ORGANIC
LETTERS
2011
Vol. 13, No. 16
4308–4311
An Unexpected Oxidation of Unactivated
Methylene CÀH Using DIB/TBHP Protocol
Yi Zhao,† Wai-Leung Yim,‡ Chong Kiat Tan,†,‡ and Ying-Yeung Yeung*,†
Department of Chemistry, National University of Singapore, 3 Science Drive 3,
Singapore 117543 and Institute of High Performance Computing, 1 Fusionopolis Way,
No. 16-16 Connexis, Singapore 138632
Received June 18, 2011
ABSTRACT
An in situ generated hypervalent iodine species, bis(tert-butylperoxy)iodobenzene, was used as a peroxy radical source for the oxidation of
unreactive, remote, and isolated alkyl (cyclic or aliphatic) esters and amides to the corresponding keto compounds under very mild conditions.
Unactivated sp3 CÀH oxidation is an important class of
organic transformation. Inexpensive hydrocarbons from
petrochemical feedstocks can be functionalized as high-
value building blocks and intermediates.1 In addition, the
direct functionalization of the inert carbons can often
shorten the synthetic sequences,2 which is of particular
interest to the manufacturing sectors.3 Despite the impor-
tance and the power of this class of reaction, this research
area remains challenging and a major obstacle is the high
energy of the unactivated CÀH bond that makes it very
inert toward many reagents.4 Over the past decades, sig-
nificantendeavors have been dedicatedinvolving the use of
metallic5,6 and nonmetallic7,8 reagents/catalysts.9 Herein
we describe an unexpected and unprecentented oxidation
of unreactive, remote, and isolated sp3 methylene CÀH to
ketone using a diacetoxyiodobenzene (DIB) (1)/tert-butyl-
hydroperoxide (TBHP) (2) protocol.
† National University of Singapore.
‡ Institute of High Performance Computing.
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r
10.1021/ol2016466
Published on Web 07/25/2011
2011 American Chemical Society