Asymmetric synthesis second-generation, examples

Significant improvement in the catalytic activity of ALB was realized without any loss of enantioselectivity by using the second-generation ALB [27] generated by the self-assembled complex formation of ALB with alkali metal-malonate or alkoxide. This protocol allowed the catalyst loading to be reduced to 0.3 mol %, for example, the Michael addition of methyl malonate to cyclohexenone catalyzed by the self-assembled complex of (ff)-ALB (0.3 mol %) and KO Bu (0.27 mol %) in the presence of MS 4A gave the adduct in 94% yield and 99% ee [28]. This reaction has been successfully carried out on a 100-g scale wherein the product was purified by recrystallization. The kinetic studies of the reactions catalyzed by ALB and ALB/Na-malonate have revealed that the reactions are second-order to these catalysts (the rate constant ALB = 0.273 M 1h 1 ALB/Na-maionate = 1-66 M 1h 1) [27]. This reaction was used as the first key step for the catalytic asymmetric total synthesis of tubifolidine (Scheme 8D. 11) [28]. 

The corresponding thioether fnnctionalised NHC without a second chiral wingtip gronp bnt an asymmetric carbon atom in the thioether sidearm was also synthesised by Ros et al. [261], However, we will tnrn our attention towards a similar example from the same research gronp [262] where the NHC is pyrido[a] annulated [263], The synthesis is again rather facile and follows standard procedures (see Figure 4.86). The chiral thioether precursor compound is accessible as the alcohol and needs to be treated with tetrabromomethane and PPhj to generate the required primary alkyl bromide. 

---