B21, B22, B34, B37, B47) as well as selected methyl alkyl (B99, B104) and the
methyl pyridinyl ketone B39 were reduced. Potassium t-butoxide (4 equiv. versus
substrate) was employed as a base but also in the presence of other bases such as
tBuONa, KOH and K 2 CO 3 , acetophenone was hydrogenated to 2-phenylethanol
with comparable activity and selectivity. Isolated yields from 87 to 99% and e.r.’s
from 90/10 to 99/1 were obtained within 10 h. Ethanol was used as a hydrogen
source. Using 2-propanol, instead, gave rise to significantly lower e.r.’s (99/1, EtOH
versus 92/8, iPrOH) [176].
A practical and sustainable method for the preparation of optically active
propargyl alcohols was developed by the Zhou’s group [177]. The tridentate spiropyridine-aminophosphine iridium complexes 65 depicted in Scheme 37 catalyse the
chemoselective reduction of a series of alkynyl ketones to the corresponding
propargyl alcohols. Both the unsubstituted complex 65a and the methyl-substituted
derivatives 65b and c were more active and enantioselective than compound 65d
having a tBu substituent. The optimised reaction conditions were 1 mol% of catalyst
65b, HCO 2 Na (2 equiv), 60
C and ethanol as solvent. Under these conditions, high
yield (86–99%) and high e.r.’s (93/7–98.5/1.5) were obtained within 4–48 h.
Alkynyl ketones containing electron-withdrawing (B130, B132, B135, B136) and
electron-donating (B123-B125, B129, B131, B133, B134) or additional ester (B127,
B128) groups as well as the trifluoromethyl ketone B126 were efficiently and
chemoselectively reduced [177].
Some remarkable features of the process are:
1. No base is required. Indeed, in the presence of tBuOK, 4-phenylbut-3-yn-2-one
(B123) only gave the Michael addition byproduct formed by the ethoxide addition to the carbon-carbon triple bond of B123.
2. The TH of B123 did not occur using HCO 2 H/NEt 3 instead of HCO 2 Na as a
hydrogen donor.
3. Other alkali metal formates such as HCO 2 Li, HCO 2 K and HCO 2 Cs can also be
used as hydrogen sources although HCO 2 Li gave lower reaction rate and
conversion.
4. Ethanol is the best solvent; indeed, the reaction in MeOH or iPrOH gave low
conversion and low enantioselectivity.
5. Under the optimised conditions but using HCO 2 Cs as a hydrogen donor, the TH
of the trifluoro alkynyl ketone B126 mediated by 65b was monitored by in situ IR
spectroscopy.
These results indicate that the formate salt and EtOH served as the hydride and
proton sources, respectively, in the TH reaction (Scheme 38) [177].
The iridium complex 66 (Scheme 37) containing a functionalised N-heterocyclic
olefin (Scheme 39) acting as a tridentate ligand has been applied as a catalyst for the
reduction of ketones, benzaldehyde and imines [178].
The reaction conditions entailed the use of 0.1 mol% of catalyst, iPrOH as a
solvent and a hydrogen donor, tBuOK (5 equiv) as a base and working at 80
C.
Under these conditions, cyclohexanone, substituted acetophenones (B1, B3, B15,
B18, B20), dialkyl (B114) and diphenyl (B66) ketones were efficiently reduced. For
example, the TH of cyclohexanone to cyclohexanol was completed in 7 min with a
Recent Advances in Iridium-Catalysed Transfer Hydrogenation Reactions
109
methyl pyridinyl ketone B39 were reduced. Potassium t-butoxide (4 equiv. versus
substrate) was employed as a base but also in the presence of other bases such as
tBuONa, KOH and K 2 CO 3 , acetophenone was hydrogenated to 2-phenylethanol
with comparable activity and selectivity. Isolated yields from 87 to 99% and e.r.’s
from 90/10 to 99/1 were obtained within 10 h. Ethanol was used as a hydrogen
source. Using 2-propanol, instead, gave rise to significantly lower e.r.’s (99/1, EtOH
versus 92/8, iPrOH) [176].
A practical and sustainable method for the preparation of optically active
propargyl alcohols was developed by the Zhou’s group [177]. The tridentate spiropyridine-aminophosphine iridium complexes 65 depicted in Scheme 37 catalyse the
chemoselective reduction of a series of alkynyl ketones to the corresponding
propargyl alcohols. Both the unsubstituted complex 65a and the methyl-substituted
derivatives 65b and c were more active and enantioselective than compound 65d
having a tBu substituent. The optimised reaction conditions were 1 mol% of catalyst
65b, HCO 2 Na (2 equiv), 60
C and ethanol as solvent. Under these conditions, high
yield (86–99%) and high e.r.’s (93/7–98.5/1.5) were obtained within 4–48 h.
Alkynyl ketones containing electron-withdrawing (B130, B132, B135, B136) and
electron-donating (B123-B125, B129, B131, B133, B134) or additional ester (B127,
B128) groups as well as the trifluoromethyl ketone B126 were efficiently and
chemoselectively reduced [177].
Some remarkable features of the process are:
1. No base is required. Indeed, in the presence of tBuOK, 4-phenylbut-3-yn-2-one
(B123) only gave the Michael addition byproduct formed by the ethoxide addition to the carbon-carbon triple bond of B123.
2. The TH of B123 did not occur using HCO 2 H/NEt 3 instead of HCO 2 Na as a
hydrogen donor.
3. Other alkali metal formates such as HCO 2 Li, HCO 2 K and HCO 2 Cs can also be
used as hydrogen sources although HCO 2 Li gave lower reaction rate and
conversion.
4. Ethanol is the best solvent; indeed, the reaction in MeOH or iPrOH gave low
conversion and low enantioselectivity.
5. Under the optimised conditions but using HCO 2 Cs as a hydrogen donor, the TH
of the trifluoro alkynyl ketone B126 mediated by 65b was monitored by in situ IR
spectroscopy.
These results indicate that the formate salt and EtOH served as the hydride and
proton sources, respectively, in the TH reaction (Scheme 38) [177].
The iridium complex 66 (Scheme 37) containing a functionalised N-heterocyclic
olefin (Scheme 39) acting as a tridentate ligand has been applied as a catalyst for the
reduction of ketones, benzaldehyde and imines [178].
The reaction conditions entailed the use of 0.1 mol% of catalyst, iPrOH as a
solvent and a hydrogen donor, tBuOK (5 equiv) as a base and working at 80
C.
Under these conditions, cyclohexanone, substituted acetophenones (B1, B3, B15,
B18, B20), dialkyl (B114) and diphenyl (B66) ketones were efficiently reduced. For
example, the TH of cyclohexanone to cyclohexanol was completed in 7 min with a
Recent Advances in Iridium-Catalysed Transfer Hydrogenation Reactions
109