic intermediates for
value-added products, such as a-amino acids, a-amino alde-
hydes, a-amino alcohols, vicinal amines, and alkaloids.[1] Classi-
cally, a-amino nitriles have been synthesized by wasteful and
substrate-limited procedures.[1] As an alternative, cross-dehy-
drogenative coupling-type a-cyanation of (tertiary) amines by
activation of C(sp3)ÀH bonds adjacent to amino groups is now
emerging as one of the most green and straightforward syn-
thetic procedures for a-amino nitriles.[2–9] To date, several stoi-
chiometric, catalytic, and photocatalytic procedures using vari-
ous oxidants such as singlet oxygen,[2] chlorine dioxide,[3] hy-
pervalent iodines,[4] tropylium ion,[5] tert-butyl (hydro)perox-
ide,[6] hydrogen peroxide,[7] and molecular oxygen (triplet
oxygen)[8,9] have been reported (Table S1). However, in almost
all cases, the substrate scopes are limited only to reactive N,N-
dialkylanilines (including N-aryltetrahydroisoquinolines) and
the recovery and reuse of the (homogeneous) catalysts are
quite difficult (Table S1).[2–9] Therefore, the development of effi-
cient and widely applicable a-cyanation systems is an impor-
tant subject. The use of heterogeneous catalysts and molecular
oxygen as a terminal oxidant would be more desirable from
the standpoint of green chemistry.[10]
be applied to the present cyanation, giving the corresponding
a-amino nitriles in moderate to high yields.
Initially, the cyanation of N,N-dimethyl-1-butylamine (1a)
was performed in the presence of various of catalysts
(Table 1).[17,18] Compound 1a was chosen as a model substrate
Table 1. a-Cyanation of 1a under various conditions.[a]
Entry
Catalyst
Conv. of
Total yield
2a/2a’
1a [%]
(2a+2a’) [%]
ratio
1
2
3
4
5
6
7
8
OMS-2[b]
89
25
90
80
38
36
19
5
15
11
34
10
56
18
4
88
23
79
66
34
5
10
4
11
6
95/5
95/5
97/3
91/9
83/17
94/6
79/21
82/18
80/20
86/14
88/12
86/14
57/43
87/13
45/55
OMS-2+BHT[c]
b-MnO2
amorphous MnO2
d-MnO2
Co3O4
CeO2
V2O5
9
RuCl3·nH2O[d]
[d]
10
11
12
13
14
15
CuCl2
FeCl3
[d]
15
7
42
8
[d]
MoO2(acac)2
AIBN[d]
[d]
I2
Manganese oxide-based octahedral molecular sieves, in par-
ticular OMS-2 (2ꢀ2 hollandite structure, KMn8O16·nH2O, Fig-
ure S1),[11] have been recognized as efficient oxidation catalysts,
owing to their excellent properties, such as large (external) sur-
face areas, redox ability, electron-conducting properties, and
oxygen reduction abilities.[11–15] By using OMS-2, various catalyt-
ic oxidation systems, e.g., dehydrogenation of alcohols,[12] de-
hydrogenation and oxygenation of primary amines,[13] oxygen-
ation of alkylarenes,[14] and oxidative amidation of primary al-
cohols and methylarenes,[15] have been developed to date.[16]
Herein, we demonstrate for the first time that OMS-2 can act
as an efficient reusable heterogeneous catalyst for the regiose-
lective a-cyanation of tertiary amines using trimethylsilyl cya-
nide (TMSCN) as a cyano source and molecular oxygen as a ter-
minal oxidant. Various structurally diverse tertiary amines can
none
2
[a] Reaction conditions: Catalyst (50 mg), 1a (0.2 mmol), TMSCN
(0.4 mmol), acetonitrile (2 mL), 808C, O2 (1 atm), 2 h. Yields were deter-
mined by GC analysis using biphenyl as an internal standard. [b] The iso-
lated yield of products (2a+2a’, 2a/2a’=95/5) was 85% in the cyana-
tion for 4 h. [c] BHT (0.2 mmol). [d] Catalyst (10 mol%).
because it is relatively less reactive in comparison with fre-
quently utilized N,N-dialkylanilines and has never been utilized
in the previously reported a-cyanation systems.[2–9] Under the
present conditions, the reaction hardly proceeded in the ab-
sence of the catalysts (Table 1, entry 15). Among various cata-
lysts examined, OMS-2 showed the highest catalytic perfor-
mance; regioselective cyanation efficiently proceeded to afford
the corresponding a-amino nitriles 2a and 2a’ in 88% total
yield and occurred at the a-methyl position (2a/2a’=95/5,
Table 1, entry 1). Other manganese-based oxides, such as b-
MnO2, amorphous MnO2, and d-MnO2 (birnessite), gave the
corresponding a-amino nitriles in moderate to high yields
(Table 1, entries 3–5). In these cases, the regioselective cyana-
tion also occurred at the a-methyl position. Co3O4 and CeO2
showed much lower catalytic activities than those of manga-
nese-based oxides (Table 1, entries 6 and 7). Although V2O5,[8b]
[a] Dr. K. Yamaguchi, Dr. Y. Wang, Prof. Dr. N. Mizuno
Department of Applied Chemistry, School of Engineering
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax: (+81)3-5841-7220
Supporting information for this article is available on the WWW under
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2013, 5, 2835 – 2838 2835