Selective ortho C?H Cyanoalkylation of (Diacetoxyiodo)arenes through [3,3]-Sigmatropic Rearrangement

Article abstract of DOI:10.1002/anie.201803455

We herein report a robust catalyst-free cross-coupling between ArI(OAc)₂ and α-stannyl nitriles, aided by TMSOTf. The transformation introduces a cyanoalkyl group to the ortho position of ArI(OAc)₂ and simultaneously reduces the aryl iodine(III) to iodide, thus providing α-(2-iodoaryl) nitrile as the product. This transformation could be completed within 5 min at ?78 °C and features superb functional-group tolerance and efficient scalability. DFT calculations indicate that the formation of a ketenimine(aryl)iodonium intermediate and subsequent [3,3]-sigmatropic rearrangement are involved as key steps.

Full text of DOI:10.1002/anie.201803455

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes via
[3,3]-Sigmatropic Rearrangement
Authors: Junsong Tian, Fan Luo, Chaoshen Zhang, Xin Huang, Yage
Zhang, Lei Zhang, Lichun Kong, Xiaochun Hu, Zhi-Xiang
Wang, and Bo Peng
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201803455
Angew. Chem. 10.1002/ange.201803455
Link to VoR: http://dx.doi.org/10.1002/anie.201803455
http://dx.doi.org/10.1002/ange.201803455

10.1002/anie.201803455
Angewandte Chemie International Edition
COMMUNICATION
Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes via
[3,3]-Sigmatropic Rearrangement
Junsong Tian, Fan Luo+, Chaoshen Zhang+, Xin Huang,* Yage Zhang, Lei Zhang, Lichun Kong,
Xiaochun Hu, Zhi-Xiang Wang,* Bo Peng*
Dedicated to Professor Benjamin List on the occasion of his 50th birthday
Abstract: We herein report a robust catalyst-free cross-coupling
between ArI(OAc)2 and α-stannyl nitriles, aided by TMSOTf. The
transformation introduces a cyanoalkyl group to the ortho position of
ArI(OAc)2 and simultaneously reduces the aryl iodine(III) to iodide,
thus providing α-(2-iodoaryl) nitrile as the product. This
transformation could be completed within 5 min at -78 °C and
features superb functional group tolerance and efficient scalability.
DFT
calculations
indicate
that
the
formation
of
a
ketenimine(aryl)iodonium intermediate and subsequent [3,3]-
sigmatropic rearrangement are involved as key steps.
Aryl iodine(III) reagents are widely used as unique oxidants, aryl
sources and catalysts in organic synthesis.1 The iodide atom of
aryliodanes is often discarded after reactions. An exceptional
example to have the iodide group retained was presented by Oh
and coworkers in their 1988 work of reductive ortho allylation of
iodosylbenzene with allylsilane (Scheme 1a).2 Although the yield
of the example was not high (36%), this unusual cross-coupling
initiated an attractive synthetic protocol to exploit aryl iodine(III)
reagents, because maintaining a transformable iodide group
facilitates the further derivatization of the product. Recently, Zhu
et al extended the scope of this chemistry to certain aryliodanes
bearing strong electron-donating groups at the meta-position.3
Compared with allylsilanes, Ochiai et al. found propargylsilanes
to be more effective for the reaction, although only a few primary
propargylsilanes and substituted aryliodanes were presented.4
Most recently, Shafir and Vallribera elegantly extended the
reaction scope to carbonyl compounds (Scheme 1a).5
Remarkably, their protocol enabled the construction of
challenging quaternary carbon centers on benzene rings ortho to
the iodide, although the scope of nucleophiles is limited to
structurally well-defined β-dicarbonyl compounds. When we
prepared the paper, Yorimitsu et al reported an impressive
synthesis of biaryls using 2-naphthols as coupling partners
(Scheme 1a).6 Despite of all the progresses made, the limited
substrate scopes and low yields associated with these
procedures call for further development of the protocol.
Scheme 1. Background and hypothesis
under much milder conditions than that of N-allyl-vinylamine
(Scheme 1b), which was systematically studied by Walters and
others between 1991 and 1996.7 The much easier
rearrangement of the former than the later was attributed to the
release of the steric congestion associated with the ketenimine
group.7a However, in comparison with the well-established
charge-accelerated [3,3]-sigmatropic rearrangement8, the
accelerated rearrangement via congestion release has not
caught much attention, which is probably due to the difficulty in
accessing the ketenimine-rearrangement precursor (Scheme 1b).
The Claisen rearrangement of N-allyl-ketenimine proceeds
[*]
J. Tian, F. Luo, X. Huang, Y. Zhang, L. Zhang, L. Kong, X. Hu, Prof.
Dr. B. Peng*
Nevertheless,
we
have
recently
found
that
a
ketenimine(aryl)sulfonium intermediate could be assembled by
treating activated arylsulfoxides with alkylnitriles and bases. In
line with Walters’ observation, this intermediate readily
undergoes [3,3]-sigamtropic rearrangement at low temperature
(-30 °C) crossing a relative low energy barrier (11.0 kcal mol-1)
(Scheme 1b).9 Therefore, we envisaged that the acceleration
effect could be used to carry out reductive ortho C-H
cyanoalkylation of aryliodanes. As illustrated in Scheme 1c, we
hypothesized that trapping electrophilic PhIX2 species with
Key Laboratory of the Ministry of Education for Advanced Catalysis
Materials, Zhejiang Normal University
Jinhua 321004, China
E-mail: pengbo@zjnu.cn
C. Zhang, Prof. Z. Wang
School of Chemistry and Chemical Engineering, University of the
Chinese Academy of Sciences
Beijing 100049, China
E-mail: zxwang@ucas.ac.cn
These authors contributed equally to this work
[+]
This article is protected by copyright. All rights reserved.

10.1002/anie.201803455
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Hypothesis verification and optimization of reaction conditionsa
entry
1
Nu
2
activator
TMSOTf
TMSOTf
TMSOTf
TMSOTf
none
temp
time
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
5 min
10 s
yieldb of 6
0
-78 °C to rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
-78 °C
2
3
11
3
4a
5
63c
0d
4
5
4a
4a
4a
4a
4a
4a
4a
4a
0c
6
BF3∙Et2O
Tf2O
46
7
45
8
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
65
9
-100 °C
68
10
11
12
-50 °C
35d
77e
76e
-78 °C
-78 °C
[a] Unless otherwise noted, the reaction was performed by the addition of Nu
(1.0 equiv) to a mixture of 1a (0.3 mmol) and activator (2.0 equiv) in DCM (3
mL). [b] Isolated yield. [c] 63% of 3 or 41% of 4a was recovered. [d] 4a or 5
deteriorated during the reaction. [e] 1.2 equiv of 4a was used. For further
examinations of alkylnitrile
information.
2 and α-silyl nitrile 3, see the supporting
suitable
nitrile
nucleophiles
could
result
in
a
ketenimine(aryl)iodonium intermediate, which can undergo
congestion-released rearrangement with to afford the desired α-
(2-iodoaryl) nitrile.
To verify our hypothesis, we commenced the study by
treating PhI(OTf)2 (formed in situ by the addition of TMSOTf to
PhI(OAc)2)10 with several nitrile nucleophiles (Table 1). Simple
nitrile 2 did not provide any desired product when treated with
PhI(OTf)2 (entry 1). To promote the deprotonation of 2, organic
bases such as DABCO, i-Pr2EtN and pyridines were introduced
in the reaction (for details, see SI).9 In spite of these efforts, the
desired product could not be determined consistently. To our
delight, α-silyl nitrile 3a afforded the desired product 6aa in 11%
yield under the indicated conditions (entry 2). However, the yield
could not be further improved through routine optimization. To
facilitate the delivery of nitrile moiety from α-silyl nitrile, we
employed “F” anion sources (CsF, TBAF, TBAT) and examined
other α-silyl nitriles (α-TIPS nitrile 3b, α-TBS nitrile 3c, α-
(dimethylsilyl) nitrile 3d) (for details, see SI). Unfortunately, all
these efforts failed to improve the yield. We ascribed the
unsatisfying results to the weak nucleophilicity of nitriles 2 and 3,
Scheme 2. Reaction scope. [a] Unless otherwise noted, reactions were
performed with 1 (0.5 mmol) under optimized conditions. [b] 4j was prepared
from corresponding alkylnitrile (1.5 mmol) and used without purification. [c] 1.8
equiv of 4 was used. [d] BF3∙Et2O was used instead of TMSOTf.
nucleophilic site of terminal carbon (entry 4). The choice of the
activator was found essential for the reaction (entries 5-7).
Without activators, PhI(OAc)2 exhibited no reactivity toward 4a
(entry 5). BF3∙Et2O and Tf2O were also effective activators for
the reaction although giving lower yields than that of TMSOTf
(entries 6 and 7). Without gradually raising the temperature, the
reaction could still proceed smoothly at -78 °C with a good yield
(65%) (entry 8). It is worthy of noting that lowering the
which
could
not
effectively
generate
the
ketenimine(aryl)iodonium intermediate (Scheme 1c). Thus, we
switched to more nucleophilic α-stannyl nitrile 4a.11,12 Excitingly,
the yield of the reaction was increased significantly and 6aa was
obtained in 63% yield (entry 3). Silyl ketenimine 5 proved
unsuitable for the reaction, which could be due to its improper
This article is protected by copyright. All rights reserved.

10.1002/anie.201803455
Angewandte Chemie International Edition
COMMUNICATION
Figure 1. Free energy profile for the reaction of PhI(OTf)2 with 4a. Complete
free energy profile with high-lying intermediates and transition states are given
in SI6.2.
carbon. However, 4t, which was also sterically hindered,
furnished quaternary nitrile 6at in poor yield (27%).
Next,
a variety of (diacetoxyiodo)arenes 1b-1y were
examined under the optimum conditions (Scheme 2).
Remarkable functional group compatibility was observed in the
use of functionalized aryliodane substrates. Aryl/alkyl halides
(6bb-6db, 6kb and 6lb), a ketone (6mb), esters (6nb and 6pb),
a nitrile (6nb), and an alkene (6pb) were well-tolerated in the
reaction. Notably benzylic halides (4k and 4l), which are typically
recognized as good electrophiles, were also adopted by the
reaction, as these functional groups are often problematic for
conventional C-C bond formation reactions. Interestingly meta-
substituted phenyl iodanes (4v-4x) furnished expected products
Scheme 3. Elaboration of products and gram-scale reactions.
temperature to -100 °C did not slow down the reaction (entry 9)
but raising the temperature to -50 °C dramatically decreased the
yield (entry 10). Strikingly, when increasing the amount of 4a to
1.2 equiv, the reaction could be completed within 5 min (entry 11)
or even shorter time (10 s, entry 12) with good yields (77% and
76%, respectively). To the best of our knowledge, there have
been no examples of aromatic cyanoalkylations which could
finish within such short time at such low temperature.
Considering the experimental convenience, we conducted all
(6vb-6xb) with
a
similar regio-selectivity (C2/C6=1/2).
Naphthalene 4y decomposed under the optimum conditions.
However, replacing TMSOTf with less electrophilic BF3∙Et2O
gave rise to 6yb albeit in a low yield (41%). To our delight,
heteroarenes, thiophenes 4z and 4a’ also underwent the
transformation to produce 6xb and 6yb, respectively, in
synthetically useful yields. However, pyridine 4b’ proved
unfeasible for the reaction which is probably due to the inhibition
of iodine(III) specie by nucleophilic pyridine nitrogen.
To demonstrate the synthetic utility of this reaction, products
6aa and 6ab were further elaborated as shown in Scheme 3.
The iodide group could be easily converted to vinyl, phenyl, and
nitrogen groups through transition-metal catalyzed cross-
coupling reactions.16 Ulven et al demonstrated that product 6ab
can be readily coupled with a terminal alkyne to produce a drug
candidate, TUG-48817. Through sequential hydrolysis of the
nitrile moiety and copper-catalyzed C-N bond formation, product
6ab was conveniently converted to an anti-inflammatory drug,
Diclofenac, in 70% yield over two steps.18 In addition to iodide
elaboration, the nitrile group of 6aa was also hydrolyzed or
reduced to primary amide 9, aldehyde 10, primary amine 11 and
ketone 12 in good yields (71-91%). Furthermore, a gram-scale
reaction using10 mmol of PhI(OAc)2 as the starting material was
performed twice under the optimum conditions (Scheme 3).
Surprisingly, both gram-scale reactions provided better chemical
yields (91% and 88%) than the original model reaction (77%).
reactions below at -78 °C for 5 min.
optimization are given in SI3.
More details for
With the optimum conditions in hand, we first examined the
reaction scope using various α-stannyl nitriles (Scheme 2). It
was found that electron-deficient functional groups such as
alkyl/aryl halides (6ag, 6ah, 6aq and 6ax), a sulfonate (6ai), a
nitrile (6aj), an electron-poor alkene (6aw), esters (6au-6az’), a
ketone (6az) and an aldehyde (6az’) are all well tolerated, as
these functional groups could be a challenge for conventional
aromatic cyanoal-kylation.13-15 Furthermore, these preserved
functionalities provide a platform for further functionalization of
the products. Remarkably, electron-rich functionalities such as
alkenes (6ak and 6al), alkyl/phenol ethers (6al, 6ao and 6aq),
an acetal (6ap), and benzene/thiophene rings (6ae, 6af and
6ay), which can be readily oxidized by aryl iodine(III) reagents,1
are also well-tolerated under the reaction conditions. We
tentatively attribute the excellent chemoselectivity to the
selective recognition of the highly electrophilic aryl iodine(III)
species by α-stannyl nitriles. Unexpectedly, a primary alcohol
6am was also partially tolerated and 6am was obtained in a low
but reasonable yield (29%). Pleasingly, when alcohol 4m
protected by TBDPS group, the reaction of 4ao afforded
corresponding 6ao in good yield (72%). It is not a surprise that
an internal alkyne group had a deleterious effect on the reaction
of 4r, which furnished 6ar in a low yield (32%). Notably sterically
hindered cyclopropyl nitrile 4s smoothly afforded 6as in a
synthetically useful yield (62%) by constructing a quaternary
This beneficial effect of
a large-scale condition strongly
demonstrates the practicality of the technology.
To shed light on the reaction mechanism, we performed DFT
computations (see SI6 for computational details) to characterize
the pathways for the reaction of PhI(OTf)2 with α-stannyl nitrile
4a, considering that PhI(OTf)2 can be formed upon mixing
This article is protected by copyright. All rights reserved.

10.1002/anie.201803455
Angewandte Chemie International Edition
COMMUNICATION
[1]
a) T. Wirth, Topics in Current Chemistry: Hypervalent Iodine Chemistry,
Springer International Publishing: Switzerland, 2016; b) V. V. Zhdankin,
Hypervalent Iodine Chemistry: Preparation, and Structure Synthetic
Application of Polyvalent Iodine Compounds, John Wiley & Sons Ltd.:
New York, 2014; c) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016,
116, 33285; d) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008, 108,
5299.
PhI(OAc)2 with TMSOTf (2.0 equiv) as demonstrated by Wirth’s
NMR studies10b. Consistently, the conversion (PhI(OAC)2
+
2*TMSOTf

PhI(OTf)2
+
2*TMSOAc) was predicted
thermodynamically favorable by 4.9 kcal mol-1. As illustrated in
Figure 1, the reaction proceeds via substitution of a OTf group of
PhI(OTf)2 by the nitrile group of 4a, generating
a
ketenimine(phenyl)iodonium triflate IM4, followed by [3,3]-
sigmatropic rearrangement, eventually leading to the product
6aa. Along the black pathway, the substitution takes place via
nucleophilic attack of 4a, first forming IM1, then IM2 after OTf-
dissociation from IM1. Subsequently, the dissociated triflate
anion attacks IM2 at the Sn center through a SN2 process. In
terms of electronic energy, the SN2 intermediate (IM3) and
transition state (TS1) could be located, but TS1 is lower than
IM3 in terms of free energy, thus IM4 could actually be formed
straightforwardly. Alternatively, the blue pathway proceeds
through a concerted mechanism to form IM4, as illustrated by
TS1a. Comparing the two pathways, the black pathway is 2.1
kcal mol-1 more favorable than the blue one. However,
considering the overestimation of the entropy penalty for the
concerted process, we speculated the two mechanisms to form
IM4 are competitive (see SI6.1). The [3,3] sigmatropic
rearrangement can readily take place via crossing a low barrier
of 2.1 kcal mol-1 (TS2), leading to IM5. In IM5, the OTf- is close
to the ortho C-H group, which facilitates the group to extract the
hydrogen for rearomatization, giving the final product 6aa.
Overall, because of the congestion release, the [3,3] sigmatropic
rearrangement is easy to take place. Thus, the formation of IM4
via IM2 or TS1a becomes a rate-determining event of the
reaction and the whole reaction is highly exergonic by 69.9 kcal
mol-1, indicating that the reaction can indeed take place facilely.
The released HOTf acid from IM5 could further react with
TMSOAc, giving less acidic HOAc, since the conversion (HOTf +
TMSOAc  TMSOTf + HOAc) is exergonic by 6.7 kcal mol-1.
Note that, in addition to the favorable pathways discussed above,
we considered other possible mechanisms with results included
in SI6.2.
[2]
[3]
a) K. Lee, D. Y. Kim, D. Y. Oh, Tetrahedron Lett. 1988, 29, 667; b) For
a recent review: A. Shafir, Tetrahedron Lett. 2016, 57, 2673.
a) H. R. Khatri, H. Nguyen, J. K. Dunaway, J. Zhu, Front. Chem. Sci.
Eng. 2015, 9, 359; b) H. Nguyen, H. R. Khatri, J. Zhu, Tetrahedron Lett.
2013, 54, 5464; c) H. R. Khatri, J. Zhu, Chem. Eur. J. 2012, 18, 12232.
a) M. Ochiai, M. Kida, T. Okuyama, Tetrahedron Lett. 1998, 39, 6207; b)
M. Ochiai, T. Ito, J. Org. Chem. 1995, 60, 2274; c) M. Ochiai, T. Ito, Y.
Masaki, J. Chem. Soc.,Chem. Commun. 1992, 1, 15; d) M. Ochiai, T.
Ito, Y. Takaoka, Y. Masaki, J. Am. Chem. Soc. 1991, 113, 1319; (e) D.
A. Gately, T. A. Luther, J. R. Norton, M. M. Miller,; O. P. Anderson, J.
Org. Chem. 1992, 57, 6496.
[4]
[5]
a) Z. Jia,. E. Gálvez, R. M. Sebastián, R. Pleixats, A. Álvarez-Larena, E.
Martin, A. Vallribera, A. Shafir, Angew. Chem. Int. Ed. 2014, 53, 11298;
b) Y. Wu, I. Arenas, L. M. Broomfield, E. Martin,; A. Shafir, Chem. Eur.
J. 2015, 21, 18779; c) Y. Wu, S. Izquierdo, P. Vidossich, A. Lledós, A.
Shafir, Angew. Chem. Int. Ed. 2016, 55, 7152.
[6] M. Hori, J.-D. Guo, T. Yanagi, K. Nogi, T. Sasamori, H. Yorimitsu, Angew.
Chem. Int. Ed. 2018, DOI: 10.1002/anie.201801132.
[7]
a) M. A. Walters, J. Org. Chem. 1996, 61, 978; b) M. A. Walters, A. B.
Hoem, C. S. McDonough, J. Org. Chem. 1996, 61, 55; c) M. A. Walters,
J. Am. Chem. Soc. 1994, 116, 11618; d) R. Bruckner, R. Huisgen,
Tetrahedron Lett. 1994, 35, 3281; e) M. A. Walters, A. B. Hoem, H. R.
Arcand, A. D. Hegeman, C. S. McDonough, Tetrahedron Lett. 1993, 34,
1453; f) P. Molina, M. Alajarín, C. López-Leonardo, J. Alcántara,
Tetrahedron 1993, 49, 5153; g) P. Molina, M. Alajarín, C .López-
Leonardo, Tetrahedron Lett. 1991, 32, 4041; (h) M. A. Walters, C. S.
McDonough, P. S., Jr. Brown, A. B. Hoem, Tetrahedron Lett. 1991, 32,
179; (i) K. C. Brannock, R. D. Burpitt, J. Org. Chem. 1965, 30, 2564.
a) U. Nubbemeyer, Top. Curr. Chem. 2005, 244, 149; b) K. C. Majum-
dar, T. Bhattacharyya, B. Chattopadhyay, B. Sinha, Synthesis 2009, 13,
2117.
[8]
[9]
L. Shang, Y. Chang, F. Luo, J.-N. He, X. Huang, L. Zhang, L, Kong, K.
Li, B. Peng, J. Am. Chem. Soc. 2017, 139, 4211.
[10] a) K. E. Lutz, R. J. Thomson, Angew. Chem. Int. Ed. 2011, 50, 4437; b)
U. Farid, T. Wirth, Angew. Chem. Int. Ed. 2012, 51, 3462; (c) T.
Kitamura, R. Furuki, K. Nagata, H. Taniguchi, P. J. Stang, J. Org. Chem.
1992, 57, 6810; d) Y. Sun, X. Huang, X. Li, F. Luo, L. Zhang, M. Chen,
In summary, we have described a catalyst-free cross-
coupling between (diacetoxyiodo)arenes with α-stannyl nitriles.
Compared with conventional aromatic cyanoalkylations,13-15 the
reaction maintains a transformable iodide group in the product,
which allows the synthesis of unique α-(2-iodoaryl) nitriles. The
robustness of the reaction (-78 °C for 5 min) gives this process
exquisite selectivity, excellent functional group compatibility and
broad substrate scope. Efficient scale-up reactions demonstrate
the practicality of the method. DFT mechanistic study unveiled
S.
Zheng,
B.
Peng,
Adv.
Synth.
Catal.
2018,
doi:
10.1002/adsc.201701237.
[11] a) A. G. Davis, Organotin Chemistry, Wiley-VCH: Weinheim, 2004; b) A.
G. Davis, M. Gielen, K. H. Pannell, E. R. T. Tiekink, Tin Chemistry-
Fundamentals, Frontiers and Applications; Wiley: United Kingdom,
2008.
[12]
For recent progresses of organotin chemistry: a) A. W. Schuppe, D.
Huang, Y. Chen, T. R. Newhouse, J. Am. Chem. Soc. 2018, DOI:
10.1021/jacs.7b13189; b) Y. Gu, R. Martin, Angew. Chem. Int. Ed.
2017, 56, 3187; c) C.-V. T. Vo, M. U. Luescher, J. W. Bode, Nat. Chem.
2014, 6, 310.
that
the
transformation
proceeds
via
forming
a
ketenimine(phenyl)iodonium intermediate, followed by a facile
[3,3]-sigmatropic rearrangement. Further mechanistic studies
and applications of the reaction are ongoing in our laboratory.
[13] For a comprehensive review on cyanoalkylation reactions: R. Lýpez, C.
Palomo, Angew. Chem. Int. Ed. 2015, 54, 13170.
[14] For reactions of nucleophilic nitriles with aryl electrophiles: a) J. You, J.
G. Verkade, Angew. Chem. Int. Ed. 2003, 42, 5051; b) L. Y. Wu, J. F.
Hartwig, J. Am. Chem. Soc. 2005, 127, 15824; c) A. Klapars, J. H.
Waldman, K. R. Campos, M. S. Jensen, M. Mclaughlin, J. Y. L. Chung,
R. J. Cvetovich, C. Chen, J. Org. Chem. 2005, 70, 10186.
Acknowledgements ((optional))
This work is supported by NSFC-21502171 and Zhejiang
Normal University. Z.X. W. acknowledges the support of NSFC-
21573233.
[15] For reactions between electrophilic nitriles and aryl nucleophiles: a) A.
He, J. R. Falck, J. Am. Chem. Soc. 2010, 132, 2524; b) J. Choi, G. C.
Fu, J. Am. Chem. Soc. 2012, 134, 9102; c) M. Nambo, M. Yar, J. D.
Smith, C. M. Crudden, Org. Lett. 2015, 17, 50.
Keywords: hypervalent iodine • sigmatropic rearrangement •
cyanoalkylation • electrophilic activationn • organotin
[16] For more details, see the supporting information.
[17] E. Christiansen, et al. J. Med. Chem. 2013, 56, 982.
[18] a) P. Moser, A. Sallmann, I. Wiesenberg, J. Med. Chem. 1990, 33, 2358;
b) S. M. Hoy, Drugs 2016, 76, 1213; c) R. Altman, B. Bosch, K. Brune,
P. Patrignani,; C. Young, Drugs 2015, 75, 859.
This article is protected by copyright. All rights reserved.

10.1002/anie.201803455
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Text for Table of Contents
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
((Insert TOC Graphic here))
Layout 2:
COMMUNICATION
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
Speed wins: A robust cross-coupling of activated aryliodanes with α-stannyl nitriles
is described. The unusually low reaction temperature and short reaction time
enable the reaction to tolerate
a large variety of functional groups. An
unprecedented [3,3]-sigmatropic rearrangement is involved in the reaction.
This article is protected by copyright. All rights reserved.