Organic Letters
Letter
Organometallics 1986, 5, 2350−2355. (b) Gaspar, B.; Carreira, E. M.
Mild cobalt-catalyzed hydrocyanation of olefins with tosyl cyanide.
Angew. Chem., Int. Ed. 2007, 46, 4519−4522.
S. L. J.; Webster, R. D. Electrochemically Induced Chemically
Reversible Proton-Coupled Electron Transfer Reactions of Riboflavin
(Vitamin B2). J. Am. Chem. Soc. 2012, 134, 5954−5964. (c) Chen,
W.; Chen, J.-J.; Lu, R.; Qian, C.; Li, W.-W.; Yu, H.-Q. Redox reaction
characteristics of riboflavin: A fluorescence spectroelectrochemical
analysis and density functional theory calculation. Bioelectrochemistry
2014, 98, 103−108.
(5) For selected examples, see: (a) Murahashi, S. I.; Nakae, T.;
Terai, H.; Komiya, N. Ruthenium-Catalyzed Oxidative Cyanation of
Tertiary Amines with Molecular Oxygen or Hydrogen Peroxide and
Sodium Cyanide: sp3 C-H Bond Activation and Carbon-Carbon Bond
Formation. J. Am. Chem. Soc. 2008, 130, 11005−11012. (b) Wagner,
A.; Han, W.; Mayer, P.; Ofial, A. R. Iron-Catalyzed Generation of α-
Amino Nitriles from Tertiary Amines. Adv. Synth. Catal. 2013, 355,
3058−3070. (c) Huang, M.; Deng, Q.; Gao, Q.; Shi, J.; Zhang, X.;
Xiong, Y. Iron-Sulfate-Catalyzed Direct Dehydrogenative Coupling
Cyanation of Secondary Phenylamines. Asian J. Org. Chem. 2018, 7,
404−410.
(15) (a) Dusel, S. J. S.; Konig, B. Visible-Light-Mediated Nitration
̈
̈
of Protected Anilines. J. Org. Chem. 2018, 83, 2802−2807.
(b) Morack, T.; Metternich, J. B.; Gilmour, R. Vitamin Catalysis:
Direct, Photocatalytic Synthesis of Benzocoumarins via (−)-Ribo-
flavin-Mediated Electron Transfer. Org. Lett. 2018, 20, 1316−1319.
(16) Nevesely, T.; Svobodova, E.; Chudoba, J.; Sikorski, M.;
Cibulka, R. Efficient Metal-Free Aerobic Photooxidation of Sulfides to
Sulfoxides Mediated by a Vitamin B2 Derivative and Visible Light.
Adv. Synth. Catal. 2016, 358, 1654−1663.
(17) Metternich, J. B.; Gilmour, R. One Photocatalyst, n Activation
Modes Strategy for Cascade Catalysis: Emulating Coumarin Biosyn-
thesis with (−)-Riboflavin. J. Am. Chem. Soc. 2016, 138, 1040−1045.
(18) Martinez-Haya, R.; Miranda, M. A.; Marin, M. L. Metal-Free
Photocatalytic Reductive Dehalogenation Using Visible-Light: A
Time-Resolved Mechanistic Study. Eur. J. Org. Chem. 2017, 2017,
2164−2169.
(6) For selected examples, see: (a) Hoshikawa, T.; Yoshioka, S.;
Kamijo, S.; Inoue, M. Photoinduced Direct Cyanation of C(sp3)−H
Bonds. Synthesis 2013, 45, 874−887. (b) Kong, S.; Zhang, L.; Dai, X.;
Tao, L.; Xie, C.; Shi, L.; Wang, M. DDQ-mediated Direct C(sp3)-H
Cyanation of Benzyl Ethers and 1,3-Diarylpropenes under Solvent-
and Metal-free Conditions. Adv. Synth. Catal. 2015, 357, 2453−2456.
(c) Wakaki, T.; Sakai, K.; Enomoto, T.; Kondo, M.; Masaoka, S.;
Oisaki, K.; Kanai, M. C. sp3)-H Cyanation Promoted by Visible-Light
Photoredox/Phosphate Hybrid Catalysis. Chem. - Eur. J. 2018, 24,
8051−8055.
(19) Ramirez, N. P.; Gonzalez-Gomez, J. C. Decarboxylative Giese-
type reaction of carboxylic acids promoted by visible-light: a
sustainable and photoredox neutral protocol. Eur. J. Org. Chem.
2017, 2017, 2154−2163.
̈
(7) For a recent comprehensive review, see: Schwarz, J.; Konig, B.
Decarboxylative reactions with and without light − a comparison.
Green Chem. 2018, 20, 323−361.
(8) (a) Klein, D. A. Nitrile Synthesis via the Acid-Nitrile Exchange
Reaction. J. Org. Chem. 1971, 36, 3050−3051. (b) Cantillo, D.;
Kappe, C. O. Direct Preparation of Nitriles from Carboxylic Acids in
Continuous Flow. J. Org. Chem. 2013, 78, 10567−10571.
(9) Song, F.; Salter, R.; Chen, L. Development of Decarboxylative
Cyanation Reactions for C-13/C-14 Carboxylic Acid Labeling Using
an Electrophilic Cyanating Reagent. J. Org. Chem. 2017, 82, 3530−
3537.
̈
(20) Bloom, S.; Liu, C.; Kolmel, D. K.; Qiao, J. X.; Zhang, Y.; Poss,
M. A.; Ewing, W. R.; MacMillan, D. W. C. Decarboxylative alkylation
for site-selective bioconjugation of native proteins via oxidation
potentials. Nat. Chem. 2017, 10, 205−211.
(21) Bockman, T. M.; Hubig, S. M.; Kochi, J. K. Direct Observation
of Ultrafast Decarboxylation of Acyloxy Radicals via Photoinduced
Electron Transfer in Carboxylate Ion Pairs. J. Org. Chem. 1997, 62,
2210−2221.
(10) (a) Barton, D. H. R.; Jaszberenyi, J. C.; Theodorakis, E. A.
Radical Nitrile Transfer with Methanesulfonyl Cyanide or p-
Toluenesulfonyl Cyanide to Carbon Radicals Generated from the
Acyl Derivatives of N-Hydroxy-2-Thiopyridone. Tetrahedron Lett.
1991, 32, 3321−3324. (b) Barton, D. H. R.; Jaszberenyi, J. C.;
Theodorakis, E. A. The Invention of Radical Reactions -Part XXIII-
New Reactions: Nitrile and Thiocyanate Transfer to Carbon Radicals
from Sulfonyl Cyanides and Sulfonyl Isothiocyanates. Tetrahedron
1992, 48, 2613−2626.
(22) (a) Persson, B.; Seita, J.; Holm, A.; Orazi, O. O.; Schroll, G.;
Williams, D. H.; Pilotti, A.-M. Anodic Oxidation of Benzenesulfinate
ion. Acta Chem. Scand. 1977, 31B, 88−89. For cyclic voltammetry of
TsCN, see: (b) Pirenne, V.; Kurtay, G.; Voci, S.; Bouffier, L.; Sojic,
N.; Robert, F.; Bassani, D. M.; Landais, Y. Eosin-Mediated
Alkylsulfonyl Cyanation of Olefins. Org. Lett. 2018, 20, 4521−4525.
(23) Depending on the solvents, values ranging from −0.80 V to
−0.45 V have been reported. See ref 18.
(24) Remucal, C. K.; McNeill, K. Photosensitized Amino Acid
Degradation in the Presence of Riboflavin and Its Derivatives. Environ.
Sci. Technol. 2011, 45, 5230−5237 The acetylation of the ribose side
chain of RF retards its phototautomerization to Lumichrome and
prevents the intramolecular HAT process from T1 that compete with
the desired SET. The ability of RF to form aggregates through
hydrogen bond interactions is also reduced. .
(25) (a) Ventre, S.; Petronijevic, F. R.; MacMillan, D. W. C.
Decarboxylative Fluorination of Aliphatic Carboxylic Acids via
Photoredox Catalysis. J. Am. Chem. Soc. 2015, 137, 5654−5657.
(b) Zhou, X.; Wang, P.; Zhang, L.; Chen, P.; Ma, M.; Song, N.; Ren,
S.; Li, M. Transition-Metal-Free Synthesis of C-Glycosylated
Phenanthridines via K2S2O8-Mediated Oxidative Radical Decarbox-
ylation of Uronic Acids. J. Org. Chem. 2018, 83, 588−603.
(26) Perry, M. A.; Morin, M. D.; Slafer, B. W.; Rychnovsky, S. D.
Total Synthesis of Lepadiformine Alkaloids using N-Boc α-Amino
Nitriles as Trianion Synthons. J. Org. Chem. 2012, 77, 3390−3400.
(27) The corresponding proline protected hemiaminals were side-
products of 3b−3e. No attempts were made to minimize their
formation using anhydrous conditions, because this side reaction was
significantly less important for other substrates examined.
(11) For recent reviews, see: (a) Romero, N. A.; Nicewicz, D. A.
Organic Photoredox Catalysis. Chem. Rev. 2016, 116, 10075−10166.
(b) Staveness, D.; Bosque, I.; Stephenson, C. R. J. Free Radical
Chemistry Enabled by Visible Light-Induced Electron Transfer. Acc.
Chem. Res. 2016, 49, 2295−2306. (c) Matsui, J. K.; Lang, S. B.; Heitz,
D. R.; Molander, G. A. Photoredox-Mediated Routes to Radicals: The
Value of Catalytic Radical Generation in Synthetic Methods
Development. ACS Catal. 2017, 7, 2563−2575. (d) Marzo, L. M.;
̈
Pagire, S. K.; Reiser, O.; Konig, B. Visible-Light Photocatalysis: Does
It Make a Difference in Organic Synthesis? Angew. Chem., Int. Ed.
2018, 57, 10034−10072. (e) Stephenson, C. R. J.; Yoon, T. P.;
Macmillan, D. W. C. Visible Light Photocatalysis in Organic Chemistry;
Wiley: Weinheim, Germany, 2018.
(12) Le Vaillant, F.; Wodrich, M. D.; Waser, J. Room temperature
decarboxylative cyanation of carboxylic acids using photoredox
catalysis and cyanobenziodoxolones: a divergent mechanism
compared to alkynylation. Chem. Sci. 2017, 8, 1790−1800.
(13) Stahmann, K. P.; Revuelta, J. L.; Seulberger, H. Three
biotechnical processes using Ashbya gossypii, Candida famata, or
Bacillus subtilis compete with chemical riboflavin production. Appl.
Microbiol. Biotechnol. 2000, 53, 509−516.
(14) (a) Lu, C.; Lin, W.; Wang, W.; Han, Z.; Yao, S.; Lin, N.
Riboflavin (VB2) photosensitized oxidation of 2′-deoxyguanosine-5′-
monophosphate (dGMP) in aqueous solution: a transient inter-
mediates study. Phys. Chem. Chem. Phys. 2000, 2, 329−334. (b) Tan,
(28) (a) Garlets, Z. J.; Nguyen, J. D.; Stephenson, C. R. J. The
Development of Visible-Light Photoredox Catalysis in Flow. Isr. J.
Chem. 2014, 54, 351−360. (b) Cambie, D.; Bottecchia, C.; Straathof,
̈
N. J. W.; Hessel, V.; Noel, T. Applications of Continuous-Flow
E
Org. Lett. XXXX, XXX, XXX−XXX