COMMUNICATION
DOI: 10.1002/chem.201300518
Gold-Catalyzed Synthesis of Glyoxals by Oxidation of Terminal Alkynes:
One-Pot Synthesis of Quinoxalines
Shuai Shi, Tao Wang, Weibo Yang, Matthias Rudolph, and A. Stephen K. Hashmi*[a]
Substituted glyoxals are versatile precursors for the syn-
thesis of biologically active heterocyclic compounds.[1] While
several synthetic strategies have been developed to obtain
glyoxal derivatives as useful building blocks, most of the
general methods are limited to the oxidation of substituted
methyl ketones by selenium dioxide under harsh reaction
conditions.[2] Alternatively, this type of compound can be
synthesized via oxidation procedures from substituted 1,2-
ethanediol,[3] dihalide compounds,[4] or Kornblum-type oxi-
dations.[5] Based on the efficient oxidation of internal al-
kynes to 1,2-diketones,[6] we envisioned that the direct oxi-
dation of terminal alkynes could also play an important role
in this field. Until now there are solely limited reports on
the use of terminal alkynes as glyoxal precursors, and either
highly toxic mercury compounds or harsh reaction condi-
tions are required.[7] Therefore it is still highly desirable to
develop an alternative method through a general and con-
venient pathway.
During the last decades, homogeneous catalysis of organic
reactions by gold complexes has been developed into a
highly useful tool for the construction of valuable building
blocks.[8] Recently, gold-catalyzed oxidation procedures
using pyridine-N-oxides,[9] diphenylsulfoxide,[10] and nitro-
nes[11] as oxygen donors were established, which strongly en-
riched the field of oxidation chemistry. In these reactions, a-
carbonyl gold carbenoids are considered as the key inter-
mediates.[12] Last year Li et al. reported on the gold-cata-
lyzed synthesis of 1,2-dicarbonyl compounds from internal
alkynes by using diphenylsulfoxide as an oxidant.[6a] In their
work, different aryl-substituted internal alkynes could be
oxidized into diketones under mild conditions but the reac-
tion scope was limited to internal aryl-substituted alkynes.
Our initial attempts to expand the substrate scope of this re-
action by the use of phenylacetylene as a starting material,
under the same reaction conditions, only delivered traces of
product (Scheme 1). Therefore we envisioned that a varia-
tion of the oxygen donor might open up the possibility for
Scheme 1. Attempts at the oxidation of terminal alkynes under the origi-
nal Li conditions.[6a] 1,2-DCE=1,2-dichloroethane.
the synthesis of valuable substituted glyoxals by an oxida-
tion procedure from terminal alkynes.
To confirm the feasibility of this hypothesis, phenylacety-
lene 2a and 2.5 equivalents of 3,5-dichloropyridine-N-oxide
3a were initially treated with 5 mol% of [AuClACHTUNGTRENNUNG(Ph3P)]/
AgNTf2 and 1.5 equivalents of methanesulfonic acid (to
avoid catalyst deactivation by the byproduct pyridine) in
DCE at room temperature (Table 1, entry 1). To our delight,
4a was indeed obtained, albeit in low yield. Chloromethyl
ketones derived from halogen abstraction of the solvent and
an addition product of the formal addition of the methylsul-
fonic acid were also observed in this reaction.[13] By chang-
ing the additive to HNTf2, the mesylate-containing byprod-
uct was excluded and the yield of 4a increased to 37%
(entry 2). Different solvents were then examined in which
toluene gave the best result (entry 4). To further optimize
the reaction, different N-oxides were applied, among which
3,5-dichloropyridine-N-oxide and 6-methoxy-quinoline-N-
oxide turned out to work equally well (entries 4 and 6).
However, no product could be obtained with electron-rich
N-oxide 3b (entry 5). Changing the catalyst system to the
combination of [AuClACHTNUGTRNEUNG(IPr)] and AgNTf2 delivered poor re-
sults and only traces of product could be obtained (entry 7).
Thus we explored the effect of the counter ion in combina-
tion with the phosphane ligand at the gold centre. [AuCl-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
phenylglyoxal was observed under acidic conditions in the
absence of the gold catalyst. A further experiment showed
that acid was necessary for maintaining the activity of the
gold catalyst.[9a,f]
To the best of our knowledge, the pure phenylglyoxal is
unstable in air and readily forms the monohydrate and poly-
mers.[2b,14] For further characterization, the more stable crys-
talline phenylglyoxal monohydrate could be obtained by
crystallization from hot water in moderate yield but at-
tempts to isolate crystalline hydrate products from 4-tert-bu-
tylphenylglyoxal and 3,5-dimethoxyphenylglyoxal failed.
Substituted glyoxals are usually used as precursors for the
[a] S. Shi, T. Wang, W. Yang, Dr. M. Rudolph, Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢀt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax : (+49)6221-54-4205
Supporting information for this article is available on the WWW
Chem. Eur. J. 2013, 00, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!
Shi, Shuai
