Stereoselective halogenation is a highly useful organic transformation for multistep syntheses because the resulting chiral organohalides can serve as precursors for various medicinally relevant derivatives. Even though decarboxylative halogenation of aliphatic carboxylic acids is a useful and fundamental synthetic method for the preparation of a variety of organohalides, an enantioselective version of this reaction has not been reported. Here we report a highly enantioselective decarboxylative chlorination of β-ketocarboxylic acids to obtain α-chloroketones under mild organocatalytic conditions. The present method is also applicable for the enantioselective synthesis of tertiary α-chloroketones. The conversions of the resulting α-chloroketones into α-aminoketones and α-thio-substituted ketones via SN2 reactions at the tertiary carbon centres are also demonstrated. These results constitute an efficient approach for the synthesis of chiral organohalides and are expected to enhance the availability of enantiomerically enriched chiral compounds with heteroatom-substituted chiral stereogenic centres.

The highly enantioselective fluorination of α-branched aldehydes was achieved using newly developed chiral primary amine catalyst.

Chiral α-chloro-α-fluoro ketones were synthesized by enantio­selective decarboxylative chlorination of α-chloro-β-ketocarboxylic acids in the presence of a chiral amine catalyst. The reaction yielded the corresponding α-chloro-α-fluoro ketones with moderate-to-high enantioselectivity (up to 90% ee). The method was also applied to the synthesis of α-bromo-α-chloro ketones with 90% ee.

A new synthetic route to α‐fluoroenones was developed. Decarboxylative chlorination of α‐fluoro‐β‐oxocarboxylic acids afforded α‐chloro‐α‐fluoroketones, and subsequent base‐mediated elimination yielded the corresponding α‐fluoroenones. The method successfully produced both cyclic and acyclic α‐fluoroenones in good yields. Furthermore, the method was applicable to the synthesis of not only aromatic but also aliphatic enones. The method allows the preparation of a variety of α‐fluoroenones, which are useful intermediates for the synthesis of various fluoroorganic compounds.

Decarboxylative fluorination of tertiary β-keto carboxylic ­acids was performed using an electrophilic fluorinating reagent. The reaction proceeded in the absence of a catalyst or base to yield the corresponding α-fluoroketones with tertiary fluorocarbons in good to high yields. Considering that the α-fluorination of asymmetrical ketones ­often causes problems with the regioselectivity between the α- and α′-positions, this method could be a good alternative to the α-fluorination of simple ketones for the synthesis of tertiary fluoroketones.