Heterogeneous Catalytic Reduction of Tertiary Amides with Hydrosilanes Using Unsupported Nanoporous Gold Catalyst

Article abstract of DOI:10.1002/adsc.201900838

We have demonstrated that the unsupported nanoporous gold (AuNPore) was a green and highly efficient heterogeneous catalyst for the reduction of amides to amines using hydrosilanes as reductants. A variety of tertiary amides with a broad functional groups were reduced to the corresponding tertiary amines in the presence of 2 mol% of AuNPore and PheMe₂SiH or (Me₂SiH)₂O under mild conditions. AuNPore catalyst was recovered by simple filtration and used for twelve times without any loss of catalytic activity. The AuNPore/hydrosilane system was also successfully applied to the hydrosilative reduction of sulfoxides and N-oxides. (Figure presented.).

Full text of DOI:10.1002/adsc.201900838

UPDATES
DOI: 10.1002/adsc.201900838
Heterogeneous Catalytic Reduction of Tertiary Amides with
Hydrosilanes Using Unsupported Nanoporous Gold Catalyst
Yuhui Zhao,a Sheng Zhang,a, b Yoshinori Yamamoto,a, b Ming Bao,a,*
Tienan Jin,a, b, c,* and Masahiro Teradab
a
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, People’s Republic of China
E-mail: mingbao@dlut.edu.cn
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
b
Tel: +81-22-795-5707
E-mail: tjin@m.tohoku.ac.jp
c
Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Manuscript received: July 9, 2019; Revised manuscript received: August 27, 2019;
Version of record online: September 10, 2019
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201900838
developed.[4,5] However, taking into consideration of
the pharmaceutical process and potential industrial
Abstract: We have demonstrated that the unsup-
ported nanoporous gold (AuNPore) was a green and
application, the use of recoverable and reusable
highly efficient heterogeneous catalyst for the
heterogeneous catalysts with a high catalytic activity
reduction of amides to amines using hydrosilanes as
for the reduction of amides would be more desirable.
reductants. A variety of tertiary amides with a broad
So far, few examples with respect to the heterogeneous
functional groups were reduced to the corresponding
catalytic processes have been reported. For example,
tertiary amines in the presence of 2 mol% of
the hydrogenation of amides based on Cu/Cr, ReO3,
AuNPore and PheMe2SiH or (Me2SiH)2O under
Rh/Re, Rh/Mo, Ru/Re, Ru/Mo, Pd/Re@graphite cata-
mild conditions. AuNPore catalyst was recovered
lysts, Pt/V/HAP, and Re/TiO2 required high temper-
by simple filtration and used for twelve times
°
atures (160–260 C) or/and high H2 pressures (30–
without any loss of catalytic activity. The AuNPore/
hydrosilane system was also successfully applied to
the hydrosilative reduction of sulfoxides and N-
oxides.
365 bar) (Scheme 1).[6] A highly efficient heterogene-
ous catalytic reduction was realized by using hydroxy-
apatite-supported gold nanoparticles (AuNPs/HAP)
combining with hydrosilane reductants, in which the
catalytic activity of AuNPs was influenced by the
Keywords: Reduction; Amides; Amine; Nanoporous
gold; Hydrosilane
supporting materials and the reaction required a high
[7]
°
temperature of 110 C (Scheme 1).
Synthesis of amines by the reduction of amides is one
of the most efficient and direct methods due to the
abundance of the structurally diverse amides.[1] Tre-
mendous progress has been made employing various
reductants.[1–7] In general, the reduction of amides
requires a stoichiometric amount of strong nucleophilic
metallic hydride reductants, such as aluminum and
boron reagents.[1b,3] In comparision, the catalytic reduc-
tion of amides with molecular hydrogen and hydro-
silane reductants has attracted increasing attention in
terms of the functional group compatibility, safety
process, and side-product diminution.[1a,c,4–7] To date,
many homogenous catalytic process using transition
Scheme 1. Heterogeneous catalytic reduction of amides to
amines.
metals, Lewis acids, such as boronic acids, B(C6F5)3,
and electrophilic phosphonium cations have been
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Table 1. Optimization of Reaction Conditions.[a]
In the last few years, we have demonstrated that
nanoporous gold (AuNPore) having a unique three-
dimensional (3D) network nanopore structure was an
active and selective heterogeneous nanocatalyst in
various organic transformations.[8,9] The high surface
area compared to bulk metals, distinct electronic
property arising from hyperboloid-like ligaments, non-
toxicity, high thermal and mechanical rigidity, simple
recovery, and high reusability of AuNPore make it
more green and sustainable in the field of heteroge-
neous catalysis. Moreover, the bulk metallic feature of
AuNPore could prevent the aggregation-induced cata-
lytic deactivation and AuNPore without any supports
may help to understand the intrinsic catalytic activity
more easily by elimination of the support-effect.
During the investigation of the catalytic activity for the
dissociation of various chemical bonds in the last
decade, we have disclosed that the SiÀ H bond is
readily activated by AuNPore, reacting with water to
produce silanols and H2,[9a] which was successfully
extended to the selective reduction of various unsatu-
rated chemical bonds.[9b–f] Herein, we report that the
unsupported AuNPore is a highly active heterogeneous
catalyst for the selective reduction of tertiary amides to
Entry
SiÀ H
Yield [%][b]
1
PhMe2SiH
Et3SiH
(Me2SiH)2O
(i-Pr)3SiH
Ph2SiH2
99 (93)
2
34
45
0
67
0
0
0
0
3[c]
4
5[c]
6[d]
7[e]
8[f]
9[g]
PhSiH3
PhMe2SiH
PhMe2SiH
PhMe2SiH
[a] Reactions were carried out with 1a (0.5 mmol) and SiÀ H
(1.5 mmol) in the presence of 2 mol% of AuNPore catalyst at
°
80 C for 6 h.
[b] 1H NMR determined using CH2Br2 as an internal standard.
[c] 1.5 equiv. of (Me2SiH)2O was used.
[d] 1.5 equiv. of PhSiH3 was used.
[e] Without using catalyst.
[f] Au30Ag70 alloy was used instead of AuNPore.
tertiary amines with hydrosilanes as reductants under [g] PdNPore was used instead of AuNPore.
mild conditions (Scheme 1). AuNPore exhibited a
remarkably high reusability, which was used for twelve
times without any loss of catalytic activity.
2a in 93% isolated yield (entry 1). Further investiga-
The AuNPore catalyst was fabricated according to tion of other hydrosilanes revealed that the steric
our previously reported method by corrosive deal- hindrance of substituents on silicon drastically influ-
loying of Au30Ag70 alloy in 70 wt% nitric acid at enced the reaction efficiency. For example, the use of
ambient temperature for 18 h.[9b] The scanning micro- triethylsilane
and
1,1,3,3-tetramethyldisiloaxne
scope (SEM) image in Figure 1a clearly indicate the (TMDS) gave moderate yields of 2a, whereas triiso-
formation of 3D open pore network structure con- propylsilane was used to be totally ineffective (en-
structed by hyperboloid-like ligaments. The average tries 2–4). Diphenylsilane (1.5 equiv.) also can be used
diameter of Au ligaments was estimated to be around as reductant, giving 2a in good yield (entry 5).
30 nm.
However, the use of phenylsilane resulted in no
In light of our previously observed hydrosilane- reaction and the amide 1a was recovery quantitatively
effect on the AuNPore-catalyzed semihydrogenation of (entry 6). It was noted that the reduction without
alkynes,[9b] we initially investigated various hydro- catalyst or with the AuNPore precursor, AuAg alloy as
silanes in the reduction of N-phenyl-2-pyrrolidone (1a) a catalyst did not proceed at all (entries 7 and 8).
to N-phenylpyrrolidine (2a) using 2 mol% of AuNPore Moreover, nanoporous palladium (PdNPore) prepared
in EtOAc at 80 C (Table 1). The reaction with from a PdAl alloy[10] was used to be totally inactive
°
PhMe2SiH as a reductant afforded the desired product (entry 9), indicating the distinct catalytic performance
of AuNPore on the reduction of amides with hydro-
silanes. In addition, among various solvents tested
instead of EtOAc, toluene was also effective, produc-
ing 2a in 94% yield, but other solvents such as THF
(68%) and CH3CN (24%) were less effective.
The catalytic performance of AuNPore was further
studied for the reduction of various tertiary amides to
the corresponding tertiary amines using PhMe2SiH as a
°
reductant in EtOAc at 80 C (Table 2). The reductions
of 5-, 6-, and 8-membered cyclic amides having
benzyl, phenyl, and methyl substituents on the nitrogen
atom proceeded effectively, affording the correspond-
Figure 1. SEM Images of AuNPore: (a) before reaction, (b)
after twelfth reuse.
ing N-substituted pyrrolidine (2b), piperidine (2c),
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Table 2. Reduction of various amides using PhMe2SiH[a]
1,2,3,4-tetrahydroquinolidine (2d), and azocane (2e),
respectively, in good to high yields (entries 1–4).
Tertiary benzamides functionalized with acyclic and
cyclic alkyl chains were reduced to the corresponding
N-benzyl-substituted alkylamines 2f–i in good yields
(entries 5–8). It was found that TMDS was a more
effective reductant compared to PhMe2SiH for the
hydrosilative reduction of benzamides 1f–h having a
benzoyl functional group, affording the corresponding
benzylamines 2f–h in high yields (entries 5–7, in
parentheses). However, the benzamide 1i having a
morpholine group produced the corresponding benzyl-
amine 2i in a lower yield of 70% with TMDS (entry 8,
in parenthesis). N-methyl-N-phenylformamide 1j (at
°
60 C) as well as N-methyl-N-arylacetamides 1k and
1l were examined to be highly reactive amides, which
were reduced smoothly to the corresponding N,N-
dialkylanilines 2j–l in high yields (entries 9–11). Over-
all, the present protocol combining AuNPore catalyst
with PhMe2SiH exhibited high compatibility for the
amides substituted with at least two alkyl groups on
the nitrogen atom or/and on the carbonyl carbon. It
was noted that primary and secondary amides showed
low selectivity under the standard conditions, resulting
in a complex mixture of products including some
amounts of the recovered starting amides.
In comparison, tertiary benzamide 1m substituted
with an N-o-tolyl group showed a low reactivity for
the reduction using PhMe2SiH as a reductant, yielding
the corresponding tertiary aniline 2m in a very low
yield of 18% (Table 3, entry 1, data in parenthesis).
After a brief screening of hydrosilanes, we found that
the use of TMDS as a reductant dramatically improved
the reduction efficiency, producing 2m in a high yield
of 92% (entry 1). Consequently, the reductions of
various tertiary amides substituted with at least two
aromatic groups were examined using TMDS as a
reductant by comparison with PhMe2SiH. Similarly
high yields of anilines 2n and 2o were obtained when
the benzamides 1n and 1o bearing N-m-toyl and N-p-
tolyl groups were used (entries 2 and 3). The hydro-
silative reduction of the benzamides 1p and 1q having
an electron-donating methyl or methoxy group at the
para-position of the benzoyl moiety with TMDS
produced the corresponding benzylamines 2p and 2q
in high yields (entries 4 and 5). In comparison, the
benzamide 1r having an electron-withdrawing ester
group at the para-position of the benzoyl moiety was
less effective, giving the corresponding benzylamine
2r in a lower yield of 72% (entry 6). The benzamides
1s and 1t having an electron-donating methoxy group
at the meta- and para- position of the aniline moiety
were reduced in good to high yields (entries 7 and 8).
Although the benzamide 1u having an electron-with-
drawing ester group at the benzene ring gave a
moderate yield of 2u with TMDS, it could not be
reduced by PhMe2SiH (entry 9). The N-isopropyl-
[a] Reaction conditions: amides 1 (0.5 mmol), AuNPore
°
(2 mol%), PhMe2SiH (3 equiv.), EtOAc (0.5 mL) at 80 C.
[b] Isolated yields are shown. The yields using (Me2SiH)2O
(1.5 equiv.) as a reductant are shown in parentheses.
[c] 5 mol% of AuNPore was used.
[d]
°
Reaction was conducted at 60 C.
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Table 3. Reduction of various amides using (Me2SiH)2O[a]
[a]
°
Reaction conditions: amides 1 (0.5 mmol), AuNPore (2 mol%), (Me2SiH)2O (1.5 equiv.), EtOAc (0.5 mL) at 80 C.
[b] Isolated yields are shown. The yields using PhMe2SiH (3 equiv.) as a reductant are shown in parentheses.
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Scheme 2. AuNPore-catalyzed chemoselective reduction of conjugated amide 1y with PhMe2SiH and TMDS.
substituted tertiary benzamide 1v was a suitable
substrate for the present reduction, giving 2v in 84%
yield (entry 10). Notably, the use of TMDS enables the
reduction of the carboxamides 1w and 1x bearing
sterically bulky cyclohexyl and adamantly groups,
producing the corresponding tertiary anilines 2w and
2x in 83% and 94% yields, respectively (entries 11 and
12), which almost cannot be reduced by PhMe2SiH
even the carboxamides possess two alkyl chains as
compared to the results in Table 2.
A remarkable chemoselectivity was observed for
the reduction of the conjugated amide (Scheme 2). For
example, when N-methyl-N-(p-tolyl)cinnamamide 1y
was treated with 3 equiv. of PhMe2SiH in the presence
of 2 mol% of AuNPore for 10 h, the alkene-reduced
amide 1y’ was obtained in 93% yield without reducing
the carbonyl moiety. Interestingly, the complete reduc-
tion of 1y was realized when the reaction conducted
with 5 equiv. of PhMe2SiH for 36 h, producing the
corresponding aniline 2y in 92% yield. Similarly high
yields and selectivity of 1y’ and 2y were also obtained
Figure 2. Reusability of AuNPore for reduction of 1o to 2o
with TMDS under standard conditions. 1H NMR yields are
shown.
when 1.5 equiv. or 2.5 equiv. of TMDS was employed from the eighth reuse (11 h) to the twelfth reuse (14 h)
as a reductant for the reduction of 1y. These results probably due to the lager ligament nano-size (Table S1
indicated the preference of the alkene reduction over for the detailed reaction times). Similarly high reus-
the deoxygenation for the conjugated amide in the ability and catalytic activity of the AuNPore catalyst
AuNPore/hydrosilane system.
was also observed for the reduction of 1a to 2a with
The AuNPore catalyst showed a remarkably high PhMe2SiH as a reductant (Table S2). AuNPore was
reusability and catalytic activity for the reduction of reused for ten cycles and the yield of 2a was almost
amide 1o to amine 2o with TMDS under the quantitative in every reuse. The reaction for the tenth
conditions illustrated in Table 3. After the complete reuse required a slightly prolonged reaction time (7 h)
reduction of 1o (10 h), AuNPore was recovered by compared to the first use (6 h). Additionally, the
simple filtration followed by washed with acetone and leaching experiments were carried out for the reduction
dried for reuse. The recovered AuNPore was reused of 1a with PhMe2SiH in the presence of AuNPore
°
for additional eleven cycles and the yields of 2o were (2 mol%) at 80 C (Scheme 3). After 30 min, the half
still over 92% (Figure 2). It was mentioned that even of supernatant was transferred to the other reaction
though the ligament size of AuNPore slightly became vessel and 2a was formed in 36% yield at this time.
larger after the twelfth reuse compared to the fresh When this supernatant without AuNPore was continu-
AuNPore from the SEM image (Figure 1b), AuNPore ously heated for 6 h, the yield of 2a was still 36%.
still exhibited a high catalytic activity, indicating its Conversely, the residual containing AuNPore under-
robustness and durability under the present reduction went the complete reduction after being heated for 6 h,
conditions. However, the reaction times became longer affording 2a in 99% yield. Moreover, no any gold
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Scheme 3. Leaching experiments of AuNPore. 1H NMR yields are shown.
atoms were detected from the reaction solution by the deuterium incorporation at the benzyl position
inductively coupled plasma (ICP-MS) analysis. These (Scheme 5). The remaining 5% of the non-deuterated
results indicated that the current reduction proceeds in amine 2f should be formed through the D/H exchange
a heterogeneous catalytic manner on the solid state of probably due to the high reactivity of the hydrosilane
AuNPore.
with a trace amount of water on AuNPore.[9b] These
On the basis of our previous reports on the results indicated the involvement of the hydride trans-
dissociative activation of the SiÀ H bond on fer from the hydrosilane to the final product in the
AuNPore[9a,d] and our experimental outcomes, the present reduction mechanism.
plausible reaction mechanism is outlined in Scheme 4.
The present AuNPore/hydrosilane system was
The adsorption of both PhMe2SiH and amide 1a on successfully extended to the reduction of sulfoxides
AuNPore may induce the SiÀ O bond interaction to and N-oxides under the standard conditions. For
form an oxacarbenium ion A together with the example, both PhMe2SiH and TMDS could sufficiently
formation of a [AuNPore-H]À species.[9d] The oxacar- reduce sulfinyldibenzene (3a) and 1-(butylsulfinyl)
benium ion A species should be stabilized via its butane (3b) to the corresponding diphenylsulfane (4a)
resonance form of the iminium ion B, which is reduced and dibutylsulfane (4b) in high yields, in which
by the hydride species on AuNPore to form a N,O- TMDS showed a slightly higher reductive reactivity
acetal intermediate C. Another equivalent of compared to PhMe2SiH (Scheme 6a). Moreover, the
PhMe2SiH gets adsorb onto AuNPore, which reacts reduction of the pyridine N-oxide 5a with PhMe2SiH
with the intermediate C to form a iminium species D or TMDS also proceeded efficiently, giving rise to the
and (Me2PhSi)2O; the siloxane formation was con- corresponding pyridine derivative 6a in 86% and 90%
firmed from the reaction mixture. Finally, the iminium yields, respectively (Scheme 6b). The reduction of
species D undergoes the rapid reduction with the isoquinoline N-oxide (5b) with PhMe2SiH or TMDS
hydride species on AuNPore to afford the correspond- produced the corresponding isoquinoline 6b in moder-
ing amine 2a. In addition, the deuterium labelling ate yields due to the formation of the over-reduced
experiment was carried out using the deuterated hydro- product of 1,2,3,4-tetrahydroisoquinoline (25% and
silane in order to support the proposed hydride transfer 10%).
from the hydrosilane to the reduced product. The
In summary, we have demonstrated that AuNPore
reduction of the benzamide 1f with PhMe2SiD without any supporting materials is a green and highly
(3 equiv.) under the standard conditions afforded the efficient heterogeneous catalyst for the selective
deuterated amine 2f-d2 in 76% yield with 95% reduction of amides to amines with hydrosilanes under
mild conditions. The AuNPore catalyst showed a
significantly high reusability, which can be used for
twelve times without any loss of catalytic activity. A
variety of tertiary amides bearing cyclic and acyclic
alkyl chains, aromatic substituents, and sterically bulky
Scheme 5. Reduction of 1f to the deuterated amine using
Scheme 4. Plausible reaction mechanism.
PhMe2SiD.
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References
[1] Fore reviews, see: a) A. M. Smith, R. Whyman, Chem.
Rev. 2014, 114, 5477–5510; b) J. Rouden, J. Blanchet,
Synthesis 2018, 50, 984–997; c) A. Y. Khalimon, K. A.
Gudun, D. Hayrapetyan, Catalysts 2019, 9, 490.
[2] Selected examples for non-catalytic reduction of amides,
see: a) N. A. Sitte, M. Bursch, S. Grimme, J. Paradies, J.
Am. Chem. Soc. 2019, 141, 159–162; b) G. Pelletier,
W. S. Bechara, A. B. Charette, J. Am. Chem. Soc. 2010,
132, 12817–12819; c) G. Barbe, A. B. Charette, J. Am.
Chem. Soc. 2008, 130, 18–19.
[3] a) J. Seyden-Penne, Reductions by the Alumino- and
Borohydrides in Organic Synthesis, 2nd ed.; Wiley-VCH:
New York, 1997; b) H. C. Brown, A. Tsukamoto, J. Am.
Chem. Soc. 1959, 81, 502–503; c) H. C. Brown, A.
Tsukamoto, J. Am. Chem. Soc. 1964, 86, 1089–1095;
d) H. C. Brown, D. B. Bigley, S. K. Arora, N. M. Yoon,
J. Am. Chem. Soc. 1970, 92, 7161–7167; e) H. C. Brown,
P. Hein, J. Org. Chem. 1973, 38, 912–916; f) G. God-
joian, B. Singaram, Tetrahedron Lett. 1997, 38, 1717–
1720; g) G. W. Gribble, Chem. Soc. Rev. 1998, 27, 395–
404.
[4] Selected examples for homogeneous catalytic reduction
of amides using molecular hydrogen, see: a) Y.-Q. Zou,
S. Chakraborty, A. Nerush, D. Oren, Y. Diskin-Posner, Y.
Ben-David, D. Milstein, ACS Catal. 2018, 8, 8014–8019;
b) M. Meuresch, S. Westhues, W. Leitner, J. Klanker-
mayer, Angew. Chem. Int. Ed. 2016, 55, 1392–1395;
c) J. R. Cabrero-Antonino, E. Alberico, K. Junge, H.
Junge, M. Beller, Chem. Sci. 2016, 7, 3432–3442; d) J.
Coetzee, D. L. Dodds, J. Klankermayer, S. Brosinski, W.
Leitner, A. M. Z. Slawin, D. J. Cole-Hamilton, Chem.
Eur. J. 2013, 19, 11039–11050; e) A. A. N. Magro, G. R.
Eastham, D. J. Cole-Hamilton, Chem. Commun. 2007,
3154–3156.
Scheme 6. Reduction of sulfoxides (a) and N-oxides (b) using
PhMe2SiH and TMDS. The 1H NMR yields of 4b are shown.
groups were successfully reduced to the corresponding
tertiary amines by PhMe2SiH or (Me2SiH)2O in good
to high yields. We also demonstrated that the present
AuNPore/hydrosilane system can be applied to the
reduction of sulfoxides and N-oxides. Further exten-
sion of the present method to the selective reduction of
various inactive multiple bonds including nitriles and
esters are in progress.
Experimental Section
[5] Selected examples for homogeneous catalytic reduction
of amides using hydrosilanes, see: a) A. Nurseiit, J.
Janabel, K. A. Gudun, A. Kassymbek, M. Segizbayev,
T. M. Seilkhanov, A. Y. Khalimon, ChemCatChem 2019,
11, 790–798; b) A. Chardon, T. M. El Dine, R. Legay,
M. De Paolis, J. Rouden, J. Blanchet, Chem. Eur. J.
2017, 23, 2005–2009; c) P. Q. Huang, Q. W. Lang, Y. R.
Wang, J. Org. Chem. 2016, 81, 4235–4243; d) A.
Augurusa, M. Mehta, M. Perez, J. Zhu, D. W. Stephan,
Chem. Commun. 2016, 52, 12195–12198; e) O. O.
Kovalenko, A. Volkov, H. Adolfsson, Org. Lett. 2015,
17, 446–449; f) R. C. Chadwick, V. Kardelis, P. Lim, A.
Adronov, J. Org. Chem. 2014, 79, 7728–7733; g) J. T.
Reeves, Z. Tan, M. A. Marsini, Z. S. Han, Y. Xu, D. C.
Reeves, H. Lee, B. Z. Lu, C. H. Senanayake, Adv. Synth.
Catal. 2013, 355, 47–52; h) S. Das, D. Addis, S. Zhou,
K. Junge, M. Beller, J. Am. Chem. Soc. 2010, 132, 1770–
1771; i) S. Das, D. Addis, S. L. Zhou, K. Junge, M.
Beller, J. Am. Chem. Soc. 2010, 132, 4971–4971; j) S.
Zhou, K. Junge, D. Addis, S. Das, M. Beller, Angew.
Chem. Int. Ed. 2009, 48, 9507–9510; k) S. Hanada, E.
Tsutsumi, Y. Motoyama, H. Nagashima, J. Am. Chem.
General procedure for the AuNPore-catalyzed reduction of
amides to amines: To a solution of amide 1a or 1m (0.5 mmol,
1.0 eq.) and PhMe2SiH (for 1a, 1.5 mmol, 3.0 equiv.) or TMDS
(for 1m, 0.75 mmol, 1.5 equiv.) in EtOAc (1 M, 0.5 mL) was
added AuNPore (2 mol%, 2.0 mg) at room temperature. The
°
reaction mixture was stirred for 6 h or 10 h at 80 C. After
reaction, the AuNPore catalyst was recovered by simple
filtration and the filtrate was evaporated. The residual was
purified by a silica gel chromatography (ethyl acetate/hexanes=
1/50 as eluent) to afford 2a (68 mg) or 2m (97 mg) as a
colorless oil. The recovered AuNPore catalyst was washed with
acetone and dried for reuse.
Acknowledgements
The authors are grateful to the National Natural Science
Foundation of China (21573032, 21602026, and 21773021) for
their financial support. This work was also supported by the
China Postdoctoral Science Foundation (No. 2016 M590226).
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Soc. 2009, 131, 15032–15040; l) R. Kuwano, M.
Takahashi, Y. Ito, Tetrahedron Lett. 1998, 39, 1017–
1020.
Bao, Y. Yamamoto, Org. Biomol. Chem. 2014, 12, 2005–
2027; d) B. S. Takale, M. Bao, Y. Yamamoto, A. I.
Almansour, N. Arumugam, R. Suresh Kumar, Synlett
2015, 26, 2355–2380; e) T. Jin, M. Terada, M. Bao, Y.
Yamamoto, ChemSusChem 2019, 12, 2936–2954.
[6] Selected examples for heterogeneous catalytic reduction
of amides using molecular hydrogen, see: a) T. Mitsu-
dome, K. Miyagawa, Z. Maeno, T. Mizugaki, K.
Jitsukawa, J. Yamasaki, Y. Kitagawa, K. Kaneda, Angew.
Chem. Int. Ed. 2017, 56, 9381–9385; b) T. Toyao,
S. M. A. H. Siddiki, Y. Morita, T. Kamachi, A. S.
Touchy, W. Onodera, K. Kon, S. Furukawa, H. Ariga, K.
Asakura, K. Yoshizawa, K.-i. Shimizu, Chem. Eur. J.
2017, 23, 14848–14859; c) M. Stein, B. Breit, Angew.
Chem. Int. Ed. 2013, 52, 2231–2234; d) G. Beamson,
A. J. Papworth, C. Philipps, A. M. Smith, R. Whyman, J.
Catal. 2011, 278, 228–238; e) G. Beamson, A. J. Pap-
worth, C. Philipps, A. W. Smith, R. Whyman, Adv. Synth.
Catal. 2010, 352, 869–883; f) G. Beamson, A. J. Pap-
worth, C. Philipps, A. M. Smith, R. Whyman, J. Catal.
2010, 269, 93–102; g) C. Hirosawa, N. Wakasa, T.
Fuchikami, Tetrahedron Lett. 1996, 37, 6749–6752;
h) H. J. Schneider, H. Adkins, S. M. Mcelvain, J. Am.
Chem. Soc. 1952, 74, 4287–4290; i) H. Adkins, B.
Wojcik, J. Am. Chem. Soc. 1934, 56, 2419–2424.
[9] For related AuNPore-catalyzed transformations reported
by our group, see: a) N. Asao, Y. Ishikawa, N.
Hatakeyama, Menggenbateer, Y. Yamamoto, M. Chen,
W. Zhang, A. Inoue, Angew. Chem. 2010, 122, 10291–
10293; Angew. Chem. Int. Ed. 2010, 49, 10093–10095;
b) M. Yan, T. Jin, Y. Ishikawa, T. Minato, T. Fujita, L.-Y.
Chen, M. Bao, N. Asao, M. Chen, Y. Yamamoto, J. Am.
Chem. Soc. 2012, 134, 17536–17542; c) M. Yan, T. Jin,
Q. Chen, E. H. Ho, T. Fujita, L.-Y. Chen, M. Bao, M.
Chen, N. Asao, Y. Yamamoto, Org. Lett. 2013, 15, 1484–
1487; d) B. S. Takale, S. M. Tao, X. Q. Yu, X. J. Feng, T.
Jin, M. Bao, Y. Yamamoto, Org. Lett. 2014, 16, 2558–
2561; e) B. S. Takale, S. Wang, X. Zhang, X. Feng, X.
Yu, T. Jin, M. Bao, Y. Yamamoto, Chem. Commun. 2014,
50, 14401–14404; f) B. S. Takale, S. M. Tao, X. Q. Yu,
X. J. Feng, T. Jin, M. Bao, Y. Yamamoto, Tetrahedron
2015, 71, 7154–7158; g) Y. Ishikawa, Y. Yamamoto, N.
Asao, Catal. Sci. Technol. 2013, 3, 2902–2905; h) B. S.
Takale, X. Feng, Y. Lu, M. Bao, T. Jin, T. Minato, Y.
Yamamoto, J. Am. Chem. Soc. 2016, 138, 10356–10364.
[10] Y. Lu, X. Feng, B. S. Takale, Y. Yamamoto, W. Zhang,
M. Bao, ACS Catal. 2017, 7, 8296–8303.
[7] Y. Mikami, A. Noujima, T. Mitsudome, T. Mizugaki, K.
Jitsukawa, K. Kaneda, Chem. Eur. J. 2011, 17, 1768–
1772.
[8] For reviews on nanoporous metal-catalyzed transforma-
tions, see: a) N. Asao, T. Jin, S. Tanaka, Y. Yoshinori,
Pure Appl. Chem. 2012, 8, 1771–1784; b) Y. Yamamoto,
Tetrahedron 2014, 70, 2305–2317; c) B. S. Takale, M.
Adv. Synth. Catal. 2019, 361, 4817–4824
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