DOI: 10.1002/cctc.201200332
Highly Selective Synthesis of Ortho-Prenylated Phenols and Chromans by
using a New Bimetallic CuAl-KIT-5 with a 3D-Cage-type Mesoporous
Structure
Shaji Varghese,[a, b, c] Chokkalingam Anand,[a, b] Dattatray Dhawale,[a, b] Gurudas P. Mane,[b]
Mohammad A. Wahab,[a] Ajayan Mano,[b] George Allen Gnana Raj,[b, c] Samuthira Nagarajan,[b] and
Ajayan Vinu*[a, b]
Prenylated phenols are interesting compounds that form
a group of marine natural products and are involved in many
biological processes.[1] They exhibit a wide range of pharmaco-
logical activities, including anti-inflammatory-,[2] anti-tumor-,[3]
anti-fungal-,[4] anti-HIV-,[5] and anti-Alzheimer’s activity.[6] The
derivatives of prenylated phenols also exhibit a broad range of
biological activities. For instance, prenylated napthaquinones,
such as shikonin, are claimed to be excellent anti-bacterial
agents, whereas prenylated ubiquinones play an important
role in cellular respiration.[7–9] On the other hand, chromans are
interesting compounds that are constituents in several biologi-
cally important compounds, such as vitamin E, which is a natu-
ral inhibitor of the peroxidation of lipids and prevents the
propagation of free radicals in tissues.[10] Some of the most-at-
tractive compounds in the family of chromans are the deriva-
tives of 2-methylchroman, which display excellent antidiabetic
activity.[10] Because of these excellent biological activities, as
well as their importance in the pharmaceutical industry, several
efforts have been devoted to the synthesis of prenylated com-
pounds, chromans, and prenylated 1,4-quinones.[11]
Strong Lewis- and Brønsted acid catalysts are generally used
for the synthesis of prenylated compounds and chromans.[12–17]
However, these catalysts are mostly homogeneous in nature.
From the view point of sustainable chemistry, most of these
catalysts suffer from several disadvantages, such as a high cost,
toxicity, long reaction times, the formation of side-products,
and difficulty in the separation of the products or in reusing
the catalysts. To overcome these disadvantages, researchers
have used heterogeneous catalysts, which represent the best
solution to both the stringent environmental legislation and
the commercial requirements because they produce minimal
amounts of pollution.[18]
One such type of emerging heterogeneous catalysts is 3D-
cage-type mesoporous aluminosilicates with a tunable pore-
size and large surface area and we have demonstrated their
excellent catalytic activity for various organic transforma-
tions.[19] It has been found that the 3D porous structure can
offer facile diffusion of the reactant molecules, which can
avoid pore-blocking and provide better textural parameters
than those of catalysts with 1D porous structures. Constructing
this above catalytic system with multiple elements and multi-
ple catalytic functions could expand its possible applications
and would be expected to enhance the activity- and selectivity
of the products. A similar system is quite common in many
biochemical processes that involve enzymes with different
active sites. However, the design of such a system in an inor-
ganic matrix is quite challenging and fascinating.
Typically, ortho-prenylated phenols are synthesized by Frie-
del–Crafts-like prenylation,[12] anionic alkylation,[13] Claisen rear-
rangement,[14] directed ortho-metalation,[15] and metal–halo-
gen-exchange reactions.[16] However, although these reported
methodologies are quite effective for their synthesis, unfortu-
nately, they often require activating groups or additional pro-
tection- and deprotection steps,[17] because the formed inter-
mediate would sometimes undergo cyclization to form the
chroman. In addition, controlling the chemo- and regioselectiv-
ity by using these above-mentioned sophisticated catalytic sys-
tems is quite difficult, which has forced researchers to look for
alternative methods.
Herein, we propose the creation of Brønsted- and Lewis- or
redox acid catalytic sites in nanocages of mesoporous systems
that are expected to operate concurrently to achieve an overall
transformation. We demonstrate that the selectivity of the
products can be controlled by simply adjusting the nature-
and quantity of the active sites.
Shown in Figure 1 are the low-angle XRD patterns of CuAl-
KIT-5-10 and CuAl-KIT-5-15. Both samples show a sharp peak at
higher angle and several higher-order peaks that correspond
to the (111), (200), and (220) reflections of the cubic space
group Fm3m, thus revealing that the structural order of the
samples is similar to that of the parent KIT-5 silica nanocage.
The HRSEM and HRTEM images of CuAl-KIT-5-15 (Figure 1,
inset) clearly show that the sample exhibits a 3D well-ordered
mesoporous structure with a spherical morphology. The well-
ordered cage-type pores in the samples were confirmed by ni-
trogen-adsorption measurements, which show a typical type-IV
isotherm with a sharp capillary-condensation step and a H2
hysteresis loop (see the Supporting Information, Figure 1S).
[a] S. Varghese, Dr. C. Anand, Dr. D. Dhawale, Dr. M. A. Wahab, Prof. A. Vinu
Australian Institute for Bioengineering and
Nanotechnology, The University of Queensland
Brisbane 4072, QLD (Australia)
[b] S. Varghese, Dr. C. Anand, Dr. D. Dhawale, G. P. Mane, A. Mano,
Dr. G. A. G. Raj, Dr. S. Nagarajan, Prof. A. Vinu
MANA, NIMS
Tsukuba 3050044, Ibaraki (Japan)
[c] S. Varghese, Dr. G. A. G. Raj
R&D Center, Bharathiar University
Coimbatore 641046 (India)
Supporting information for this article is available on the WWW under
ChemCatChem 0000, 00, 1 – 4
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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