N-Atom Deletion in Nitrogen Heterocycles

Article abstract of DOI:10.1002/anie.202107356

Excising the nitrogen in secondary amines, and coupling the two residual fragments is a skeletal editing strategy that can be used to construct molecules with new skeletons, but which has been largely unexplored. Here we report a versatile method of N-atom excision from N-heterocycles. The process uses readily available N-heterocycles as substrates, and proceeds by N-sulfonylazidonation followed by the rearrangement of sulfamoyl azide intermediates, providing various cyclic products. Examples are provided of deletion of nitrogen from natural products, synthesis of chiral O-heterocycles from commercially available chiral β-amino alcohols, formal inert C?H functionalization through a sequence of N-directed C?H functionalization and N-atom deletion reactions in which the N-atom can serve as a traceless directing group.

Full text of DOI:10.1002/anie.202107356

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: N-Atom Deletion in Nitrogen Heterocycles
Authors: Haitao Qin, Wangshui Cai, Shuang Wang, Ting Guo, Guigen
Li, and Hongjian Lu
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.202107356
Link to VoR: https://doi.org/10.1002/anie.202107356

10.1002/anie.202107356
Angewandte Chemie International Edition
COMMUNICATION
N-Atom Deletion in Nitrogen Heterocycles
Haitao Qin,[a] Wangshui Cai,[a] Shuang Wang,[a] Ting Guo,[a] Guigen Li[a,b] and Hongjian Lu*[a]
[a]
H. Qin, W. Cai, S. Wang, T. Guo, Prof. G. Li and Prof. H. Lu
Institute of Chemistry and BioMedical Sciences, Jiangsu Key Laboratory of Advanced Organic Materials,
School of Chemistry and Chemical Engineering
Nanjing University, Nanjing, 210093, China.
E-mail: hongjianlu@nju.edu.cn.
[b]
Prof. G. Li
Department of Chemistry and Biochemistry
Texas Tech University, Lubbock, Texas 79409-1061, United States.
Supporting information for this article is given via a link at the end of the document.
Abstract: Excising the nitrogen in secondary amines, and coupling
the two residual fragments is a skeletal editing strategy that can be
used to construct molecules with new skeletons, but which has been
largely unexplored. Here we report a versatile method of N-atom
excision from N-heterocycles. The process uses readily available N-
heterocycles as substrates, and proceeds by N-sulfonylazidonation
followed by the rearrangement of sulfamoyl azide intermediates,
providing various cyclic products. Examples are provided of deletion
of nitrogen from natural products, synthesis of chiral O-heterocycles
from commercially available chiral β-amino alcohols, formal inert C–H
N bonds via the rearrangement of a 1,2-diazene intermediate
(Scheme 1D).13 Because N-heterocycles are ubiquitous structural
motifs9 and can be easily produced by versatile methods,14 we
questioned whether it is possible to provide a general skeletal
editing strategy to transform (n+1)-membered N-heterocycles to
n-membered cycles. Given the large number of organic molecules
with cyclic structures, this transformation would be extremely
useful. Levin et al. recently reported a N-atom deletion reaction
from an anomeric amide which was prepared in three steps from
an amide (Scheme 1E).15 The anomeric amide reacted with a
secondary amine to generate an intermediate 1,1-diazene, loss of
nitrogen from which led to desired nitrogen-free product. The
reaction has shown broad functional group tolerance and has
been used in the synthesis of bioactive compounds. However, the
reaction failed to tolerate some functional groups such as
dimethoxyphenyl due to the oxidative ability of the anomeric
amide reagent. For N-heterocycles used in this reaction, one N-
substituent must be benzhydryl, or both N-substituents must bear
stabilizing elements such as benzyl, allyl or be positioned α to a
carbonyl group. Inspired by our previous work,13,16 herein we
report a N-atom deletion of N-heterocycles via a sequence of N-
sulfonylazidonation, Curtius-type rearrangement and subsequent
rearrangement of the 1,2-diazene intermediate, providing a
unique opportunity to promote ring contraction17 of N-
heterocycles (Scheme 1F).
functionalization through
a
sequence of N-directed C–H
functionalization and N-atom deletion reactions in which the N-atom
can serve as a traceless directing group.
Compared to the wide deployment of C–H functionalization
chemistry which can edit the periphery of a molecule, selective
breaking and derivatization of inert C–C,1 C–O 2 or C–N 3 bonds,
which will alter the skeleton of a molecule are receiving increasing
interest but reactions of this sort await development.4,5 A synthetic
process which can delete an internal N-atom of a secondary
amine and couple the remaining fragments is an attractive
synthetic strategy (N-atom deletion, Scheme 1A),6 in which one
new C–C bond is formed through the consumption of two sp3C–
N
bonds which can be constructed by versatile reliable
methods.7,8 In addition, secondary amine motifs, which are
common in natural products, organic materials, agrochemicals
and pharmaceuticals can lead to an endless supply of substrates
for synthetic transformations.9 It is known that the rearrangement
of 1,1-diazene can break two C–N bonds and form one C–C bond,
and this may provide a good opportunity to realize the synthetic
possibilities of N-atom deletion.10-12 In 1965, Rave et al. found that
the reaction of the dibenzyl amines with Angeli’s salt (Na2ONNO2)
in aqueous acidic solution could generate 1,1-diazenes, which
can rearrange to dibenzyl product (Scheme 1B).11 Possibly due to
the instability of Angeli’s salt, especially under acidic conditions,
Tetrahydroisoquinoline 1a, containing an active benzylic C–N
bond and an inert C–N bond, was selected as the substrate to test
this method. We found that 1a reacts with N3SO2N3 to produce a
sulfamoyl azide intermediate,18 which decomposes under thermal
and basic conditions to the desired N-free product, 2,3-
dihydroindene 1b which is formed in 80% yield (Scheme 2A). In
absence of base or at a lower reaction temperature, very little 1b
was observed (see details in Table S1 of the Supporting
Information - SI). The reagent N3SO2N3 was first reported in 1979
and can be easily prepared from SO2Cl2 and NaN3 in one step
(Scheme 2B) but its use and applications have apparently not
been explored.19 The crystal structure of N3SO2N3 was
determined19a and its solution in DCM was stored in a refrigerator
for several months without significant change, indicating its
stability.20 Using the optimal reaction conditions, we explored the
scope of this reaction (Scheme 2C). The 6- and 7-membered N-
heterocycles are all feasible substrates, and are converted to the
5- or 6-membered, nitrogen-free rings 1b-15b in good yields. The
silylated product 3b was produced in low yield, possibly due to
steric hindrance. Compounds with 7-membered (16b) and 8-
membered rings (17b) can be achieved in reasonable yields by
only dibenzyl amine was reported to undergo such
a
transformation. A general protocol to realize such transformation
would involve for example N-nitrosation of a secondary amine,
reduction of N-nitroso compounds and oxidation of 1,1-
hydrazines (Scheme 1C).12 Since both reduction and oxidation
steps are necessary and toxic oxidants are likely to use, this
inconvenient and multistep synthetic procedure has failed to
attract significant attention.
In 2017, we found that sulfamoyl azides derived from linear
alkylamines could undergo a Curtius-type rearrangement to
generate a new C–C bond while simultaneously breaking two C–
1
This article is protected by copyright. All rights reserved.

10.1002/anie.202107356
Angewandte Chemie International Edition
COMMUNICATION
Scheme 1. Skeletal edition through N-atom deletion
Standard conditions: N-heterocycle a (0.2 mmol), DBU (0.4 mmol), DCM (dichloromethane, CH2Cl2) (0.5 mL), N2SO2N3 (0.2 M in DCM, 5 mL), rt, 2-3 h; then tBuOLi
(1.0 equiv), 1,4-dioxane (2 mL), 120 oC, 3 h, isolated yield of product b based on substrate a. [a] Using a•HCl (0.2 mmol) instead of a, DBU (0.6 mmol). [b] N2SO2N3
(0.2 M in DCM, 10 mL), tBuOLi (2.0 equiv). [c] NMR yield.
Scheme 2. N-atom deletion of N-heterocycles
2
This article is protected by copyright. All rights reserved.

10.1002/anie.202107356
Angewandte Chemie International Edition
COMMUNICATION
Standard conditions: substrate a (0.2 mmol), N2SO2N3 (0.2 M in DCM, 5 mL), DBU (0.4 mmol), DCM (0.5 mL), rt, 2-3 h; thentBuOLi (1.0 equiv), 1,4-dioxane (2 mL),
120 oC, 3 h, isolated yield of product b based on substrate a. [a] Gram scale preparation, see details in SI.
Scheme 3. Applications of N-atom deletion
this method. Macrocyclic bibenzyl 9- to 20-membered rings (18b-
22b), including a chiral binaphthyl structure (23b) can also be
constructed efficiently. Natural bibenzyl compounds, including
macrocyclic bisbibenzyl compounds are known to be the key motif
of various important pharmaceuticals and natural products.21 By
increasing the amount of N3SO2N3, the di(N-deletion)
transformation can be achieved, and the desired macrocyclic
products 24b and 25b in which four C–N bonds were broken while
two new C–C bonds were constructed, are achieved in moderate
yields. Notwithstanding the disadvantages of a strained 4-
membered ring and the stability of the 5-membered ring, the
contraction of 2-phenyl pyrrolidine produced the desired
cyclobutane 26b, albeit in low yield. In addition to the 4- to 20-
membered cyclic rings that are formed in this reaction, different
type of rings such as carbocycles, O-heterocycles and N-
heterocycles are all produced in this reaction. Although steric
effects have been shown to affect the reactivity, some functional
groups such as an isopropyl group in the α-position of nitrogen
can be tolerated, producing for example, the desired N-deletion
product 10b in good yield. The functionalized compounds such as
ester (4b), aryl bromide (5b), furan’s (6b) and pyridine’s (7b)
derivative, and amide (14b) are suitable substrates. Two
activated C–N bonds (such as benzylic C–N bond) are not a
requirement for N-heterocycles, as demonstrated by reactions
leading to compounds 1b-11b, in which an inert C–N bond is one
of the two reacting C–N bonds.
The synthetic applications of these N-atom deletion reactions
were studied (Scheme 3). Many natural products contain benzyl
3
This article is protected by copyright. All rights reserved.

10.1002/anie.202107356
Angewandte Chemie International Edition
COMMUNICATION
amine structures which may provide ample resources for use of
these compounds with skeletal edition. The natural product rac-
reactions were carried out in the presence of radical trapping
reagents, it was found that the addition of a stoichiometric amount
norlaudanosine 27a, containing a tetrahydroisoquinoline structure, of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or BHT (2,6-di-
is a substrate which can produce the dihydroindene derivative
27b in a good yield. It’s interesting since that numerous natural
products and useful compounds possess the dihydroindene
skeleton,22 and the easily oxidized dimethoxyphenyl group can be
tolerated in this reaction. In conjunction with known methods, this
novel synthetic methodology may lead to the development of
tert-butyl-4-methylphenol) had no significant effect (Scheme 4B).
3-Methyleneazetidine was designed as a new type of radical
probe for N-atom deletion reactions (Scheme 4C).29 After the
derivatives of 3-methyleneazetidine (40a, 41a) were subjected to
the standard conditions, vinylcyclopropanes (40b, 41b), which
were thought to be generated from a 1,3-radical shift process,
were isolated with moderate yields. These observations are
consistent with the results from Levin et al.15 and with our previous
report,13 in which the C–C bond-forming mechanism was shown
to involve a barrierless intramolecular radical coupling reaction.
Due to the ring tension in the four-membered ring, the unexpected
4-phenylstyrene 26b' was achieved with a four-membered ring
arylcyclobutane 26b as a minor product in the reaction of the five-
membered N-heterocycle 26a (Scheme 4D). It was proposed that
26b and 26b' were produced from the rearrangement of a
biradical intermediate I. When the 9-membered N-heterocycle
17a was used as the substrate, the side products 17c and 17d
were obtained, indicating that the biradical intermediate II may be
involved (Scheme 4E).
fundamentally new retrosynthetic routes. Cyclization of
a
molecular with nitrogen and a second heteroatom is commonly
used in the construction of N-heterocyclic compounds (Scheme
3B).23 The chiral β-amino alcohol presents as a privileged motif in
nature, medicine and catalysis. Thus, nucleophilic substitution of
commercially available (1R,2S)-1-amino-2-indanol is employed
for the preparation of 1,4-oxazepanes 28a-31a. Removal of
nitrogen from these compounds could be a means of synthesizing
chiral tetracyclic chroman derivatives 28b-31b.24 Not only good to
high yields and high diastereoselectivity (> 17/1) but also high
asymmetric induction (28b, > 99% ee) can be achieved, indicating
that the chiral center β to the N-atom remained unchanged during
the reaction. The tetracyclic chroman 32b, the enantiomer of 28b,
could be obtained as a single isomer from the conversions of
commercially available (1S,2R)-1-amino-2-indanol 32a1'. When
32a2, a mixture of cis and trans isomers, was used as substrate,
a single isomer 32b was obtained in 79% yield, indicating that the
C–C bond formation was largely controlled by the adjacent chiral
carbon and was not a consequence of the configuration of the
initial C–N bond. Cyclization of (1S, 2R)-1,2-aminocyclohexanol
produces 1,4-oxazepane 33a, which could be transformed to the
tricyclic chroman derivative 33b with excellent stereoselectivity.
An N-atom can be the directing group in C–H functionalization.25
For example, direct α C–H functionalization of unprotected
secondary cyclic amines was recently developed by Seidel et al.26
Inspired by this, we developed an N-directed C–H
functionalization and subsequent N-deletion reaction, providing a
form inert C–H functionalization by using N-atom as a traceless
directing group (Scheme 3C).27 For example, the selective C–H
functionalizations of tetrahydroisoquinoline 34a' were followed by
N-deletion reactions, providing α-alkylated (34b), arylated (35b)
and olefinated (36b) dihydroindenes in good yields. Similarly, this
method also enables the synthesis of 4-phenylchromane 37b and
arylcycloheptane 38b from the tetrahydrobenzo[1,4]-oxazepane
37a' and azocane 38a' respectively. The reaction of 35a has been
performed on a gram scale (Scheme 3, note a), and the desired
product 35b was produced in 83% yield, demonstrating the
practicality of this method.
Based on previous studies,11,13,28 a mechanism is proposed in
Scheme 1F. Nucleophilic substitution by N3SO2N3 of a cyclic
amine forms a sulfamoyl azide, which undergoes a Curtius-type
rearrangement to generate a 1,1-diazene intermediate. The base
(tBuOLi) can abstract the side product, SO2 to facilitate the
reaction. The rearrangement of 1,1-diazene forms a biradical
intermediate, whose intramolecular radical coupling reaction
produces final N-atom deletion product. In an effort to better
understand the reaction mechanism, several experiments were
conducted and some side products were identified (Scheme 4).
The tetrahydroisoquinoline 39a, bearing a cyclopropyl unit, was
designed and synthesized to probe the reaction (Scheme 4A). Its
N-atom deletion product 39b was isolated in 56% yield and no
rearrangement was observed. When the N-atom deletion
Scheme 4. Mechanistic studies
4
This article is protected by copyright. All rights reserved.

10.1002/anie.202107356
Angewandte Chemie International Edition
COMMUNICATION
[7]
[8]
a) J. Bariwal, E. Van der Eycken, Chem. Soc. Rev. 2013, 42, 9283–9303;
b) L. Kürti, Science 2015, 348, 863-864.
In summary, we have developed a new skeletal editing strategy
based on direct deletion of the N-atom from N-heterocycles. This
protocol works well with a wide range of N-heterocycles, efficiently
providing various useful cyclic compounds with new skeletons.
Ring sizes from 3- to 20-membered rings and various type of
cyclic structures including carbocycles, O-heterocycles and N-
heterocycles can be achieved by this reaction. The advantages of
this method include its innovative utility with natural products
containing N-heterocycles, generating fundamentally new
retrosynthetic routes by combining with known methods, non-
oxidative reaction conditions, and cheap and commercially
available reagents. This is a new method for the synthesis of
different cyclic compounds from easily obtained N-heterocycles,
and may have great potential in pharmaceutical chemistry and
natural products synthesis.
a) L. Huang, M. Arndt, K. Gooßen, H. Heydt, L. J. Gooßen, Chem. Rev.
2015, 115, 2596–2697; b) R. N. Salvatore, C. H. Yoon, K. W. Jung,
Tetrahedron. 2001, 57, 7785–7811; c) K. C. K. Swamy, N. N. B. Kumar,
E. Balaraman, K. V. P. P. Kumar, Chem. Rev. 2009, 109, 2551–2651; d)
A. F. Abdel-Magid, S. J. Mehrman, Org. Process Res. Dev. 2006, 10,
971–1031.
[9]
a) H. J. Knoner, (ed) The Alkaloids: Chemistry and Biology Vol. 70
(Elsevier, San Diego, 2011); b) G. Ćirić-Marjanović, Synth. Met. 2013,
177, 1–47; c) E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem.
2014, 57, 10257–10274.
[10] a) C. G. Overberger, J. G. Lombardino, R. Hiskey, J. Am. Chem. Soc.,
1957, 79, 6430–6435; b) L. A. Carpino, J. Am. Chem. Soc., 1962, 84,
2196–2201; c) P. G. Schultz, P. B. Dervan, J. Am. Chem. Soc., 1982,
104, 6660–6668; d) R. D. Miller, P. Gӧlitz, J. Janssen, J. Lemmens, J.
Am. Chem. Soc., 1984, 106, 7277–7279.
[11] D. M. Lemal, T. W. Rave, J. Am. Chem. Soc. 1965, 87, 393–394.
[12] a) C. G. Overberger, J. G. Lombardino, R. Hiskey, J. Am. Chem. Soc.,
1957, 79, 6430–6435; b) W. H. Urry, H. W. Kruse, W. R. McBride, J. Am.
Chem. Soc. 1957, 79, 6568–6569; c) R. L. Hinman, K. L. Hamm, J. Am.
Chem. Soc. 1959, 81, 3294–3297; d) C. G. Overberger, N. P. Marullo, R.
G. Hiskey, J. Am. Chem. Soc. 1961, 83, 1374–1378; e) W. D. Hinsberg,
P. B. Dervan, J. Am. Chem. Soc. 1978, 100, 1608–1610.
Acknowledgements
We are grateful for financial support by National Natural Science
Foundation of China (22071100, 21871131), the Natural Science
[13] X. Zou, J. Zou, L. Yang, G. Li, H. Lu, J. Org. Chem. 2017, 82, 4677–4688.
[14] C. V. T. Vo, J. W. Bode, J. Org. Chem. 2014, 79, 2809–2815.
[15] S. H. Kennedy, B. D. Dherange, K. J. Berger, M. D. Levin, Nature 2021,
593, 223–227.
Foundation of Jiangsu Province (BK20191244).
Keywords: N-atom deletion • C-N bond cleavage • C-C coupling
•N-heterocycles • skeletal editing
[16] Y. Zhang, X. Ge, H. Lu, G. Li, Angew. Chem. 2021, 133, 1873-
1880; Angew. Chem. Int. Ed. 2021, 60, 1845–1852.
[17] L. F. Silva, Synlett. 2014, 25, 466-476.
[1]
a) Z. Nairoukh, M. Cormier, I. Marek, Nat. Rev. Chem. 2017, 1, 0035.; b)
F. Song, T. Gou, B. -Q. Wang, Z. J. Shi, Chem. Soc. Rev. 2018, 47,
7078–7115; c) B. Wang, M. A. Perea, R. Sarpong, Angew. Chem. 2020,
132, 19058-19080; Angew. Chem. Int. Ed. 2020, 59, 18898–18919; d) Y.
Xia, G. Dong, Nat. Rev. Chem.2020, 4, 600–614.
[18] a) H. Lu, H. Jiang, L. Wojtas, X. P. Zhang, Angew. Chem. 2010, 122,
10390-10394; Angew. Chem. Int. Ed. 2010, 49, 10192–10196; b) H. Lu,
C. Li, H. Jiang, C. L. Lizardi, X. P. Zhang, Angew. Chem. 2014, 126,
7148–7152; Angew. Chem. Int. Ed. 2014, 53, 7028–7032.
[19] a) X. Q. Zeng, H. Beckers, E. Bernhardt, H. Willner, Inorg. Chem. 2011,
50, 8679−8684; b) X. Dong, G. Deng, J. Xu, H. Li, X. Zeng, J. Phys.
Chem. A. 2018, 122, 8511–8519.
[2]
a) M. Tobisu, N. Chatani, Acc. Chem. Res. 2015, 48, 1717–1726; b) E.
Bisz, M. Szostak, ChemSusChem. 2017, 10, 3964-3981; c) A. N.
Desnoyer, J. A. Love, Chem. Soc. Rev. 2017, 46, 197–238; d) S. Q.
Zhang, X. Hong, Acc. Chem. Res. 2021, 54, 2158–2171.
[20] Caution! Pure covalent azides are in general explosive! Use of pure
N3O2SN3 is not necessary, and the DCM solution of N3O2SN3 was applied
in this work. Although no explosions occurred during this work, safety
precautions are strongly recommended.
[3]
[4]
a) K. Ouyang, W. Hao, W.X. Zhang, Z. Xi, Chem. Rev. 2015, 115, 12045–
12090; b) Q. Wang, Y. Su, L. Li, H. Huang, Chem. Soc. Rev. 2016, 45,
1257–1272.
[21] D. C. Harrowven, S. L. Kostiuk, Nat. Prod. Rep. 2012, 29, 223–242.
[22] N. S. El Din, Acta Pharm., 1999, 49, 119–125.
a) L. Hie, N. F. F. Nathel, T. K. Shah, E. L. Baker, X. Hong, Y. F. Yang,
P. Liu, K. N. Houk, N. K. Garg, Nature. 2015, 524, 79–83; b) Y. Xia, G.
Lu, P. Liu, G. Dong, Nature 2016, 539, 546–550; c) J. B. Roque, Y.
Kuroda, L. T. Göttemann, R. Sarpong, Nature, 2018, 564, 244–248; d)
H. Wang, I. Choi, T. Rogge, N. Kaplaneris, L. Ackermann, Nat. Cat. 2018,
1, 993-1001; e) J. B. Roque, Y. Kuroda, L. T. Göttemann, R. Sarpong,
Science, 2018, 361, 171–174; f) K. A. Goulas, A. V. Mironenko, G. R.
Jenness, T. Mazal, D. G. Vlachos, Nat. Cat. 2019, 2, 269–276; g) P. S.
Fier, S. Kim, K. M. Maloney, J. Am. Chem. Soc. 2019, 141, 18416–
18420; h) A. J. Smaligo, M. Swain, J. C. Quintana, M. F. Tan, D. A. Kim,
O. Kwon, Science, 2019, 364, 681–685; i) Y. Xu, X. Qi, P. Zheng, C. C.
Berti, P. Liu, G. Dong, Nature, 2019, 567, 373–378; j) G.W. Wang, O. O.
Sokolova, T. A. Young, E. M. S. Christodoulou, C. P. Butts, J. F. Bower,
J. Am. Chem. Soc. 2020, 142, 19006–19011; k) J. Caoꢀ, H. Wu, Q. Wang,
J. Zhu,ꢀ Nat. Chem., 2021, 13, 671–676.
[23] a) Wijtmans, R.; Vink, M. K. S.; Schoemaker, H.E.; van Delft, F. L.;
Blaauw, R. H.; Rutjes, F. P. J. T. Synthesis 2004, 641–662; b) F. Crestey,
M. Witt, J. W. Jaroszewski, H. Franzyk, J. Org. Chem. 2009, 74, 5652–
5655.
[24] W.-J. Bai, J. G. David, Z.-G. Feng, M. G. Weaver, K.-L. Wu, T. R. R.
Pettus, Acc. Chem. Res. 2014, 47, 3655–3664.
[25] a) K. R. Campos, Chem. Soc. Rev. 2007, 36, 1069–1084; b) E. A.
Mitchell, A. Peschiulli, N. Lefevre, L. Meerpoel, B. U. W. Maes, Chem.
Eur. J. 2012, 18, 10092–10142.
[26] a) W. Chen, L. Ma, A. Paul, D. Seidel, Nat. Chem. 2018, 10, 165–169; b)
A. Paul, D. Seidel, J. Am. Chem. Soc. 2019, 141, 8778–8782.
[27] F. Zhang, D. R. Spring, Chem. Soc. Rev. 2014, 43, 6906–6919.
[28] a) H. E, O'neal, S. W. Benson, J. Phy. Chem., 1968, 72, 1866–1887; b).
L. J. Johnston, J. C. Scaiano, Chem. Rev., 1989, 89, 521–547.
[29] H. Lu, H. Jiang, Y. Hu, L. Wojtas, X. P. Zhang, Chem. Sci. 2011, 2, 2361–
2366.
[5]
[6]
A. M. Szpilman, E. M. Carreira, Angew. Chem. 2010, 122, 9786–9823;
Angew. Chem. Int. Ed. 2010, 49, 9592–9628; b) T. Cernak, K. D. Dykstra,
S. Tyagarajan, P. Vachal, S. W. Krska, Chem. Soc. Rev. 2016, 45, 546–
57; c) Y. Hu, D. Stumpfe, J. Bajorath, J. Med. Chem. 2017, 60, 1238–
1246; d) B. Mahjour, Y. Shen, W. Liu, T. Cernak, Nature. 2020, 580, 71–
75.
Shi group in 2007 reported a nickel catalyzed oxygen-atom deletion
reaction, featuring as a highly economic route to construct sp3C− sp3C
bonds however, the scope of products is quite limited and most of them
are limited to symmetric 1,2-dinaphthalenylethane derivatives. See: Z. C.
Cao, Z.J. Shi, J. Am. Chem. Soc. 2017, 139, 6546–6549.
5
This article is protected by copyright. All rights reserved.

10.1002/anie.202107356
Angewandte Chemie International Edition
COMMUNICATION
N-atom deletion from N-heterocycles via N-sulfonylazidonation, Curtius-type rearrangement and rearrangement of 1,2-diazene
intermediates is described. It provides a unique opportunity to achieve ring contraction of (n+1)-membered N-heterocycles to n-
membered cycles.
6
This article is protected by copyright. All rights reserved.