Professor Michael North

Professor of Organic Chemistry and joint director of the URC in Catalysis and Intensified Processing

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The formation of carbon-carbon bonds is the heart of organic chemistry. Much of my current research is concerned with the development of new catalytic (and usually asymmetric) methods for the construction of carbon-carbon bonds.

An additional interest is the chemistry of CO₂, particularly the conversion of waste CO₂ into useful chemicals which can provide an economical alternative to carbon capture and storage.

This work is wide ranging, and has attracted support from EPSRC, TSB, the EU and industry.

For details of current vacancies within my research group see the vacancies page.

Specific current areas of interest are given below.

Catalytic Asymmetric Cyanohydrin Synthesis

Cyanohydrins are versatile starting materials for the synthesis of a wide range of other industrially important compounds, as well as being components of the pyrethroid insecticides in their own right. There are however, very few routes for the asymmetric synthesis of cyanohydrins. Over recent years we (in collaboration with Prof. Y.N. Belokon’) have developed metal salen complexes such as 1 and 2 as highly efficient catalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes and ketones (Scheme 1). Catalysts 1 and 2 have the following beneficial features compared to other catalysts for this reaction:

· Only 0.1mol% of the catalyst is required

· The reactions can be carried out at room temperature without the need for dry solvents and reagents

· A wide range of aldehydes are substrates for the catalyst

· Complex 1 will also accept ketones as substrates

· Good to excellent enantiomeric excesses are obtained

· The mechanism of the reaction has been determined

· The origin of the asymmetric induction is understood

· The catalysts are readily prepared in two steps

The main disadvantage of this process is the need to employ trimethylsilyl cyanide as the cyanide source. This reagent is expensive and a volatile liquid. More recently, we have also shown that catalyst 1 will catalyse the addition of other cyanide sources including ethyl cyanoformate (Scheme 2) and potassium cyanide (Scheme 3) to aldehydes. The latter reaction is unique to our catalysts. Ongoing work in this area is concerned with:

· Using physical organic chemistry techniques to study the mode of action of the catalysts

· Studying the mechanism of cyanohydrin synthesis in general

· Further developing the catalysts for use with ketone substrates

· Investigating the role of the counterion X in catalysis by vanadium complexes 2

· Demonstrating that catalysts 1 and 2 can be used in ‘green’ solvents derived from CO₂

Information on the commercialisation of catalysts 1 and 2 is also available Here

A list of publications arising from the use of catalysts 1 and 2 for asymmetric cyanohydrin synthesis is available

Synthesis and Application of Heterobimetallic Catalysts

We have shown that catalysts 1 and 2 are catalytically active as bimetallic complexes. Both metal ions play a role in the catalysis, one activating the aldehyde and the other activating the cyanide (Figure 1). Recently, we have shown that when catalysts 1 and 2 are mixed, a new bimetallic complex such as 3 is formed. This opens up the possibility of preparing a whole range of hetero-bimetallic complexes analogous to 3 in which both the metals and ligands attached to the metals can be independently varied. These complexes can then be sterically and electronically tuned to exhibit catalysis for a wide range of reactions for which complexes 1 and 2 are themselves inactive. Examples of important carbon-carbon bond forming reactions that may be amenable to catalysis by hetero-bimetallic complexes of this sort are shown in Scheme 4, though many other reactions can also be envisaged.

For our publications in this area see references 21 and 31 of our papers on asymmetric cyanohydrin synthesis.

Asymmetric Enolate Alkylation

Following on from the asymmetric cyanohydrin synthesis project, we have been developing asymmetric catalysts for other carbon-carbon bond forming reactions. A recent discovery has been that copper(II) salen complex 4 and the corresponding cobalt(II) salen complex 5 will catalyse the asymmetric alkylation of enolates of amino ester derivatives 6, giving a,a-disubstituted amino-acids with up to 90% enantiomeric excess (Scheme 5). This reaction has a number of remarkable features:

· It can be carried out at room temperature using toluene as solvent

· Only an inexpensive and relatively mild base (sodium hydroxide) is required

· The reaction is an example of phase-transfer-catalysis since solid sodium hydroxide is employed

· Only 2 mol% of the catalyst is required

· A wide range of a-methyl-a-amino acids have been prepared in this way

　　　

Ongoing work is aimed at understanding the mechanism of this reaction and hence optimizing the asymmetric induction. Extension of the chemistry to other enolates and to other reactions (Michael additions, aldol reactions etc) is also under investigation and we have recently shown that Darzens reactions (Scheme 6) can be catalysed in this way, allowing both the diastereo- and the enantioselectivity to be controlled.

A list of our publications on asymmetric amino acid synthesis using phase transfer catalysts is available.

A list of our publications on asymmetric Darzens condensations using phase transfer catalysts is available.

Synthesis of Cyclic Carbonates from CO₂ and Epoxides

Possibly the biggest single challenge facing the human race during the 21^st century is the mitigation of global warming due to ever increasing emissions of CO₂ which a major greenhouse gas. In addition, supplies of fossil fuels are limited and yet hydrocarbons are currently employed not only to power the chemicals industry, but also to provide the necessary raw materials. One approach to solving these problems would be to find commercially viable routes to use waste CO₂ as a starting material for the chemicals industry. We have recently developed bimetallic aluminium(salen) complex 6 and shown that it will catalyse the insertion of CO₂ into epoxides to form commercially important cyclic carbonates (Scheme 7). The synthesis of cyclic carbonates is currently operated commercially at high temperatures and pressures making it unsuitable for use with waste CO₂. However, complex 6 will catalyse the reaction at room temperature and one atmosphere pressure, thus giving it the potential to exploit waste CO₂ from a fossil fuel power station. In ongoing work, we have developed versions of catalyst 6 which do not require a tetrabutylammonium bromide cocatalyst and shown that these one-component catalysts can be immobilised and used in a continuous flow reactor. The mechanism of action of the catalysts has also been studied in detail. In collaboration with the group of Professor Ian Metcalfe (Newcastle Chemical Engineering), we have also shown that the catalysts can utilise CO₂ from the flue-gas of an oxy-fuel combustion system. Ongoing work is concerned with:

· Investigating the tolerance of the catalysts to impurities present in flue gas

· Optimising the structure of the catalyst with respect to both catalyst activity and catalyst lifetime

· Minimising the cost of production of the catalyst

· Studying the use of CS₂ and related species instead of CO₂ to allow a wide range of heterocycles to be synthesised

A list of our publications on cyclic carbonate synthesis is available.

Organo-Catalysis

In the early 1990’s, the North group were the only UK based research group working on asymmetric catalysis using purely organic based catalysts (i.e without the use of a metal). This area of research has recently undergone a major revival of interest world-wide, with the naturally occurring amino acid – proline being particularly widely used to catalyse many important carbon-carbon bond forming reactions including: aldol reactions, nitro-Henry reactions, Mannich reactions, and Diels-Alder reactions. Whilst the use of proline as a catalyst has many ‘green’ features as the catalyst is available from renewable sources and the reactions it catalyses tend to be 100% atom economical, one problem with proline based catalysis is the choice of solvent. Reactions are often carried out in either polar aprotic solvents such as DMF or chlorinated solvents. Therefore, in ongoing work we have shown that ethylene 7 and propylene carbonates 8 which can be prepared from waste CO₂ (see above) make excellent solvents for proline catalysed aldol reactions (Scheme 8). There are intriguing differences between the two solvents which can be related to the difference in polarity between the solvents and to the fact that propylene carbonate is chiral. Ongoing work in this area is concerned with:

· Studying the differences between ethylene and propylene carbonate as solvents

· Extending the chemistry to the use of other amino acids as catalysts

· Investigating other proline catalysed reactions in cyclic carbonates as solvents

· Extending the chemistry to other classes of organocatalysts

· Extending the use of cyclic carbonates as solvents to other classes of asymmetric and non-asymmetric reactions (including asymmetric cyanohydrin synthesis – see above)

For a list of our publications on organo-catalysis, see references 1-6 of our publications on asymmetric cyanohydrin synthesis.

A list of our publications on use of cyclic carbonates as solvents is available.

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