C O M M U N I C A T I O N S
Table 2. Asymmetric Hydrogenation of R-Phthalimide Ketonea
Scheme 2. High anti-Selectivity and Efficient Dynamically Kinetic
Resolution Lead the Formation of Optically Pure allo-Threonine via
Ru-Catalyzed Asymmetric Hydrogenation
entry
R
T (°C)
conv (%)
ee (%)b
1
2
3
4
5
6
7
8
p-MeOC6H5
p-MeOC6H5
p-MeC6H5
p-FC6H5
p-ClC6H5
p-ClC6H5
p-BrC6H5
m-MeOC6H5
o-MeOC6H5
Me
80
60
80
60
80
60
80
80
60
60
80
100
60
100
100
100
30
100
100
100
100
100
95.3
98.5
>99.0
>99.0
92.3
94.0
>99.0
>99.0
>99.0
>99.0
>99.0
9
10
11
Et
a The reaction was carried out with 2 mol % Ru catalyst. b The ee values
were detected via HPLC.
Scheme 1. Highly Enantioselective and Practical Synthesis of
1-Amino-2-propanol
chemistry, and bioorganic chemistry. The mechanistic study and
further synthetic utilities of this new type of substrate are currently
being explored in this lab and will be reported in due course.
Acknowledgment. This work was supported by NIH grants.
We gratefully acknowledge Dr. Wenjun Tang for helpful discus-
sions.
Supporting Information Available: Spectroscopic data, GC, HPLC
spectra, and experimental details (PDF). This material is available free
References
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provides the (S)-(+)-1-amino-2-propanol (1 g/$25.50, Acros) in the
reflux ethanol in the presence of NH2NH2 in 98% yield.
The most exciting application for this catalyst system is a
dynamically kinetic resolution for the synthesis of threonine
(Scheme 2). Using catalyst 3c, we obtained allo-threonine derivative
in more than 99% ee and >97:3 dr. Compared with Noyori’s
system,10 the syn/anti selectivity was totally reversed. We obtained
a ratio of more than 97:3 anti/syn selectivity. Thus, using our
catalysts (R-C3-TunePhos and S-C3-TunePhos), both (2R,3R)-(-)-
allo- and (2S,3S)-(+)-allo-threonine derivatives can be obtained
in high optical purity, in which the allo-threonines are more
expensive isomers (25 mg/$39 for D-form and 100 mg/$71.80 for
L-form, Aldrich) compared with threonine (5 g/$15.80 for D-form
and 100 g/$76.50 for L-form, Aldrich). Thus, four isomers of
threonine can be selectively obtained by catalyst system choice.
To our knowledge, this is the first report of using hydrogenation
to achieve high anti configuration of chiral amino alcohols.
In summary, a new type of R-phthalimide ketone was asym-
metrically hydrogenated in excellent enantioselectivity. This pro-
vides an efficient method to synthesize enantiomerically pure amino
alcohols, which is important in synthetic chemistry, medicinal
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