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COMMUNICATION
Journal Name
Proton Source
Stern-Volmer Analysis
· DFMS acts as quencher
· Imine does not quench
3
4
(a) K. Müller, C. Faeh and F. Diederic
881; (b) J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del
Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok and H.
Liu, Chem. Rev., 2014, 114, 2432.
(a) S. Purser, P. R. Moore, S. Swallow and V. Gouverneur,
Chem. Soc. Rev., 2008, 37, 320; (b) W. K. Hagmann, J. Med.
Chem., 2008, 51, 4359.
(a) N. A. Meanwell, J. Med. Chem., 2011, 54, 2529; (b) Y.
Zafrani, D. Yeffet, G. Sod-Moriah, A. Berliner, D. Amir, D.
Marciano, E. Gershonov and S. Saphier, J. Med. Chem., 2017,
60, 797.
·
·
CH3CN provides H
Confirmed with CD3CN
h, Scie.1nce, 2007, 317,
DOI: 10 039/D0CC01353F
(fully deuterated product)
1
Rh-6G
*Rh-6G
Ph
Ph
(
D)HN
N
O
S
Ph
CF2H
Ph
CF2H
5
6
O
CF2H
2a
II
-
SO2
Rh-6G
DFMS
Ph
Ph
N
N
CF2H
Ph
CF2H
Ph
CF2H
Ph
N
CF2H
II
I
CF2H2
undesired)
Ph
1a
(
7
8
(a) J.-A. Ma and D. Cahard, J. Fluorine Chem., 2007, 128, 975;
(b) O. A. Tomashenko and V. V. Grushin, Chem. Rev., 2011,
111, 4475; (c) A. Studer, Angew. Chem., Int. Ed., 2012, 51,
Quantum Yield Measurement
·
·
φ < 1 indicates photocatalytic cycle
Radical chain propagation cannot
be ruled out
Hydrogen Atom Transfer
· Does not take place in the reaction
· Excess of HAT donor inhibits product formation
8
950.
(a) J. Hu, W. Zhang and F. Wang, Chem. Commun., 2009,
2
Scheme 3. Mechanistic proposal for the photocatalytic CF H radical addition to C=N
7
465; (b) D. E. Yerien, S. Barata-Vallejo and A. Postigo, Chem.
bonds.
Eur. J., 2017, 23, 14676.
9
1
C. Ni, M. Hu and J. Hu, Chem. Rev., 2015, 115, 765.
(a) Y. Li and J. Hu, Angew. Chem., Int. Ed., 2005, 44, 5882; (b)
Y. Li and J. Hu, Angew. Chem., Int. Ed., 2007, 46, 2489; (c) J.
Liu, Y. Li and J. Hu, J. Org. Chem., 2007, 72, 3119; (d) J. Liu and
J. Hu, Chem. Eur. J., 2010, 16, 11443; (e) S. Fustero, J.
Moscardó, M. Sánchez-Roselló, E. Rodríguez and P. Barrio,
Org. Lett., 2010, 12, 5494. Via Reformatsky reactions, see: f)
T. Poisson, M.-C. Belhomme and X. Pannecoucke, J. Org.
Chem., 2012, 77, 277; g) C.-R. Cao, M. Jiang and J.-T. Liu, Eur.
J. Org. Chem., 2015, 1144.
when used as co-solvent (bottom right, Scheme 3).
Consequently, the most plausible pathway for intermediate I
would involve reduction to form intermediate II. This reduction
0
•-
step could be enforced by Rh-6G – closing the photocatalytic
cycle – or could initiate a radical chain mechanism by oxidation
of DFMS (bottom left, Scheme 3). However, quantum yield
determination ( < 1) suggests that the catalytic reduction is
taking place, although a radical chain process cannot be ruled
2
3
11 Y. Zhao, W. Huang, J. Zheng and J. Hu, Org. Lett., 2011, 13,
342.
1
3
out. Lastly, use of deuterated solvent (CD CN) confirmed
5
acetonitrile as the proton source for the final step of the
reaction, as evidenced by the formation of the fully deuterated
product.
2
G. K. S. Prakash, M. Mandal and G. A. Olah, Angew. Chem.,
Int. Ed., 2001, 40, 589.
13 a) G. K. S. Prakash, R. Mogi and G. A. Olah, Org. Lett., 2006,
, 3589; b) G. K. S. Prakash, Y. Wang, R. Mogi, J. Hu, T.
Mathew and G. A. Olah, Org. Lett., 2010, 12, 2932.
8
In conclusion, a direct difluoromethyl addition to C=N bonds
has been developed. The photocatalytic activation of 14 Visible Light Photocatalysis in Organic Chemistry, (Eds.: C. R.
commercially available DFMS as difluoromethylating reagent
delivers a new radical approach which benefits from the mild
conditions to achieve impressive structural diversity; diaryl-
substituted aldimines, quinolines, quinoxalinones and
dibenzazepines are successfully functionalized with the
J. Stephenson, T. P. Yoon and D. W. C. MacMillan), Wiley-
VCH, Weinheim, 2018.
(a) T. Chatterjee, N. Iqbal, Y. You and E. J. Cho, Acc. Chem.
Res., 2016, 49, 2284; (b) S. Barata-Vallejo, M. V. Cooke and
A. Postigo, ACS Catal., 2018, 8, 7287; (c) T. Koike and M.
Akita, Org. Biomol. Chem., 2019, 17, 5413.
1
5
pharmacologically crucial CF
proposal based on several experimental trials is presented, in
which •CF H addition and subsequent reduction of the aminyl
2
H group. Finally, a mechanistic 16 T. Koike and M. Akita, Acc. Chem. Res., 2016, 49, 1937.
1
1
1
7
8
9
Y. Fujiwara, J. A. Dixon, R. A. Rodriguez, R. D. Baxter, D. D.
Dixon, M. R. Collins, D. G. Blackmond and P. S. Baran, J. Am.
Chem. Soc., 2012, 134, 1494.
2
radical constitute the key steps of the process.
(a) J. Rong, C. Ni and J. Hu, Asian J. Org. Chem., 2017, 6, 139;
(
b) A. Lemos, C. Lemaire and A. Luxen, Adv. Synth. Catal.,
Financial support was provided by the European Research
Council (ERC-CoG, contract number: 647550), Spanish
Government (RTI2018-095038-B-I00), “Comunidad de Madrid”
and European Structural Funds (S2018/NMT-4367).
2
019, 361, 1500.
(a) Y. Fujiwara, J. A. Dixon, F. O’Hara, E. D. Funder, D. D.
Dixon, R. A. Rodriguez, R. D. Baxter, B. Herlé, N. Sach, M. R.
Collins, Y. Ishihara and P. S. Baran, Nature, 2012, 492, 95; (b)
F. O’Hara, R. D. Baxter, A. G. O’Brien, M. R. Collins, J. A. Dixon,
Y. Fujiwara, Y. Ishihara and P. S. Baran, Nat. Protoc., 2013, 8,
1
042.
Conflicts of interest
There are no conflicts to declare.
2
2
0
1
Heterocycles in Life and Society: An Introduction to
Heterocyclic Chemistry, Biochemistry and Applications, (Eds.:
A. F. Pozharskii, A. T. Soldatenkov and A. R. Katritzky), Wiley:
Chichester, 2011, pp. 139-183.
L. Shi, W. Hu, J. Wu, H. Zhou, H. Zhou and X. Li, Mini-Rev.
Med. Chem., 2018, 18, 392.
Notes and references
1
(a) D. B. Harper and D. O’Hagan, Nat. Prod. Rep., 1994, 11, 22 S. Jafari, F. Fernandez-Enright and X.-F. Huang, J.
1
23; (b) X.-H. Xu, G.-M. Yao, Y.-M. Li, J.-H. Lu, C.-J. Lin, X.
Neurochem., 2012, 120, 371.
Wang and C.-H. Kong, J. Nat. Prod., 2003, 66, 285.
23 Indeed, a radical chain reaction hypothesis might be
excluded when < 1, although quantum yield determination
can only serve as conclusive evidence when > 1; see: M. A.
Cismesia and T. P. Yoon, Chem. Sci., 2015, 6, 5426.
2
(a) C. Hollingworth and V. Gouverneur, Chem. Commun.,
2
012, 48, 2929; (b) T. Liang, C. N. Neumann and T. Ritter,
Angew. Chem., Int. Ed., 2013, 52, 8214.
4
| J. Name., 2012, 00, 1-3
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