Enantioselective α-heterofunctionalization reactions of catalytically generated C1-Lewis base enolates.

Chiral Lewis base (LB) organocatalysis has emerged as a powerful covalent catalysis concept which allows for highly selective asymmetric C-C and C-heteroatom bond formations. Considering significant recent progress in the development of strategies to access α-heterofunctionalized carboxylic acid derivatives under chiral LB catalysis, we wish to summarize the most significant concepts and advances in this field within this mini review now.

Photochemical Wolff Rearrangement Initiated Generation and Subsequent α-Chlorination of C1 Ammonium Enolates.

The enantioselective synthesis of α-chlorinated carboxylic acid esters with er up to 99:1 and yields up to 82% was achieved via a one-pot multistep protocol starting from α-diazoketones. This process proceeds via a photochemical Wolff rearrangement, trapping of the generated ketene with a chiral Lewis base catalyst, subsequent enantioselective α-chlorination, and a final nucleophilic displacement of the bound catalyst. The obtained products were successfully utilized for stereospecific nucleophilic displacement reactions with - and -nucleophiles.

Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions.

The asymmetric α-chlorination of activated aryl acetic acid esters can be carried out with high levels of enantioselectivities utilizing commercially available isothiourea catalysts under base-free conditions. The reaction, which proceeds via the in situ formation of chiral C1 ammonium enolates, is best carried out under cryogenic conditions combined with a direct trapping of the activated α-chlorinated ester derivative to prevent epimerization, thus allowing for enantioselectivities of up to e.r.

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane.

We herein report a method for the kinetic resolution of racemic 4-hydroxy[2.2]paracyclophane by means of a chiral isothiourea-catalyzed acylation with isobutyric anhydride. This protocol allows for a reasonable synthetically useful -factor of 20 and provides a novel entry to obtain this interesting planar chiral motive in an enantioenriched manner.