Addition–Rearrangement of Ketenes with Lithium N-tert-Butanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α-Hydroxycarboxylic Acid Derivatives

Abstract

Addition of the lithium salts of chiral Nsubstituted tert-butanesulfinamides to ketenes and subsequent silylation initiates stereoselective [2,3]-rearrangement, which affords enantioenriched α,α-disubstituted α-sulfenyloxy carboxamides through a reaction that faithfully transfers the absolute stereochemistry of the lithiated sulfinylamides to the α-carbon of the amide products. This addition−rearrangement can be performed together with ketene formation from acyl chloride in a single flask, providing a new and practical synthetic route to α-hydroxycarboxylic acid derivatives.

Synthesis of degradable and chemically recyclable polymers using 4,4-disubstituted five-membered cyclic ketene hemiacetal ester (CKHE) monomers

“…If the 4-position is not di-substituted (but mono-substituted or non-substituted), the compound 3 is unstable, spontaneously generating an undesired compound (a ketene). 35 This requirement is also another reason why we studied 4,4-disubstituted DMDL and PhDL. The stability of the DMDL monomer (8.9 wt%) was studied in DMSO-d 6 (89.3 wt) under moisture (1.8 wt% water) at room temperature.…”

1,4-Aryl migration in ketene-derived enolates by a polar-radical-crossover cascade

“…These reactions often follow a stepwise mechanism with the addition of a nucleophile onto the ketene as the initial step. Equally important but underrepresented in synthesis is conversion of ketenes to the corresponding enolates by nucleophilic attack of C 33 , 34 -, N 35 , 36 -, Si 37 - and O 38 , 39 -anions. This is particularly interesting for the generation of sterically demanding enolates with controlled cis / trans -stereochemistry.…”

Enantioselective Formal 1,2-Diamination of Ketenes with Iminosulfinamides: Asymmetric Synthesis of Unnatural α,α-Disubstituted α-Amino Acid Derivatives

“…On the basis of our prior success in the formal 1,2-aminooxygenation of ketenes via the aza-Mislow–Evans rearrangement, we hypothesized that asymmetric formal 1,2-diamination of disubstituted ketenes could be realized using iminosulfinamides, also known as sulfinamidines (Scheme B). The proposed mechanism involves the nucleophilic addition of NH-deprotonated iminosulfinamides to ketenes, leading to the formation of N -iminosulfinyl amide metalloenolates.…”