Journal of the American Chemical Society
Article
a synthetically important carbonyl functionality could be
tolerated (14−17), and meanwhile, olefins without other
functional groups were also oxidatively cleaved to furnish
ketone products in good yields (18−21 and 23). However, 3-
fluoro-2-methyltridec-1-ene, in which the CC double is
deactivated by an adjacent electron-withdrawing fluorine
group, could not afford any cleavage product (22), highlighting
the sensitivity of the catalyst to substrate electronic effect. In
contrast, the electron-withdrawing, but well-separated, bro-
mide did not stop the formation of ketone 25. The presence of
halogen substituents in the oxidation products, such as
chloride in 24 and bromide in 25, makes the ketone products
more versatile in further applications. Still worth noting is that
the oxidation-susceptible benzylic C−H bond (viz. 23, 24 and
below) remained intact during the oxidation, showing the
protocol to be chemoselective. The catalysis thus makes 1,1-
disubstitued CC bonds an easily accessible latent carbonyl
functionality.
Table 1. Oxidation of Mono-, Di-, Tri-, and Tetrasubstituted
Alkenes and Dialkenes
a
As maybe expected, this photo-Mn enabled protocol is well
suited for activated alkenes. Thus, as is seen in Scheme 3,
styrene and related derivatives were oxidatively cleaved to yield
carbonyl compounds in a highly selective manner and good to
excellent yields. Moreover, it shows an excellent functional
group compatibility, with halogen, nitro, ester, acid, cyclo-
propyl, alkynyl, pyridine, and boronic ester units all tolerated
(26−48). Both benzylic and tertiary C−H bonds, which are
prone to oxidation, were also tolerated during the oxidation
(42, 44−46), adding more support to the high chemo-
selectivity mentioned above. A gram-scale oxidative cleavage
was also demonstrated. Under the standard conditions but
with 0.01% mol (0.9 mg) of catalyst, α-methylstyrene (1.18 g,
10 mmol) was oxidized to ketone 26 with a turnover number
of 4000 in 12 h (Scheme S2). It is noted that this new strategy
allows for milder reaction conditions in comparison with the
previously reported Fe- and organo-catalytic methods,8b,d,9a,b
and shows improved compatibility with electron-withdrawing
groups in comparison with the photocatalytic method
developed by Wang et al.8c
a
The oxidation was then extended to monosubstituted,
internal disubstituted, trisubstituted, and tetrasubstituted
alkenes as well as dialkenes. As shown in Table 1, a diverse
range of such alkenes can be oxidized to afford the
corresponding carbonyls or their methanol-protected form,
dimethyl acetals. Thus, the unsaturated fatty acid derivative 49
was cleaved into an aldehyde, which was in situ converted into
the acetal 50. Cyclooctene 51 gave rise to two isolable,
valuable oxidation products 52 and 53 in 41% overall yield, the
former of which is likely to result from the oxidation of the
initially formed aldehyde. Worth noting is that the formation of
the epoxide 53 may indicate the involvement of a high valent
Mn−oxo species during the oxidation.15 The CC double
bonds of trisubstituted alkenes, such as those in 54, 56, and 58,
were all oxidized, affording carbonyl products and derivatives.
For instance, the cleavage of 58 led to benzophenone 38 and
the overoxidation product of benzaldehyde, methyl benzoate
The viability of the protocol in oxidatively cleaving
tetrasubstituted alkenes is seen in the examples of 59, 61,
and 62, the isolated products being the ketones of higher
molecular weight in the case of 59 and 61. Note that the
cyclopentene 62 underwent ring-opening, affording the
diketone 16. Interestingly, dialkenes are also viable for this
transformation, with both the CC double bonds selectively
All the reactions were performed with alkene (0.5 mmol),
[Mn(dtbpy)2(OTf)2] (2 mol %), in MeOH/TFE (1:1, 2 mL) with
blue light (9 W, 470 nm) at 20 °C under O2 (1 atm) overnight.
b
Isolated yields are given. The yield was obtained by 1H NMR
analysis with mesitylene as internal standard.
oxidized to afford the corresponding dicarbonyl compounds in
good yields (63−65 and 67).
To further demonstrate the practical applicability of this
photo-Mn protocol in aerobic oxidation of CC double
bonds, we attempted the oxidative cleavage of a wide range of
natural products and their derivatives. As shown in Table 2,
terpenes could be selectively oxidized into terpenoids, which
are interesting chemical intermediates for fragrance (70 and
72). The nopinone 70, produced industrially from ozonolysis
of 69, has been used to synthesize Nabilone,16 a synthetic
cannabinoid used to treat nausea and vomiting during cancer
treatment, and the prostaglandin D2 (PGD2) receptor
antagonist S-5751.17 However, a detailed safety study of the
industrial ozonolysis has revealed the high risk of explosion and
a runaway reaction in this multistep process (−57, −27, 0, and
finally 25 °C).17 (+)-Nootkatone 73, a sesquiterpene ketone
from the heartwood of yellow cedar, was cleaved to afford the
corresponding methyl ketone in good yield. Interestingly,
although there are two CC double bonds in the structure of
10008
J. Am. Chem. Soc. 2021, 143, 10005−10013