C O M M U N I C A T I O N S
Table 3. Transfer Hydrogenation Catalyzed by C-6 and C-8a
entry
ketone
ligand
%conv
%ee
config.
1
2
3
4
acetophenone
acetophenone
3-methyl-2-butanone
3-methyl-2-butanone
(S)-6
(R)-8
(S)-6
(R)-8
96
97
92
98
64
22
30
55
S
R
R
S
Figure 1. Single-pulse unlocked, unshimmed, nonspinning 13C NMR of
reaction in eq 2 with catalyst A-13 at 5 days.
a %Conv and %ee determined by GC analysis on â-dex 120 column.
Table 1. Arrayed Evaluation Using Isotopically Chiral Probe 1a
2-butanone (Table 3) indicates that 1-substituted ethanolamines may
be a promising starting point for development of simple catalysts
for reduction of dialkyl ketones.
In conclusion, we have reported a simple method for high-
throughput asymmetric reaction analysis that uses standard instru-
mentation. We expect that this approach may be useful for the study
of a number of asymmetric transformations since 2 may be readily
converted to a range of functionalized probe substrates.
Acknowledgment. This work was supported by the NIH (GM
59417-03). J.P.M. is grateful to Bristol-Myers Squibb, Dow,
DuPont, GlaxoSmithKline, and the David and Lucile Packard
Foundation for support in the form of research awards. We thank
Albert Russell for executing preliminary experiments.
4
5
6
7
8
9
10
97 100 100 100 100 28
20
100 15 100 100 100
11
12
13
62
A %conv 100 14
%ee 11 22
8
Supporting Information Available: Characterization data and
experimental procedures (PDF). This material is available free of charge
27 -48 -12
8
-7 -15 -50
B
93
1
55
96 46
-2
87 36
17
-4
80
26
0
66
20
96 50
48 -1
7
16
98
70
19 -37
96 98
76 -81
9
C
References
-3 -75
1
-7 -17
(1) For a comprehensive recent review, see: Dahmen, S.; Brase, S. Synthesis
2001, 1431.
a Note: %ee corrected for enantiomeric excess of probe substrate.
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3198.
Table 2. Comparison of GC- and NMR-Determined %eea
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b
precatalyst
% ee by 13C NMR
% ee by chiral GC
A8
A13
B7
-47
-48
13
-44
-44
16
B8
B12
C6
-38
-38
-1
-3
70
66
C7
73
70
C8
C10
C13
-79
-71
-20
-78
-66
-18
a Determined after 20 days of reaction. b Using 8 FT pulses and a 25 s
relaxation delay.
in addition to ee analysis one can also gain insight into reaction
rates and catalyst lifetime by integrating product relative to starting
material.
As expected in the reaction assay, the highest levels of enantio-
selection were achieved with hexamethylbenzene-ruthenium com-
plexes, although it is surprising, in light of prior art, that simple
primary amino alcohols such as phenyl glycinol (8) provided
product with highest levels of enantiocontrol.17 A brief examination
of the utility of ligands 6 and 8 with acetophenone and 3-methyl-
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JA026703T
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J. AM. CHEM. SOC. VOL. 124, NO. 31, 2002 9021