JOURNAL PRE-PROOF
3
Scheme 2. Substrate Scope of the Isocyanates.
the reaction of tosyl isocyanate and 2-(trimethylsilyl)phenyl
triflate, tosyl amine 5a was formed first via hydrogen abstraction
under the diarylation conditions.
R1
R1
CsF (3.0 equiv.)
O
TfO
R2
C
+
N
CH3CN (0.1 M), 100 oC, 14 h
Conclusion
R2
2
TMS
2
N
(1.2 equiv.)
1b 1e
or
(1.0 equiv.)
4
In conclusion, we describe a facile, transition-metal free
strategy to prepare diarylamine derivatives via the coupling of
arynes with isocyanates. This work demonstrates that isocyanates
are appropriate coupling partners for this transformation, and a
diverse range of functional groups on the benzynes and
isocyanates are tolerated under the present reaction conditions.
The exemplified diversity of C-N bond formation via diarylation
provides a new route to access potential materials and bioactive
compounds. Further investigations to develop effective, efficient
coupling partners for this diarylation are in progress.
R1 = OMe (
OCH3
OCH3
OCH3
1b)
O
O
S
O O
S
O
S
O
2
2
2
N
N
N
a
a
a
4a
4c
, 80%
4b
, 95%
, 91%
H3C
F
OCH3
OCH3
OCH3
CH3
F
H3CO
2
2
2
N
N
N
H3C
a
4f
4d
4e
, 55%
, 71%
, 71%
OCH3
OCH3
Author information
H3C
F3C
†W.C.J. and D.W.H. contributed equally.
2
2
N
4g
N
a
a
, 51%
4h
, 28%
R1 = H (
1e)
CH3
Acknowledgments
O
S
O
O
O
This research was supported by the Basic Science Research
Program through the National Research Foundation of Korea
(NRF), funded by the Ministry of Science, ICT & Future
2
N
4j
S
2
N
2
N
H3C
H3C
a
a
a
F
, 82%
4k
, 87%
4i
, 98%
Planning
(NRF-2015R1C1A2A01051829,
NRF-
tBu
H3CO
2018R1D1A1B07042179, NRF-2017R1A4A1015594).
2
2
2
N
N
N
4m
4n
4l
, 43%
, 40%
, 46%
F3C
F
Cl
Supplementary data
2
2
2
N
N
N
Supplementary data associated with this article can be found,
in the online version, at
a
4q
4p
, 15%
, 28%
4o
, 88%
CH3
N
2
H3C
4s
2
N
, complex mixtures
References and notes
, complex mixtures
4r
aIsocyanate (0.6 equiv.).
1.
(a) Yen, H. -J.; Liou, G. -S. Polym. Chem. 2018, 9, 3001-3018; (b)
Agarwala, P.; Kabra, D. J. Mater. Chem. A, 2017, 5, 1348-1373; (c)
Velusamy, M.; Thomas, K. R. J.; Lin, J. T.; Hsu, Y.; Ho, K. Org. Lett.
2005, 7, 1899-1902; (d) Hagberg, D. P.; Edvinsson, T.; Marinado, T.;
Boschloo, G.; Hagfeldt, A.; Sun, L. Chem. Commun. 2006, 2245-
2247; (e) Drzyzga, O. Chemosphere, 2003, 53, 809-818; (f) Tanaka,
I.; Shizuka, H.; Takayama, Y.; Morita, T. J. Am. Chem. Soc. 1970, 92,
7270-7277; (g) Rahman, D. E. A. Chem. Pharm. Bull. 2013, 61, 151-
159; (h) Suzuki, T.; Khan, M. N. A.; Sawada, H.; Imai, E.; Itoh, Y.;
Yamatsuta, K.; Tokuda, N.; Takeuchi, J.; Seko, T.; Nakagawa, H. J.
Med. Chem. 2012, 55, 5760-5773; (i) Li, H.; Guan, A.; Huang, G.;
Liu, C.-L.; Li, Z.; Xie, Y.; Lan, J. Bioorg. Med. Chem. 2016, 24, 453-
461; (j) Suzuki, T.; Imai, K.; Imai, E.; Iida, S.; Ueda, R.; Tsumoto,
H.; Nakagawa, H.; Miyata, N. Bioorg. Med. Chem. 2009, 17, 5900-
5905; (k) Wen, H.; Xue, N.; Wu, F.; He, Y.; Zhang, G.; Hu, Z.; Cui,
H. Molecules 2018, 23, 1063-1076; (l) Kozako1, T.; Mellini, P.;
Ohsugi, T.; Aikawa1, A.; Uchida, Y.-I.; Honda, S.-I.; Suzuki, T. BMC
Cancer 2018, 18, 791-801; (m) Abbot, V.; Sharma, P.; Dhiman, S.;
Noolvi, M. N.; Patelc, H. M.; Bhardwaj, V. RSC Adv. 2017, 7, 28313-
28350; (n) Abou-Seri, S. M. Eur. J. Med. Chem. 2010, 45, 4113-
4121; (o) Kumar, A.; Mishra, A. K. J Pharm Bioallied Sci. 2015, 7,
81-85.
Selected papers for Ullmann reactions: (a) Yang, K. ; Qiu, Y.; Li, Z.;
Wang, Z.; Jiang, S. J. Org. Chem. 2011, 76, 3151-159; (b) Wang, H.;
Li, Y.; Sun, F.; Feng, Y.; Jin, K.; Wang, X. J. Org. Chem. 2008, 73,
8639-8642; (c) Antilla, J. C.; Klapars, A.; Buchwald, S. L. J. Am.
Chem. Soc. 2002, 124, 11684-11688; (d) Nandurkar, N. S.;
Bhanushali, M. J.; Bhor, M. D.; Bhanage, B. M. Tetrahedron Lett.
2007, 48, 6573-6576; (e) Larsson, P.-F.; Correa, A.; Carril, M.;
Norrby, P.-O.; Bolm, C. Angew. Chem. 2009, 121, 5801; Angew.
Chem. Int. Ed. 2009, 48, 5691-5693; (f) Alakonda, L.; Periasamy, M.
Scheme 3. Proposed Reaction Mechanism.
O
R2
C
CsF
R2
+
N
TMS
2
N
OTf
H
F-
H2O
H2N R2
H
N
R2
5a
5b
H
However, the use of aliphatic or polyaromatic isocyanates led to
complex mixtures of the products 4p and 4r.
2.
On the basis of these results, we proposed a plausible pathway
for the formation of 3a, as illustrated in Scheme 3. Hydrolysis of
the isocyanate gives intermediate 5a, which then reacts with the
in situ generated aryne to furnish the N-arylation product 5b.
Then, 5b is transformed into the desired product in the presence
of CsF, followed by C-N bond coupling with another aryne. In