I’ve been an organic chemist (at the doctorate level) for over ten years. More precisely, I’m a synthetic organic chemist. I piece together small chemical building blocks into larger ones, continuing to perform reactions until I reach the goal of my research – a new adhesive, or a new medicinal compound, etc. The reactions I use are usually ones which are in the open literature (published by other authors). Occasionally, I’ll use everything I know about chemistry and the behavior of molecules to devise a new reaction; I won’t attempt it if I don’t think it’ll work, as it’s a waste of time and resources, but if it stands a good chance and it gets me where I need to be, I’ll go ahead with it. The point is, there’s usually some precedence for what I attempt in the laboratory, whether it’s someone else’s published work or my own experience and intuition.
Imagine my surprise, then, when I read a very recent paper in the prestigious journal Science where the authors took a completely different approach to organic synthesis. By using an automated, computer-controlled robotic instrument whereby more than 1,000 chemical reactions could be performed and analyzed in one day, scientists at Princeton are relying on the “shotgun approach” to finding new and interesting chemical reactions. Instead of intensely researching one approach and then carefully performing it on a relatively large scale (several grams), an approach which can take several days when purification and analysis are considered, the chemists do a thousand miniature reactions at once.
Even more astonishing, the chemists deliberately choose molecular pairings that they don’t think will react with each other. Normally a trained organic chemist such as myself wouldn’t dream of doing the synthetic equivalent of mixing oil and water – I know they’re not compatible, they’re not going to do anything interesting, and so I’m not going to waste several hours work setting up the flasks and weighing out all of the starting materials. However, even as experienced as I am, I don’t know everything. Molecules surprise me all the time; it’s part of what makes organic chemistry such a challenging field, as you have to be adaptable and capable of attacking a target from multiple directions. Maybe, one in a thousand times, “oil and water” do mix.
In the context of this journal article, this means that the researchers placed together two molecular components that would normally not be expected to react with each other. They weren’t particular interesting molecules and most of them were fairly stable, and were simply stirred together at a variety of temperatures in a neutral solvent with some irradiation by a light. However, that “one in a thousand” clause rears it’s head when you actually do perform a thousand reactions in a day, and so the authors of the Science paper stumbled upon some very interesting reactivity that is clearly useful and will be brought into labs worldwide as a valuable synthetic technique for the production of benzylic amines.
It’s an interesting technique. It’s something that you would never experience in a normal lab, where you’d be hard pressed to do three to four reactions a day, let alone a thousand. However, by taking advantage of miniaturization as well as automation, many different combinations were able to be screened. Some genuinely fascinating reactivity emerged, reactivity that no-one was able to predict, but which now makes sense (after the fact). No-one would have thought to try it before, but now it’s a valuable part of a synthetic chemists toolbox.
New reactions are discovered all the time. I keep up with most of the major chemical journals and many of them describe new methodology. What is interesting about this particular paper is the manner in which the new reaction was discovered. It makes me very curious as to what other reactions are out there, just waiting to be unearthed. As a synthetic chemist of more than a decade, I’m indebted to researchers such as these that give me more tools to accomplish my goals.
The source of this article can be found at:
McNally, A.; Prier, C.K.; MacMillan, D.W.C. “Discovery of an Amino C-H Arylation Reaction using the Strategy of Accelerated Serendipity”. Science 2011, 334, 1114.