Catalyst 57a proved to be more active than its congeners 57b and 57c. With
complex 57a as the catalyst and at the standard conditions of a S/C ratio of 20,000,
5 equiv. of HCOOH, at 90
C and under N 2 atmosphere, a series of diverse aldehydes
(A1, A2, A16, A19, A23, A24, A28, A30-A32, A34, A36-A38, A42, A44, A46,
A47, A50, A55, A59, A63, A64, A67, Scheme 3) were reduced in excellent isolated
yield (90–99%), after 2 h of reaction [113].
Catalysts 57 also actively reduce ketones. Like for Tang’s imidazolyl-pyridine
iridium catalysts, to obtain good results, an excess of formic acid (15 equiv) greater
than that for TH of aldehydes (5 equiv) has to be used. Higher excess of formic acid
provides more acidic conditions to activate carbonyl groups and dissolves ketones.
In fact, ketones that were not reduced in the presence of 5 equiv. of formic acid were
easily reduced by using 15 equiv. of this acid.
A variety of substituted acetophenones with electron-donating or withdrawing
group was reduced to the corresponding alcohols. Halogen (B20-B22), nitro (B27)
and cyano (B24) groups were compatible as well as heterocyclic substituents (B38,
B41). Methyl alkyl ketones (B100, B107), cyclohexanone, cycloheptanone or
ketones containing acidic functional groups (B25) were also reduced.
Again, complex 57a was the catalyst of choice. With this complex, yields from
78 to 99% were obtained after 12 h of reaction, with an S/C ratio of 10,000, at 90
C
and under N 2 atmosphere [113].
2.4 Biological Transfer Hydrogenation
Artificial metalloenzymes (ArMs) are hybrid catalysts that result from combining an
abiotic metal cofactor with a protein with the aim of taking advantage of the features
of both metal-based and enzymatic catalysis [114, 115]. In the field of artificial
transfer hydrogenases, many efforts have been devoted to the development of imine
reductases. Since 2005, the Ward’s group has been using Noyori-type piano stool
metallic cofactors combined with either wild-type streptavidin (Sav WT) or
streptavidin mutants as host proteins to develop artificial asymmetric transfer
hydrogenases. The metallic cofactor was completed by bonding the Noyori’s
diamine ligand to biotin which acts as an anchor to the protein [116–118] (Scheme
15). The intricate network of interactions in the biological scaffold creates a chiral
second coordination sphere environment around the catalytic metal site responsible
for enantioselection. Given the prevalence of the chiral 1,2,3,4-tetrahydroquinoline
in natural alkaloids and synthetic drugs [119], the salsolidine precursor imine
1-methyl-6,7-dimethoxy-3,4-dihydroquinoline was usually employed as a model
substrate (Scheme 15). 3-(N-morpholino)propanesulfonic acid (MOPS) buffer and
sodium formate were usually employed as the reaction medium and the hydrogen
source, respectively, [120–122] (Scheme 15).
Based on the biotin-streptavidin technology developed by the Ward’s group,
Rimoldi et al. have investigated the catalytic activity of the iridium complexes
Recent Advances in Iridium-Catalysed Transfer Hydrogenation Reactions
93
complex 57a as the catalyst and at the standard conditions of a S/C ratio of 20,000,
5 equiv. of HCOOH, at 90
C and under N 2 atmosphere, a series of diverse aldehydes
(A1, A2, A16, A19, A23, A24, A28, A30-A32, A34, A36-A38, A42, A44, A46,
A47, A50, A55, A59, A63, A64, A67, Scheme 3) were reduced in excellent isolated
yield (90–99%), after 2 h of reaction [113].
Catalysts 57 also actively reduce ketones. Like for Tang’s imidazolyl-pyridine
iridium catalysts, to obtain good results, an excess of formic acid (15 equiv) greater
than that for TH of aldehydes (5 equiv) has to be used. Higher excess of formic acid
provides more acidic conditions to activate carbonyl groups and dissolves ketones.
In fact, ketones that were not reduced in the presence of 5 equiv. of formic acid were
easily reduced by using 15 equiv. of this acid.
A variety of substituted acetophenones with electron-donating or withdrawing
group was reduced to the corresponding alcohols. Halogen (B20-B22), nitro (B27)
and cyano (B24) groups were compatible as well as heterocyclic substituents (B38,
B41). Methyl alkyl ketones (B100, B107), cyclohexanone, cycloheptanone or
ketones containing acidic functional groups (B25) were also reduced.
Again, complex 57a was the catalyst of choice. With this complex, yields from
78 to 99% were obtained after 12 h of reaction, with an S/C ratio of 10,000, at 90
C
and under N 2 atmosphere [113].
2.4 Biological Transfer Hydrogenation
Artificial metalloenzymes (ArMs) are hybrid catalysts that result from combining an
abiotic metal cofactor with a protein with the aim of taking advantage of the features
of both metal-based and enzymatic catalysis [114, 115]. In the field of artificial
transfer hydrogenases, many efforts have been devoted to the development of imine
reductases. Since 2005, the Ward’s group has been using Noyori-type piano stool
metallic cofactors combined with either wild-type streptavidin (Sav WT) or
streptavidin mutants as host proteins to develop artificial asymmetric transfer
hydrogenases. The metallic cofactor was completed by bonding the Noyori’s
diamine ligand to biotin which acts as an anchor to the protein [116–118] (Scheme
15). The intricate network of interactions in the biological scaffold creates a chiral
second coordination sphere environment around the catalytic metal site responsible
for enantioselection. Given the prevalence of the chiral 1,2,3,4-tetrahydroquinoline
in natural alkaloids and synthetic drugs [119], the salsolidine precursor imine
1-methyl-6,7-dimethoxy-3,4-dihydroquinoline was usually employed as a model
substrate (Scheme 15). 3-(N-morpholino)propanesulfonic acid (MOPS) buffer and
sodium formate were usually employed as the reaction medium and the hydrogen
source, respectively, [120–122] (Scheme 15).
Based on the biotin-streptavidin technology developed by the Ward’s group,
Rimoldi et al. have investigated the catalytic activity of the iridium complexes
Recent Advances in Iridium-Catalysed Transfer Hydrogenation Reactions
93