Stereocontrolled Construction of Acyclic Quaternary Carbon Centers via α-Hydroxymethylation of α-Branched N-tert-Butanesulfinyl Ketimines

Hydroxymethylation of alpha-branched N-tert-butanesul-finyl ketimines with formaldehyde equivalents was developed to stereoselectively construct acyclic quaternary stereocenters bearing two sterically and electronically similar substituents. The stereo-selective tBuOK-promoted alpha-deprotonation of acyclic ketimines allowed for the stereodefined formation of fully substituted aza-enolates, followed by facially selective C-C bond formation involving formaldehyde formed in situ, yielding alpha-hydroxymethylated products with precise stereocontrol.

Automated summary

In this study, a method for the hydroxymethylation of alpha-branched ketimines using formaldehyde equivalents was developed, allowing for the stereoselective construction of acyclic quaternary stereocenters bearing two similar substituents.