Amidyl Radicals by Oxidation of α-Amido-oxy Acids: Transition-Metal-Free Amidofluorination of Unactivated Alkenes

Article abstract of DOI:10.1002/anie.201804966

A three-component transition-metal-free amidofluorination of unactivated alkenes and styrenes is presented. α-Amido-oxy acids are introduced as efficient and easily accessible amidyl radical precursors that are oxidized by a photoexcited organic sensitizer (Mes-Acr-Me) to the corresponding carboxyl radical. Sequential CO₂ and aldehyde/ketone fragmentation leads to an N-centered radical that adds to an alkene. Commercial Selectfluor is used to trap the adduct radical through fluorine-atom transfer. The transformation features by high functional-group tolerance, broad substrate scope, and practical mild conditions. Mechanistic studies support the radical nature of the cascade.

Full text of DOI:10.1002/anie.201804966

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Accepted Article
Title: Amidyl Radicals via Oxidation of α-Amido-oxy Acids: Transition-
Metal-Free Amidofluorination of Unactivated Alkenes
Authors: Heng Jiang and Armido Studer
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201804966
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Amidyl Radicals via Oxidation of -Amido-oxy Acids: Transition-
Metal-Free Amidofluorination of Unactivated Alkenes
Heng Jiang and Armido Studer*
Abstract:
A
three-component
transition-metal-free
under mild conditions using copper catalysis[7] or photoredox
catalysis (Scheme 1b).[8] N-halo amides and hydroxyamine
derivatives among others are named as reagents at this place for
radical alkene amidation. In contrast, amidyl radical generation
via SET oxidation is not well explored and in particular examples
describing intermolecular alkene amidation are still very rare.[9]
The Knowles group applied a photo-excited iridium complex to
oxidize the NH bond in sulfonamides by proton-coupled electron
transfer.[10] The sulfonamidyl radicals were successfully used for
hydro-sulfonamidation of alkenes (Scheme 1c). In our eyes,
oxidative amidyl radical generation has great potential and
exploration of novel methods for implementing this strategic
approach in intermolecular CN bond forming reactions involving
alkenes is of importance.
amidofluorination of unactivated alkenes and styrenes is
presented. α-Amido-oxy acids are introduced as efficient and
easily accessible amidyl radical precursors that are oxidized by a
photo-excited organic sensitizer (Mes-Acr-Me) to the
corresponding carboxyl radical. Sequential CO2 and
aldehyde/ketone fragmentation leads to an N-centered radical
that adds to an alkene. Commercial Selectfluor is used to trap the
adduct radical through fluorine atom transfer. The transformation
convinces by high functional group tolerance, broad substrate
scope and practical mild conditions. Mechanistic studies support
the radical nature of the cascade.
CN Bond forming reactions are of fundamental interest in
synthesis and are of high importance in various fields of chemistry
such as in materials science, medicinal and agrochemical
industry.[1] Along these lines, radical chemistry has contributed to
the portfolio of CN bond forming processes and reactivity of N-
centered radicals has been intensively explored for several
decades.[2] Due to the generally high reactivity of N-radicals,
cyclizations are more readily accomplished as compared to
intermolecular N-radical additions.[3b] Yet, during recent years,
great progress in the field of intermolecular reactions involving
amidyl radicals has been achieved, especially for C-H amidation
of arenes that are often used as solvents/cosolvents.[3]
Intermolecular radical amidation of alkenes is more difficult to
achieve, since the amidyl radical adduct has to be selectively
trapped, whereas for arene addition a rather simple oxidation step
has to be conducted.[3b,4]
Strategically, there are several approaches towards reactive N-
radicals, which could be potentially used in radical alkene
amidation. Due to the strong NH bond in amines/amides, the
most obvious direct H abstraction is a difficult process for N-
radical generation.[5] This problem was tackled by our group and
we introduced amidated cyclohexadienes and dihydropyridines
as reagents for radical alkene hydroamidation (Scheme 1a).[6]
These proaromatic[6e] compounds allow for N-radical generation
by “indirect” H-abstraction from the methylenic site of the reagent
and subsequent fragmentation via a redox-neutral process. Many
examples belong to the category of N-radical generation via single
electron transfer (SET) reduction of an appropriate precursor
Scheme 1. Different strategies for iminyl and amidyl radical generation and
application in intermolecular addition reactions.
[*]
Dr. H. Jiang, Prof. Dr. A. Studer
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität
Corrensstraß 40, 48149 Münster (Germany)
E-mail: studer@uni-muenster.de
Recently, the Leonori team and our group developed practical
methods for generation of iminyl radicals from -imino-oxy acids,
that engage in cyclization and -C(sp3)H abstraction reactions
(Scheme 1d).[11] In these transformations, the iminyl radicals are
Supporting information for this article is given via a link at the end of
the document.
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generated via SET oxidation of -imino-oxy acids by a photo-
excited redox catalyst[12] and subsequent fragmentation of CO2
and an aldehyde/ketone. Motivated by these studies, we
envisioned that -amido-oxy acids should serve as easily
accessible and valuable precursors for amidyl radicals, although
the fragmentation pathway does not fully obey the principle of
perfect atom economy. We report herein the realization of that
approach and disclose vicinal alkene amidofluorination by using
Selectfluor as the C-radical trapping reagent[13] in an overall redox
neutral process. This transformation is of importance due to the
ubiquity of amines in various fields of chemistry and due to the
beneficial effect of F-substituents on the properties of
pharmaceuticals and materials.[14] To our knowledge, transition-
metal-free intermolecular amidofluorination of unactivated
alkenes has not been reported to date.[15]
dimethyl substitution pattern. To our delight, Troc-protected
amino-oxy-acid 2f gave 3ac in very good 83% yield (determined
by 19F NMR spectroscopy), whereas only 27% of product 3ab
resulted by using the Boc-protected acid 2e. Reagents 2g-i
bearing other common N-protecting groups such as benzoyl (Bz)
and trifluoroacetyl (Tfa) did not engage in this transformation. The
imidyl radical derived from the corresponding phthaloyl-protected
acid did also not work in this sequence (see SI). As expected, the
monomethyl or -unsubstituted Troc-protected amino-oxy-acids
2j and 2k provided worse results. Notably, the organic
photocatalyst Mes-Acr-Me can readily be replaced by an Ir-
catalyst (Ir(dFCF3ppy)2(dtbbpy)PF6, 1 mol%) without diminishing
the yield (81% with 2f, see Supporting Information).
Table 1. Amidofluorination of various alkenes.[a],[b]
But-3-en-1-yl benzoate 1a was selected as the amidyl radical
acceptor and Mes-Acr-Me as the photocatalyst due to its high
oxidative ability in the excited state.[16] Cbz-protected amino-oxy-
acids 2a-d (1.5 equiv) were first screened in combination with Acr-
Mes-Me (5 mol%), Selectfluor (2 equiv) and Na2HPO4 in the
mixed solvent system consisting of CH3CN and H2O.
Scheme 2. Amidofluorination of 1a with various amido-oxy-acids. Reaction
conditions: A mixture of 1a (1 equiv, 0.1 mmol), 2 (1.5 equiv, 0.15 mmol), Mes-
Acr-Me (5 mol%, 0.005 mmol), Selectfluor (2 equiv, 0.2 mmol), Na2HPO4 (3
equiv, 0.3 mmol) in CH3CN (0.7 mL) and H2O (0.35 mL) was irradiated by a 10
W blue LEDs at 25 ℃ for 16 h. The yields are calculated based on 1a and are
determined by 19F NMR analysis using C6F6 as an internal standard. Bz =
benzoyl; Tfa = trifluoroacetyl. [a] Isolated yield is presented in parenthesis.
Amido-oxy-acetic acid 2a lacking any -substituents gave only
traces of the targeted product 3aa. With the corresponding -Me-,
-Ph- and -dimethyl-substituted acids 2b-d, 3aa was obtained in
moderate yields (40-49%). Likely, the -substituents increase the
rate of the radical decarboxylation step. As the 2-(amidooxy)-2-
methylpropanoic acid 2d was established as the best reagent in
this series, we next varied the N-protecting group keeping the -
[a] Reaction conditions: A mixture of 1 (1 equiv, 0.2 mmol), 2f (1.5 equiv, 0.3
mmol), Mes-Acr-Me (5 mol%, 0.01 mmol), Selectfluor (2 equiv, 0.4 mmol),
Na2HPO4 (3 equiv, 0.6 mmol) in CH3CN (1.4 mL) and H2O (0.7 mL) was
irradiated by a 10 W blue LEDs at 25 ℃ for 16 h. [b] Isolated yields are
calculated based on 1.
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To explore reaction scope, various alkenes were examined in
the radical amidofluorination (Table 1). Non functionalized
alkenes underwent this transformation to give amidofluorinated
Selectfluor (3 equiv used) to give the corresponding allyl
fluorides,[17] that further react as substrates in the novel radical
amidofluorination to the isolated difluorides 4a and 4b. To further
support the suggested sequence, we prepared allylic fluoride 1ad
in 90% yield from ene-type fluorination of 6-methylhept-5-en-2-
one (1ac) with Selectfluor. Alkenes 1ac and 1ad both provided
under optimized amidofluorination conditions the same product
4c in 81% and 85% yield, respectively. These results demonstrate
that the allylic fluorides are the intermediates in the one-pot 2,3-
difluoroamidation reactions of tri- and tetra-substituted alkenes.
Radical clock experiments were conducted to address the
mechanism of the alkene amidofluorination. The product 5
resulting from a typical 5-exo cyclization was obtained from 1,6-
diene 1ae in 47% yield, supporting that radical intermediates are
involved. The radical mechanism was further documented by the
amidofluorination of vinylcyclopropane 1af which gave exclusively
the ring opening product 6 in 74% yield.
The
proposed
mechanism
of the radical
alkene
amidofluorination is presented in Scheme 4. The catalytic cycle
starts by photo-excitation of Mes-Acr-Me upon visible light
irradiation to generate the excited Mes-Acr-Me*, which is SET
reduced by carboxylate A, formed by deprotonation of substrate
1, to generate the carboxyl radical B along with acridine radical 7.
Sequential fragmentation of CO2 and acetone from B generates
the amidyl radical C, which adds to the alkene to give the adduct
radical D. F-atom transfer from Selectfluor to D eventually delivers
the amidofluorination product 3 with concomitant formation of the
aminyl radical cation E. The photoredox cycle is closed through
SET reduction of E by the acridine radical 7 to give F, thereby
regenerating the ground-state photocatalyst Mes-Acr-Me.
Alternatively, aminyl radical cation E might directly react with
carboxylate A in a chain propagation step (hole catalysis)[4b] to
generate carboxyl radical B along with F. To address that point,
we measured the quantum yield (Φ) for the transformation of 1a
(Φ = 1.96) which indicates that hole catalysis is occurring to some
extent, as indicated in the mechanism.
Scheme 3. Amidofluorination of tri- and tetra-substituted alkenes and radical
clock experiments.
products in satisfactory yields (3b,3c). Various functional groups
are tolerated including halo (3d,3e), ester (3f), ketone (3g), nitro
(3h), nitrile (3i), phosphonate (3j), alcohol (3k), tosyloxy (3l), and
epoxide
(3m)
functionalities
and
the
corresponding
amidofluorinated compounds were isolated in moderate to
excellent yields (41-95%). Phthalimide and tosyl-protected
amines containing terminal alkenes engage in this sequence (3n,
3o). Along with these terminal alkenes, 2,2-disubstituted alkenes
could also be amidofluorinated to give 3p-r in high yields (81-
93%). We were pleased to find that styrene and its derivatives are
eligible substrates. Both electron-rich and electron-poor
substituents such as Me, t-Bu, F, Cl, Br, OAc and OMe are well
tolerated at the aryl moiety and the Troc-protected 2-fluoro-2-aryl
ethylamines 3s-z were obtained in good yields (50-77%). With
internal alkenes such as cyclohexene, reaction was lower yielding
and product 3za was obtained in 21% yield and high
diastereoselectivity. As expected, the activated norbornene
reacted more efficiently to provide 3zb in 45% yield with 6:1
diastereoselectivity.
Interestingly, tri- and tetra-substituted alkenes afforded 2,3-
difluoro Troc-amides in this transformation. For example, 2-
methylbut-2-ene (1aa) gave 4a in 87% yield and 2,3-difluoro
amine 4b was obtained in 85% yield from 2,3-dimethylbut-2-ene
(1ab, Scheme 3). These products are formed by initial ene-type
fluorination of the tri- and tetra-substituted alkenes with
Scheme 4. Suggested mechanism.
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[6]
a) C.-M. Chou, J. Guin, C. Mück-Lichtenfeld, S. Grimme, A. Studer,
Chem. Asian J. 2011, 6, 1197; b) J. Guin, R. Fröhlich, A. Studer, Angew.
Chem. Int. Ed. 2008, 47, 779; Angew. Chem. 2008, 120, 791; c) J. Guin,
C. Mück-Lichtenfeld, S. Grimme, A. Studer, J. Am. Chem. Soc. 2007,
129, 4498; d) J. Kemper, A. Studer, Angew. Chem. Int. Ed. 2005, 44,
4914; Angew. Chem. 2005, 117, 4993; e) J. C. Walton, A. Studer, Acc.
Chem. Res. 2005, 38, 794.
In summary, we have established a practical method for vicinal
amidofluorination of unactivated alkenes and styrenes. The
readily accessible -amido-oxy acid 2f was identified as a highly
valuable reagent for oxidative generation of the Troc-amidyl
radical by photo-excited Mes-Acr-Me. The overall transition-
metal-free and redox neutral process proceeds under mild
conditions and a wide range of functional groups are tolerated.
Notably, the Troc-group used herein is a common N-protecting
group in organic synthesis. The ubiquity of amines and the
importance of fluorine chemistry render this transformation to be
of significant value for medicinal and agrochemical research.
[7]
[8]
[9]
For amidation of alkenes by copper catalysis with NFSI, see: a) D. Wang,
L. Wu, F. Wang, X. Wan, P. Chen, Z. Lin, G. Liu, J. Am. Chem. Soc.
2017, 139, 6811; b) H. Zhang, W. Pu, T. Xiong, Y. Li, X. Zhou, K. Sun,
Q. Liu and Q. Zhang, Angew. Chem. Int. Ed. 2013, 52, 2529; Angew.
Chem. 2013, 125, 2589.
For amidation of alkenes by photoredox catalysis, see: a) X.-D. An, Y.-Y.
Jiao, H. Zhang, Y. Gao, S. Yu, Org. Lett. 2018, 20, 401; b) Q. Qin, Y.-Y.
Han, Y.-Y. Jiao, Y. He, S. Yu, Org. Lett. 2017, 19, 2909; also see c) Q.
Qin, D. Ren, S. Yu, Org. Biomol. Chem. 2015, 13, 10295; d) K. Miyazawa,
T. Koike, M. Akita, Chem. Eur. J. 2015, 21, 11677.
Acknowledgements
For examples of oxidative cross N-H/C-H coupling of amidyl radicals with
arenes: a) E. Ito, T. Fukushima, T. Kawakami, K. Murakami, K. Itami,
Chem 2017, 2, 383; c) T. Yamaguchi, E. Yamaguchi, A. Itoh, Org. Lett.
2017, 19, 1282; d) S. Das, P. Natarajan, B. König, Chem. Eur. J. 2017,
23, 18161; a) K. Tong, X. Liu, Y. Zhang, S. Yu, Chem. Eur. J. 2016, 22,
15669.
This work was supported by the Alexander von Humboldt
Foundation (postdoctoral fellowship to H. J.). We also thank Dr.
Ying Cheng (WWU Münster) for providing some alkenes.
[10] Q. Zhu, D. E. Graff, R. R. Knowles, J. Am. Chem. Soc. 2018, 140, 741.
For intermolecular aminyl radical cation addition, see: A. J. Musacchio,
B. C. Lainhart, X. Zhang, S. G. Naguib, T. C. Sherwood, R. R. Knowles,
Science 2017, 355, 727. For a review on PCET, see: E. C. Gentry, R. R.
Knowles, Acc. Chem. Res. 2016, 49, 1546.
Conflict of Inerest
The authors declare no conflict of interest.
Keywords: amidyl radical • -amido-oxy acid • alkene
[11] a) E. M. Dauncey, S. P. Morcillo, J. J. Douglas, N. S. Sheikh, D. Leonori,
Angew. Chem. Int. Ed. 2018, 57, 744; Angew. Chem. 2018, 130, 752; b)
H. Jiang, A. Studer, Angew. Chem. Int. Ed. 2018, 57, 1692; Angew.
Chem. 2018, 130, 1708; c) H. Jiang, A. Studer, Angew. Chem. Int. Ed.
2017, 56, 12273; Angew. Chem. 2017, 129, 12441; d) J. Davies, N. S.
Sheikh, D. Leonori, Angew. Chem. Int. Ed. 2017, 56, 13361; Angew.
Chem. 2017, 129, 13546.
amidofluorination • photoredox catalysis • transition-metal-free
[1]
For selected books and reviews, see: a) M. Taillefer, D. Ma, Amination
and Formation of sp2 C-N Bonds, Springer, Berlin, Heidelberg, 2013; b)
A. Ricci, Amino Group Chemistry: From Synthesis to the Life Science,
Wiley-VCH: Weinheim, 2008; c) Y. Park, Y. Kim, S. Chang, Chem. Rev.
2017, 117, 9247; d) R.-C. Paula, S. L. Buchwald, Chem. Rev. 2016, 116,
12564.
[12] Representative reviews on photoredox catalysis, see: a) M. H. Shaw, J.
Twilton, D. W. C. MacMillan, J. Org. Chem. 2016, 81, 6898; b) C. K. Prier,
D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113, 5322; c) J.
Xuan, W.-J. Xiao, Angew. Chem. Int. Ed. 2012, 51, 6828; Angew. Chem.
2012, 124, 6934; d) J. M. R. Narayanam, C. R. J. Stephenson, Chem.
Soc. Rev. 2011, 40, 102; e) T. P. Yoon, M. A. Ischay, J. Du, Nat. Chem.
2010, 2, 527.
[2]
[3]
For selected reviews on N-centered radicals, see: a) S. Z. Zard, Chem.
Soc. Rev. 2008, 37, 1603; b) L. Stella, Angew. Chem. Int. Ed. Engl. 1983,
22, 337; c) A. G. Fallis, I. M. Brinza, Tetrahedron 1997, 53, 17543; d) S.
Z. Zard, Synlett 1996, 7, 1148; e) M. E. Wolff, Chem. Rev. 1963, 63, 55.
Recent reviews: a) X.-D. An, S. Yu, Tetrahedron Lett. 2018, 59, 1605; b)
Y. Zhao, W. Xia, Chem. Soc. Rev. 2018, 47, 2591; c) M. D. Kärkäs, ACS
Catal. 2017, 7, 4999; d) J. Jiao, K. Murakami, K. Itami, ACS Catal. 2016,
6, 610; e) T. Xiong, Q. Zhang, Chem. Soc. Rev. 2016, 45, 3069. f) J.-R.
Chen, X.-Q. Hu, L.-Q. Lu, W.-J. Xiao, Chem. Soc. Rev. 2016, 45, 2044;
For representative examples on C-H amination of arenes: g) C. B.
Tripathi, T. Ohtani, M. T. Corbett, T. Ooi, Chem. Sci. 2017, 8, 5622; h) J.
Davies, T. D. Svejstrup, D. F. Reina, N. S. Sheikh, D. Leonori, J. Am.
Chem. Soc. 2016, 138, 8092; i) T. Kawakami, K. Murakami, K. Itami, J.
Am. Chem. Soc. 2015, 137, 2460; j) T. W. Greulich, C. G. Daniliuc, A.
Studer, Org. Lett. 2015, 17, 254; k) K. Foo, E. Sella, I. Thom, M. D.
Eastgate, P. S. Baran, J. Am. Chem. Soc. 2014, 136, 5279. l) L. J. Allen,
P. J. Cabrera, M. Lee, M. S. Sanford, J. Am. Chem. Soc. 2014, 136, 5607;
m) Q. Qin, S. Yu, Org. Lett. 2014, 16, 3504; n) L. Song, L. Zhang, S. Luo,
J.-P. Cheng, Chem. Eur. J. 2014, 20, 14231; o) H. Kim, T. Kim, D. G.
Lee, S. W. Roh, C. Lee, Chem. Commun. 2014, 50, 9273; p) G. B.
Boursalian, M.-Y. Ngai, K. N. Hojczyk, T. Ritter, J. Am. Chem. Soc. 2013,
135, 13278.
[13] a) M. P. Sibi, Y. Landais, Angew. Chem. Int. Ed. 2013, 52, 3570; Angew.
Chem. 2013, 125, 3654; b) C. Chatalova-Sazepin, R. Hemelaere, J.-F.
Paquin, G. M. Sammis, Synthesis 2015, 47, 2554.
[14] a) K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881; b) S. Purser,
P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320.
[15] For a review, see: a) P. Chen, G. Liu, Eur. J. Org. Chem. 2015, 2015,
4295; Intermolecular amidofluorination of styrenes: b) J. Saavedra-
Olavarría, G. C. Arteaga, J. J. Lópeza, E. G. Pérez, Chem. Commun.
2015, 51, 3379; c) J. Saavedra-Olavarria, G. C. Arteaga, J. J. Lꢀpez, E.
G. Pꢁrez, Chem. Commun. 2015, 51, 3379; d) H. Zhang, Y. Song, J.
Zhao, J. Zhang, Q. Zhang, Angew. Chem. Int. Ed. 2014, 53, 11079;
Angew. Chem. 2014, 126, 11259; e) S. Qiu, T. Xu, J. Zhou, Y. Guo, G.
Liu, J. Am. Chem. Soc. 2010, 132, 2856; f) S. Stavber; T. S. Pecǎn, M.
Papeꢂ, M. Zupan, Chem. Commun. 1996, 2247. An elusive example of
amidofluorination of unactivated alkenes: g) D.-F. Lu, C.-L. Zhu, J. D.
Sears, H. Xu, J. Am. Chem. Soc. 2016, 138, 11360. For an
intramolecular radical amidofluorination, see: Z. Li, L. Song, C. Li, J. Am.
Chem. Soc. 2013, 135, 4640.
[4]
[5]
a) M. P. Plesniak, H.-M. Huang, D. J. Procter, Nat. Rev. Chem. 2017, 1,
0077; b) A. Studer, D. P. Curran, Angew. Chem. Int. Ed. 2016, 55, 58;
Angew. Chem. 2016, 128, 58; c) A. Studer, D. P. Curran, Nature Chem.
2014, 6, 765.
[16] a) N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075; b) K. A.
Margrey, D. A. Nicewicz, Acc. Chem. Res. 2016, 49, 1997. c) D. A.
Nicewicz, T. M. Nguyen, ACS Catal. 2014, 4, 355.
[17] a) P. T. Nyffeler, S. G. Durón, M. D. Burkart, S. P. Vincent, C.-H. Wong,
Angew. Chem. Int. Ed. 2005, 44, 192; b) H.-Q. Luo, T.-P. Loh,
Tetrahedron Lett. 2009, 50, 1554; c) J. Wu, Y.-M. Wang, A. Drljevic, V.
a) J. M. Mayer, Acc. Chem. Res. 2011, 44, 36; b) Y. R. Luo, Handbook
of Bond Dissociation Energies in Organic Compounds; CRC Press: Boca
Raton, FL, 2003.
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Rauniyar, R. J. Phipps, F. D. Toste, Proc. Natl. Acad. Sci. USA 2013,
110, 13729.
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Layout 2:
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H. Jiang, A. Studer*
Page No. – Page No.
Amidyl Radicals via Oxidation of -
Amido-oxy Acids: Transition-Metal-
Free Amidofluorination of
Unactivated Alkenes
Fluorination and amidation both useful! Transition-metal-free amidofluorination
of unactivated alkenes has been achieved using a Troc-protected -amido-oxy acid
as the amidyl radical precursor and commercial Selectfluor as the radical
fluorinating reagent applying photoredox catalysis.
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