Small steps by synthetic chemists could mean giant leaps for those who follow, says Karl Collins
Synthetic organic chemistry underpins many of the major advances in scientific research. The careers of synthetic chemists may lack the glamour and media attention associated with materials research, climate science or medicines, but their work is fundamental to progress in each of these fields, and many more besides.
Synthetic chemistry’s role now extends far beyond what Friedrich Wöhler could have ever conceived when he completed his synthesis of urea in 1828, and Nobel prizes throughout the 20th and 21st centuries recognise the continuing impact of synthetic chemistry. Today, using methods developed by masters of their trade, the modern greats of total synthesis demonstrate that almost any molecule can be prepared given time and effort.
However, excitingly, as scientific boundaries continue to blur, synthetic chemistry is no longer confined to the labs of expert practitioners, but is applied by anybody in need of organic compounds. In light of this, we should consider how the communication of synthetic methodology might evolve to support this growth.
In developing new synthetic methods, I hope for one of two outcomes: that the chemistry is applied to solve a problem directly; or that it delivers insight that enables a further discovery, which in turn solves a problem. I cannot consciously choose to undertake research that will be applied by others – the impact of any scientific discovery can only be known retrospectively – but I believe my work has the greatest chance of fulfilling these hopes if I enable as many people as possible to apply it.
I neither offer, nor intend, criticism of current practice, but rather propose some simple additions to the reporting of synthetic methodology that might enable new chemistry to be applied more easily. This would benefit the author, those using the chemistry, and the synthetic community as a whole. The suggestions are not all novel (some already enjoy widespread use) and should be considered with a view to directly applying a given synthetic methodology – their relevance to conceptual and fundamental advances may of course be less:
1. Chemistry is capricious. Thus, repeating a reaction multiple times, and reporting all yields, rather than the average, would reveal the consistency and the boundaries of a given reaction. Reporting this information for two or three substrates of differing electronic or steric properties would also provide a much fuller overview. Scalability, failed substrates and alternate conditions – including those less than optimal – are also of interest.1
2. From working in, and through contact with, the chemical industry, it is clear that the single most common question asked of a new synthetic methodology is: ‘How well does it work outside the idealised conditions?’ To address this issue, Frank Glorius and I recently devised a simple and rapid screen to assess the likely tolerance of a given reaction to a broad range of functionalities.1-3 This screen also provides information about the stability of these functionalities to the reaction conditions, and their effect on the rate of reaction. We believe this information is complementary to that presented in a traditional substrate scope. This typically assesses a limited number of bifunctional substrates – in which the reactive group and the other functionality directly influence each other – under standard reaction conditions. We hope the additional information generated in the screen will assist in designing synthetic routes and applying new chemistry to more complex molecules.2
3. In a practical sense, many aspects of running an experiment do not cross the mind of those developing methodology, and reporting new methods within the ‘standard template’ of an experimental report highlights this. There is no room for ‘don’t put the tip of the needle too close to the solution because it will freeze’, or ‘the initial separation takes about an hour’ in traditional experimental details, yet this information is incredibly useful, especially to the less experienced chemist. Some journals specifically address these finer points, but it is not feasible that all methods are investigated and reported in this way. A straightforward solution would be the inclusion of this additional information in a ‘hints and tips’ section for example, within the supporting information of a report.3
The points discussed here are simple, but could significantly increase the likelihood that a given methodology will be adopted, or at least attempted. Many of the suggestions are absent from my previous work, but my realisation of their value means this will change. Starting my career, my ideals may be naïve or overly optimistic, and perhaps experience will change my perception and my practice, but I sincerely hope not. Synthetic organic chemistry is fundamental to so much scientific progress; we should make it as easy as possible for those who want to use it.
Karl Collins is a research associate at the University of Münster, Germany