Visible Light Mediated Aryl Migration by Homolytic C?N Cleavage of Aryl Amines

Article abstract of DOI:10.1002/anie.201806659

The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4-aryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino group

Full text of DOI:10.1002/anie.201806659

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Accepted Article
Title: Visible light mediated aryl migration by homolytic C‒N cleavage
of aryl amines
Authors: Dirk Alpers, Kevin Cole, and Corey Stephenson
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201806659
Angew. Chem. 10.1002/ange.201806659
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10.1002/anie.201806659
Angewandte Chemie International Edition
COMMUNICATION
Visible light mediated aryl migration by homolytic C‒N cleavage
of aryl amines
Dirk Alpers,[a] Kevin P. Cole,[b] and Corey R. J. Stephenson*[a]
Abstract: The photocatalytic preparation of aminoalkylated
a)
heteroarenes from haloalkylamides via a 1,4-aryl migration from
ipso
addition

C Y
nitrogen to carbon, conceptually analogous to a radical Smiles
rearrangement, is reported. This method enables the substitution of
amino groups in heteroaromatic compounds with aminoalkyl motifs
under mild, iridium(III)-mediated photoredox conditions. It provides
rapid access to thienoazepinone, a pharmacophore present in
multiple drug candidates for potential treatment of different conditions,
including inflammation and psychotic disorders.
cleavage
Ar
reverse connectivity
Ar
desired connectivity
Y
n
n
Y
X
n
Y
carbonyl formation
b)
R
Ar
R
Ar
Ar
Ar
R
O
Me
Me
HO Me
HO Me
extrusion of SO2
The migration of remote aryl groups, such as the Smiles
rearrangement, is a powerful tool for the synthesis of substituted
aromatic and heteroaromatic structural motifs. Conceptually, it
relies on the introduction of functional groups in an easily
achieved, reverse connectivity and subsequent rearrangement
into a desired product, bearing a difficult to construct connectivity
(Scheme 1a). Due to groundbreaking developments in the field of
transition metal and photoredox catalysis in recent years, radical-
based protocols for the Smiles rearrangement have gained
increased attention.[1] Formation of stable functional groups (e.g.
carbonyls from benzylic alcohols) or extrusion of small molecules
(e.g. CO2 or SO2) are often used as driving forces to facilitate
efficient aryl transfer from carbon- or heteroatom-connected
arenes[2-4] to carbon-centered radicals (Scheme 1b). For example,
hydroxy- and amidoalkylated thiophenes were prepared by
Bu3SnH
AIBN
HN
Ar
I
Ar
-SO2
N
N
Me
Me
S
S
O O
O
O
c)
d)
Ar
this work
Smiles-Truce
Ar
X
n
N
R
NHR
n
O
H
N
aryl migration
N to C
CO2R
CO2R
NHPG
key C-C-bond
N
I
S
S
S
key pharmacophore
PG
1
2
3
easily accessible,
inexpensive
means of
a radical Smiles rearrangements using arene
NHPh
O
e)
H
N
N
sulfonamides and sulfonate esters under extrusion of SO2.[3]
However, these aromatic sulfonamides are often prepared from
N
O
N
H
N
N
N
N
S
the corresponding aromatic amines through
a three-step
S
NBn
S
4
5
6
procedure consisting of diazotation, Sandmeyer-type
lipoxygenase
inhibitor
serotonin receptor agonists
chlorosulfonylation and sulfonamide/sulfonate ester formation.[5]
In order to circumvent this step-intensive substrate synthesis, we
questioned the possibility of a radical Smiles rearrangement
through cleavage of an CAr‒N bond to directly furnish the desired
C‒C bond, a transformation with only a small number of examples
reported so far.[6] To thermodynamically enable desired reactivity,
we intended to use
Scheme 1. a) Concept of radical aryl migration (X = radical precursor, Y =
radical stabilizing group); b) Radical Smiles rearrangements driven by C=O
formation (top, R• = N3 , CF3 )[2a] and extrusion of SO2 (bottom)[3h]; AIBN =
Azobisisobutyronitrile; c) Radical aryl migration from N to C via Smiles-Truce
rearrangement (this work); d) Retrosynthetic approach to thienoazepinone 1
with aryl migration from N to C as the key step; PG = protecting group; e)
Examples for biologically active compounds containing the thienoazepinone
pharmacophore.
•
•
[a]
[b]
Dr. D. Alpers, Prof. Dr. C. R. J. Stephenson
Department of Chemistry, University of Michigan
Ann Arbor, MI 48109 (USA)
E-mail: crjsteph@umich.edu
Homepage: www.umich.edu/~crsgroup/
electron withdrawing N-protecting groups as well as alkyl halides
as precursors for primary alkyl radicals to enhance the probability
for a C‒N cleavage in a Smiles-Truce like rearrangement
(Scheme 1c). Potential products 2 of this reaction, using easily
accessible 2-aminothiophenes 3 as starting materials, show great
potential to serve as substrates for the synthesis of
tetrahydrothienoazepinone 1, which has received significant
attention in drug development (Scheme 1d). Potential
applications of this pharmacophore include the treatment of
Dr. K. P. Cole
Small Molecule Design and Development
Lilly Research Laboratories, Eli Lilly and Company
Indianapolis, IN 46285 (USA)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201806659
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COMMUNICATION
inflammations caused by proinflammatory cytokines through
inhibition of nitric oxide synthase (NOS),[7] asthma through
inhibition of lipoxygenase (LOX)[8] or psychotic disorders through
agonistic binding to serotonin receptors[9] (Scheme 1e).
An existing synthesis route to a thienoazepinone related to 1
involves the functionalization of a thiophene using numerous
steps in order to forge two carbon-carbon bonds at C-2 and C-3
of the thiophene core.[10] Use of this route necessitates multiple
telescoped steps due to the non-crystalline nature of the
intermediates and utilizes chromatographic purifications, which
are ill-suited for potential manufacturing applications. We
hypothesized that the inexpensive 2-amino thiophene ester 3
could be used as a starting point to expedite the lactam
preparation. The key transformation would entail the replacement
of a C‒N bond with a C‒C bond in order to append the requisite
three carbon linker (Scheme 1d).
Alkyliodides have been shown to serve as viable sources for
carbon centered radicals through Ir-mediated photocatalytic
reduction.[11] Upon irradiation of alkyliodide 3a with blue light in
the presence of 1 mol% [Ir(ppy)2(dtbbpy)]PF6
I
(E1/2(M/M-)
= -1.51 V vs. SCE, ppy = 2-phenylpyridine, dtbbpy = 4,4’-di-tert-
butyl-2,2’-bypyridine)[12] and 5.0 equiv of iPr2NEt in MeCN,
product 2a was isolated in 87% yield after 3 h (Table 1, Entry 1).
While [Ru(bpy)3](PF6)2 II (E1/2(M/M-) = -1.33 V vs. SCE, bpy = 2,2’-
bipyridine)[13] only led to 44% conversion of 3a (Entry 2), [Ir(ppy)3]
III (E1/2(M*/M+) = -1.73 V vs. SCE)[14] provided 2a in 81% yield
(Entry 3). Utilization of the strong reductant 10-phenylpheno-
thiazine IV (E1/2(P*/P+) = -2.1 V vs. SCE)[15] gave 29% of the
rearrangement product, accompanied by several side products
(Entry 4). Isophthalonitrile based photocatalyst 4-CzIPN V
(E1/2(P/P-) = -1.21 V vs. SCE)[16] furnished Smiles-product 2a in
83% yield after purification, however complete removal of the
catalyst by chromatography could not be achieved (Entry 5). The
reaction proceeds well with loadings of Ir-catalyst I as low as 0.01
mol%, but complete conversion could not be achieved in this case
within 24 h (Entry 6). When iPr2NEt was substituted with Et3N, the
triethylammonium salt of starting material 3a was formed by
nucleophilic substitution of the iodide to a notable extent, leading
to a decreased yield (Entry 7, see SI for details). Notably, full
conversion to 2a was achieved when the reaction was conducted
in non-degassed solvent (Entry 8).
Table 1. Optimization of Smiles-Truce rearrangement
Catalyst
(mol%)
Entry
Base (equiv)
annotations
Yield %[a]
1
2
3
4
5
6
7
8
I (1.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
Et3N (5.0)
>95 (87)
44
II (1.0)
III (1.0)
IV (10)
V (5.0)
I (0.01)
I (1.0)
81
29
370 nm
>95 (83)
67
54
I (1.0)
iPr2NEt (5.0)
under air
>95
Unactivated alkylbromides are generally inaccessible for
mesolytic cleavage via visible light photoreduction due to a
stronger C Br bond, only UV light driven methods have been
‒
reported.[17] Irradiation of bromide 7a in presence of catalyst I only
provided undesired side products (Entry 9, see SI for details). To
facilitate 2a in a single step from 7a, we added 1.0 equiv NaI to
induce the in situ formation of alkyliodide 3a and subsequently
obtained 2a in 55% yield (Entry 10). Elevation of the temperature
9
I (1.0)
I (1.0)
I (1.0)
I (1.0)
I (1.0)
I (1.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (5.0)
iPr2NEt (3.0)
0
55
10
11
12
13
14
1.0 equiv NaI
to 60 °C led to full conversion within 24
h (Entry 11).
1.0 equiv NaI, 60 °C
0.5 equiv NaI, 60 °C
0.2 equiv NaI, 60 °C
0.5 equiv NaI, 60 °C[b]
>95
Substoichiometric amounts of NaI were sufficient to lead to full
conversion, however with 20 mol%, we observed the same
decomposition products that were present in the reaction of
bromide 7a alone (Entries 12 and 13). Optimization of the process
>95
16
i
>95 (95)
revealed that 3.0 equiv of Pr2NEt was the minimum amount
required and the starting material concentration should not
exceed 0.2 M. Under these conditions, product 2a could be
isolated in 95% yield (Entry 14). Notably the protocol could be
scaled up to 1 g of starting material without significant reduction
in yield (see Scheme 2). Additional data on the optimization is
provided in the SI.
PC* = excited photocatalyst. All reactions were conducted on 0.1 mmol scale
at 0.1 M in degassed MeCN unless otherwise noted. See Structures of
catalysts I-III are given in the SI. [a] Determined by HPLC analysis; numbers
in parentheses indicate isolated yield; [b] c = 0.2 M.
The optimized conditions of the Finkelstein/Smiles one-pot
reaction were applied to a selection of different starting materials
(Scheme 2). Variation of the N-protecting group showed the tosyl
group to be most suitable for this reaction (2a-c). To prevent
formation of side products, reactions with trifluorotosyl and Boc-
protected substrates had to be run under diluted conditions
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10.1002/anie.201806659
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COMMUNICATION
(0.05 M). Product 2b was isolated in 50% yield, while 2c was
achieved along with a putative spirocyclic thioaminal side product,
Chloroacylated aminothiophenes 10 either underwent fast
elimination of HCl in the presence of a base (n = 1) or formed a
pyrrolidinone via intramolecular nucleophilic substitution (n = 2).
A plausible mechanism for this aminoalkylation method is
depicted in Scheme 3. Formation of primary alkyl radical 11
occurs via mesolytic cleavage of alkyliodide 3a by the reduced
form [IrII(ppy)2(dtbbpy)] of the iridium photocatalyst I. Subsequent
ipso addition to the the thiophene core breaks the aromaticity of
the π-system but produces a tertiary radical 12 that is additionally
stabilized by its electron withdrawing substituent. Homolytic
1.0 mol-%[Ir(ppy)2(dtbbpy)]PF6
I
EWG
EWG
n
i
3.0 equiv Pr2NEt, 0.5 equiv NaI
NHPG
NHBoc
NHTs
N
Br
X
MeCN (0.2 M)
24 h, hv, 60 °C
n
X
2
PG
7
CO2Me
CO2Me
CO2Me
NHTs
)
NHTsF3
S
2a
S
2b
S
2c
[a]
[b]
[b,c]
cleavage of the C N bond reestablishes the aromaticity of the
‒
95% (80%
CO2Me
50%
67%
thiophene and leads to N-centered radical 13. The final product
2a is presumably generated by H-atom transfer (HAT), whereby
the amine base is the likely source of hydrogen-atom. Further
mechanistic aspects are discussed in the SI.
CO2Me
NHTs
CO2Et
Me
Me
NHTs
S
S
S
[b]
2d
2e
2f
85%
59%
82%
CO2Et
Me
CO2Me
CO2Me
BocN
[Ir(ppy)2(dtbbpy)]PF6
CO2Me
N
CO2Me
iPr2NEt, NaI
NHTs
NHTs
NHTs
NHTs
NHTs
NHTs
NHTs
S
S
S
NHTs
Br
2g
2h
2i
MeCN
24 h
90%
CN
95%
68%
S
S
2a
7a
Ts
CO2Me
OMe
S
H-atom
transfer
[IrIII]*
Br
NHTs
NHTs
S
R3N
CO2Me
2j
2k
2l
81%
76%
45%
SET
[IrIII
]
N
R3N
Ts
S
CO2Et
CO2Et
CO2Et
13
BocN
I
[IrII]
SET
2m 93%
2n 82%
2o 69%
CO2Me
CO2Me
N
CO2Me
N
I-
unsuccessful substrates
S
N
I
S
S
CO2Me
O
CO2Me
CO2Me
3a
11
Ts
Ts
Ts
12
N
Smiles
rearrangement
Cl
n
n = 1,2
N
Br
N
Br
N
H
S
Ts
Ts
8
9
10
Scheme 3. Proposed mechanism.
Scheme 2. Substrate scope. All reactions were conducted on a 0.1 mmol scale
in undegassed solvent. [a] 2.3 mmol (1.0 g) of starting material was used;
[b] c = 0.05 M; [c] acidic aqueous workup procedure required, (see SI for
details); EWG = electron withdrawing group, Ts = tosyl group, TsF3 = 4-trifluoro-
methylbenzene sulfonyl group, Boc = tert-butyloxycarbonyl group.
We finally investigated the conversion of alkylthiophenes 2 into
the pharmaceutically important tetrahydrothienoazepinone 1.
Therefore, Boc-protected thiophene 2c was treated with 5.0 equiv
of HCl in 1,4-dioxane furnishing free amine 14 as the sole product
after neutralization. Upon heating to 65 °C with 3.0 equiv of
NaOMe in MeOH, cyclization to azepinone 1 was achieved with
an overall yield of 58% over two steps starting from Boc-protected
thiophene 2c.
that could be transformed into the desired product by an acidic
workup (see SI for details) to give 2c in 67% yield. Introduction of
a butenyl linker, thus requiring a 1,5-aryl shift to occur after radical
formation, furnished product 2d in 85% yield, also under diluted
conditions. Formation of an allylic radical by reduction of an allyl
halide led to alkenyl compound 2e in 59% yield. Various alkyl
substituents in 4- and 5-positions of the thiophene, including a
Boc-protected amine, were well tolerated (2f-i), as was
substitution of a nitrile group for the ester in the 3-position. The
regioisomer of thiophene 3a obtained by reversing substituents in
the 2- and 3-positions afforded the expected product 2k in 76%
yield. This result suggests that the method is not limited to specific
thiophene substitution patterns. Anisidine derivative 2l was
prepared in 45% yield, which represents an improvement over a
previously reported tin-based method (30%),[6c] while acceptor
substituted benzene and pyridine based compounds 8 and 9 were
decomposed under the given conditions. Interestingly, non-
aromatic electron poor cycloalkene derivatives worked well and
provided aminoalkylated cyclopentene 2m, cyclohexene 2n and
Boc-protected tetrahydropyridine 2o in good to excellent yields.
O
H
N
CO2Me
CO2Me
HCl·dioxane
NaOMe
NHBoc
NH2
CH2Cl2
23 °C
MeOH
65 °C
S
S
S
2c
14
1
58%
over 2 steps
Scheme 4. Synthesis of tetrahydrothienoazepinone 1.
In conclusion, we have developed a visible light mediated,
scalable and mild protocol for the Smiles rearrangement of
heteroarylamines and N-tosyl alkenylamides by means of a
radical aryl migration featuring a C‒N-cleavage. The products of
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10.1002/anie.201806659
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COMMUNICATION
[8]
[9]
a) A. Büge, C. Locke, T. Köhler, P. Nuhn, Arch. Pharm. 1994, 327, 99;
b) R. Schneider, H. Lettau, A. Michael, P. Nuhn, A. Schwalbe,
DE 4114542, Arzneimittelwerk Dresden GmbH, 1992.
this method can readily be transformed into pharmaceutically
relevant fused lactams.
a) T. Nakao, H. Tanaka, H. Yamato, T. Akagi, S. Takehara, US5141930,
Welfide Corp., 1990; b) I. Akritopoulou-Zanze, W. Braje, S. W. Djuric, N.
S. Wilson, S. C. Turner, A. W. Kruger, A.-L. Relo, S. Shekhar, D. S.
Welch, H. Zhao, J. Gandarilla, A. F. Gasiecki, H. Li, C. M. Thompson, M.
Zhang, WO2010135560, Abbott Laboratories, 2010.
Acknowledgements
Financial support from Eli Lilly and Company is gratefully
acknowledged.
[10] Unpublished route developed by Eli Lilly and company.
[11] a) D. Alpers, M. Gallhof, J. Witt, F. Hoffmann, M. Brasholz, Angew. Chem.
Int. Ed. 2017, 56, 1402; Angew. Chem. 2017, 129, 1423; b) Y. Shen, J.
Cornella, F. Juliá-Hernández, R. Martin, ACS Catal. 2017, 7, 409; c) J.
D. Nguyen, E. M. D’Amato, J. M. R. Narayanam, C. R. J. Stephenson,
Nat. Chem. 2012, 4, 854; d) H. Kim, C. Lee, Angew. Chem. Int. Ed. 2012,
51, 12303; Angew. Chem. 2012, 124, 12469.
Keywords: catalysis • heterocycles • photocatalysis • radical
reactions • rearrangement
[1]
Reviews on radical aryl migration reactions: a) W. Li, W. Xu, J. Xie, S.
Yu, C. Zhu, Chem. Soc. Rev. 2018, 47, 654; b) I. Allart-Simon, S. Gérard,
J. Sapi, Molecules 2016, 21, 878; c) Z.-M. Chen, X.-M- Zhang, Y.-Q. Tu,
Chem. Soc. Rev. 2015, 44, 5220; d) A. Studer, M. Bossart, Tetrahedron
2001, 57, 9649.
[12] J. D. Slinker, A. A. Gorodetsky, M. S. Lowry, J. Wang, S. Parker, R. Rohl,
S. Bernhard, G. G. Malliaras, J. Am. Chem. Soc. 2004, 126, 2763.
[13] A. Juris, V. Balzani, P. Belser, A. von Zelewsky, Helv. Chim. Acta 1981,
64, 2175.
[14] L. Flamigni, A. Barbieri, C. Sabatini, B. Ventura, F. Barigelletti,
Photochemistry and Photophysics of Coordination compounds: Iridium
in V. Balyani, S. Campagna (Eds.), Photochemistry and Photophysics of
Coordination Compounds II, Top. Curr. Chem, Vol. 281, Springer, Berlin,
Heidelberg, 2007.
[2]
Examples for radical aryl migration under C‒C bond cleavage: a) L. Li,
Q.-S. Gu, N. Wang, P. Song, Z.-L. Li, X.-H. Li, F.-L. Wang, X.-Y. Liu,
Chem. Commun. 2017, 53, 4038; b) W. Shu, A. Genoux, Z. Li, C. Nevado,
Angew. Chem. Int. Ed. 2017, 56, 10521; Angew. Chem. 2017, 129,
10657; c) Z. Wu, D. Wang, Y. Liu, L. Huan, C. Zhu, J. Am. Chem. Soc.
2017, 139, 1388; d) L. Li, Z.-L. Li, F.-L. Wang, Z. Gua, Y.-F. Cheng, N.
Wang, X.-W. Dong, C. Fang, J. Liu, C. Hou, B. Tan, X.-Y. Liu, Nat.
Commun. 2016, 7, 13852; e) W. Thaharn, D. Soorukram, C. Kuhakarn,
P. Tuchinda, V. Reutrakul, M. Pohmakotr, Angew. Chem. Int. Ed. 2014,
53, 2212; Angew. Chem. 2014, 126, 2244; f) P. Gao, Y.-W. Shen, R.
Fang, X.-H. Hao, Z.-H. Qiu, F. Yang, X.-B. Yan, Q. Wang, X.-J. Gong,
X.-Y. Liu, Y.-M. Liang, Angew. Chem. Int. Ed. 2014, 53, 7629; Angew.
Chem. 2014, 126, 7759.
[15] E. H. Discekici, N. J. Treat, S. O. Poelma, K. M. Mattson, Z. M. Hudson,
Y. Luo, C. J. Hawker, J. Read de Alaniz, Chem. Commun. 2015, 51,
11705.
[16] J. Luo, J. Zhang, ACS Catal. 2016, 6, 873.
[17] a) G. Revol, T. McCallum, M. Morin, F. Gagosz, L. Barriault, Angew.
Chem. Int. Ed. 2013, 52, 13342; Angew. Chem. 2013, 125, 13584; b) S.
J. Kaldas, A. Cannillo, T. McCallum, L. Barriault, Org. Lett. 2015, 17,
2864.
.
[3]
Examples for radical aryl migration under C‒S bond cleavage: a) E. D.
Nacsa, T. H. Lambert, Org. Chem. Front. 2018, 5, 64; b) E. Brachet, L.
Marzo, M. Selkti, B. König, P. Belmont, Chem. Sci. 2016, 7, 5002; c) J.
J. Douglas, M. J. Sevrin, K. P. Cole, C. R. J. Stephenson, Org. Proc. Res.
Dev. 2016, 20, 1148; d) J. J. Douglas, H. Albright, M. J. Sevrin, K. P.
Cole, C. R. J. Stephenson, Angew. Chem. Int. Ed. 2015, 54, 14898;
Angew. Chem. 2015, 127, 15111; e) N. Fuentes, W. Kong, L. Fernández-
Sánchez, E. Merino, C. Nevado, J. Am. Chem. Soc. 2015, 137, 964; f) F.
Ujjainwalla, M. L. E. N. da Mata, A. M. K. Pennell, C. Escolano, W. B.
Motherwell, S. Vázquez, Tetrahedron 2015, 71, 6701; g) W. B.
Motherwell, A. M. K. Pennell, J. Chem. Soc., Chem. Commun. 1991, 877;
h) M. Pudlo, I. Allart-Simon, B. Tinant, S. Gérard, J. Sapi, Chem.
Commun. 2012, 48, 2442; i) M. Bossart, R. Fässler, J. Schoenberger, A.
Studer, Eur. J. Org. Chem. 2002, 2742
[4]
Examples for radical aryl migration under C‒O bond cleavage: a) S.-F.
Wang, X.-P. Cao, Y. Li, Angew. Chem. Int. Ed. 2017, 56, 13809; Angew.
Chem. 2017, 129, 13997 b) S. Ni, W. Sha, L. Zhang, C. Xie, H. Mei, J.
Han, Y. Pan, Org. Lett. 2016, 18, 712-715; c) S. Ni, Y. Zhang, C. Xie, H.
Mei, J. Han, Y. Pan, Org. Lett. 2015, 17, 5524; d) T. Miao, D. Xia, Y. Li,
P. Li, L. Wang, Chem. Commun. 2016, 52, 3175.
[5]
[6]
I. Shcherbakova in C. A. Ramsden (Ed.), Science of Synthesis: Houben-
Weyl Methods of Molecular Transformations Vol. 31a, Georg-Thieme-
Verlag, Stuttgart, 2007.
Examples for radical aryl rearrangement reactions from N to C; a) V. Rey,
A. B. Pierini, A. B. Peñéñory, J. Org. Chem. 2009, 74, 1223; b) E. Bacqué,
M. El Qacemi, S. Z. Zard, Org. Lett. 2005, 7, 3817; c) E. Lee, H. S.
Whang, C. K. Chung, Tet. Lett. 1995, 36, 913; d) J. Grimshaw, R.
Hamilton, J. Trocha-Grimshaw, J. Chem. Soc., Perkin Trans. 1 1982,
229; e) L. Benati, P. Spagnolo, A. Tundo, G. Zanardi, J. Chem. Soc.,
Chem. Commun. 1979, 142.
[7]
D. Cheshire, S. Connolly, D. Cox, P. Hamley, T. Luker, A. Mete, A. Pimm,
M. Stocks, WO2000064904, AstraZeneca Ab, 2000.
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Entry for the Table of Contents
COMMUNICATION
Dirk Alpers, Kevin P. Cole, Corey R. J.
Stephenson*
Page No. – Page No.
Visible light mediated aryl migration
via homolytic C‒N cleavage of aryl
amines
Aminoalkylated heteroarenes are synthesized by radical Smiles rearrangement of
haloalkylamides via a key C‒N cleavage under mild, iridium (III)-mediated
photoredox conditions. The method provides rapid access to the pharmaceutically
relevant thienoazepinone scaffold.
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