Journal of the American Chemical Society
Communication
aerobic alcohol oxidation reactions. A rationale for the
Scheme 3. Simplified Mechanism for Fe(NO
)
3
3
/Aminoxyl-
III
observations is that Fe -promoted TEMPO disproportiona-
III
tion generates TEMPO anion, which coordinates to Fe and
provides the reducing equivalents needed to convert nitrate
into catalytically relevant NO species. Iron species likely play
x
34
an active role in nitrate reduction and initiation of catalysis.
The above results show that Fe(NO ) and Brønsted acid
3
3
NO -based catalyst systems feature similar mechanisms for
x
aerobic alcohol oxidation that involve serial cooperativity
(
Scheme 2C). This pathway, which contrasts the integrated
(
NO ) system not only tolerates acidic groups but also can
3 3
20
cooperativity of (bpy)Cu cocatalyst systems (Scheme 2B), has
important synthetic implications. A series of substrate probes
and kinetic comparisons were used to illuminate the
similarities and differences among three prototypical catalyst
oxidize 1° alcohols to the carboxylic acid products.
The substrate reactivity data in Figure 4 pair with the
mechanistic data in Figures 1−3 to support serial cooperativity
between Fe(NO ) and TEMPO during catalytic aerobic
35
3 3
systems for aerobic alcohol oxidation: Cu/TEMPO, Fe-
3+
alcohol oxidation (Scheme 2C). The combination of Fe and
nitrate represents an appealing NO cocatalyst system that is
capable of generating oxoammonium species with O (Scheme
2
0,21
+
36
(
NO ) /TEMPO,
and H /NO /TEMPO. These efforts
3
3
x
x
prioritized mechanistic insights over synthetic optimization, as
the latter has been emphasized in previous reports. The diol
substrates in Figure 4A,B feature an electronically activated 2°
benzylic alcohol with a sterically less hindered 1° benzylic or
aliphatic alcohol. In both cases, the Cu/TEMPO catalyst
shows a preference for 1° alcohol oxidation. The Fe(NO3)3
and NaNO /HNO cocatalyst systems exhibit similar reac-
2
3
). We anticipate that aerobic alcohol oxidation catalysts that
feature nitrate or other NO components also take advantage
x
of similar reactivity. Examples include recently reported
Cu(NO ) /TEMPO and Fe(NO ) /bpy/TEMPO sys-
43
44
3
2
3 3
45
tems. The mechanism in Scheme 3 contrasts the integrated
cooperativity mechanism of Cu/aminoxyl catalysts. These
divergent modes of cooperativity are manifested by different
chemoselectivities and synthetic scopes for the catalytic
reactions. The user-friendly and complementary synthetic
features of these two catalyst systems should contribute to
broader adoption of aerobic alcohol oxidation methods in
2
3
tivity, with little selectivity between 1°/2° benzylic alcohols
(
Figure 4A) but high selectivity for 2° benzylic over 1°
aliphatic alcohol oxidation (Figure 4B). This selectivity
contrasts that observed with the Cu/TEMPO catalyst system
but matches that expected from oxoammonium-mediated
alcohol oxidation under acidic conditions, aligning with the
22,46−48
organic synthesis, including large-scale applications.
37,38
serial mechanistic pathway in Scheme 2C.
To compare 1° and 2° aliphatic alcohols, oxidations of
ASSOCIATED CONTENT
sı Supporting Information
■
cyclohexanol and cyclohexylmethanol were monitored via gas-
*
39
uptake methods (Figure 4C). Reaction time courses show
that Cu/TEMPO oxidizes cyclohexylmethanol approximately
2
-fold faster than cyclohexanol. In contrast, Fe(NO ) /
3 3
Experimental details, additional electrochemical data,
TEMPO oxidizes cyclohexanol approximately 3-fold faster
than cyclohexylmethanol, following an induction period at the
start of the reaction (attributed to in situ generation of NOx
species as discussed above). The NaNO /HNO system shows
2
3
Corresponding Author
poor reactivity with aliphatic alcohols, and kinetic data were
not recorded. The latter observation highlights a benefit of the
Fe(NO ) -based catalyst system relative to other NO -based
■
Shannon S. Stahl − Department of Chemistry, University of
3
3
x
catalysts that use a similar mechanism.
The Cu/TEMPO and Fe(NO ) /TEMPO catalyst systems
3
3
show complementary features with other substrates (Figure
4
D). For example, Cu/TEMPO catalysts show good tolerance
35,40−42
Authors
of basic and oxidatively sensitive functional groups.
Jordan E. Nutting − Department of Chemistry, University of
Kaining Mao − Department of Chemistry, University of
Wisconsin-Madison, Madison, Wisconsin 53706, United
States
This feature is evident in the oxidation of the quinoline- and
aniline-containing substrates 9 and 11. In contrast, little
reactivity for these substrates is observed with the Fe(NO3)3
catalyst system, probably because of interference of the basic
III
functional groups with the Lewis acidity of Fe and/or
generation of the NO cocatalyst species. The Fe(NO )
x
3 3
catalyst system can be advantageous in other cases. Cu/
TEMPO reacts poorly with 1° alcohol 13, which has a terminal
alkyne; a mixture of unreacted starting material and products,
including the aldehyde, are observed. In contrast, 13 shows
good reactivity with the Fe(NO ) /TEMPO catalyst system,
Notes
The authors declare no competing financial interest.
3
3
affording carboxylic acid 15 in good yield. This result
highlights another complementary feature of the Cu- and
Fe(NO ) -based catalyst systems: Cu/TEMPO catalysts
convert 1° alcohols to aldehydes and are poisoned by acidic
functional groups (e.g., carboxylic acids), whereas the Fe-
ACKNOWLEDGMENTS
■
We thank Prof. M. Rafiee (University of Missouri-Kansas City)
for many helpful discussions. This work was funded by the U.S.
Department of Energy (DE-FG02-05ER15690). J.E.N. ac-
3
3
1
0568
J. Am. Chem. Soc. 2021, 143, 10565−10570