Amplification of Enantioselectivity in Organocatalysis: Fast Catalyst Screening, Developments & Synthetic Applications – AMPLI

The Ampli project aims at addressing the two major following issues in modern enantioselective catalysis :

1/ How to quickly select a good catalyst among a library of available molecules, hence minimizing optimisation experimental studies which can turn to be tedious ?

2/ How, starting from this catalyst (good but not excellent), to obtain excellent enantioselectivity results ?

The AMPLI project proposes to answer to these questions by combining High Resolution Mass Spectrometry study of chiral catalysts behaviour through a combinatorial approach to a strategy based on the use of Horeau type amplification effects, and therefore to obtain the best enantioselectivities. The work described is divided into three tasks :

- A screening of commercial, or easily available, catalysts by means of an electronspray ionisation high resolution mass spectrometry study, a technique which can be used to characterize quasi-enantiomeric products or intermediates through a combinatorial approach. The goal is to identify the best catalysts, along with the associated experimental conditions, for the organocatalyzed acyl transfer reaction on monofunctionnalized substrates.

- The use of the selected catalysts with bi-functionnalized substrates, such as diols, diesters and aminoalcohols, on similar reactions. In all cases, we will be taken advantage of the Horeau effect to obtain the best enantiomeric excess. Applications of these reactions to the synthesis of bioactive molecules of pharmaceutical interest is also planned.

- Based on the previous results, development of a multicatalytis enantioconvergent dynamic amplified process which allows, through a catalytic epimerization and an enantioselective acylation, to prepare a single enantiomer starting from a diastereomeric mixture of a given compound.