O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 4 of 5
COMMUNICATION
Journal Name
Me3NBD3 (4.0 equiv.)
NaO Bu (4.0 equiv.)
H
Notes and references
1. (a) S. A. Lawrence, Amines: Synthesis, Properties, and
DOI: 10.1039/D0OB01054E
NH2
t
N
D
D
D
DCON(CD ) ,100 C, 15 min
Applications, Cambridge University Press, Cambridge, U.K.,
2004; (b) E. J. Barreiro, A. E. Kümmerle and C. A. M. Fraga,
Chem. Rev., 2011, 111, 5215-5246.
3
2
1a
2a-D , 86%
3
>98% D3)
(
Scheme 3 Synthesis of N-CD
3
aniline 2a-D
3
2. (a) J. Chatterjee, C. Gilon, A. Hoffman and H. Kessler, Acc. Chem.
Res., 2008, 41, 1331-1342; (b) J. Chatterjee, F. Rechenmacher
and H. Kessler, Angew. Chem. Int. Ed., 2013, 52, 254-269; (c)
Y. Chen, Chem. Eur. J., 2019, 25, 3405-3439.
Based on these deuterium-labeled results and our previous
reports on methylation reaction with R N‒BH /DMF system as the
a plausible mechanism for the
3
3
3
. (a) X. Ge, C. Luo, C. Qian, Z. Yu and X. Chen, RSC Advances, 2014,
, 43195-43203; (b) K. Natte, H. Neumann, R. V. Jagadeesh
1
5,17
methyl and methylene source,
4
present N-monomethylation of anilines was outlined in Scheme 4.
Deprotonation of primary aniline 1 by NaH generates nitrogen anion
I, which attacks the formyl group of DMF to give intermediate II.
There is an equilibrium between II and III through the intramolecular
proton shift. Elimination of a hydroxyl group in III occurs to afford
and M. Beller, Nat. Commun., 2017, 8, 1344; (c) H. Wang, Y.
Huang, X. Dai and F. Shi, Chem. Commun., 2017, 53, 5542-
5545.
. (a) S. Hayat, R. Atta ur, M. Iqbal Choudhary, K. M. Khan, W.
Schumann and E. Bayer, Tetrahedron, 2001, 57, 9951-9957;
(b) C. Chiappe, P. Piccioli and D. Pieraccini, Green Chem., 2006,
4
1
8
3 3
amidine IV. The ensuring reduction by Me N–BH affords aminal V.
8
, 277-281; (c) R. M. Yebeutchou and E. Dalcanale, J. Am.
Subsequently, base-promoted elimination of dimethylamino anion
takes place, producing imine VI. The second hydride reduction
eventually furnishes the desired N-monomethylated aniline 2. 12
Chem. Soc., 2009, 131, 2452-2453.
5
6
. T. Lebleu, X. Ma, J. Maddaluno and J. Legros, Chem. Commun.,
2
014, 50, 1836-1838.
. (a) Y. Ono, Appl. Catal. A-Gen., 1997, 155, 133-166; (b) P.
Tundo and M. Selva, Acc. Chem. Res., 2002, 35, 706-716; (c) A.
B. Shivarkar, S. P. Gupte and R. V. Chaudhari, J. Mol. Catal. A:
Chem., 2005, 226, 49-56; (d) J. Zheng, C. Darcel and J.-B.
Sortais, Chem. Commun., 2014, 50, 14229-14232; (e) Y. Li, I.
Sorribes, C. Vicent, K. Junge and M. Beller, Chem. Eur. J., 2015,
21, 16759-16763.
7. (a) S. Savourey, G. Lefèvre, J.-C. Berthet and T. Cantat, Chem.
Commun., 2014, 50, 14033-14036; (b) I. Sorribes, K. Junge and
M. Beller, Chem. Eur. J., 2014, 20, 7878-7883; (c) M.-C. Fu, R.
Shang, W.-M. Cheng and Y. Fu, Angew. Chem. Int. Ed., 2015,
54, 9042-9046; (d) L. Zhu, L.-S. Wang, B. Li, W. Li and B. Fu,
Catal. Sci. Technol., 2016, 6, 6172-6176.
O
H H
H+ shift
H
NMe2
NaH
N
NMe2
Ar NH2
Ar
II
Ar NH
O
1
I
H–
H
H
N
NMe2 reduction
N
NMe2
N
NMe2
Ar
Ar
Ar
–
HO
H
H H
OH
III
IV
V
H–
reduction
H
base
Me2N
N
H
N
H
H
Ar
Ar
H
–
H
8
. (a) J. R. Cabrero-Antonino, R. Adam and M. Beller, Angew.
Chem. Int. Ed., 2019, 58, 12820-12838; (b) K. Beydoun, T. vomꢀ
Stein, J. Klankermayer and W. Leitner, Angew. Chem. Int. Ed.,
VI
2
Scheme 4 A proposed reaction mechanism
2
013, 52, 9554-9557; (c) O. Jacquet, X. Frogneux, C. Das Neves
Gomes and T. Cantat, Chem. Sci., 2013, 4, 2127-2131; (d) Y. Li,
X. Fang, K. Junge and M. Beller, Angew. Chem. Int. Ed., 2013,
Conclusions
5
2, 9568-9571; (e) Y. Li, I. Sorribes, T. Yan, K. Junge and M.
In summary,
monomethylation of primary anilines was developed by using
DMF/Me N-BH system as the methyl source. Selective
introduction of CDH and CD H motifs was realized with high
levels of deuterium incorporation under Me ‒B /d -DMF
and Me ‒B /DMF systems, respectively. We hope this
a
new protocol for the selective N-
Beller, Angew. Chem. Int. Ed., 2013, 52, 12156-12160; (f) K.
Beydoun, G. Ghattas, K. Thenert, J. Klankermayer and W.
Leitner, Angew. Chem. Int. Ed., 2014, 53, 11010-11014; (g) E.
Blondiaux, J. Pouessel and T. Cantat, Angew. Chem. Int. Ed.,
3
3
2
2
2
014, 53, 12186-12190; (h) X. Cui, X. Dai, Y. Zhang, Y. Deng
3
N
H
3
7
and F. Shi, Chem. Sci., 2014, 5, 649-655; (i) S. Das, F. D.
Bobbink, G. Laurenczy and P. J. Dyson, Angew. Chem. Int. Ed.,
2014, 53, 12876-12879; (j) A. Tlili, X. Frogneux, E. Blondiaux
and T. Cantat, Angew. Chem. Int. Ed., 2014, 53, 2543-2545; (k)
W.-C. Chen, J.-S. Shen, T. Jurca, C.-J. Peng, Y.-H. Lin, Y.-P.
Wang, W.-C. Shih, G. P. A. Yap and T.-G. Ong, Angew. Chem.
Int. Ed., 2015, 54, 15207-15212; (l) J. Klankermayer and W.
Leitner, Science, 2015, 350, 629-630; (m) X.-F. Liu, R. Ma, C.
Qiao, H. Cao and L.-N. He, Chem. Eur. J., 2016, 22, 16489-
N D
3 3
strategy may find some applications in the synthesis and
modification of N-methyl aniline-containing bioactive
molecules.
Acknowledgement
1
6493.
9
. (a) B. N. Atkinson and J. M. J. Williams, ChemCatChem, 2014, 6,
1860-1862; (b) X. Jiang, C. Wang, Y. Wei, D. Xue, Z. Liu and J.
Xiao, Chem. Eur. J., 2014, 20, 58-63.
This work is supported by the National Natural Science
Foundation of China (21705078, 21702201, and 21971226),
Natural Science Foundation for Youth of Jiangsu Province 10. (a) M. H. S. A. Hamid, P. A. Slatford and J. M. J. Williams, Adv.
Synth. Catal., 2007, 349, 1555-1575; (b) T. D. Nixon, M. K.
Whittlesey and J. M. J. Williams, Dalton Trans., 2009, 753-762;
(BK20170972), and Nanjing Tech University (39837119).
(c) G. E. Dobereiner and R. H. Crabtree, Chem. Rev., 2010, 110,
6
2
81-703; (d) G. Guillena, D. J. Ramón and M. Yus, Chem. Rev.,
010, 110, 1611-1641; (e) S. Bähn, S. Imm, L. Neubert, M.
Conflicts of interest
There are no conflicts to declare.
Zhang, H. Neumann and M. Beller, ChemCatChem, 2011, 3,
1
853-1864; (f) Q. Yang, Q. Wang and Z. Yu, Chem. Soc. Rev.,
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins