Photocatalytic Generation of N-Centered Hydrazonyl Radicals: A Strategy for Hydroamination of β,γ-Unsaturated Hydrazones

Article abstract of DOI:10.1002/anie.201406491

A visible-light photocatalytic generation of N-centered hydrazonyl radicals has been accomplished for the first time. This approach allows efficient intramolecular addition of hydrazonyl radical to terminal alkenes, thus providing hydroamination and oxyamination products in good yields. Importantly, the protocol involves deprotonation of an N-H bond and photocatalytic oxidation to an N-centered radical, thus obviating the need to prepare photolabile amine precursors or the stoichiometric use of oxidizing reagents.

Full text of DOI:10.1002/anie.201406491

Angewandte
Chemie
DOI: 10.1002/anie.201406491
Heterocycle Synthesis
Photocatalytic Generation of N-Centered Hydrazonyl Radicals:
A Strategy for Hydroamination of b,g-Unsaturated Hydrazones**
Xiao-Qiang Hu, Jia-Rong Chen,* Qiang Wei, Feng-Lei Liu, Qiao-Hui Deng,
Andrꢀ M. Beauchemin, and Wen-Jing Xiao*
Abstract: A visible-light photocatalytic generation of N-
centered hydrazonyl radicals has been accomplished for the
first time. This approach allows efficient intramolecular
addition of hydrazonyl radical to terminal alkenes, thus
providing hydroamination and oxyamination products in
good yields. Importantly, the protocol involves deprotonation
a powerful and important platform for identifying new inter-
and intramolecular hydroamination by using suitable N-
radical precursors and radical initiators.[5,6] In this regard,
both 1,3-diazaallyl radicals, derived from amidine by copper-
catalyzed oxidation,[7] and hydrazonyl radicals, generated
from hydrazones by stoichiometric use of TEMPO or
azodicarboxylates, have proven to be valuable N-radicals
for intramolecular cyclization.[8] To our knowledge, however,
À
of an N H bond and photocatalytic oxidation to an N-centered
radical, thus obviating the need to prepare photolabile amine
precursors or the stoichiometric use of oxidizing reagents.
À
direct catalytic transformation of the N H bond of hydrazone
into an N-centered radical, and exploitation of such radical
species in hydroamination of alkenes remains largely unex-
plored.
N
itrogen-containing heterocycles are ubiquitous in biolog-
ically active natural isolates and pharmaceuticals,[1] and have
also found broad application in chemical, medical, and life
sciences.[2] The development of atom-economic and direct
synthetic approaches to these heterocycles has received
considerable attention. In this context, intramolecular
alkene hydroamination has been emerging as a versatile
method for the synthesis of structurally diverse N-hetero-
cycles.[3] Despite impressive achievements in the field of
transition-metal-catalyzed hydroamination, the catalytic
modes, substrate scope, and functional-group tolerance of
this protocol are still limited.[4] Therefore, the exploration of
new strategies and reagents to develop more efficient and
greener methodologies for the rapid assembly of N-hetero-
cycles is highly desirable. Given the functional-group com-
patibility and versatile reactivity of radicals, radical hydro-
amination involving neutral N-centered radicals should be
Recently, visible-light photocatalysis has spurred exten-
sive research efforts because of its ability to generate various
reactive radical or ionic species, thus allowing the design of
new reactions proceeding under mild reaction conditions.[9] In
this regard, three main activation modes for N-containing
molecules have been developed using such a catalytic strategy
(Scheme 1a), including: 1) direct oxidation of amines to the
[*] X.-Q. Hu, Prof. Dr. J.-R. Chen, Q. Wei, F.-L. Liu, Q.-H. Deng,
Prof. Dr. A. M. Beauchemin, Prof. Dr. W.-J. Xiao
CCNU–uOttawa Joint Research Centre
Key Laboratory of Pesticide & Chemical Biology
Ministry of Education, College of Chemistry
Central China Normal University (CCNU)
152 Luoyu Road, Wuhan, Hubei 430079 (China)
and
Scheme 1. Visible-light-induced photocatalytic activation of N-contain-
ing compounds and reaction design on N-centered radical.
Ts =4-toluenesulfonyl.
Collaborative Innovation Center of Chemical Science and
Engineering, Tianjin (China)
E-mail: chenjiarong@mail.ccnu.edu.cn
wxiao@mail.ccnu.edu.cn
Homepage: http://chem-xiao.ccnu.edu.cn/
Prof. Dr. A. M. Beauchemin
Centre for Catalysis Research and Innovation, Department of
Chemistry
nitrogen radical cation A by the excited state of a photo-
catalyst;[10] 2) further transformation of A into the iminium
ion B upon release of a hydrogen atom, and its trapping by
a wide range of nucleophiles;[11] and, 3) further conversion of
A into the radical C after deprotonation.[12] Despite these
advances, little attention has been devoted to the application
of visible-light photocatalysis to the generation of neutral N-
centered radicals of the type D. Reaction design with such
radical species remain largely unexploited because of the
University of Ottawa, ON, K1N 6N5 (Canada)
[**] We are grateful to the National Science Foundation of China (NO.
21272087, 21472058, 21232003, and 21202053) and the National
Basic Research Program of China (2011CB808603) for support of
this research.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201406491.
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Table 1: Optimization for the photocatalytic N-radical hydroamination[a]
requisite use of unstable precursors (e.g., N-halogen, N-
nitrosoamides) or tedious preparation procedure.[5] More-
over, traditional methods involving high-energy UV irradi-
ation or high reaction temperature has also caused limitations
in functional-group tolerance and substrate scope.
Recently, the group of MacMillan reported an imidazo-
lidinone-catalyzed enantioselective a-amination of aldehydes
by using electrophilic N-centered radicals generated from
carbamate reagents by photocatalysis (Scheme 1a).[13] San-
Entry
Solvent
Photocatalyst
Base
Yield [%][b]
1
2
3
4
5
6
7
8
CH2Cl2
MeOH
DMF
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
EosinY
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
NaHCO3
NaOH
NaOH
NaOH
–
17
26
15
<5
40
11
43
54
57
68
67
71
74 (71)
trace
trace
trace
À
ford and co-workers developed a photocatalytic C H amina-
tion of arenes using N-acyloxyphthalimides as N-centered
radical precursors.[14] In these processes, the incorporation of
a photolabile group as a handle for the amine substrates was
essential to the formation of the N-radical. Based on our
recent success in photocatalytic synthesis of heterocycles,[15]
DMSO
CHCl3
CH3CN
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
[Ir(ppy)2(dtbbpy)]PF6
À
we hypothesized that the direct transformation of the N H
.
9
[Ru(bpy)3]Cl2 6H2O
.
bond into an N-centered radical by photocatalysis would
provide a new strategy for the hydroamination of alkenes.
However, realization of this concept would encounter a major
challenge in that H-atom transfer from an N- to C-centered
radical usually is not an efficient process.[16] Herein, we report
a photocatalytic entry to N-centered hydrazonyl radicals from
b,g-unsaturated hydrazones,[17] and show that this activation
mode leads to efficient intramolecular hydroamination reac-
tivity (Scheme 1b).
10
11
12
13[c]
14[d]
15[e]
16[f]
[Ru(bpy)3]Cl2 6H2O
.
[Ru(bpy)3]Cl2 6H2O
.
[Ru(bpy)3]Cl2 6H2O
.
[Ru(bpy)3]Cl2 6H2O
–
.
[Ru(bpy)3]Cl2 6H2O
[Ru(bpy)3]Cl2 6H2O
.
NaOH
[a] Reaction conditions: 1a (0.2 mmol), photocatalysts (2 mol%), base
(0.3 mmol), solvents (3.0 mL), 18 W white LEDs, at room temperature.
[b] Determined by GC using biphenyl as an internal standard. [c] Using
3 W blue LEDs as the light source. Yield of isolated product given within
parentheses. [d] Without photocatalyst. [e] Without base. [f] Without
visible light irradiation. bpy=2,2’-bipyridine, dtbbpy=4,4’-di-tert-butyl-
2,2’-bipyridine, ppy=2-phenylpyridine, DMF=N,N-dimethylformamide,
DMSO=dimethylsulfoxide.
Initially, we selected the b,g-unsaturated hydrazone 1a as
a model substrate to test the feasibility of its intramolecular
hydroamination using [Ir(ppy)2(dtbbpy)]PF6 as a photocata-
lyst under irradiation by an 18W white LED light (Table 1).
Gratifyingly, the reaction does indeed occur with Cs2CO3 as
the base in CH2Cl2 at room temperature, thus giving the
desired 4,5-dihydropyrazole 2a in 17% yield (entry 1). The
structure of 2a was unambiguously confirmed by NMR
spectroscopy and X-ray diffraction analysis.[18] Encouraged by
this result, other reaction parameters were then extensively
investigated to improve the efficiency. A brief survey of
reaction media showed that the reaction in CHCl3 gave rise to
a 40% yield of 2a (entry 5), while DMF and DMSO only led
to low yields (entries 3 and 4). In addition, the effect of
photocatalysts on the reaction was also examined, and the
yield of 2a was dramatically improved to 57% with [Ru-
Table 2: Scope of photocatalytic N-radical hydroamination of b,g-
unsaturated hydrazones.[a,b]
.
(bpy)3]Cl2 6H2O as the catalyst (entry 9). Interestingly,
a screen of common inorganic bases identified NaOH as the
best of choice, thus affording 2a in 71% yield, when using 3 W
blue LEDs as light source (entry 13). To confirm that the
observed reactivity was due to the visible-light photocatalytic
activation, some control experiments were performed. It was
found that the photocatalyst, base, and light source are all
critical to this transformation (entries 14–16).
Then, we investigated the scope of this N-radical hydro-
amination reaction by using a series of b,g-unsaturated
hydrazones. As shown in Table 2, substitution patterns and
electronic properties of the phenyl ring of the b,g-unsaturated
hydrazones had no obvious influence on the reaction
efficiency. A range of b,g-unsaturated hydrazones bearing
electron-donating and electron-withdrawing groups at either
the 2-, 3-, or 4-position of the aromatic ring underwent the
desired reaction smoothly to give the corresponding products
2b–k in 60–88% yield. Notably, the hydrazones 1g and 1h,
[a] Reaction conditions: 1 (0.3 mmol), [Ru(bpy)3]Cl2·6H2O (2 mol%),
NaOH (0.45 mmol), CHCl3 (4.5 mL), 3 W blue LEDs (450–460 nm), at
room temperature for 12–16 h. [b] Yield is that of the isolated product.
having sensitive groups such as 3-Br and 4-Br substituents,
were also well tolerated and produced 2g (63%) and 2h
(68%), respectively. Strong electron-withdrawing group such
2
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as CF3 group can be present on the aromatic ring, thus
furnishing a 70% yield of 2k. Moreover, the reaction also
proceeds efficiently with aliphatic hydrazones. The cyclohex-
yl-substituted hydrazone 1l proved to be suitable for this
reaction to provide 2l in 76% yield. An array of other
representative alkyl groups, such as isopropyl, tert-butyl,
benzyl, and phenylethyl groups, were tolerated under the
standard reaction conditions, thus giving 2m–q in 62–84%
yield. The reaction with 1r, bearing geminal methyl groups at
the a-position also worked well to give 2r in 38% yield.
According to the reaction design, a C-centered radical is
likely a key intermediate during the process, and might be
intercepted by radical quenchers. As expected, addition of
TEMPO (2.0 equiv) to the model reaction resulted in the
formation of 3a in 81% yield (Table 3). This finding suggests
Scheme 2. Synthetic applications. mCPBA=m-chloroperbenzoic acid,
THF=tetrahydrofuran.
À
tion sequence. The N O bond of 3a can easily be cleaved to
afford the alcohol 6 in 78% yield (Scheme 2b).
To gain some insight into the mechanism, we first carried
out a series of luminescence-quenching experiments to
support the hypothesis that the b,g-unsaturated hydrazone
1a might be initially oxidized by the excited state of the
photocatalyst *[Ru(bpy)3]2+.[19] Surprisingly, no decrease of
[Ru(bpy)3]2+ luminescence was observed by only adding 1a.
Based on studies from the group of Nicewicz on photo-
catalytic alkene hydrofunctionalization,[20] the low oxidizing
power of the excited state of the photocatalyst *[Ru(bpy)3]2+
rendered it unable to oxidize the terminal double bond of 1a
to the corresponding radical cation. Given the important role
of the base on the reaction, we conducted the luminescence
quenching experiments under basic conditions. A significant
decrease of [Ru(bpy)3]2+ luminescence was observed, and
suggested that the nitrogen anion of 1a quenched the excited
photocatalyst *[Ru(bpy)3]2+.
Table 3: Trapping of C-centered radical intermediates with TEMPO or
PhTeTePh: Preliminary scope study.[a,b]
The photocatalytic oxyamination of b,g-unsaturated
hydrazones with TEMPO further indicated that the reaction
is a radical process and the C-centered radical was involved as
a key intermediate (Table 3). To identify the hydrogen source
of the desired product 2a, the model reaction of 1a was
performed in CDCl3. It was found that the reaction afforded
a mixture of 2a and 2a’ (1:1 ratio) in 23% combined yield
(Scheme 3). These results confirmed that CHCl3 worked as
[a] Reaction conditions: 1 (0.3 mmol), TEMPO (0.6 mmol) or PhTeTePh
(1.2 mmol), [Ru(bpy)3]Cl2·6H2O (2 mol%), NaOH (0.45 mmol), CHCl3
(4.5 mL), 3 W blue LEDs (450–460 nm), at room temperature for 12–
16 h. [b] Yield is that of the isolated product. TEMPO=2,2,6,6-tetrame-
thylpiperidine-N-oxyl.
that the process does indeed involve radical intermediates. It
should also be noted that this reactivity provides an oppor-
tunity to develop photocatalytic oxyamination of olefins.
Thus, we quickly surveyed the scope of the reaction. The
hydrazones bearing electron-donating (4-MeO) or electron-
withdrawing (3-Br) groups participated in the reaction
smoothly to give the products 3b (72%) and 3c (62%),
respectively. Importantly, tert-butyl, isopropyl-, and phenyl-
ethyl-substituted b,g-unsaturated hydrazones can also
undergo the desired reaction efficiently, thus affording the
oxyamination products 3d and 3 f, respectively, in 56–95%
yield. When using PhTeTePh, the radical cyclization/inter-
molecular addition cascade proceeded well to produce 3g in
56% yield.
To demonstrate the synthetic potential of this method-
ology, several transformations of 4,5-dihydropyrazole prod-
ucts were carried out. The Ts group of 2a can be easily
removed under basic conditions to give the pyrazole 4 in 96%
yield (Scheme 2a). Moreover, the oxyamination product 3a
can be oxidized directly to the biologically important pyrazole
5 by mCPBA through a Baeyer–Villiger oxidation/elimina-
Scheme 3. Deuterium-labeling experiment.
hydrogen source to facilitate the hydroamination process,
À
while the direct H-transfer from N H to the C-based radical
is unfavorable.[16] The on-off light experiments also support
that a radical chain process is not the predominant pathway
under the reaction conditions.[19]
Finally, a possible reaction mechanism was proposed
(Scheme 4). Deprotonation of the hydrazone 1 occurs under
basic conditions to affords the anionic intermediate A’. A
single-electron oxidation of A’ by the excited state of the
photocatalyst (*[Ru(bpy)3]2+) gives the N-centered radical B’
through a reductive quenching process. A 5-exo-trig cycliza-
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2981 – 3019; d) T. J. Donohoe, C. K. Callens, A. Flores, A. R.
Lacy, A. H. Rathi, Chem. Eur. J. 2011, 17, 58 – 76.
[4] For recent transition-metal-free intramolecular hydroamina-
tions, see: a) J.-G. G. Roveda, C. Clavette, A. D. Hunt, S. I.
Gorelsky, C. J. Whipp, A. M. Beauchemin, J. Am. Chem. Soc.
2009, 131, 8740 – 8741; b) N. Guimond, M. J. MacDonald, V.
Lemieux, A. M. Beauchemin, J. Am. Chem. Soc. 2012, 134,
16571 – 16577; c) A. R. Brown, C. Uyeda, C. A. Brotherton,
E. N. Jacobsen, J. Am. Chem. Soc. 2013, 135, 6747 – 6749.
[5] For reviews, see: a) S. Z. Zard, Chem. Soc. Rev. 2008, 37, 1603 –
1618; b) G. J. Rowlands, Tetrahedron 2010, 66, 1593 – 1636.
[6] For applications of carbamoyl radicals in transfer hydroamina-
tion, see: a) J. Kemper, A. Studer, Angew. Chem. Int. Ed. 2005,
44, 4914 – 4917; Angew. Chem. 2005, 117, 4993 – 4995; b) J. Guin,
C. Mꢀck-Lichtenfeld, S. Grimme, A. Studer, J. Am. Chem. Soc.
2007, 129, 4498 – 4503; c) J. Guin, R. Frohlich, A. Studer, Angew.
Chem. Int. Ed. 2008, 47, 779 – 782; Angew. Chem. 2008, 120, 791 –
794; for IBX-mediated formation of N-aryl amide radical, see:
d) K. C. Nicolaou, P. S. Baran, Y.-L. Zhong, S. Barluenga, K. W.
Hunt, R. Kranich, J. A. Vega, J. Am. Chem. Soc. 2002, 124, 2233 –
2244.
[7] For examples, see: a) Y.-F. Wang, X. Zhu, S. Chiba, J. Am. Chem.
Soc. 2012, 134, 3679 – 3682; b) Y.-F. Wang, H. Chen, X. Zhu, S.
Chiba, J. Am. Chem. Soc. 2012, 134, 11980 – 11983; c) H. Chen, S.
Sanjaya, Y.-F. Wang, S. Chiba, Org. Lett. 2013, 15, 212 – 215.
[8] a) X. Zhu, Y.-F. Wang, W. Ren, F.-L. Zhang, S. Chiba, Org. Lett.
2013, 15, 3214 – 3217; b) M.-K. Zhu, Y.-C. Chen, T. P. Loh, Chem.
Eur. J. 2013, 19, 5250 – 5254; c) X.-Y. Duan, X.-L. Yang, R. Fang,
X.-X. Peng, W. Yu, B. Han, J. Org. Chem. 2013, 78, 10692 –
10704; d) X.-Y. Duan, N.-N. Zhou, R. Fang, X.-L. Yang, W. Yu,
B. Han, Angew. Chem. Int. Ed. 2014, 53, 3158 – 3162; Angew.
Chem. 2014, 126, 3222 – 3226; e) L.-L. Zhou, S. Tang, X.-T. Qi,
C.-T. Lin, K. Liu, C. Liu, Y. Lan, A.-W. Lei, Org. Lett. 2014, 16,
3404 – 3407.
Scheme 4. Plausible reaction mechanism.
tion of B’ affords the C-centered radical C’. Subsequent H-
transfer from CHCl3 to C’ gives the product 2, together with
generation of trichloromethyl radical D’. The formed radical
intermediate D’ can regenerate the photocatalyst ([Ru-
(bpy)3]2+) through a single electron-transfer process.
In conclusion, we have developed a photocatalytic gen-
eration of N-centered hydrazonyl radicals from b,g-unsatu-
rated hydrazones. This strategy provides efficient access to
intramolecular alkene hydroamination and oxyamination,
thus furnishing the corresponding 4,5-dihydropyrazoles in
good yields. We believe that this photocatalytic strategy will
find broad applications in nitrogen-containing molecule syn-
thesis. Further study on the reaction mechanism as well as
intermolecular variants is underway.[21]
Experimental Section
Representative procedure: 1a (0.3 mmol), [Ru(bpy)3]Cl2 6H2O
.
(0.006 mmol), NaOH (0.45 mmol), and dry CHCl3 (4.5 mL) were
added to a 10 mL Schlenk flask equipped with a stirring bar. The
resulting mixture was degassed by using a freeze-pump-thaw proce-
dure (3 times). Then, the solution was stirred at a distance of about
5 cm from a 3 W blue LEDs (450–460 nm) at room temperature for
12 h. Upon the completion of reaction, as monitored by TLC, the
solvent was removed in vacuum. The crude reaction mixture was
purified by flash chromatography on silica gel (silica: 200–300; eluent:
petroleum ether/ethyl acetate (20:1–10:1) to provide product 2a as
a white solid in 71% yield.
[9] For reviews, see: a) T. P. Yoon, M. A. Ischay, J. Du, Nat. Chem.
´
2010, 2, 527 – 532; b) F. Teply, Collect. Czech. Chem. Commun.
2011, 76, 859 – 917; c) J. M. R. Narayanam, C. R. J. Stephenson,
Chem. Soc. Rev. 2011, 40, 102 – 113; d) J. Xuan, W.-J. Xiao,
Angew. Chem. Int. Ed. 2012, 51, 6828 – 6838; Angew. Chem.
2012, 124, 6934 – 6944; e) L. Shi, W.-J. Xia, Chem. Soc. Rev. 2012,
41, 7687 – 7697; f) Y.-M. Xi, H. Yi, A.-W. Lei, Org. Biomol.
Chem. 2013, 11, 2387 – 2403; g) C. K. Prier, D. A. Rankic,
D. W. C. MacMillan, Chem. Rev. 2013, 113, 5322 – 5363;
h) D. M. Schultz, T. P. Yoon, Science 2014, 343, 985 – 994;
i) M. N. Hopkinson, B. Sahoo, J.-L. Li, F. Glorius, Chem. Eur.
J. 2014, 20, 3874 – 3886.
Received: June 23, 2014
Revised: August 15, 2104
Published online: && &&, &&&&
[10] For pioneering examples, see: a) S. Maity, M. Zhu, R. S.
Shinabery, N. Zheng, Angew. Chem. Int. Ed. 2012, 51, 222 –
226; Angew. Chem. 2012, 124, 226 – 230; b) S. Maity, N. Zheng,
Angew. Chem. Int. Ed. 2012, 51, 9562 – 9566; Angew. Chem.
2012, 124, 9700 – 9704.
Keywords: heterocycles · hydrazones · photocatalysis · radicals ·
.
ruthenium
[11] For recent examples, see: a) A. G. Condie, J. C. Gonzalez-
Gomez, C. R. Stephenson, J. Am. Chem. Soc. 2010, 132, 1464 –
1465; b) J. W. Tucker, Y. Zhang, T. F. Jamison, C. R. Stephenson,
Angew. Chem. Int. Ed. 2012, 51, 4144 – 4147; Angew. Chem. 2012,
124, 4220 – 4223; c) J. Xie, Q.-C. Xue, H.-M. Jin, H.-M. Li, Y.-X.
Cheng, C.-J. Zhu, Chem. Sci. 2013, 4, 1281 – 1286; d) D. A.
DiRocco, T. Rovis, J. Am. Chem. Soc. 2012, 134, 8094 – 8097;
e) J.-J. Zhong, Q.-Y. Meng, G.-X. Wang, Q. Liu, B. Chen, K.
Feng, C.-H. Tung, L.-Z. Wu, Chem. Eur. J. 2013, 19, 6443 – 6450;
f) Z.-Q. Wang, M. Hu, X.-C. Huang, L.-B. Gong, Y.-X. Xie, J.-H.
Li, J. Org. Chem. 2012, 77, 8705 – 8711; g) S.-Q. Zhu, M.
Rueping, Chem. Commun. 2012, 48, 11960 – 11962; h) M.
Rueping, C. Vila, Org. Lett. 2013, 15, 2092 – 2095.
[1] a) B. A. Trofimov, L. N. Sobenina, A. P. Demenev, A. b. I.
Mikhaleva, Chem. Rev. 2004, 104, 2481 – 2506; b) F. Bellina, R.
Rossi, Tetrahedron 2006, 62, 7213 – 7256; c) M. A. P. Martins,
C. P. Frizzo, D. N. Moreira, N. Zanatta, H. G. Bonacorso, Chem.
Rev. 2008, 108, 2015 – 2050; d) G. S. Singh, Z. Y. Desta, Chem.
Rev. 2012, 112, 6104 – 6155; e) A. V. Gulevich, A. S. Dudnik, N.
Chernyak, V. Gevorgyan, Chem. Rev. 2013, 113, 3084 – 3213.
[2] Privileged Chiral Ligands and Catalysts (Ed.: Q.-L. Zhou),
Wiley-VCH, Weinheim, 2011.
[3] For selected reviews, see: a) T. E. Mꢀller, K. C. Hultzsch, M.
Yus, F. Foubelo, M. Tada, Chem. Rev. 2008, 108, 3795 – 3892;
b) S. R. Chemler, Org. Biomol. Chem. 2009, 7, 3009 – 3019;
c) R. I. McDonald, G. Liu, S. S. Stahl, Chem. Rev. 2011, 111,
[12] a) A. McNally, C. K. Prier, D. W. MacMillan, Science 2011, 334,
1114 – 1117; b) P. Kohls, D. Jadhav, G. Pandey, O. Reiser, Org.
Lett. 2012, 14, 672 – 675; c) Y. Miyake, K. Nakajima, Y.
4
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Chemie
Nishibayashi, J. Am. Chem. Soc. 2012, 134, 3338 – 3341; d) Y.
Miyake, K. Nakajima, Y. Nishibayashi, Chem. Eur. J. 2012, 18,
16473 – 16477; e) S.-Q. Zhu, A. Das, L. Bui, H.-J. Zhou, D. P.
Curran, M. Rueping, J. Am. Chem. Soc. 2013, 135, 1823 – 1829;
f) L. Ruiz Espelt, E. M. Wiensch, T. P. Yoon, J. Org. Chem. 2013,
78, 4107 – 4114.
[17] For a recent review, see: a) O. A. Attanasi, L. De Crescentini, G.
Favi, P. Filippone, F. Mantellini, F. R. Perrulli, S. Santeusanio,
Eur. J. Org. Chem. 2009, 3109 – 3127.
[18] CCDC 1004591 (2a) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[19] We also tried the hydroamination of 1a using AIBN and DTBP
as classical radical initiators and thiol (PhSH) as a catalyst.
However, all the reactions resulted in no formation of the
desired product.
[20] a) D. Nicewicz, D. Hamilton, Synlett 2014, 1191 – 1196; b) J. M.
Grandjean, D. A. Nicewicz, Angew. Chem. Int. Ed. 2013, 52,
3967 – 3971; Angew. Chem. 2013, 125, 4059 – 4063; c) M. Riener,
D. A. Nicewicz, Chem. Sci. 2013, 4, 2625 – 2629.
[13] G. Cecere, C. M. Konig, J. L. Alleva, D. W. MacMillan, J. Am.
Chem. Soc. 2013, 135, 11521 – 11524.
[14] L. J. Allen, P. J. Cabrera, M. Lee, M. S. Sanford, J. Am. Chem.
Soc. 2014, 136, 5607 – 5610.
[15] a) Y.-Q. Zou, L.-Q. Lu, L. Fu, N.-J. Chang, J. Rong, J.-R. Chen,
W.-J. Xiao, Angew. Chem. Int. Ed. 2011, 50, 7171 – 7175; Angew.
Chem. 2011, 123, 7309 – 7313; b) J. Xuan, X.-D. Xia, T.-T. Zeng,
Z.-J. Feng, J.-R. Chen, L.-Q. Lu, W.-J. Xiao, Angew. Chem. Int.
Ed. 2014, 53, 5653 – 5656; Angew. Chem. 2014, 126, 5759 – 5762.
[16] It has been documented that the H transfer from C- to N-radical
is unfavored in the Hoffmann – Lçffler– Freytag reaction, see: P.
Mackiewicz, R. Furstoss, Tetrahedron 1978, 34, 3241 – 3260.
[21] All the attempts for the intermolecular variants met failure.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
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.
Angewandte
Communications
Communications
Heterocycle Synthesis
X.-Q. Hu, J.-R. Chen,* Q. Wei, F.-L. Liu,
Q.-H. Deng, A. M. Beauchemin,
W.-J. Xiao*
&&&& — &&&&
Photocatalytic Generation of N-Centered
Hydrazonyl Radicals: A Strategy for
Hydroamination of b,g-Unsaturated
Hydrazones
Centered on N: A visible-light-induced
photocatalytic generation of N-centered
hydrazonyl radicals has been accom-
plished for the first time. This approach
allows efficient intramolecular addition of
hydrazonyl radical to terminal alkenes,
thus providing hydroamination and oxy-
amination products in good yields.
Importantly, the protocol involves direct
À
N H oxidation under mild reaction con-
ditions. Ts=4-toluenesulfonyl.
6
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!