Light-Activated Approaches to Highly Challenging Organic Electron Transfer Reactions

Reduction and oxidation are central to chemistry and biology and relate to the addition of electrons or the removal of electrons from substances. Until now, many important but difficult reductions have only been accomplished with very powerful metal reducing agents, like sodium, but we have recently discovered simple neutral organic compounds, composed exclusively of the plentiful elements carbon, hydrogen and nitrogen, that act as powerful reducing agents. In 2012, we found that these substances become even more powerful reducing agents when irradiated with ultra-violet light and are even able to donate electrons to benzene rings that contain no significant electron-withdrawing groups.
We now propose to develop this approach to determine the scope of the chemistry, using visible light to trigger the reactions, rather than untraviolet light, and converting our transformations it into protocols that use our electron donors catalytically.
We believe that the principal reactions that are currently undertaken by sodium dissolved in liquid ammonia can be undertaken by our reagents in organic solvent and irradiated with light. This will not only add economic benefit through use of catalytic processes, but also convenience and enhancements in safety through avoiding reactive species like sodium that are hazardous both to use and to transport.

Who will benefit from the research?

We are exploring advances that should have wide application in industry. They will benefit chemists in all sectors who are engaged in preparative chemistry.

(i) The pharmaceuticals industry would use our methods in preparing substances that will be tested for use in human healthcare. (We attach 2 letters of support to illustrate the views of industry on the potential impact of our research).

(ii) Likewise the agrochemicals industry could use our chemistry in enhancing food production, both through animal healthcare and crop production.

(iii) The knowledge gained from our work should have broader implications for the organic electronics industry since their molecules function through electron transfer and we are extending the limits for electron transfer in neutral organic molecules.

(iv) Our work could also impact on the renewable fuels industry, since we will obtain information about how key steps occur in conversion of carbon dioxide to methane by methanogens.

As a result of using our methods, the general public will benefit indirectly through provision of medicines and enhanced food production, and the economy should benefit through improved processes being used in UK industry.

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How will they benefit from the research?

(i) The pharmaceuticals industry and (ii) the agrochemicals industry routinely need to remove protecting groups from alcohols, acids and amines. Very frequently these are benzyl or benzyloxycarbonyl groups that are removed by aggressive reagents like sodium in liquid ammonia. Reductions of arenes with the same reagents are also used by these industries as rapid routes to access some of their key target molecules.
A big disadvantage is that the use and transport of sodium is hazardous since it reacts violently with water. Liquid ammonia is also hazardous, particularly on a large scale, because of the possibility of unintentional venting as a gas. The alternative common method of deprotection of benzyl and benzyloxycarbonyl groups uses hydrogen gas and noble metal catalysts. Reactions with hydrogen gas on a large scale are dangerous, since it forms explosive mixtures with air. In addition, palladium catalysts are expensive and the activated catalyst must be carefully disposed of to avoid fire risks. These disadvantages would be avoided by our reagents.

By contrast, the protocols that we are proposing use organic reducing agents that are composed simply of the abundant elements carbon, hydrogen and nitrogen, and are therefore easily and economically prepared. Moreover they are transported and manipulated in the form of convenient air-stable and moisture-stable non-hygroscopic salts.

An additional benefit is that our reagents can be regenerated throughout the reaction and so they can be used catalytically. This means that their use causes minimal or zero waste and therefore industry would avoid the costs of treating that waste.

Our reagents have the added benefit of using visible light to make them fully reactive, and this use of activation without adding additional reagents is economical. Our regeneration route involves electrochemical regeneration at -1 V, while our photoactivated donors can achieve reductions equivalent to -3.5 V, again saving electricity costs.