Good old condensation reactions

We have finished our grant proposal and managed to submit it on time. As I mentioned yesterday, this grant deals with the chemistry of boron-containing heterocycles and their biological properties as serine protease inhibitors. A preliminary account of our borocycle chemistry driven by boryl isocyanides, appeared earlier this summer (see my July 21 post). Besides what I think is an interesting structure-driven means to optimizing the cellular permeability and activity of these molecules, we have an approach to place boron in heterocycles using simple condensation reactions. As I was thinking about condensation chemistry, I recalled to mind some of my favorite papers from the past. A lot has been said about enamines in recent years, and for a good reason. Originally developed by Stork, enamines are the engine of many innovative synthetic approaches, including organocatalysis. Yet, if you think about the parent “NH2” enamine, it has remained a curiosity due to its highly unstable nature. Back in 2001, Novak and colleagues published a thought-provoking paper that trapped these species in a radical-mediated polymerization. This publication has always been one of my all-time favorite papers. The way to generate the parent enamine shown below is not through condensation (can’t really use thermodynamically controlled reactions). Instead, the authors used transition metal-catalyzed isomerization. Afterwards, they cleverly co-polymerized the enamine under radical  conditions before it had a chance to undergo tautomerization. To me, this is super cool.

Imagehttp://pubs.acs.org/doi/pdf/10.1021/ja011609i

P.S. I am sure my lab might notice the wording “simple enamines” in the paper title…

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