Cu-Catalyzed Chemoselective Reduction of N-Heteroaromatics with NH3·BH3 in Aqueous Solution

Article abstract of DOI:10.1002/cjoc.202100259

An efficient catalytic system was successfully developed on reduction of N-heteroaromatics with H₃N?BH₃ as hydrogen source in CuSO₄ solution, featuring excellent chemoselectivity as well as very broad functional group tolerance. Various challenging substrates, such as OH-, NH₂-, Cl-, Br-, etc., contained quinolines, quinoxalines, 1,5-naphthyridines and quinazolines were all reduced smoothly. Mechanistic studies suggested that [Cu-H] intermediate might be generated from NH₃?BH₃, which was believed to form with H₃N?BH₃ in CuSO₄ solution.

Full text of DOI:10.1002/cjoc.202100259

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Accepted Article
Title: Cu-Catalyzed Chemoselective Reduction of N-Heteroaromatics with NH3∙BH3
in Aqueous Solution
Authors: Chao Gao, Qingqing Xuan,* and Qiuling Song*
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Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Cu-Catalyzed Chemoselective Reduction of N-Heteroaromatics
with NH3∙BH3 in Aqueous Solution
Chao Gao, a Qingqing Xuan, *,a and Qiuling Song *, a,b,c
a Institute of Next Generation Matter Transformation, College of Chemical Engineering and College of Material Sciences Engineering at
Huaqiao University, 668 Jimei Boulevard, Xiamen, Fujian, China, 361021.
b Key Laboratory of Molecule Synthesis and Function Discovery Fujian Province University College of Chemistry at Fuzhou University Fuzhou,
Fujian, 350108 (P. R. China)
c State key laboratory of Organometallic Chemistry and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China.
Keywords
N-Heteroaromatics |NH3∙BH3 |Chemoselective Hydrogenation |[Cu-H] Intermediate
Main observation and conclusion
An efficient catalytic system was successfully developed on reduction of N-heteroaromatics with H3N∙BH3 as hydrogen source in CuSO4
solution, featuring excellent chemoselectivity as well as very broad functional group tolerance. Various challenging substrates, such as
OH-, NH2-, Cl-, Br-, etc. contained quinolines, quinoxalines, 1,5-naphthyridines and quinazoline were all reduced smoothly. Mechanistic
studies suggested that [Cu-H] intermediate might be generated from NH3∙BH3, which was believed forming with H3N∙BH3 in CuSO4
solution.
Comprehensive Graphic Content
H
X
X
X
mol
CuSO
NH3 BH
%)
4 (5
⋅
X
X
equiv)
R
3 (3
R
60 o
N
H
H
2O,
N
C,
2
X
N
⋅
=
X
N
NH3 BH3
Acids
C,
MSA, Solvent
Advantages:
Ph
N
N
♦
water was
as
solvent;
employed
♦
excellent
tolerance:
group
and
S
-
NH2
various OH-
were
substituted
smoothyl;
substrates
reduced
N
CF3
N
♦
♦
scale
were
large
experiments
feasible;
were
various
obtained.
N-alkylated products
*E-mail:
View HTML Article
Supporting Information
Chin. J. Chem. 2021, 39, XXX－XXX©
2021
SIOC,
CAS,
Shanghai,
&
WILEY-VCH
GmbH
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202100259
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Scheme 1 Hydrogenations of N-heteroarenes in B2pin2/H2O system and
our design
Background and Originality Content
Hydrogenation of arenes and heteroarenes is an important re-
search field, as the corresponding saturated and partially saturated
molecules bearing cyclic skeletons, have always played important
roles as biologically active building blocks and key intermediates in
organic synthesis.[1] Although, many valuable strategies had been
developed on the reduction of N-heteroaromatics,[2] there are still
some problems to be solved. First, the substrates scope was limited.
OH- and NH2- substituted substrates were always challenging in ho-
mogeneous hydrogenation process, as these groups might poison
or deactivate the transition metal catalysts.[3] Second, precious
metals were usually used, which were noneconomic and environ-
mentally harmful. Third, H2 has long been employed in direct hydro-
genations and alcohols, formic acid, Hantzsch esters etc. have been
used often in transfer hydrogenations (Fig 1).[4] The former was
flammable and dangerous, and the latter hydrogen sources were
poor atom-economic. Thus, the development of generic, green and
practical transfer hydrogenation of N-heteroarenes is of great sig-
nificance.
Results and Discussion
8-Hydroxyquinoline is always a challenging substrate for
chemoselective hydrogenation,[9] and 1,2,3,4-tetrahydro-8-hy-
droxyquinoline is not only an important biologically active com-
pound, which can inhibit leukotriene formation in macrophages,
but also can be employed as coordination ligands.[10] So we directly
employed 8-Hydroxyquinoline as model substrate to screen the re-
action conditions (Table 1). Our first try was carried out with
Cu(NO3)2 and 3.0 equivalent of NH3∙BH3 in H2O. The reaction was
stirred at 60 oC for 12 h under N2 atmosphere, and the desired prod-
uct 2a was obtained in 37% isolated yield (entry 1). The result
thrilled us, as it proven that this expedient and green reaction sys-
tem was effect in hydrogenation of OH-contained quinoline. As we
have stated in the preface, hydrogenation of OH-contained quino-
lines were rarely reported, so we decided to further optimize the
reaction conditions. Various copper salts were first studied (entries
2-4). When 5 mol % CuBr was used, the yield of 2a could be im-
proved to 60% yield (entry 2), the result illustrated that the kind of
copper salts affected the result largely. Then, Cu(OTf)2 and CuSO4
were also tested, the desired product of 2a was got in 79% and 81%
yield respectively (entries 3-4). According to the reported literature,
one molecular of NH3∙BH3 could afford two molecular of hydride
ion, so in theory 1.0 equivalent of NH3∙BH3 was enough. However,
when the amount of NH3∙BH3 was decreased, the yield suffered a
lot (entries 5-7). When 1.0 equivalent of NH3∙BH3 was used, 2a was
only got in 43% yield (entry 7). The release of H2 would consume
some NH3∙BH3, so excess amount of NH3∙BH3 was needed. The ne-
cessity of CuSO4 was tested at last and no hydrogenation reaction
was happened (entry 8). Herein, the optimal reaction conditions
were got as: 1a (0.5 mmol), NH3∙BH3 (1.5 mmol) and CuSO4 (5 mol %)
were stirred in H2O (1.0 mL) under N2 at 60 oC for 12 h.
Fig 1 Challenges in hydrogenation of N-heteroarenes
Our group has reported Pd-catalyzed transfer hydrogenation of
various N-heteroaromatic compounds in the presence of B2pin2.
Despite of its’importance that H2O was employed as both hydrogen
source and solvent, chemical equivalent of B2pin2 was used,[5] that
was non-atomic.[6] What’s more, the substrate scope was limited,
as OH-, NH2-, Cl- and Br-contained substrates were failed to be hy-
drogenated (Scheme 1 left). In order to solve these problems to
some extent, a new catalytic system was developed in our labora-
tory (Scheme 1 right). Ammonium borane (NH3∙BH3), which is at-
tractive owing to its high hydrogen capacity (about 19.6 wt %), low
molecular weight, easy handling, and excellent stability against air
and moisture, was selected as hydrogen source.[7] H2O, which is one
of the most abundant and green molecule in world was also used
as solvent.[8]
a Department, Institution, Address 1
E-mail:
c Department, Institution, Address 3
E-mail:
b Department, Institution, Address 2
E-mail:
Chin. J. Chem. 2018, template© 2018 SIOC, CAS, Shanghai,
&
WILEY-VCH Verlag GmbH
&
Co. KGaA,
Weinheim

Running title
Chin. J. Chem.
Table 1 Optimization of the reaction conditions a
Scheme 2 Substrate’s scope of quinoline derivatives a
With the optimized reaction condition in hand, various OH-,
NH2- and other group substituted quinolines were examined
(Scheme 2). It’s found that the site of OH- affected the reaction
largely, 8-OH and 7-OH substituted quinolines afforded higher
yields of the desired products comparing with 6-OH and 5-OH sub-
stituted substrates (2a, 2b vs 2c, 2d). Interestingly, 6-hydroxymethyl
substituted quinoline could also go through the hydrogenation
smoothly and gave the desired product 2e in 67% yield. Although 3-
OH substituted quinoline failed to be hydrogenated, quinolin-3-
amine (1f) could afford the corresponding (2f) in 56% yield. 3-
amino-1,2,3,4-tetrahydroquinoline constitutes the core structure of
sumanirole (PNU-95666E), a dopamine D2 receptor agonist that is
considered as a candidate drug for the treatment of Parkinson’s dis-
ease.[11] What’s more, 5-NH2, 7-NH2 and 8-NH2 substituted quino-
lines could also be reduced smoothly, affording the desired product
in 89%, 74% and 45% yield separately (2g-2i). It worthy of remark
that 8-amino-1,2,3,4-tetrahydroquinoline can be employed as dia-
mino ligand.[12] Next, halogen group substituted quinolines were
also examined. 5-fluoro and 8- fluoroquinoline, which were easier
for hydrogenation, could give the corresponding products in mod-
erate to good yield (2j, 2k). Noticeably, Cl- and Br- substituted sub-
strates, which were challenging for transition metal catalytic sys-
tems, as dehalogenations might occur, could be reduced success-
fully under our reaction systems (2l-2n). The electronic effects of
the substituents on the aromatic ring had little effect on the hydro-
genation, as either ester or alkoxyl group substituted quinolines
could give the desired products smoothly (2o-2r). In addition, un-
substituted and various alkyl substituted substrates were also
tested, and all of them could afford the corresponding products in
good yield (2s-2aa).
compounds, 2,3-dihydroquinazolin-4(1H)-one (4l), 3,4-dihydro-
quinolin-2(1H)-one (4m) and 2,3,3-trimethylindoline (4n) were
were also synthesized via our catalytic system (See supporting in-
formation for details). N-alkylated amines have been widely applied
in pharmaceuticals and natural products, and reductive N-alkyla-
tions with carboxylic acids were an expedient strategy, as carboxylic
acids are stable and readily available.[14] Here, reductive N-alkyla-
tions of 2s were fully realized with some interesting acids, including
bicyclic (5), cyclopropyl (7), unsaturated (9) and trifluoromethyl in-
corporated (11) carboxylic acids, in the presence of NH3∙BH3 as hy-
drogen source and methanesulfonic acid (MSA) as catalyst (See sup-
porting information for details). And the desired products were all
obtained in medium to good yields (6, 8, 10, 12).
Scheme 3 Substrate’s scope of other N-Heteroarenes a
To further prove its universality, a series of quinoxalines and pol-
ycyclic N-heteroarenes were also examined (Scheme 3). Luckily,
quinoxaline (3a) could be reduced successfully to give 1,2,3,4-te-
rahydroquinoxaline, which are very useful moieties and present in
a wide range of biologically and medicinally useful molecules. So
next some other quinoxalines were tried, 2-, 5- and 6-methyl sub-
stituted quinoxalines were all showed good reactivity and gave the
desired products in medium to high yields (4b-4d). Good functional
group tolerance also applied to quinoxalines, as 6-bromo-quinoxa-
line (4e) was also reduced smoothly, although the yield was suf-
fered a little. Interestingly, some polycyclic aromatic compounds
could also be hydrogenated, in relative low yields (4f-4i). It’s note-
worthy that 1.5-naphthyridine could selectively be hydrogenated
on one pyridine ring into compound (4j), which is a core unit of
topoisomerase I inhibitor.[13] Another interesting core 1,2,3,4-tetra-
hydroquinazoline (4k) was also obtained in 82% yield under our re-
action system. At last, based on our interest in N-heterocyclic
Chin. J. Chem. 2021, 39, XXX－XXX
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First author et al.
Report
Scheme 4 Large-scale experiments and N-alkylations of 2s with various ac-
ids a
Conclusions
In conclusion, we had successfully developed a CuSO4 catalyzed
hydrogenation of N-heteroaromatics in H2O, in which H3N∙BH3 was
employed as hydrogen source. The catalytic system showed excel-
lent chemoselectivity as well as very broad functional group toler-
ance. Various challenging substrates, such as OH-, NH2-, Cl-, Br-, etc.
contained quinolines, quinoxalines, 1,5-naphthyridine and quinazo-
line were all successfully reduced. According to the proposed mech-
anism, [Cu-H] intermediate could be generated from H3N∙BH3 and
H2N=BH2 in CuSO4/H2O system. Meanwhile, the polymerization by-
product borazine was produced, which was proven by 11B NMR
spectrum. H2 was detected in our reaction system, which might de-
crease the efficiency of H3N∙BH3. Next, we will strive to improve the
utilization of H3N∙BH3.
Experimental
General procedure for scheme 2 and 3: To a Schenk tube
equipped with a stir bar, NH3∙BH3 (1.5 mmol, 3.0 equiv) was added
to a mixture of CuSO4 (6.45 mg, 5 mol %) and N-Heteroaromatics
(0.5 mmol, 1.0 equiv) in H2O (1.0 mL). Then the Schenk tube was
stirred at 60 °C under N2 for 12 h. Upon completion of the reaction,
the solvent was evaporated under reduced pressure and the resi-
due was purified by flash column chromatograph (silica gel,
PE:EtOAc = 5:1, v/v) to give the desired product.
Supporting Information
According to the results and the reported literature the mecha-
nism was proposed in Scheme 5.[15] It’s believed that [Cu-H] inter-
mediate was generated from NH3∙BH3 in CuSO4/H2O system and at
the same time H2N=BH2 was obtained.[16] H2N=BH2 would coordi-
nate to the copper salt and also afford [Cu-H] intermediate.[17]
Meanwhile, the polymerization byproduct borazine was produced,
which was proven by 11B NMR spectrum (See supporting infor-
mation for details).[18] The the afforded [Cu-H] would then hydro-
genate quinolines via 1,4-addition affording Int I, which would then
isomerized to Int II. At last Int II would be hydrogenated by [Cu-H]
giving the final product. Based on the proposed mechanism, 1.0
equivalent of H3N∙BH3 could afford 2.0 equivalent of [Cu-H] inter-
mediate, however, according to the experiments when 1.0 equiva-
lent of H3N∙BH3 was used, the desired product was isolated in 43%
yield (Entry 7, Table 1). That’s because the release of H2 might con-
sume H3N∙BH3 to some extent. So, next we will work on how to sup-
press the release of H2 and improve the transfer hydrogenation ef-
ficiency of H3N∙BH3.
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgement (optional)
Financial support from the National Natural Science Foundation
(21702065, 21772046 and 2193103) and the Promotion Program
for Young and Middle-aged Teacher in Science and Technology Re-
search of Huaqiao University are gratefully acknowledged.
References
(a) Sridharan, V.; Suryavanshi, P. A.; Menéndez, J. C. Advances in the
Chemistry of Tetrahydroquinolines. Chem. Rev. 2011, 111, 7157-7259.
(b) Bull, J. A.; Mousseau, J. J.; Pelletier, G.; Charette, A. B. Synthesis of
Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselec-
tive Addition to N-Activated Pyridines. Chem. Rev. 2012, 112, 2642-
2713.
Scheme 5 Plausible mechanisms
(a) Zhou, Y. Asymmetric Hydrogenation of Heteroaromatic Com-
pounds. Acc. Chem. Res. 2007, 40, 1357-1366. (b) Wang, D.; Chen, Q.;
Lu, S; Zhou, Y. Asymmetric Hydrogenation of Heteroarenes and Arenes.
Chem. Rev. 2012, 112, 2557-2590. (c) Wiesenfeldt, M. P.; Nairoukh, Z.;
Dalton, T.; Glorius, F. Selective Arene Hydrogenation for Direct Access
to Saturated Carbo- and Heterocycles. Angew. Chem. Int. Ed. 2019, 58,
10460-10476.
(a) Sorribes, I.; Liu, L.; Doménech-Carbó, A.; Corma, A. Nanolayered
Cobalt–Molybdenum Sulfides as Highly Chemo- and Regioselective
Catalysts for the Hydrogenation of Quinoline Derivatives. ACS Catal.
2018, 8, 4545-4557. (b) Karakulina, A.; Gopakumar, A.; Akcok, I.; Rou-
lier, B. L.; LaGrange, T.; Katsyuba, S. A.; Das, S.; Dyson, P. J. A Rhodium
Nanoparticle–Lewis Acidic Ionic Liquid Catalyst for the Chemoselective
Reduction of Heteroarenes. Angew. Chem., Int. Ed. 2016, 55, 292-296.
(c) Liu, C.; Rong, Z.; Sun, Z.; Wang, Y.; Du, W.; Lu, L. Quenched skeletal
Ni as the effective catalyst for selective partial hydrogenation of poly-
cyclic aromatic hydrocarbons. RSC Adv. 2013, 3, 23984-23988. (d)
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Zhong, Y.; Zhou, T.; Zhang, Z.; Chang, R. Copper-Catalyzed Transfer Hy-
drogenation of N-Heteroaromatics with an Oxazaborolidine Complex.
ACS Omega. 2019, 4, 8487-8494.
Wang, D.; Astruc, D. The Golden Age of Transfer Hydrogenation. Chem.
Rev. 2015, 115, 6621-6686.
Xuan, Q.; Song, Q. Diboron-Assisted Palladium-Catalyzed Transfer Hy-
drogenation of N-Heteroaromatics with Water as Hydrogen Donor and
Solvent. Org. Lett. 2016, 18, 4250-4253.
Zou, M. F.; Keck, T. M.; Kumar, V.; Donthamsetti, P.; Michino, M.;
Burzynski, C.; Schweppe, C.; Bonifazi, A.; Free, R. B.; Sibley, D. R.; Jan-
owsky, A.; Shi, L.; Javitch, J. A.; Newman, A. M. Novel Analogues of (R)-
5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one
(Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Se-
lectivity. J. Med. Chem. 2016, 59, 2973-2988.
Alonso, C.; Fuertes, M.; Gonzalez, M.; Rubiales, G.; Tesauro, C.; Knud-
sen, B. R.; Palacios, F. Synthesis and biological evaluation of in-
deno[1,5]naphthyridines as topoisomerase I (TopI) inhibitors with an-
tiproliferative activity. Eur. J. Med. Chem. 2016, 115, 179-190.
(a) Beydoun, K.; Ghattas, G.; Thenert, K.; Klankermayer, J.; Leitner, W.
Ruthenium-Catalyzed Reductive Methylation of Imines Using Carbon
Dioxide and Molecular Hydrogen. Angew. Chem. Int. Ed. 2014, 53,
11010-11014. (b) Blondiaux, E.; Pouessel, J.; Cantat, T. Carbon Dioxide
Reduction to Methylamines under Metal-Free Conditions. Angew.
Chem. Int. Ed. 2014, 53, 12186-12190. (c) Wei, Y.; Xuan, Q.; Zhou, Y.;
Song, Q. Reductive N-alkylation of primary and secondary amines us-
ing carboxylic acids and borazane under mild conditions. Org. Chem.
Front., 2018, 5, 3510-3514. (d) Sorribes, I.; Cabrero-Antonino, R. J.; Vi-
cent, C.; Junge, K.; Beller, M. Catalytic N-Alkylation of Amines Using
Carboxylic Acids and Molecular Hydrogen. J. Am. Chem. Soc. 2015, 137,
13580-13587.
(a) Jiang, C.; Blacque, O.; Fox, M.; Frech, V. M.; Berke, H. Activation of
Terminal Alkynes by Frustrated Lewis Pairs. Organometallics., 2010, 29,
125-133. (b) Jiang, Y.; Berk, H. Dehydrocoupling of dimethylamine-bo-
rane catalysed by rhenium complexes and its application in olefin
transfer-hydrogenations. Chem. Commun., 2007, 3571-3573.
(a) Rossin, A.; Peruzzini, M. Ammonia–Borane and Amine–Borane De-
hydrogenation Mediated by Complex Metal Hydrides. Chem. Rev.,
2016, 116, 8848-8872. (b) Korytiaková, E.; Thiel, N. O.; Pape, F.;
Teichert, J. F. Copper(I)-catalysed transfer hydrogenations with ammo-
nia borane. Chem. Commun., 2017, 53, 732-735. (c) Rossin, A.; Pe-
ruzzini, M. Stereoselective Alkyne Hydrohalogenation by Trapping of
Transfer Hydrogenation Intermediates. Org. Lett., 2018, 20, 4926-4929.
(d) Zhong, Y.; Zhou, T.; Zhang, Z.; Chang, R. Copper-Catalyzed Transfer
Hydrogenation of N-Heteroaromatics with an Oxazaborolidine Com-
plex. ACS Omega, 2019, 4, 8487-8794.(e) Hamilton, C. W.; Baker, R. T.;
Staubitz, A.; Manners, I. B–N compounds for chemical hydro-
genstorage. Chem. Soc. Rev., 2009, 38, 279-293.
(a) Deutsch, C.; Krause, N. Cu-H-Catalyzed Reactions. Chem. Rev. 2008,
108, 2916-2927. (b) Jordan, A. J.; Lalic, G.; Sadighi, J. P. Coinage Metal
Hydrides: Synthesis, Characterization, and Reactivity. Chem. Rev. 2016,
116, 8318-8372. (c) Pirnot, M. T.; Wang, Y.; Buchwald, S. L. Copper Hy-
dride Catalyzed Hydroamination of Alkenes and Alkynes. An-
gew.Chem.Int. Ed. 2016, 55, 48-57.
(a) Yang, X.; Zhao, L.; Fox, T.; Wang, Z.; Berk, H. Transfer Hydrogenation
of Imines with Ammonia-Borane: A Concerted Double-Hydrogen-
Transfer Reaction. Angew. Chem. Int. Ed. 2010, 49, 2058-2062. (b)
Yang, X.; Fox, T.; Berke, H. Facile metal free regioselective transfer hy-
drogenation of polarized olefins with ammonia borane. Chem. Com-
mun., 2011, 47, 2053-2055. (c) Chong, C. C.; Hirao, H.; Kinjo, R. A Con-
certed Transfer Hydrogenolysis: 1,3,2‐ Diazaphospholene-Catalyzed
Hydrogenation of N-N Bond with Ammonia–Borane. Angew. Chem. Int.
Ed. 2014, 53, 3342-3346.
Xia, Y.; Sun, X.; Zhang, L.; Luo, K.; Wu, L. Metal-Free Hydrogen Atom
Transfer from Water: Expeditious Hydrogenation of N-Heterocycles
Mediated by Diboronic Acid. Chem. Eur. J. 2016, 22, 17151-17155.
(a) Ai, W.; Zhong, R.; Liu, X.; Liu, Q. Hydride Transfer Reactions Catalyzed
by Cobalt Complexes. Chem. Rev. 2019, 119, 2876-2953. (b) Meng, W.;
Feng, X.; Du, H. Frustrated Lewis Pairs Catalyzed Asymmetric Metal-
Free Hydrogenations and Hydrosilylations. Acc. Chem. Res. 2018, 51,
191-201. (c) Hamilton, C. W.; Baker, R.; Staubitzc, A.; Manners, I. B. B–
N compounds for chemical hydrogenstorage. Chem. Soc. Rev., 2009,
38, 279-293. (d) Zhou, Q.; Meng, W.; Yang, J.; Du, H. A Continuously
Regenerable Chiral Ammonia Borane for Asymmetric Transfer Hydro-
genations. Angew. Chem. Int. Ed. 2018, 57, 12111-12115. (e) Li, S.;
Meng, W.; Du, H. Asymmetric Transfer Hydrogenations of 2,3-Disub-
stituted Quinoxalines with Ammonia Borane. Org. Lett. 2017, 19, 2604-
2606. (f) Li, S.; Li, G.; Meng, W.; Du, H. A Frustrated Lewis Pair Cata-
lyzed Asymmetric Transfer Hydrogenation of Imines Using Ammonia
Borane. J. Am. Chem. Soc. 2016, 138, 12956-12962. (g) Fu, S.; Chen, N.;
Liu, X.; Shao, Z.; Luo, S.; Liu, Q. Ligand-Controlled Cobalt-Catalyzed
Transfer Hydrogenation of Alkynes: Stereodivergent Synthesis of Z-
and E-Alkenes. J. Am. Chem. Soc. 2016, 138, 8588-8594. (h) Wang, Y.;
Zhu, L.; Shao, Z.; Li, G.; Lan, Y.; Liu, Q. Unmasking the Ligand Effect in
Manganese-Catalyzed Hydrogenation: Mechanistic Insight and Cata-
lytic Application. J. Am. Chem. Soc. 2019, 141, 17337-17349. (i) Lau, S.;
Gasperini, D.; Webster, R. L. Amine–Boranes as Transfer Hydrogena-
tion and Hydrogenation Reagents: A Mechanistic Perspective. Angew.
Chem. Int. Ed. 2021, 60, 2-25. (j) Das, M.; Kaicharla, T.; Teichert, J. F.
Stereoselective Alkyne Hydrohalogenation by Trapping of Transfer Hy-
drogenation Intermediates. Org. Lett. 2018, 20, 4926-4929. (k) Ding, F.;
Zhang, Y.; Zhao, R.; Jiang, Y.; Bao, R.; Lin, K.; Shi, L. B(C6F5)3-Promoted
hydrogenations of N-heterocycles with ammonia borane. Chem. Com-
mun., 2017, 53, 9262-9264. (l) Chiara, F.; Maurizio, O. Ammonia bo-
rane as a reducing agent in organic synthesis. Chem. Commun., 2020,
18, 7719-7813. (m) Yang, C.; Xie, Z.; Yu, L. Research Progress of Direct
Transfer Hydrogenation Based on Ammonia Borane. Chinese Journal
of Chemistry. 2015, 35, 603-609.
(a) Xuan, Q.; Zhao, C.; Song, Q. Umpolung of protons from H2O: a
metal-free chemoselective reduction of carbonyl compounds via
B2pin2/H2O systems. Org. Biomol. Chem. 2017, 15, 5140-5144. (b) But-
ler, R. N.; Coyne, A. G. Water: Nature’s Reaction Enforcer—Compara-
tive Effects for Organic Synthesis “In-Water” and “On-Water”. Chem.
Rev. 2010, 110, 6302-6337.
(a) Czaplik, W. N.; Neudo¨rfl, J. M.; Wangelin, A. J. On the quantitative
recycling of Raney–Nickel catalysts on a lab-scale. Green Chem. 2007,
9, 1163-1165. (b) Wei, Z.; Chen, Y. Wang, J.; Su, D.; Tang, M.; Mao, S.;
Wang, Y. Cobalt Encapsulated in N-Doped Graphene Layers: An Effi-
cient and Stable Catalyst for Hydrogenation of Quinoline Compounds.
ACS Catal. 2016, 6, 5816-5822.
(The following will be filled in by the editorial staff)
Zhandarev, V. V.; Goshin, M. E.; Kostrova, U. M.; Shishkina, A. L.; Kazin,
V. N.; Mironov, G. S.; Abramov, I. G.; Smirnov, A. V.; Ramenskaya, L. M.
Synthesis and antibacterial activity of tetrahydroquinolin-8-ols. Phar-
maceutical Chemistry Journal 2006, 40, 557-559.
Kim, S. K.; Jacobsen, E. N. General Catalytic Synthesis of Highly Enanti-
omericaally Enriched Terminal Aziridines from Racemic Epoxides. An-
gew. Chem. Int. Ed. 2004, 43, 3952-3954.
Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
Manuscript accepted: XXXX, 2021
Accepted manuscript online: XXXX, 2021
Version of record online: XXXX, 2021
Chin. J. Chem. 2021, 39, XXX－XXX
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Cu-Catalyzed Chemoselective Reduction of N-Heteroaromatics with NH3∙BH3 in Aqueous Solution
Chao Gao, a Qingqing Xuan, *,a and Qiuling Song *, a,b,c
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
H
X
X
X
X
X
X
mol
4 (5
CuSO
NH3 BH
%)
R
R
−
equiv)
3 (3
N
N
H
H
60 o
N
2O,
C,
2
=
X
N
C,
ect.
NH Br-,
R=OH-,
2-,
We Have developed the hydrogenation reduction reaction of N-heteroaromatic compounds in the CuSO4/H2O system with ammonia borane as a reduc-
ing agent. The use of H2O as a solvent meets the requirements of green chemistry, and the substrates substituted by OH-, NH2-, Cl-, Br- etc. can be
smoothly reduced. Mechanism studies indicate Cu-H intermediate was generated from CuSO4/H2O system.
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX