Journal of the American Chemical Society
Communication
This CuI/ABNO protocol is readily amenable to larger-scale
application. The oxidation of cyclohexanemethanol, 2-octanol,
and N-Boc-valinol were performed on a 10 mmol (1−2 g) scale
and afforded products 16, 18, and 30 in ≥90% yield. In each
case, the reaction was carried out in an open reaction flask at
room temperature and were complete within 1 h. The N-Boc-
azetidinone product 37 was prepared on a 50 mmol scale
(approximately 9 g) in a similar manner, albeit with a somewhat
longer reaction time (3 h). Reactions with a 1 mol % MeObpy/
Cu loading suggest that the catalyst deactivates before reaching
full conversion of the substrate (cf. Table S1). The origin of this
deactivation and efforts to overcome it are the focus of ongoing
work.
In summary, we have identified a highly effective, broad-
scope catalyst system for aerobic alcohol oxidation. Numerous
practical features associated with this method should facilitate
its use in synthetic chemistry, including fast reaction rates, mild
reaction conditions, compatibility with air as the source of
oxidant, and use of a common organic solvent (acetonitrile).
The CuI/ABNO catalyst complements the recently developed
CuI/TEMPO catalyst system. Whereas CuI/TEMPO shows
high chemoselectivity for primary alcohols, CuI/ABNO is
equally effective with all classes of alcohol substrates. Together,
these catalyst systems provide compelling aerobic alternatives
to traditional alcohol oxidation methods.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Full catalyst screening data, experimental procedures, product
characterization data for all products. This material is available
AUTHOR INFORMATION
Corresponding Author
■
Notes
(8) We have recently measured the redox potentials for each of the
nitroxyls in Figure 1 under a uniform set of conditions. See ref 7k. A
number of other nitroxyl redox potentials are reported in: Shibuya, M.;
Pichierri, F.; Tomizawa, M.; Nagasawa, S.; Suzuki, I.; Iwabuchi, Y.
Tetrahedron Lett. 2012, 53, 2070−2073.
(9) As shown in refs 3d and 3i, Cu/TEMPO-catalyzed oxidation of
activated alcohols benefit from electron-rich bpy derivatives. In
contrast, Cu/TEMPO-catalyzed oxidation of aliphatic alcohols exhibit
negligible bpy-based electron effects (see Figure S1 and Table S9).
(10) When more challenging substrates were encountered, we first
tested whether the reaction was successful at elevated temperatures
(50−70 °C). If this approach failed to provide satisfactory results, we
tested the use of pure O2 or the use of both elevated temperature and
pure O2.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work was provided by the DOE (DE-
FG02-05ER15690), ACS GCI Pharmaceutical Roundtable, a
consortium of pharmaceutical companies (Eli Lilly, Pfizer, and
Merck), and the NSF (predoctoral fellowship to J.E.S.). NMR
spectroscopy facilities were partially supported by the NSF
(CHE-9208463) and NIH (S10 RR08389).
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