Chemistry Reference
In-Depth Information
OH
O
trans
-RuCl
2
[(
S
)-TolBINAP][(
R
,
R
)-DPEN]
(0.01 mol %)
i
PrOH, 24-30
o
C, 10 atm H
2
,48h
94% ee
100% yield
(7.48)
O
OH
RuCl
2
[(
S
)-BINAP](DMF)n, (
R
,
R
)-DPEN, KOH
i
PrOH, 28
o
C, 4 atm H
2
,3.5h
100% de
100% yield
(7.49)
7.3.2.3. Transfer Hydrogenation of Ketones
Asymmetric transfer hydrogenation of
ketones and imines with chiral transition-metal catalysts is a powerful and practical
method to prepare chiral alcohols and amines. Instead of molecular hydrogen, different
hydrogen donors such as 2-propanol [311] or mixture of formic acid and triethylamine
[312] are used in the transfer hydrogenation (Fig. 7.26).
Doering and Young reported the fi rst asymmetric reduction of ketones using chiral
alcohols, (
S
) - 2 - butanol, or (
S
) - 3 - methyl - 2 - butanol as the hydrogen donor in the presence
of metal alkoxides, typically aluminum 2-propoxide [313]. This reduction is known as
Meerwein-Ponndorf-Verley (MPV) reduction. They suggested that the hydrogen trans-
fer proceeds through a six-membered transition state, and the hydrogen of the alcohol
is directly transferred to the carbonyl carbon. Although many chiral catalysts have been
developed since then, such as lanthanide [314] and aluminum [315] complexes, the suc-
cesses have been very limited. Chiral Sm(III) was used in enantioselective MPV-type
reduction of acetophenone derivatives giving up to 97% ee [316].
Chiral transition-metal complexes bearing nitrogen-based ligands have been
extensively studied in the asymmetric transfer hydrogenation. The efforts have mainly
focused on the reduction of unfunctionalized ketones [311b,c]. In most cases, this
transformation requires a strong base such as KOH,
i
PrONa, or
t
BuOK as cocatalyst
Table 7.17 ).
Noyori, Ikariya, and others reported a phosphine-free prototype catalyst featuring
amino sulfonamide and amine alcohols. When TsDPEN was used as the ligand with the
[RuCl
2
(arene)]
2
precursor, the catalyst effectively promoted the reduction of acetophe-
none to give (
S
)-pheylethanol in 95% yield and 97% ee [317,318]. A Ru complex with
tridentate nitrogen-base ligand AMBOX catalyzed the reduction of a series of aromatic
and aliphatic ketones with up to 98% ee [319]. A few other chiral β - amino alcohols were
also effective ligands for the asymmetric transfer hydrogenation of α - aryl ketones [320] .
Some chiral alcohol ligands were also studied with notably lower enantioselectivity.
More successfully, Ru complexes of many oxazoline ligands were proved to deliver good
effi ciency. For example, preformed RuCl
2
[(
S
) -
135
](PPh
3
) served as highly active catalyst
for the reduction of
iso
butyrophenone. Up to 92% ee was achieved with only 0.1% cata-
lyst loading [321]. It was observed that the enantioselectivity decreased with substrates
bearing larger alkyl groups. Ligand (
S
) -
131
provided up to 96% ee in the asymmetric
reduction of acetophenone derivatives [322]. Chiral auxiliary (
R
,
R
) -
136
was found to be
