Catalyst-Free and Solvent-Free Facile Hydroboration of Imines

Article abstract of DOI:10.1002/asia.201901016

A facile process for the catalyst-free and solvent-free hydroboration of aromatic as well as heteroaromatic imines is reported. This atom-economic methodology is scalable, compatible with sterically and electronically diverse imines, displaying excellent tolerance towards various functional groups, and works efficiently at ambient temperature in most of the cases, affording secondary amines in good to excellent yield after hydrolysis.

Full text of DOI:10.1002/asia.201901016

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Catalyst-Free and Solvent-Free Facile Hydroboration of Imines
Authors: Arnab Rit, Vipin K Pandey, and Siva Nagendra Reddy
Donthireddy
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Asian J. 10.1002/asia.201901016
Link to VoR: http://dx.doi.org/10.1002/asia.201901016
A Journal of
A sister journal of Angewandte Chemie
and Chemistry – A European Journal

Chemistry - An Asian Journal
10.1002/asia.201901016
COMMUNICATION
Catalyst-Free and Solvent-Free Facile Hydroboration of Imines
[
a]
[a]
[a]
Vipin K. Pandey, S. N. R. Donthireddy, and Arnab Rit*
Dedication ((optional))
Abstract: A facile process for the catalyst-free and solvent-free
hydroboration of aromatic as well as heteroaromatic imines is
reported. This atom-economic methodology is scalable, compatible
with sterically and electronically diverse imines displaying excellent
tolerance towards various functional groups, and works efficiently at
ambient temperature for majority cases affording secondary amines
in good to excellent yield after hydrolysis.
utilizing Lewis acid (mainly boron based), Brønsted acid, and
recently, diazaphospholene-based phosphorus hydride as
catalyst have been reported (Scheme 1).[7a,10c,12] However,
hydroboration of imines with most of these catalysts demands
either elevated reaction temperature or longer reaction duration
along with high catalyst loading.[5-8] Thus, development of
alternative atom-economic and catalyst-free green process for the
hydroboation of imines with broad functional group tolerance
under mild conditions is desirable for future sustainable catalytic
methods.
Hydrogenation of imines is an important reaction in synthetic
organic chemistry as the produced amine compounds find
versatile utility in several fields such as natural products,
pharmaceuticals, agrochemicals, polymers, and dyes.[1] Although
traditional hydrogenation process using either stoichiometric
reducing agents or pressurized hydrogen gas as hydrogen source
are well-exploited, the efficacy of these methodologies is
restricted due to poor selectivity over other potentially reducible
unsaturated functionalities, requirement of high-pressure setup,
and formation of inorganic byproducts.[1c-e] In contrary, catalytic
hydroboration of imines offers a moderate and efficient way to get
access of diverse secondary amines.[2a-b] However, only few
examples of imine hydroboration have been described[2] when
compared to a variety of protocols having been developed for
catalytic hydroboration of other unsaturated functionalities like
carbonyl, alkyne, and alkene.[3]
Initially, catecholborane (H-Bcat) was utilized as
hydroboration agent for coinage metal catalyzed hydroboration of
imines[4a] and later on, pinacolborane (H-Bpin) having lower Lewis
Scheme 1. Overview of prior reports on hydroboration reaction of imines and
this work.
acidity got much attention for the same purpose.[2a,4b] Among
metal catalyzed processes, transition metal[5] and even rare earth
A solvent as well as catalyst-free approach not only leads
to an environment-friendly greener process by diminishing
waste generation but also produces reactions, which are
metal complexes[6] have been studied (Scheme 1). There is also
a recent surge in utilization of s- and p-block elements[7] and till
[
13a-b]
practically more convenient.
However, catalyst-free
date, several research groups have studied the hydroboration of
carbonyl[3a] and to some extent imine compounds using main-
processes to attain target molecules did not get much
momentum over the years after pioneering works on
hydroboration of alkenes and alkynes by the group of
Knochel and Piers.[13c-d] Only in recent years, development of
group element (Ca,[7b] Mg,[8a] Al,[7c-d] Si[8b]) based systems
n
(
Scheme 1). Alkali metal based compounds e.g. BuLi and NaOH
have also been utilized for the same process.[9] Although substantial
green
(catalyst-free
and
solvent-free)
organic
efforts have been directed towards exploitation of main-group
based systems as an alternative to precious transition metal
catalysts, area of metal-free catalysis is also emerging
expeditiously in recent years due to environmental and economic
demands.[4b,10] In this area, frustrated Lewis pairs (FLPs) have
transformations such as dehydrocoupling of protic substrates
with boranes,[14a-c] hydroboration of aldehydes/ketone,
and reduction of carboxylic acid via hydroboration[14f-h] has
gained attention from the researchers. In line with these
efforts, we delved in developing a green protocol for the
hydroboration of imine and herein, we present the catalyst-
free and solvent-free ambient temperature hydroboration of
imines with excellent functional group tolerance.
[14d-e]
demonstrated themselves as prominent catalytic systems for the
reduction of imines.[10d] In 2012, Crudden and co-workers
reported an efficient FLP system generated from DABCO,
.[11] After this report, various protocols
pinacolborane and B(C F )
6 5 3
To explore the feasibility of aldimine hydroboration under
catalyst-free condition, initially, we performed the hydroboration
of N-benzylideneaniline using H-Bpin as hydroborating agent at
ambient temperature. Hydroboration using 1.1 equiv. of H-Bpin in
organic solvents resulted in moderate conversion and after
hydrolysis N-benzylaniline was attained in about 60% yield (Table
[
[
a]
b]
Vipin K. Pandey, S. N. R. Donthireddy, Arnab Rit
Department of Chemistry
Indian Institute of Technology Madras
Chennai - 600036
E-mail: arnabrit@iitm.ac.in
Supporting information (experimental details, characterization data,
NMR spectra of the synthesized compounds) for this article is given
via a link at the end of the document
1; entry 1-2). However, to our delight, reaction under neat
condition goes smoothly and the desired amine was isolated in
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901016
COMMUNICATION
excellent yield of 89% which increases marginally when 1.3 equiv.
H-Bpin was used (entry 3-4). Reactions at higher temperature (60
Table 2. Substrate scope for catalyst-free and solvent-free hydroboration of
various aldimines.[
a]
⁰
C) require less time to complete (entry 5-6). Although reaction
under neat condition using 1.1 eqiv. H-Bpin with respect to N-
benzylideneaniline delivered competent yield of the N-
benzylaniline, use of 1.3 eqiv. of H-Bpin was chosen as optimized
condition for the hydroboration process at ambient temperature
due to solubility problem of some other aldimines.
Table 1. Optimization of the hydroboration reaction.[a]
Entry
Solvent
Temperature
Time (h)
Yield (%)[b]
1
2
3
4
5
6
Acetonitrile
THF
-
-
-
-
RT
RT
RT
RT
60 ⁰C
60 ⁰C
6
6
6
6
3
2
62
56
89
92
93
80
[
c]
[
a] Reaction condition: N-Benzylideneaniline (0.5 mmol), H-Bpin (0.55
mmol), room temperature (RT). [b] all are isolated yields. [c] 1.3 equiv. H-
Bpin was used.
With this optimized reaction condition in hand, we then probed
the potential of this protocol and investigated a wide range of
imines, synthesized via condensation of readily available
aldehydes and amines following reported procedure, [15a] under
catalyst-free and solvent-free condition. We were delighted to find
that the hydroboration of electronically and sterically diverse
amines, which include aromatic and heteroaromatic amines with
varying substituents was realized efficiently. After hydrolysis
followed by purification via column chromatography provided the
corresponding secondary amines in good to excellent yields
[
a] Reaction condition: imine (0.5 mmol), H-Bpin (0.65 mmol), 6-24 h. The
hydroborated products were hydrolysed with SiO in methanol; all are
isolated yields. [b] 1.5 equiv. H-Bpin was used. [c] Reactions were
performed at 60 ⁰C. [d] 2.3 equiv. H-Bpin was used.
2
(
Table 2).
Both the C- and N-phenyl ring of the imine moiety bearing
Our catalyst-free and solvent-free approach can also be
utilized for the reduction of heteroaromatic-substituted
imines although higher temperature (60 ⁰C) is required to
diverse substituents resulted the desired products. Various
substituents on C-phenyl ring afforded the secondary amines (3a-
e) in excellent yields of 85-92% and these results are significantly
realize decent yields in 24 h (3r-3t) possibly due to change
better than those observed for Co(II)-CP,[5a] Ru(II),[5b] and
in electrophilicity of the imine moiety. Poly-aromatic
compound 1-naphthyl substituted imine 1u is also reactive
and yielded the corresponding amine 3u after hydrolysis in
6c]
(
MeCp)
3
La[ systems which require higher temperature (60-70
⁰
C) and longer reaction duration. Presence of substituents at the
N-phenyl ring demands longer reaction span than their analogues
C-phenyl substituted imines (3h-j vs 3a-e). However, substrates
having both N- and C-phenyl rings substituents gave excellent
yield of the products at the same reaction duration as required for
only C-phenyl substituents (3l-m vs 3c-d). Notably, variation of
substituents on the C- and N-phenyl ring of the imine moiety (3a-
e and 3h-j) does not have much effect on the reaction outcome.
Importantly, position of the C-phenyl substituents does not have
any influence on the reaction (3d vs 3g) and compounds with
moderate steric congestion around the imine moiety can be
reduced efficiently at ambient temperature (3k and 3n) although
sterically more congested imine (1o) requires higher temperature
9
3% yield at ambient temperature. Satisfyingly, this
approach can also be extended to diimine compound and the
corresponding diamine compound 3v could be attained in
excellent yield of 96%.
Table 3. Substrate scope for catalyst-free hydroboration of ketimines.[a]
(
3o, 92%). It is important to note that Mg-based catalyst performs
sluggishly for this type of bulky substrates although found to be
suitable for other aldimines.[8a] Possibly because of low solubility
of 1p, reaction temperature of 60 ⁰C is necessary for the
completion of reaction and the amine 3p was isolated in 90%
yield. Hydroboration of N-benzyl substituted imine 1q proceeds at
60 ⁰C and the dibenzylamine (3q) could be isolated in 65% yield.
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901016
COMMUNICATION
[
4
a] Reaction condition: imine (0.5 mmol), H-Bpin (0.75 mmol), 60 ⁰C, 24-
8 h. The hydroborated products were hydrolysed with SiO in methanol;
all are isolated yields.
2
Catalyst-free hydroboration of ketimines is expected to be
difficult as compared to analogues aldimines[15b] due to less
electrophilicity coupled with more steric congestion around the
imine moiety. After having success with aldimines, we focused on
the hydroboration of ketimines using our catalyst-free and
solvent-free approach. As expected, hydroboration at ambient
temperature using 1.5 equiv. of H-Bpin with respect to ketimine
was not successful. However, hydroboration was realized when
reaction was performed at higher temperature of 60 ⁰C (Table 3)
although effectiveness is much lower than previously reported
catalyzed reactions[8a,10c,12c] and the corresponding amines were
obtained in moderate to good yields after hydrolysis. Reduction of
N-(-methylbenzylidene)aniline 4a followed by hydrolysis yielded
the N-(-methylbenzyl)aniline 6a in good yield of 70%.
Hydroboration of imines with both electron withdrawing and
donating substituents on the C-phenyl ring (4b-4d) was attained.
Scheme 2. Intramolecular chemoselective hydroboration of imine (isolated
yield). Yield at 60 ⁰C are given in parenthesis.
After having success in intermolecular chemoselective
hydroboration, we then targeted substrates installed with
[
15a]
both aldimine and nitro/nitrile moiety
at the p-positions of
a phenyl ring. Gratifyingly, we found excellent functional
group tolerance of our present method for nitro and nitrile
moiety. The corresponding secondary amines 8a and 8b
having the nitro/nitrile group unaltered were exclusively
obtained in moderate yields at ambient temperature which
can be improved by conducting the reaction at higher
temperature of 60 ⁰C (Scheme 3). It is worth to mention that
the efficiency our protocol is much higher when compared to
previously reported Er, Ca, and Si-based catalyst
systems.[6a,7b,8b]
However, presence of methoxy group substantially reduces the
activity[4b] and corresponding amine (6d) could only be isolated in
37% yield even after prolonged reaction time (48 h) which may be
due to reduced electrophilicity of the imine moiety. Similarly,
presence of ethyl (4e) instead of methyl group at the -position as
well as N-benzyl (4f) instead of phenyl group required longer time
to realize the corresponding amines (6e and 6f) in moderate yield.
Importantly, the present system also works for large-scale
synthesis as demonstrated by gram scale reaction of N-
benzylideneaniline (1a) under optimized conditions providing N-
benzylaniline (3a) upon hydrolysis in 85% isolated yield (Scheme
4).
Scheme 4. Gram scale hydroboration of N-benzylideneaniline.
Based on previously reported related literatures,[2b,4b,9b,14d]
a
plausible mechanistic pathway for this catalyst-free process is
depicted in Scheme 5. It is proposed that a Lewis adduct between
the imine and H-Bpin of type A is first formed, which possibly
Scheme 2. Intermolecular chemoselective hydroboration of imine. [a] Isolated
yield.
enhances the hydridic character of the B-H moiety of H-Bpin via
weakening of the bond[
9b,14d-e]
and thereby, promotes the hydride
To explore the suitability of the developed process in
chemoselective
hydroboration,
1:1
mixture
of
N-
transfer to reduce the imine functionality likely via four membered
benzylideneaniline and 4-bromostyrene/diphenyl acetylene/4-
methylacetophenone were reacted with H-Bpin under our
standard condition. To our delight, essentially quantitative
hydroboration of only N-benzylideneaniline was observed (based
cyclic transition state (B) in the next step.
1
on H NMR analysis) and we could isolate the N-benzylaniline 3a
after hydrolysis in about 90% yield (Scheme 2). No hydroboration
of other potential functional moieties was observed which was
confirmed by 95% recovery of diphenyl acetylene along with H
Scheme 5. A plausible mechanistic pathway.
1
NMR analysis of the reaction mixture (see Supporting
Information).
Conclusion
In conclusion, we have developed a general, ambient
temperature catalyst-free and solvent-free efficient protocol
for the hydroboration of imines, which upon hydrolysis
produces the corresponding secondary amines. This simple
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901016
COMMUNICATION
protocol is pertinent to synthetically diverse imines which
include aromatic and heteroaromatic aldimines as well as
[9]
a) D. Yan, X. Wu, J. Xiao, Z. Zhu, X. Xu, X. Bao, Y. Yao, Q. Shen, M.
Xue, Org. Chem. Front. 2019, 6, 648−653; b) Y. Wu, C. Shan, J. Ying, J.
Su, J. Zhu, L. L. Liu, Y. Zhao, Green Chem. 2017, 19, 4169−4175.
For selected references, see: a) P. A. Chase, G. C. Welch, T. Jurca, D.
W. Stephan, Angew. Chem. Int. Ed. 2007, 46, 8050−8053; b) K. Wen , J.
Chen, F. Gao, P. S. Bhadury, E. Fan, Z. Sun, Org. Biomol. Chem. 2013, 11,
ketimines
conversion of imine over alkene, alkyne, ketone, nitro, and
nitrile).
and
offers
excellent
chemoselectivities
[
10]
(
6350−6356; c) Q.Yin, Y. Soltani,
R. L. Melen, M. Oestreich,
Organometallics 2017, 36, 2381−2384; d) D. W. Stephan, G. Erker,
Angew. Chem. Int. Ed. 2015, 54, 6400−6441.
Acknowledgements
[11]
P. Eisenberger, A. M. Bailey, C. M. Crudden, J. Am. Chem. Soc. 2012,
134, 17384−17387.
[
12]
For selected references, see: a) J. R. Lawson, L. C. Wilkins, R. L. Melen,
Chem. Eur. J. 2017, 23, 10997–11000; b) D. Enders, A. Rembiak, M.
Seppelt, Tetrahedron Lett. 2013, 54, 470–473; c) C.-H. Tien, M. R.
Adams, M. J. Ferguson, E. R. Johnson, A. W. H. Speed, Org. Lett. 2017,
19, 5565−5568.
We gratefully acknowledge SERB and DST, India (Project
No. ECR/2016/001272 and DST/INSPIRE/04/2015/002219)
for financial support. V. K. P. and S. N. R. D. thank IIT Madras
and UGC, respectively for research fellowship. We are
thankful to the Department of Chemistry, IIT Madras for
instrumental facility.
[
13]
a) A. Sarkar, S. Santra, S. K. Kundu, A. Hajra, G. V. Zyryanov, O. N.
Chupakhin, V. N. Charushin, A. Majee, Green Chem. 2016, 18, 4475–
4525; b) M. B. Gawande, V. D. B. Bonifácio, R. Luque, P. S. Branco, R.
S. Varma, ChemSusChem 2014, 7, 24−44; c) C. E. Tucker, J. Davidson,
P. Knochel, J. Org. Chem. 1992, 57, 3482−3485; d) D. J. Parks, R. E.
von, H. Spence, W. E. Piers, Angew. Chem. Int. Ed. 1995, 34, 809–811.
For selected references, see: a) E. A. Romero, J. L. Peltier, R. Jazzar,
G. Bertrand, Chem. Commun. 2016, 52, 10563−10565; b) K. Kuciński,
G. Hreczycho, ChemSusChem 2017, 10, 4695−4698; c) J.
Kaźmierczak, K. Kuciński, H. Stachowiak, G. Hreczycho, Chem. Eur. J.
Conflict of Interest
[
14]
The author declares no conflict of interest.
2
018, 24, 2509−2514; d) H. Stachowiak, J. Kaźmierczak, K. Kuciński, G.
Keywords: Catalyst-free • Hydroboration • Imines • Green
chemistry • Chemoselective
Hreczycho, Green Chem. 2018, 20, 1738−1742; e) W. Wang, M. Luo,
W. Yao, M. Ma, S. A. Pullarkat, L. Xu, P.-H. Leung, New J. Chem. 2019,
43, 10744−10749; f) A. Harinath, J. Bhattacharjee, T. K. Panda, Chem.
Commun. 2019, 55, 1386−1389; g) X. Xu, D. Yan, Z. Zhu, Z. Kang, Y. Yao,
Q. Shen, M. Xue, ACS Omega 2019, 4, 6775−6783; h) W. Wang, M.
Luo, D. Zhu, W. Yao, L. Xu, M. Ma, Org. Biomol. Chem. 2019, 17,
[
1]
For selected references, see: a) K. Hayes, Appl. Catal. A 2001, 221,
87−195; b) T. E. Mueller, K. C. Hultzsch, M. Yus, F. Foubelo, M. Tada,
1
Chem. Rev. 2008, 108, 3795−3892; c) J. Seyden-Penne, Reductions by
Alumino- and Borohydrides in Organic Synthesis, 2nd edn, Wiley-VCH, New
York, 1997; d) S. Nishimura, Handbook of heterogeneous catalytic
hydrogenation for organic synthesis, Wiley-VCH, New York, 2001; e) ed.
J. G. de Vries, C. J. Elsevier, Handbook of homogeneous hydrogenation,
Wiley-VCH, Weinheim, 2006.
3604−3608.
[
15]
a) A. Saini, C. R. Smith, F. S. Wekesa, A. K. Helms, M. Findlater, Org.
Biomol. Chem. 2018, 16, 9368−9372; b) M. Bhunia, P. K. Hota, G.
Vijaykumar, D. Adhikari, S. K. Mandal, Organometallics 2016, 35,
2930−2937.
[
[
2]
3]
For review, see: a) C. C. Chong, R. Kinjo, ACS Catal. 2015, 5,
3
1
238−3259; b) M.-X. Zhang, H.-L. Xu, J. Comput. Chem.2019, 40,
772−1779; c) M. Montury, J. Gore, Bull. Soc. Chim. Fr. 1975, 2622.
For selected references, see: a) M. L. Shegavi, S. K. Bose, Catal. Sci.
Technol. 2019, 9, 3307−3336; b) K. Kuciński, G. Hreczycho, Green
Chem. 2019, 21, 1912–1915; c) H. Yoshida, ACS Catal. 2016, 6,
1799−1811; d) J. Carreras, A. Caballero, P. J. Pérez, Chem. Asian J.
2019, 14, 329−343; e) R. Mamidala, V. K. Pandey, A. Rit, Chem.
Commun. 2019, 55, 989−992; f) W. Fan, L. Li, G. Zhang, J. Org. Chem.
2
2
019, 84, 5987−5996; g) C. M. Vogels, S. A. Westcott, Curr. Org. Chem.
005, 9, 687−699.
[
[
4]
5]
a) R. T. Baker, J. C. Calabrese, S. A. Westcott, J. Organomet. Chem.
995, 498, 109−117; b) B. S. N. Huchenski, A. W. H. Speed, Org. Biomol.
Chem. 2019, 17, 1999−2004.
For selected references, see: a) J. Wu, H. Zeng, J. Cheng, S. Zheng, J.
A. Golen, D. R. Manke, G. Zhang, J. Org. Chem. 2018, 83, 9442−9448;
b) A. Kaithal, B. Chatterjee, C. Gunanathan, J. Org. Chem. 2016, 81,
1
11153−11161; c) R. Arévalo, C. M. Vogels, G. A. MacNeil, L. Riera, J.
Pérez, S. A. Westcott, Dalton Trans. 2017, 46, 7750−7757; d) D.
Mukherjee, A.-K. Wiegand, T. P. Spaniol, J. Okuda, Dalton Trans. 2017,
46, 6183−6186.
[
[
6]
7]
a) Z. Huang, S. Wang, X. Zhu, Q. Yuan, Y. Wei, S. Zhou, X. Mu, Inorg.
Chem. 2018, 57, 15069−15078; b) S. Saha, M. S. Eisen, ACS Catal.
2019, 9, 5947−5956; c) D. Yan, P. Dai, S. Chen, M. Xue, Y. Yao, Q.
Shen, X. Bao, Org. Biomol. Chem. 2018, 16, 2787−2791.
For selected references, see: a) M. R. Adams, C-H. Tien, B. S. N.
Huchenski, M. J. Ferguson, A. W. H. Speed, Angew. Chem. Int. Ed.
2017, 56, 6268−6271; b) S. Yadav, S. Pahar, S. S. Sen, Chem.
Commun. 2017, 53, 4562−4564; c) V. A. Pollard, M. Ángeles Fuentes,
A. R. Kennedy, R. McLellan, R. E. Mulvey, Angew. Chem. Int. Ed. 2018,
57, 10651–10655; d) W. Liu, Y. Ding, D. Jin, Q. Shen, B. Yan, X. Ma, Z.
Yang, Green Chem. 2019, 21, 3812–3815.
[
8]
a) M. Arrowsmith, M. S. Hill, G. Kociok-Köhn, Chem. Eur. J. 2013, 19,
2776−2783; b) M. K. Bisai, S. Pahar, T. Das, K. Vanka, S. S. Sen, Dalton
Trans. 2017, 46, 2420−2424.
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.

Chemistry - An Asian Journal
10.1002/asia.201901016
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
[
a]
Vipin K. Pandey, S. N. R.
A general method for catalyst-free and
solvent-free ambient temperature
hydroboration of imines has been
developed which after hydrolysis gives
access to sterically and electronically
diverse secondary amines
Donthireddy,[ and Arnab Rit *
a]
[a]
Page No. – Page No.
Catalyst-Free and Solvent-Free Facile
Hydroboration of Imines
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.