Page 6 - Periodic Issue 01

POTLIGHT
3

ON 2ESEARCH IN THE 7ILLIS 'ROUP 4RANSITION -ETAL #ATALYSIS

"Y #ATHERINE "ALL

In the modern era of organic chemistry, aims such as group have developed general heterocycle precursors
reaction efficiency, sustainability and versatility have whereby a variety of different products can be accessed
become increasingly important. When developing new from one key structural template via the action of a
synthetic methodology, reaction yield is no longer the sole palladium and/or copper catalyst.
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focus of the transformation. The product must be formed
via the least number of chemical steps, the process must One such precursor, the alkenyl/aryl dihalide (or halide
generate the minimal amount of waste and must allow equivalent) shown in Figure 1, can provide access to
for the rapid construction of a variety of different product a variety of different heterocyclic products via judicious
analogues. choice of reaction conditions and transition metal catalyst.
As shown, indoles and aza-indoles, benzimidazoles,
As a strategy to achieve these goals, processes involving quinolones and isoquinolones can all be accessed from
transition metal catalysis have gained prominence. Such the same key starting material as well as the comparatively
reactions allow for the catalytic formation of key carbon- unusual cinnoline, aza-cinnoline and quinazolinone
carbon or carbon-heteroatom bonds and have become structures. This rapid access to a variety of diverse
crucial weapons in the modern-day synthetic organic scaffolds has particular relevance from a medicinal
chemist’s armoury. Indeed three of the pioneers of these chemist’s perspective; many different analogues could
reactions were the recipients of the 2011 Nobel Prize for be readily synthesised, aiding the discovery of potential
chemistry. pharmaceutical compounds.

In our group, led by Dr. Michael Willis, we aim to develop Continuing the group’s theme of research with particular
new reaction methodology involving the use of palladium, relevance to the pharmaceutical industry is our work on
copper or rhodium catalysts. The research falls largely into easy-to-handle sources of SO2 in synthesis and catalysis.
three project areas, though our focus throughout the group Traditionally, reactions involving SO2 incorporation are
is the same: to develop novel processes which fulfil the performed using SO2 in its gaseous form. However, due
aforementioned goals of modern organic synthesis and, to its high toxicity and hence the danger involved with
particularly, to create processes that could find application its use, such processes are often avoided. Furthermore,
in the pharmaceutical and agrochemical industries. Indeed, SO2, unlike fellow noxious gas CO, has never enjoyed
many members of the Willis group are sponsored by such success in transition metal chemistry: no analogues of
companies. the highly established, and widely employed, palladium-

One focus of the group is the palladium-
and copper-catalysed synthesis of
heterocycles. The relevance of these
structures cannot be understated. Over
half of the top 200 highest-grossing
drugs, as surveyed in 2010 by the
University of Arizona, contained such
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a motif. Furthermore heterocyclic &IGURE
compounds are also ubiquitous
throughout nature. Thus, expedient, facile
and versatile routes to these structures
are a key area of research.

Transition metal catalysis has found
particular success in the pursuit of
this goal as more traditional syntheses
often require long reaction times, high
temperatures and strong acids or bases
in stoichiometric quantities. The Willis

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Periodic The Magazine of the Department of Chemistry