Tetrahedron Letters
Mild propargylic oxidation using a diacetoxyiodobenzene/tert-butyl
hydroperoxide protocol
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Yi Zhao, Angela Wan Ting Ng, Ying-Yeung Yeung
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild propargylic oxidation of alkynes is reported using a diacetoxyiodobenzene/tert-butyl hydroperox-
Received 10 May 2014
Revised 23 May 2014
Accepted 5 June 2014
Available online xxxx
ide (DIB/TBHP) protocol. The reactions proceed smoothly at 0 °C and a number of a,b-unsaturated alky-
noic ketones are obtained.
Ó 2014 Published by Elsevier Ltd.
Keywords:
Oxidation
Hypervalent iodine
Alkyne
Selectivity
Ynone
previous work
The C–H oxidation of hydrocarbons has been widely applied in
the syntheses of functional molecules and useful building blocks.
Examples such as allylic oxidation,1 ether oxidation to esters,2 alkyl
amine oxidation to amides,3 and unactivated sp3 C–H oxidation4
have been studied extensively. In contrast, methods on the propar-
AcO
I OAc
+
I
2 tBuOOH
gylic oxidation toward the synthesis of
a,b-unsaturated alkynoic
O
ketones as useful building blocks are less reported.5 Among the
examples in the literature, methods using metallic catalysts/
oxidants are well documented.6 Herein we report a metal-free
tBuOO
OOtBu
n
n
O
X
X
n
n
n
1
X = O, NR
X = O, NR
oxidation of alkynes to
a,b-unsaturated alkynoic ketones using a
O
O
O
hypervalent iodine reagent.
CN
R3
R1
X
R3 N3
R1
X
n
We previously developed an efficient allylic oxidation reaction
using the diacetoxyiodobenzene/tert-butyl hydroperoxide (DIB/
TBHP) protocol.7a In this reaction, bis(tert-butylperoxy)iodoben-
zene (1) is believed to be an active oxidant and an ester solvent
was found to be necessary in order to obtain high yields. This
method was also applied to the oxidation of cyclic ethers to lac-
tones, cyclic amines to amides,7b azides to nitriles,7c and unactivat-
ed remote C–H oxidation of alkyl esters7d (Scheme 1). We reasoned
that this method would also be applicable to the oxidation of
alkynes to alkynoic ketones.
X = O, NR2
X = O, NR2
this work
tBuOO
I
OOtBu
O
1
R5
R5
R4
R4
Scheme 1. Oxidation using the DIB/TBHP protocol.
Thus, alkyne 2a was selected as a model substrate for the inves-
tigation. n-Butyl butanoate, which was found to be a superior med-
ium for oxidation reactions,7 was used as the solvent. To our
delight, the alkynoic ketone 3a was obtained in 67% yield (Table 1,
entry 1). After a brief solvent screening, it was found that using
ethyl propionate led to a slightly increased yield of 70% (Table 1,
entry 3). On the other hand, n-butyl acetate as the solvent gave
only 59% yield of the desired product 3a (Table 1, entry 2).
Having demonstrated the usefulness of the hypervalent iodine
protocol in the oxidation of the model alkyne, we expanded the
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Corresponding author. Tel.: +65 65167760; fax: +65 67791691.
0040-4039/Ó 2014 Published by Elsevier Ltd.