Exclusive chemoselective reduction of imines in the coexistence of aldehydes using AuNPore catalyst

Article abstract of DOI:10.1021/ol500958p

Aldimines (R¹HC=NR²) were reduced in the coexistence of aldehydes (R¹CHO) with 100% chemoselectivity by the use of AuNPore giving corresponding amines (R¹H₂C-NHR²) in high chemical yields.

Full text of DOI:10.1021/ol500958p

Letter
pubs.acs.org/OrgLett
Exclusive Chemoselective Reduction of Imines in the Coexistence
of Aldehydes Using AuNPore Catalyst
Balaram S. Takale,† Shan Mou Tao,† Xiao Qiang Yu,† Xiu Juan Feng,† Tienan Jin,‡ Ming Bao,*,†
and Yoshinori Yamamoto*,†,‡
†State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China
‡WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai 980-8577, Japan
S
* Supporting Information
ABSTRACT: Aldimines (R1HCNR2) were reduced in the coexistence of aldehydes
(R1CHO) with 100% chemoselectivity by the use of AuNPore giving corresponding
amines (R1H2C-NHR2) in high chemical yields.
coexistence of aldehydes. The reduction of a 1:1 mixture of
t is widely accepted in the organic community that
Inucleophilic addition (including hydride) to an aldehyde takes benzaldehydes 2 and the corresponding imines 1 is summarized
in Table 1.
place much easier than that to the corresponding imine. Actually, a
C-13 chemical shift of the aldehyde carbon of benzaldehyde
appears at δ 192.61 ppm, and the carbon of the correspond-
ing imine, PhCHNPh, appears at δ 160.64 ppm (see the
Supporting Information), indicating that benzaldehyde is more
electrophilic than the imine under ordinary conditions. We
have found that aldimines (R1HCNR2) were reduced in the
coexistence of aldehydes (R1CHO) with exclusive chemo-
selectivity using an AuNPore catalyst/PhMe2SiH/water system
(Scheme 1).
The reactions with NaBH4, LiAlH4, and homogeneous Pd
catalyst Pd(OAc)2, under conditions B−D, favored reduction of
the CO bond rather than the CN bond. Use of 0.25 equiv
of NaBH4 resulted in 30% selectivity toward reduction of
CN and ca. 70% selectivity toward CO bond, while use of
0.25 equiv of LiAlH4 resulted in 1% selectivity for reduction
CN bond and nearly 99% selectivity for reduction of CO
bond (entry 1, conditions B and C). Even use of an excess of
these reagents showed still higher selectivity toward a CO
bond than a CN bond. The use of Pd(OAc)2 and 10 bar of
H2 gas proved less efficient for the reduction of the CN bond
(all the entries), and additionally, in a certain case parent aniline
was also isolated (entry 2, conditions D). Remarkably, totally
different results were observed in the case of the AuNPore/
PhMe2SiH system; only imines could undergo reduction, and
aldehydes could not undergo hydrogenation at all (entries 1−6,
condition A). Further, it should be mentioned that reduction of
imine 1a using a gold homogeneous catalysts/PhMe2SiH system
resulted in very low yield (7−10%) of the desired product.5
This exclusive imine reduction property of nanoporous gold
was further extended to a variety of imines. Accordingly, imine
1a was treated with 5 mol % of AuNPore catalyst, 1.2 equiv of
PhMe2SiH, and 1.2 equiv of H2O in acetonitrile as a solvent
(Table 2). After being stirred for 5 h at room temperature, the
desired product could be obtained in 90% yield. It is note-
worthy to mention that even the use of PdNPore as a catalyst
gave the desired product in 65% yield, but the use of PdNPore
was avoided for further study owing to its leaching property.6
Among other imines studied, those having electron-donating or
weak electron-withdrawing groups at the aromatic ring resulted
Scheme 1. Exclusively Chemoselective Reduction of Imines
in the Co-existence of Aldehydes
In recent years, the nanoporous gold (AuNPore) skeleton
catalyst proved to be an efficient and robust catalyst for a
variety of organic reactions,1 and its well-defined structure was
also established.2 In the research of liquid phase reactions
using robust, easily available, and reusable nanoporous gold
(AuNPore) catalyst, we reported an AuNPore/silane system
for reduction of carbon−carbon multiple bonds for selective
reduction of alkynes to alkenes3 and quinolines to tetrahy-
droquinolines.4 We were interested in investigating the reduc-
tion of carbon−heteroatom multiple bonds, such as CO and
CN, through this new reducing system, and we accidentally
discovered that reduction of imines took place exclusively in the
Received: April 1, 2014
Published: April 16, 2014
© 2014 American Chemical Society
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Letter
Table 1. Chemoselectivities in the Reduction of Imines and
Aldehydes with Representative Reducing Reagents/
Catalysts
Table 2. Reduction of Simple Imines Using AuNPore/
a
PhMe2SiH
a
a
Reaction conditions: 1 (0.5 mmol), AuNPore (5 mol %), PhMe2SiH
b
(0.6 mmol), H2O (0.6 mmol), acetonitrile (2.0 mL), at rt. Isolated
yield. Reactions were carried out at 80 °C.
c
Scheme 2. Deuterium Labeling Experiment in the Reduction
of Enimine
Scheme 3. Plausible Pathway for Imine Reduction
a
Reaction conditions: a mixture of 1 (0.5 mmol) and 2 (0.5 mmol)
(entries 8 and 14). However, bulky substitutions at R2 resulted
in lower yields of the desired products (entries 6 and 14). It
should be noted that tosyl-protected enimine 7m underwent
1,2 reduction without problem (entry 13).
After establishing the intermolecular chemoselectivity and
scope of selective imine reduction, we were interested in the
intramolecular selectivity using representative reducing agents.
Accordingly, we treated enimines 9 with three different con-
ditions: AuNPore/silane, NaBH4, and LiAlH4 (Table 4). To
our delight, use of AuNPore resulted in selective reduction of
imine groups, and no other functional groups such as ketones
or esters were reduced (entry 1). However, use of NaBH4 or
LiAlH4 as a reducing agent resulted in a mixture of products
(entry 2 and 3).
Catalyst reusability of AuNPore catalyst was tested, and
remarkably, the catalyst activity did not show any change even
after the fifth use (see the Supporting Inforamtion). Generally,
the catalyst was recovered by picking up with tweezers, washing
5 times with acetone, and drying under vacuum. It was used
without further activation.
We carried out the deuterium-labeling experiment using
deuterated silane 12 (Scheme 2). α-Deuterated amine 8a-1′ was
obtained in 57% yield with 92% deuterium labeling.
was treated with the representative reagents and catalysts under four
b
different sets of conditions (A−D). Isolated yield calculated on the
c
d
basis of 1. Isolated yield calculated on the basis of 2. Use of
0.25 equiv of NaBH4 resulted in 3a in 29% yield and 4a in 66% yield.
e
Use of 0.25 equiv of LiAlH4 resulted 3a in <1% yield and 4a in 82%
yield. Parent aniline (4-methoxyaniline) was isolated in 58% yield.
f
in good to excellent yields of desired amines, while strong
electron-withdrawing groups such as −COOH and −COOMe
resulted in moderate yields of the respective products (entries 6
and 7). Notably, these acid and ester groups were tolerated
under the reaction conditions and did not undergo reduction.
Encouraged by these results, we next examined the scope of
this reducing system for enimine reduction to examine whether
allylamines7 can be obtained selectively (Table 3). The enimine
7a was reduced by AuNPore/PhMe2SiH at 80 °C to give 75%
yield of 8a (as a 9:1 mixture of 1,2-reduction 8a-1 and complete
reduction 8a-2). Electron-donating groups on the aryl group
attached to N (R2 group) led to good yields of the desired
products (entries 2−5 and 7), while electron-donating groups
at R1 did not exert significant effect on the yield or even gave a
bit lower yields in some cases (entries 9−12). A bromine
substituent at R2 or a benzyl group gave high chemical yields
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Letter
a
Table 3. Allylamines from Enimines via Reduction Using
AuNPore/PhMe2SiH
Table 4. Intramolecular Selective Reduction Study
a
a
Reaction conditions: 9 (0.5 mmol) were treated with the reducing
b
c
reagents under the mentioned conditions. Isolated yield. AuNPore
(5 mol %), PhMe2SiH (0.6 mmol), H2O (0.6 mmol), acetonitrile
(2.0 mL), at 80 °C, 5 h. NaBH4 (0.25 mmol), methanol (2.0 mL), rt,
10 h. NaBH4 (0.6 mmol), methanol (2.0 mL), at 60 °C, 10 h. LiAlH4
(0.25 mmol), diethyl ether (2.0 mL), rt, 10 h. LiAlH4 (0.6 mmol),
d
e
f
g
diethyl ether (2.0 mL), rt, 10 h.
selectivity toward reduction of imines in coexistence of aldehydes
and other reducible groups. The catalyst can be reused several
times without any loss in activity.
ASSOCIATED CONTENT
* Supporting Information
■
S
a
Experimental procedure and characterization data for all
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
Reaction conditions: 7 (0.5 mmol), AuNPore (5 mol %), PhMe2SiH
(0.6 mmol), H2O (0.6 mmol), acetonitrile (2.0 mL), 80 °C, 5 h.
b
c
d
Isolated yield. Reaction time was increased to 7 h. Reaction time
was increased to 10 h.
AUTHOR INFORMATION
Corresponding Authors
■
On the basis of this deuterium-labeling experiment a
plausible pathway for the reduction of imine is shown in
Scheme 3. Adsorption of silane and water on AuNPore would
result in [AuNPore−H]− species.3,4 It was interesting to know
that no H2 bubbling was observed in this reaction, while it was
observed clearly in the absence of amine additives.3 This
strongly suggests that the N atom of imine holds the other
proton of water to avoid rapid elimination of H2 gas. The
resulting protonated imine further abstracts hydride from
Au−H species to give the product via regeneration of the
AuNPore catalyst. In the case of aldehyde, the oxygen atom of
CO would not be strong enough to hold the proton of water,
compared to N atom of imine, leading to no reduction of
aldehyde.
*E-mail: mingbao@dlut.edu.cn.
*E-mail: yoshi@dlut.edu.cn.
Notes
The authors declare no competing financial interest.
REFERENCES
■
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Letter
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