Journal of the American Chemical Society
Page 6 of 8
mation in 18, thereby increasing the net asymmetric induction of
the catalyst.
Present Addresses
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†Roxanne Clément, High-Throughput Experimentation Facility,
Centre for Catalysis Research and Innovation, University of Ottawa,
Ottawa, Ontario, K1N 6N5, Canada
As discussed above, it is likely the active catalyst is the mono-
deprotonated species 18. Similar mono-deprotonated catalysts
were first proposed by Chen based upon rate studies of ketone
hydrogenations.22 They were also investigated by computational
studies on ketone hydrogenations.23 As well, there are many stud-
ies on the role of alcohols on the rate and selectivity of ketone
bifunctional hydrogenations.24 Apart from our preliminary obser-
vations, we are aware of no detailed mechanistic studies on amide
bifunctional hydrogenations. Figure 4 shows some of the hydro-
gen and ionic bonds that may form between 2-PrOH (R = 2-Pr)
and the N-H or N--Na+ groups in 18. In principle, any of these
interactions would influence the enantioselectivity of the hydro-
Funding Sources
This work was supported by Natural Sciences and Engineering Re-
search Council of Canada (NSERC), GreenCentre Canada, and the
University of Alberta.
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ACKNOWLEDGMENT
We sincerely appreciate the assistance of the University of Alberta
High field NMR Laboratory and Mass Spectrometry Laboratory.
t
genation. In principle, THF, BuOH, the product alcohol, the
various alkoxides present over the course of the amide reduction,
and piperidene can engage in similar bonding with 18. The sys-
tem is complex, and a detailed study of the structure and reactivi-
ty of the putative intermediates would be required to unravel the
stereochemical forces that lead to the major enantiomer of the
product.
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EXPERIMENTAL SECTION
For experimental details see supplementary information.
ASSOCIATED CONTENT
Supporting Information
Text tables and figures giving experimental procedures and character-
ization data. This material is available free of charge via the internet at
AUTHOR INFORMATION
Corresponding Author
E-mail for S. H. B.: steve.bergens@ualberta.ca
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