On the novel function of the additive DBU. Catalytic stereoselective deprotonation by a mixed dimer of lithiated DBU and a chiral lithium amide

Abstract

The additive DBU is used to increase the selectivity and reactivity of e.g. chiral lithium amides in both catalysed and non-catalysed asymmetric syntheses. This has been attributed to the coordinating ability of DBU favoring more reactive aggregates. However, we have found that LDA in THF deprotonates DBU to yield lithiated DBU (1) as shown by multinuclear NMR studies. Furthermore, compound 1 is found to form a mixed dimer (5) with e.g. the norephedrine-derived chiral lithium amide 2. Results of an investigation of the stereoselectivity of this novel reagent in the epoxide deprotonation are also reported. Computational studies using PM3 and DFT show possible structures of 1 and 5 in line with the NMR results. In addition, the role of THF and DBU in the solvation of the aggregates has been investigated by computational modelling and favoured complexes in the equilibria between homo- and heterocomplexes are also reported.