DOI: 10.1002/chem.201505214
Communication
&
Allylic Amination
Iron-Catalyzed Allylic Amination Directly from Allylic Alcohols
[
a]
Balakumar Emayavaramban, Moumita Roy, and Basker Sundararaju*
Abstract: Allylic amination, directly from alcohols, has
been demonstrated without any Lewis acid activators
using an efficient and regiospecific molecular iron catalyst.
Various amines and alcohols were employed and the reac-
tion proceeded through the oxidation/reduction (redox)
pathway. A direct one-step synthesis of common drugs,
such as cinnarizine and nafetifine, was exhibited from cin-
namyl alcohol that produced water as side product.
Figure 1. A general overview of allylic amination directly from alcohol.
Since the first report of Tsuji’s allylic substitution reaction cata-
recent applications in various CÀC and CÀN bond formations,
[1]
lyzed by a transition metal, many efficient and widely appli-
cable protocols have been developed for various carbon–
motivated us to explore the possibility of allylic alkylation of
amines directly from allyl alcohols through the hydrogen bor-
[2]
[10,11]
carbon and carbon–heteroatom bond formations. Especially,
noble metals, such as Pd, Ru, Ir, are utilized widely by activat-
rowing methodology.
Based on the redox nature of the Fe
catalyst A, we hypothesize that the direct activation of allylic
alcohols with the Knçlker’s catalyst would lead to a,b-unsatu-
rated aldehydes, which upon condensation with amines would
form enimines. Susequent selective 1,2-reduction of enimine
instead of 1,4-conjugate addition by the metal hydride species
would lead to allyl amines as products and regeneration of the
catalyst (Figure 2). At the same time, it may also be possible
that the allylic alcohol undergoes isomerization using the Fe
catalyst followed by condensation with the amine, subsequent
reduction of the resulted imine could lead to the reductive
[
3]
ing various allylic derivatives via metal–p–allyl species. Such
allylic substitution reactions are mainly developed using allylic
derivatives containing a leaving group, such as acetate, car-
bonate, halides, phosphate, that are derived from their parent
alcohols. The direct utilization of allyl alcohols not only mini-
mizes the prefunctionalization step but is also environmental
friendly. However, allylic alcohols are rather difficult to activate
due to the unreactive nature of the -OH moiety. Hence,
a direct activation of allylic alcohols catalyzed by a transition
metal is of interest because it produces only water as side
product. Recently, the above-mentioned noble metals were uti-
lized for a direct activation of allylic alcohols via metal–p–allyl
species that following nucleophilic attack led to CÀC and CÀX
[
12]
amination product instead of allylic amination.
[4]
bond formation (Figure 1a).
In addition, few reports have been documented for the
Lewis acid-mediated activation of allylic alcohols for mostly re-
[5]
giospecific transformations (Figure 1b). However, only very
few recent reports describe using well-defined earth-abundant
first-row transition metals as catalysts for the allylic substitu-
Figure 2. Fe-catalyzed allylic amination by hydrogen borrowing method.
[6]
tion directly from the alcohol. In a continuous exploration of
our research theme on the development of a base-metal cata-
[7]
lyst for sustainable transformations, we became interested on
the utilization of iron catalyst for a novel allylic substitution
transformation directly from allylic alcohols. The exceptional re-
By keeping both the possible pathways in mind, we began
our investigation by using cinnamyl alcohol (1a) and piperi-
dine (2a) in the presence of Fe catalyst A (5 mol%) and
[8,9]
activity of Knçlker’s catalyst exemplified in the past
and its
Me NO (10 mol%) as additive in toluene at 1308C (oil bath
3
temperature) for 24 h, giving the corresponding allylic amina-
tion product 3a in 60% isolated yield based on 2a without any
isomerization (Table 1). Further investigations were carried out
on the compatibility with various solvents. Among them, tolu-
ene was the best, although xylene also gave comparable yield
[
a] B. Emayavaramban, M. Roy, Prof. Dr. B. Sundararaju
Fine Chemical Laboratory, Department of Chemistry
Indian Institute of Technology Kanpur
Kanpur, Uttar Pradesh (India)
E-mail: basker@iitk.ac.in
(
entries 2–4). Surprisingly, when we employed water as a sol-
vent, 3a was obtained, albeit in a moderate yield (42%,
Chem. Eur. J. 2016, 22, 3952 – 3955
3952
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