Page 7 - Periodic Issue 01

appropriate choice of reaction conditions we
aim to fully control the nature of the product
generated from the reaction. To this end
we have developed new catalysts, whose
properties have been fine-tuned to facilitate
the desired outcome of a reaction.

A variety of different aldehydes and
unsaturated components can be used in
&IGURE of synthetically useful products, including
the process. This results in the generation

those which can be used to access
heterocycles via traditional cyclisation
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procedures as shown in Figure 3. A
stipulation of the process is that the
aldehyde used must contain a chelating
catalysed carbonylation processes exist, despite the similar atom, most commonly sulfur, to stabilise
properties of CO and SO2. a crucial rhodium intermediate in the catalytic process.
Though work is underway to overcome this prerequisite,
To overcome these drawbacks, the Willis group have it has been demonstrated that such a group can act as a
developed solid SO2 surrogates based on charge-transfer handle for further functionalisation of the product molecule,
complexes formed between amines and SO2 gas. DABSO thereby increasing the efficiency and atom economy of the
(1,4-diazabicyclo[2.2.2]octane bis (sulfur dioxide) adduct), reaction.
our most successful of these bench-stable complexes
so far, has recently become available to purchase from Though our work in the Willis group spans a variety
Sigma-Aldrich and it is hoped that this will become a of different areas, our research has the same goal: to
widely used reagent. As shown in Figure 2, we have meet the demands of modern organic synthesis via the
demonstrated that it can replace SO2 gas in a variety of use of transition metal catalysis. With particular focus
known transformations, making procedures involving SO2 on the development of processes which could find
incorporation more attractive to the modern-day synthetic application in the pharmaceutical and agrochemical
organic chemist. industries, we strive for sustainability and efficiency in the
3
synthetic methodology we develop. With these aims, our
We are also investigating the use of this reagent in catalysis contributions towards the expanding field of transition metal
and have developed the synthesis of N-aminosulfonamides catalysis can only continue.
via the action of a palladium catalyst,
in analogy to established carbonylation
chemistry (Figure 2). Given the
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prevalence of the sulfonamide motif
in medicinal agents this procedure
is particularly relevant. Investigations &IGURE
into the development of other catalytic
processes involving SO2 incorporation
and palladium catalysis are currently
underway.

Continuing our pursuit towards the
development of sustainable and
efficient reactions, rhodium catalysis,
particularly the development of the
synthetically useful hydroacylation
reaction, is the third focus of the group’s research.
Such a process is inherently atom economical since Key references:
hydroacylation involves the addition of the elements of an 1. Njardarson research group, University of Arizona:
http://cbc.arizona.edu/njardarson/group/top-pharmaceuticals-poster
aldehyde across an unsaturated bond, such as an alkene 2. Sadig, J.E.R., Willis, M.C. Synthesis 2011, 1.
5
or an alkyne (Figure 3). Thus there is no wastage; all the 3. Woolven, H., González-Rodríguez, C., Marco, I., Thompson, A.L. Willis,
M.C. Org. Lett. 2011, 13, 4876.
component parts of the starting materials are retained in 4. Emmett, E.J., Richards-Taylor, C.S., Nguyen, B., Garcia-Rubia, A., Hayter,
the products generated. B.R., Willis, M.C. Org. Biomol. Chem. 2012, 10, 4007.
5. Willis, M.C. Chem. Rev. 2010, 110, 725.
6. Lenden, P., Entwhistle, D.A., Willis, M.C. Angew. Chem. Int. Ed. 2011,
The targets of our research are to develop the selectivity, 50, 10657.
scope and generality of the procedure. Through A full list of our publications can be found on our website,
http://mcwillis.chem.ox.ac.uk/MCW/Home.html.

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Periodic
The Magazine of the Department of Chemistry