Chemistry Reference
In-Depth Information
- amino
ketones [265]. High enantioselectivities and turnover numbers are achieved under rela-
tively mild conditions. Zhang and others' Ru-C3-TunePhos catalyst also showed excel-
lent enantioselectivities (
proved to be highly effi cient for the hydrogenation of a wide range of
α
- ,
β
- , or
γ
- phthalimide
ketones with turnover numbers up to 10,000 (Table 7.13) [23d]. A few Rh catalysts
bearing chiral phosphorous ligands such as BPPOH [12b], MCCPM [232f-k], Cy,
Cy - oxoProNOP [234c,e] , Cp,Cp - oxoProNOP [234c,e] , and IndoNOP [234g] have also
provided excellent enantioselectivities and reactivities in the hydrogenation of
>
99% ee) for the asymmetric hydrogenation of
α
α
- ,
β
- ,
or
-amino ketones. The Zhang group recently reported a highly effi cient hydrogenation
of a series of unprotected
γ
α
- and
β
- amino ketones using the electron - rich DuanPhos
[266] and BINAPINE [267] .
The effi cient preparation of chiral amino alcohols via asymmetric hydrogenation
has been employed for the syntheses of many important chiral intermediates and
drugs. For example, the enantioselective hydrogenation of 3 - aryloxy - 2 - oxo - 1 -
propylamine derivatives can directly afford the 1 - amino - 3 - aryloxy - 2 - propanol deriva-
tives as chiral
-adrenergic blocking agents. This transformation has been successfully
accomplished with a neutral MCCPM-Rh complex as the catalyst [232f]. With
0.01 mol %
β
of
an
(
S
,
S
) - MCCPM - Rh
complex,
(
S
) - propranolol
was
synthesized
in
90.8% ee from the corresponding
- amino ketone substrate (Eq. 7.38 ). The
tran
s -
RuCl
2
[(
R
) - XylBINAP][(
R
)-daipen] complex has been applied as a catalyst to the
enantioselective synthesis of (
R
) - denopamine, a
α
1
-receptor agonist used for the treat-
ment of congestive heart failure (Scheme 7.10) [265]. Zhang and others' short synthe-
sis afforded this compound via the hydrogenation of unprotected amino ketone
precursor using the Rh - DuPhos catalyst [267] . (
R
) - arbutamine was also synthesized
with reasonable enantioselectivity. A
β
-functionalized amino ketone is also hydroge-
nated effi ciently with 99% ee to provide BMS181100, a potent antipsychotic agent
(Eq. 7.39 ) [265] . Two chiral
γ
-secondary amino alcohols, which are key precursors
to pharmarceuticals (
S
) - fl uoxetine and (
S
)-duloxetine, were synthesized with Rh-
DuanPhos catalyst with high enantioselectivities (up to
γ
>
99% ee) and up to 6000 turn-
over numbers (Scheme 7.11 ) [266] .
O
COPh
N
OCH
3
trans
-[RuCl
2
[(
R
)-XylBINAP)][(
R
)-daipen]}
(0.05 mol %)
H
2
O
OCH
3
OH
COPh
OH
N
N
OCH
3
OCH
3
HCl
O
OCH
3
HO
OCH
3
97% ee
(
R
)-denopamine hydrochloride
Scheme 7.10.
Synthesis of (
R
)-denopamine hydrochloride via asymmetric hydrogenation.
