Rylan J. Lundgren, Ashraf Wilsily, Nicolas Marion, Cong Ma, Ying Kit Chung, and Gregory C. Fu
Angew. Chem. Int. Ed.
A carbonyl group provides a pivot point for the functionalisation of its proximal positions – α and β. This can be demonstrated by the reactivity of classical enolates as α-functionalisation nucleophiles and Michael acceptors as β-functionalisation electrophiles, as well as their corresponding reactivities in enamine and imminium organocatalysis.
In a recent report Lundgren et al. have successfully demonstrated that γ-functionalisation of carbonyl compounds is also achievable, both intra- and inter- molecularly. Using a spirophospine ligand to induce stereoselectivity, the group has demonstrated the feasibility of asymmetric C-N bond formation with nitrogen nucleophiles and alkynoates or allenoates as electrophiles.
Investigating the scope of the reaction revealed that a good range of functional groups can be accommodated in either intramolecular reactions with alkynoates or intermolecular reactions with allenoates.
The process provides access to novel reactivity and it may even prove complementary to the classical α- and β- asymmetric functionalisation of carbonyl compounds. It would be interesting to see if a γ-, β-, α-cascade addition would be possible.