Silver catalyzed pyridine-directed acceptorless dehydrogenation of secondary alcohols

Article abstract of DOI:10.1002/jccs.202000517

A silver catalyzed pyridine-directed acceptorless dehydrogenation of secondary benzyl alcohols was developed. This general procedure delivers ketones with high atom-economy and hydrogen was the sole byproduct. This dehydrogenation reaction has a good functional group tolerance and high efficiency (up to 90% yield and 10,000/1 substrates-to-catalyst ratio).

Full text of DOI:10.1002/jccs.202000517

Received: 15 November 2020
DOI: 10.1002/jccs.202000517
Revised: 6 December 2020
Accepted: 11 January 2021
C O M M U N I C A T I O N
Silver catalyzed pyridine-directed acceptorless
dehydrogenation of secondary alcohols
Xin Zhuang | Jing Tao | Zhen Luo | Chuan-Ming Hong | Zheng-Qiang Liu |
Qing-Hua Li | Li-Qing Ren | Qun-Li Luo
| Tang-Lin Liu
School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China
Correspondence
Tang-Lin Liu and Qun-Li Luo, School of
Abstract
Chemistry and Chemical Engineering,
Southwest University, Chongqing 400715,
China.
A silver catalyzed pyridine-directed acceptorless dehydrogenation of secondary
benzyl alcohols was developed. This general procedure delivers ketones with
high atom-economy and hydrogen was the sole byproduct. This dehydrogena-
tion reaction has a good functional group tolerance and high efficiency (up to
90% yield and 10,000/1 substrates-to-catalyst ratio).
Email: liuschop@swu.edu.cn (T.-L. L.)
and qlluo@swu.edu.cn (Q.-L. L.)
Funding information
National Natural Science Foundation of
China, Grant/Award Numbers: 21801209,
21801210; Venture & Innovation Support
Program for Chongqing Overseas
K E Y W O R D S
acceptorless dehydrogenation, atom-economy, silver catalyzed
Returnees, Grant/Award Number:
cx2018085; Fundamental Research Funds
for the Central Universities, Grant/Award
Numbers: SWU118028, SWU118117,
XDJK2019AA003; Natural Science
Foundation of Chongqing, China, Grant/
Award Number: cstc2020jcyj-msxmX0130
1 | INTRODUCTION
acceptorless dehydrogenation (CAD) has been well devel-
oped for its good atom economy, wherein hydrogen as the
The dehydrogenation of alcohols to carbonyl compounds
is one of the most important reactions in organic chemis-
try, which also played an important role in industry.[1]
The classical procedure employed the use of stoichiometric
oxidants, which often produces large quantities of
wastes.[2] As an important alternative, transition-metal cat-
alyzed dehydrogenation in the presence of some accep-
tors[3] (aka transfer hydrogenation;[4] Scheme 1a) attracted
much attention for several decades. These hydrogen accep-
tors, however, were usually loaded in stoichiometric or
large excessive amounts, which may bring some negative
environmental effects. Obviously, both stoichiometric oxi-
dation and transfer hydrogenation have the drawback of
low atom-economy. Recently, transition-metal catalyzed
sole byproduct.[5] Several VIII group transition metals
complexes such as iron,[6] rhodium,[7] ruthenium,[8] and
iridium,[9] etc. have been developed for the dehydrogena-
tion of alcohols to aldehydes or ketones (Scheme 1b).[10,11]
This CAD strategy also found wide applications in bio-
chemistry, material, and energy science, since it provided
a unique way to release hydrogen under mild conditions
from sustainable sources.[12]
Silver is an easily available transition metal, which
has often been used as stoichiometric oxidant.[13] The
dehydrogen oxidation of alcohols catalyzed by
nanoparticles supported silver have been developed,[14]
while the catalytic oxidation with homogeneous silver
has been rarely recorded. In 2014, a combination of
silver(I) and NHC (N-heterocyclic carbene) has been suc-
cessfully used for the catalytic aerobic oxidation of
Xin Zhuang and Jing Tao contributed equally to this study.
J Chin Chem Soc. 2021;68:245–249.
http://www.jccs.wiley-vch.de
© 2021 The Chemical Society Located in Taipei & Wiley-VCH GmbH
245

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ZHUANG ET AL.
primary alcohol to aldehydes,[15] carboxylic acids could
also be achieved by silver catalyzed dihydrogen oxidation
of primary alcohols.[16] Li and co-workers reported the
silver-catalyzed aerobic oxidation of aldehydes to
carboxylic acids in 2015.[17] They also developed the
silver(I)-catalyzed aerobic cleavage of 1,2-diols to form
the corresponding ketones or carboxylic acids.[18] Silver
catalytic oxidation of alcohols to carbonyl compounds
in the presence of oxygen[19] and the oxidant-free alco-
hols dehydrogenation to aldehydes or ketones cata-
lyzed by hydrotalcite-supported silver nanoparticle
catalyst[14a] have been developed. Of note, no pre-
cedential examples of CAD of alcohols with homoge-
neous silver catalyst have been reported. Herein, we
developed a silver catalyzed anaerobic acceptorless
dehydrogenation of secondary alcohols to ketones with
high yields and release hydrogen as the sole side prod-
uct (Scheme 1c).
Initially, we selected (4-methoxyphenyl)(2-[pyridin-
2-yl]phenyl)methanol 1a[20] as the model substrate and
metallic silvers as the catalyst to optimize the reaction
conditions (Table 1). Some common silver(I) salts like
CF3CO2Ag, Ag2CO3, AgF, and AgNO3 were ineffective
for this catalytic dehydrogenation (see Supporting Infor-
mation). Encouragingly, the corresponding ketone 2a
was obtained with 77% yield when AgSbF6 was applied
(entry 1). Further improvement in the yield was observed
when AgPF6 and AgOTf were used (81%, entry 2, 3).
Finally, AgOTf was selected as the optimal catalyst since
SCHEME 1 The dehydrogenation of alcohols to carbonyl
compounds
TABLE 1 Optimization of reaction conditions in the Ag-catalyzed dehydrogenation of 1aa
Entry
[Ag]
x
Solvent
DCM
Yield (%)b
1
AgSbF6
AgPF6
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
—
20
20
20
20
20
20
20
5
77
2
DCM
81
3
DCM
81
4
PhMe
CHCl3
CH3CN
TBME
TBME
TBME
TBME
TBME
TBME
TBME
NR
58
5
6
70
7
82
8
65
9
1
64
10
11
12
13c
0.1
0.01
—
20
43
31
Trace
Trace
AgOTf
aThe reaction was carried out with 0.1 mmol of 1a, 20 mol% [Ag], and 50 mol% Lewis acid in 0.5 ml of solvent at 75ꢀC for 24 hr.
bIsolated yield.
cThe reaction was carried out in the absence of Ti(Oi-Pr)4. TBME = Methyl tert-butyl ether.

ZHUANG ET AL.
247
the lower cost. Then, the effect of solvent was tested.
No target product was detected when the dehydroge-
nation reaction was carried out in toluene (entry 4).
The model reaction in other polar solvents like CHCl3
and CH3CN delivered 58 and 70% yield, respectively
(entry 5–6). The highest yield of 82% was achieved in
TBME (entry 7).
Reducing the catalyst loading led to a lower yield
(entry 8–11), of the desire product. When 5 or 1 mol% of
the catalyst was used, the yields were 65 and 64%, respec-
tively (Table 1, entries 8 and 9). The catalyst loading
could be further lowered to 0.01 mol% (S/C = 10,000),
and the dehydrogenation went smoothly and delivered
the product with 31% yield (TON = 3,100) (Table 1,
entry 11). The control experiments indicated that both
silver and titanium were indispensable, since no 2a was
detected in the absence of sliver or titanium (Table 1,
entries 12 and 13).
With the optimal reaction in hands, we next investi-
gated the scope and limitation of diaryl methanols for
this silver CAD (Scheme 2). We then tested the substi-
tutes with electron-donating, electron-neutral, and the
electron-withdrawing groups in place of the para-
methoxyl of the phenyl group (Scheme 2,2b–e). All of
them reacted smoothly to afford the desire ketones. The
substrates bearing electron-donating group gave a higher
yield than those with electron-neutral and electron-
withdrawing groups (82 and 90% vs 54–64%). The ortho
chloro (1f) or methoxy (1h) substituted substrates deliver
the corresponding ketones (2f and 2g) with lower yields.
However, a high yield of 85% was achieved with ortho
methyl substituent (2h). CH3 (2i) and OCH3 (2j) groups
in the meta position were well-tolerated, and the yields
were 80 and 86%, respectively. The substrates with
electron-neutral aromatic groups such as 1-naphthyl and
2-naphthyl, also went smoothly to afford 2k and 2l in
moderate yields. The aryl groups of the diaryl methanols
could also tolerate multiple substituents (2m and 2n).
Besides, the aryl alkyl methanols like 1-(2-[pyridin-
2-yl]phenyl)propan-1-ol (1o) and 1-(2-[pyridin-2-yl]phe-
nyl)butan-1-ol (1p) could also undergo dehydrogenation
under the optimal reaction condition, furnishing
corresponding ketones 63 and 46% yields, respectively.
Further evaluation of the scope of pyridine directed
diaryl methanols to this silver CAD revealed that a vari-
ety of substituted 2-(pyridin-2-yl)phenyl groups could be
tolerated, affording the corresponding diaryl ketones in
moderate to good yields. 2-(Pyridin-2-yl)phenyl groups
bearing electron-withdrawing groups, such as 5-Cl (2r),
5-Br (2s), 5-OCF3 (2t), and 3-F (2v) or electron-donating
groups, such as 5–CH3 (2q) and 4-Me (2u) were subjected
to the dehydrogenation, and proceed smoothly. Surpris-
ingly, when the substitutes were on the 6-position of
SCHEME 2 The scope of diaryl methanols
2-(pyridin-2-yl)phenyl groups, neither the electron-
withdrawing nor the electron-donating groups can realize
in this transformation, probably because of steric hin-
drance (not shown in Scheme 2). Use of diaryl methanol
with pyridine-2-yl group bearing a methyl substituent

248
ZHUANG ET AL.
(c) T. Mallat, A. Baiker, Chem. Rev. 2004, 104, 3037. (d) G. E.
Dobereiner, R. H. Crabtree, Chem. Rev. 2010, 110, 681.
(e) J. Choi, A. H. MacArthur, M. Brookhart, A. S. Goldman,
Chem. Rev. 2011, 111, 1761. (f) S. E. Allen, R. R. Walvoord, R.
Padilla-Salinas, M. C. Kozlowski, Chem. Rev. 2013, 113, 6234.
(g) C. Wang, J. Xiao, Chem. Commun. 2017, 53, 3399.
[2] (a) J. D. Albright, L. Goldman, J. Am. Chem. Soc. 1969, 91,
4317. (b) R. J. Sundberg, D. Eugene Rearick, H. F. Russell,
J. Pharm. Sci. 1977, 66, 263. (c) D. B. Dess, J. C. Martin, J. Org.
Chem. 1983, 48, 4155. (d) O. Dann, H. Char, P. Fleischmann,
H. Fricke, Liebigs Ann. Chem. 1986, 1986, 438. (e) E. M.
Beccalli, G. Broggini, A. Farina, L. Malpezzi, A. Terraneo, G.
Zecchi, Eur. J. Org. Chem. 2002, 2002, 2080. (f) S. Palaniappan,
C. Kumar, C. Devi, V. Rao, Synlett 2008, 2008, 2023. (g) J. Liu,
S. Ma, Org. Biomol. Chem. 2013, 11, 4186.
SCHEME 3 Gram scale reaction
(1w) showed good yield. Benzo[h]quinolin-10-yl(phenyl)
methanol (1x) was tested, and the desired product 2x was
obtained in 70% yield. By contrast, the substrates without
any nitrogen-containing directing groups (1y-1ab) were
submitted to the standard reaction conditions, no desire
products were achieved, which indicated that the
directing groups were indispensable.
To further demonstrate the potential and the practi-
cality of this silver-catalyzed dehydrogenation, a gram-
scale reaction was performed. When the reaction was
conducted at 4.0 mmol (1.16 g), diaryl methanone 2a
could be prepared in 58% yield with 1 mol% of silver cata-
lyst (Scheme 3).
[3] (a) D. Morales-Morales, R. Redón, Z. Wang, D. W. Lee, C.
Yung, K. Magnuson, C. M. Jensen, Can. J. Chem. 2001, 79,
823. (b) T. Suzuki, K. Morita, M. Tsuchida, K. Hiroi, J. Org.
Chem. 2003, 68, 1601. (c) A. N. Ajjou, J.-L. Pinet, Can. J. Chem.
2005, 83, 702. (d) M. Königsmann, N. Donati, D. Stein, H.
Schönberg, J. Harmer, A. Sreekanth, H. Grützmacher, Angew.
Chem., Int. Ed. 2007, 46, 3567. (e) B. Jiang, Y. Feng, E. A. Ison,
J. Am. Chem. Soc. 2008, 130, 14462. (f) R. Levy, C. Azerraf,
D. Gelman, K. Rueck-Braun, P. N. Kapoor, Catal. Commun.
2009, 11, 298. (g) A. Prades, E. Peris, M. Albrecht, Organome-
tallics 2011, 30, 1162. (h) G. Giachi, M. Frediani, W.
Oberhauser, E. Passaglia, J. Polym. Sci. A Polym. Chem. 2012,
50, 2725. (i) S. Gowrisankar, H. Neumann, D. Gordes, K.
Thurow, H. Jiao, M. Beller, Chem. Eur. J. 2013, 19, 15979.
(j) K. Chung, S. M. Banik, A. G. De Crisci, D. M. Pearson,
T. R. Blake, J. V. Olsson, A. J. Ingram, R. N. Zare, R. M.
Waymouth, J. Am. Chem. Soc. 2013, 135, 7593. (k) A. J.
Ingram, D. Solis-Ibarra, R. N. Zare, R. M. Waymouth, Angew.
Chem. Int. Ed. 2014, 53, 5648. (l) D. Sengupta, R.
Bhattacharjee, R. Pramanick, S. P. Rath, N. Saha Chowdhury,
A. Datta, S. Goswami, Inorg. Chem. 2016, 55, 9602. (m) R.
Pramanick, R. Bhattacharjee, D. Sengupta, A. Datta, S.
Goswami, Inorg. Chem. 2018, 57, 6816. (n) D. Ye, Z. Liu, J. L.
Sessler, C. Lei, Chem. Commun. 2020, 56, 11811.
2 | CONCLUSIONS
In summary, we have developed a novel catalytic accept-
orless dehydrogenation of secondary alcohols catalyzed
by silver under mild reaction conditions. High atom-
efficiency was observed considering that hydrogen is the
sole byproduct in this reaction. A wide range of aryl pyri-
dinyl methanols was tolerated and the corresponding
ketones were achieved with moderate to good yields.
Study of the sliver-CAD with traceless directing groups is
in progress and will be reported in due course.
[4] (a) F. Alonso, P. Riente, M. Yus, Acc. Chem. Res. 2011, 44,
379. (b) D. Wang, D. Astruc, Chem. Rev. 2015, 115, 6621.
(c) A. Quintard, J. Rodriguez, Chem. Commun. 2016, 52,
10456.
ACKNOWLEDGMENTS
[5] (a) A. Friedrich, S. Schneider, ChemCatChem 2009, 1, 72.
(b) T. C. Johnson, D. J. Morris, M. Wills, Chem. Soc. Rev. 2010,
39, 81. (c) C. Gunanathan, D. Milstein, Science 2013, 341,
1229712. (d) B. Zhou, Y. Hu, C. Wang, Angew. Chem. Int. Ed.
2015, 54, 13659. (e) R. H. Crabtree, Chem. Rev. 2017, 117, 9228.
(f) K. Sordakis, C. Tang, L. K. Vogt, H. Junge, P. J. Dyson, M.
Beller, G. Laurenczy, Chem. Rev. 2018, 118, 372.
We are grateful for the financial support provided by the
National Natural Science Foundation of China (21801209
and 21801210), the Fundamental Research Funds for the
Central Universities (SWU118117, SWU118028, and
XDJK2019AA003), and Venture and Innovation Support
Program for Chongqing Overseas Returnees (cx2018085).
[6] (a) H. Song, B. Kang, S. H. Hong, ACS Catal. 2014, 4, 2889.
(b) E. A. Bielinski, P. O. Lagaditis, Y. Zhang, B. Q. Mercado, C.
Würtele, W. H. Bernskoetter, N. Hazari, S. Schneider, J. Am.
Chem. Soc. 2014, 136, 10234. (c) T. Zell, Y. Ben-David, D.
Milstein, Angew. Chem. Int. Ed. 2014, 53, 4685.
ORCID
Qun-Li Luo https://orcid.org/0000-0002-9724-5674
Tang-Lin Liu https://orcid.org/0000-0002-7318-4520
[7] (a) A. J. Blacker, E. Clot, S. B. Duckett, O. Eisenstein, J. Grace,
A. Nova, R. N. Perutz, D. J. Taylor, A. C. Whitwood, Chem.
Commun. 2009, 2009, 6801. (b) T. P. Brewster, A. J. M. Miller,
D. M. Heinekey, K. I. Goldberg, J. Am. Chem. Soc. 2013, 135,
16022.
REFERENCES
[1] (a) G. Tojo, M. Fernandez, Oxidation of Alcohols to Aldehydes
and Ketones, Springer, New York 2006. (b) R. A. Sheldon,
I. W. C. E. Arends, A. Dijksman, Catal. Today 2000, 57, 157.

ZHUANG ET AL.
249
[8] (a) M. Matsumoto, N. Watanabe, J. Org. Chem. 1984, 49, 3435.
(b) P. E. Morris, D. E. Kiely, J. Org. Chem. 1987, 52, 1149.
(c) G. Barak, J. Dakka, Y. Sasson, J. Org. Chem. 1988, 53, 3553.
(d) M. L. S. Almeida, M. Beller, G.-Z. Wang, J.-E. Bäckvall,
Chem. Eur. J. 1996, 2, 1533. (e) R. Noyori, T. Ohkuma, Angew.
Chem. Int. Ed. 2001, 40, 40. (f) J. Zhang, M. Gandelman,
L. J. W. Shimon, H. Rozenberg, D. Milstein, Organometallics
2004, 23, 4026. (g) J. van Buijtenen, J. Meuldijk, J. A. J. M.
Vekemans, L. A. Hulshof, H. Kooijman, A. L. Spek, Organo-
metallics 2006, 25, 873. (h) H. Mizoguchi, T. Uchida, K. Ishida,
T. Katsuki, Tetrahedron Lett. 2009, 50, 3432. (i) A. Taketoshi,
X. N. Beh, J. Kuwabara, T.-a. Koizumi, T. Kanbara, Tetrahe-
dron Lett. 2012, 53, 3573. (j) S.-S. Wang, J. Zhang, C.-L. Zhou,
G. Vo-Thanh, Y. Liu, Catal. Commun. 2012, 28, 152. (k) S.
Manzini, C. A. Urbina-Blanco, S. P. Nolan, Organometallics
2013, 32, 660.
[9] (a) K.-i. Fujita, N. Tanino, R. Yamaguchi, Org. Lett. 2007, 9,
109. (b) K.-i. Fujita, T. Yoshida, Y. Imori, R. Yamaguchi, Org.
Lett. 2011, 13, 2278. (c) S. Musa, I. Shaposhnikov, S. Cohen, D.
Gelman, Angew. Chem., Int. Ed. 2011, 50, 3533. (d) R.
Kawahara, K. Fujita, R. Yamaguchi, J. Am. Chem. Soc. 2012,
134, 3643. (e) W. Tang, S. Johnston, J. A. Iggo, N. G. Berry, M.
Phelan, L. Lian, J. Bacsa, J. Xiao, Angew. Chem. Int. Ed. 2013,
52, 1668. (f) A. H. Ngo, M. J. Adams, L. H. Do, Organometal-
lics 2014, 33, 6742. (g) K.-i. Fujita, R. Tamura, Y. Tanaka,
M. Yoshida, M. Onoda, R. Yamaguchi, ACS Catal. 2017, 7,
7226.
Zheng, L.-Q. Zheng, L.-Z. Wu, C.-H. Tung, B. Chen, Green
Chem. 2019, 21, 1401.
[12] (a) H. Junge, B. Loges, M. Beller, Chem. Commun. 2007, 2007,
522. (b) M. Nielsen, A. Kammer, D. Cozzula, H. Junge, S.
Gladiali, M. Beller, Angew. Chem. Int. Ed. 2011, 50, 9593.
(c) M. Trincado, D. Banerjee, H. Grützmacher, Energy Environ.
Sci. 2014, 7, 2464. (d) S. Waiba, B. Maji, ChemCatChem 2020,
12, 1891. (e) K. R. Rohit, S. Radhika, S. Saranya, G.
Anilkumar, Adv. Synth. Catal. 2020, 362, 1602.
[13] K. Oshima, B. Tollens, Ber. Dtsch. Chem. Ges. 1901, 34, 1425.
[14] (a) T. Mitsudome, Y. Mikami, H. Funai, T. Mizugaki, K.
Jitsukawa, K. Kaneda, Angew. Chem., Int. Ed. 2008, 47, 138.
(b) E. Yazdani, A. Heydari, J. Organomet. Chem 2020, 924,
121453.
[15] L. Han, P. Xing, B. Jiang, Org. Lett. 2014, 16, 3428.
[16] H. G. Ghalehshahi, R. Madsen, Chem. Eur. J. 2017, 23, 11920.
[17] M. Liu, H. Wang, H. Zeng, C.-J. Li, Sci. Adv. 2015, 1, e1500020.
[18] Z. Z. Zhou, M. Liu, L. Lv, C. J. Li, Angew. Chem. Int. Ed. 2018,
57, 2616.
[19] (a) M. J. Beier, T. W. Hansen, J.-D. Grunwaldt, J. Catal. 2009,
266, 320. (b) J. Wang, Y. Li, Y. Peng, G. Song, J. Chin. Chem.
Soc. 2014, 61, 517.
[20] (a) H. Li, Y. Li, X. S. Zhang, K. Chen, X. Wang, Z. J. Shi,
J. Am. Chem. Soc. 2011, 133, 15244. (b) H. Wang, I. Choi,
T. Rogge, N. Kaplaneris, L. Ackermann, Nat. Catal. 2018, 1,
993. (c) Y. Qiu, A. Scheremetjew, L. Ackermann, J. Am. Chem.
Soc. 2019, 141, 2731.
[10] (a) K. Shimizu, K. Sugino, K. Sawabe, A. Satsuma, Chem.
Eur. J. 2009, 15, 2341. (b) G. Zhang, S. K. Hanson, Org. Lett.
2013, 15, 650. (c) S. Chakraborty, P. O. Lagaditis, M. Förster,
E. A. Bielinski, N. Hazari, M. C. Holthausen, W. D. Jones, S.
Schneider, ACS Catal. 2014, 4, 3994. (d) H. Fuse,
H. Mitsunuma, M. Kanai, J. Am. Chem. Soc. 2020, 142, 4493.
[11] (a) J. G. West, D. Huang, E. J. Sorensen, Nat. Commun. 2015,
6, 10093. (b) Z. Chai, T.-T. Zeng, Q. Li, L.-Q. Lu, W.-J. Xiao, D.
Xu, J. Am. Chem. Soc. 2016, 138, 10128. (c) H. Kasap, C. A.
Caputo, B. C. M. Martindale, R. Godin, V. W.-h. Lau, B. V.
Lotsch, J. R. Durrant, E. Reisner, J. Am, Chem. Soc. 2016, 138,
9183. (d) L.-M. Zhao, Q.-Y. Meng, X.-B. Fan, C. Ye, X.-B. Li, B.
Chen, V. Ramamurthy, C.-H. Tung, L.-Z. Wu, Angew. Chem.
Int. Ed. 2017, 56, 3020. (e) J.-J. Zhong, W.-P. To, Y. Liu, W. Lu,
C.-M. Che, Chem. Sci. 2019, 10, 4883. (f) X.-J. Yang, Y.-W.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Zhuang X, Tao J, Luo Z,
et al. Silver catalyzed pyridine-directed acceptorless
dehydrogenation of secondary alcohols. J Chin
Chem Soc. 2021;68:245–249. https://doi.org/10.
1002/jccs.202000517