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consists of hydrodeoxygenation, leading to the N-methyl
amines. Therefore, while the reduction of carbonates provides
the corresponding O-Bpin-protected alcohols (Scheme 1b),
the reduction of carbamates affords the N-methyl amines
(Scheme 1c).
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In summary, a new earth-alkaline metal-catalyzed reduction
of carbamates has been developed. The mild and effective
magnesium-catalyzed protocol allows the synthesis of N-
methyl amines as well as selective formation of N-methylated
amino alcohols starting from linear or cyclic carbamates.
Moreover, by using DBpin as the reducing agent, N-CD3
containing amines could be obtained in excellent yields and
with quantitative D-incorporation. These deuterated com-
pounds are relevant in medicinal and pharmaceutical
chemistry. Importantly, even N-Boc protected amines can be
transformed to the N-methyl amines. Thus, the Boc-group can
now be considered a masked methyl group which is important
for synthesis and retrosynthesis planning. Experimental and
spectroscopic investigations provide an insight into the
reaction mechanism and suggest that the active Mg-hydride
species is involved in all reduction steps and the cleavage of a
C−O bond. Therefore, we anticipate further developments and
applications of this new magnesium catalytic system in
synthesis and sustainable catalysis.
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ASSOCIATED CONTENT
* Supporting Information
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sı
The Supporting Information is available free of charge at
Experimental procedures, characterization, and NMR
AUTHOR INFORMATION
Corresponding Author
■
(7) (a) Harbeson, S. L.; Tung, R. D. Annu. Rep. Med. Chem. 2011,
46, 403−417. For examples highlighting the importance of isotope
labeling: (b) Atzrodt, J.; Derdau, V. J. Labelled Compd. Radiopharm.
2010, 53, 674−685. (c) Gant, T. G. J. J. Med. Chem. 2014, 57, 3595−
3611. (d) Atzrodt, J.; Derdau, V.; Kerr, W. J.; Reid, M. Angew. Chem.,
Magnus Rueping − KAUST Catalysis Center (KCC), King
Abdullah University of Science and Technology (KAUST),
Thuwal 23955-6900, Saudi Arabia; Institute of Organic
Chemistry, RWTH Aachen University, 52074 Aachen,
́
́
Int. Ed. 2018, 57, 1758−1784. (e) Zachleder, V.; Vítova, M.; Hlavova,
̌
̌
́
̌
̌
́
M.; Moudríkova, S.; Mojzes, P.; Heumann, H.; Becher, J. R.; Bisova,
K. Biotechnol. Adv. 2018, 36, 784−797.
(8) (a) Onaka, M.; Ishikawa, K.; Izumi, Y. Chem. Lett. 1982, 11,
1783−1786. (b) Chiappe, C.; Piccioli, P.; Pieraccini, D. Green Chem.
2006, 8, 277−281.
Authors
(9) For leading examples with iron/silane: (a) Zheng, J.; Darcel, C.;
Sortais, J.-B. Chem. Commun. 2014, 50, 14229−14232. With
platinum/silane: (b) Li, Y.; Sorribes, I.; Vicent, C.; Junge, K.;
Beller, M. Chem. - Eur. J. 2015, 21, 16759−16763. Ruthenium/
hydrogen: (c) Cabrero-Antonino, J. R.; Adam, R.; Junge, K.; Beller,
M. Catal. Sci. Technol. 2016, 6, 7956−7966. For a general review:
(d) Cabrero-Antonino, J. R.; Adam, R.; Beller, M. Angew. Chem., Int.
Ed. 2019, 58, 12820−12838.
Marc Magre − Institute of Organic Chemistry, RWTH Aachen
Marcin Szewczyk − Institute of Organic Chemistry, RWTH
Aachen University, 52074 Aachen, Germany
Complete contact information is available at:
(10) Pritchard, J.; Filonenko, G. A.; van Putten, R.; Hensen, E. J. M.;
Pidko, E. A. Chem. Soc. Rev. 2015, 44, 3808−3833.
Notes
(11) For an excellent example of a metal-free reduction of amides,
see: Sitte, N. A.; Bursch, M.; Grimme, S.; Paradies, J. J. Am. Chem. Soc.
2019, 141, 159−162.
The authors declare no competing financial interest.
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