DOI: 10.1002/ejoc.201501423 Communication
1,2-Diones
Copper-Assisted Synthesis of 2-Hydroxyphenyl-1,2-diones from
Phenols and 2-Oxoaldehydes
Narsaiah Battini,
[a,b]
Satyanarayana Battula,
[a,b]
and Qazi Naveed Ahmed*
[a,b]
Abstract: An efficient copper(II)-catalyzed protocol for the or-
tho-functionalization of phenols was developed. A wide variety
of 2-oxoaldehydes and phenols were tolerated, and the corre-
Introduction
Derivatives of benzils, such as 2-hydroxyphenyl-1,2-diones
(HPDs), are widely distributed in nature.
[1]
These compounds
possess intriguing structures and exhibit important biological
activities such as anticancer,
[1a,1b]
antimicrobial,
[1c]
antioxid-
ant,
[1d]
antibacterial, and hypertensive
[1e]
activities, and they
also show inhibition of the enzymatic activity of carboxyl ester-
ases
[2]
(Figure 1). As a result, the development of new practical
methods for the synthesis of this scaffold is of considerable
interest. In this context, Thasana and co-workers developed a
method for the synthesis of HPDs through intramolecular cycli-
zation of anionic benzylic esters of aryl benzyl ethers in the
presence of a base followed by dioxirane oxidation.
[3]
This
Scheme 1. Various synthetic approaches to 2-hydroxyphenyl-1,2-diones.
[a] Medicinal Chemistry Division, Indian Institute of Integrative Medicine
(IIIM/1871/2015),
Jammu 180001, India
E-mail: naqazi@iiim.ac.in
http://www.iiim.res.in
[b] Academy of Scientific and Innovative Research (AcSIR),
2-Rafi Marg, New Delhi, India
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501423.
Eur. J. Org. Chem. 2016, 658–662 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 658
sponding 2-hydroxyphenyl-1,2-diones were afforded in appreci-
able yields.
Figure 1. Naturally occurring bioactive 2-hydroxyphenyl-1,2-diones.
method, however, suffers with limitations in terms of using
complex starting materials and the products are obtained in
low yields. Li et al. reported the synthesis of HPDs by Fe
II
cata-
lyzed ortho-functionalization of phenols with α-hydroxy ket-
ones.
[4]
The yields were comparatively good, but longer reac-
tion times and an external oxidant were required. Our group
also established a synthetic strategy for the generation of HPDs
through an amine-catalyzed cross-coupling approach. In this