Ruthenium-Catalyzed Transfer Hydrogenation
was then concentrated, and the crude product was purified by flash
column chromatography to afford the corresponding alcohol in
good yield.
Standard Procedure for the Reduction of Amidoacetophenones: 1,4-
Butanediol (0.53 mL, 6 mmol) and 1,2-dimethoxyethane (3 mL)
were added to an oven-dried, nitrogen-purged Young’s tube con-
taining [Ru(PPh3)3(CO)(H)2] (138 mg, 0.15 mmol) and the amido
ketone (3 mmol). The reaction tuve was then purged with nitrogen
for 10 min before it was heated to 115 °C for 24 h. On completion,
the reaction mixture was cooled to room temperature before con-
centrating under vacuum. The crude product was purified by flash
column chromatography before recrystallizing from CH2Cl2/hexane
to afford the corresponding alcohol in good yield.
Scheme 3. Ring opening of imides.
group, actually had very little effect on the reaction yield
(88%). Finally, both ethyl- and phenyl-substituted ketones
5 and 6 were found to be good substrates for the reaction
(73 and 68%, respectively), which indicates application of
the process beyond acetophenones.
Supporting Information (see footnote on the first page of this arti-
cle): Complete experimental details, characterization data, and
1
copies of the H and 13C NMR spectra.
Acknowledgments
We would like to thank the University of Canterbury for providing
funding for A. J. A. W. We would also like to thank Dr. Marie
Squire for her help with running the MS and NMR services.
Scheme 4. Substrate scope.
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Conclusions
This study represents the first systematic examination of
ruthenium-catalyzed transfer hydrogenation of amino- and
amido-substituted aromatic ketones. It was found that 1,4-
butanediol was the best hydrogen source under the reaction
conditions. Furthermore, the yields were generally good for
a challenging reduction reaction, and a range of amines,
amides, and substituted ketones were tolerated. It is there-
fore concluded that this method provides a robust catalytic
alternative to traditional reducing agents. Future areas for
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Experimental Section
Standard Procedure for the Formation of Amino Ketones: 4-Fluoro-
acetophenone (3.6 mL, 30 mmol) was dissolved in DMSO (40 mL)
under N2, and the amine (66 mmol, 2.2 equiv.) was added before
the mixture was heated to 115 °C for 16 h. The mixture was then
cooled to room temperature before it was poured into H2O
(100 mL) and mixed with brine (100 mL). The mixture was ex-
tracted with Et2O (3ϫ 100 mL), and the combined organic layers
were then dried (MgSO4), filtered, and concentrated under vacuum.
The crude material was then purified by column chromatography
(petroleum ether/EtOAc) to afford the corresponding ketone in
good yield.
Standard Procedure for the Reduction of Aminoacetophenones: 1,4-
Butanediol (0.53 mL, 6 mmol) and 1,2-dimethoxyethane (3 mL)
were added to an oven-dried, nitrogen-purged Young’s tube con-
taining [Ru(PPh3)3(CO)(H)2] (138 mg, 0.15 mmol) and the amino
ketone (3 mmol). The reaction tube was then purged with nitrogen
for 10 min before diluting with CH2Cl2 (50 mL). The mixture was
then extracted with aqueous NaOH (1 m, 20 mL). The organic layer
Eur. J. Org. Chem. 2013, 6784–6788
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