ACS Catalysis
oxidized by transferring a hydride from C of the
Research Article
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1
0a
dihydronicotinamide to C of F4 via imine reduction. The
generated intermediate 8 then isomerized into the reduced
and S27) provided strong support for this mechanism. There
are two possible routes for the regeneration of F4, one in which
the reduced flavin 9 is reoxidized via a sequence of
disproportionations and two successive single-electron transfers
2
2
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2
(
1
4
a
to O through a C -flavin hydroperoxide adduct, as usually
2
̈
hler, B. Green Chem. 2011, 13, 226−265.
2
1
known for natural flavin reacting with O . However,
according to a recent study, another route (as illustrated in
2
(c) Hollmann, F.; Arends, I. W. C. E.; Holtmann, D. Green Chem.
2011, 13, 2285−2313.
22
Scheme 1) is also possible; following activation of O that
̈
(3) (a) Weckbecker, A.; Groger, H.; Hummel, W. Adv. Biochem. Eng.
2
resulted in the formation of a transient pseudobase 10 that
Biotechnol. 2010, 120, 195−242. (b) Hollmann, F.; Arends, I. W. C. E.;
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1
0a
carries the −OOH group at the C position, the catalytic cycle
is finally completed by protonation of 10 with a concomitant
elimination to produce the starting flavinium cation F4 and
H O .
1
(
789. (d) Liu, W. F.; Wang, P. Biotechnol. Adv. 2007, 25, 369−384.
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3
. CONCLUSION
(
4) (a) Riebel, B. R.; Gibbs, P. R.; Wellborn, W. B.; Bommarius, A. S.
In conclusion, a simple, clean, and highly efficient oxidized
cofactor regeneration system using a water-soluble artificial
flavinium organocatalyst is presented. It has the following
advantages. (1) It avoids the use of a metal or irritant organic
cocatalyst. (2) It does not rely on any special illumination or
equipment. (3) The water solubility of the catalyst makes a fully
homogeneous system, thereby circumventing diffusion limi-
tations, which is an obvious advantage for the real enzyme
catalysis system. (4) The regeneration efficiency is high, as
evidenced by TOFs for various biotransformations. (5) Mild
reaction conditions are used (air atmosphere, more adaptable
pH, and temperature tolerant range). Moreover, the presented
system provides an easy scale-up protocol. Hence, we believe
that it will find wide applications in organic synthesis as well as
in industry.
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2
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(
2
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Kochius, S.; Holtmann, D.; Arends, I. W. C. E.; Ludwig, R.; Hollmann,
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ASSOCIATED CONTENT
Supporting Information
■
*
S
All reaction details and analytical data (PDF)
(7) (a) Hilt, G.; Lewall, B.; Montero, G.; Utley, J. H. P.; Steckhan, E.
Liebigs Ann. 1997, 1997, 2289−2296. (b) Schro
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der, I.; Steckhan, E.;
Liese, A. J. Electroanal. Chem. 2003, 541, 109−115. (c) Hilt, G.;
AUTHOR INFORMATION
Notes
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Jarbawi, T.; Heineman, W. R.; Steckhan, E. Chem. - Eur. J. 1997, 3,
7
2
(
9−88. (d) Li, H.; Worley, K. E.; Calabrese Barton, S. ACS Catal.
012, 2, 2572−2576.
*
8) Gargiulo, S.; Arends, I. W. C. E.; Hollmann, F. ChemCatChem
The authors declare no competing financial interest.
2
011, 3, 338−342.
9) (a) Maid, H.; Bo
Jux, N.; Groger, H. Angew. Chem., Int. Ed. 2011, 50, 2397−2400.
b) Greschner, W.; Lanzerath, C.; Reβ, T.; Tenbrink, K.; Borchert, S.;
Mix, A.; Hummel, W.; Groger, H. J. Mol. Catal. B: Enzym. 2014, 103,
0−15. (c) Maenaka, Y.; Suenobu, T.; Fukuzumi, S. J. Am. Chem. Soc.
012, 134, 367−374.
10) (a) Poizat, M.; Arends, I. W. C. E.; Hollmann, F. J. Mol. Catal.
B: Enzym. 2010, 63, 149−156. (b) Hildebrand, F.; Lutz, S. Chem. - Eur.
J. 2009, 15, 4998−5001.
11) Jones, J. B.; Taylor, K. E. J. Chem. Soc., Chem. Commun. 1973,
05−206.
12) (a) Jakovac, I. J.; Goodbrand, H. B.; Lok, K. P.; Jones, J. B. J.
(
̈
hm, P.; Huber, S. M.; Bauer, W.; Hummel, W.;
ACKNOWLEDGMENTS
̈
■
(
The authors acknowledge financial support from the Program
for Changjiang Scholars and Innovative Research Team in
University (Grant IRT_14R28), The Major Research Plan of
the National Natural Science Foundation of China (Grant
1390204), the National Natural Science Foundation of China
Grant 21406110), and the Jiangsu National Synergetic
̈
1
2
(
2
(
̈
Innovation Center for Advanced Materials (SICAM).
(
2
(
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ACS Catal. 2016, 6, 4989−4994