Engineered serendipity

23 December 2011 - Lazy chemistry II

Serendipity McMillan 2011  McNally, Prier & MacMillan are also on the trail of high-throughput organic reaction discovery in what this blog likes to call lazy chemistry (DOI). The main theme is serendipity and the quotes are fantastic: "Recently, we questioned whether serendipity could be forced or simulated to occur on a predictable basis in the realm of reaction discovery, thereby providing a reliable platform to access valuable transformations or unexpected pathways" and "assuming that serendipity is governed by probability...".
The research protocol looks very similar to the one described by Hartwig (DOI) just 4 months ago and features a 96-well plate that was filled horizontally and vertically with up to 19 different simple organic substrates such as benzaldehyde or pyridine. A known reaction type between any two reaction partners should not be obvious. A solvent containing transition-metal catalysts / ligands was then added and after exposure to a 26 watt fluorescent lamp and a certain reaction time the reaction product was analysed by GC-MS and a MS library. The article boasts up to a thousand reactions per day can be screened in this semi automatic way.
The main find was a novel carbon-carbon coupling reaction between 1,4-dicyanobenzene and N-phenyl-pyrrolidine using photoredox catalyst iridium tris(2-phenylpyridine).