The exploration of NHC-ligated iridium HIE catalysts had revealed promising
(proof-of-concept) developments beyond the popular and established works of Hesk
and Heys. Kerr and co-workers later developed a synthesis of previously
unattainable complexes 53a–53c, bearing large phosphine and large NHC ligands
N
N
N
N
Mes
Mes
DiPP
DiPP
IMes
IPr
Ir
NHC
PF 6
N
N
Cy
Cy
ICy
N
N
Cy
Cy
N
N
Mes
Mes
N
N
IMe
SICy
SIMes
NHCs
Catalysts
N
Ir
NHC
PF 6
PR 3
a: NHC = IMe
b: NHC = ICy
c: NHC = SICy
d: NHC = IMes
e: NHC = SIMes
f: NHC = IPr
a: NHC = IMe; R = Ph
b: NHC = IMe; R = Cy
c: NHC = IMe; R = n Bu
d: NHC = IMes; R =
n Bu
e: NHC = SIMes; R =
n Bu
Cy =
Mes =
DiPP =
51
52
Scheme 15 NHC-ligated iridium catalysts for hydrogenation later explored by HIE chemists
a: PR 3 = PPh 3
b: PR 3 = PBn 3
c: PR 3 = PMe 2 Ph
Ir
PF 6
PR 3
N
N
Mes
Mes
O
O
53a (0.5 mol%)
D
D
D
D/H
D/H
k H / k D = 3.7
D
D
D
Primary Kinetic Isotope Effect
55
54
D
D
Ir
PR 3
D
D
O
H
N
N Mes
Mes
+
Calculated Rate-Limiting TS
56
+ low catalyst loadings
+ broad scope
+ applicable to drug molecules
+ broad solvent tolerance
+ clean tritiations
Ir
PR 3
D
D
O NH
H
N
N Mes
Mes
+
57
53
Selected examples:
N
NO 2
CF 3
NH
O
O
H 2 N
S
O
O
N
N
CF 3
N
O
N
NEt 2
O
N
H
Cl
NO 2
OH
Cl
[98]
[12]
[6]
[94 D, 92 T]
[19 D, 2 T]
[85]
[65]
[55]
[52]
[52]
Nilutamide
Celecoxib
Perebron
Niclosamide
[X] = %D in adjacent position
Scheme 16 Highly active NHC/phosphine ortho-HIE iridium catalysts
Iridium Catalysts for Hydrogen Isotope Exchange
283