Ag/Cu-mediated decarboxylative cyanation of aryl carboxylic acids with K4Fe(CN)6 under aerobic conditions

Article abstract of DOI:10.1080/00397911.2018.1494840

A method for facile synthesis of aryl nitriles has been well established via Ag/Cu-mediated decarboxylative cyanation of benzoic acids with K₄Fe(CN)₆ under aerobic conditions. The approach of using readily accessible aryl carboxylic acids and green K₄Fe(CN)₆ as starting material provides a feasible alternative to previous cyanation protocols. Control experiments revealed the key role of Cu for the process and excluded the possibility of a radical mechanism for the transformation.

Full text of DOI:10.1080/00397911.2018.1494840

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Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Ag/Cu-mediated decarboxylative cyanation of
aryl carboxylic acids with K4Fe(CN)6 under aerobic
conditions
Zhengjiang Fu, Ligao Jiang, Zhaojie Li, Yongqing Jiang & Hu Cai
To cite this article: Zhengjiang Fu, Ligao Jiang, Zhaojie Li, Yongqing Jiang & Hu Cai (2019): Ag/
Cu-mediated decarboxylative cyanation of aryl carboxylic acids with K4Fe(CN)6 under aerobic
conditions, Synthetic Communications, DOI: 10.1080/00397911.2018.1494840
To link to this article: https://doi.org/10.1080/00397911.2018.1494840
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https://doi.org/10.1080/00397911.2018.1494840
Ag/Cu-mediated decarboxylative cyanation of aryl
carboxylic acids with K4Fe(CN)6 under aerobic conditions
Zhengjiang Fu, Ligao Jiang, Zhaojie Li, Yongqing Jiang, and Hu Cai
College of Chemistry, Nanchang University, Nanchang, Jiangxi, China
ABSTRACT
ARTICLE HISTORY
Received 10 May 2018
A method for facile synthesis of aryl nitriles has been well estab-
lished via Ag/Cu-mediated decarboxylative cyanation of benzoic
acids with K4Fe(CN)6 under aerobic conditions. The approach of
using readily accessible aryl carboxylic acids and green K4Fe(CN)6 as
starting material provides a feasible alternative to previous cyanation
protocols. Control experiments revealed the key role of Cu for the
process and excluded the possibility of a radical mechanism for the
transformation.
KEYWORDS
Aerobic conditions; aryl
carboxylic acids; aryl nitriles;
Ag/Cu bimetallic system;
decarboxylation
GRAPHICAL ABSTRACT
Introduction
Nitrile serves as a versatile synthetic platform that can be facilely converted into a wide
variety of functional groups in organic synthesis, including amine, amide, aldehyde,
tetrazole and others.[1] Moreover, aryl nitriles are widely found as core structural motifs
in value-added pharmaceuticals, agrochemicals, dyes and materials.[2] Conventionally,
Sandmeyer reaction and Rosenmund-von Braun transformation are the common syn-
thetic routes to access aryl nitriles;[3] nevertheless, the methods typically hinge on the
laborious pre-preparation of unstable aryldiazonium salt and use of stoichiometric
amounts of cuprous cyanide under drastic conditions. From the standpoint of the
employment of both available aryl donor and safe cyano source, there is significant
room for improvement with respect to practical and efficient cyanation procedure.
Transition-metal-mediated reaction for cost-effective and environmentally friendly
synthesis of aryl nitriles is a significant topic of current interest in organic chemistry, in
this context, transition-metal-promoted cyanation of aryl halides C–X bonds or arenes
CONTACT Hu Cai
caihu@ncu.edu.cn
College of Chemistry, Nanchang University, Nanchang, Jiangxi,
330031, China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data (full experimental detail, 1H, 13C and 19F NMR spectra data and references for all the products)
for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

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Z. FU ET AL.
2
Table 1. Selected results of screening the optimal conditions.a
Entry
Alteration from standard conditions
Isolated yield (%)
1
2
3
4
5
6
7
8
None
85
77
79
74
56
48
23
47
72
68
77
56
60
48
0
Ag2O [instead of Ag2SO4]
Ag2CO3 [instead of Ag2SO4]
5 mol% Ag2SO4
Cu2O [instead of Cu(OAc)2]
Cul [instead of Cu(OAc)2]
Cu(OTf)2 [instead of Cu(OAc)2]
0.5 equiv Cu(OAc)2
1,10-phen [instead of 2,9-DMP]
4,7-DPP [instead of 2,9-DMP]
15 mol% 2,9-DMP
9
10
11
12
13
14
15
16
0.5 equiv K4Fe(CN)6
2 mL DMSO
DMF [instead of DMSO]
N2 [instead of O2]
120 ꢀC [instead of 140 ꢀC]
77
aStandard conditions: 1a (0.2 mmol), K4Fe(CN)6 (0.18 equiv.), Ag2SO4 (0.1 equiv.), Cu(OAc)2 (1 equiv.), 2,9-DMP (0.3
equiv.), DMSO (4 mL), O2 (1 atm).
C–H bonds with various cyano source have been intensively investigated, respectively.[4]
The cyano source used in the above reactions could be generated in situ from either an
organic molecule (CH3NO2, DMF, AIBN)[5] or an organic/inorganic combination (DMF
with NH3 or an ammonium salt, DMSO with an ammonium salt);[6] additionally, cyano
group transferred to an aromatic ring usually originated from CN-containing com-
pounds with the whole cyanide unit, such as inorganic metal cyanides salts (KCN,
NaCN, Zn(CN)2 and CuCN)[7] and organic CN-containing compounds (cyanohydrin,
TMSCN, CH3CN and malononitrile, N-cyanosuccinimide, N-cyano-N-phenyl-p-toluene-
sulfonamide (NCTS)).[8] However, the inherent toxicity of metal cyanides and irrevers-
ible deactivation of the metal catalysts with too much-dissolved cyanide ions are major
concerns that restrict wide application of the reactions. In stark contrast to the afore-
mentioned cyano source, potassium hexacyanoferrate(II) K4Fe(CN)6 is usually used as a
nontoxic additive in the food industry for residual metal precipitation. Since K4Fe(CN)6
has high stability constant and low dissociation, thus, it can gradually deliver cyanide
ions into reaction mixture and prevent transition-metal catalyst poisoning to a great
extent. Based on its commercial availability, bench stability and cheapness, as reported,
K4Fe(CN)6 is a green cyanide source to synthesize aryl nitriles with Pd catalyst.[9]
Among various aryl donors in the preparation of aryl nitriles, aryl carboxylic acids are
widely found in nature with innocuity and commercially available in a large variety.
Because carboxylic acids can act as distinctly attractive alternatives to traditional electro-
philic aryl halides or nucleophilic organometallic counterparts in coupling reactions to
minimize waste products with loss of nontoxic CO2 and enhance the synthetic utility of
cross-coupling chemistry, it opens up novel perspective to employ a large pool of readily
available aromatic carboxylic acids as arylating reagents.[10] During the last decade, a

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Table 2. Ag/Cu-mediated coupling of benzoic acids with K4Fe(CN)6 under aerobic conditions.a
Entry
1
Ar-COOH
Product
Yield (%)b
85
1a
1b
2a
2b
2
3
4
71
70
63
1c
2c
1d
2d
5
6
7
1e
1f
2e
2f
39
70
65
1g
2g
8
9
1h
1i
2h
2i
46
34
10
11
1j
2j
45c
40c
1k
2k
aReaction conditions: 1 (0.2 mmol), K4Fe(CN)6 (0.18 equiv), Ag2SO4 (0.1 equiv.), Cu(OAc)2 (1 equiv.), 2,9-DMP (0.3 equiv.),
DMSO (4 mL), O2 (1 atm), 140 ꢀC, 20 h.
bIsolated yield by an average of two runs.
c0.2 equivalent of Ag2SO4 used.
great contribution has been made to create C–C and C–Hetero bonds from the powerful
tool of transition-metal-promoted decarboxylative coupling of aromatic carboxylic acids
with various carbon- and heteroatom-based coupling partners, including alkenes,[11] aryl
halides,[12] alkynes,[13] arenes,[14] organoboron compounds,[15] imines,[16] trifluoromethy-
lating agents,[17] silicate esters,[18] H-phosphine oxides,[19] trifluoromethylthiolating
reagents,[20] thiols and disulfides.[21]