3
underwent a decarboxylation and oxidation to generate
intermediate VI and diketone VII consequentely.
12
Under
d
1
r
s
2r (99%)
irradiation of visible light and with assistance of photoredox
catalyst, diketone VII was then oxidized to peroxide intermediate
VIII by molecular oxygen. Under basic condition and through
another nucleophilic addition intermediate VIII was converted to
intermediate IX, which was eventually transformed to carboxylic
acid 2n and trifluoroacetic acid after elution of one equivalent of
hydrogen peroxide. Even though the exact mechanism is still
unclear and most of the proposed intermediates are not isolated
1
1
g
2g (87%)
1
d
h
2s (98%)
2t (99%)
2
h (54%)
1
9
1
t
d
or identified, the
F experimental results showed that
1
1
i
2i (50%)
trifluoroacetic acid is one of the major by-products of this
oxidation which is in agreement with our proposed mechanism.
1
u
d
j
2u (95%)
2
j (75%)
c
1
k
2a (67%)
1v
2
t (0%)
1
l
1w
2
t (trace)
2l (99%)
a
Reaction condition: photoredox catalyst (0.01 mmol) was added to a
stirred solution of 2 mL CH CN, 1 (1.0 mmol) with 4 Å molecular sieve (200
mg) and NaHCO (84 mg, 1.0 mmol), the mixture was stirred under
3
3
Scheme 2 A Plausible mechanism of aerobic oxidative
cleavage of β-diketones to carboxylic acids.
irradiation of 20 W blue LED and charged with oxygen balloon for 4 h unless
b
otherwise noticed. Yield based on the isolated product after chromatography
c
through silica gel. Reaction was not complete even for an extended time of
In summary, we have discovered a mild and highly efficient
process for the synthesis of carboxylic acids through a
photoredox mediated oxidative cleavage β-diketones under
visible light irradiation. This method provides a potential general
and practical protocol for both laboratory synthesis and industrial
production of carboxylic acids in a green manner. Other
applications of this methodology are currently underway and will
be disclosed in due course.
d
4
4
8 h. Yield based on GC analysis, reaction was scaled up from 1.0 mmol to
3-100 mmol.
To test that the optimized reaction is practical and scalable, a
100 mmol scale reaction of 1n was carried out in a 1000 mL
round flask under sunlight. The reaction showed identical results
as that processed in the laboratory hoods, carboxylic acid 2n was
generated in 98% yield (Scheme 1). It is to be mentioned this
specific substrate possessing a terminal -CF
oxidative cleavage with or without adding NaHCO
3
group underwent
to provide
Acknowledgments
3
the corresponding acid in nearly quantitative yield which
demonstrated the potentiality of this protocol for both laboratory
synthesis and industrial production. The structure of 2n was
confirmed by NMR and X-ray.
This work was supported by Wuhan University of Technology
and the Natural Sciences Foundation of Hubei Province.
References and notes
1
2
.
.
(a) Ravelli, D.; Fagnoni, M.; Albini, A. Chem. Soc. Rev. 2013, 42,
9
4
7; (b) Lang, X.; Chen, X.; Zhao, J. Chem. Soc. Rev. 2014, 43,
73.
For some recent reviews, see: (a) Zeitler, K. Angew. Chem., Int.
Ed. 2009, 48, 9785; (b) Yoon, T. P.; Ischay, M. A. and Du, J. Nat.
Chem. 2010, 2, 527; (c) Narayanam, J. M. R. and Stephenson, C.
R. J. Chem. Soc. Rev. 2011, 40, 102; (d) Xuan, J. and Xiao, W.-J.
Angew. Chem., Int. Ed. 2012, 51, 6828; (e) Prier, C. K.; Rankic,
D. A. and MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322; (f)
Schultz, D. M.; Yoon, T. P. Science. 2014, 343, 985.
Scheme 1 A practical and scalable example of the oxidative
cleavage reaction.
The mechanism of this oxidation was proposed in Scheme 2,
taking 1n as an example, we envisioned that, the photoredox
catalysts transferred energy to molecular oxygen and
3.
For some recent review, see: (a) Punniyamurthy, T.; Velusamy, S.;
Iqbal, J. Chem. Rev. 2005, 105, 2329; (b) Burns, N. Z.; Baran, P.
S.; Hoffmann, R. W. Angew. Chem., Int. Ed. 2009, 48, 2854; (c)
Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41,
10
subsequently generated singlet oxygen which initially oxidized
3
381; (d) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.;
1
1
1
,3-diketone 1n to peroxide intermediate I, and I was then
Kozlowski, M. C. Chem. Rev. 2013, 113, 6234; (e) Campbell, A.
N.; Stahl, S. S. Acc. Chem. Res. 2013, 45, 851.
(a) Larock, R. C.; Comprehensive Organic Transformations, 2nd
ed.; Wiley-VCH: New York, 1999, 1625; (b) Smith,M. B.; March,
J. March’s Advanced Organic Chemistry, 6th ed.; John Wiley and
Sons: Hoboken, 2007, 1745.
converted to triketone II through oxidative elimination one
equivalent of water. The triketone II was subsequently converted
to intermediate III under basic condition through a nucleophilic
addition, intermediate III was consequently transformed to
intermediate IV and V through a base-catalysed reverse benzilic
acid rearrangement process. Moreover, the intermediate V
4
5
.
.
For recent examples, see: (a) Allpress, C. J.; Miłaczewska, A.;
Borowski, T.; Bennett, J. R.; Tierney, D. L.; Arif, A. M.; Berreau,