B117 (Scheme 4) under base-free conditions [83]. At 80
C, in 2-propanol, at catalyst
loading of 0.1–0.5 mol%, conversions in the 66–98% range were obtained, after
1–6 h of reaction. For iridacycles 38 and 39, a mechanism involving the loss of the
Cp* ring was proposed [83].
The iridium dimer [Cp*IrCl 2 ] 2 reacts with methyl (S)-2-phenyl-4,5dihydrooxazole-4-carboxylate selectively giving a N,C- (42) or a N,O-chelated
(43) complex (Scheme 9) depending on the reaction conditions [84]. Interestingly,
the N,O-chelated complex 43 is much more active and selective in the asymmetric
TH of ketones than its N,C-chelated isomer 42, using mixtures of formic acid/amine
as a hydrogen source, in CH 2 Cl 2 . Furthermore, the sense of asymmetric induction is
different for each isomer. The favoured configuration of the alcohol is S for the N,Ochelated complex 43 and R for N,C-chelated analogue 42. Thus, for example, in the
presence of 1 mol% of complexes 42 or 43, 4-nitroacetophenone could be reduced
by using an azeotropic mixture of formic acid/triethylamine, in CH 2 Cl 2 at
RT. However, while with precatalyst 43 100% of the corresponding alcohol was
obtained after 2 h of reaction, with an 86.5/13.5 of e.r. in favour of the S enantiomer,
with the analogous precatalyst 42, only 75% of conversion was measured after 15 h
of treatment with a 48/52 e.r. in favour of the R enantiomer. Regarding the formic
acid/amine mixture, besides NEt 3 , also Et 2 NH, Cy 2 NH, iPrNH 2 and tBuNH 2 have
been tested. Using the catalyst precursor 43, the highest e.r. (99/1) for the TH of
ketone B27 was obtained with a formic acid/iPrNH 2 , 2/1 mixture. No reasons have
been proposed for this behaviour.
The N,O-chelated complex 43 catalyses the TH of a variety of methyl aryl
(B1-B6, B14, B15, B17, B18, B22, B27, B30-B33, B35) and alkyl aryl ketones
(B47, B49, B55, Scheme 4) using a formic acid/iPrNH 2 , 2/1 mixture. Excellent e.r.’s,
between 95/5 and 99.5/0.5, were obtained with yields ranging from 7 to 98%, when
the reactions were carried out overnight, at RT in CH 2 Cl 2 . The lowest activity
corresponds to acetophenones that bear highly electro-donating substituents
(e.g. B17, 7% yield) or 2-substituted acetophenones (e.g. B2, 18% yield) [84].
Half-sandwich iridium complexes 44–47 (Scheme 9) containing a triazenide
group as a ligand have been tested as precatalysts in the TH of acetophenone, in
2-propanol as both hydrogen donor and solvent, at 70
C [85]. Reactions were
performed in the presence of KOH as a base with a catalyst loading of 2 mol%.
The chloride compounds 44 and 45 need 42 and 62 h of reaction, respectively, to
achieve, in both cases, 95% yield. However, if the hydride complex 46, derived from
45, is used as the catalyst, a yield of 83% was obtained just after 4 h and in the
absence of a base. Complex 47, without imidazole substituents on the triazenido
moiety, also reduced acetophenone without a base (98% yield in 86 h) [85].
The chiral iridium complex 48 (Scheme 9) in cooperation with the chiral phosphoric acid depicted in Scheme 10 efficiently catalysed the asymmetric TH of Nbenzyl C15-C25, N-p-methoxybenzyl C16, N-p-methoxyphenyl C26-C31 and C33,
dialkyl substituted C34, C35 and aryl ethyl C32 imines [86]. Unexpectedly, the
efficiency and enantioselectivity of the TH can be tuned by the use of different
alcohols as the hydrogen donor. In general, benzylic alcohols provided high
Recent Advances in Iridium-Catalysed Transfer Hydrogenation Reactions
87
C, in 2-propanol, at catalyst
loading of 0.1–0.5 mol%, conversions in the 66–98% range were obtained, after
1–6 h of reaction. For iridacycles 38 and 39, a mechanism involving the loss of the
Cp* ring was proposed [83].
The iridium dimer [Cp*IrCl 2 ] 2 reacts with methyl (S)-2-phenyl-4,5dihydrooxazole-4-carboxylate selectively giving a N,C- (42) or a N,O-chelated
(43) complex (Scheme 9) depending on the reaction conditions [84]. Interestingly,
the N,O-chelated complex 43 is much more active and selective in the asymmetric
TH of ketones than its N,C-chelated isomer 42, using mixtures of formic acid/amine
as a hydrogen source, in CH 2 Cl 2 . Furthermore, the sense of asymmetric induction is
different for each isomer. The favoured configuration of the alcohol is S for the N,Ochelated complex 43 and R for N,C-chelated analogue 42. Thus, for example, in the
presence of 1 mol% of complexes 42 or 43, 4-nitroacetophenone could be reduced
by using an azeotropic mixture of formic acid/triethylamine, in CH 2 Cl 2 at
RT. However, while with precatalyst 43 100% of the corresponding alcohol was
obtained after 2 h of reaction, with an 86.5/13.5 of e.r. in favour of the S enantiomer,
with the analogous precatalyst 42, only 75% of conversion was measured after 15 h
of treatment with a 48/52 e.r. in favour of the R enantiomer. Regarding the formic
acid/amine mixture, besides NEt 3 , also Et 2 NH, Cy 2 NH, iPrNH 2 and tBuNH 2 have
been tested. Using the catalyst precursor 43, the highest e.r. (99/1) for the TH of
ketone B27 was obtained with a formic acid/iPrNH 2 , 2/1 mixture. No reasons have
been proposed for this behaviour.
The N,O-chelated complex 43 catalyses the TH of a variety of methyl aryl
(B1-B6, B14, B15, B17, B18, B22, B27, B30-B33, B35) and alkyl aryl ketones
(B47, B49, B55, Scheme 4) using a formic acid/iPrNH 2 , 2/1 mixture. Excellent e.r.’s,
between 95/5 and 99.5/0.5, were obtained with yields ranging from 7 to 98%, when
the reactions were carried out overnight, at RT in CH 2 Cl 2 . The lowest activity
corresponds to acetophenones that bear highly electro-donating substituents
(e.g. B17, 7% yield) or 2-substituted acetophenones (e.g. B2, 18% yield) [84].
Half-sandwich iridium complexes 44–47 (Scheme 9) containing a triazenide
group as a ligand have been tested as precatalysts in the TH of acetophenone, in
2-propanol as both hydrogen donor and solvent, at 70
C [85]. Reactions were
performed in the presence of KOH as a base with a catalyst loading of 2 mol%.
The chloride compounds 44 and 45 need 42 and 62 h of reaction, respectively, to
achieve, in both cases, 95% yield. However, if the hydride complex 46, derived from
45, is used as the catalyst, a yield of 83% was obtained just after 4 h and in the
absence of a base. Complex 47, without imidazole substituents on the triazenido
moiety, also reduced acetophenone without a base (98% yield in 86 h) [85].
The chiral iridium complex 48 (Scheme 9) in cooperation with the chiral phosphoric acid depicted in Scheme 10 efficiently catalysed the asymmetric TH of Nbenzyl C15-C25, N-p-methoxybenzyl C16, N-p-methoxyphenyl C26-C31 and C33,
dialkyl substituted C34, C35 and aryl ethyl C32 imines [86]. Unexpectedly, the
efficiency and enantioselectivity of the TH can be tuned by the use of different
alcohols as the hydrogen donor. In general, benzylic alcohols provided high
Recent Advances in Iridium-Catalysed Transfer Hydrogenation Reactions
87