Efficient chemoselective hydrogenation of organic azides catalyzed by palladium nanoparticles with alkyne-derived homogeneous supports

Article abstract of DOI:10.1016/j.tetlet.2016.08.002

Catalytic chemoselective hydrogenation of organic azides using palladium nanoparticles stabilized by alkyne derivatives was studied. A broad range of aromatic and aliphatic azides were smoothly reduced to the corresponding amines in excellent yields with a quite small amount of the catalyst. Hydrogenation of 3-phenylpropylazide gave 3-phenylpropylamine almost quantitatively with a substrate-to-palladium molar ratio (S/Pd) of 12,900 under 8?atm of H₂. The reaction under 1?atm of H₂also proceeded smoothly with an S/Pd of 1000. Several reduction-sensitive functional groups, such as carbonyl, halide, benzylic OH, and aliphatic nitro were well tolerated under the reaction conditions.

Full text of DOI:10.1016/j.tetlet.2016.08.002

Accepted Manuscript
Efficient chemoselective hydrogenation of organic azides catalyzed by palladi-
um nanoparticles with alkyne-derived homogeneous supports
Noriyoshi Arai, Nozomi Onodera, Takeshi Ohkuma
PII:
S0040-4039(16)30979-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.08.002
TETL 47973
Reference:
Tetrahedron Letters
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29 July 2016
2 August 2016
Please cite this article as: Arai, N., Onodera, N., Ohkuma, T., Efficient chemoselective hydrogenation of organic
azides catalyzed by palladium nanoparticles with alkyne-derived homogeneous supports, Tetrahedron Letters
(2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.08.002
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Efficient chemoselective hydrogenation of
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homogeneous supports
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Noriyoshi Arai, Nozomi Onodera, and Takeshi Ohkuma*

1
Tetrahedron Letters
Efficient chemoselective hydrogenation of organic azides catalyzed by palladium
nanoparticles with alkyne-derived homogeneous supports
Noriyoshi Araia, Nozomi Onoderaa, and Takeshi Ohkumaa,
aDivision of Applied Chemistry and Frontier Chemistry Center, Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Catalytic chemoselective hydrogenation of organic azides using palladium nanoparticles
stabilized by alkyne derivatives was studied. A broad range of aromatic and aliphatic azides
were smoothly reduced to the corresponding amines in excellent yields with a quite small
amount of the catalyst. Hydrogenation of 3-phenylpropylazide gave 3-phenylpropylamine
almost quantitatively with a substrate-to-palladium molar ratio (S/Pd) of 12,900 under 8 atm of
H2. The reaction under 1 atm of H2 also proceeded smoothly with an S/Pd of 1,000. Several
reduction-sensitive functional groups, such as carbonyl, halide, benzylic OH, and aliphatic nitro
were well tolerated under the reaction conditions.
Available online
Keywords:
Palladium
Nanoparticles
Hydrogenation
Organic azide
Chemoselective
2009 Elsevier Ltd. All rights reserved.
Amines are quite important compounds in various research
fields, including pharmaceuticals, dyes, agrochemicals, and so
on.1 Reduction of azides is one of the simplest and most reliable
methods for the preparation of amines.2 Although a number of
reactions have been reported for this important transformation,3–5
catalytic hydrogenation is superior to the others both from an
economical and ecological point of view, especially in a large
scale preparation.6 Palladium(0) supported on charcoal is widely
used as a catalyst in this reaction.7 However, problems in
chemoselectivity are occasionally encountered when the substrate
contains functional groups sensitive under the reaction conditions
of hydrogenation.8,9 To address this issue, deliberately designed
catalysts have been developed for the chemoselective
hydrogenation.10,11
Scheme 1. Preparation of Pd NPs 1.
We chose 3-phenylpropylazide (3a) as a standard substrate to
optimize the reaction conditions (Table 1). When the azide 3a
was hydrogenated in THF at 50 °C under 8 atm of hydrogen in
the presence of a catalytic amount of Pd NPs 1b (substrate-to-
palladium molar ratio (S/Pd) = 1.3×104, loaded as a 5.0 mM
DMF solution), the reaction was completed within 16 h to give 3-
phenylpropylamine (4a) in nearly quantitative yield (Table 1,
Entry 1). The S/Pd per time-to-full conversion (TOFav) was
7.9×102 h–1. The reaction also proceeded under atmospheric
pressure of hydrogen (Entry 2). The starting material 3a was
completely consumed, but the yield of 4a was 79%. 1H NMR
analysis of the crude reaction mixture showed that remaining 3a
was converted to dimeric imine, though the reaction pathway was
not clear. THF was a solvent of choice, but methanol, ether, and
hexane were also useful solvents (Entries 3–5). On the other
hand, the reactions in toluene, dichloromethane, and ethyl acetate
were much slower than those in the solvents described above,
resulting in unsatisfactory product yields (Entries 6–8).
We recently reported novel palladium nanoparticles (Pd NPs
1) prepared from Pd(OCOCH3)2 and 2 equiv of t-C4H9OK (1a) or
NaBH4 (1b) with 10 equiv of 4-octyne in DMF at ambient
temperature for 12 h (Scheme 1).12 Pd NPs 1 in DMF (10 mM)
are homogeneously dispersed and have a shelf-life of more than a
year at ambient temperature without aggregation. These Pd NPs
exhibited excellent catalytic activity in selective partial
hydrogenation of alkynes and chemoselective hydrogenation of
nitroarenes.12,13 In the course of our study, we found that the Pd
NPs 1b efficiently catalyze chemoselective hydrogenation of aryl
and alkyl azides. Here, we would like to describe the features of
the convenient functional group transformation.
———
 Corresponding author. Tel.: +81-11-706-6599; fax: +81-11-706-6598; e-mail: ohkuma@eng.hokudai.ac.jp

2
Tetrahedron
Table 1. Hydrogenation of Azide 3a Catalyzed by Pd NPs 1b
Table 2. Substrate Scope in the Hydrogenation of Azides 3 with
Pd NPs 1b
Entry
S/Pd
12700
1000
12700
13000
12900
12600
12800
12500
Solvent
THF
THF
CH3OH
Et2O
Hexane
Toluene
CH2Cl2
AcOEt
Conv. (%) Yielda (%)
1
2b
3
4
5
6
7
8
100
100
100
100
100
56
>99
79
95
95
97
54
23
3
25
6
a Estimated by 1H NMR by using 1,3,5-trimethoxybenzene as an
internal standard.
b Under 1 atm of H2.
The stage was set for investigating the scope of this
transformation. Hydrogenation of a range of aromatic and
aliphatic azides was carried out, and the results are summarized
in Table 2. Hydrogenation of azide 3a proceeded smoothly to
give the corresponding amine 4a, which was isolated as Boc
carbamate with a slight loss of the product (Entry 1). Benzyl,
phenyl, and cyclohexyl azides (3b–d) were also successfully
converted to the amines in high yields (Entries 2–5). Methanol
could be employed as well as THF in some cases. In the
hydrogenation of 4'-azidoacetophenone (3e), the azide moiety
was selectively reduced to amine without loss of the carbonyl
group to afford 4'-aminoacetophenone (4e) in excellent yield
(Entry 6).14 We generally performed the reactions under gentle
warming in a water bath in order to secure the catalyst activity
and to keep the temperature constant throughout the reaction;
however, the reaction could also be carried out at ambient
temperature (Entry 7). It should be noted that the hydrogenation
of 4-halobenzyl azides (3f and 3g) gave the amines 4f and 4g
without hydrogenolysis of the halide moieties (Entry 8 and 9).15
The hydroxy group at the benzylic position remained intact
throughout the hydrogenation of 3h to give the amine 4h in
nearly quantitative yield (Entry 10).16 Unfortunately, the
hydrogenation of thienyl azide 3i hardly proceeded, even with a
relatively large amount of the catalyst, probably due to poisoning
by sulfur (Entry 11). In the hydrogenation of 4-formylbenzyl
azide, azide group was hydrogenated faster than formyl group.
The reaction must be carried out in the presence of Boc2O to
avoid self-condensation, although the addition of Boc2O caused
retardation of the reaction. The starting material 3j was
consumed in 46 h to give 4i in 53% yield, accompanied by the
formation of p-phthaldehyde, 4-cyanobenzaldehyde (apprx. 5%
each), and a mixture of unidentified compounds (Entry 12).
Selective hydrogenation in the presence of alkene moiety turned
out to be difficult.
Entry
1
2
3
4
S/Pd
12900
10800
11000
1100
5100
10000
5000
4900
5600
9900
2000
5000
Solvent
THF
THF
CH3OH
CH3OH
THF
THF
CH3OH
THF
THF
THF
Time (h)
16
21.5
24
Yield of 4a (%)
>99 (87)b,c
99 (88)b,c
83
3
3a
3b
3b
3c
3d
3e
3e
3f
3g
3h
3i
24
24
18
8
24
22
24
24
94
5
94 (84)b,d
99 (93)b
>99 (99)b
89 (78)b,c
86 (94)b,c,f
>99 (99)b,c
53
6
7e
8
9
10
11
12g
THF
THF
46
52 (53)b
3j
a Estimated by 1H NMR by using 1,3,5-trimethoxybenzene
(Entries 2–4, 6–8), triphenylmethane (Entry 5, 9, and 12), or
1,1,2,2-tetrachloroethane (Entries 1, 10, and 11) as an internal
standard.
b The isolated yield is given in parentheses.
c Isolation was carried out after Boc protection.
d Isolation was carried out after benzoylation.
e Carried out at ambient temperature.
f Small amounts (apprx. 10%) of homodimeric imine were
detected in the crude mixture (see ref.18). The isolated yield
higher than NMR yield was attributed to reproduction of amine
4g by the hydrolysis of the imine during Boc protection.
g The hydrogenation was carried out in the presence of Boc2O in
order to avoid self-condensation.
To demonstrate the chemoselective feature of this catalyst, we
compared the hydrogenation of 3e by using conventional
hydrogenation conditions with commercially available Pd/C
(Scheme 2).17 When the azide 3e was hydrogenated at 25 °C
under 1 atm of hydrogen in the presence of Pd NPs 1b (3e/Pd
molar ratio was 1000), 4'-aminoacetophenone (4e) was produced
quantitatively, with complete retention of the carbonyl moiety
without any control of the reaction. In marked contrast,
hydrogenation of 3e under typical reaction conditions with
commercial Pd/C (10%) gave about 10% of over-reduced
compounds 5 and 6 as byproducts. Although, we can not rule out
the possibility that 4e would be selectively obtained by stopping
the reaction at an earlier stage, much care must be taken to avoid
over reduction.
Chemoselective hydrogenation of azides catalyzed by
palladium on boron nitride was reported.11a The amine products
were obtained with keeping functionalities, such as ketone, nitro,
alkene, and benzylic ester intact. The catalyst turnover number
reached to 990. Though our catalytic system has room for
improvement in the chemoselectivty, it has an advantage over the
preceding method from a standpoint of catalyst turnover.

3
This work was supported by Grants-in-Aid from the Japan
Society for the Promotion of Science (JSPS) (No. 15H03802) and
the MEXT (Japan) program "Strategic Molecular and Materials
Chemistry through Innovative Coupling Reactions" of Hokkaido
University.
References and notes
1.
(a) Travis, A. S. In The Chemistry of Anilines, Part 1; Rappoport,
Z., Ed.; Wiley: Chicherster, 2007; p. 1; (b) Kahl, T.; Schröder, K.-
W.; Lawrence, F. R.; Marshall, W. J.; Höke, H.; Jäckh, R.
Ullmann’s Encyclopedia of Industrial Chemistry; Wiley-VCH:
Weinheim, 2011. Aniline; (c) Franzen, F.; Eysell, K. Biologically
Active Amines Found in Man: Their Biochemistry, Pharmacology,
and Pathophysiological Importance; Pergamon Press: Oxford,
New York, 1969.
2.
3.
(a) Haase, J. In Organic Azides: Synthesis and Applications;
Bräse, S.; Banert, K., Eds.; Wiley: Chicherster, 2009; p. 29; (b)
Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297.
Reduction by metal hydride reagents: (a) Maddani, M. R.;
Moorthy, S. K.; Prabhu, K. R. Tetrahedron 2010, 66, 329; (b)
Fringuelli, F.; Pizzo, F.; Vaccaro, L. Synthesis 2000, 646; (c)
Hays, D. S.; Fu, G. C. J. Org. Chem. 1998, 63, 2796; (d) Raja
Ram, S.; Charly, K.P.; Iyengar, D. S. Synth. Commun. 2000, 30,
4495; (e) Sun, J.-H.; Teleha, C. A.; Yan, J.-S.; Rodgers, J. D.;
Nugiel, D. A. J. Org. Chem. 1997, 62, 5627; (f) Salunkhel, A. M.;
Brown, H. C. Tetrahedron Lett. 1995, 36, 7987; (g) Ranu, B. C.;
Sarkar, A.; Chakraborty, R. J. Org. Chem. 1994, 59, 4114; (h)
Rao, H. S. P.; Siva, P. Synth. Commun. 1994, 24, 549; (i) Yoon,
N. M.; Choi, J.; Young, S. Synth. Commun. 1993, 23, 3047; (j)
Soai, K.; Yokoyama, S.; Ookawa, A. Synthesis 1987, 48; (k)
Rolla, F. J. Org. Chem. 1982, 47, 4327.
Reduction by low valent metal reagents: (a) Reddy, G. V.; Rao, G.
V.; Iyengar, D. S. Tetrahedron Lett. 1999, 40, 3937; (b) Huang,
Y.; Zhang, Y.; Wang, Y. Tetrahedron Lett. 1997, 38, 1065; (c)
Goulaouic-Dubois, C.; Hesse, M. Tetrahedron Lett. 1995, 36,
7427; (d) Fitz, W.; Schwark, J.-R.; Wong, C.-H. J. Org. Chem.
1995, 60, 3663; (e) Mati, S. N.; Spevak, P.; Reddy, A. V. N.
Synth. Commun. 1988, 18, 1201.
Reduction by phosphines, sulfides, and other reagents: (a)
Cantillo, D.; Moghaddam, M. M.; Kappe, C. O. J. Org. Chem.
2013, 78, 4530; (b) Kamal, A.; Shankaraiah, N.; Reddy, K. L.;
Devaiah, V. Tetrahedron Lett. 2006, 47, 4253; (c) Kamal, A.;
Ramana, K. V.; Ankati, H. B.; Ramana, A. V. Tetrahedron Lett.
2002, 43, 6861; (d) Kamal, A.; Rao, N. V.; Laxman, E.
Tetrahedron Lett. 1997, 38, 6945; (e) Suzuki, H.; Takaoka, K.
Chem. Lett. 1984, 1733; (f) Vaultier, M.; Knouzi, N.; Carrié, R.
Tetrahedron Lett. 1983, 24, 763; (g) Bayley, H.; Standring, D. N.;
Knowles, J. R. Tetrahedron Lett. 1978, 3633.
Scheme 2. Comparison with commercial Pd/C.
Since we already found that the Pd NPs 1b shows excellent
catalytic activity in the hydrogenataion of aromatic nitro
compounds,13 chemoselective reduction of azide over aromatic
nitro group seems difficult. However, an aliphatic azide 3a was
hydrogenated prior to an aliphatic nitro compound 7 as
demonstrated in Scheme 3. The competitive reaction was
conducted under the typical conditions. The Boc-protected
amine 4a was obtained in high yield after treatment with Boc2O,
while nitro compound 7 was recovered quantitatively.
4.
5.
6.
(a) Brown, M. F.; Mitton-Fry, M. J.; Arcari, J. T.; Barham, R.;
Casavant, J.; Gerstenberger, B. S.; Han, S.; Hardink, J. R.; Harris,
T. M.; Hoang, T.; Huband, M. D.; Lall, M. S.; Lemmon, M. M.;
Li, C.; Lin, J.; McCurdy, S. P.; McElroy, E.; McPherson, C.;
Marr, E. S.; Mueller, J. P.; Mullins, L.; Nikitenko, A. A.; Noe, M.
C.; Penzien, J.; Plummer, M. S.; Schuff, B. P.;
Scheme 3. Competitive reaction between azide 3a and nitro compound 7.
It may be worth noting that the Pd NPs 1b can be handled as
dilute stock solution with a shelf-life of longer than one year
under the air and easily added to a reaction mixture in very small
amounts, whereas the solid Pd/C is occasionally susceptible to
poisoning by impurities in its use of very small quantity.
Shanmugasundaram, V.; Starr, J. T.; Sun, J.; Tomaras, A.; Young,
J. A.; Zaniewski, R. P. J. Med. Chem. 2013, 56, 5541; (b)
Welschoff, N.; Waldvogel, S. R. Synthesis 2010, 3596; (c)
Breitenlechner, C. B.; Wegge, T.; Berillon, L.; Graul, K.;
Marzenell, K.; Friebe, W.-G.; Thomas, U.; Schumacher, R.;
Huber, R.; Engh, R. A.; Masjost, B. J. Med. Chem. 2004, 47,
1375.
In summary, the Pd NPs stabilized by alkyne derivatives
exhibit excellent catalytic activity in hydrogenation of organic
7.
8.
(a) Levy, J.-N.; Latham, C. M.; Roisin, L.; Kandziora, N.; Di
Fruscia, P.; White, A. J. P.; Woodward, S.; Fuchter, M. J. Org.
Biomol. Chem. 2012, 10, 512; (b) Saravanan, P.; Corey, E. J. J.
Org. Chem. 2003, 68, 2760; (c) Carboni, B.; Benalil, A.; Vaultier,
M. J. Org. Chem. 1993, 58, 3736; (d) Moore, A. T.; Rydon, H. N.
Org. Synth., Coll. Vol. 5 1973, 586.
(a) Soliman, S. E.; Kováč, P. J. Org. Chem. 2015, 80, 4851. (b)
Jean-Gérard, L.; Macé, F.; Ngo, A. N.; Pauvert, M.; Dentel, H.;
Evain, M.; Collet, S.; Guingant, A. Eur. J. Org. Chem. 2012,
4240. (c) Lamb, P. B.; McElhinny, C. J.; Sninski, T.; Purdom, H.;
Carroll, F. I.; Lewin, A. H. J. Labelled Compd. Radiopharm.
2009, 52, 457. (d) Banwell, M. G.; Haddad, N.; Hudlicky, T.;
Nugent, T. C.; Mackay, M. F.; Richards, S. L. J. Chem. Soc.,
Perkin 1 1997, 1779. (e) Plé, N.; Turck, A.; Couture, K.;
Quéguiner, G. Synthesis 1996, 838.
azide compounds.
The substrate-to-palladium molar ratio
reaches over 104. The reaction under atmospheric pressure of
hydrogen is also available. A range of aromatic and aliphatic
azides that have a sensitive functional group under reductive
conditions are hydrogenated to the corresponding amines in high
yields, while retaining their sensitive functionality.
Acknowledgments

4
Tetrahedron
9.
(a) Sweis, R. F.; Wang, Z.; Algire, M.; Arrowsmith, C. H.;
14. Aromatic ketones are easily reduced to the corresponding alcohols
under hydrogenation conditions with Pd/C. See: Deodhar, M.;
StC Black,D.; Kumar, N. Tetrahedron 2007, 63, 5227.
15. Pd/C is an efficient catalyst for the hydrogenolysis of arylhalides;
see: Baltzly, R.; Phillips, A. P. J. Am. Chem. Soc. 1946, 68, 261.
See also ref. 8.
Brown, P. J.; Chiang G. G.; Guo, J.; Jakob, C. G.; Kennedy, S.; Li,
F.; Maag, D.; Shaw, B.; Soni, N. B.; Vedadi, M.; Pappano, W. N.
ACS Med. Chem. Lett. 2015, 6, 695. (b) Schrittwieser, J. H.;
Coccia, F.; Kara,S.; Grischek, B.; Kroutil, W.; d’Alessandrod, N.;
Hollmann, F. Green Chem. 2013, 15, 3318. (c) Bughin, C.;
Masson, G.; Zhu, J. J. Org. Chem. 2007, 72, 1826. (d) Boruwa, J.;
Borah, J. C.; Gogoi, S.; Barua, N. C. Tetrahedron Lett. 2005, 46,
1743.
16. Benzylic hydroxy groups are replaced with hydrogen under
hydrogenation conditions with Pd/C. See: (a) Rob, T.; Ogi, T.;
Maarisit, W.; Taira, J.; Ueda, K. Molecules 2011, 16, 9972. (b)
Geng, H.; Zhang, W.; Chen, J.; Hou, G.; Zhou, L.; Zou, Y.; Wu,
W.; Zhang. X. Angew. Chem. Int. Ed. 2009, 48, 6052.
17. Takahashi, K.; Yamagishi, G.; Hiramatsu, T.; Hosoya, A.; Onoe,
K.; Doi, H.; Nagata, H.; Wada, Y.; Onoe, H.; Watanabe, Y.;
Hosoya, T. Bioorg. Med. Chem. 2011, 19, 1464.
10. (a) Ahammed, S.; Saha, A.; Ranu, B. C. J. Org. Chem. 2011, 76,
7235; (b) Hemantha, H. P.; Sureshbabu, V. V. Org. Biomol.
Chem. 2011, 9, 2597; (c) Cho, B. T.; Kang, S. K.; Shin, S. H.
Tetrahedron: Asymmetry 2002, 13, 1209: (d) Kantam, M. L.;
Chowdari, N. S.; Rahman, A.; Choudary, B. M. Synlett 1999,
1413; (e) Corey, E. J.; Nicolaou, K. C.; Balanson, R. D.; Machida,
Y. Synthesis 1975, 590.
11. (a) Yabe, Y.; Sawama, Y.; Yamada, T.; Nagata, S.; Monguchi, Y.;
Sajiki, H. ChemCatChem 2013, 5, 2360; (b) Esaki, H.; Hattori, T.;
Tsubone, A.; Mibayashi, S.; Sakata, T.; Sawama, Y.; Monguchi,
Y.; Yasuda, H.; Nosaka, K.; Sajiki, H. ChemCatChem 2013, 5,
3629; (c) Takahashi, T.; Yoshimura, M.; Suzuka, H.; Maegawa,
T.; Sawama, Y.; Monguchi, Y.; Sajiki, H. Tetrahedron 2012, 68,
8293; (d) Maegawa, T.; Takahashi, T.; Yoshimura, M.; Suzuka,
H.; Monguchi, Y.; Hironao Sajiki, H. Adv. Synth. Catal. 2009,
351, 2091; (c) Mori, A.; Mizusaki, T.; Kawase, M.; Maegawa, T.;
Monguchi, Y.; Takao, S.; Takagi, Y.; Sajiki, H. Adv. Synth. Catal.
2008, 350, 406; (f) Ikawa, T.; Sajiki, H.; Hirota, K. Tetrahedron
2005, 61, 2217; (g) Hattori, K.; Sajiki, H.; Hirota, K. Tetrahedron
2000, 56, 8433.
18. Formation of homodimeric imines from benzylic azides catalyzed
by Pd catalyst. See: Martínez-Sarti, L.; Díez-González, S.
ChemCatChem 2013, 5, 1722.
Supplementary Material
Supplementary data (preparative method of Pd NPs 1b and NMR
spectra of compounds 4a–j) associated with this article can be
found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.###.
Click here to remo ve in struction text...
12. Hori, J.; Murata, K.; Sugai, T.; Shinohara, H.; Noyori, R.; Arai,
N.; Kurono, N.; Ohkuma, T. Adv. Synth. Catal. 2009, 351, 3143.
13. Arai, N.; Onodera, N.; Dekita, A.; Hori, J.; Ohkuma, T.
Tetrahedron Lett. 2015, 56, 3913.

5
Highlights
• Original Pd NPs for hydrogenation, which are
readily prepared from Pd(OAc)2, NaBH4, and 4-
octyne.
• Efficient chemoselective hydrogenation of
organic azides.
• Complete conversion with a substrate/catalyst
ratio over 10,000.