Metal-free aza-Claisen type ring expansion of vinyl aziridines: An expeditious synthesis of seven membered N-heterocycles

Article abstract of DOI:10.1039/c8ob03029d

A metal-free approach for the synthesis of 7-membered aza-heterocycles has been developed by the intermolecular [5 + 2] cycloaddition of non-activated vinylaziridines and alkynes. This method has a broad substrate scope under mild reaction conditions to a

Full text of DOI:10.1039/c8ob03029d

Organic &
Biomolecular Chemistry
View Article Online
View Journal
COMMUNICATION
Metal-free aza-Claisen type ring expansion of vinyl
aziridines: an expeditious synthesis of seven
membered N-heterocycles†
Cite this: DOI: 10.1039/c8ob03029d
Received 5th December 2018,
Accepted 4th January 2019
Deepak Singh and Hyun-Joon Ha
*
DOI: 10.1039/c8ob03029d
rsc.li/obc
A metal-free approach for the synthesis of 7-membered aza-het- sation,5j–r and metal-catalyzed cycloaddition (Scheme 1).6–8
erocycles has been developed by the intermolecular [5 + 2] cyclo- Among all available strategies, the metal-mediated hetero
addition of non-activated vinylaziridines and alkynes. This method [5 + 2] cycloaddition is one of the good tools that lead to an
has a broad substrate scope under mild reaction conditions to azepine framework. Wender et al. did pioneering work for the
afford structurally diverse 7-membered N-heterocycles in high synthesis of azepines by [5 + 2] cycloaddition of cyclopropyl
yield up to 92%.
imines and alkynes using [Rh(CO)2]Cl as a catalyst.6e However,
these protocols require high temperature, high loading of a
toxic metal catalyst, and the use of a specific directing group
in the substrate. Recently, vinyl aziridine as a nitrogen-contain-
ing three membered ring along with an external functional
group was used to access the larger N-heterocycles (Scheme 1).
The highly strained three membered ring, the electron-with-
drawing nature of nitrogen, and the presence of an external
multiple bond make this substance to participate in various
chemical transformations. Among them, the [3 + 2], [5 + 2] and
[4 + 3] cycloaddition reactions of vinyl aziridines with alkenes
and alkynes were a commonly used protocol for the synthesis
Cycloaddition reaction is one of the most prominent, atom
economical protocols for the construction of structurally
complex carbocycles, heterocycles and natural products from
readily available materials.1 The cycloaddition strategy allows
for multiple carbon–carbon or carbon–heteroatom bonds to be
generated by the way of the ring expansion of the small ring
system along with the involvement of additional functionality
present in the substrate, which is tedious to achieve by conven-
tional reactions.1,2 Numerous reports are available in the litera-
ture describing the synthesis of relatively stable five and six
membered cyclic compounds by a cycloaddition reaction.2
However, there are relatively few reports on the assembling of
a 7-membered ring especially N-heterocycles, by the cyclo-
addition strategy. This is due to its instability, nonbonding
interaction, and the entropy factor. There is significant interest
in developing an efficient and selective method to prepare
7-membered N-heterocycles (azepines), due to their presence
as a core moiety in natural products and pharmaceuticals
and their interesting biological profiles.3 The 7-membered
N-heterocycles, azepines, are also utilized as unique building
blocks on which structurally complex molecules such as
glucosepane and iboxyphylline are assembled.4 However, very
limited synthetic methods are available to access the azepine
heterocycles. These include olefin metathesis,5a–d ring expan-
sion,5e,f radical cyclisation,5g–i transition metal-catalyzed cycli-
Department of Chemistry, Hankuk University of Foreign Studies, Yongin, 17035,
Korea. E-mail: hjha@hufs.ac.kr; Tel: +82-31-330-4659
†Electronic supplementary information (ESI) available: Experimental details and
1H NMR and 13C NMR spectra of all compounds. See DOI: 10.1039/c8ob03029d
Scheme 1 Formal [5 + 2] cycloaddition of vinyl aziridines with alkynes.
This journal is © The Royal Society of Chemistry 2019
Org. Biomol. Chem.

View Article Online
Communication
Organic & Biomolecular Chemistry
of pyrrolidine and azepine compounds. Zhang’s group has
Initially a reaction of 1a (1.00 mmol) and 2a (1.5 mmol)
reported the synthesis of azepines by [5 + 2] and [4 + 3] cyclo- with BF3·OEt2 (1.2 mmol) under a nitrogen atmosphere in
addition of vinyl aziridines with alkynes.6d,7a However, these toluene for 12 hours gave rise to the desired 7-membered
methods require a very expensive and toxic transition metal azepine 3a in 62% yield. The yield was further improved by
catalyst and specific functionalities in the starting substrates changing the solvents and it was found that the reaction pro-
such as benzo-fused activated aziridines with an electron-with- duced the excellent yield of 72% by using CH2Cl2 as the
drawing group at the ring nitrogen and benzylic activation. solvent. The comparative studies using other Lewis acids such
The activated vinyl aziridine was decomposed under acidic as CeCl3, HBF4, FeCl3 and HSbF6 did not improve the reaction
conditions for [5 + 2] cycloaddition in the presence of Lewis yields. We have also attempted the reaction of 1a and 2a by
acids such as AgSbF6, FeCl3, and Sc(OTf)3, even though these use of a catalytic amount of BF3·OEt2 (20 mol%). This resulted
conditions are well documented for the [3 + 2] cycloaddition in a decrease in yield with most of the starting material
reaction of phenylaziridines with alkynes.6d The ring expan- unreacted. In the absence of a Lewis acid the reaction did not
sion has a big disadvantage in that there is great difficulty proceed at all. This demonstrates the crucial role of Lewis
generating the anion for initiation. Regardless of the method acids in this reaction (see, Table S1, ESI†).
available, all aziridines used till date are “activated” bearing
Based on the optimized reaction conditions, the character-
electron-attracting substituents at the ring nitrogen such istics and the reaction scope were investigated to explore the
as sulfones and phthalate, which are difficult to remove.6,7 synthesis of structurally diverse azepines with various aziri-
Moreover, the chemistry of “activated” aziridines is different dines and alkynes depicted in the reaction as starting
not only in the ring strain energy but also in the method for materials (Table 1).
achieving ring openings and ring transformations.8 These
This synthesis takes advantage of the non-activated aziri-
rings are easily opened or rearranged without the assistance of dines with diverse substituents at R1. Several different elec-
any additional additive due to the highly activated aziridine tron-donating groups in R1 such as phenyl ethyl (3a, 3r, 3t, 3v
ring with
a
narrow scope of regiochemical pathway.8 and 3w), benzyl (3b, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3q, 3s and 3u),
Furthermore, introducing diverse groups at the ring nitrogen dimethoxy benzyl (3c) and p-t-butyl benzyl (3d) in the aziridine
is highly limited. Therefore, utilization of “non-activated” ring nitrogen afforded the final products with the aforemen-
aziridine9b provides an exceptionally good advantage in carry- tioned groups in high yields without much change in reactiv-
ing out the reaction with structurally diverse starting materials. ity. The alkyl chain represented by the dodecyl group in R1
But its chemistry is tough to carry out owing to the intrinsic also gave rise to the product (3l) in 76% yield without any
low reactivity of the ring opening reactions compared to those difficulty. All other cases with R1 as the primary, secondary,
of the “activated” aziridine. Over the last three decades, our and tertiary aliphatic group and cyclohexyl as the alicyclic
group has been highly engaged in exploring the chemistry of group are more or less similar in the formation of products in
non-activated aziridines by ring opening, cyclisation and cyclo- the yield range of 76–86% (3m, 3n, 3o and 3p). The phenyl
addition for synthesis of various natural products and hetero- substituent at R2 drastically increased the reaction yield to
cyclic compounds.9
92% (entry 3e). A similar result was obtained by starting with
In this communication, we describe a metal-free and aziridine and other substituted phenyl groups at R2 bearing
reliable synthetic method for the preparation of a 7-membered 4-methoxy and 4-bromo substituents, which yielded the pro-
aza-heterocycle that starts from Lewis acid mediated formal [5 ducts 3f and 3g in 88% and 90%, respectively. The formation
+ 2] cycloaddition of non-activated aziridines with alky- of the product in high yield with the aryl substituent R2 stems
nes.9b,10a Mechanistically, this synthetic method is based on from the stability of the starting material due to conjugation.
the aza-Claisen type rearrangement in association with a three In addition, the lowered transition state energy involving the
membered aziridine ring leading to a [5 + 2] type electrocycli- bond-breaking step of the allylic weakened bond between N1
zation. At first, a model reaction between vinyl aziridine 1a and C2 of the aziridine leading to the aza-Claisen type cyclo-
and a diethyl but-2-ynedioate 2a was carried out under various addition at ease. The reaction was explored further by taking
conditions by which two critical huddles were overcome: the R2 as an alkyl substituent. The reaction proceeded smoothly
proper activation of non-activated aziridines and the sub- with n-propyl (3h), isobutyl (3i), and isopropyl (3j) groups at
sequent reaction with the counter alkyne leading to the aza- R2 which afforded the corresponding azepine in 78, 76 and
Claisen type rearrangement to give a 7-membered aza-hetero- 84% yields, respectively. Similarly, the aziridine having cyclic
cycle. All of the non-activated aziridines are relatively stable groups at R2 such as cyclopentyl, also reacted well to create the
compared to the activated aziridines and less reactive toward product (3k) in 81% yield without any difficulty. In addition
almost all electron-rich nucleophiles.9 Prior to the ring trans- the reactions starting from aziridines having carboxylate and
formation, those non-activated aziridines should be activated keto groups at R3 are also coupled with the counterpart to
by the use of various activators including Lewis acids. Among produce the expected 7-membered aza-heterocycles (3q, 3r, 3s)
many previously known activators, BF3·OEt2 is sometimes in relatively low yield in the range of 64–66% yields, possibly
good for the ring transformation and the ring opening reac- due to the low activity of the olefin to make a new C–C bond
tion, and it activates to a moderate extent without altering the to yield aza-heterocycles. As a counterpart of the aziridine,
substrate.9c
alkynes should be properly activated with carboxylates.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2019

View Article Online
Organic & Biomolecular Chemistry
Communication
Table 1 Exploration of the substrate scopea
Therefore, we used diethyl but-2-ynedioate (2a) in most cases.
However, ethyl but-2-ynoate (2c) with only one carboxylate was
also a good partner to create the corresponding products
(3u and 3v) in 81 and 80% yields, respectively. Instead of the
carboxylate, ethynyl methyl ketone (2d) was also reacted to give
the product 3w in 84% yield.
Interestingly, when we carried out the reaction with the
starting aziridine (2r) bearing the carboxylate at R3 we were
able to isolate the by-product 5 in 10% yield, which provides
us with a good clue regarding the reaction mechanism of the
formation of 7-membered aza-heterocycles 3r (Scheme 2). Even
though the whole reaction scheme seems to proceed through
[5 + 2] type cycloaddition to prepare 7-membered aza-hetero-
cycles, the actual reaction mechanism is stepwise including
Michael type addition and cyclization. At first, the electron-
rich nucleophilic aziridine ring nitrogen as an advantage of
non-activated aziridine was added to the alkynyl carboxylate as
a good Michael acceptor, as we observed in our early study.9c
The C–N bond formation leaves an anion at the α-position of
carboxylate 4, which is added to the vinylic position of aziri-
dine at C2 with the formation of a new C–C bond generating
7-membered aza-heterocycles, as shown in Scheme 2. Thereby
this reaction sequence appeared to be a [5 + 2] type cyclo-
addition, but the sequential reaction includes the Michael
reaction and is followed by the aza-Claisen rearrangement.
The initial adduct 4 with the newly formed C–N bond gener-
ated the acyclic product 5 in the presence of adventitious water
or during the work-up with the expected regiochemical
pathway as predicted on the basis of our early study. Once the
initial adduct 5 was generated, the cycloaddition was retarded
by relatively poor reactivity of the α-carbon bearing carboxylate,
which gave rise to the acyclic ring opened product.
Furthermore, ring expansion and the bond formation with
the breakage of the strained aziridine require relatively less
energy2i,10 compared to the corresponding cyclopropane11a
and oxirane.11b The formation of an aziridinium ion exerting
the ring expansion reaction is a key driving force that makes
this pathway most valuable compared to the other hetero [5 +
2]-cycloaddition of vinyl aziridines. This is the reason why all
hetero [5 + 2]-cycloadditions reported up to date have required
metallic catalysts with activated aziridines as a starting substrate.
In conclusion, we have developed a novel strategy for metal-
free synthesis of 7-membered aza-heterocycles by the inter-
a Reaction conditions: The reaction mixture containing vinyl aziridine
(1, 1.0 mmol), alkyne (2, 1.5 mmol), and Lewis acid (1.2 mmol) in the
specified solvent (3.0 mL) was stirred at 25 °C. Yield reported refers to
the isolated yield of compound 3.
Scheme 2 Plausible mechanism for aza-heterocycles.
This journal is © The Royal Society of Chemistry 2019
Org. Biomol. Chem.

View Article Online
Communication
Organic & Biomolecular Chemistry
molecular [5 + 2]-type-cycloaddition of non-activated vinylaziri-
dines and alkynes with a broad substrate scope of both com-
pounds under mild conditions. This method enables us to
build structurally diverse 7-membered aza-heterocycles in high
yield.
(d) P. Kulanthaivel, Y. F. Hallock, C. Boros, S. M. Hamilton,
W. P. Janzen, L. M. Ballas, C. R. Loomis, J. B. Jiang, B. Katz,
J. R. Steiner and J. Clardy, J. Am. Chem. Soc., 1993, 115,
6452; (e) S. Ohshima, M. Yanagisawa, A. Katoh, T. Fujii,
T. Sano, S. Matsukuma, T. Furumai, M. Fujiu, K. Watanabe,
K. Yokose, M. Arisawa and T. Okuda, J. Antibiot., 1994, 47,
639; (f) H. Yamaguchi, S. Sato, S. Yoshida, K. Takada,
M. Itoh, H. Seto and N. Otake, J. Antibiot., 1986, 39, 1047;
(g) J. Hu and M. J. Miller, Tetrahedron Lett., 1995, 36, 6379;
(h) R.-W. Jiang, P.-M. Hon, Y. Zhou, Y.-M. Chan, Y.-T. Xu,
H.-X. Xu, H. Greger, P.-C. Shaw and P. P.-H. But, J. Nat.
Prod., 2006, 69, 749; (i) W.-H. Lin and H.-Z. Fu, J. Chin.
Pharm. Sci., 1999, 8, 1; ( j) K. Sakata, K. Aoki, C.-F. Chang,
A. Sakurai, S. Tamura and S. Murakoshi, Agric. Biol. Chem.,
1978, 42, 457; (k) Y. Ye, G.-W. Qin and R.-S. Xu,
Phytochemistry, 1994, 37, 1205; (l) D. G. Brown,
P. R. Bernstein, Y. Wu, R. A. Urbanek, C. W. Becker,
S. R. Throner, B. T. Dembofsky, G. B. Steelman, L. A. Lazor,
C. W. Scott, M. W. Wood, S. S. Wesolowski, D. A. Nugiel,
S. Koch, J. Yu, D. E. Pivonka, S. Li, C. Thompson, A. Zacco,
C. S. Elmore, P. Schroeder, J. Liu, C. A. Hurley, S. Ward,
H. J. Hunt, K. Williams, J. McLaughlin, V. Hoesch,
S. Sydserff, D. Maier and D. Aharony, ACS Med. Chem. Lett.,
2013, 4, 46.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work is supported by the National Research Foundation
of Korea (NRF-2012M3A7B4049645 and 2014R1A5A1011165
with Centre for New Directions in Organic Synthesis).
Notes and references
1 Reviews on cycloaddition reaction: (a) T. Hashimoto and
K. Maruoka, Chem. Rev., 2015, 115, 5366; (b) G. Masson,
C. Lalli, M. Benohoud and G. Dagousset, Chem. Soc. Rev.,
2013, 42, 902; (c) H. Pellissier, Adv. Synth. Catal., 2018, 360,
1551; (d) K. E. O. Ylijoki and J. M. Stryker, Chem. Rev.,
2013, 113, 2244; (e) M. Lautens, W. Klute and W. Tam,
Chem. Rev., 1996, 96, 49; (f) C. P. Dell, Contemp. Org.
Synth., 1997, 4, 87; (g) L. Yet, Chem. Rev., 2000, 100, 2963;
(h) S. Kobayashi and K. A. Jørgensen, Cycloaddition
Reactions in Organic Synthesis, Wiley-VCH, Weinheim, 2002;
(i) F. Lopez and J. L. MascareÇas, Beilstein J. Org. Chem.,
2011, 7, 1075.
2 Recent reports on the [3 + 2] cycloaddition of aziridines:
(a) J.-J. Feng and J. Zhang, ACS Catal., 2016, 6, 6651;
(b) J. B. Sweeney, Chem. Soc. Rev., 2002, 31, 247;
(c) I. D. G. Watson, L. Yu and Y. K. Yudin, Acc. Chem. Res.,
2006, 39, 194; (d) X. L. Hou, J. Wu, R. H. Fan, C. H. Ding,
Z. B. Luo and L. X. Dai, Synlett, 2006, 181; (e) P. Dauban
and G. Malik, Angew. Chem., Int. Ed., 2009, 48, 9026;
(f) S. H. Krake and S. C. Bergmeier, Tetrahedron, 2010, 66,
7337; (g) I. Coldham and R. Hufton, Chem. Rev., 2005, 105,
2765; (h) G. S. Singh, M. Dhooghe and N. D. Kimpe,
Chem. Rev., 2007, 107, 2080; (i) A. L. Cardoso and
T. M. V. D. Pinho e Melo, Eur. J. Org. Chem., 2012, 6479;
( j) I. Ungureanu, P. Klotz and A. Mann, Angew. Chem., Int.
Ed., 2000, 39, 4615; (k) T. Ozawa, T. Kurahashi and
S. Matsubara, Synlett, 2013, 24, 2673, and references
therein; (l) P. A. Wender and D. Strand, J. Am. Chem. Soc.,
2009, 131, 7528; (m) J. Fan, L. Gao and Z. Wang, Chem.
Commun., 2009, 5021.
4 (a) M. E. Kuehne and J. B. Pitner, J. Org. Chem., 1989, 54,
4553; (b) C. Draghici, T. Wang and D. A. Spiegel, Science,
2015, 350, 294.
5 Classical methods for azepine synthesis: Ring-closing
metathesis: (a) M. E. Maier, Angew. Chem., Int. Ed., 2000,
39, 2073; (b) M. L. Bennasar, E. Zulaica and S. Alonso,
Tetrahedron Lett., 2005, 46, 7881; (c) P. Gonzalez-Perez,
L. Perez-Serrano, L. Casarrubios, G. Dominguez and
J. Perez-Castells, Tetrahedron Lett., 2002, 43, 4765;
(d) A. Deiters and S. F. Martin, Chem. Rev., 2004, 104, 2199;
Ring-expansion: (e) T. J. V. Bergen and R. M. Kellogg, J. Org.
Chem., 1971, 36, 978; (f) H. F. Motiwala, M. Charaschanya,
V. W. Day and J. Aube, J. Org. Chem., 2016, 81, 1593; and
references thereinRadicalcyclisation. (g) S. Caddick,
K. Aboutayab and R. I. West, J. Chem. Soc., Chem. Commun.,
1995, 1353; (h) L. Yet, Tetrahedron, 1999, 55, 9349;
(i) R. Guo, J. Huang, H. Huang and X. Zhao, Org. Lett.,
2016, 18, 504; Metal-catalyzed cyclization: ( j) L. F. Tietze
and R. Schimpf, Synthesis, 1993, 876; (k) H. Ohno,
H. Hamaguchi, M. Ohata, S. Kosaka and T. Tanaka, J. Am.
Chem. Soc., 2004, 126, 8744; (l) T. O. Vieira and H. Alper,
Org. Lett., 2008, 10, 485; (m) I. Nakamura, M. Okamoto,
Y. Sato and M. Terada, Angew. Chem., Int. Ed., 2012, 51,
10816; (n) Z. Shi, T. O. Grohmann and F. Glorius, Angew.
Chem., Int. Ed., 2013, 52, 5393; (o) W. Zhu, L. Zhao and
M.-X. Wang, J. Org. Chem., 2015, 80, 12047; (p) Z. Zuo,
J. Liu, J. Nan, L. Fan, W. Sun, Y. Wang and X. Luan, Angew.
Chem., Int. Ed., 2015, 54, 15385; (q) Y.-P. Han, X.-R. Song,
Y.-F. Qiu, H.-R. Zhang, L.-H. Li, D.-P. Jin, X.-Q. Sun,
X.-Y. Liu and Y.-M. Liang, Org. Lett., 2016, 18, 940;
(r) G. Yin, Y. Zhu, P. Lu and Y. Wang, J. Org. Chem., 2011,
76, 8922.
3 References for azepines in natural products and pharma-
ceuticals.(a) R. K. Smalley, in Comprehensive Heterocyclic
Chemistry, Pergamon, Oxford, 1984, vol. 7, pp. 491–546;
(b) W.-H. Lin, Y. Ye and R.-S. Xu, J. Nat. Prod., 1992, 55,
571; (c) S. Shiotani, T. Kometani, K. Mitsuhasi, T. Nozawa,
A. Kurobe and O. Futsukaichi, J. Med. Chem., 1976, 19, 803;
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2019

View Article Online
Organic & Biomolecular Chemistry
Communication
6 Azepines by 5 + 2 cycloaddition. (a) E. L. Stogryn and
S. J. Brois, J. Am. Chem. Soc., 1967, 89, 605;
(b) S. Baktharaman, N. Afagh, A. Vandersteen and
A. K. Yudin, Org. Lett., 2010, 12, 240; (c) A. Hassner,
R. DÏCosta, A. T. McPhail and W. Butler, Tetrahedron Lett.,
1981, 22, 3691; (d) J.-J. Feng, T.-Y. Lin, C.-Z. Zhu, H. Wang,
H. H. Wu and J. Zhang, J. Am. Chem. Soc., 2016, 138, 2178;
(e) P. A. Wender, T. M. Pedersen and M. J. C. Scanio, J. Am.
Chem. Soc., 2002, 124, 15154; (f) M.-B. Zhou, R.-J. Song,
C.-Y. Wang and J.-H. Li, Angew. Chem., Int. Ed., 2013, 52,
10805; (g) Y. Yang, M.-B. Zhou, X.-H. Ouyang, R. Pi,
R.-J. Song and J.-H. Li, Angew. Chem., Int. Ed., 2015, 54,
6595; (h) R. Shenje, M. C. Martin and S. France, Angew.
Chem., Int. Ed., 2014, 53, 13907; (i) C. Hu, R.-J. Song,
M. Hu, Y. Yang, J.-H. Li and S. Luo, Angew. Chem., Int. Ed.,
2016, 55, 10423; ( j) J.-J. Feng, T.-Y. Lin, H.-H. Wu and
J. Zhang, Angew. Chem., Int. Ed., 2015, 54, 15854;
(k) J.-J. Feng, T.-Y. Lin, H.-H. Wu and J. Zhang, J. Am. Chem.
Soc., 2015, 137, 3787; (l) N. Iqbal and A. Fiksdahl, J. Org.
Chem., 2013, 78, 7885; (m) L. Cui, L. Ye and L. Zhang,
Chem. Commun., 2010, 46, 3351; (n) M. M. Montero-
Campillo, E. M. Cabaleiro-Lago and J. Rodriguez-Otero,
J. Phys. Chem. A, 2008, 112, 9068.
(h) Y. Tian, Y. Wang, H. Shang, X. Xu and Y. Tang, Org.
Biomol. Chem., 2015, 13, 612; (i) H. Shang, Y. Wang,
Y. Tian, J. Fang and Y. Tang, Angew. Chem., Int. Ed., 2014,
53, 5662; ( j) S. Kim, J. Mo, J. Kim, T. Ryu and P. H. Lee,
Asian J. Org. Chem., 2014, 3, 926; (k) K. Liu, H.-L. Teng and
C.-J. Wang, Org. Lett., 2014, 16, 4508.
8 Azepines by [3 + 2 + 2] cycloaddition. (a) M.-B. Zhou,
R.-J. Song and J.-H. Li, Angew. Chem., Int. Ed., 2014, 53,
4196; (b) T. Li, F. Xu, X. Li, C. Wang and B. Wan, Angew.
Chem., Int. Ed., 2016, 55, 2861.
9 (a) C. Yu, M. A. Shoaib, N. Iqbal, J. S. Kim, H. J. Ha and
E. J. Cho, J. Org. Chem., 2017, 82, 6615; (b) S. Stankovic,
M. D′hooghe, S. Catak, H. Eum, M. Waroquier,
V. V. Speybroeck, N. D. Kimpe and H. J. Ha, Chem. Soc.
Rev., 2012, 41, 643; (c) N. N. Yadav, H. Jeong and H. J. Ha,
ACS Omega, 2017, 2, 7525; (d) J. Dolfen, N. N. Yadav,
N. D. Kimpe, M. D’hooghe and H. J. Ha, Adv. Synth. Catal.,
2016, 358, 3483; (e) H. J. Jung, S. Kim, H. Eum, W. K. Lee
and H. J. Ha, Tetrahedron, 2017, 73, 5993; (f) S. I. Son,
W. K. Lee, J. Choi and H. J. Ha, Green Chem., 2015, 17,
3306; (g) H. Lee, J. H. Kim, W. K. Lee, J. H. Jung and
H. J. Ha, Org. Lett., 2012, 14, 3120.
10 (a) G. Callebaut, T. Meiresonne, N. D. Kimpe and
S. Mangelinckx, Chem. Rev., 2014, 114, 7954; (b) Aziridines
and Epoxides in Organic Synthesis, ed. A. K. Yudin, Wiley-
VCH, Weinheim, 2006; (c) B. P. Woods, M. Orlandi,
C. Y. Huang, M. S. Sigman and A. G. Doyle, J. Am. Chem.
Soc., 2017, 139, 5688; (d) X. E. Hu, Tetrahedron, 2004, 60,
2701; (e) C. Y. Huang and A. G. Doyle, Chem. Rev., 2014,
114, 8153; (f) H. Ohno, Chem. Rev., 2014, 114, 7784.
7 Azepines by 4 + 3 cycloaddition of vinyl aziridines.
(a) C. Z. Zhu, J. J. Feng and J. Zhang, Angew. Chem., Int. Ed.,
2017, 56, 1351; (b) N. D. Shapiro and F. D. Toste, J. Am.
Chem. Soc., 2008, 130, 9244; (c) H. Liu, X. Li, Z. Chen and
W.-X. Hu, J. Org. Chem., 2012, 77, 5184; (d) G. Zhan,
M.-L. Shi, Q. He, W. Du and Y.-C. Chen, Org. Lett., 2015, 17,
4750; (e) C. S. Jeffrey, K. L. Barnes, J. A. Eickhoff and
C. R. Carson, J. Am. Chem. Soc., 2011, 133, 7688; 11 (a) M. S. Gordon, J. Am. Chem. Soc., 1980, 102, 7419;
(f) A. Acharya, J. A. Eickhoff and C. S. Jeffrey, Synthesis,
2013, 45, 1825; (g) E. E. Schultz, V. N. G. Lindsay and
R. Sarpong, Angew. Chem., Int. Ed., 2014, 53, 9904;
(b) K. M. Morgan, J. A. Ellis, J. Lee, A. Fulton, S. L. Wilson,
P. S. Dupart and R. J. Dastoori, J. Org. Chem., 2013, 76,
8922.
This journal is © The Royal Society of Chemistry 2019
Org. Biomol. Chem.