Aromatic Aza-Claisen Rearrangement of Arylpropargylammonium Salts Generated in situ from Arynes and Tertiary Propargylamines

Article abstract of DOI:10.1002/chem.202004356

The charge-accelerated aza-Claisen rearrangement of ammonium salts serves as a key step in the construction of complex nitrogen-containing molecules. However, much less attention has been paid to the aromatic aza-Claisen rearrangement than to the aliphatic one. Herein, we report an unprecedented aromatic aza-Claisen rearrangement of arylpropargylammonium salts, generated in situ from arynes and tertiary propargylamines, delivering structurally diverse 2-propargylanilines in moderate to good yields with high regioselectivity. This rearrangement proceeds in the absence of strong bases or transition metals, is compatible with moisture and air, tolerates a wide variety of functional groups, and is amenable to forming 11- to 13-membered heterocycles with a triple bond. The 2-propargylaniline products were treated with aluminum chloride in ethanol to afford multisubstituted indoles in moderate to excellent yields. Finally, a series of deuterium-labeling experiments was performed to elucidate the reaction mechanism.

Full text of DOI:10.1002/chem.202004356

Accepted Article
Accepted Article
Title: Aromatic Aza-Claisen Rearrangement of Arylpropargylammonium
Salts Generated in Situ from Arynes and Tertiary
Propargylamines
Authors: Shi-Kai Tian, Lu Han, Sheng-Jun Li, and Xue-Ting Zhang
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To be cited as: Chem. Eur. J. 10.1002/chem.202004356
Link to VoR: https://doi.org/10.1002/chem.202004356
01/2020

10.1002/chem.202004356
Chemistry - A European Journal
FULL PAPER
Aromatic Aza-Claisen Rearrangement of Arylpropargylammonium
Salts Generated in Situ from Arynes and Tertiary
Propargylamines
Lu Han,[a] Sheng-Jun Li,[a] Xue-Ting Zhang,[a] and Shi-Kai Tian*[a,b]
[a]
L. Han, S.-J. Li, X.-T. Zhang, Prof. Dr. S.-K. Tian
Hefei National Laboratory for Physical Sciences at the Microscale, Center for Excellence in Molecular Synthesis (CAS), and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, China
E-mail: tiansk@ustc.edu.cn
[b]
Prof. Dr. S.-K. Tian
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032,
China
Supporting information for this article is given via a link at the end of the document.
Abstract: The charge-accelerated aza-Claisen rearrangement of
ammonium salts serves as a key step in the construction of complex
nitrogen-containing molecules. In contrast to the aliphatic aza-
Claisen rearrangement, much less attention has been paid to the
aromatic one. Herein, we report an unprecedented aromatic aza-
Claisen rearrangement of arylpropargylammonium salts, generated
in situ from arynes and tertiary propargylamines, delivering
structurally diverse 2-propargylanilines in moderate to good yields
with high regioselectivity. This rearrangement proceeds in the
absence of strong bases and transition metals, is compatible with
moisture and air, tolerates a wide variety of functional groups, and is
amenable to form eleven- to thirteen-membered heterocycles
embedded with a triple bond. The 2-propargylaniline products were
treated with aluminum chloride in ethanol to afford multisubstituted
indoles in moderate to excellent yields. Moreover, a series of
deuterium-labelling experiments were performed to elucidate the
reaction mechanism.
arylpropargylammonium salts, generated in situ from arynes and
tertiary propargylamines, participate in the aromatic aza-Claisen
rearrangement followed by isomerization to afford 2-
propargylanilines, which further cyclize in the presence of
aluminum chloride to yield multisubstituted indoles (Scheme
1b).[6] This new aromatic aza-Claisen rearrangement paves the
way for the use of readily available arylpropargylammonium
salts in the regiospecific construction of functionalized nitrogen-
containing molecules.
Introduction
The aza-Claisen rearrangement is a completely atom-economic
C−N bond cleavage reaction that requires much more drastic
conditions than its oxy-analogue, the Claisen rearrangement.[1]
Conversion of allyl- or propargylamines into the corresponding
ammonium salts through protonation, Lewis acid coordination, or
quaternization prior to the aza-Claisen rearrangement
significantly reduces the reaction temperature due to charge
acceleration, permitting the process to serve as a key step in the
construction of complex nitrogen-containing molecules.[2] This
charge-acceleration strategy has been frequently applied to the
aliphatic aza-Claisen rearrangement, but proves to be much less
successful for the aromatic one, which provides convenient
access to ortho-substituted anilines. While allylarylammonium
salts have been reported to participate in the aromatic aza-
Claisen rearrangement, the corresponding rearrangement of
arylpropargylammonium salts, to our knowledge, remains
unexplored (Scheme 1a). Principally, the aromatic aza-Claisen
rearrangement of arylpropargylammonium salts would produce
2-allenylanilines,[3] which might further isomerize to 2-
propargylanilines under certain conditions. To date, there are
only sporadic examples available for the synthesis of 2-
propargylanilines including Friedel−Crafts propargylation of 4-
substituted anilines[4] and multistep transformation of 2-
Scheme 1. Aromatic aza-Claisen rearrangements of ammonium salts.
Results and Discussion
In 2009, Greaney and co-workers reported an elegant charge-
accelerated
aromatic
aza-Claisen
rearrangement
of
allylarylammonium salts, generated in situ via nucleophilic
addition of tertiary allylamines to arynes, to yield 2-allylanilines
(Scheme 1a).[7,8] This aryne-mediated rearrangement was later
extended to diallylarylamines,[9] 2 ‑ vinylazetidines,[10] and 2 ‑
vinylaziridines[11] for the synthesis of various nitrogen-containing
heterocycles. In sharp contrast to tertiary allylamines,[12] much
less attention has been paid to tertiary propargylamines in the
aryne-mediated sigmatropic rearrangements.[13] In this context,
we envisioned that in situ generated arylpropargylammonium
salts would undergo similar aromatic aza-Claisen rearrangement
azidobenzophenone.[5]
Herein,
we
report
that
1
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to afford 2-allenylanilines (Scheme 1b). We initially investigated
the reaction of α-unbranched propargylamine 1a (0.2 mmol) with
benzyne, generated in situ from 2-(trimethylsilyl)phenyl triflate
(2a) (1.2 equiv) in the presence of CsF (2 equiv) in
tetrahydrofuran at 60 oC (Scheme 2).[14] Unfortunately, this
reaction gave a complex mixture and no rearrangement product
was isolated. We then performed the reaction of α-branched
propargylamine 1b under the same conditions. While a 2-
allenylaniline compound was not isolated as the desired aza-
Claisen rearrangement product, we unexpectedly isolated its
isomer, 2-proparylaniline 3b, as a single regioisomer in 22%
yield (Scheme 2).
synthesis of 2-proparylaniline 3v, wherein the N-propargyl group
participated in the aromatic aza-Claisen rearrangement, and in
sharp contrast, the N-allyl group did not at all (Table 1, entry
21).[16] The benzyne-mediated rearrangement was successfully
extended to some cyclic amines bearing an N-propargyl group
(R3 and R4 are tethered), wherein the nitrogen-containing
heterocycles did not participate in the rearrangement (Table 1,
entries 23-25). On the other hand, cyclic amines bearing an N-
alkynyl groups (R1 and R4 are tethered) smoothly underwent
ring-expansion under the standard conditions to form eleven- to
thirteen-membered heterocycles embedded with a triple bond
(Table 1, entries 27-29). Notably, the synthesis of such type of
strained benzoheterocycles has not been reported previously.
Table 1. Scope of tertiary propargylamines.[a]
Scheme 2. Early attempts.
Entry
1
3
Yield[%][b]
The above reaction we discovered represents a new type of
aromatic aza-Claisen rearrangement of ammonium salts, and
moreover, it may evolve into a unique yet powerful approach for
the synthesis of 2-propargylanilines in a regiospecific manner.[4,5]
Therefore, we decided to optimize the reaction conditions to
improve the yield for the formation of 2-proparylaniline 3b.[15] We
surveyed a few readily available fluoride sources such as NH4F,
TBAF, NaF, CsF, and KF, and found that the use of KF gave the
best yield: 37%. Gratifyingly, addition of 18-crown-6 dramatically
enhanced the yield to 65%. While no better yield was achieved
when replacing tetrahydrofuran with some other common
solvents such as acetonitrile, 1,4-dioxane, toluene, 1,2-
dichloroethane, DMF, and DMSO, performing the reaction at an
elevated temperature (80 oC) in a sealed tube enhanced the
yield to 75%. Notably, the reaction is not sensitive to moisture
and air, and untreated tetrahydrofuran (containing 0.1 wt.%
water) was directly used as the solvent. Moreover, increasing
the scale from 0.2 mmol to 2 mmol afforded 2-proparylaniline 3b
in 82% yield.
Under the optimized conditions, we observed broad
substrate scope for the tertiary propargylamines in the
rearrangement reaction using 2-(trimethylsilyl)phenyl triflate (2a)
as a benzyne precursor (Table 1). While a range of tertiary
propargylamines bearing alkyl groups at the propargylic position
participated in the aromatic aza-Claisen rearrangement to afford
the desired 2-proparylanilines as single regioisomers in
moderate to good yields (Table 1， entries1-6), a complex
mixture was observed with the substrate bearing an aryl group
at the propargylic position due to some unidentified side
reactions (Table 1, entry 7). In contrast, the reaction proceeded
well with tertiary propargylamines bearing arylacetylenyl groups
(Table 1, entries 8-19), but not well with the one bearing an
alkylacetylenyl group (Table 1, entry 20). The above reactions
provided a variety of multisubstituted 2-proparylanilines bearing
functional groups such as trifluoromethoxy, amide, sulfonamide,
halo, cyano, ketone, and ester. Although amides, sulfonamides,
and esters were reported previously to undergo addition or
insertion into arynes,[8a-d,j] in our cases they were well tolerated
due to their much lower nucleophilicity relative to tertiary amines.
Interestingly, very high site selectivity was observed in the
1
2
3
4
5
6
7
1b, R1 = Me
1c, R1 = Et
1d, R1 = n-C7H15
1e, R1 = i-Pr
1f, R1 = Cy
1g, R1 = Bn
1h, R1 = Ph
3b
3c
3d
3e
3f
75
75
64
77
67
3g
3h
47
complex
8
1i, R2 = 4-F3COC6H4
1j, R2 = 4-Me(Ac)NC6H4
1k, R2 = 4-Me(Ts)NC6H4
1l, R2 = 4-F3CC6H4
1m, R2 = 4-FC6H4
3i
81
57
44
61
72
74
50
56
85
84
48
52
9
3j
10
11
12
13
14[c]
15[d]
16
17
18
19
3k
3l
3m
3n
3o
3p
3q
3r
1n, R2 = 4-BrC6H4
1o, R2 = 4-NCC6H4
1p, R2 = 4-MeCOC6H4
1q, R2 = 4-EtO2CC6H4
1r, R2 = 3-F-4-BrC6H3
1s, R2 = 2-MeC6H4
1t, R2 = 1-Np
3s
3t
20
1u
3u
0
21
22
23
24
25
1v, R3 = Me, R4 = allyl
1w, R3 = Me, R4 = Bn
1x, R3, R4 = (CH2)4
1y, R3, R4 = (CH2)5
1z, R3, R4 = (CH2)2O(CH2)2
3v
3w
3x
3y
3z
39
34
64
62
66
2
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4[d]
5
6
2e, R = MeO
2f, R = Me
2g, R = F
3ah
3ai
3aj
69
63
52
26
1aa, n = 1
1ab, n = 2
1ac, n = 3
1ad, n = 4
3aa
3ab
3ac
3ad
0
27
55
60
50
28
29[e]
[a] Reaction conditions: 1 (0.20 mmol), 2a (0.24 mmol), KF (0.40 mmol),
18-crown-6 (0.40 mmol), untreated tetrahydrofuran (containing 0.1 wt.%
water, 1.0 mL), heated in a sealed tube at 80 oC (oil bath) for 3 h. [b]
Isolated yield. [c] The reaction was run for 1 h. [d] The structure of
compound 3p was unambiguously confirmed by X-ray crystallography
(CCDC 2021039). [e] The reaction was first run with CsF (0.40 mmol) in
acetonitrile (1.0 mL) at room temperature for 12 h, then the solvent was
evaporated, and finally, the mixture was heated in tetrahydrofuran (1.0
mL) in a sealed tube at 80 oC (oil bath) for 3 h.
7
8
2h
2i
3ak
3al
complex
0
[a] Reaction conditions: 1b (0.20 mmol), 2 (0.24 mmol), KF (0.40 mmol),
18-crown-6 (0.40 mmol), untreated tetrahydrofuran (containing 0.1 wt.%
water, 1.0 mL), heated in a sealed tube at 80 oC (oil bath) for 3 h. [b]
Isolated yield. [c] The reaction of 2d gave a 56:44 mixture of 3ag and 3af.
[d] The reaction was run for 1 h.
We then surveyed a few 2-(trimethylsilyl)aryl triflates (2b-g)
bearing either electron-donating or electron-withdrawing groups
in the reaction with tertiary propargylamine 1b and obtained the
corresponding multisubstituted 2-propargylanilines in good
yields (Table 2, entries 1-6). In line with previous reports, the
regioselectivity of amine addition highly depends on the position
of substituents in the in situ generated unsymmetrical arynes.[17]
While the amine addition to 3-methoxybenzyne or 3-
methybenzyne took place exclusively distal to the methoxy or
the methyl group and the corresponding 2-proparylaniline was
obtained as a single regioisomer (Table 2, entries 1 and 2), the
position of both propargyl and amine groups was
incommensurate with the position of the aryne triple bond,
indicating that the incipient phenyl anion is being quenched prior
to the aza-Claisen rearrangement (see below: Scheme 5). We
As aforementioned, the reaction of tertiary propargylamine
1h with benzyne precursor 2a gave a complex mixture under the
standard conditions (Table 1, entry 7). In this case we failed to
isolate the desired 2-propargylaniline 3h in a pure form, but
isolated indole 4a (Scheme 3) in 10% yield. Performing the
reaction in the presence of CsF (2 equiv) in acetonitrile at 100 oC
improved the yield to 45% for the formation of indole 4a
(Scheme 3). Similarly, the reaction of tertiary propargylamine 1b
with 2,3-naphthalyne precursor 2h under the modified conditions
afforded benzo[e]indole 4b in 57% yield. Presumably, the 2-
propargylanilines generated in both cases are amenable to
cyclize to form indoles via intramolecular nucleophilic addition of
the amino group to the alkyne group under basic conditions (see
below: Scheme 7).
observed
a complex mixture from the reaction of 2,3-
naphthalyne precursor 2h, and failed to isolate the desired
rearrangement product 3ak (Table 2, entry 7). Moreover, the
rearrangement reaction did not occur between tertiary
propargylamine 1b and 2,3-pyridyne precursor 2i (Table 2, entry
8).
Table 2. Scope of arynes.[a]
Scheme 3. Synthesis of indoles from tertiary propargylamines and arynes.
Entry
2
3
Yield[%][b]
Further studies show that the transformation of 2-
propargylanilines into substituted indoles proceeded well in the
presence of stoichiometric aluminum chloride in ethanol in a
sealed tube at 120 oC (oil bath) (Table 3).[15] A range of 2-
propargylanilines, which we obtained from the above aromatic
aza-Claisen rearrangement reaction, were smoothly converted
into the corresponding indoles in good to excellent yields (Table
3, entries 1-11). The reaction well tolerated functional groups
such as trifluoromethoxy, amide, bromo, and ketone. The
nitrogen-containing heterocycles in 2-propargylanilines 3x and
3z were opened by a chloride ion under the standard conditions
to afford functionalized indoles 5a and 5b in good yields (Table 3,
entries 12 and 13). Treatment of benzoheterocycle 3ac with
1
2b
2c
2d
3ae
3af
61
60
68
2
3[c]
3ag
3
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stoichiometric aluminum chloride afforded indoles 4n and 6a via
demethylation and ring-opening, respectively (Table 3, entry 14).
A significant portion of benzoheterocycle 3ac did not participate
in the indole formation. Instead, its propargyl group was
converted into a 1-chloroallyl group, delivering benzoheterocycle
7a embedded with a cis-double bond.
hand, the use of dry deuterated acetonitrile as the solvent
resulted in 20% and 55% deuterium incorporation at the ortho-
position of the aniline ring (X) and at the propargylic position (Y),
respectively. These results suggest that the zwitterion
intermediate, generated from an aryne and
a
tertiary
propargylamine (see below: Scheme 5), abstracts a proton from
water, which exists in a trace amount in the untreated solvent as
well as in the air, and/or from a solvent. This point is
substantially supported by the following experiment. Decreasing
the temperature for the latter reaction from 80 oC to room
temperature permitted us to isolate ammonium salt 8a-XY with
72% and 46% deuterium incorporation at the ortho-position of
the N-phenyl ring (X) and at the propargylic position (Y),
respectively (Scheme 4b).[7,18] As demonstrated by the reactions
Table 3. Transformation of 2-propargylanilines into indoles.[a]
Entry
3
4-6
Yield[%][b]
of ammonium salt
8a
shown in Scheme 4c,[19]
hydrogen/deuterium exchange should account for the deuterium
incorporation at the propargylic position (Y) either in 2-
propargylaniline 3b-XY or in ammonium salt 8a-XY. Moreover,
the acidic proton at the propargylic position in the ammonium
salt should be in part responsible for significant erosion of the
enantiopurity in the reaction of optically active propargylamine
(R)-1b with benzyne precursor 2a under the standard conditions
(Scheme 4d).[20]
1
2
3
4
5
6
7
8
9
3b
3e
3g
3i
4c, R1 = Me, R2 = Ph
94
93
90
87
70
95
92
90
91
4d, R1 = i-Pr, R2 = Ph
4e, R1 = Bn, R2 = Ph
4f, R1 = Me, R2 = 4-CF3OC6H4
4g, R1 = Me, R2 = 4-Me(Ac)NC6H4
4h, R1 = Me, R2 = 4-BrC6H4
4i, R1 = Me, R2 = 4-MeCOC6H4
4j, R1 = Me, R2 = 2-MeC6H4
4k, R1 = Me, R2 = 1-Np
3j
3n
3p
3s
3t
(a)
10
11
3ae
3ai
4l, R = 6-OMe
4m, R = 5,6-Me2
94
92
(b)
(c)
12
13
3x
3z
5a, X = CH2
5b, X = CH2O
87
78
14
3ac
24 (4n)
20 (6a)
40 (7a)
[a] Reaction conditions: 3 (0.10 mmol), AlCl3 (0.10 mmol), ethanol (0.50
mL), heated in a sealed tube at 120 oC (oil bath) for 12 h. [b] Isolated
yield.
To gain more insights into the reaction mechanism for the
above rearrangement of arylpropargylammonium salts
generated in situ from arynes and tertiary propargylamines, we
carried out a series of deuterium-labelling experiments (Scheme
4). Treatment of propargylamine 1b with benzyne precursor 2a
in deuterated tetrahydrofuran did not result in deuterium
incorporation into the rearrangement product (Scheme 4a). In
contrast, addition of deuterated water (2 equiv) to the reaction
mixture afforded 2-propargylaniline 3b-XY with 38% and 42%
deuterium incorporation at the ortho-position of the aniline ring
(X) and at the propargylic position (Y), respectively. On the other
(d)
Scheme 4. Deuterium-labelling experiments and chirality transfer.
4
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On the basis of the above experimental results and previous
relevant studies, we propose the following reaction pathway for
the synthesis of 2-propargylanilines from arynes and tertiary
propargylamines in tetrahydrofuran. As depicted in Scheme 5,
nucleophilic addition of tertiary propargylamine 1 to aryne 9,
generated in situ by fluoride-induced 1,2-elimination of 2-
(trimethylsilyl)aryl triflate 2, affords zwitterion 10, which abstracts
a proton from water to afford arylpropargylammonium salt 8.[18]
This salt participates in a charge-accelerated aromatic aza-
Claisen rearrangement, which is driven by the following
deprontonation under the basic reaction conditions to afford 2-
allenylaniline 12.[21] Finally, isomerization of the allenyl group to
Scheme 6. Additional deuterium-labelling experiments.
The above deuterium-labelling experimental results
permitted us to propose that the cyclization of 2-propargylaniline
3 proceeds either via intramolecular nucleophilic attack of the
amino group on the alkyne triple bond followed by protonation
under basic conditions or via alkyne protonation-assisted
nucleophilic addition under acidic conditions (Scheme 7).[23] The
resulting arylvinylammonium salt 13 undergoes isomerization via
deprotonation followed by protonation to afford indolium salt 14.
Selective attack of the N-alkyl groups in indolium salt 14 by a
chloride ion affords indole 4, 5, or 6.[24]
a
propargyl group under basic conditions affords 2-
propargylaniline 3.[22]
Scheme 5. Proposed reaction pathway for the synthesis of 2-propargylanilines
from arynes and tertiary propargylamines in tetrahydrofuran.
Additional deuterium-labelling experiments were carried out
for the synthesis of indoles (Scheme 6). The reaction of
propargylamine 1h with benzyne precursor 2a in deuterated
acetonitrile afforded indole 4a-ZZ' with 21% deuterium
incorporation at the benzylic position (Z and Z') (Scheme 6a). A
much higher level of deuterium incorporation (66%) was
observed when performing the reaction in the presence of
deuterated water (2 equiv). On the other hand, no deuterium
incorporation was detected in the reaction of deuterated 2-
propargylaniline 3b-Y (10% D) in the presence of aluminum
chloride in ethanol (Scheme 6b). In sharp contrast, the reaction
of 2-propargylaniline 3b in deuterated methanol afforded indole
4c-ZZ' with 76% deuterium incorporation at the benzylic position
(Z and Z'). These results suggest that the protons at the newly
generated benzylic position of the indole product originates from
external sources such as water and the solvent under either
basic or acidic conditions.
Scheme 7. Proposed reaction pathway for the transformation of 2-
propargylanilines into indoles.
Conclusion
In summary, we have established an unprecedented aromatic
aza-Claisen rearrangement of arylpropargylammonium salts,
which are generated in situ from arynes and tertiary
propargylamines. A range of tertiary propargylamines smoothly
reacted with arynes, generated in situ via fluoride-induced 1,2-
elimination of 2-(trimethylsilyl)aryl triflates, to afford structurally
diverse 2-propargylanilines in moderate to good yields with high
regioselectivity. It is noteworthy that the reaction proceeds in the
absence of strong bases and transition metals, is compatible
with moisture and air, tolerates a wide variety of functional
groups, and is amenable to form eleven- to thirteen-membered
heterocycles embedded with
a triple bond. A series of
(a)
deuterium-labelling experiments substantially support that the
reaction proceeds via aromatic aza-Claisen rearrangement of
the in situ generated arylpropargylammonium salts followed by
allenyl-to-propargyl
isomerization.
Moreover,
the
2-
propargylaniline products were treated with aluminum chloride in
ethanol to afford multisubstituted indoles in moderate to
excellent yields.
(b)
Experimental Section
5
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For experimental details, see Supporting Information.
[15] For more details on the optimization of reaction conditions, see the
Supporting Information.
[16] Serious side reactions are responsible for the unsatisfied yields in the
synthesis of 2-proparylanilines 3v and 3w. Depropargylation,
deallylation, and debenzylation occurred to afford N-methyl-N-
phenylaniline as a by-product in 10-12% yield.
Acknowledgements
We are grateful for the financial support from the National
Natural Science Foundation of China (21772182) and the
Fundamental Research Funds for the Central Universities.
[17] For examples, see: a) H. Yoshida, H. Fukushima, J. Ohshita, A. Kunai,
J. Am. Chem. Soc. 2006, 128, 11040-11041; b) Y. Zeng, L. Zhang, Y.
Zhao, C. Ni, J. Zhao, J. Hu, J. Am. Chem. Soc. 2013, 135, 2955-2958;
c) Y. Zeng, J. Hu, Chem. Eur. J. 2014, 20, 6866-6870; d) J. M. Medina,
J. L. Mackey, N. K. Garg, K. N. Houk, J. Am. Chem. Soc. 2014, 136,
15798-15805.
Keywords: amines • ammonium salts • arynes • aza-Claisen
rearrangement • indoles
[18] a) S. S. Bhojgude, T. Kaicharla, A. T. Biju, Org. Lett. 2013, 15, 5452-
5455; b) A. V. Varlamov, N. I. Guranova, T. N. Borisova, F. A. A. Toze,
M. V. Ovcharov, S. Kristancho, L. G. Voskressensky, Tetrahedron 2015,
71, 1175-1181; c) M. Hirsch, S. Dhara, C. E. Diesendruck, Org. Lett.
2016, 18, 980-983; d) Y. Gui, S.-K. Tian, Org. Lett. 2017, 19, 1554-
1557; e) G. Min, J. Seo, H. M. Ko, J. Org. Chem. 2018, 83, 8417-8425.
[19] The aromatic aza-Claisen rearrangement of ammonium salt 8a did not
occur in the absence of KF and 18-crown-6.
[1]
[2]
[3]
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10.1002/chem.202004356
Chemistry - A European Journal
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An unprecedented aromatic aza-Claisen rearrangement of arylpropargylammonium salts, generated in situ from arynes and tertiary
propargylamines, has been established, delivering structurally diverse 2-propargylanilines, which further cyclize in the presence of
aluminum chloride to afford multisubstituted indoles.
7
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