with up to 95% ee [253]. Another interesting example can be found in the successful
hydrogenation of iminium salts of N-alkyl tetrahydroisoquinolines (ees up to 96%,
Fig. 39) [254] and of N-alkyl-2-arylpyridium salts (ees up to 98%, Fig. 39) [255]
using SegPhos-type ligands. Recently, a new strategy has been developed, in which
pyridinium and isoquinolinium salts are generated in situ by employing halogenide
trichloroisocyanuric acid as a traceless activation reagent. Mechanistic studies indicated that hydrogen halide generated in situ acted as an activator. This method
allowed the Ir/(R)-SegPhos-mediated hydrogenation of a range of isoquinolines
and pyridines in excellent yields and enantioselectivities (up to 99% ee, Fig. 39)
while avoiding tedious steps of installation and removal of the activating groups
[256]. Finally, it should be mentioned that not only Ir/diphosphine catalysts are able
to catalyze the reduction of iminium salts. Thus, it should be highlighted the recent
works of Qu’s group in the use of dihydrobenzooxaphosphole-pyridine ligand
MeO-BoQPhos for the asymmetric hydrogenation of 2-alkyl-pyridinium salts
including examples containing an α-heteroaryl substituent [257, 258].
Similarly, the successful hydrogenation of 6-membered ring cyclic imines has not
been only limited to the use of SynPhos-based system. Thus, for instance, a range of
quinoline derivatives have been successfully hydrogenated with diphosphines and
monophosphoroamidites. (S,S)-f-Binaphane ligand has been also efficiently used in
the reduction of 1-substituted 3,4-dihydroisoquinolines (ees up to >99%) [259]. Similarly, a range of 1-aryl-substituted tetrahydroisoquinolines were obtained in ees of
up to >99% and good TON (up to 4,000) using Josiphos-type binaphane ligand
[260]. Higher TONs (up to 43,000) were achieved in the reduction of a range of
quinolines using both Ir/(R)-Difluorphos [261] and Ir/(R)-P-Phos [262] catalytic
systems (Fig. 40). A successful example of the use of monophosphoramidite ligand
can be found in the use of (R
ax ,S,S)-Siphos-pe ligand (Fig. 40) in the hydrogenation
of 1-alkyl-dihydroisoquinolines with ees of up to 96%. The usefulness of the latter
reaction was demonstrated with the synthesis of the tetracyclic alkaloid (S)xylopinine in 85% yield and 96% ee [263].
Besides quinoline derivatives, the range of 6-membered ring cyclic amines
successfully hydrogenated has been extended. Thus, for instance, Ir-SegPhos catalyst was successfully used in the hydrogenation of 1,4-benzoxazines [264] and
quinazolines [265] (ees up to 98%, Fig. 41). The utility of the method was demonstrated with the synthesis of the bioactive compounds Eg5 inhibitor and (À)-SDZ
267-489 in excellent enantioselectivities (>99% and 99% ee, respectively)
[265]. Another example can be found in the use of cationic dinuclear iridium(III)
chloride catalyst {[IrH((S)-Difluorphos)] 2 (μ-Cl) 3 }Cl for the reduction of 2-alkyl and
2-aryl- substituted dihydroquinoxalines [266–268] and tosylamido-substituted
pyrazines [269] (ees up to 95%, Fig. 41). Ir-catalyst modified with phosphinephosphite ligand L45 proved to be highly efficient in the asymmetric hydrogenation
of benzoxazines, benzoxazinones, benzothiazones, and quinoxalinones (ees up to
99%; Fig. 41) [270, 271].
Most of the literature dealing with the hydrogenation of cyclic imines reports
examples on 6-membered ring systems. Examples on the successful hydrogenation
of 7-membered cyclic imines are rare. In particular, Ir/C3*-TunePhos catalysts
Iridium-Catalyzed Asymmetric Hydrogenation
189
hydrogenation of iminium salts of N-alkyl tetrahydroisoquinolines (ees up to 96%,
Fig. 39) [254] and of N-alkyl-2-arylpyridium salts (ees up to 98%, Fig. 39) [255]
using SegPhos-type ligands. Recently, a new strategy has been developed, in which
pyridinium and isoquinolinium salts are generated in situ by employing halogenide
trichloroisocyanuric acid as a traceless activation reagent. Mechanistic studies indicated that hydrogen halide generated in situ acted as an activator. This method
allowed the Ir/(R)-SegPhos-mediated hydrogenation of a range of isoquinolines
and pyridines in excellent yields and enantioselectivities (up to 99% ee, Fig. 39)
while avoiding tedious steps of installation and removal of the activating groups
[256]. Finally, it should be mentioned that not only Ir/diphosphine catalysts are able
to catalyze the reduction of iminium salts. Thus, it should be highlighted the recent
works of Qu’s group in the use of dihydrobenzooxaphosphole-pyridine ligand
MeO-BoQPhos for the asymmetric hydrogenation of 2-alkyl-pyridinium salts
including examples containing an α-heteroaryl substituent [257, 258].
Similarly, the successful hydrogenation of 6-membered ring cyclic imines has not
been only limited to the use of SynPhos-based system. Thus, for instance, a range of
quinoline derivatives have been successfully hydrogenated with diphosphines and
monophosphoroamidites. (S,S)-f-Binaphane ligand has been also efficiently used in
the reduction of 1-substituted 3,4-dihydroisoquinolines (ees up to >99%) [259]. Similarly, a range of 1-aryl-substituted tetrahydroisoquinolines were obtained in ees of
up to >99% and good TON (up to 4,000) using Josiphos-type binaphane ligand
[260]. Higher TONs (up to 43,000) were achieved in the reduction of a range of
quinolines using both Ir/(R)-Difluorphos [261] and Ir/(R)-P-Phos [262] catalytic
systems (Fig. 40). A successful example of the use of monophosphoramidite ligand
can be found in the use of (R
ax ,S,S)-Siphos-pe ligand (Fig. 40) in the hydrogenation
of 1-alkyl-dihydroisoquinolines with ees of up to 96%. The usefulness of the latter
reaction was demonstrated with the synthesis of the tetracyclic alkaloid (S)xylopinine in 85% yield and 96% ee [263].
Besides quinoline derivatives, the range of 6-membered ring cyclic amines
successfully hydrogenated has been extended. Thus, for instance, Ir-SegPhos catalyst was successfully used in the hydrogenation of 1,4-benzoxazines [264] and
quinazolines [265] (ees up to 98%, Fig. 41). The utility of the method was demonstrated with the synthesis of the bioactive compounds Eg5 inhibitor and (À)-SDZ
267-489 in excellent enantioselectivities (>99% and 99% ee, respectively)
[265]. Another example can be found in the use of cationic dinuclear iridium(III)
chloride catalyst {[IrH((S)-Difluorphos)] 2 (μ-Cl) 3 }Cl for the reduction of 2-alkyl and
2-aryl- substituted dihydroquinoxalines [266–268] and tosylamido-substituted
pyrazines [269] (ees up to 95%, Fig. 41). Ir-catalyst modified with phosphinephosphite ligand L45 proved to be highly efficient in the asymmetric hydrogenation
of benzoxazines, benzoxazinones, benzothiazones, and quinoxalinones (ees up to
99%; Fig. 41) [270, 271].
Most of the literature dealing with the hydrogenation of cyclic imines reports
examples on 6-membered ring systems. Examples on the successful hydrogenation
of 7-membered cyclic imines are rare. In particular, Ir/C3*-TunePhos catalysts
Iridium-Catalyzed Asymmetric Hydrogenation
189