Diastereoselective Synthesis of Less Accessible Fluorine-Containing Acyclic Tetrasubstituted Stereocenters via Electrophilic Fluorination of β,β-Disubstituted Metalloenamines

Abstract

A stereocontrolled protocol was developed to construct less accessible fluorine-containing acyclic tetrasubstituted stereocenters bearing two sterically and electronically similar alkyl groups at the α-position of carbonyls. In this process, tBuOKpromoted stereospecific α-deprotonation of α,α-disubstituted Ntert-butanesulfinyl ketimines or NH deprotonation of β,βdisubstituted enesulfinamides generates geometry-defined multisubstituted metalloenamines, followed by stereoselective electrophilic fluorination with the N-fluoro ammonium salt of quinine, affording the acyclic α-fluorinated ketimines with excellent diastereoselectivities.

Asymmetric Construction of Ethenyl-Substituted Acyclic Quaternary Stereocenters at the α-Position of Carbonyl Surrogates via Stereoselective Sulfonylvinylation–Reductive Desulfonylation

“…Recently, we have developed three approaches to stereoselectively access the β,β-disubstituted aza-enolates and also explored their applications in stereoselective construction of the less-accessible quaternary or tetrasubstituted stereocenters at the α-position of the aza-analogs of ketones, namely N - tert -butanesulfinyl ( N - t BS) ketimines . For example, persubstituted metalloenamines, generated from deprotonation of the NH in the β-methyl, β-ethyl-substituted enesulfinamides, underwent conjugate addition–elimination cascade with β-nitro α,β-unsaturated ketones or β-tosyl acrylonitrile to afford α-alkenylated ketimines with high stereocontrol (Scheme A) .…”