Tetrahedron Letters
Efficient transfer hydrogenation reactions with quinazoline-based
ruthenium complexes
a
b
c
Semistan Karabuga a, , Songul Bars , Idris Karakaya , Selcuk Gumus
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a Department of Chemistry, Faculty of Science and Letters, Kahramanmaras Sutcu Imam University, 46100 Kahramanmaras, Turkey
b Department of Chemistry, Faculty of Science and Letters, Osmaniye Korkut Ata University, 80000 Osmaniye, Turkey
c Department of Chemistry, Faculty of Science, Yuzuncu Yil University, 65080 Van, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
(4-Phenylquinazolin-2-yl)methanamine was synthesized in high yield by starting from naturally and
commercially available glycine in a few steps. The ligand was reacted with RuCl2(PPh3)3 and RuCl2(PPh3)
dppb to obtain N-heterocyclic ruthenium(II) complexes. We have examined these catalysts in transfer
hydrogenation of acetophenone derivatives and excellent conversions of up to 99% and high TOF values
of up to 118,800 hÀ1 using 0.1 mol % of catalyst were achieved.
Received 2 September 2014
Revised 22 October 2014
Accepted 6 November 2014
Available online 13 November 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Ruthenium
Quinazoline
Transfer hydrogenation
Ketone
Secondary alcohols
Hydrogen transfer reduction processes have attracted signifi-
cant interest from synthetic chemists as a result of their operational
simplicity and high selectivity.1 Applications using a small amount
of a catalyst are important in green chemistry. The ability to reduce
the C@O and C@N group by transfer hydrogenation creates the need
for designing new ligands and preparing metal complexes (Rh, Pt, Ir,
Pd, Os and Ru).2,3 After Noyori et al., discovered the BINAP-Ru-
catalyst system including a 1,2-diamine, which has been shown
to be highly efficient for the reduction of ketones, attention has
been paid towards this type of complex with different P and N
ligand combinations.4 Organometallic complexes containing
nitrogen donor ligands generally exhibit high reactivity; hence,
N-heterocyclic catalysts, having appropriate geometric structures
to generate complexes with metals have attracted attention.5–10
Baratta and co-workers have synthesized several catalysts bearing
amine and pyridyl donor groups for transfer hydrogenation of
ketones.11–14 In a similar vein, the large number of efficient
ruthenium complexes containing pyridyl,15–18 pyrazolyl,19–21
imidazolyl,5,22,23 benzimidazolyl,24,25 oxazolinyl,26 and aminophos-
phines27 have been widely used.
ruthenium complexes of quinazoline for transfer hydrogenation
has been applied for the first time in this study. For this purpose,
the readily available amino acid glycine was used to synthesize
(4-phenylquinazolin-2-yl)methanamine. The quinazoline ligand
was coordinated with RuCl2(PPh3)dppb and RuCl2(PPh3)3 and the
catalytic activity of the complexes in transfer hydrogenation reac-
tions of acetophenone derivatives was investigated.
The quinazoline compound 7 was easily synthesized starting
from glycine according to the general synthetic route outlined in
Scheme 1. In the first step, glycine (1) was protected with Boc2O
in the presence of Na2CO3. Protected glycine 2 was converted into
tert-butyl {2-[(2-carbamoylphenyl)amino]-2-oxoethyl}carbamate
(3) via treatment with anthranilamide, ethyl chloroformate and
Et3N. Cyclization of this amide was achieved using NaOH in EtOH
at ambient temperature. 4-Chloroquinazoline 5 was obtained by
chlorination of quinazolinone derivative 4 by treatment with phos-
phoryl chloride and N,N-diethylaniline. The synthesis of 6 was
accomplished by a Suzuki coupling reaction using phenylboronic
acid and a catalytic amount of Pd(PPh3)4 (2 mol %) at reflux under
an N2 atmosphere. The 4-phenylquinazoline amine 7 was finally
obtained by removal of the Boc group by treatment of 6 with TFA.
Treatment of RuCl2(PPh3)dppb and RuCl2(PPh3)3 with 1.2 equiv
Ligands bearing a quinazoline structure have been used in
various reactions such as catalytic asymmetric organozinc
addition28,29 and asymmetric allylic alkylation.30 Also, the use of
i
of 4-phenylquinazoline 7 in the presence of Et3N and PrOH at
reflux temperature for three hours resulted in the formation of
ruthenium complexes 8 and 9 in moderate yields (Scheme 2).
Due to the fact that the quinazoline ligand bears two nitrogen
atoms, it can be expected that two types of ruthenium complexes
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