Indium-mediated reductive coupling of acyl cyanides: A convenient synthesis of 1,2-diketones

Article abstract of DOI:10.1016/S0040-4039(00)01411-8

The indium-mediated reductive coupling of acyl cyanides afforded the corresponding 1,2-diketones in moderate to good yields under neutral and mild conditions. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01411-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8097–8099
Indium-mediated reductive coupling of acyl cyanides: a
convenient synthesis of 1,2-diketones
Heung Soo Baek,a Sung Jae Lee,a Byung Woo Yoo,a,* Jae Jung Ko,a Sung Hoon Kimb,*
and Joong Hyup Kimb
aDepartment of Chemistry, Korea University, Chochiwon, Chungnam 339-700, South Korea
bBiochemical Research Center, Korea Institute of Science and Technology, Cheongryang,
Seoul 130-650, South Korea
Received 26 April 2000; revised 16 August 2000; accepted 18 August 2000
Abstract
The indium-mediated reductive coupling of acyl cyanides afforded the corresponding 1,2-diketones in
moderate to good yields under neutral and mild conditions. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: indium and compounds; coupling reactions; cyanides; sonochemistry.
Indium-mediated reactions1 have gained much attention over the last decade in a variety of
reactions such as cyclopropanations,2 Reformatsky reactions,3 allylation reactions of carbonyl
compounds,4 or aldimines.5 In particular, the reductive coupling of carbonyl derivatives is one
of the most valuable methods for establishing carbonꢀcarbon bonds. It has recently been found
that aromatic aldehydes6 and aldimines7 are transformed into pinacols and vicinal diamines,
respectively, with indium. However, to our knowledge, there is no report on the reductive
coupling of acyl cyanides by the use of indium. Although the reductive coupling of acyl
cyanides8 or acid chlorides9 mediated by SmI2 to give 1,2-diketones was described in the
literature, these methods have been somewhat limited because they are very sensitive to air and
moisture. We have discovered that indium is effective for the reductive coupling reaction of acyl
cyanides to afford the corresponding 1,2-diketones under neutral and mild conditions. The
reaction does not require exclusion of oxygen or anhydrous conditions as required by SmI2 for
effecting the same transformation (Eq. (1)). Due to their utility in organic synthesis and their
biological activities, 1,2-diketones have attracted considerable interest and several important
preparative methods for 1,2-diketones have been developed.10
(1)
* Corresponding authors.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01411-8

8098
Herein we wish to report a simple, convenient procedure for the coupling of acyl cyanides to
form 1,2-diketones using indium under sonication.11 The reaction proceeds efficiently in moder-
ate to good yields at room temperature. However, it was found that acyl chlorides reacted under
the same conditions to give complex mixtures. Any significant self-coupling of acyl chlorides to
give 1,2-diketones was not observed.
In a typical experimental procedure, a mixture of benzoyl cyanide (0.25 g, 1.9 mmol) and
indium powder (100 mesh, 0.33 g, 2.9 mmol) in DMF (2 mL) was stirred at room temperature
under sonication for a certain period of time until completion of the reaction (TLC). The
reaction mixture was quenched with a few drops of water and extracted with diethyl ether.
Evaporation of the solvent followed by purification via silica gel chromatography afforded
benzil in 62% yield. Table 1 indicates the results of the reductive coupling of acyl cyanides using
indium. The furfuroyl cyanide was also reductively coupled to give 1,2-diketone (entry 12), but
the application of this approach to aliphatic acyl cyanide proved unsuccessful and only
recovered starting material was isolated (entries 9 and 10).
Table 1
Reductive coupling of acyl cyanides with indium
In the course of the process, substituents such as methoxy, chloro, or bromo groups (entries
5–8) are not affected. All products obtained showed NMR, IR and mass spectral data
compatible with the structure. The structures of known compounds were determined by
comparison of their spectral data with those previously reported.12
Indium metal has some reducing power (In+3/In=−0.34 V) in solution and the choice of the
solvent is critical in the indium-mediated reaction. The reaction was carried out in several

8099
solvents but failed in THF, THF/H2O, DMF/H2O, CH3CN and water. DMF has been found to
be the most suitable solvent for the reaction. Presumably, indium is somewhat more reactive in
an organic solvent like DMF. It is speculated that the present reductive coupling reaction
mediated by indium goes through a single electron transfer (SET) process like other metal-medi-
ated reactions. Although the mechanism of the reaction is not yet clear, we assume that indium
−
’
may transfer one electron to RCOCN to form the radical anion intermediate (RCOCN) , which
−
’
’
was cleaved into RCO and CN and the coupling of the radical RCO gives 1,2-diketones 2.
−
’
Another equally likely mechanism is that the radical anion intermediate (RCOCN) can
dimerize to give the dialkoxide, which slowly decomposes to 1,2-diketones 2.
In conclusion, we have demonstrated that the reductive coupling reaction of acyl cyanides
using indium provides a simple and convenient method for the synthesis of 1,2-diketones under
neutral and mild reaction conditions. Further investigation on the extension of the reaction and
the mechanistic detail is currently in progress.
Acknowledgements
This work was financially supported by Korea Institute of Science and Technology (2E16180)
and partially by Korea University.
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