Chemistry Reference
In-Depth Information
for the synthesis of lilial (Eq. 7.22). Heterocyclic N,P-ligands, HetPHOX
66
was also
effi cient for similar substrates [214].
[Ir(
S
)-
PHOX
(cod)]PF
6
OH
OH
CH
2
Cl
2
,23
o
C, 50 atm H
2
t
Bu
t
Bu
94% ee
(7.22)
7.3.1.7. Unfunctionalized Olefi ns
Despite great success achieved on asymmetric
hydrogenation of olefi ns, the substrate scope has been limited to functionalized olefi ns
where at least one coordinating group is adjacent to the double bond. Rh- or Ru-
catalyzed hydrogenation of unfunctionalized olefi ns only showed low reactivities and
unsatisfactory enantioselectivities [215]. Some chiral metallocene catalysts such as chiral
titanocene [216] or zirconocene [217] have been found to be effi cient for the hydrogena-
tion of tri- or tetrasubstituted unfunctionalized olefi ns although from the high loading
of catalysts and high pressure of hydrogen required for reasonable yield. Inspired by the
Crabtree's catalyst, which has shown high activity toward the hydrogenation of hindered
olefi ns [218], Roseblade and Pfaltz developed a series of P,N-ligand for the hydrogena-
tion of unfunctionalized olefi ns [219]. Excellent enantioselectivities and catalytic activi-
ties have been achieved by the so-called PHOX ligand family and its analogues. A large
number of previously challenging unfunctionalized substrates including some tri- or
tetrasubstituted olefi ns have been hydrogenated with good to excellent ee. It was also
found that the counterion in the Ir catalysts plays an important role in the reaction rate
[220]. Weakly coordinated counterions such as BArF
−
does not interfere with the coor-
dination of the substrate to Ir and provided the most active catalysts [221]. Some of the
results from the asymmetric hydrogenation of a standard substrate, 2-methyl stilbene,
are shown in Table 7.8 .
A threonine - derived phosphinite - oxazoline ligand (
S
) -
82
has provided high enanti-
oselectivities for the hydrogenation of both (
E
) - and (
Z
) - 2 - (4 - methoxyphenyl) - 2 -
butene, resulting in the opposite confi gurations of the products (Eqs. 7.23 and 7.24)
[207]. Hydrogenation of a hindered tetrasubstituted olefi n was accomplished by an Ir
complex to give a product with 97% ee and a complete conversion (Eq. 7.25) [209,229].
A cyclic analogue olefi n was hydrogenated with a related Ir catalyst to give excellent
diastereo- and enantioselectivities (Eq. 7.26) [229]. A highly rigid cyclic tetrasubstituted
substrate was also reduced with 96% ee using Ir-
65
as the catalyst (Eq. 7.27) [229].
The substrate scope was further expanded to purely alkyl-substituted olefi ns. Up to
97% ee was obtained from a cyclohexylalkene substrate using an Ir catalyst (Eq. 7.28)
[219,230]. Very recently, Andersson and others reported the hydrogenation of a few
vinyl fl uoride substrates using a series of hindered P,N-ligand [231]. The cleavage of
the fl uoride can be avoided by ligand optimization. Excellent enantioselectivities were
achieved under reasonable reaction conditions (Eq. 7.29).
Ir-(
S
)-
82
CH
2
Cl
2
,23
o
C, 50 bar H
2
MeO
MeO
(7.23)
99% ee
