A Pd-Catalysed Synthesis of Highly Functionalised Piperidines

When research papers are of particular significance, they can be featured as front covers or back pages. One such paper highlights research performed in Prof. Harity's group on palladium catalysed synthesis of piperidine products. A summary of the paper is detailed below. To read the full article, visit the Chemistry A European Journal website.

This work describes a new method for the synthesis of piperidines, a highly important molecular fragment present in pharmaceuticals, agrochemicals and natural products. The key objective was to generate a zwitterionic intermediate (a charged but neutral molecule) using a palladium catalyst and to exploit this in a coupling reaction with a carbonyl containing compound. Specifically, we envisaged that a nitrogen anion would be sufficiently basic to deprotonate a pronucleophile which could subsequently attack the positively-charged Pd-π-allyl moiety in this intermediate (Scheme 1). This allows the formation of a new C-C bond at a quaternary stereocentre – a challenging feat in synthetic chemistry.

Schematic for the formation of a new C-C bond through Pd-catalysed synthesis

Upon completion of this first step, we planned to use acid (H+) to remove the protecting group (PG) on the nitrogen atom in order to initiate a condensation reaction with the carbonyl to deliver our piperidine products.

Schematic of the ring-closing reaction to synthesis piperidine

One of the most promising aspects of this chemistry is the ability to control the stereoselectivity of the reaction using chiral ligands on the palladium catalyst. This offers the opportunity to access a wide range of piperidine architectures with control of absolute stereochemistry.

This is one of many journal front covers detailing research performed in the department. To see the full collection, visit our research website.