Unprecedented 1,3-: Tert -butyl migration via the C-N single bond scission of isonitrile: An expedient metal-free route to N -sulfonyl amidines

Article abstract of DOI:10.1039/d0cc02430a

An unprecedented 1,3-migration of the tert-butyl group was observed while reacting tert-butyl isonitrile with N,N-dibromoaryl sulfonamides and nitrile. The reaction involves the simultaneous C-N single bond scission of isonitrile and the migration of the tert-alkyl group to the adjacent unsaturated nitrogen centre of the nitrile precursor, which eventually results in the formation of N-sulfonyl amidine. This method constitutes a new route for sulfonyl amidine, which does not rely on transition metals. The protocol exhibits a significant advantage in terms of substrate scope and additionally offers an easy synthesis route to guanidine molecules.

Full text of DOI:10.1039/d0cc02430a

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Unprecedented 1,3-tert-Butyl migration via C-N single bond
scission of isonitrile: An expedient metal-free route to N-sulfonyl
amidines
Received 00th January 20xx,
Accepted 00th January 20xx
Debashish Mishra, Arun Jyoti Borah, Pinakinee Phukan, Debojit Hazarika and Prodeep Phukan*
DOI: 10.1039/x0xx00000x
www.rsc.org/
An unprecedented 1,3-migration of tert-butyl group was dibromosulfonamides,7 herein, we disclose an unprecedented
observed while reacting tert-butyl isonitrile with N,N- migration of tert-butyl group of isocyanaide from a carbamimidic
dibromoaryl sulfonamides and nitrile. The reaction involves bromide intermediate while reacting tert-alkyl isonitrile and N,N-
simultaneous C-N single bond scission of isonitrile and migration dibromoaryl sulfonamides in presence of nitriles and water. This
of the tert-alkyl group to adjacent unsaturated nitrogen centre of method provides a complementary route to N-sulfonyl amidines,
the nitrile precursor which eventually results in the formation of which does not rely on transition metals (Fig 1b).
N-sulfonyl amidine. Formation of a carbamimidic bromide
a) Cleavage of C-N single bond of isocyanaides:
species at the intermediate stage of the reaction has been
Me
M
path a
R
path b
speculated which was confirmed by LC-MS study of the reaction
mixture. This method constitutes a new route for sulfonyl
amidine which does not rely on transition metals. The protocol
exhibits significant advantage in terms of substrates scope and
additionally offers easy synthesis of guanidine molecules.
t
or t
tBu
C
N C
R-CN
Bu
Bu
N
M C N
Me
Me
Me PdLn
Me
Me
Me
Pd(II),Ar
path c
H
Me
Me
tBu
C
C
Ar-CN
N
Ar
b) Present work: Metal free C-N bond cleavage via t-Bu group migrtaion of isocyanide
Me
Me
The isocyanides are extensively used in synthetic chemistry because
of their electrophilic divalent carbon and nucleophilic zwitterionic
nature. Ever since the Passerini and Ugi reactions were discovered,1
the isocyanide based multicomponent reactions exhibit wide spread
applications in the synthesis of various nitrogen-containing
heterocycles via C-C, C-N, and C-O bond formation reactions.2
Several types of reactions involving isocyanides such as nucleophilic
attack, electrophilic addition, imidoylation reactions, and oxidation
etc have been reported. Transition metal catalyzed scission of C-N
single bond of isocyanides has been utilized to generates metal
cyanides.3 The formation of a highly thermodynamically stable C-
bound metal cyanides drives the dealkylation either by hemolytic or
heterolytic C-N bond cleavage (Fig 1a, path a). Transition metal
catalyzed insertion of isocyanide to C-H bond can readily cleave the
C-N bond affording cyano product (Fig 1a, path c).4 The stability of
the tertiary carbon cation is the driving forces to break the C-N bond.
An alternative pathway for the cleavage of isonitrile C-N bond has
also been reported where a radical attacks on tert-butyl isonitriles to
facilitate the formation of an imidoyl radical species, which
subsequently get fragmented into a nitrile and a tert-butyl radical
(Fig 1a, path b).5 So far, no report is available in literature for
simultaneous cleavage of C-N single bond of isonitrile and migration
of tert-butyl counterpart to adjacent atom in a cascade process.
Recently, Yamashita et al reported an elegant approach for the
cleavage of isonitrile carbon–nitrogen triple bond using a diborane
reagent, where the migration of tert-butyl group to adjacent boron
centre was observed.6 In continuation of our work on N,N-
Me
Me
Me
-BrCN
Me Me
N
Me
Me
N
C
N
Br
C
H
Ar-SO2-NBr2
N
C
N
CH3
C
CH3
H2O, CH3CN
K2CO3
H-shift
SO2Ar
N
SO2Ar
H
an unprecedented tert-butyl group migration
good functional group tollerance
catalyst free, high efficiency and product yield
c) Sulfonyl amidine as bioactive pharmacophores
O
R
S
O
1O
Me
N
N
Me
O
NH2
R1
O
Me
Me
O
S
R2
O
N
R3
O
NH
N
O
S
S
X
N
NHR
2 O
O
O
O
N
N
O
Me
Me
Me
N
H
NR1R2
O
Me
N
N
O
Antiproliferative
Antiproliferative
Antiresorptive
Antitumor
d) Synthesis of N-sulfonyl amidine from Sulfonamides
O
S
R
R2
O
N
O
metal
[Cu]
N
R1
R3
O
R3
N
R
S
NH2
R1
ynamine
intermediate
Stahl (2015)
carbenoid
N
O
R2
S
R
Wan (2017, 2018 )
O
e) Synthesis of N-sulfonyl amidine from sulfonyl azide
O
S
Ar
O
Ar
O
N
S
[Ag]
[Rh]
O
NH
Enamine
Intermediate
R1
NHR
carbodiimide
intermediate
HN
R
Zhang (2017 )
O
O
Bi (2019 )
S
N3
Ar
R2
R3
N
R1
R2
[Pd], CO
[Cu]
N
R1
O
N
O
R
O
ketenimine
intermediate
N
S
sulfonyl isocyante
intermediate
Ar
S
Ar
Chang (2005, 2008 )
O
Odell (2017 )
Department of Chemistry, Gauhati University,
Guwahati, Assam, India
E-mail: pphukan@yahoo.com; pphukan@gauhati.ac.in
Fig 1: Cleavage of C-N bond of isonitrile and synthesis of N-
sulfonyl amidine
This journal is © The Royal Society of Chemistry 2020
J. Name., 2020, 00, 1-4 | 1
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Journal Name
Amidine derivatives, due to their profound biological and
We have recently established an elegant proVtoiecwoAlrticfloerOntlihnee
pharmacological activities, receive diverse applications in medicinal synthesis of guanidine derivatives by reDacOtIi:n1g0.1N03,N9/-Dd0ibCrCo0m2o4a3r0yAl
and synthetic chemistry.8 The use of sulfonyl amidines as bioactive sulfonamides with isonitrile in presence of an amine.7j Accordingly,
pharmacophores (Figure 1c) with antitumor,9 antiresorptive,10 and the reaction of TsNBr2 (1a), tert-butyl isonitrile (2a) and acetonitrile
antiproliferative11 properties has led to numerous new synthetic (3a) was chosen for initial studies to establish the optimum reaction
developments. Several reports disclosed the utility of sulfonamide condition. Results are outlined in Table 1. It was found that the
(Fig 1d) and sulfonyl azides (Fig 1e) in catalytic synthesis of N- simple combination of TsNBr2 (1 equiv) and isonitrile (1 equiv) in
sulfonyl amidines in presence of an amine. Stahl et al. had reported a acetonitrile (2 mL) in the presence of a weak base K2CO3 (2 equiv)
three-component aerobic oxidative coupling of sulfonamides, afforded N-tert-butyl-N'-tosylacetimidamide in 64% yield within a
terminal alkynes, and amines catalyzed by Cu(OTf)2 via an ynamine short period at room temperature (Table 1, entry 1). The use of 1
intermediate.12 Tertiary or secondary amide ylides triggered by metal equivalent of acetonitrile was found to be promising as it did not
carbenoid species can react with sulfonamides to produce N-sulfonyl alter the yield significantly (Table 1, entry 2). The reaction was then
amidines.13 Chang and co-workers had revealed that terminal alkyne, examined in presence of 1 equivalent of acetonitrile in different
sulfonyl azide, and secondary amine can be coupled in a Cu-catalytic solvents such as dichloromethane, chloroform and dichloroethane.
process to derive N-sulfonyl amidines through ketenimine However, these experiments did not produce better result even at
intermediate.14 Oxidative dehydrogenation of tertiary amine that higher temperature. We observed the formation of a small amount of
produces enamine can be subjected to a 1,3-dipolar cycloaddition carbodiimide as side product depending on the reaction condition.7j
reaction with sulfonyl azide to achieve the goal.15 Very recently Bi et Reaction at higher temperature produced significant amount of
al. reported the synthesis of sulfonyl amidine from in situ generated carbodiimide. Gratifyingly, addition of a minute amount of water in
enamine through
reaction.16 In situ generated sulfonyl isocyantes from azides through 73% (optimum yield, entry 7). However, the yield of the product
Pd-catalyzed carbonylation process undergoes cycloaddition could not be improved further by changing the concentration of
a silver-catalyzed, one-pot, four-component the reaction system (0.1 mL/mmol) improved the product yield to
a
reaction with substituted amides to produce sulfonyl amidines.17 water. When the reaction was tested by lowering the amount of base,
Rhodium(I)-catalyzed tandem reaction of sulfonyl azides with the product yield was found to be diminished (entries 9-10). The
isonitriles and boronic acids via a carbodiimide intermediate has also reaction was also screened in presence of various bases which
been found helpful to synthesize the sulfonyl amidines.18 Although produced inferior results (entries 11-13).
these works represent promising advances, it is still highly desirable
Table 2: Scope of nitrilesa
to explore novel strategy for the synthesis of sulfonyl amidines.
Conventionally the isocyanides are utilized in the synthesis of
NTs
amidines where it builds the imine moiety.19 In contrast we have
K2CO3 (2 equiv.)
But
TsNBr2
NC
RCN
N
H
R
observed the cleavage of R-N bond of isocyanide (R=tertiary- alkyl)
during the synthesis of amidine that proceed via a tert-butyl group
migration process.
H2O (50 L), rt
2a
1a
4a-r
3
NTs
NTs
NTs
But
But
But
N
Table 1: Optimization of reaction conditionsa
N
H
N
H
H
4a, 73%, 30 min
4b, 71%, 30 min
4c, 69%, 30 min
NTs
K2CO3 (2 equiv.)
But
TsNBr2
NC
CH3CN
NTs
NTs
NTs
N
Me
4a
H2O (50 L), rt
But
But
N
H
But
2a
3a
1a
N
H
N
H
H
Entry Acetonitrile / Solvent
Base (equiv)
Temp Yieldb (%)
4f, 78%, 30 min
4e, 75%, 30 min
4d, 67%, 30 min
Br
Cl
NTs
NTs
NTs
1
2
3
CH3CN (2 mL)
K2CO3 (2)
K2CO3 (2)
K2CO3(2)
RT
RT
RT
64
63
51
But
But
But
N
N
H
N
H
CH3CN (1 equiv)
H
4g, 67%, 45 min
4h, 61%, 45 min
4i, 64%, 45 min
NTs
CH3CN (1 equiv) +
DCM (2mL)
NTs
NTs
But
N
But
But
4
5
6
7
8
9
CH3CN (1 equiv) +
Chloroform (2mL)
K2CO3(2)
K2CO3(2)
K2CO3(2)
K2CO3(2)
K2CO3(2)
K2CO3(1)
K2CO3(1.5)
KF (2)
RT
RT
80
48
47
N
N
H
H
H
Cl
Cl
Br
4j, 77%, 30 min
4l, 74%, 30 min
4k, 71%, 30 min
CH3CN (1 equiv) +
DCE (2mL)
NTs
NTs
NTs
But
But
But
N
NO2
CH3CN (1 equiv) +
DCE (2mL)
Trace
73
N
N
H
H
H
NO2
4o, 58%, 60 min
Br
CH3CN (1 equiv) +
H2O (0.1mL/mmol)
RT
80
4m, 76%,30 min
4n, 63%, 30 min
NTs
NTs
NTs
But
But
N
But
CH3CN (1 equiv) +
H2O (0.1mL/mmol)
55
N
H
N
H
H
Cl
Ac
4r, 72%, 30 min
4p, 71%, 30 min
4q, 62%, 30 min
CH3CN (1 equiv) +
H2O (0.1mL/mmol)
RT
RT
RT
RT
RT
48
10 CH3CN (1 equiv) +
H2O (0.1mL/mmol)
56
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), K2CO3 (1 mmol), RCN (3,
1 equiv), H2O (50 L), rt; Isolated yield
11 CH3CN (1 equiv) +
H2O (0.1mL/mmol)
58
With the optimized conditions, the reaction was extended for
the C-N bond cleavage reaction using tert-butyl isonitrile in presence
of various nitriles (Table 2). The reaction was found to be very
effective for different nitriles with alkyl, aryl and benzyl substituents
to produce the N-sulfonyl amidines. In case of long chain alkyl
nitriles, a minor decrease in yield was observed with increasing
chain length (4a-4d). Cyclopropyl group appended on the nitrile was
12 CH3CN (1 equiv) +
H2O (0.1mL/mmol)
KHCO3(2)
Cs2CO3(2)
47
13 CH3CN (1 equiv) +
H2O (0.1mL/mmol)
[a] Reaction condition: 1a (0.5 mmol), 2a (0.5 mmol), K2CO3 (1 mmol), 30 min;
37
[b] Isolated yield.
2 | Chem. Commun., 2020, 00, 1-4
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found to be tolerable under the reaction conditions (4f). The LC-MS analysis of the reaction mixture at the intermediate stage
View Article Online
formation of the vinyl substituted amidines (4e) shows the potential reveals the presence of intermediate III in the reaction mixture (Pl.
DOI: 10.1039/D0CC02430A
of the present protocol for further synthetic modifications of the see SI). The reaction proceeds further via a 1,3-migration of tertiary
amidine products. Benzyl and aryl nitriles could also be used to butyl group and simultaneous release of BrCN species (detected in
produce the desired amidine products in moderate to high yield LC-MS) to produce the desired amidine product.
irrespective of the electronic nature and position of the substituents
Table 4: Synthesis of guanidine moleculesa
on the benzene ring (4g-4r). Additional synthetic examples
O
S
R
H
O
S
illustrating the substrate scope of N,N-dibromosulfonamides are
presented in Table 3. wide variety of N,N-dibromoaryl
Br
Br
K2CO3 (2 equiv.)
N
N
NC
+
N
CN
+
N
N
O
R
H2O (50 L),rt
A
O
1
2a
6a
7a-j
sulfonamides could be converted using tert-butyl isonitrile (2a) and
acetonitrile (3a) to corresponding N-sulfonyl amidines in high yields
(5a-5i). The structure of this particular class of amidines was further
confirmed by determining the single crystal X-ray structure of 5g
(Table 3). The halo-functionalities (F, Cl, Br) are well tolerated in
the present protocol and exhibited high reactivity highlighting the
potential of this process. We have also extended our investigations to
check the compatibility of various dibromosulfonmaides with
different nitriles in the course of the C-N bond cleavage process
(Table 3). These experiments generated a library of N-sulfonyl
amidines (5j-5q). Finally using cynamides as the nitrile source, a
variety of N-sulfonyl guanidines were synthesized very effectively
(Table 4).20 An important aspect of the present protocol is its
amenability to gram-scale applications (72% for 4a, pl. see the ESI).
F
tBu
N
Cl
tBu
tBu
N
tBu
N
HN
HN
O
O
S
HN
HN
O
S
O
O
S
S
N
N
N
N
N
O
O
O
7c, 75%
tBu
7d, 69%
tBu
7a, 81%
7b, 74%
Br
Br
tBu
N
HN
HN
O
O
S
HN
O
S
N
S
O
7g, 74%
N
N
O
O
N
N
7e, 84%
7f, 78%
Cl
O2N
MeO
tBu
tBu
N
tBu
N
HN
O
S
HN
HN
O
O
S
S
N
N
N
N
O
O
O
7h, 76%
7j, 79%
7i, 78%
[a] Reaction conditions: 1a-1j (0.5 mmol), 2a (0.5 mmol), 6a (1 equiv), H2O (50
L), K2CO3 (1 mmol), rt, 30 min; Isolated yield.
Table 3: Scope of N,N-dibromoaryl sulfonamides and compatibility
of the substratesa
K2CO3, H2O
O
O
Br
Br
K2CO3 (2 equiv.)
R1
HN
R1
O
S
S
N
NC
N C
O
+
RCN
N
C
Br
+ TsNH2
S
H2O (50 L), rt
NBr2
N
R
II
I
O
O
5a-q
2a
1
3
N
C
N
Br
C
K2CO3
-H+
1) CH3CN
Cl
Br
N
C
Br
tBu
Cl
tBu
tBu
tBu
N
C Br
CH3
Ts
HN
O
HN
O
HN
O
S
:
2) TsNH2 (II)
N
C
N
CH3
Ts
N
S
S
I
N
N
H
N
O
H
O
O
H
5a, 72%
5b, 68%
5c, 67%
III, detected in LC-MS
F
tBu
tBu
H-shift
-BrCN
H
HN
HN
HN
N
C
CH3
Ts
N
C
N
CH3
Ts
III
O
O
O
S
O
tBu-group
migrtaion
S
S
Br
N
N
N
N
O
O
H
5d, 68%
5e, 71%
5f, 70%
Scheme 1: Plausible mechanistic pathway for formation of N-
sulfonyl amidine
O2N
tBu
tBu
HN
HN
O
S
HN
O
S
N
To further confirm the involvement of nitrile in the reaction, we have
also carried out an experiment using CD3CN as the substrate which
produced corresponding deuterated product in high yield (Scheme
2). The stability of the tertiary carbon cation is the driving forces for
the migration.
N
O
O
5h, 72%
5g, 79%
tBu
tBu
MeO
tBu
tBu
HN
O
HN
O
S
O
S
O
S
O
N
N
N
O
5k, 78%
5j, 69%
5i, 70%
H3C
H3C
Br
tBu
Cl
tBu
K2CO3 (2 equiv.)
NH
N CD3
O
S
HN
HN
O
O
O
HN
O
CD3CN
NC
S
S
O
S
H2O (50 L), rt, 30 min
NBr2
S
N
N
O
O
N
O
O
1a
2a
4s, 64 %
Br
5l, 76%
5m, 71%
5n, 76%
Scheme 2: Synthesis of N-sulfonyl amidine using CD3CN
O2N
tBu
O2N
tBu
HN
O
tBu
The migration of tert-alkyl group was further established with
utilization of 1-adamantyl isocyanide (2b) and 1,1,3,3-
tetramethylbutyl isocyanide (2c). Here also the desired sulfonyl
amidine products were isolated in high yield (Scheme 3). Having
established a convenient procedure for the synthesis of amidines, we
further focused on their synthetic utility to derive highly
functionlaized amidines derivatives which are difficult to access
HN
O
HN
O
S
N
O
S
Br
S
O
N
N
O
5p, 71%
5q, 73%
5o, 70%
[a] Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), K2CO3 (1 mmol), RCN (1
equiv), H2O (50 L), rt; 30 min; Isolated yield
directly
(Scheme
4).
N-tert-
butyl-3-chloro-N'-
From the above experimental results, a plausible mechanism has
been proposed in Scheme 1. In presence of base, TsNBr2 eliminate
bromonium ion and produced an intermediate I and sulfonamide (II)
reacting with isonitrile. The subsequent reaction of the intermediate I
with CH3CN and sulfonamide (II) produced the carbamimidic
bromide intermediate III. The formation of this intermediate has
been speculated from LC-MS analysis of the reaction mixture. The
tosylpropanimidamide (11) was synthesized refluxing 4e in CH2Cl2
in presence of conc. HCl. When the compound 4e was treated with a
mixture of TMSN3 and TsNBr2, in CH3CN, corresponding vicinal
bromoazide (12) could be isolated in high yield.7d We could also
successfully transform the same compound to corresponding
azridine (13) using TsNBr2 via a nitrene transfer process.7e
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Journal Name
NC
6
7
H. Asakawa, K. H. Lee, Z. Lin and M. Yamashita, Nature Commun.,
View Article Online
H3C
H3C
K2CO3 (2 equiv.)
HN
O
S
2014, 5, 4245.
DOI: 10.1039/D0CC02430A
O
S
CH3CN
H2O (50 L), rt, 30 min
NBr2
O
N
Me
For Review: (a) I. Saikia, A. J. Borah and P. Phukan, Chem. Rev.,
2016, 12, 6837; (b) K. K. Rajbongshi, A. J. Borah and P. Phukan,
Synlett, 2016, 27, 1618; Selected examples: (c) P. Phukan, P.
Chakraborty and D. Kataki, J. Org. Chem., 2006, 71, 7533; (d) I.
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Saikia, B. Kashyap and P. Phukan, Chem. Commun., 2011, 47, 2967;
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K. K. Rajbongshi, I. Saikia, L. D. Chanu, S. Roy and P. Phukan, J.
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(a) J. V. Greenhill and P. Lue, Prog. Med. Chem., 1993, 30, 203; (b)
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O
1a
2b
NC
3a
8, 69 %
H3C
H3C
H3C
K2CO3 (2 equiv.)
CN
HN
O
O
S
O
S
H2O (50 L), rt, 30 min
N
NBr2
O
1a
1a
2b
3e
9, 73 %
H3C
K2CO3 (2 equiv.)
NH
Me
O
S
O
CH3CN
S
NC
NBr2
H2O (50 L), rt, 30 min
N
O
O
3a
2c
10, 70 %
Scheme 3: Tert-butyl group migration with 1-adamantyl and 1,1,3,3-
tetramethylbutyl isocyanide.
O
H
conc. HCl
N
N
S
DCM,Reflux
O
11, 84%
8
9
Cl
O
S
O
S
TsNBr2 , TMSN3
MeCN,rt
H
H
N
N
N
N
O
O
Br
4e
12, 81%
N3
O
S
H
K2CO3, TsNBr2
EtOAc, rt
N
N
(a) Z. L. Song, H. L. Chen, Y. H. Wang, M. Goto, W. J. Gao, P. L.
Cheng, S. L. Morris-Natschke, Y. Q. Liu, G. X. Zhu, M. J. Wang
and K. H. Lee, Bioorg. Med. Chem. Lett., 2015, 25, 2690; (b) M. –J.
Wang, Y. –Q. Liu, L. C. Chang, C. –Y. Wang, Y. –L. Zhao, X. –B.
Zhao, K. Qian, X. Nan, L. Yang, X. –M. Yang, H. –Y. Hung, J. -S.
Yang, D. -H. Kuo, M. Goto, S. L. Morris-Natschke, S. –L. Pan, C. –
M. Teng, S. –C. Kuo, T. –S. Wu, Y. –C. Wu and K.-H. Lee, J. Med.
Chem., 2014, 57, 6008.
O
NTs
13, 84%
Scheme 4: Synthesis of highly functionalized N-sulfonyl amidine
In conclusion, a new reaction pathway has been established for
simultaneous cleavage of single C–N σ-bond of isonitrile and
migration of tert-alkyl fragment via a cascade pathway. The reaction
proceeds via an carbamimidic bromide intermediate which
undergoes a 1,3-migration of tertiary alkyl group to the adjacent
unsaturated nitrogen centre along with elimination of BrCN. The
results constitute a practical, operationally simple and scalable
protocol for sulfonyl amidine via a one-pot reaction of tert-alkyl
isonitrile with N,N-dibromoaryl sulfonamides in presence of nitrile
and water. Highly functionalized sulfonyl amidines could further be
derived by synthetic manipulation of a suitable precursor.
10 (a) M. Y. Lee, M. H. Kim, J. Kim, S. H. Kim, B. T. Kim, I. H.
Jeong, S. Chang, S. H. Kim and S. Chang, Bioorg. Med. Chem. Lett.,
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S. Chang and S. H. Kim, Bioorg. Med. Chem. Lett., 2011, 21, 727.
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Kamal, Bioorg. Med. Chem. Lett., 2016, 26, 2072; (b) L. Krstulović,
D. Saftić, H. Ismaili, M. Bajić and L. Glavaš-Obrovac, Croat. Chem.
Acta, 2017, 90, 625.
12 J. Kim and S. S. Stahl, J. Org. Chem., 2015, 80, 2448.
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Commun.,2017, 53, 13256.
Financial support from SERB, India (Grant No. EMR/2016
/007883) is gratefully acknowledged. We thank SAIF, GU for
providing single crystal X-ray data and analysis. DH thanks UGC,
India for the BSR fellowship.
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2038; (b) J. Kim, S. Y. Lee, J. Lee, Y. Do and S. Chang, J. Org.
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Notes and references
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Fluorine Chem., 2000, 104, 195; (d) A. Contini, E. Erba and S.
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1
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3
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4 | Chem. Commun., 2020, 00, 1-4
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ChemComm
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DOI: 10.1039/D0CC02430A
Graphical Abstract
Unprecedented 1,3-tert-Butyl migration via C-N single
bond scission of isonitrile: An expedient metal-free
route to N-sulfonyl amidines
Debashish Mishra, Arun Jyoti Borah, Pinakinee Phukan, Debojit
Hazarika and Prodeep Phukan*
Metal-free
C-N bond cleavage
tBu-migration
N
C
N
Br
Ar-SO2-NBr2
HN
C
CH3
SO2Ar
N
C
:
C
N
CH3
N
-BrCN
H2O, CH3CN
K2CO3
SO2Ar
H-shift
H
52 examples, 58-84 %
carbamimidic bromide
intermediate
Treatment of tert-butyl isonitrile with N,N-dibromoaryl sulfonamides
and nitrile led to simultaneous C-N single bond scission of isonitrile
and migration of the tert-alkyl group to adjacent unsaturated nitrogen
centre of the nitrile precursor which eventually results in the
formation of N-sufonyl amidine.