Some amine tricks worth noting

Over the years, Professor Tohru Fukuyama of the University of Tokyo has come up with a multitude of imaginative ways to make bioactive amines. In the past, I mentioned some of his chemistry on my blog. As someone who is constantly on the lookout for new ways of making electronically challenged amide structures, I recently learned to appreciate Fukuyama’s way of making N-acylpyrroles, which are valuable synthetic intermediates without a particularly straightforward synthesis. Until Fukuyama’s Org. Lett. publication that is…

N-Acyl pyrroles are fascinating amides due to the aromaticity of the leaving group when the time comes for the corresponding tetrahedral intermediate to collapse. Fukuyama’s method to make acyl pyrroles starts from the tetramethoxy derivative shown below. The amine intermediate obtained by a straightforward sequence is converted into an N-acylpyrrole under acidic conditions. The fact that Boc-L-phenylalanine can be converted into the corresponding N-acylpyrrole without racemization is particularly striking. While in Brazil 2 weeks ago, I heard Professor Ludger Wessjohann talk about an adaptation of Fukuyama’s N-acyl pyrrole sequence in the area of multicomponent reactivity. You probably guessed that this involved making a convertible isocyanide. As a result, it is now possible to treat a range of Ugi-based products and cleanly generate the products of acyl transfer to your favourite nucleophiles.