Iron-catalysed 1,2-aryl migration of tertiary azides

Article abstract of DOI:10.1039/d0cc04579a

1,2-Aryl migration of α,α-diaryl tertiary azides was achieved by using the catalytic system of FeCl2/N-heterocyclic carbene (NHC) SIPr·HCl. The reaction generated aniline products in good yields after one-pot reduction of the migration-resultant imines.

Full text of DOI:10.1039/d0cc04579a

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Iron-catalysed 1,2-aryl migration of tertiary azides
Kaijie Wei a, Tonghao Yanga,b, Qing Chena, Siyu Lianga and Wei Yu*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
1,2-Aryl migration of ,-diaryl tertiary azides was achieved by isoquinolone and 2-benzazepin-1-one.8 Encouraged by this
using the catalytic system of FeCl2/N-heterocyclic carbene (NHC) result, we envisioned that iron catalysis might enable as well
SIPrHCl. The reaction generated aniline products in good yields the 1,2-aryl migration from carbon to nitrogen when applied
after one-pot reduction of the migration-resultant imines.
to
-aryl azides. Indeed, by using a catalytic system of FeCl2
and N-heterocyclic carbene (NHC) SIPr

HCl, the expected 1,2-
Transition metal-catalysed amination reactions involving
azides as precursors have aroused great interest because of
their potential usefulness in the synthesis of amines and
amides.1 In this context, much attention has been paid
recently to the iron-catalysed aminaton reactions of azides2
because of the benefits of using iron as catalyst.3 Iron salts and
complexes can react with the azido group to form iron-imido
species, which are highly reactive as nitrene transfer agents for
aryl migration was realized; in situ reduction of the thus
formed imines by NaBH4 delivered aniline products. Herein we
report our result.
amination reactions such as C–H insertion, cycloaddition and
amination of heteroatoms.2a-d Considering the versatile
properties of nitrene species, it is expected that more reaction
patterns will be found for the iron-catalysed reactions of
azides.
1,2-Group migration from a carbon atom to a neighbouring
nitrogen atom constitutes an important type of rearrangement
that has long attracted interest of organic chemists.4,5. It has
been known that aryl substituted tertiary alkyl azides can
undergo 1,2-aryl carbon to nitrogen migration via a nitrene
intermediate or in a concerted way to afford imines at high
temperature or when irradiated by UV light.6 A 1,2-aryl radical
rearrangement of alkyl azides has also been realized under the
condition of Bu3SnH/AIBN.7 Despite these previous studies,
however, similar 1,2-aryl rearrangement by transition metal
catalysis has not been reported so far to our knowledge.
Recently, we found that iron(II) salts and complexes are
Scheme 1 Iron-catalysed 1,2-group rearrangement.
At the initial stage of this study, azide 1a was chosen as the
model compound for searching for screening of the reaction
conditions. Our previous work shows that the catalytic system
of FeCl2 and
intramolecular C–H amination of
β
-diketiminate ligand L1 can promote

-azido amides.9 Thus, this
catalytic system was firstly employed to effect the reaction of
1a. It was found that the anticipated 1,2-phenyl migration did
occur in a solvent such as chlorobenzene or 1,2-dichloroethane
(DCE) under the condition of FeCl2 and L1 at 80 oC, giving rise to
the anticipated imine product 1,3-triphenylpropan-1-imine. As
imines are liable to hydrolysis, the product 1,3-
triphenylpropan-1-imine was then reduced by NaBH4 in a one-
pot fashion to afford N-(1,3-diphenylpropyl)aniline 2a, which is
easier to purify. This one-pot procedure was employed for the
subsequent examination of reaction conditions. The result is
summarized in Table 1.
capable of promoting the 1,2-acyl migration of tertiary
-azido
ketones to afford enamides and hereocycles such as
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Table 1. Screening of reaction conditionsa
our interest to see that if NHCs ligands are capablVeietwoAprtircolemOnolitnee
the phenyl migration reaction of 1a. We chose five commonly
DOI: 10.1039/D0CC04579A
used NHCs compounds (L6-L10), and used them together with
o
FeCl2 on 1a in PhCl at 80 C (entries 7-11). It was found that
among these NHCs ligands, L6 and L9 exhibited good catalytic
performance, while L7 and L8 were ineffective. The reactions
also took place when L10 was used, but the yield was low.
Apparently, the counter anion of NHCs exerted a critical
influence under the current circumstance. Notably, using L6
and L9 delivered higher yield of 2a (87% and 86%, respectively)
Entry
1
2
3
4
5
6
7
8
Ligand
none
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L6
L6
L6
L6
L6
Time (h)
Yield (%)b
N.R.c
73
8
8
8
8
8
8
8
8
8
8
8
2
8
8
8
8
77
traced
traced
27
than using β-diketiminate ligand L1 under the otherwise same
conditions. 80 oC proved to be the optimal reaction
temperature. Under the condition of 10 mol % of FeCl2 and L6
o
in PhCl at 80 C, 1a was nearly completely consumed in 2 h
87
traced
traced
86
(entry 12) (see Table S2 in Supplementary Information (SI)).
Oxygen is detrimental to the reaction (entry 15). Apart from
FeCl2, several other ferrous salts were also tested, but they
were all found to be inferior to FeCl2 for this reaction (See
Table S1 in SI).
The optimal conditions were then applied to a variety of
,-diphenyl tertiary azides bearing different alkyl chains, and
the result is illustrated in Scheme 2. The desired 1,2-phenyl
migration reaction took place for all these substrates, and the
yields were good in general except for 1i and 1j. In the cases of
1i and 1j, no other products apart from 2i and 2j were
obtained, and both 1i and 1j were consumed completely.
Notably, the reaction can be implemented on gram scale with
little loss in yield (footnote a in Scheme 2). Triphenylmethyl
azide also reacted well under the standard conditions (2v).
However, when one phenyl group was replaced with a thienyl
or a pyridyl group, as in the case of 1w and 1x, no migration
product was generated.
9
10
11
12
13
14
15
16
35
85
69e
89f
N.R.g
N.R.h
a The reaction was conducted on 0.3 mmol scale in 2.5 mL solvent. After the
migration reaction finished, the reaction mixture was subjected to 0.6 mmol of
NaBH4 in 3.0 mL of methanol to convert the thus formed 1,3-triphenylpropan-1-
imine to 2a.b Isolated yield. c No reaction took place. d Most of 1a was recovered.
g
e
f
5 mol % of FeCl2 and L6 were used. 20 mol % of FeCl2 and L6 were used. The
reaction was conducted under the aerobic atmosphere. h In the absence of FeCl2.
Subsequent examination showed that compound 1y or 1z
was unreactive under the standard conditions, indicating that
the presence of two phenyl groups at the
-position is
necessary for the reaction to take place (Scheme 3, (1)).
Figure 1 The structures of tested ligands.
As shown in Table 1, compound 1a reacted well in
o
chlorobenzene at 80 C under the condition of 10 mol % of
FeCl2 and L1, affording 2a in 73% yield after reduction (entry 2).
Besides L1, β-diketiminate ligands L2-L5 were also tested,
among which, L2 exhibited better efficacy (entry 3), while the
other three were found to be much less effective (entries 4-6).
Control experiment shows that the reaction did not occur in
the absence of the ligand (entry 1).
Scheme 3 The reaction scope-2.
When compound 1aa, was subjected to the standard
conditions, 2aa was generated in a yield of 96%. The para-
methyl group apparently has a beneficial effect on the reaction.
To gain more insight into the impact of the substituent effect,
Encouraged by this initial success, we went on to test other
types of ligands. N-Heterocyclic carbenes (NHCs) belongs to a
unique class of stable carbene compounds that can form
ligands with a variety of transition metals.10 As such, many
iron-NHC complexes of different structure features have been
prepared and investigated concerning their catalytic
capacities.11 Recent studies demonstrate that iron-NHC
complexes can be used to catalyse various transformations
including cross coupling,12 C−X bond formation13 and
polymerization.14 Their catalytic capacity for azide-based
amination reactions has also been investigated.10c,15,16 It is to
the reactions of compounds 3a-d were investigated. The result
is presented in Scheme 4. It can be seen clearly that the
migrating capacity of the phenyl ring is largely dependent on
its electronic nature. The more electron-rich the phenyl ring,
the stronger the aptitude for it to migrate. In the case of
compound 3d, the reaction only afforded 4d, with its Ph-
migrating isomer not obtained at all.
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Scheme 2 The reaction scope-1.
The reactions were carried out on 0.3 mmol scale. Isolated yields. a The reaction was carried out on 5.0 mmol scale. b 1w was decomposed. c No reaction took place.
phenyl migration to generate the imine product (path (a)),
with the iron catalyst being released at the same time. That
compounds 1y and 1z failed to react suggests the
-carbon
atom bear a lot of positive charge at the transition state, so a
stabilizing phenyl group is required for the migration to take
place. It is even possible that a carbocation intermediate (C) is
involved during the migration (path (b)). Apart from these
mechanisms, a radical mechanism similar to that under the
condition of n-Bu3SnH and AIBN7 might also operate for the
present reactions (path (c)). Iron(III)-iminyl complexes have a
Scheme 4 Electronic effect on the reaction.
As aforementioned, iron complexes can effectively promote
the intramolecular C(sp3) H insertion of alkyl azides.17-21
–
radical character at the nitrogen atom, and thus
behave like typical nitrogen radicals to attack the phenyl ring
to give a spiro cyclohexadienyl radical . This nitrogen radical-
B might
However, under the current circumstances, no C(sp3)
–H
D
insertion was observed for the substrates that can potentially
undergo this reaction. As Boc2O was generally used in the
previously reported methods,17-21 subsequent experiment was
conducted with 1z in the presence of Boc2O to see if the
mediated aryl migration is also expected to be sensitive to
substituent effect.7
C(sp3)
–H insertion could be effected (Scheme 5). The result
showed that even without the competition of phenyl
migration, 1z still failed to undergo the anticipated
intramolecular C(sp3)
–H insertion.
Scheme 5 Reaction of 1z in the presence of Boc2O.
Recent mechanistic studies reveal that Iron(II) salts and
complexes can react with azides to form high valent iron(IV)-
imido species or radical-type iron(III)-iminyl complexes, which
would react in a way analogous to nitrenes.2a-d According to
these studies as well as the previous reports on the 1,2-aryl
migration of azides, a plausible mechanism is proposed to
Scheme 6 Proposed reaction mechanism.
account for the aryl migration of compounds
shown in Scheme 6, might first react with the in situ formed
iron-NHC complex to form an iron-imido species or an
iron(III)-iminyl species , which would then undergo 1,2-
1 (and 3). As
Scheme 7 Preparation of phenanthridines.
1
A
This method can be applied to the preparation of
phenanthridines. As such, when 9-azidofluorenes 6a and 6b
B
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7
8
S. Kim and J. Y. Do, J. Chem. Soc. Chem. Commun., 1995,
were used as the substrates, phenanthridines 7a and 7b were
generated in yield of 55% and 59%, respectively (Scheme 7).
The yields are much higher than those obtained under the
condition of n-Bu3SnH and AIBN.7
In conclusion, we have demonstrated that the catalytic
system of FeCl2/NHC SIPrHCl (L6) can enable diphenyl tertiary
azides to be converted to imines via 1,2-phenyl migration.
One-pot reduction of the thus formed imines by NaBH4
provides aniline products in high yield. Further study is
undergoing in our lab to elucidate the mechanistic issues as
well as to exploit the catalytic capacity of FeCl2/NHC system for
other types of azide-involved amination reactions.
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DOI: 10.1039/D0CC04579A
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Table of contents
Iron-catalysed 1,2-aryl migration of tertiary azides
Kaijie Wei, Tonghao Yang, Qing Chen, Siyu Liang and Wei Yu*
(1) FeCl2 (10 mol %)
L
(10 mol %)
Ph
Ph
PhCl, N2, 80 oC
N
N
dipp
dipp
Ph
Ph
N3
R
(2) NaBH4, MeOH
R
N
Cl
H
L
1,2-Carbon to nitrogen aryl migration of ,-diaryl tertiary azides was realized by
using FeCl2 and N-heterocyclic carbene SIPrHCl as catalyst.