Stitching with acetonitrile

Acetonitrile is rapidly turning into one of my favourite reagents. Its nucleophilicity can be quite instrumental under special circumstances, which is why acetonitrile is not just an overpriced HPLC solvent whose cost goes through the roof whenever Chinese economy tanks. The Ritter reaction instantly comes to mind whenever the nucleophilic properties of acetonitrile are considered. Of course, there are other examples, particularly in the organometallic literature.

Below is a recent case published by Lavilla and coworkers. This chemistry reminds us that acetonitrile can be a useful stitching element when employed at the right place and at the right time. The multicomponent reaction developed by the Lavilla group involves a cyclic imine that, upon activation by a Lewis acid (scandium triflate), undergoes a Mannich-type process. The resulting oxonium endpoint cannot undergo Povarov ring closure (my colleague Doug Stephan might call this a “Povarov-frustrated oxonium ion”). It appears that the oxonium ion’s reluctance to undergo Povarov reaction with the aromatic indoline fragment is due to geometrical constraints. Well, mother Nature hates voids and acetonitrile gladly fills the gap. The nucleophilic addition leads to the formation of a nitrilium ion (a special “hello” to my lab members is due at this point – they know what I am talking about), which is rapidly trapped by the nitrogen center. This is an awesome new multicomponent reaction that is rooted in the exceptional properties of acetonitrile.

lll

http://onlinelibrary.wiley.com/doi/10.1002/anie.201202927/abstract

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