DOI: 10.1002/chem.201501109
Communication
&
Homogeneous Catalysis
Alkylation of Amines with Alcohols and Amines by a Single
Catalyst under Mild Conditions
Qingzhu Zou,[a] Chao Wang,*[a] Jen Smith,[b] Dong Xue,[a] and Jianliang Xiao*[a, b]
amines, but not with both. Shvo’s catalyst,[7p] a [Cp*IrCl2(NHC)]
Abstract: An efficient catalytic system for the alkylation of
complex reported by Peris and co-workers,[7g] and a recent ex-
amines with either alcohols or amines under mild condi-
ample from Li and co-workers[21] are the only catalysts that are
tions has been developed, using cyclometallated iridium
able to catalyse both reactions under different reaction condi-
complexes as catalysts. The method has broad substrate
tions or temperatures. Thus, a versatile catalyst capable of pro-
scope, allowing for the synthesis of a diverse range of sec-
moting alkylation both with alcohols and with amines is desira-
ondary and tertiary amines with good to excellent yields.
ble. However, to perform amine alkylation with alcohols and
By controlling the ratio of substrates, both mono- and bis-
amines using the same catalyst system under mild conditions
alkylated amines can be obtained with high selectivity. In
is challenging, as the amine cross-coupling reaction normally
particular, methanol can be used as the alkylating reagent,
requires high temperature (>1508C). To our knowledge, a mild
affording N-methylated products selectively. A strong sol-
catalytic system for alkylation of amines with both alcohols
vent effect is observed for the reaction.
and amines has not been reported to date.
We have developed efficient catalytic systems based on cy-
clometallated iridium complexes for the reductive amination of
carbonyl compounds to afford amines.[6b,c,22] Apart from reduc-
The development of methods for the synthesis of amines is of
great importance because of the widespread presence of
amine moieties within natural products, pharmaceuticals and
fine chemicals.[1] Classical methods for the preparation of
amines include reduction of nitro,[2] nitrile or amide groups,[3]
functionalisation of alkenes or alkynes,[1u,4] alkylation with alkyl
halides[5] and reductive amination of carbonyl com-
pounds.[1c,k,v,6] An alternative and greener method for the pro-
duction of amines is the alkylation of amines with alcohols by
the use of “borrowing hydrogen” or “hydrogen autotransfer”
strategy.[7] The first examples of alkylation of amines with alco-
hols by homogeneous catalysis were reported independently
by the groups of Grigg[8] and Watanabe.[9] Since then, great
progress has been made in this area, allowing the reaction to
be carried out under milder conditions,[7j,10] with broader sub-
strate scope,[7h] or even in an enantioselective manner.[7m,11] No-
table contributions have come from the groups of Bel-
ler,[3,7p,q,s,12] Williams,[7a,c,d,f,h,r,t–v,x,13] Fujita,[14] Kempe,[7z,10,15] Martín-
Matute,[16] Crabtree,[17] Yus,[7b,18] Peris,[7g] Andersson,[7j] Mil-
stein,[19] Zhao[7m,11b] and others.[20] The strategy could be further
extended to the cross coupling of amines as reported by the
groups of Beller,[7p,q] Peris[7g] and Williams.[7r] However, most of
the catalysts reported only work for alkylation with alcohols or
tion reactions, these iridium complexes were found to be able
to catalyse dehydrogenation reactions as well.[23] The dehydro-
genation and reduction abilities of these iridium complexes
render them possible catalysts for borrowing hydrogen reac-
tions. This hypothesis has now been verified by the alkylation
of amines with alcohols catalysed by a cyclometallated iridium
complex. Compared with our previously reported reductive
amination reactions, the alkylation with alcohols is greener,
avoiding the use of extra reductant. Further studies have dem-
onstrated that the catalyst is also viable for cross coupling of
amines under relatively mild conditions, thus providing a versa-
tile protocol for alkylation of amines with both alcohols and
amines (Scheme 1). Herein, we report the details of our find-
ings.
Scheme 1. Alkylation of amines with both alcohols and amines catalysed by
a single cyclometallated iridium complex under the same mild conditions.
[a] Q. Zou, Prof. Dr. C. Wang, Prof. Dr. D. Xue, Prof. Dr. J. Xiao
Key Laboratory of Applied Surface and Colloid Chemistry
Ministry of Education, Department of Chemistry & Chemical Engineering
Shaanxi Normal University, Xi’an, 710062 (P. R. China)
In our previous work, the iridium complex 1a demonstrated
superior activity for the reduction of imines in 2,2,2-trifluoroe-
thanol (TFE; Scheme 2).[6b] Thus, the reaction of benzyl alcohol
with aniline was initially carried out with 1a as precatalyst in
TFE in the presence of 5 mol% of K2CO3 as base. Pleasingly,
68% conversion of benzyl alcohol to the alkylation product
was observed in 6 h at 1008C. The use of TFE as solvent is criti-
[b] J. Smith, Prof. Dr. J. Xiao
Department of Chemistry, University of Liverpool
Liverpool, L69 7ZD (UK)
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2015, 21, 9656 – 9661
9656
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