Efforts in our group are focused towards the synthesis of aminoboronic acids of general structure 1. We recently highlighted the potential for these types of structures to catalyse organic reactions by using 2 as an efficient catalyst for amide bond formation.

Based on the above, and recent developments in organocatalysis such as proline-catalysed reactions, we suggested boronoproline 3 and its homologue 4 as potential catalysts for organic reactions. In this presentation, we report the first direct asymmetric syntheses of these types of structures based on sparteine-mediated asymmetric lithiation chemistry. Boc-boronoproline can be directly obtained using triisopropyl borate as the electrophile of choice to quench the intermediate lithium anion. Subsequent deprotection of the amine using TFA:DCM affords 3 in 50% overall yield and 90% enantiomeric excess. In the case of the homologue 4, chloromethylboronate pinacol ester (ClCH₂Bpin) was used as the electrophile to yield the boronate ester. Successive deprotection using diethanolamine, then HCl hydrolysis and TFA:DCM Boc deprotection afforded 4 in 27% overall yield and 96% enantiomeric excess.

Further structural investigations have been carried out using a combination of pH titration and ¹¹B NMR spectroscopy to determine the pK values for 3 and highlight the presence of a transient B-N chelated species and boronate “ate” complexes.