A Highly Stereoselective Metal-Free Hydrogenation of Diimines for the Synthesis of Cis -Vicinal Diamines

Article abstract of DOI:10.1021/acs.orglett.5b01380

A highly stereoselective metal-free hydrogenation of vicinal diimines has been successfully realized for the first time using 5-10 mol % of Piers borane as a catalyst under mild conditions, and a variety of cis-1,2-diamines were obtained in 92-99% yields.

Full text of DOI:10.1021/acs.orglett.5b01380

Letter
pubs.acs.org/OrgLett
A Highly Stereoselective Metal-Free Hydrogenation of Diimines for
the Synthesis of Cis-Vicinal Diamines
Xiaxia Zhu and Haifeng Du*
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China
S
* Supporting Information
ABSTRACT: A highly stereoselective metal-free hydrogenation of vicinal
diimines has been successfully realized for the first time using 5−10 mol %
of Piers’ borane as a catalyst under mild conditions, and a variety of cis-1,2-
diamines were obtained in 92−99% yields. The current work provides a
novel and efficient approach for the synthesis of vicinal diamines.
icinal diamines are extremely important moieties present
in many natural products with notable biological activities
direct hydrogenation of vicinal diimines seems to be an efficient
and straightforward approach for the synthesis of vicinal
diamines (Scheme 2). Strangely, to the best of our knowledge,
V
and a large number of drugs.1 Meanwhile, they can also be used
as effective ligands or catalysts in asymmetric catalysis, and as
building blocks in synthetic chemistry.1 Various methodologies
have been well established for their synthesis, for example,
reduction of imidazoles or diimines,2 the nitro-Mannich
reaction,3 reductive coupling of imines,4 oxidative coupling of
amines,5 nucleophilic addition of diimines,6 substitution of
diols,7 C−H amination,8 and direct diamination of olefins.1g−j
For the important 1,2-diarylethane-1,2-diamines, many ap-
proaches can provide trans-isomers as predominate products,
but few can give cis-isomers in high selectivities (Scheme 1). In
Scheme 2. Metal-Catalyzed Hydrogenation of Imines
the catalytic hydrogenation of vicinal diimines has been rarely
reported, which might be partially attributed to the bulky steric
hindrance and/or the poison of the catalyst by a chelating
coordination with vicinal diimines. Exploration for an effective
catalytic system for the hydrogenation of vicinal diimines is a
challenging but highly desirable subject.
Scheme 1. Representative Approaches to 1,2-Diarylethane-
1,2-diamines
The frustrated Lewis pair (FLP) chemistry provides a novel
and powerful approach for the metal-free hydrogenation.11
Numerous classes of unsaturated compounds can be success-
fully hydrogenated under FLP catalysis, and imines have been
among the most widely investigated substrates.12,13 Some
important advances in asymmetric transformation have also
been achieved.14,15 Significantly, in 2011, Stephan and co-
workers reported a B(C6F5)3-catalyzed metal-free hydro-
genation of ethane-1,2-diimines (Scheme 3).12e Recently, our
group reported the stereo- or enantioselective hydrogenation of
imines, 2,6-disubstituted pyridines, silyl enol ethers, 2,3-
disubstituted quinoxalines, and 2,3,4-trisubstituted quinolines
using borane catalysts derived in situ from alkenes or
Scheme 3. Metal-Free Hydrogenation of Ethane-1,2-
diimines
fact, some unique properties for cis-1,2-diarylethane-1,2-
diamines in catalysis have been reported, and some other
usages still await further exploration.9 The development of
stereospecific access to cis-diamines is therefore of great
interest.
The transition-metal catalyzed hydrogenation of imines as
well as its asymmetric version has become one of the most
useful tools for the synthesis of amines.10 Accordingly, the
Received: May 12, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01380
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
alkynes.16−18 In comparison with transition metal catalysts, FLP
catalysts are not necessary to coordinate with substrates and
more compatible with the bulky steric hindrance, which
therefore provides good potential in solving the challenging
hydrogenation of vicinal diimines. Herein, we report our
preliminary efforts on this subject.
Scheme 4. Hydrogenation of Symmetrical Diimines
Initially, the reduction of vicinal diimine 1a with 6 equiv of
NaBH4 or NaBH3CN in ethanol at room temperature or 60 °C
was first conducted, but this reaction did not occur. The metal-
free hydrogenation of vicinal diimine 1a using 5 mol % of
B(C6F5)3 (3a)19 under H2 (20 bar) in toluene at 20 °C was
then examined. To our pleasure, this reaction proceeded very
quickly to furnish the cis-1,2-diamine product 2a in a
quantitative conversion (Table 1, entry 1). It was noteworthy
a
b
c
a
3a (5 mol %), 0.5 h. 3a (5 mol %), 2 h. 3a (10 mol %), 4 h.
Table 1. Metal-Free Hydrogenation of Diimine 1a
Scheme 5. Hydrogenation of Unsymmetrical Diimines
b
b
entry
borane 3
solvent
time (h)
conv (%)
cis/trans
1
2
3
4
5
6
7
8
3a
3b
3c
3a
3a
3a
3a
3a
3a
toluene
toluene
toluene
CH2Cl2
Et2O
0.5
2
>99
29
>99:1
>99:1
>99:1
−
2
65
c
2
nr
c
2
nr
−
pentane
mesitylene
C6H5F
2
60
>99:1
>99:1
>99:1
>99:1
2
90
2
>99
54
d
9
toluene
2
a
Diimine 1a (0.25 mmol), borane (5 mol %), and H2 (20 bar) in
b
c
d
solvent (1.0 mL) at 20 °C. By crude 1H NMR. No reaction. 1 mol
% of borane 3a.
a
b
c
3a (5 mol %), 2 h. 3a (10 mol %), 3 h. 3a (10 mol %), 2 h.
that this hydrogenation gave only a single cis-isomer. The bulky
steric hindrance of the diimine substrates might be a possible
explanation for the observed high cis-stereoselectivities. Using
in situ generated borane catalysts 3b and 3c derived from
styrene or 1,2,3,4,5-pentafluorostyrene with HB(C6H5)2 gave a
relatively lower conversion (Table 1, entries 2 and 3). Solvents
had a large impact on the reactivity: dichloromethane and
diethyl ether were not suitable solvents, while toluene proved
to be the optimal solvent for this hydrogenation (Table 1,
entries 4−8). Further reducing the catalyst loading to 1 mol %
can also give a reasonable conversion (Table 1, entry 9).
A variety of symmetrical vicinal diimines 1a−i were next
subjected to the metal-free hydrogenation under the optimal
reaction conditions. As shown in Scheme 4, all these reactions
went smoothly to produce the desired cis-1,2-diaryl-1,2-
diamines 2a−i as single isomers in 94−99% yields. To afford
chiral 1,2-diamines, various unsymmetrical vicinal diimines
were employed as substrates for this hydrogenation. Both
electron-donating and -withdrawing substituents on the phenyl
group were well tolerated to give 1,2-diamine products 2j−u in
92−99% yields (Scheme 5). The stereochemistry for the
obtained vicinal diamines was determined to be cis by an X-ray
structure of compound 2b (Figure 1).
Figure 1. X-ray structure of compound 2b.
borane catalyst formed in situ by the hydroboration of chiral
diene 4 with HB(C6F5)2 was further studied. It was found that
vicinal diamine 2v can be obtained in a quantitative conversion
with 10% ee (Scheme 6). Further efforts are still needed to
explore more efficient chiral catalysts.
In summary, a metal-free hydrogenation of 1,2-diaryl-1,2-
diimines was realized for the first time by using 5−10 mol % of
B(C6F5)3 as the catalyst under mild conditions. Significantly,
this hydrogenation is a highly stereoselective reaction to furnish
With these excellent results in hand, the asymmetric
hydrogenation of diimine 1v using 10 mol % of the chiral
B
DOI: 10.1021/acs.orglett.5b01380
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Scheme 6. Asymmetric Hydrogenation of Diimine 1v
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ASSOCIATED CONTENT
* Supporting Information
■
S
Procedure for the synthesis of diimines and the metal-free
hydrogenation of diimines, characterization of diimines and
products, a CIF file for the single crystal, and data for the
determination of enantiomeric excesses along with the NMR
spectra. The Supporting Information is available free of charge
on the ACS Publications website at DOI: 10.1021/
acs.orglett.5b01380.
(10) For a recent review, see: Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L.
Chem. Rev. 2011, 111, 1713.
AUTHOR INFORMATION
■
(11) For a seminal work, see: Welch, G. C.; Juan, R. R. S.; Masuda, J.
D.; Stephan, D. W. Science 2006, 314, 1124.
(12) For leading reviews, see: (a) Stephan, D. W. Org. Biomol. Chem.
2008, 6, 1535. (b) Stephan, D. W. Dalton Trans. 2009, 3129.
(c) Stephan, D. W.; Erker, G. Angew. Chem., Int. Ed. 2010, 49, 46.
Corresponding Author
*E-mail: haifengdu@iccas.ac.cn.
Notes
The authors declare no competing financial interest.
́
(d) Soos, T. Pure Appl. Chem. 2011, 83, 667. (e) Stephan, D. W.;
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ACKNOWLEDGMENTS
■
We are grateful for the generous financial support from the
National Basic Research Program of China (973 program,
2011CB808600) and the National Natural Science Foundation
of China (21222207).
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