Organic Letters
Letter
reduction of the imines.14,18 Dehydrogenation of methanol
could occur then via barrierless interactions between the
ketone function of VI and the cesium cation in CsOMe. The
release of formaldehyde from the iron center is again
barrierless. Finally, reduction of the imine function is a
concerted mechanism with an energy barrier of 19.7 kcal.mol‑1
for aniline derivatives (see Figure S67d in the SI) and 23.1
kcal.mol‑1 for alkylamine derivatives (see Table S84 in the SI).
All these results highlight both an easier condensation of
alkylamines and a lower reducibility of the corresponding
imines. Finally, the methylated amine coordinated the iron
center but can dissociate easily to regenerate VI.
In conclusion, we have developed a general ethylation and
methylation procedure for a broad range of aliphatic and
aromatic amines using ethanol or methanol as an alkylating
reagent in the presence of a well-defined bifunctional iron
complex. This alkylation process provided alkylated amines in
high yields, in the presence of other reducible functionalities.
Both DFT calculations and experimental work unveil some key
features in this process: the lower reactivity of alkylamines
compared to anilines, the role of the hydrogen pressure and of
the base, and finally the participation of the solvent in the
synthesis of some intermediates.
Int. Ed. 2014, 53, 11010−11014. (f) Santoro, O.; Lazreg, F.;
Minenkov, Y.; Cavallo, L.; Cazin, C. S. J. Dalton Trans. 2015, 44,
18138−18144. (g) Beydoun, K.; Thenert, K.; Streng, E. S.; Brosinski,
S.; Leitner, W.; Klankermayer, J. ChemCatChem 2016, 8, 135−138.
(h) Liu, X.-F.; Qiao, C.; Li, X.-Y.; He, L.-N. Green Chem. 2017, 19,
1726−1731.
(3) (a) Zheng, J.; Darcel, C.; Sortais, J.-B. Chem. Commun. 2014, 50,
14229−14232. (b) Li, Y.; Sorribes, I.; Vicent, C.; Junge, K.; Beller, M.
Chem. - Eur. J. 2015, 21, 16759−16763. (c) Cabrero-Antonino, J. R.;
Adam, R.; Junge, K.; Beller, M. Catal. Sci. Technol. 2016, 6, 7956−
7966.
(4) (a) Sorribes, I.; Junge, K.; Beller, M. Chem. - Eur. J. 2014, 20,
̀
7878−7883. (b) Savourey, S.; Lefevre, G.; Berthet, J.-C.; Cantat, T.
Chem. Commun. 2014, 50, 14033−14036. (c) Qiao, C.; Liu, X.-F.;
Liu, X.; He, L.-N. Org. Lett. 2017, 19, 1490−1493.
(5) For selective reviews on alkylation of amine with alcohols, see:
(a) Bahn, S.; Imm, S.; Neubert, L.; Zhang, M.; Neumann, H.; Beller,
M. ChemCatChem 2011, 3, 1853−1864. (b) Yang, Q.; Wang, Q.; Yu,
Z. Chem. Soc. Rev. 2015, 44, 2305−2329. For general reviews on the
borrowing hydrogen technology, see: (c) Corma, A.; Navas, J.;
Sabater, J. Chem. Rev. 2018, 118, 1410−1459. (d) Dobereiner, G. E.;
Crabtree, R. H. Chem. Rev. 2010, 110, 681−703. (e) Guillena, G.;
́
Ramon, D. J.; Yus, M. Chem. Rev. 2010, 110, 1611−1641.
(6) (a) Michlik, S.; Hille, T.; Kempe, R. Adv. Synth. Catal. 2012,
354, 847−862. (b) Li, F.; Xie, J.; Shan, H.; Sun, C.; Chen, L. RSC
Adv. 2012, 2, 8645−8652. (c) Liang, R.; Li, S.; Wang, R.; Lu, L.; Li, F.
Org. Lett. 2017, 19, 5790−5793.
ASSOCIATED CONTENT
* Supporting Information
■
(7) (a) Huh, K.-T.; Tsuji, Y.; Kobayashi, M.; Okuda, F.; Watanabe,
Y. Chem. Lett. 1988, 17, 449−452. (b) Del Zotto, A.; Baratta, W.;
Sandri, M.; Verardo, G.; Rigo, P. Eur. J. Inorg. Chem. 2004, 2004,
524−529. (c) Naskar, S.; Bhattacharjee, M. Tetrahedron Lett. 2007,
48, 3367−3370. (d) Dang, T. T.; Ramalingam, B.; Seayad, A. M. ACS
Catal. 2015, 5, 4082−4088. (e) Yang, F.-L.; Wang, Y.-H.; Ni, Y.-F.;
Gao, X.; Song, B.; Zhu, X.; Hao, X.-Q. Eur. J. Org. Chem. 2017, 2017,
3481−3486. (f) Paul, B.; Shee, S.; Chakrabarti, K.; Kundu, S.
ChemSusChem 2017, 10, 2370−2374. (g) Choi, G.; Hong, S. H.
Angew. Chem., Int. Ed. 2018, 57, 6166−6170. (h) Maji, M.;
Chakrabarti, K.; Paul, B.; Roy, B. C.; Kundu, S. Adv. Synth. Catal.
2018, 360, 722−729. (i) Roy, B. C.; Debnath, S.; Chakrabarti, K.;
Paul, B.; Maji, M.; Kundu, S. Org. Chem. Front. 2018, 5, 1008−1018.
(j) Paul, B.; Shee, S.; Panja, D.; Chakrabarti, K.; Kundu, S. ACS Catal.
2018, 8, 2890−2896.
S
The Supporting Information is available free of charge on the
Preparation details, optimization conditions, NMR
spectra, computational details, DFT calculations (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
ORCID
(8) (a) Elangovan, S.; Neumann, J.; Sortais, J.-B.; Junge, K.; Darcel,
C.; Beller, M. Nat. Commun. 2016, 7, 12641−12649. (b) Neumann,
J.; Elangovan, S.; Spannenberg, A.; Junge, K.; Beller, M. Chem. - Eur. J.
2017, 23, 5410−5413. (c) Bruneau-Voisine, A.; Wang, D.; Dorcet, V.;
Roisnel, T.; Darcel, C.; Sortais, J.-B. J. Catal. 2017, 347, 57−62.
(9) Liu, Z.; Yang, Z.; Yu, X.; Zhang, H.; Yu, B.; Zhao, Y.; Liu, Z. Adv.
Synth. Catal. 2017, 359, 4278−4283.
(10) For recent reviews on iron-catalyzed tandem reactions
involving hydrogenation and autotransfer reactions, see: (a) Renaud,
J.-L.; Gaillard, S. Synthesis 2016, 48, 3659−3683. (b) Quintard, A.;
Rodriguez, J. ChemSusChem 2016, 9, 28−30.
(11) (a) Yan, T.; Feringa, B. L.; Barta, K. Nat. Commun. 2014, 5,
5602−5609. (b) Yan, T.; Feringa, B. L.; Barta, K. ACS Catal. 2016, 6,
381−388. (c) Emayavaramban, B.; Roy, M.; Sundararaju, B. Chem. -
Eur. J. 2016, 22, 3952−3955. (d) Emayavaramban, B.; Sen, M.;
Sundararaju, B. Org. Lett. 2017, 19, 6−9. (e) Brown, T. J.; Cumbes,
M.; Diorazio, L. J.; Clarkson, G. J.; Wills, M. J. Org. Chem. 2017, 82,
10489−10503. (f) Vayer, M.; Morcillo, S. P.; Dupont, J.; Gandon, V.;
Bour, C. Angew. Chem., Int. Ed. 2018, 57, 3228−3232.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from the
■
̀
“Ministere de la Recherche et des Nouvelles Technologies”,
́
Normandie Universite, CNRS, and the LABEX SynOrg (ANR-
11-LABX-0029). A.P. thanks the Spanish MINECO for a
project CTQ2014-59832-JIN, and the EU for a FEDER fund
(UNGI08-4E-003).
REFERENCES
■
(1) (a) Ge, X.; Luo, C.; Qian, C.; Yu, Z.; Chen, X. RSC Adv. 2014, 4,
43195−43203. (b) Yan, G.; Borah, A. J.; Wang, L.; Yang, M. Adv.
Synth. Catal. 2015, 357, 1333−1350.
(12) Elangovan, S.; Sortais, J.-B.; Beller, M.; Darcel, C. Angew.
Chem., Int. Ed. 2015, 54, 14483−14486.
(13) During the preparation of this manuscript, Morrill reported
methylation of ketones, indoles, oxindoles, and amines catalyzed by
(2) (a) Li, Y.; Fang, X.; Junge, K.; Beller, M. Angew. Chem., Int. Ed.
2013, 52, 9568−9571. (b) Li, Y.; Sorribes, I.; Yan, T.; Junge, K.;
Beller, M. Angew. Chem., Int. Ed. 2013, 52, 12156−12160. (c) Jacquet,
O.; Frogneux, O.; Das Neves, C.; Gomes, T. C. Chem. Sci. 2013, 4,
2127−2131. (d) Tlili, A.; Frogneux, X.; Blondiaux, E.; Cantat, T.
Angew. Chem., Int. Ed. 2014, 53, 2543−2545. (e) Beydoun, K.;
Ghattas, G.; Thenert, K.; Klankermayer, J.; Leitner, W. Angew. Chem.,
̈
the iron tricarbonyl Knolker’s complex: Polidano, K.; Allen, B. D. W.;
Williams, J. M. J.; Morrill, L. C. ACS Catal. 2018, 8, 6440−6445.
(14) (a) Pagnoux-Ozherelyeva, A.; Pannetier, N.; Mbaye, D. M.;
Gaillard, S.; Renaud, J.-L. Angew. Chem., Int. Ed. 2012, 51, 4976−
E
Org. Lett. XXXX, XXX, XXX−XXX